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} } - body {font-family: Georgia, serif; text-align: justify; } - table {font-size: .9em;margin-bottom: 1em; } - .footnote {font-size: .9em; } - div.footnote p {text-indent: 2em; margin-bottom: .5em; } - .figcenter {font-size: .9em; page-break-inside: avoid; } - div.titlepage {text-align: center; page-break-before: always; - page-break-after: always; } - div.titlepage p {text-align: center; text-indent: 0em; font-weight: bold; - line-height: 1.5; margin-top: 3em; } - .overflow {font-size: small; } - @media handheld {.overflow {font-size: 50%; page-break-before: always; - page-break-inside: avoid;} } - .vincula{ text-decoration: overline; } - .fraction {display: inline-block; vertical-align: middle; text-align: center; - font-size: 75%;text-indent: 0; } - </style> - </head> - <body> - - -<pre> - -The Project Gutenberg EBook of Studies on Epidemic Influenza, by -University of Pittsburgh School of Medicine - -This eBook is for the use of anyone anywhere in the United States and -most other parts of the world at no cost and with almost no restrictions -whatsoever. You may copy it, give it away or re-use it under the terms -of the Project Gutenberg License included with this eBook or online at -www.gutenberg.org. If you are not located in the United States, you'll -have to check the laws of the country where you are located before using -this ebook. - - - -Title: Studies on Epidemic Influenza - Comprising Clinical and Laboratory Investigations - -Author: University of Pittsburgh School of Medicine - -Release Date: December 1, 2019 [EBook #60822] - -Language: English - -Character set encoding: UTF-8 - -*** START OF THIS PROJECT GUTENBERG EBOOK STUDIES ON EPIDEMIC INFLUENZA *** - - - - -Produced by Richard Tonsing and the Online Distributed -Proofreading Team at http://www.pgdp.net (This file was -produced from images generously made available by The -Internet Archive) - - - - - - -</pre> - - -<div class='tnotes covernote'> - -<p class='c000'><b>Transcriber’s Note:</b></p> - -<p class='c000'>The cover image was created by the transcriber and is placed in the public domain.</p> - -</div> - -<div class='titlepage'> - -<p class='c001'>PUBLICATIONS FROM -THE UNIVERSITY OF PITTSBURGH -SCHOOL OF MEDICINE</p> -<div class='figcenter id001'> -<img src='images/title.jpg' alt='' class='ig001' /> -</div> - -<div> - <h1 class='c002'><em>Studies on Epidemic Influenza</em><br /> <span class='large'>COMPRISING</span><br /> <span class='xlarge'><span class='sc'>Clinical and Laboratory Investigations</span></span></h1> -</div> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div><span class='small'>BY</span></div> - <div class='c004'><span class='sc'>Members of the Faculty</span></div> - <div><span class='sc'><span class='small'>of the</span></span></div> - <div><span class='sc'>School of Medicine</span></div> - <div class='c004'>UNIVERSITY OF PITTSBURGH</div> - <div class='c004'>1919</div> - </div> -</div> - -</div> - -<div class='chapter'> - <h2 class='c005'>TABLE OF CONTENTS</h2> -</div> - -<table class='table0' summary='TABLE OF CONTENTS'> - <tr> - <th class='c006'></th> - <th class='c006'> </th> - <th class='c007'>Page</th> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>History and Epidemiology of Epidemic Influenza</td> - <td class='c007'><a href='#Page_9'>9</a>–33</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'> </td> - <td class='c006'>James I. Johnston, M.D., F.A.C.P.,<br />Assistant Professor of Medicine.</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>A Clinical Description of Influenza as It Appeared in the Epidemic of 1918–19</td> - <td class='c007'><a href='#Page_35'>35</a>–63</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'> </td> - <td class='c006'>J. A. Lichty, Ph.M., M.D.,<br />Associate Professor of Medicine.</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>The Urine and Blood in Epidemic Influenza</td> - <td class='c007'><a href='#Page_65'>65</a>–79</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'> </td> - <td class='c006'>P. I. Zeedick, M.D.,<br />Demonstrator in Medicine.</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>The Treatment of Influenza</td> - <td class='c007'><a href='#Page_81'>81</a>–95</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'> </td> - <td class='c006'>W. W. G. Maclachlan, M.D., C.M.,<br />Assistant Professor of Medicine.</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>The Prevention of Epidemic Influenza with Special Reference to Vaccine Prophylaxis</td> - <td class='c007'><a href='#Page_97'>97</a>–153</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'> </td> - <td class='c006'>S. R. Haythorn, M.D.,<br />Director of the Singer Memorial Research Laboratories.</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>Physiological and Physiological Chemical Observations in Epidemic Influenza</td> - <td class='c007'><a href='#Page_155'>155</a>–160</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'> </td> - <td class='c006'>C. C. Guthrie, Ph.D., M.D.,<br />Professor of Physiology.</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>The Bacteriology of Epidemic Influenza with a Discussion of B. Influenzæ as the Cause of This and Other Infective Processes</td> - <td class='c007'><a href='#Page_161'>161</a>–205</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'> </td> - <td class='c006'>W. L. Holman, B.A., M.D.,<br />Professor of Bacteriology.</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>The Pathology of Epidemic Influenza</td> - <td class='c007'><a href='#Page_207'>207</a>–293</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'> </td> - <td class='c006'>Oskar Klotz, M.D., C.M.,<br />Professor of Pathology.</td> - <td class='c007'> </td> - </tr> -</table> - -<div class='chapter'> - <span class='pageno' id='Page_5'>5</span> - <h2 class='c005'>PREFACE</h2> -</div> - -<p class='c008'>This report is based upon a series of investigations carried on -during the epidemic of influenza at Pittsburgh. This epidemic -reached Pittsburgh about the last week of September, 1918, -rapidly spreading through the community during the first days -of October. Pittsburgh had been warned of its coming through -the experience of Boston, where the epidemic made its appearance -during the late days of August. To a certain extent the -warning from the East permitted the making of preparations to -control its ravages. But even with the attempt for the protection -of public health the epidemic advanced with all its virulence, -rapidly picking out the susceptible individuals and leading to a -high death rate.</p> - -<p class='c009'>At the time of the coming of the epidemic there were stationed -at Pittsburgh two military camps, comprising about 7,000 men. -It was with the presence of the disease among these men that -our investigations were chiefly concerned. The men at their -respective camps (on the campus of the University of Pittsburgh -and at the Carnegie School of Technology) were housed in barracks -which had been erected only a short time previously. These -barracks contained large dormitories, in which the individuals -freely mingled with each other. In them there was no opportunity -of complete isolation, and by this means of housing good -opportunity was available for the propagation of any communicable -infectious disease. The ordinary sanitary arrangements -for these groups were well provided. The first cases of recognized -influenza made their appearance on October 2. On this -day two men were found with the disease and were isolated. On -the following day there were four, and on the third day eight. -It was soon recognized that the increasing number of the infected -cases was growing so rapidly that definite arrangements for their -segregation and care had to be undertaken. This was provided -for on October 4, when the Elizabeth Steel Magee Hospital was -in part taken over by the military authorities and wards were -rapidly adapted for the coming epidemic. For the foresight in -making the adequate arrangements for its control and management -we shall always remain indebted to Major E. W. Day. His -<span class='pageno' id='Page_6'>6</span>indefatigable work in the early days of the epidemic will always -be remembered, and the fact that the epidemic was kept within -reasonable bounds of control was the result of his stringent -quarantine regulations along with the organization of his medical -forces. Working under his direction, Capt. H. H. Hendershott -undertook the management of the hospital and rendered -most efficient service. The capacity of the hospital was soon -overburdened, so that from a normal 150–bed institution it was -on the sixth day of its conversion into an emergency hospital -carrying more than 300 cases of influenza. This hospital in itself -was unable to accommodate all of the cases falling ill, and provision -for these had to be made in some of the municipal institutions. -On October 5, 1918, the Medical School of the University -of Pittsburgh undertook to provide the laboratory facilities for -the emergency Military Hospital. It was at first intended to equip -only those laboratory departments which were deemed essential -for the clinical care of the patients in the wards. Inasmuch, -however, as the epidemic of influenza was spreading with alarming -rapidity throughout the city, it was deemed advisable to close -the Medical School and to place at the disposal of the Military -Hospital all the laboratory facilities which could in any way be -of use in the care and study of the influenza patients. This -permitted the establishment of departments in pathology, bacteriology, -physiology, physiological-chemistry and clinical microscopy. -The following workers partook in the investigations -which were here carried out: Dr. Oskar Klotz, director of laboratories; -physiology, Dr. C. C. Guthrie (chief), Dr. A. Rhode, Dr. -M. Menten, Mrs. C. C. Macklin, Miss S. Waddell and Miss M. Lee; -bacteriology, Dr. W. L. Holman (chief), Miss A. Thorton, Miss -C. Prudent and Miss R. Jackson; pathology, Dr. Oskar Klotz -(chief), Mr. A. D. Frost, Mr. J. L. Scott and Miss A. Totten; -clinical microscopy, Miss R. Thompson, Mr. M. Marshall and Mr. -H. Mock; records, Miss H. Turpin. Intensive work was undertaken -by each over a period of about five weeks, when the epidemic -was again on the road to disappearance and few new cases were -being admitted. These laboratories discontinued their work at -the Military Hospital on November 9.</p> - -<p class='c009'>The clinical observations which are contained in this report -were made at the Mercy Hospital. This institution set aside -upward of 100 beds for the care of the overflow which could not -<span class='pageno' id='Page_7'>7</span>be accommodated at the Military Hospital. It is unfortunate -that the clinical observations and the laboratory findings contained -in this report were not made upon the same cases. With -the number of cases suddenly thrust upon the medical staff of -the army, it was not possible for them to devote detailed attention -to clinical investigation. Furthermore, during the progress of -the epidemic these medical officers were transferred to new posts, -so that it was impossible to obtain a summary of the clinical -findings at the Military Hospital by any of the officers who had -but recently been detailed to the work. We were fortunate, -however, that the clinical investigations were carried out on a -similar group of cases to those studied by the laboratory, and it -might be said that their clinical findings on the patients housed -at the Mercy Hospital are parallel with those observed in other -institutions. Necessarily the researches carried out during such -an epidemic were intensive, and all the workers in the various -branches feel that if they had to live through another such -plague they would be much better prepared to approach their -problem. During the heat of such investigations valuable time -is often lost in perfecting methods of technique, and one sorrowfully -finds oneself without available material when the technical -work has been accomplished but the epidemic has passed by. In -the studies in bacteriology we were fortunate in having some of -the technical difficulties for the isolation of the B. influenzæ -previously solved. It may be that this in part explains the -broad success which Dr. Holman has had in isolating the B. influenzæ -from so many cases. In other fields the road was less -broken, and it was not until late in the course of the epidemic -that results were obtained in the investigation which seemed to -point to valuable leads.</p> - -<p class='c009'>Dr. S. R. Haythorn, director of the Singer Memorial Laboratory, -early in the epidemic became interested in the protection -of individuals against the infection. In certain quarters much was -claimed for the immunity which could be conferred by vaccination, -either by the inoculation of pure B. influenzæ vaccines or -by mixed vaccines. Hoping for some results by the use of -such vaccines, Dr. Haythorn undertook the preparation of these -materials. The value of this procedure could only be estimated -after the lapse of some time and at a period when the epidemic -was again waning.</p> - -<p class='c009'><span class='pageno' id='Page_8'>8</span>The clinical work at Mercy Hospital was carried on under the -direction of Dr. J. A. Lichty, and assisted by Dr. W. W. G. Maclachlan, -Dr. P. I. Zeedick, Dr. F. Klein and Dr. W. J. Fetter. By -the close co-operation of the members of this group it was possible -to put the clinical findings of one or other member to severe -test, so that the recorded observations and deductions are of the -greater value and less flavored by the personal element. This is -of the more value, since, with the great amount of work which -had to be done at the time of the height of the epidemic, it was -often not possible for the same individual to bestow the amount -of time upon each and all cases as he desired.</p> - -<p class='c009'>We are much indebted to Dr. Ogden M. Edwards, dean of the -School of Medicine, for making available the facilities for carrying -out the work, and for encouraging the publication of the -reports.</p> - -<div class='lg-container-r'> - <div class='linegroup'> - <div class='group'> - <div class='line'><span class='sc'>Oskar Klotz.</span></div> - </div> - </div> -</div> - -<div class='lg-container-l'> - <div class='linegroup'> - <div class='group'> - <div class='line'><em>Pittsburgh</em>, June, 1919.</div> - </div> - </div> -</div> - -<div class='chapter'> - <span class='pageno' id='Page_9'>9</span> - <h2 class='c005'>HISTORY AND EPIDEMIOLOGY OF INFLUENZA</h2> -</div> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>By <span class='sc'>James I. Johnston</span>, M. D.</div> - </div> -</div> - -<p class='c008'>The history of epidemic influenza extends back with definite -authenticity to the Middle Ages, with a fair amount of assurance -to the beginning of the Christian Era and with presumptive reliability -even before that period. Beyond this statement, nothing -definite can be said until the first epidemic reported by Short and -found in the English Annals in the year 1510. This, the first -reliable record, presented some features not unlike those occurring -in the present epidemic. Two or three striking things stand -out in this record—namely, the presence of nose bleed, pneumonia -and the very great danger to gravid women. Here, for the -first time, the meteorological conditions were elaborately studied -and persistently dwelt upon. One other impressive thing, also -reported by Short, was that in 1580 the disease showed a tendency -to return after a period of quiescence. Attention is called to this -because the epidemic, while it was exceedingly prevalent in the -months of August and September, became pandemic in October -and November. Another feature was that during the years intervening -between 1580 and 1658 sporadic cases of this disease were -frequently reported. During the latter year another epidemic -appeared in the month of April. In 1657 and 1658 at London the -summer was very warm, the winter came on early, there was -much snow and the spring was very moist.</p> - -<p class='c009'>The prevailing opinion at this time, and the first stated by -Willis, was that the widespread disease was due to the weather -influences on the circulation, poisoning the blood of the patients, -and “not blasts of malignant air.” The disease prevailed in the -large cities, recurring again in the autumn in an extensive form -through the villages and country. Sydenham, in his communication -on the epidemic in 1675, wrote emphatically on the influence -of the infection on pregnant women, and here used the term -“tussis epidemicus” as a name for the disease. The summer of -1675 was wet with an inconstant autumn. La Grippe prevailed in -<span class='pageno' id='Page_10'>10</span>France and Germany, according to Atmuller. In England in 1676, -the autumn was pleasant, but suddenly became cold and moist. -La Grippe then started in Germany during September after a -summer and a beginning autumn which was very rainy. Molyneux -in his description of the epidemic of 1693 in Dublin called attention -to a feature, very striking to the recent pandemic, that the -aged to a great extent escaped the infection. This would seem a -somewhat unique feature until that epidemic is compared with -the present one. In 1729 Morgagni and others stated that over -all Europe the winter of 1728 was very rigorous, the spring was -cold and the summer and autumn very variable, while January -and February of that year were very moist. Huxham in his -record of 1729, the fifth extensive one on record in the English -Annals, which extended into 1733, stated from his study at -Plymouth that the epidemic was exceedingly mild in the year -1733, and, with the exception of infants and consumptive old -people, the mortality was very low. Like many of his predecessors, -he emphasized greatly the conditions of the weather at -the time and presented an elaborate study of it. The epidemic of -1732 was one of the longest and most persistent, extending up to -1737. All authors do not hesitate to attribute as a cause the very -frequent variations of temperature which characterized this -period. Of this epidemic Arbuthnot also emphasized the importance -of the air, assigning the prevalence and widespread features -of the disease to the thick and frequent fogs. From November, -1732, until March, 1733, this disease spread from Germany to -Italy and thence to England. He called attention to a very -striking feature—namely, that people in prisons and in hospitals -escaped the disease. This, as we know, where such institutions -are placed under preventive quarantine, is not such a unique -feature during this present scourge. He, more than former -writers, devoted pages to the elaborate and accurate description -of instruments for meteorological observation and their findings, -which meteorological records were published in detail, covering -the whole period of a year—June, 1732, to June, 1733—with -almost daily regularity. Huxham in 1737 in his record first used -the term “epidemic catarrhal fever”—a name often used subsequently -to describe this disease. Here attention was first called -to the prostration which characterized the convalescents, and his -belief that consumption frequently followed the disease. The -<span class='pageno' id='Page_11'>11</span>next epidemic, which occurred in 1742 and 1743, was also reported -by Huxham, who stated that the weather was very rigorous. This -disease, according to his description, extended over all Europe, -and the term “influenza” seems to have been first used by him -during this time. The cases were mild in England, but more -severe in Southern Europe. Whytt in his record of the epidemic -of 1758 was the first who did not consider that the air condition -or the seasons had the significance attributed to them by former -writers, since the weather conditions during the prevalence of the -disease were generally mild and dry. In Edinburgh at this time -not even one out of seven escaped. Nevertheless, he did not hesitate -to express his opinion that the disease did not spread by contagion -from one person to another. One other observation of his -is worthy of note, which is: that frequent relapses occurred when -patients were re-exposed too soon after the first infection and -such relapses were much more severe than the original disease.</p> - -<p class='c009'>The epidemic of 1762 called forth the opinion of Baker, emphasizing -an opinion already expressed by Whytt, that the origin of -epidemic disease is not due to changeable winds nor to their -nature or character as recorded by the barometer. This epidemic -also prevailed over all Europe and appears to have begun following -sharp alterations of cold and moisture. In 1766 in Spain, -France and other parts of Europe the epidemic appears to have -begun after a warm summer, followed by an autumn moist and -cold. In 1767 Heberden placed on record his observations during -this period, but nothing new was reported. In 1775 the disease -began in Germany in the summer after a dry and warm spring -and spread over all Europe. During the prevalence of the disease -in 1775 a questionnaire was sent to the leading English physicians, -and letters from Fothergill, Sir John Pringle, Heberden, Reynolds -and others seemed to express a consensus of opinion that weather -conditions had nothing to do with the prevalence or spread of the -disease, and that the cause and reason for its spread were unknown. -Following sharp alterations in temperature in 1780, the -disease appeared in France and then throughout the world. The -epidemic of 1782 began in Russia, starting January 2 at St. -Petersburg. The thermometer underwent a variation of 40 -degrees and the same day 4,000 were afflicted with La Grippe. -It reached Koenigsburg in March, Copenhagen in April, London -in May, France in June and July, Italy in July and August, Spain -<span class='pageno' id='Page_12'>12</span>and Portugal in August and September, and then reached America. -Edward Gray, writing of the epidemic of 1782 for the first time, -expressed emphatically his opinion on the contagiousness of the -disease and stated what we now know—that close contact is -necessary. To him also is attributed the opinion first mentioned -by him, that there is a possibility of carriers in this disease. -During this time Dr. Hamilton, in a published letter, protested -against venesection in influenza, a practice long prevalent, and -Hogarth called attention to the fact that the disease began in -cities and villages first and that it was brought to these places by -visitors from without.</p> - -<p class='c009'>The first American writer on this subject was Noah Webster -in 1647 and 1655. Following him was Warren, writing of the -epidemic of 1789 and 1790, just 100 years before the last and -greatest epidemic which preceded the present one. Rush and -Drake also reported this epidemic. During that epidemic which -prevailed in America from September to December, 1789, and -appeared again in the spring of 1790, President Washington -suffered a very severe attack. The year before, in 1788, when -the epidemic prevailed abroad, the summer temperature in Paris -was very variable, variations of 8, 10 and 12 degrees occurring -on various days. La Grippe predominated all the time. The same -variations were true in Vienna. At the end of the year 1799 the -epidemic struck Russia, following very cloudy, misty weather, -was prevalent in Lithuania in January of the year 1800 and in -Poland during February.</p> - -<p class='c009'>The next great epidemic occurred in 1802 and 1803, was very -general, beginning in France and coinciding with a cold and moist -autumn following a very dry summer. It was of six months’ -duration in England. Many schools, jails, asylums and workhouses, -although located in the area swept by this plague, at first -escaped. As mentioned before, this striking feature has not been -so unique in subsequent epidemics. One feature noticed here -and commented upon freely was that elsewhere throughout the -country there seemed to arise endemic foci. During this time -there was also the prevailing belief that the disease was followed -by phthisis. One other observation made here, which was accurate, -lasting and is accepted today, was that no family was -affected <i><span lang="fr" xml:lang="fr">en masse</span></i>, but always one individual case occurred first, -to be followed by general infection of the others. At this time -<span class='pageno' id='Page_13'>13</span>early bleeding was still adhered to. The French spoke of seven -varieties of the disease, but one can only see in the classification -emphasis laid on certain individual symptoms in this disease of -complex symptomatology. During this epidemic pneumonia is -said to have been very infrequent. The disease was particularly -fatal to pregnant women, and the patients suffering from pulmonary -tuberculosis were hurried off by the influenza.</p> - -<p class='c009'>Burns, writing of the epidemic of 1831, mentioned that in 1810 -the disease was very widespread in China and Manila, and also -emphasized the fact mentioned in many works that certain epidemics -prevailed among animals at the same time, stating that -in 1831 these diseases were of choleric nature. This epidemic -began in 1830 in the East, reached Paris in the summer of 1831, -reappeared in Europe in 1833, following the same route that -cholera had taken in 1832. In the epidemic of 1833, Hingeston -also laid great stress on the fact that horses were often affected. -These features, as mentioned by Burns and Hingeston, are frequently -quoted by authors, and such observations seem to have -been widely accepted.</p> - -<p class='c009'>One of the greatest epidemics of influenza began in 1836 and -extended until 1837, and was called at this time epidemic catarrh. -It began in England in January, spread to France, and during all -the time that it was in Paris there were continual penetrating -rains with cold and humidity. At Montpelier on February 20, -1837, the thermometer passed from 12 to 15 degrees above to -2 and 3 degrees below zero, and it was then that La Grippe -appeared suddenly. In reply to the circular letter sent out by -the Council of the Provincial Medical Association of England, -comprising 18 questions, the following opinions prevailed. The -disease was greatest from September to February; the great -prevalence of the epidemic in all parts of the kingdom was recognized—attacks -were irrespective of age, sex or temperament; it -was milder in children, and the aged suffered most from it. -Further, the disease was extensive in all neighborhoods; the mortality -was 1 in 50, old age predisposed to fatal termination, and -the duration of the disease occupied two periods, one terminating -in 4 or 5 days and one in 5 to 14 days. Also relapses were -frequent; those exposed to employment in the open air were not -more liable to the disease than others; there was no proof of the -disease being communicated from one person to another, and influenza -<span class='pageno' id='Page_14'>14</span>aggravated an existent pneumonia or pulmonary phthisis. -And finally previous attacks of influenza offered no protection; -the symptoms were uniform; the most common of unusual symptoms -were those of meningitis, inflammation of the lungs and -syncope, and aside from ordinary care and treatment, general -venesection was not endorsed. Evidence of fine weather and good -telluric conditions were at this time also appended. The same -symptoms and complications, particularly those of the lungs, -occurred irrespective of seasons, civilization or place. It was believed -and stated that the plague described in Homer was probably -influenza. For the first time there is noticed here a point -well worth consideration—the association of other epidemics with -influenza, either anticipating, following or superseding. That -some such association may follow the present pandemic is not to -be entirely ignored. For example, cholera is already reported as -prevailing abroad, following an earlier influenza outbreak. During -the period, as if anticipating bacteriology, one writer -explained the epidemic in an article called “The Dust of Regular -Winds,” and Groves (1850) wrote on “Epidemics Examined, or -Living Germs as a Source of Disease.”</p> - -<p class='c009'>In 1846 and 1847 a slight epidemic occurred in London, Paris, -Nancy and Geneva. In France during the last week of 1857, and -extending into January and February, 1858, there was a mild -epidemic. During this period there alternated frequent frosts -with soft weather, misty and humid. Among the numerous small -epidemics between 1837 and 1889, one occurred on the continent -of Europe in 1860, but little of value or interest was noted. In -Paris in March, after great and sharp variations in temperature, -a series of epidemics extended from 1870 to 1875. These were -unimportant. Atmospheric modifications occupied first rank in -the minds of some as a cause for the outbreaks. Rapid changes -from hot to cold or from cold to hot were given weight. Other -undetermined modifications of conditions were probably important.</p> - -<p class='c009'>In a recent article published by Loy McAfee (J. A. M. A., 1917, -72, 445) he discussed the confusion which existed between the -diagnosis of cerebro-spinal meningitis and epidemic influenza in -1863. These were believed the same by some—that is, the same -disease of varying degree. There was a great diversity of opinion -among clinicians at this time, and the American Medical Association -<span class='pageno' id='Page_15'>15</span>appointed a committee to make an investigation. McAfee -quotes from the Medical and Surgical History of the War of the -Rebellion that in 1861 and 1862 an epidemic existed among the -troops called epidemic catarrh, which was afterward changed to -read acute bronchitis. In September, 1861, there existed an -epidemic of influenza in one of the regiments which lasted more -than two weeks, and in another camp there was a similar epidemic -at the same time. It is stated that there were in all 168,715 -cases among the white troops, with a mortality of 650, and 22,648 -among the negro troops, with a mortality of 255, making about -4 per thousand, and over 11 per thousand, respectively.</p> - -<p class='c009'>The next great epidemic, and the last until the present, -occurred in the years 1889 and 1892, and was pandemic in its -nature. The death rate during this time was lower in the cities -than in the country. This was probably due to the fact that -the greatest mortality was among children and old people, and -as old people were generally left in the country, this explains the -observation. The highest number of deaths was among males, -believed to be due to the exposure and fatigue of work. Forty -per cent. of the world’s population was said to have been attacked -during this period. The yearly or seasonal repetition, as shown -in this pandemic, had occurred in other epidemics. In the great -pandemic of 1889 and 1890, five decades after the last important -epidemic, it was stated that the medical profession found itself -confronted by a new disease of which it had knowledge through -medical history, so also in our time few physicians recognized at -first the reappearance of influenza. This 1889 epidemic is extensively -reported in the literature, and has been elaborately worked -out by many observers. One important feature has been emphasized -by Leichtenstern, which, although recognized by the profession -after the last epidemic had been fully reported and -recorded, is not appreciated by the profession during the present -epidemic—namely, that while shortly after the last epidemic -there were smaller relightings of the infection throughout various -parts of the country, those diseases which we erroneously -call grippe or influenza, occurring commonly in the spring and -fall, are in no way connected with the disease with which we are -dealing, and which occurs at rather long intervals. Any speculation -in regard to these periods, which history has shown to -be fairly wide apart, has very little basis. This pandemic, like -<span class='pageno' id='Page_16'>16</span>many of former days, is believed to have originated in Asia, -and from there to have spread over Europe and hence over -the world. The disease spread rapidly over countries, affected -probably about 40 per cent. of the world’s population, disappeared -rapidly after several weeks, was thought to have had -nothing to do with weather conditions, had a great morbidity -but small mortality, and affected all ages and occupations. There -is no doubt, as stated by some, that the development of traffic -and travel was a large factor in the rapid and extensive spread -of influenza during this pandemic. The course which the disease -followed, springing from its supposed beginning in Asia, has been -fully and amply described by writers after that period, but the -great rapidity of its dissemination over all countries is the most -remarkable feature in the epidemiology of any disease. This, -during 1889, made many prominent physicians disregard the -opinion that influenza spread by contagion and accept again the -opinion expressed by observers of epidemics in former ages, that -miasma as a pathogenic agent was responsible for its distribution; -but anyone who reads closely the history of this epidemic, -and in the light of modern medical science, must feel that the -rapidity of distribution was nowhere greater than the most -speedy means of transportation. This very necessary close connection -was demonstrated also in regard to the mode of spread -of the disease; the large cities and the commercial centers were -affected earlier, smaller and country districts followed later, -railroad towns were more frequently attacked than isolated villages, -and even from jails, prisons and workhouses, where quarantine -was immediately attempted, as well as from remote villages -where the disease had been brought, there could be traced -a zone of infection spreading into the country. One interesting -point was raised at this time—namely, that in some places it -seemed to spread by leaps and bounds, and at other places -radiating as stated above.</p> - -<p class='c009'>The old controversy of whether influenza is distributed in a -radiating manner or in so-called leaps and bounds is believed to -be settled by consensus of opinion that it occurs in both ways. -An opinion expressed by the study at this time as to whether -influenza spreads more rapidly than any other infectious disease -is found in the statement that the contagion is markedly virulent, -the micro-organisms are easily conveyed from their original seat -<span class='pageno' id='Page_17'>17</span>in the mucous membrane by coughing, sneezing and expectoration, -the great number of persons who, though slightly affected, -carried on their ordinary way of life without hindrance, the -probable longevity of the organisms in convalescents, the brief -period of incubation of two or three days, the susceptibility of all -people of every age and vocation, and the possibility of carrying -the contagion by merchandise and even through short distances -in the air, are all suggestive reasons for this. No one at present -accepts the so-called miasmatic nature of the contagion. Proofs -are ample to show that one case must be present in a locality -or even family, although it may be frequently overlooked, from -which the epidemic spreads. During this period of 1889 and -1890 the duration of the actual epidemic period in different localities -in Europe was from four to six weeks. This was subsequently -shown to be consistent with the recorded reports from -the various cities in the United States. Following this pandemic -in the first part of the year in 1891 there were numerous epidemic -outbreaks in various parts of America, including New Orleans, -Chicago, Boston, and simultaneously in England. Strange to -say, at this time neither Germany nor France had such epidemics, -although both were exposed by travelers, particularly -from England and America. The question was raised at that -time whether the Germans, French or other continental nations -were more immune than Americans and English. In the fall of -1891 and the entire winter of 1892 the disease was extensively -prevalent both in Europe and Northern America. In these later -epidemics there was no definite direction of spread. They probably -would come more clearly under the so-called radiation from -numerous rural districts. In almost every case at the point of -its origin in these countries the epidemic developed and spread -slowly, lasting months and with very varying morbidity and -mortality. They had none of the explosive characteristics of -the pandemic. The general diminished morbidity of the later -epidemic, the diminished geographic distribution of the disease -and the scarcely recognizable character of its contagion, its slow -development and extension over several months, the continuous -diminution in frequency and in intensity since its onset in 1889, -have been explained by presumptive successive lessening of susceptibility -of the population, possibly due to acquired immunization. -Observers at that time, as well as ourselves, could question -this last statement.</p> - -<p class='c009'><span class='pageno' id='Page_18'>18</span>There was observed one noteworthy thing about seasons. -While the great pandemic of 1889 and 1890 had no definite connection -with seasons, the epidemic types which followed in 1891 -and 1892 seemed to show a lighting up in either spring or fall, -remaining dormant in the summer months. It has also been -shown by the history of former epidemics that almost all the -pandemics started from Russia in the fall, winter and spring -months. Such was the case in 10 of the great pandemics of -1729 to 1889. This, no doubt, was the reason so many of the -former historical writers were impressed by seasons and meteorological -conditions. The statement made by observers during -the epidemic that influenza presented two phases, one pandemic -and the other endemic, and that each follows different epidemiological -rules, seems possible. The question raised during the last -epidemic of the spread of the disease in families, the disease -occurring at high altitudes and even at sea, we know does not -interfere with the recognition of its spread by direct contagion. -Definite examples of families or villages being infected by a -returned member of such family or citizen from abroad are -reported frequently, and even the appearance of the disease in -isolated places has often been traced and verified from a definite -source, to say nothing of the question of carriers and those supposed -to be suffering from other diseases.</p> - -<p class='c009'>Striking examples are shown also in this epidemic that many -institutions, frequently those isolated from the world, were -markedly exempt until, through servants or outside visitors, the -disease gained access to them. This gave a most favorable field -for the study of invasion, spread and decline of the disease. -Observations made at this time in regard to hospitals seemed to -suggest that certain institutions were more or less exempt, -although not closed institutions, while others suffered from the -first. These two types of hospital invasion are hard to reconcile.</p> - -<p class='c009'>Great stress was laid in this epidemic upon the very great -morbidity and the low mortality. Simple, uncomplicated influenza -at this time was looked upon as a disease that was rarely dangerous -to life. Studies have shown that after this period there -seemed to have been lessened morbidity. As previously stated, -nearly all the numerous pandemics at various times have had -their origin in Russia and arose in the late autumn or winter -months. This pandemic of 1889 and the succeeding severe epidemics -<span class='pageno' id='Page_19'>19</span>in Europe and North America in the years of 1891 and -1892 occurred almost exclusively in the cold weather, the summer -remaining free. It is generally believed now, and was at the end -of that pandemic, that atmospheric or telluric conditions had -nothing to do with the spread. The origin of epidemics following -the pandemics seemed to be influenced in their recurrence by the -season of the year. It was conceded by observers in that pandemic -also that contagion might be carried by merchandise and -even flies and healthy individuals.</p> - -<h3 class='c010'><em>1918 Epidemic in Large Cities</em></h3> - -<p class='c011'>In the city of Boston during the week ending August 28, at the -Naval Station at the Commonwealth Pier, 50 cases of influenza -occurred and within the next two weeks more than 2,000 were -reported in the naval forces of the First Naval District. Of these -5 per cent. developed broncho-pneumonia with a mortality of more -than 60 per cent. From here it probably spread to Camp Devens -and thence ran rapidly over the country. There can hardly be a -question that it spread along the lines of traffic. Up to November -9 there were reported 3,339 cases among the civilian population -of Boston. There were 3,430 deaths from influenza, the presumption -being that these were due to bronchial pneumonia, -although not reported as such. The deaths from all forms of -pneumonia were reported as 942, making in all 4,372 deaths from -September 7 to November 9. This discrepancy—that is more -deaths than reported cases of influenza—is due to the fact that -influenza was not made a reportable disease until the date of -October 4, fully a month from the time the epidemic appeared. -The weather conditions were generally fair and no noted abnormality -is recorded as compared with other years. The statement -of the Health Department of this city was that, after a practical -disappearance of influenza in October, there was a slight recurrence -in November and a more pronounced recurrence about the -first of December, since which time the cases have slowly but -steadily decreased, until at present—December 21—the fatalities -attributable to influenza are about 20 daily.</p> - -<p class='c009'>In the city of New York the epidemic first appeared September -18. Up to and including December 27 there were reported to -the Department of Health 136,061 cases of influenza and 21,388 -<span class='pageno' id='Page_20'>20</span>cases of pneumonia. The number of deaths since September 18 -was 11,725 attributed to influenza in the death certificates filed -in the Health Department and 11,601 attributed to pneumonia. -The epidemic reached its peak during the week of October 19, -slowly subsided and was practically at an end on November 9. -While the epidemic is reported as ending on this date, the mortality -rate from influenza and pneumonia is still very much above -normal. No particular features concerning the meteorological -conditions were noted, except that in this city the weather was -clear and delightful during the months of September and October -when the epidemic was rampant.</p> - -<p class='c009'>In the city of Philadelphia on July 22 the Health Department -issued its first health bulletin on so-called Spanish influenza, -announcing the possible spread of this disease into the United -States. On September 18 a warning was issued against an epidemic, -the department starting a public campaign against coughing, -sneezing and spitting. On September 21 the Bureau of -Health made influenza a reportable disease. At this time the -authorities stated an epidemic of influenza was recognized as -existing among the civil population of similar type to that found -in the naval stations and cantonments; that a large percentage -of cases was accompanied by pneumonia; that patients should be -isolated and attendants wear masks; that isolation be practiced -for a period of ten days after recovery to prevent carriers; that -patients be guarded against relapse and that the public be cautioned -against large assemblages and crowded places, as well as -to avoid coughing, sneezing and spitting. On October 3 the -churches, saloons and theatres were closed, funerals were made -private and food handlers were required to protect their wares. -The number of cases reported from September 23 to November 8 -was 48,131, but the Bureau states, from a rough estimate, the -number of cases was probably 150,000. The total number of -deaths reported was 7,915 from influenza and 4,772 from pneumonia -in all its forms, the presumption being that the deaths -during this period were due to influenzal pneumonia. The -weather condition during this time is recorded as mild and fair.</p> - -<p class='c009'>The influenza cases began to be reported in Cleveland on -October 5, and up to December 20, 22,703 cases had been recorded. -Certificates recording deaths due to influenza alone numbered -2,497, while pneumonia amounted to 833. The epidemic was at -<span class='pageno' id='Page_21'>21</span>its height in the latter half of October and the weather was -spoken of as pleasant fall weather. During the week of October -26 the epidemic reached its greatest height, abated in the week -ending November 23, increased later, but showed a drop for the -week ending December 21.</p> - -<p class='c009'>The epidemic first reached Chicago on September 21, and -from that date on it rapidly increased throughout the city for a -period of 26 days until October 17, when it reached its maximum -both in the number of deaths from influenza and from pneumonia. -On that day the total number of deaths from influenza and from -pneumonia reported was 2,395. From September 21 until November -16 there were reported 37,921 cases of influenza and -13,109 cases of pneumonia. On September 8 at the Great Lakes -Naval Training Station, which is 32 miles north of the city, an -extensive outbreak of influenza occurred. This was 13 days -before the outbreak in the city of Chicago itself. Camp Grant, -located at Rockford, 92 miles northwest of the city, suffered an -outbreak on September 21. A suggestion of the likelihood that -influenza was prevalent in this country in a mild and unrecognized -form in the spring of this year is shown by the fact that -numerous local outbreaks of acute respiratory diseases were -brought to the attention of the Health Department of Chicago. -These occurred especially in large office buildings and in industrial -departments. The total number of deaths from influenza -and pneumonia during 14 weeks was 51,915. This would indicate -that a very great number of cases were not reported to the -Bureau of Health until they died or else there must have been a -large number of deaths due to lobar pneumonia. One naturally -obtains from these figures the impression that the disease was -not recognized for a long time, that the pneumonia must have -been called lobar pneumonia, and that the actual figures gathered -by this city, as well as others, must have been greatly confused -at the onset of the epidemic. It is not unlikely that records from -many of the army cantonments and naval stations may be considered -from the same viewpoint. Weather conditions were considered -normal at the height of the epidemic, the weather being -dry. There has been a flare-up of influenza recently, but not in -sufficient numbers to justify calling it epidemic.</p> - -<p class='c009'>In the city of Louisville, Ky., the epidemic started September -26, and the total number of cases up to December 21 is reported -<span class='pageno' id='Page_22'>22</span>as being 9,445. Out of this number 772 deaths occurred from -pneumonia. No distinction is made here between broncho-pneumonia -and lobar pneumonia, but the presumption from the records -of other cities at this time is that these were cases of broncho-pneumonia -following influenza. The weather was described as -being delightful fall weather. The statement is made by the -authorities that while the epidemic is still prevalent, it is confined -largely to children and is rapidly abating.</p> - -<p class='c009'>The first case in the city of St. Louis was reported about October -7, and up to December 23 there had been 31,531 cases reported -to the Bureau of Health. They recorded 1,920 deaths with -influenza given as a contributing cause. Preceding the time when -the epidemic was at its height the weather was fair and warm, -and the statement is made that, “without going into the matter -exactly, we have been of the opinion that damp, rainy weather -has been a help in controlling the disease.” The opinion was -expressed by the Commissioner of Health that the disease had -now abated.</p> - -<p class='c009'>No information could be obtained as to when the epidemic first -reached the city of New Orleans, but during the months of October -and November 43,954 cases of influenza were recorded. Of -this number 2,188 died from a combination of influenza and pneumonia. -They stated in their health report that during the period -from January 1 to December 31 there were 239 deaths attributable -to broncho-pneumonia. The weather was mild and on -December 24 the epidemic was stated to have abated.</p> - -<p class='c009'>The city of Minneapolis recorded its first case on October 7, -but the authorities expressed their belief that a few cases had -appeared before that date. Up to December 21, 15,000 cases had -been reported to the Bureau of Health and of these there had been -735 deaths from broncho-pneumonia. They had in their city a -late, rainy fall and up to that period they had had no cold weather.</p> - -<p class='c009'>The record obtained from the city of San Francisco stated that -the epidemic first appeared September 23 and that it was very -widespread in that city early in October. There were two invasions -and 53,260 cases reported. At the height of the epidemic -more than 2,000 cases were reported in one week; 188 deaths -occurred from influenzal pneumonia. The following week, after -the institution of mask wearing, in which between 80 and 90 per -cent. of the population concurred, it was stated that the number -<span class='pageno' id='Page_23'>23</span>of cases decreased to about 200. It was stated that the weather -was generally very fair during the epidemic.</p> - -<p class='c009'>From the city of Portland, Oregon, the following information -was obtained: The epidemic first appeared October 11, with a -second one toward the end of the year. There were 8,079 cases -reported, with 658 deaths from influenza and 250 from pneumonia. -Weather conditions were stated to be varied, but the -health officer believed that during the worst wave the weather -was clear and dry, with easterly wind. He believed that a decrease -in influenza was noticed immediately after a Chinook wind and -warm rain. Similar observations were made by Coutant in -Manila.</p> - -<p class='c009'>A weather comparison of 12 large cities, well distributed over -the United States, studied during this pandemic of influenza and -checked with normal weather during that of many years, shows: -Boston, fair with no abnormality; New York, clear and delightful, -no abnormality; Philadelphia, mild and fair; Pittsburgh, mild -and cloudy; Cleveland, pleasant fall weather; Chicago, normal -and dry; Louisville, delightful fall weather; St. Louis, fair and -warm-damp, rainy weather later seemed to control the epidemic; -New Orleans, mild; Minneapolis, a rainy fall and no cold weather, -which is unusual there; San Francisco, generally fair, and Portland, -Oregon, clear and dry.</p> - -<h3 class='c010'><em>The Epidemic in Universities and Colleges</em></h3> - -<p class='c011'>At Bryn Mawr College, in Pennsylvania, an institution devoted -to the higher education of women, located within 10 miles of the -city of Philadelphia, the epidemic occurred at the beginning of -the college year—October 1. This college at the time had an -enrollment of 465 students. There were 85 cases of influenza, -with an additional 25 who suffered from influenza in their homes. -There were no deaths from pneumonia. The weather conditions -were clear and warm, and since November 29 there have been no -new cases occurring in the college and only three or four of the -students have been ill at their homes since that time.</p> - -<div class='figcenter id002'> -<span class='pageno' id='Page_24'>24</span> -<img src='images/i_024.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p><span class='sc'>Dates of the Appearance of Influenza Endemic in various Cities of the</span> UNITED STATES<br />1918.</p> -</div> -</div> - -<p class='c009'><span class='pageno' id='Page_25'>25</span>The enrollment at Smith College, Northampton, Mass., was -2,103, and the first case of influenza appeared with the arrival -of the students on September 18 and reached its height on September -30. All group gatherings indoors were stopped from -October 3 to October 18, and the epidemic was over by October -20. A recurrence began November 15 and continued until December -17. There were 182 cases in the first epidemic and 100 cases -in the second. There were only two deaths from influenza -pneumonia. During the rise of the epidemic the weather was -rainy, followed by good, clear weather. The change in weather -conditions seemed to make no difference. The second epidemic -was still prevalent when the students left for their holidays.</p> - -<p class='c009'>In Wellesley College, where there were enrolled 1,593 students, -the epidemic first appeared on September 18. Up to the middle of -December they had had 280 cases. During six weeks of the -epidemic 265 cases were reported and only one death occurred -from broncho-pneumonia. For the most part, bright and sunny -days were present, with only a few cloudy and rainy days. This -college has not been without cases since September, but the -epidemic lasted only about six weeks.</p> - -<p class='c009'>In a communication from Columbia University it is stated that -the epidemic appeared during the week beginning September 22. -No records were available for the student body at the time of -inquiry, but in the Student Army Training Corps of 2,200 men -between 8 and 9 per cent. had the disease during the period from -October 1 to December 14. In this army group during this period -two deaths from influenza and pneumonia occurred. The weather -conditions in the city during this time were considered normal -for fall weather—that is, mostly clear, with high winds. The -opinion expressed was that the epidemic was still prevalent and -increasing, and that a return wave seemed to be more virulent -and affected the children of the city more than had the first one -in the early fall.</p> - -<p class='c009'>There were enrolled at Harvard on October 1, 3,193 students. -The first case of influenza occurred on September 20. There were -227 cases of influenza reported; of these there were 46 cases of -broncho-pneumonia, with five deaths. There were two waves to -the epidemic; the first wave height was in October and the second -the last of November. The weather conditions were not severe -nor particularly unfavorable at either time. The epidemic abated -at the university largely because of the demobilization of the -Student Army Training Corps. At that time it was still prevalent -in Cambridge and Greater Boston.</p> - -<p class='c009'><span class='pageno' id='Page_26'>26</span>At Yale University the disease first appeared in the New -Haven Hospital on September 21. There were registered in all -departments of the university 2,265 students. Up to the date of -December 24, 1,013 cases have been treated. The number of -deaths from broncho-pneumonia has been 249. At the height of -the epidemic, which occurred in the third week of October, typical -fall weather prevailed. An unusually clear, dry October with -very little rain, much sunshine and rather low humidity was the -weather report.</p> - -<p class='c009'>During the period of the epidemic at Princeton that university -had 1,050 students, and the first cases appeared shortly after the -opening of the college term on September 24. As a precautionary -measure, every case, when even only suspicious, was sent to the -infirmary. In all, there were about 70 cases in the university -and about 45 cases from the United States School of Military -Aeronautics. Only one member in the latter school died of pneumonia. -There were no deaths among the students at the university. -In this part of the country the weather was most -delightful all autumn, being warm and dry, very little rain -having occurred since the end of July. At the date of the inquiry -the epidemic had disappeared—that is, about December 21—there -being only two very mild cases under suspicion. In the town of -Princeton, outside of the university, the conditions were much -more serious than in the university itself. Influenza appeared -in the homes of many of the poor people of the immigrant class, -so that it was not uncommon for four or five members of one -family to be infected at once. In one family of seven, five serious -cases of pneumonia developed. An emergency hospital was opened -by the authorities and 40 cases of pneumonia were treated. Of -these approximately one-half died. At the time this report was -furnished the epidemic seemed to have disappeared.</p> - -<p class='c009'>The number of students enrolled at the University of Virginia -was 957. The first cases occurred as early as September 24. -There were 290 of these in number, and three died of broncho-pneumonia. -The epidemic was reported as having abated on -December 15, but a few cases appeared after that date.</p> - -<h3 class='c010'><em>1918 Epidemic at Pittsburgh</em></h3> - -<p class='c011'>At the Army General Hospital No. 24, located at Hoboken, a -few miles outside of the city of Pittsburgh, on September 28 -<span class='pageno' id='Page_27'>27</span>two soldiers were taken ill and, with the disease unrecognized, -they were removed to the cantonment hospital at Point Breeze, -within the city proper. The men were found a few days later -to be suffering from influenza, and from this presumable source an -epidemic spread rapidly among the troops and student soldiers -located here.</p> - -<p class='c009'>From September 28 until November 20, 1,392 cases of influenza -occurred among the enlisted men. How the infection reached the -first two cases at Hoboken is not known. The command here -consisted of the Student Army Training Corps of the University -of Pittsburgh, and Carnegie Institute of Technology, Motor -Mechanics of the University of Pittsburgh and the Ordnance and -Quartermasters’ Department on detached service. The strength -of this command was approximately 7,000. The first case -appeared on September 30 and the diagnosis was made on the -following day. Beginning October 13, all soldiers of this group -were inoculated with two 1 cc. doses of vaccine, obtained from the -New York State Board of Health. At the height of the epidemic -there were about 840 soldier patients in the several hospitals -of the city at one time. Cubicles were used in the hospitals, -and in the barracks a floor space of 50 square feet was -allowed to each man. The men slept alternately head to foot, -with paper screens intervening, which were changed daily. In -company formation they were instructed to gargle their throats -and clean their teeth morning and night under the supervision -of their officers. Strict military quarantine was maintained -throughout the entire camp, no congregating was allowed, classes -were suspended and only open-air drills were permitted. For the -entire command there were 220 cases of pneumonia, with 99 -deaths, an average mortality of 44 per cent. The dishes were -boiled in the hospitals, and sanitary dishwashers were used in all -mess halls. The kitchen help and personnel were inoculated with -influenza vaccine, with apparently good results. The Magee -Hospital, with 375 beds, was under strict military control. When -this was full, all others were treated in the civilian hospitals.</p> - -<p class='c009'>In the city of Pittsburgh the disease was not made reportable -until October 5. However, one case was reported on October 1, -and it was known that there were a few isolated cases in Pittsburgh -previous to that date. During the months of October, -November and up to December 21 there were 23,268 cases of -influenza reported, and the deaths were 1,374 from lobar pneumonia -<span class='pageno' id='Page_28'>28</span>and 678 from broncho-pneumonia. We cannot but feel -that most of the deaths reported during the period of the epidemic -as lobar pneumonia were broncho-pneumonia associated -with influenza. It was well known among civilians that true -lobar pneumonia was exceedingly rare and has remained so up -to the present time. This is especially noticeable, as this is the -time of the year when lobar pneumonia is usually widespread in -Western Pennsylvania. This district was particularly favored -with a mild fall and winter. On October 1 the first case was -reported, on October 15 the epidemic reached its peak—on that -day 957 persons being reported ill with the disease. From October -16 until October 28 it maintained an average of 600 cases -daily; from October 29 until October 31 there was a sharp decline -from 600 cases daily down to 200 cases daily. From November -1 until December 21 the decline has been uniform, and on this -latter date 58 cases of influenza and 7 of pneumonia were reported. -The height of the epidemic was reached between October -15 and October 29. During the period of the epidemic in Pittsburgh, -from October 1 until December 15, 62 days were recorded -as cloudy, or partially cloudy, and only 14 days as clear, although -the cloudy days seemed distributed and not in decided groups. -The mean temperature for October was 58 degrees, with normal -54.9; for November, 44 degrees, normal 42.9; for December, 41 -degrees, normal 34.7. The precipitation in October was 3.08, as -against a normal of 2.36; in November, 1.79, with normal 2.55; -and in December, 3.50, normal 2.73. From a study of these -weather reports we see that the epidemic occurred during a -period of abnormally warm, cloudy and slightly more moist -autumnal season than usual, but these variations were relatively -slight and far from decided. The confusion of diagnosis between -lobar pneumonia and broncho-pneumonia, associated with or following -influenza, occurred in the Pittsburgh health reports as -well as in other cities. The presumption that almost all, if not -all, of the cases reported as pneumonia of different types were -really cases of influenzal pneumonia, seems justified.</p> - -<h3 class='c010'><em>Epidemic Incidents in Institutions and Towns of Western Pennsylvania</em></h3> - -<p class='c011'>During the time the epidemic was at its height in Pittsburgh -the Western Pennsylvania Institution for the Blind was in session. -<span class='pageno' id='Page_29'>29</span>This school is located in the heart of the educational center -and was surrounded by the barracks of the Student Army Training -Corps of the University of Pittsburgh and the Carnegie Institute -of Technology. When the influenza was recognized as epidemic -in this neighborhood, the attending physician at this -institution advised a quarantine against the public. The children -were refused visitors in the buildings, and the usual week-end -trips home were forbidden. This school was continuously in -session from September 24 until November 30. During this time -there was not a single case of influenza in the school and the -children were free from any infectious disease. On December 1 -the pupils returned to school after the Thanksgiving holiday, -and one week later, on December 8, the first case of influenza -appeared. In a period of five days following 15 cases developed. -It was considered wise to close the school, and all well children -were sent to their homes. The institution was kept closed until -January 1, since which time no cases have developed. Very few -of these children had influenza at home, and only one death -occurred.</p> - -<p class='c009'>A reliable report, subsequently confirmed by the health officer, -stated that in Masontown, Pa., the start and course of the epidemic -were very striking. A dance was held in the town and the -musicians were brought from nearby cities. One of the musicians -employed was not very well upon his arrival, and became so ill -that after the dance he was put to bed in the hotel. He was -found to be suffering from influenza when examined the following -day, and from him as the primary case the town was swept -by the epidemic.</p> - -<p class='c009'>In Mercer, Pa., the physician to the Board of Health reported -that during September they had a general epidemic of coryza -and sneezing, with slight fever, which lasted for three or four -days. This was looked upon by the people as hay fever. In the -midst of this, or about September 16, a man, 74 years of age, -who had been away from home, developed true influenza, followed -by pneumonia, from which he recovered about October 10. -Another man, employed in Greenville, a nearby town, where -influenza was already prevalent, returned to his family here -suffering from the disease. The whole family and all who were -exposed to this family were infected. From this family as a -focus the disease spread rapidly in every direction. There were -<span class='pageno' id='Page_30'>30</span>about 350 cases in the town of 2,000 inhabitants, and there were -9 deaths. Sporadic cases have occurred since, ranging in number -from one to a dozen at a time. These numbers do not include -scores of cases called colds by the people, but it seems that all -these cases had an influenza element.</p> - -<p class='c009'>In the town of New Castle it was not possible to trace the onset -of the influenza epidemic to a definite case. As the health officer -stated, several cases were reported at once.</p> - -<p class='c009'>The first case of influenza in Indiana, Pa., of which there was -any definite knowledge occurred on September 15. A clothing -merchant who had just arrived from New York, where he had -been buying stock for his store, was the first case identified. The -next case occurred several weeks later, the disease being contracted -at the mining town of Coal Run, in Indiana County.</p> - -<p class='c009'>A man resident in Sharpsburg who had suffered from influenza -visited friends in Fraser Township, Allegheny County, to convalesce. -Previous to his coming that section had been free from -the disease. He was still coughing at the time, and, moreover, -he is said to have been a great talker and visited largely among -the neighbors of his host. Threshings in that part of the township -were going on and these he also attended. The date of his -coming was October 13. By October 15 his hostess was taken ill. -By October 16 some of the threshers were affected, and by October -17 enough were sick to break up the work of threshing. -Eventually all the men engaged became ill, and 11 families were -infected from this source.</p> - -<h3 class='c010'><em>Summary</em></h3> - -<p class='c011'>Reviewing the history of former epidemics and pandemics, I -have gained the impression, as have many others, that we are -not dealing with any new disease. Further, our knowledge of -this pandemic with its high incidence of broncho-pneumonia -shows that it is in no way markedly different from that of former -manifestations of influenza. One is impressed by the fact that -in different outbreaks of this disease of complex symptomatology -certain symptoms or complications have been prominent, overshadowing -others, and making such complications the striking -feature at the time. The failure to recognize that these varying -features are merely different manifestations of one disease has -<span class='pageno' id='Page_31'>31</span>resulted in much confusion. The observation made in the last -epidemic—and one which can be endorsed during the present -plague—is that influenza has been and is the most widespread, -rapid and extensive of all diseases. One thing also that -attracts attention at the present time is the long period existing -between the several pandemics. Whether, as one observer during -the present pandemic has stated, it requires a long period for -the infection to become active and easily carried, or whether -any possible reason can be suggested for these phenomena, admits -of no satisfactory explanation. The outstanding feature during -this epidemic is the complication of broncho-pneumonia, and yet, -from very early times, this complication has been repeatedly -spoken of as a striking characteristic. Reviewing the health -reports from the large cities of deaths from pneumonia, the presumptive -opinion seems justified that almost all, if not all, pneumonias -reported as associated with influenza were of the broncho-pneumonia -type. The infrequent presence, indeed the rare finding, -of lobar pneumonia during this period in Pittsburgh seems -to verify the aforesaid opinion. The great frequency and the -high mortality of broncho-pneumonia were particularly noted -during the present epidemic. During the present epidemic the -great mortality among pregnant women was another striking -feature, and yet this is by no means new, having been recorded -by some of the earliest writers. Such also may be said of the -recurrence of the disease in the same patient. One important -observation brought out in the study of the pandemic of 1889 to -1892 was that the ordinary infections occurring in the spring -and fall known as grippe or La Grippe are in no way connected -with the pandemics which have occurred. There seems to be a -consensus of opinions among the records of the more recent epidemics, -as well as during the present pandemic, that weather -conditions in no way influence the spread of the disease. Furthermore, -a study of weather conditions throughout the United -States, and particularly those of our own city, seem to bear out -the truth of this observation. While clinicians during other -epidemics expressed their belief in the incident of a primary case -producing infection, it has only been during the present one that -such an opinion has not been assailed. The large number of -military training camps and cantonments have undoubtedly -offered splendid opportunity for the spread of influenza. The -<span class='pageno' id='Page_32'>32</span>futility of attempting to control it even under normal conditions -is still questionable. Consistent with former reported invasions -of the disease, the present epidemic lasted a definite period. This -period was about six weeks in most of our large cities, colleges -and institutions, extending approximately from October 1 to -November 15.</p> - -<p class='c009'>It is imperative to note the accurate clinical observations recorded -from the numerous epidemics of the past by men with -far less data to go upon than is available at the present day. The -high morbidity among the personnel of many of our hospitals and -institutions where the infection occurred and the relatively low -mortality deserve attention. This may be partly explained -by the methods of treatment of those infected, but not entirely. -The great likelihood of carriers of influenza, who either are not -ill or who are suffering from very mild infection, is an observation -also noted by former writers which cannot be ignored. The -value of the masks has not been established, although they have -been extensively used in many parts of the country. Frequent -throat lavage was generally accepted as a rational preventive -measure. Relightings of the disease have been noted in most of -our cities after the subsidence of the epidemic. Vaccination -against influenza is fully discussed in Dr. Haythorn’s paper in -this series.</p> - -<p class='c009'>The presence of influenza in San Quentin prison, California, -in April, 1918 (Public Health Reports, May 9, 1919); an epidemic -of respiratory disease in Chicago in the spring of 1918; the report -of Soper of influenza in our army camps in March and April, -1918; the occurrence of influenza in Porto Rico in June; influenza -on a United States Army transport from San Francisco, as -reported by Coutant, seem to point to the possibility that influenza -had a footing in America long before the disease became pandemic. -The view held by some that the beginning of influenza -was in America, subsequently being transferred to Europe and -then reimported here, is worthy of consideration. Coutant believed -the disease originated in Manila, others that it traveled from “a -permanent endemic focus in Turkestan,” and there are many -other theories which attempt to discover the original source of -the disease. The question is today an unsettled one. The pandemic -of influenza in its severest form swept so suddenly over -the world that before the profession realized it or had become -<span class='pageno' id='Page_33'>33</span>stabilized it had changed its character and the great plague was -gone. The consequence has been that we have really learned -little that is new and have done scarcely more than establish on -a firm basis many of the opinions formed after the great outbreak -of some 30 years ago. Because transportation is today more -rapid than it was at that time, so the spread of the disease has -been correspondingly swift. Our modern life, the congregating -crowds in theatres, moving-picture houses and in lecture halls, as -well as of the men in our training camps, the development of -street cars and the more frequent traveling by train—these and -many more changes in our mode of living have served to aggravate -the conditions favoring the widespread distribution of the -infecting agent. A higher proportion of the population was, -therefore, attacked than in any previous pandemic, and the period -during which the disease was widely prevalent has for the same -reason been relatively much shorter.</p> - -<p class='c009'>The characters differed somewhat in different regions, but the -evidence shows clearly that we are not dealing with any new -disease. It will be years before we are able to fully analyze the -data that have been collected from such wide sources and by so -large a body of trained men, so that important epidemiological -facts may still be forthcoming from the material already at hand. -We are too close to the events to get the most helpful perspective, -and the object of this report has been to add, in however small a -degree, to the general knowledge of this great pandemic as it has -appeared to us in Pittsburgh and its surroundings.</p> - -<div class='chapter'> - <span class='pageno' id='Page_35'>35</span> - <h2 class='c005'>A CLINICAL DESCRIPTION OF INFLUENZA AS IT APPEARED IN THE EPIDEMIC OF 1918–1919</h2> -</div> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>By <span class='sc'>J. A. Lichty, M. D.</span></div> - </div> -</div> - -<p class='c008'>The epidemics of influenza which have been recorded from -time to time during the past few centuries have always contributed -an interesting chapter to the history of medicine. The -protean character of the disease with its many complications is -always an excuse for another attempt at the description of the -clinical manifestations of a recent epidemic. This is not, however, -the only incentive at the present time for describing the -clinical aspect of the disease as it appeared in the epidemic -through which we have just passed. The study of the disease -from other aspects, such as the pathological, the bacteriological -and the physiological, by well-organized groups of workers has -made it necessary to co-ordinate, if possible, the clinical findings -in every detail with these apparently basic principles. It would -be interesting to review here the peculiarly fortunate circumstances -which have led to the investigations. On account of -the great war many temporary laboratory organizations which -otherwise would not have existed were in operation, and these -organizations, moreover, were keen to undertake any laboratory -problem which might arise. The present epidemic presented the -opportunity, and that the work was taken up with great enthusiasm -is evidenced by the reports coming from the various army -hospitals, base hospitals and civilian hospitals throughout the -world. The permanent laboratories connected with medical -schools and with institutions for medical research took up the -problems with equal endeavor. This brief reference is made only -to call attention to the fact that from such organizations a great -mass of information has come which must be critically reviewed -and coordinated before it can add to the permanent fund of our -knowledge of the disease under consideration.</p> - -<p class='c009'><span class='pageno' id='Page_36'>36</span>The material upon which the following clinical observations -have been made is peculiarly adapted to review because it consists -of two distinct groups of patients which were admitted to -the Mercy Hospital. One group of 153 men was composed of -soldiers between the ages of 18 and 23, which had been recently -inducted into the Student Army Training Corps, and were living -in barracks in the immediate vicinity of the hospital. Another -group consisted of civilians (394), ranging from youth to old age, -which came from various parts of the city and surrounding towns -and country. The first group came to the hospital early, or as -soon as the disease was recognized; the second group came -usually after several days of illness had elapsed, or when a complication -had already arisen. Many of this group had been ambulatory -cases for the first part of the disease. The entire number -of patients admitted to the Mercy Hospital from the first admission, -September 21 to December 1, the end of the quarantine, -was 547. After December 1 very few simple influenza cases were -admitted. These 547 cases form the basis of the observations -which will be referred to in this paper.</p> - -<p class='c009'>From the last great epidemic or pandemic of influenza, that -of 1889 and 1890, have come clinical descriptions which should -be reviewed before speaking of the clinical manifestations which -have characterized the present epidemic as shown in the two -groups studied.</p> - -<p class='c009'>One of the best descriptions of that epidemic was given by -Dr. O. Leichtenstern in Nothnagel’s Encyclopedia of Practical -Medicine. This contribution, among many others, describing the -epidemic of 1889 and 1890 is one of the first to refer to the -Pfeiffer bacillus as being etiologically associated with the disease. -It differs, therefore, greatly from descriptions of previous epidemics. -Leichtenstern says: “The typical influenza consists of -a sudden pyrexia of from one to several days duration, commencing -with a rigor, and accompanied by severe headache, generally -frontal, with the pains in the back and limbs, by prostration -quite out of proportion to other symptoms and marked loss -of appetite.” He continues by saying that to these characteristic -symptoms may be added the catarrhal phenomena arising from -the affection of the respiratory tract, particularly the upper -(coryza) and “occasionally” the lower, the trachea and bronchi. -This description is so in accord with the symptoms of uncomplicated -<span class='pageno' id='Page_37'>37</span>influenza as found in the present epidemic that very little -need be added. Any difference which may occur in the description -of the disease is likely to be accounted for by the peculiarity -of onset, whether in the upper or lower respiratory tract, and by -the different ways of interpreting complications which may have -arisen. It is evident from this description that the upper -respiratory tract was affected more generally than the lower in -the epidemic of 1889 and 1890. In the present epidemic it can -safely be said that the reverse was the usual state of affairs. It -was a rather unusual occurrence when the affection was limited -only to the nose, pharynx, larynx, trachea and larger bronchi. A -very large number, no doubt, had a peculiar œdema, a so-called -“wet lung,” which we shall discuss later; others went on to a -capillary bronchitis or a bronchiolitis, and a large number had -broncho-pneumonia. This sequence we shall attempt to show in -the statistics at hand. In some cases the lesion in the lower -respiratory tract seemed to be primary, there having been no -initial coryza. At least none was observed and no history was -obtained.</p> - -<h3 class='c010'><em>Prodromal Stage and Communicability</em></h3> - -<p class='c011'>The length of the prodromal stage—the stage from the time -of contact to the earliest onset of symptoms—has always led to -interesting observations and discussion. In this epidemic we -have rather definite information bearing upon this subject.</p> - -<p class='c009'>A young married farmer living in a rural community where -no influenza had occurred up to the time of the present experience -went to a city about 40 miles distant. On the train he sat -in the same seat with a man who was apparently ill, and who -was sneezing and coughing. He was in the city only a few hours, -and was not in any place of congregation except the railway -train. Forty-eight hours after his return to his home he noticed -the first symptoms and began a mild course of influenza. About -50 hours later his wife was taken with the same symptoms, and -in two days more their only child was afflicted. Other members -of the household were also afflicted, and one of them died of -pneumonia.</p> - -<p class='c009'>It might be interesting to quote a similar observation made by -Macdonald and Lyth, of York, England, published in a recent -issue of the British Medical Journal (November 2, 1918, p. 488), -which corroborates this experience. They say: “We traveled -<span class='pageno' id='Page_38'>38</span>from London together on Thursday, October 3, by train, leaving -King’s Cross at 5.30 P. M., arriving in York at 9.30, and as we -were leaving the carriage a young flying officer, who had come -the whole way with us and was coughing and sneezing at intervals, -informed us that he was ill and had had influenza for several -days. On Saturday, October 5, we both became ill and had developed -typical attacks of influenza. With both of us the illness -developed suddenly with laryngitis; in both the first signs were a -severe attack of coughing; and in both the time was noted fairly -accurately as being between 2 and 2.30 P. M. One case was quite -mild, the temperature never over 101. The other was more -severe; the temperature arose to 104½ and the catarrh extended -to the bronchi. His wife and two children also developed influenza, -and in their case the symptoms showed suddenly, about -2 P. M., on Monday, October 7. Now we are convinced that we -became infected from our traveling companion during the train -journey—more likely toward the end of the journey; and if we -take the time of infection as 9.30, this fixes the incubation period -for both of us at a minimum of 41 hours, with a maximum -margin of error of 4 hours. The three cases developing in the -family of one of us point to a similar incubation period, as their -illness started almost exactly 48 hours after his, and as it is -likely that the infection would not take place until a few hours -after the first symptom, the incubation period in these three -cases must have been nearly the same as our own two.</p> - -<p class='c009'>“It can be readily understood that we were in no position to -conduct extensive bacteriological examinations, but a culture -taken from the posterior nares of one of us on October 10 with a -guarded swab showed colonies of Pfeiffer’s bacillus and of micrococcus -catarrhalis.”</p> - -<p class='c009'>This observation is so convincing, I have quoted it at length -and in full.</p> - -<p class='c009'>The communicability of influenza has been observed by all, and -the ease with which it passes from one individual to another -noted. One observation made by us was of considerable interest. -In a house where a patient lay sick with a severe attack of -influenza for nearly three weeks several members of the household -passed the door of the sick room a number of times daily, -and yet they did not contract the disease. This is in marked -contrast with the immediate contact between the two physicians -<span class='pageno' id='Page_39'>39</span>and the young flying officer, who sat in the same railway carriage -compartment for four hours. The same observation was made in -the hospital among nurses in direct contact with patients. A -large number of these contracted the disease, while those not -immediately associated with influenza patients almost invariably -escaped. This speaks strongly against the idea that the epidemic -was a so-called “plague,” or that it passed without intermediate -means through the air and pervaded all places.</p> - -<p class='c009'>From information thus far at hand it seems, therefore, that -the prodromal stage, or stage of incubation, is one which covers -about 48 hours, and that it is usually without symptoms unless -it be a peculiar prostration which had been described by some -patients. It would also appear from the experiences just narrated -that it was necessary to be in rather close contact with a -patient, so that there could be an exchange of respired air before -infection could take place.</p> - -<h3 class='c010'><em>Duration of the Disease</em></h3> - -<p class='c011'>In all descriptions of the disease the duration is spoken of as -“several days, more or less,” “a three-day fever,” or “a seven-day -fever.” Because of the careful supervision under which the -soldiers were kept while in the barracks an excellent opportunity -was afforded to note the duration of uncomplicated cases. The -shortest time observed was 1 day, and the longest 10 days. The -average duration of temperature among 87 soldiers without -inflammation of the lungs or other certain complications was -6⅓ days. Among the civilians the shortest time of pyrexia was -a few hours only, while the longest in 73 male patients was 14 -days, and in 84 female patients was 16 days. The average length -of pyrexia in the males was 4⅝ days, and in the females was -5¼ days.</p> - -<p class='c009'>While the very definite clinical description of the former epidemics -of a so-called uncomplicated influenza seems to have -served satisfactorily to the present time, the laboratory studies -and the possibly more thorough clinical observations which have -been carried out recently in this epidemic make it necessary to -present anew the whole disease picture of influenza, with the hope -of suggesting a classification more in accord with our present -knowledge of the disease.</p> - -<div> - <span class='pageno' id='Page_40'>40</span> - <h3 class='c010'><em>Forms and Varieties of Influenza</em></h3> -</div> - -<p class='c011'>A few words as to “forms” or varieties of influenza might be -helpful before suggesting a classification of symptoms. In former -epidemics of influenza considerable importance was attached to -the early manifestations or first symptoms as characterizing the -“form” of influenza which was in evidence in the individual -patient. These were reported as a “respiratory form,” a “nervous -form,” a “gastro-intestinal form,” and other forms—circulatory, -renal, psychic, etc. In the epidemic of 1889 and 1890 particularly -these types were noted, and they have been described in the subsequent -small epidemics, practically characterizing them as being -of one or the other, and frequently as being without any respiratory -symptoms. In the study of our group of cases in the present -epidemic every effort was made to recognize the non-respiratory -cases, but we were unable to find a single case which did not have -definite respiratory symptoms, either early or late, in addition -to any other symptoms present. Only occasionally were nausea, -vomiting and diarrhea or tachycardia, or certain neuroses or -psychoses, the leading symptoms. The respiratory symptoms in -some cases seemed to be at the onset primarily of the lower -respiratory system—that is, without the preliminary coryza. -These usually ran a rapidly fatal course, characterized by marked -cyanosis and confusingly irregular chest signs. We would say, -therefore, in so far as our experience goes in this epidemic, we -are not justified in speaking of any particular forms except the -respiratory form, and whenever pronounced manifestations occurred -justifying a characterization of any other form they could -more easily be interpreted as a complication, or the manifestation -of a coincident disease, or of a severe toxæmia.</p> - -<p class='c009'>The classification of the symptoms, therefore, takes into consideration -largely those symptoms arising from the respiratory -system. We are of the impression that the pathology demonstrated -by Dr. Klotz and described by others justifies the following -classification. Clinically we would recognize two distinct -groups of epidemic cases.</p> - -<p class='c009'>The first includes those <em>without lung involvement</em> having -symptoms arising from the upper respiratory tract, including the -trachea and the larger bronchi. These were practically without -any chest signs except for the rather indefinite signs of an acute -<span class='pageno' id='Page_41'>41</span>bronchitis, and the only symptoms referable to the respiratory -tract were a coryza, soreness of the throat, hoarseness and a -cough of varying degree and character. If to these symptoms -are added those of Leichtenstern just mentioned, one will have a -good description of a so-called simple, uncomplicated influenza.</p> - -<p class='c009'>The second includes those <em>with lung involvement</em> and associated -with physical chest signs, in some indefinite and confusing, -while in others definitely conforming with the existing pathology. -These symptoms and chest signs were those associated at one -time with what appeared to be an acute œdema of the lungs. At -another time the physical signs were those of a bronchiolitis -(capillary bronchitis), or most frequently of a broncho-pneumonia, -of an isolated type or of a massive type. Finally there -were some forms of lobar pneumonia which at times we were -unable to differentiate from a true lobar (croupous) pneumococcic -pneumonia.</p> - -<h3 class='c010'><em>Influenza Without Lung Involvement</em></h3> - -<p class='c011'>Of the group without lung involvement nothing further would -seem necessary to be said in addition to what one finds in standard -text-books describing the disease picture of former epidemics. -The incidence of influenza of this type among our group was as -follows: Of 153 soldiers 93, or about 60 per cent., had a so-called -simple, uncomplicated influenza, and of the 394 civilians 185, or -about 52 per cent., had no lung involvement. There are a few -points in which the symptoms of the present epidemic seem to be -so peculiar that they merit special consideration.</p> - -<h3 class='c010'><em>The Temperature</em></h3> - -<p class='c011'>This can be described as showing a sudden rise to 102–104, at -which point it is maintained for a few days, and subsides by -lysis in a few days more. A typical chart is as follows:</p> - -<div class='figcenter id002'> -<span class='pageno' id='Page_42'>42</span> -<img src='images/i_042a.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>CHART I</p> -</div> -</div> - -<p class='c009'>Or the temperature might fall one or two degrees for a day -or so after the first rise, and then go up again for one or two -more days, and subside by lysis as is shown in Chart II.</p> - -<div class='figcenter id002'> -<img src='images/i_042b.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>CHART II</p> -</div> -</div> - -<p class='c009'>This would occur without our being able to find any lung lesion -unless we accept the acute œdema or wet lung as a complication, -<span class='pageno' id='Page_43'>43</span>and this we were rarely able to recognize by any definite physical -signs in the chest. Cyanosis frequently accompanied this second -rise of temperature, and was later interpreted as being associated -with the so-called wet lung. When the temperature remained up -longer than five days it could safely be concluded that lung involvement -must be present.</p> - -<h3 class='c010'><em>The Pulse and Respirations</em></h3> - -<p class='c011'>The pulse was invariably slow, or rather out of proportion to -the temperature. Even when the patient seemed very ill the -pulse remained from 84 to 96, and of surprisingly good quality. -This was noted also when some of the more severe pulmonary -involvements or some complications arose. The pulse frequently -did not become rapid until shortly before death. The respirations -in an uncomplicated case also remained about normal. The -rate was not accelerated until lung complications arose, and then -a gradually increasing rate was often the first herald of oncoming -danger and a sign of grave prognostic import. The relation of -the pulse phenomena toward the end of a fatal case was most -remarkable. The respiratory rate was accelerated, as has been -noted above, but the pulse rate frequently remained unchanged, -being characteristically slow. In a patient seen in consultation -with Dr. Lester H. Botkin, of Duquesne, Pa., death took place -while we were in the sick room. It was a case of apparently -uncomplicated influenza of seven days’ duration. The respirations -were rapid and the pulse was only 96. In the last five -minutes of life the heart beats as observed with the stethoscope -never varied, until they suddenly ceased; during the same time -the respiratory efforts were only three agonal ones, the last being -a minute or so before the last heart beat. There were no physical -signs of consolidation at any time recognized in this case, but -we feel that the lung, had we seen it at autopsy, would in all -likelihood have shown the peculiar hemorrhagic and œdematous -character so often observed in the fatal cases.</p> - -<p class='c009'>There were, of course, marked exceptions to the description -of slow pulse and later rapid respirations observed. In some the -pulse rate and respirations increased, together with or without -definite signs of a grave complication.</p> - -<div> - <span class='pageno' id='Page_44'>44</span> - <h3 class='c010'><em>Cyanosis</em></h3> -</div> - -<p class='c011'>This was recognized early in the epidemic. It was sometimes -preceded by a peculiar flushing of the face, such as accompanies -belladonna poisoning. It might be noticed in the very first days -of the attack. The cyanosis was looked upon as being a very -early symptom of lung involvement. With our later knowledge -from autopsies, and especially as shown by Dr. Klotz, we feel it -was surely an accompaniment of, or may even have preceded, the -changes in the lung which have been designated as œdematous, -“wet” or cyanotic. At the earliest appearance of the cyanosis we -were frequently unable to find any change in the physical signs -of the chest. Of course, the indefinite signs of an acute bronchitis -were present, and in some cases an additional “impaired -resonance” was noted over one or both lower lobes, but when this -was definitely present other more definite signs soon followed, -and our case was shifted suddenly from Group I, i. e., without -apparent lung involvement, to Group II, i. e., with definite lung -involvement. This cyanosis was noticed first in the face, and -frequently was marked on the dorsal surface of the hands. It -was not unlike the cyanosis which may sometimes be seen when -large doses of certain coal tar derivatives are taken. In fact, the -question arose whether in the epidemic of 1889 and 1890, when -the coal tar derivatives were prescribed with such freedom and -with accompanying cyanosis and apparently such deleterious -effects, the cyanosis may not after all have been due more largely -to the infection than to the medication. After that epidemic it -was said: “Influenza has slain its thousands, but the coal tar -products have slain their tens of thousands.” There was no gross -hæmaturia or hæmoglobinuria present in these cases, although -a few red blood cells were seen microscopically. There was, however, -epistaxis, sometimes early in the disease or later associated -with the cyanosis. In a few cases there was hæmoptysis, which -we regard as always arising in cases where the wet or hemorrhagic -lung was present. Cyanosis in disease of the lungs, and -especially in the terminal stage of lobar pneumonia, is a familiar -and common occurrence, but the cyanosis observed in this epidemic -seemed quite different from the ordinary. The points of -difference were these: (a) it came early in the disease; (b) it -seemed to be more generally present when very little lung involvement -could be demonstrated physically, and was just as likely to -<span class='pageno' id='Page_45'>45</span>disappear when more definite chest signs were demonstrable; -(c) it was not associated with embarrassment of respiration; -(d) it had no relation with a demonstrable circulatory disturbance. -The pulse did not become rapid; the quality of the pulse -did not change; <em>the right heart was not dilated</em>, as is so frequently -the case in the terminal stage of a lobar pneumonia when -cyanosis appears; (e) and finally there was no associated œdema -of the lungs, or at least that œdema of the lungs which occurs -in the later stage of lobar pneumonia, when the pulse becomes -rapid, when there is rapid and labored respiration, when the right -heart dilates, when there is cold perspiration, and when the signs -of impending death are plainly evident. The cyanosis of influenzal -pneumonia seemed to be due to an entirely different -cause or combination of conditions from those present in lobar or -pneumococcic pneumonia. The cyanosis of influenzal pneumonia -was, therefore, most confusing, and became all the more so when -it was recognized that it did not yield to the respiratory and -circulatory stimulants usually employed when cyanosis is present. -The inhalation of oxygen was resorted to rather routinely early -in the epidemic. It seemed to temporarily influence the cyanosis, -but the results were not permanent, and the outcome of the cases -did not seem to be different from those in which oxygen inhalations -were not used.</p> - -<p class='c009'>The blood pressure in those cases in which cyanosis was -observed was invariably low. This seemed to be due to the infection, -for in several private patients not belonging to this group -of patients with previously known high blood pressures the blood -pressure was observed as much lower throughout the course of -the infection.</p> - -<h3 class='c010'><em>Leucopenia</em></h3> - -<p class='c011'>The peculiar behavior of the white blood corpuscles will be discussed -more fully in another paper of this series. Our remarks -will deal more particularly with the clinical observations and -interpretations. The leucocytes fell below the normal from the -very onset of the disease; they varied very little regardless of -great changes in temperature; they did not always increase, or if -they did increase at all it was comparatively little, even in an -extensive invasion of the lungs or in severe complications. Concerning -the leucopenia we have no explanation to suggest, save -<span class='pageno' id='Page_46'>46</span>that it is a clinical characteristic of the disease. Our first thought -was that the infection came on so suddenly and profoundly there -was no time for a leucocyte reaction. But when we recall other -diseases associated with a leucopenia, notably typhoid fever, -which does not come on with such suddenness, our explanation -for the leucopenia of influenza does not seem to hold. The leucopenia -must be simply a peculiar toxic blood reaction characteristic -of the Pfeiffer bacillus invasion. Such an explanation has long -been accepted in the Eberth bacillus infection.</p> - -<h3 class='c010'><em>Asthenia</em></h3> - -<p class='c011'>A condition which was frequently noted by the patient was an -indescribable weakness and prostration which appeared early, -sometimes before any other symptoms were noted or before any -elevation of temperature. The young soldier was in apparent -perfect condition when he arose in the early morning. During -the “setting up” exercises he did not feel so fit, and a few hours -later appeared extremely weak. When his condition was called -to the attention of the medical officers he was found to have a -slight elevation of temperature and was sent to his bed.</p> - -<p class='c009'>In former epidemics, as also in this one, marked prostration -was recognized as coming at the height of the disease and remaining -persistently during convalescence. But it does not seem -to be recorded as among the first symptoms.</p> - -<h3 class='c010'><em>Influenza with Lung Involvement</em></h3> - -<p class='c011'>Of the group with lung involvement much may be written from -a clinical standpoint, and much confusion may be brought about. -Especially is this so if one has no definite idea of the pathology -present, or if one enters into a discussion of the character of the -infection—a point upon which there is as yet no unanimity of -opinion. From the many reports which have been put forth -from the base hospitals of the various cantonments, and also -from the reports coming from civilian practice, it is evident that -scarcely any two groups of laboratory men or any two individuals -of those separate groups have the same idea as to the bacteriology -and the pathology peculiar to this epidemic.</p> - -<p class='c009'>As long as there is this confusion and element of doubt in the -minds of those to whom we are accustomed to look, the clinician -<span class='pageno' id='Page_47'>47</span>must necessarily speak with considerable hesitancy, especially -when he attempts to interpret the physical signs observed. In -our own group the observations of Klotz, Guthrie, Holman and -others have given us an interpretation of our clinical findings -which, at present at least, is more or less satisfactory. We shall -definitely keep in mind their observations and conclusions as we -go on with the description of the physical signs of the chest in -cases having lung involvement.</p> - -<p class='c009'>In the description of this group it will readily be seen that the -lower respiratory tract stood the brunt of the infection. Of the -153 soldiers under our care, 60, or about 40 per cent., were recognized -as having pneumonia. Of these, 34 had undoubted demonstrable -signs, while 26 were questionable, and yet from the temperature -and other symptoms we concluded there was a pneumonia. -Of the 394 civilians, 189, or about 50 per cent., had -pneumonia. Of this group there were again some 28 or 30 in -which the diagnosis was doubtful, according to the ordinary way -of making a diagnosis, but we felt sure from the temperature -course that more than a simple influenza was present. In the -description of the physical findings of the chest in these influenzas -with lung involvement it will be readily seen why the -diagnosis must sometimes be in doubt.</p> - -<p class='c009'>Before referring to the physical signs it might be well to -describe the condition and general appearance of the patient -when the lungs became involved. The patient who had been -progressing with an apparently simple influenza, with no chest -signs except those of bronchitis or tracheitis, occasionally slightly -cyanotic, became more cyanotic, the elevation of temperature -continued longer than three to seven days, or if it came to the -normal began to rise again, his respirations gradually increased -and the pain in the chest became well localized. One could safely -assume that the patient had developed a lesion in the chest. This -could not always be localized during the first few hours or on the -first day. The evidence of increased bronchial disturbance was -frequently recognized, and later impairment of resonance and -diminished breath sounds associated with “a few crackles” were -noted. This, so far as we can tell, may have been the only evidence -of the stage of œdema or “wet lung.” After this, as the -disease advanced, definitely increased vocal fremitus and rather -definite tubular breathing with greater impairment of resonance -<span class='pageno' id='Page_48'>48</span>were noticed. These signs were usually observed first at the apex -of the left lower lobe, and from here they extended forward along -the inter-lobar sulcus, or downward along the spinal column. If -the lesion was noticed first on the left side, in a day or two it was -found more or less definitely in the right lower lobe also. It -seemed to occur more frequently first in the body of the right -lobe, instead of in the apex of the lobe as on the left side. In both -lobes it might spread to contiguous areas and form a massive -consolidation, or it might be found in small separate areas, some -of which would clear up in a day, while others would persist.</p> - -<p class='c009'>The expectoration was frothy, containing either blood or -masses of yellowish, greenish purulent material floating in a -watery sanguiolent or clear fluid, or enmeshed in frothy mucus. -The amount of expectoration in some cases was enormous, but -as a rule it was scanty. It was thick and ropy at times and distinctly -annoying to the patient.</p> - -<p class='c009'>At this stage the physical signs were very much in accord with -those of broncho-pneumonia. In a few hours sometimes, or in a -day, the small areas of consolidation became confluent and massive -consolidation was formed. It appeared as though the whole -lobe would in time become solid, as in a true lobar pneumonia. Or -the original areas may apparently have cleared and other areas -involved, became the centers of massive consolidations. In many -cases both lower lobes were thus similarly affected, and one had -the physical signs of a double lobar pneumonia. However, nearly -always a small angle of the lobe remained clear, thus differing -from the entire lobe involvement characteristic of a true croupous -pneumonia. Other signs, such as the absence of vesicular breathing -and presence of the crepitant râle, moist râles of all sizes to -very coarse râles, could be noted. As in certain stages of a complete -consolidation, the lung might be dry; no râles present, but -definite tubular breathing present. This in a day or two, or after -a longer time, might give the signs of resolution. The stage of -resolution, however, was almost invariably prolonged, sometimes -extending over weeks. With these variable lung signs were often -mingled the signs of a fibrinous or serofibrinous pleurisy, which -occasionally but remarkably infrequently went on to effusion or -empyæma.</p> - -<div class='nf-center-c0'> - <div class='nf-center'> - <div>[Click on any image for larger version]</div> - </div> -</div> - -<div class='figcenter id003'> -<a href='images/i_048a_full.jpg'><img src='images/i_048a.jpg' alt='' class='ig001' /></a> -</div> - -<div class='figcenter id003'> -<a href='images/i_048b_full.jpg'><img src='images/i_048b.jpg' alt='' class='ig001' /></a> -</div> - -<div class='figcenter id003'> -<a href='images/i_048c_full.jpg'><img src='images/i_048c.jpg' alt='' class='ig001' /></a> -</div> - -<p class='c009'><span class='pageno' id='Page_49'>49</span>As stated above, the demonstrable pathology was in the lower -lobe, and more frequently in the left than in the right, only occasionally -in the middle lobe, and never, we might say, in the upper -lobes. The very earliest definite signs were found at the apex of -the left lower lobe.</p> - -<p class='c009'>This observation seems to be entirely contradictory to that of -the pathologist, who found in 65 per cent. of all cases coming to -autopsy a lesion in all the lobes of the lungs (Klotz). The only -explanation we can give which seems at all satisfactory to us is -that the pathology in the upper and middle lobes must not have -been sufficient, or must have been of such a nature that it did not -yield the physical signs, i. e., definite impaired percussion resonance, -increased vocal fremitus and tubular breathing, with varying -shades of moist râles—signs upon which we insisted before -we were willing to state definitely that there is a demonstrable -pneumonia present.</p> - -<p class='c009'>In this description it has been attempted to follow the order of -invasion in a lung which seemed to go through the entire course -of the disease. There were, necessarily, all degrees of the -process, some cases showing few signs and yet being remarkably -ill, and others all of the signs with very little other evidence of -serious illness.</p> - -<p class='c009'>We were continually impressed with the notion that the -pathology in the lung, at least the pathology demonstrable -physically, did not tell the whole story of the case, and that the -outcome depended as much or possibly more upon a general -infection or toxæmia of which the recognized condition in the -respiratory system was only a small part. We were particularly -impressed with this in the success or failure following the application -of any therapeutic measures. It was quite a common -remark, therefore, in the wards of the hospital among those associated -in the work that “the patient died too quickly to permit -of the succession of the various stages of pneumonia”; or, in the -autopsy room, that if the patient had lived long enough he would -have had demonstrable, well-recognized pathology of the lung, -instead of the cyanotic, wet, spongy lung which was found.</p> - -<p class='c009'>The temperature course in the pulmonary cases was characterized -by its irregularities, and by its being entirely out of harmony -with the extent and severity of the lung invasion in so far as it -could be interpreted by the physical signs. The temperature as -described in a simple influenza might not come to the normal in -the time of three to seven days, and might even go higher, with -<span class='pageno' id='Page_50'>50</span>no demonstrable chest signs, but with every other evidence of -lung involvement. Later the temperature might come down by -lysis, which was the usual way, and the chest signs gradually -or suddenly become evident. The temperature might remain -normal throughout the rest of the course, and a lobe or even -both lower lobes of the lungs be as solid as in a true lobar -pneumonia. Occasionally the temperature fell by crisis, but there -was no associated change in the physical signs of the chest. In -short, the temperature seemed to run a course entirely independent -of the physical signs in the chest. In two remarkable -cases seen in consultation on two consecutive days the physicians -in charge declared that no signs of consolidation could be found, -though all other evidences of pneumonia were present. In the -12 hours which had elapsed from the time the last examination -was made the temperature fell by crisis. At the consultation, -to the surprise of the family physicians, we found both lower -lobes consolidated, it having occurred apparently with the crisis. -Both patients were healthy-looking, robust, young men, and both -recovered with delayed resolution. In the convalescence of such -cases, if the patient got up too soon or if any other indiscretion -took place, a relighting of the lung occurred. From the above -description it can be readily seen that a diagnosis of the conditions -in the chest in influenzal pneumonia was frequently impossible, -because one had to abandon all his previous ideas of pneumonia, -in so far as onset, crisis, blood picture, sputum, temperature, -respiratory and circulatory phenomena, physical signs and -prognosis were concerned.</p> - -<p class='c009'>Assistance from the laboratory was meager, especially in the -early days of the epidemic. This was due largely to the inability -to get laboratory workers in sufficient numbers to follow the -work through, but more largely to the fact that we were unable -to interpret the unusual laboratory results which were available. -When we were once fully aware of the difficulties in diagnosis -which confronted us, we utilized every practical means at our -disposal. Among these was an examination of the chest with -the X-ray. On account of lack of facilities and of help, it was -impossible to make routine X-ray examinations of the chest in -all cases. Besides, it was difficult to interpret the X-ray findings, -on account of the unusual character of the lesions. Also, many -of the patients were so desperately ill one hesitated to disturb -<span class='pageno' id='Page_51'>51</span>them. We hear that other clinics had similar experiences, and -that very little substantial help came from the X-ray, except in -cases with complications. Several attempts were made to determine -the kind of shadow, if any, the “cyanotic, œdematous, -wet” lung would make, but no satisfactory observations have -been forthcoming. From our own observations and from the discussions -of other observers, it would seem to us that the stereoscopic -examination of these chests is the only possible way of -getting satisfactory plate readings in these cases where the -pathology seems so lawless in its extent and peculiar in its distribution. -This method of examination, however, demands facilities -convenient at the bedside and perfect co-operation of the -patient—difficult conditions to meet under the circumstances. In -the acute cases, when the desire to make a diagnosis not only of -the presence but of the extent of the disease was keen, X-ray -examination was largely impractical. In cases of delayed resolution, -or in cases with complications with prolonged convalescence, -X-ray examinations were extremely helpful.</p> - -<h3 class='c010'><em>Diagnosis of Influenzal Pneumonia</em></h3> - -<p class='c011'>In the consideration of any disease the well-trodden path of a -painstaking history, a thorough physical examination, and reliable -laboratory investigation, together with an intelligent interpretation, -will usually lead to a definite diagnosis. In certain -diseases, as is well known, the stress must be placed about equally -on all of these factors, while in others one or other factor predominates. -In influenzal pneumonia, until more is known of the -etiology (bacteriology) and of the pathological changes and of -the physiological disturbances, the controlling factor in the -diagnosis (we feel embarrassed to admit) must be the history. -This is true not only of the diagnosis of influenza with or without -pulmonary involvement, but is also true of the diagnosis of the -various complications, and will be found to be particularly true -in the recognition of the bizarre sequelæ, which no doubt in the -succeeding months or years will be attributed to or will follow in -the train of influenza.</p> - -<p class='c009'>With the knowledge that there is a prevailing epidemic of -influenza and that the manifestations are largely in the respiratory -tract, any pulmonary disturbance will necessarily make one -<span class='pageno' id='Page_52'>52</span>suspicious of the presence or the oncoming of an influenzal pneumonia -in the patient under consideration. The history of the -onset, as of simple influenza, is the greatest factor. This with a -continued temperature, cough, cyanosis, slow pulse, continued -asthenia, or even an unusual leucopenia, may have a greater -weight in determining the diagnosis of lung involvement than -will the apparently definite or, as it may happen, the confusing -chest signs. To differentiate from ordinary bronchitis, broncho-pneumonia -and catarrhal pneumonia, one need only refer additionally -to the severity and persistency of the disease when it is -of the influenzal type, as compared with the mildness of the -ordinary type. To differentiate it from croupous pneumonia, one -need only compare the confusing symptom picture of the influenzal -pneumonia with the definite, clear picture of ordinary -pneumonia; or the confusing kaleidoscopic chest signs of the one -with the definite, clear-cut signs of the other. The laboratory -thus far has been the smallest factor in making the diagnosis, -in that sputum examinations, blood examinations, blood cultures -and urine examinations are mostly negative in their results, or -at least the findings are not specific. We do not, however, mean -to indicate that these tests are not of the greatest value. The -leucopenia is the one outstanding feature which seems to have -separated this infection from other acute lung infections, excepting -miliary tuberculosis. The differentiation of influenzal pneumonia -from an acute tuberculous process in the lung may be -difficult, especially if there is no reliable history available. However, -the fact that pulmonary tuberculosis usually begins at the -apices of the lungs and influenzal pneumonia at the bases or at the -apices of the lower lobes is quite helpful. Of course, the examination -of the sputum for tubercle bacilli will be a deciding factor.</p> - -<p class='c009'>The differentiation between influenzal pneumonia and diseases -of the pleura is one which practically rarely needs to be made, -for there seem to be very few cases of influenzal infection of the -lungs in which the pleura is not also involved to a greater or -lesser extent.</p> - -<h3 class='c010'><em>Complications</em></h3> - -<p class='c011'>In considering the complications of influenza one again comes -up squarely against the question: What is influenza and what is -the specific micro-organism responsible for it? If the Pfeiffer -<span class='pageno' id='Page_53'>53</span>bacillus is the specific cause, what pathology can be attributed -to it? It has been an almost universal observation that the lesions -in the lungs and pleura which characterized the group of cases -with lung involvement rarely yielded a pure culture of the Pfeiffer -bacillus, and that secondly in a large percentage of cases the -Pfeiffer bacillus apparently was absent, and that other micro-organisms, -such as the pneumococcus, streptococcus, micro-organisms -commonly found in the pneumonic processes, were -present and predominated. The question arises, therefore, may -not all the influenzas with lung involvement be <em>complications</em> of -influenza? It is our feeling that Pfeiffer bacillus is present -throughout the respiratory tract in all cases, and while it may -of itself produce a lesion like a broncho-pneumonia or a lobar -pneumonia, it chiefly prepares the soil for other germs which may -happen to be present, and which are more commonly found in the -pneumonias. We, therefore, look upon the lesion commonly found -in the lung as being a part of rather than a complication of influenza, -and look upon lesions elsewhere, due to the influenzal or -other micro-organisms, as a definite complication.</p> - -<p class='c009'>There is no doubt that the most frequent complication of -influenza, especially in the present epidemic, is in connection -with the pleural membranes. When one recalls that pneumonia -rarely occurs without there being also a pleuritis, and also when -one recognizes that in an influenzal infection of the lungs the -specific micro-organism, together with any other micro-organism -which may happen to be present, seems to run riot, apparently -abandoning its usual mode of invasion, it can be readily understood -why this complication is so frequent and so varied. The -pleurisy was usually of the fibrinous type, and rarely was accompanied -with demonstrable fluid. Of the 153 soldiers in only 3 -was fluid detected in the chest, and of the 394 civilians only 10 -showed fluid. In many more cases fluid was suspected, but X-ray -examinations and free needling of the chest showed that we had -misinterpreted the physical signs.</p> - -<p class='c009'>After our experience in the epidemic of pneumonia in the spring -of 1918, when the disease was also so prevalent in the cantonments, -we of course expected to see many cases of empyæma -and lung abscess in the present epidemic. In this we were agreeably -disappointed. Only one case of empyæma and only one case -with abscess of the lung were found up to the time of collecting -<span class='pageno' id='Page_54'>54</span>our data and the compiling of our statistics. Both of these were -among the civilians. From our experience since the compiling of -our statistics, we are inclined to believe that this low incidence -of empyæma may not altogether represent the real state of -affairs, as we have since received in the hospital several cases -of empyæma, as well as of abscess of the lung, which seemed to -have followed an influenzal infection which had occurred three or -four months previously. One of these cases was a particularly -remarkable one, in that the patient had already been admitted to -the hospital twice since his initial attack of influenza in October -for suspected pleurisy with effusion. We were unable to find any -fluid with the needle, though we felt certain of having demonstrated -it a number of times physically and with the X-ray. About -eight weeks after the second admission, however, pus was found -after several needlings in the left chest, axillary space, apparently -along the inter-lobar sulcus. This case was a good example -of many we have seen in which a pneumonia, or possibly, as we -see it now, a pleurisy, or even a localized empyæma, seemed to -confine itself about the sulcus or fissure between the upper and -lower lobes of the lung. Frequently the process began posteriorly, -apparently at the apex of the lower lobe, and traveled -forward and downward across the axillary space until it appeared -in the anterior part of the chest. In most cases we interpreted -our signs as those of a consolidated lung, and scarcely knew -whether the consolidation was in the upper part of the lower lobe -or in the lower part of the upper, or in both. In some cases we -suspected a localized empyæma or an abscess in the sulcus, but in -none did we find pus after exploring with the needle until this -recent case occurred. The passage of the needle in this case, -which was done several times before pus was found, always gave -the impression that it was going through dense fibrous tissue -for some distance before the abscess was finally found. From -this experience, and from the extensive and irregular invasion of -the pleura which we have seen demonstrated at autopsies, there -can be no doubt that the clinical history of the complications of -influenza in this epidemic is not a closed chapter.</p> - -<p class='c009'>In six patients there was a purulent inflammation of the -pharynx, larynx and trachea. It was extensive and produced -profound general symptoms, dyspnœa and profuse purulent expectoration. -The lungs were clear, but the patient seemed for -<span class='pageno' id='Page_55'>55</span>a time in danger of death. The condition was considered a grave -complication. There was only one case of acute sinusitis, one case -of antrum disease, and only four cases of middle ear infection were -recognized. This is in marked contrast to other epidemics which -have occurred to our knowledge in the past fifteen years or more, -and which have been spoken of as influenza or “grippe.” Disease -of the tonsils, middle ear disease, mastoid disease and sinus disease -occurred with great frequency in those sporadic epidemics. -This again seems to show that the deep respiratory tract was -more generally and more severely affected in this epidemic than -the upper respiratory tract.</p> - -<p class='c009'>With the exception of the pleura, the serous membranes were -remarkably free from infection. Only one case of acute endocarditis, -three cases of meningitis (all pneumococcic), none of -pericarditis, peritonitis or arthritis were recognized among the -547 cases of influenza.</p> - -<p class='c009'>The kidneys did not seem to be involved in the infection. Albumen -was present in the urine, as might be expected in febrile -conditions, but no evidence of acute clinical nephritis, such as -suppression of urine, general œdema or uræmia, was recognized. -The condition of the urine in this epidemic will be described more -in detail in another paper of this series.</p> - -<p class='c009'>A peculiar pathological process in the muscles was brought to -our attention by Dr. Klotz, who demonstrated a myositis or -hyaline degeneration of the lower end of the recti abdominalis. -This lesion is carefully described in the pathological section. -After our attention had been called to this lesion we recognized -several cases clinically having the same condition. One was in -the right sterno-cleido-mastoid muscle and another was in the -left ilio-psoas muscle. This last patient while he was convalescing -developed a severe pain in the left hip, extending upward -into the lumbar region and downward into the thigh. His decubitus -was like that of one suffering with psoas abscess. Every -test available was made to confirm this diagnosis, but all the -findings were negative. The patient rested in the hospital, in bed, -for some time, gradually improved, and eventually made a complete -recovery.</p> - -<p class='c009'>In several cases we also detected an osteitis, especially of the -bodies of the vertebræ. One was of the cervical vertebræ and -the other of the dorsal. The first died after intense suffering. -<span class='pageno' id='Page_56'>56</span>An autopsy was not obtained. The other had a plaster cast -applied as in Pott’s disease, and improved sufficiently to leave the -hospital in comfort. One hesitates under the circumstances to -attribute these bone lesions definitely to the same infecting -micro-organism which was responsible for the epidemic of influenza, -as it might easily have happened that a coincident quiescent -tuberculous lesion was present and relighted during the -epidemic. However, in one case from the service of Dr. J. O. -Wallace the possibility of the bone lesions being due to the -Pfeiffer bacillus was demonstrated. This was a child of 16 -months with an epiphysitis of the upper end of the tibia. The -inflamed area was incised and pus was found. A smear at the -time showed the B. influenzæ, which was grown in pure culture.</p> - -<p class='c009'>A most interesting complication noted in a few of our cases -was a transient glycosuria. The first case brought to our attention -was a middle-aged female, who complained of failure of -vision. Upon making an ophthalmoscopic examination a papillitis -of a mild type was noticed. This led to a careful study of -the urine, and sugar was found in a small amount for a short -period of three days, although the glycosuria readily disappeared -by cutting down the carbohydrate intake, the vision came back -to normal more slowly. In fact, it was almost one month before -the symptoms and signs of the retinal change had entirely disappeared. -It is interesting in this connection to recall similar -cases referred to in Allbutt’s System of Medicine, vol. vi, on -influenza, following the epidemic of 1890 in England. Other -transient glycosurias showed no visual changes. We do not consider -these to be true cases of diabetes mellitus. In all a transient -hyperglycæmia was also noted.</p> - -<h3 class='c010'><em>Pregnancy</em></h3> - -<p class='c011'>A condition which can scarcely be considered as a complication -of influenza, but which, however, was a large factor in increasing -the mortality among women, was pregnancy. Among the cases -included in this study were five pregnant women, who came to -the hospital and were referred to the medical service. As soon -as a complication relative to the existing pregnancy arose they -were referred to the Obstetrical Department. On account of the -<span class='pageno' id='Page_57'>57</span>great amount of work in caring for the influenzal patients, and -on account of the scarcity of physicians and nurses, we were -unable to follow these cases closely enough to give any such -definite data as we wish. Three miscarried or went into premature -labor. Happily only one of them died. The two which did -not miscarry recovered and left the hospital well.</p> - -<p class='c009'>We very soon recognized in consultation with the obstetricians -that the pregnant woman was in a really dangerous condition -if she contracted influenza. She was likely to have a termination -of her pregnancy in the height of the infection, no matter -how recent or how remote pregnancy had taken place. If pregnancy -did not terminate, the chances of recovery were less than -those of the non-pregnant woman; if it did terminate, the -chances for recovery were still less. To the pregnant woman -with pneumonia very little hope of recovery could be offered. I -am indebted to Dr. Paul Titus, of the Obstetrical Department of -the School of Medicine, University of Pittsburgh, for a report -which includes the cases seen by himself and his assistant, Dr. -J. M. Jamison, during this epidemic. Dr. Titus was kind enough -to include in his report certain conclusions which merit consideration. -The report is as follows: “A series of 50 cases, at -all stages of gestation. Interruption of pregnancy occurred in -21, or 42 per cent., of the cases; 29, or 58 per cent., in which -pregnancy was uninterrupted. Mortality of pregnant women -developing epidemic influenza is higher than that of ordinary -individuals, even though their pregnancy is undisturbed, since -14 of the 29 in whom pregnancy was not interrupted died, an -incidence of 48<span class='fraction'>2<br /><span class='vincula'>10</span></span> per cent. If a pregnant woman miscarries or -falls into labor, the mortality increases to 80<span class='fraction'>9<br /><span class='vincula'>10</span></span> per cent. (17 of -the 21 in whom pregnancy was interrupted died). The period -of gestation has less influence on the outcome than the interruption -itself. Of 10 at term, 3 lived and 7 died after delivery.</p> - -<p class='c009'>“Two main features of this condition as a complication of pregnancy -are: First, pregnant women developing epidemic influenza -are liable to an interruption of their pregnancy (42 per cent. -aborted, miscarried or fell into labor); second, the prognosis, -which is already grave on account of the existence of pregnancy, -becomes more grave if interruption of pregnancy occurs.</p> - -<p class='c009'><span class='pageno' id='Page_58'>58</span>“The cause of the frequency of interruption of pregnancy is -probably a combination of factors: (1) The theory of Brown-Sequard -that a lowering of the carbon-dioxid content of the blood -causes strong uterine contractions sufficient to induce labor. -(2) The toxæmia causes the death of the fœtus, particularly if -not mature, when it acts as a foreign body and is extruded (10 -premature fœtuses were born dead, while 1 was born alive, -although 9 out of 10 at full term were born alive and survived).</p> - -<p class='c009'>“The cause of the frequency of death following interruption of -pregnancy is also due in all probability to a combination of -factors: (1) Shock incident to labor. (2) Increase from muscular -labor of carbon-dioxid in blood already overloaded by the deficiency -of the diseased respiratory organs. (3) Sudden lowering -of intra-abdominal pressure by the delivery. (4) Lowering of -blood pressure by the hemorrhage of the delivery. (5) Strain of -labor on an already impaired myocardium.”</p> - -<p class='c009'>If one had been told a year ago that an epidemic could occur -which would result in the death of 60 per cent. of all pregnant -women affected, it would have been thought too unlikely to warrant -any consideration. Though the effect upon pregnancy of -the acute infectious diseases forms an important chapter in the -pathology of pregnancy, it seems that the profession, and in this -the obstetrician is no exception, has never realized how pernicious -and tragic the results of an influenzal epidemic can be in a community. -From the experience in previous epidemics we cannot -but feel that the infection in the present epidemic was unusually -fatal. Whitridge Williams (“Text-book of Obstetrics”) speaks -of the interruption of pregnancy as having occurred in 6 out of -7 cases with one observer, and in 16 out of 21 in another, while -a third has found it only twice in 41 cases. However, none of -these writers speaks of having had a death.</p> - -<h3 class='c010'><em>Sequelæ</em></h3> - -<p class='c011'>In referring to some of the associated conditions of influenza -one scarcely knows whether to consider them as complications -or sequelæ. The pathological process certainly had its origin -from the influenzal attack, but at times apparently assumed an -inactive stage. The patient is usually free from any specific -influenzal symptoms, but retains for a long time other symptoms -<span class='pageno' id='Page_59'>59</span>referable to various organs, or he may have been normal for a -shorter or a longer period and then suddenly develop symptoms -apparently independent of the previous infection. It may be well -to consider all such conditions which followed the febrile attack, -whether immediately or more remotely, as sequelæ, and I shall -therefore speak of them as such.</p> - -<p class='c009'>The first and probably the most interesting and confusing are -the conditions found in the lungs following influenza. A chronic -bronchitis, an old bronchiectasis, or a previous tuberculous lesion -in whatsoever stage, may present acute symptoms and signs -which are difficult to interpret. The question always arises in -the individual case—is this a process due to the recent influenzal -attack, or was it there before the attack? Is it of streptococcic, -pneumococcic, or tuberculous origin? The history of previous -diseases of the lungs may help to arrive at a diagnosis. The history -of the severity of the influenzal attack is of very little help, -because the apparently mildest attack may be followed by the -most profound changes in the lungs, and the gravest attack with -a history of definite lung infection may leave the lungs without -a trace of the previous pathology. The physical examination is -helpful, of course, in determining whether the lesion is at the -apices or at the bases, and from this a reasonably safe inference -may be drawn as to whether it is from a previous tuberculous -lesion or a recent influenzal infection. The Roentgenologist depends -almost entirely upon this localization. If the linear striæ -are only at the apex, it is probably tuberculous; but if they are -only at the base, or also at the base, it is likely to be an influenzal -lung. In fact, the Roentgenologist with his present information -is ready to admit that it is most difficult to speak definitely of -the lungs in these cases. The possibility of confusing the post-influenzal -lung with a tuberculous lesion is not peculiar to this -epidemic. After the epidemic of 1889 and 1890 the same condition -was observed by clinicians. Dr. Roland G. Curtin, of Philadelphia, -in 1892 and 1893 conducted a series of clinics at the -Philadelphia Hospital, in which he spoke of the “non-bacillary -form of phthisis,” and showed case after case which he said -might be diagnosed as pulmonary tuberculosis, but because of -the recent epidemic and the absence of the tubercle bacillus he -diagnosed them as post-influenzal lung.</p> - -<p class='c009'><span class='pageno' id='Page_60'>60</span>In the present stage of our knowledge, many of these post-influenzal -lungs will not be diagnosed properly until sufficient -time is given for either the lung to clear up or the tubercle bacillus -to appear in the sputum. We would emphasize the importance -at the present time of finding the tubercle bacillus in all -suspicious lung lesions before giving a positive opinion as to the -tuberculous nature, even though the physical signs are very -definite.</p> - -<p class='c009'>Another group of sequelæ is that due to thyroid disturbance, -or disturbance of the endocrin system in general. Since the epidemic -a number of patients have been seen who noticed an -enlargement of a previously normal thyroid gland or greater -enlargement of a previously hypertrophied gland. In the same -way the symptoms of hyperthyroidism appeared, new in some -or a recrudescence in others.</p> - -<p class='c009'>In some of these there was a disturbance of carbohydrate -metabolism, as shown by an occasional glycosuria and an increase -in the blood sugar, or by a possible disturbance of the suprarenals, -as brought out by the administration of adrenalin hypodermatically -(Goetsch test). In the application of this test in -post-influenzal patients it appeared that the whole endocrin system -was in a state of imbalance.</p> - -<p class='c009'>It appears to us not at all improbable that the so-called psychoneuroses -of which fatigue, nervousness, irritability and tachycardia -play such an important part might also be explained in the -same way. These constitute a group of sequelæ which were frequently -recognized after previous epidemics, and which are again -coming to the foreground.</p> - -<p class='c009'>We are of the opinion, on account of the apparent absence of -any specific pathology of the gastro-intestinal tract and its -appendages during the attack of influenza, that the sequelæ -referred to the digestive system are largely due to exacerbations -of previous physiological disturbances or pathological processes. -The patient with a previous peptic ulcer has a recurrence of his -ulcer. The patient with an infection of the biliary tract has an -acute exacerbation, or may have an attack of biliary colic. In -fact, there seem to have been many more cases of this kind since -the epidemic than before, and most of the patients date the time -of the onset from a period soon after recovering from influenza.</p> - -<p class='c009'><span class='pageno' id='Page_61'>61</span>Very few, if any, patients in our experience have exhibited -sequelæ due to disease of the cardio-vascular or genito-urinary -systems. It may be that these will appear later when the more -remote effects of an acute infection are recorded.</p> - -<p class='c009'>A very commonplace sequel, but of more or less interest, is the -tendency to furunculosis. Our attention was particularly called -to the associated hyperglycæmia. The blood sugar readings varied -from 0.2 to 0.41. There was no glycosuria, acetone or diacetic -acid. We have no explanation to offer for this, although one -might dilate readily on many attractive theories. The hyperglycæmia, -one may add, was readily reduced by a lowered carbohydrate -intake, which also had a curative action on the furunculosis.</p> - -<p class='c009'>Finally we would mention the peculiar epidemic which has -been observed apparently over the world, encephalitis lethargica. -We do not for a moment put ourselves on record as regarding this -disease as a post-influenzal affair, but no one will deny that it has -a peculiar time relation to the epidemic; and further, that its distribution -is apparently identical. Its bacteriology seems to be -unknown. Its local pathology in the mid-brain is not peculiar or -at variance with encephalitis produced by known organisms. We -have seen five cases; three of whom had had undoubted influenza, -while the other two were entirely free from even the slightest -suggestion of any type of illness previous to the attack. All of -these cases recovered. It has been stated that following the 1890 -epidemic a clinical condition was observed in Europe which bears -a close resemblance to what has been termed at the present time -encephalitis lethargica.</p> - -<h3 class='c010'><em>Prognosis and Mortality of Influenza</em></h3> - -<p class='c011'>In giving a prognosis of influenza one has to take into consideration -the peculiar manifestations of the disease, especially -the possible and sudden changes which are liable to take place -in the lungs. The points which lead one to feel that the outlook -is grave occur in about the following order, which is also about -the order of the severity of the symptoms. First, <em>cyanosis</em>. -This usually appeared quite early and was considered a forerunner -of definite lung infection. It may have been a symptom -only of the “wet lung,” to which reference has been made, but -it was usually followed with definitely recognized pathology in -<span class='pageno' id='Page_62'>62</span>the chest, and it immediately made the outlook unfavorable. -Second, <em>continuation of elevated temperature</em>. If the temperature -fell to normal in three or four days, the outlook was, of -course, good; but if it went up again, or if the temperature did -not fall in that time, the chances were that there was a lung -involvement, even though the chest signs were negative or only -those of an acute bronchitis. Strange to say, however, when -definite chest signs were once recognized, the height of the temperature -or the continuation of fever was not so important a -prognostic factor. Third, <em>increase in pulse rate</em>. The pulse, as -was noted before, was unusually slow, even though the patient -seemed desperately ill; when, however, it began to increase in -rate the condition was usually very grave. Fourth, <em>the extent -of lung involvement</em>. This was of very little prognostic value. -Both lower lobes might be solid, and yet if there was no cyanosis -and the pulse and respirations were satisfactory, the outlook -was rather good. On the other hand, there might be the slightest -involvement of the lung, and if the pulse were rapid and cyanosis -present the outlook was grave. Fifth, <em>depression and stupor</em>, or -loss of so-called “morale.” If the patient remained clear in his -mind, bright and hopeful, no difference how extensive the involvement -or how grave the symptoms, the prospect of recovery was -better. This is, of course, not peculiar to influenza, but it seemed -particularly striking during the epidemic. Sixth, <em>a gradually -rising rate in respiration</em>, which often was not more than two per -minute per day, if progressive, even in the absence of other -untoward signs, conveyed a serious prognosis.</p> - -<p class='c009'>Our mortality among the civilians in comparison with the soldiers -was exceedingly high. The first cases seen by us were -among the soldier patients sent to the hospital. These were as -fine a lot of healthy young men as one can well imagine. They -came to the hospital comparatively early in the infection. After -the first week it appeared as though our experience would be -entirely different from those in other localities, for we had very -few deaths. In another week our mortality began to rise, but -never as high as among the civilians, as will be seen by the -following figures.</p> - -<p class='c009'>Of the 153 soldiers 87 were without lung involvement, and of -these none died; 66 had lung involvement, and of these 16 died. -Mortality among the 153 was 10 per cent. Of the 394 civilians -<span class='pageno' id='Page_63'>63</span>157 were without lung involvement, and of these 1 died; 237 had -lung involvement, or some other complication, and of these 93 -died. Mortality among the 394 was 23.6 per cent.</p> - -<p class='c009'>It will be seen that the mortality in the civilians was more than -twice as high as in the soldiers. It has already been mentioned -that the soldiers were ordered to the hospital promptly. The -civilian patients, on the other hand, were later in coming to the -hospital, some of them appearing when they had already developed -serious complications. Another factor in determining the -mortality were the ages of the patients. The soldiers ranged from -18 to 34 years, with an average of 20 years. The civilians -ranged from 6 months to 73 years, with an average of 30 years. -Generally speaking, the greater the age the higher was the mortality.</p> - -<p class='c009'>A third factor which should be considered in determining the -actual mortality is the result of later complications and sequelæ. -The figures as given are those of 547 patients, 110 of whom had -died in the Mercy Hospital and 437 of whom had been discharged -therefrom between September 22 and November 30, 1918, the -length of the quarantine. Those who were discharged had been -up and about for a week or 10 days before leaving the hospital. -From our experience with post-influenzal patients admitted to the -Mercy Hospital since November 30, we are of the opinion that -some of the patients discharged before November 30 as recovered -may have later developed sequelæ which might have proved fatal. -No follow-up system has been pursued as yet which enables us -to speak definitely and statistically of the present condition of -those discharged.</p> - -<p class='c009'>This compilation does not readily lend itself to drawing any -more specific conclusions, but we cannot desist from expressing -our opinion that in the clinical study of this recent epidemic we -find very little that may not have been observed by clinicians in -previous epidemics.</p> - -<div class='chapter'> - <span class='pageno' id='Page_65'>65</span> - <h2 class='c005'>THE URINE AND BLOOD IN EPIDEMIC INFLUENZA</h2> -</div> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>By <span class='sc'>Peter I. Zeedick, M. D.</span></div> - </div> -</div> - -<p class='c008'>Epidemic influenza, unlike other acute infectious processes as -diphtheria and scarlet fever, seemingly attacks the kidney in a -rather mild manner. This statement refers only to the uncomplicated -cases, as other bacterial or toxic agents do play a part -in the nephritides occurring so often with the pneumonias or -other complications following influenza. It is, however, true that -in many simple epidemic cases there is evidence of a transient -mild nephritis, or possibly, more correctly stated, a nephrosis. -Some writers observed albuminuria in 80 per cent. of the cases, -while the incidence in other reports varies from 4 to 66 per cent. -It is not always stated with reference to these figures that the -patients clinically were free from the common complication—pneumonia. -The findings of various observers differ greatly, -but they all agree that acute nephritis as a serious sequel is -somewhat rare.</p> - -<p class='c009'>In the literature of the past epidemics general acknowledgment -has been accorded to the presence of albumin in the urine -during the acute stage of the disease. Many times this has -received no further notice or comment than “febrile albuminuria.” -The association of occasional hyaline and granular casts has also -been mentioned. One is impressed with the fact that the older -observers laid but little emphasis on the urinary findings. It -also seems to be true that nephritis as a clinical entity is not -prone to follow the epidemics. In general, our conclusions from -the last epidemic are about the same.</p> - -<p class='c009'>The data for this paper was obtained from examination of 994 -specimens of urine from 750 patients; of this number 517 specimens -were examined at the Magee Hospital, where members of -the S. A. T. C., all young men, were treated, and 447 specimens -from the Mercy Hospital, where, in addition to the S. A. T. C., -we had men, women and children. On account of the large -<span class='pageno' id='Page_66'>66</span>amount of material and work on hand, as a rule only one specimen -of urine was examined from each patient, but where complications -were suspected repeated daily examinations were made. -We have grouped our results in tables, so that the various points -may be more readily followed.</p> - -<p class='c009'>Table I shows the urinary findings of uncomplicated influenza -cases admitted to the wards of the Mercy Hospital. None of -these cases developed pneumonia and, after running the usual -course, recovered. We would call attention to the fact that 25 -per cent. showed albuminuria. The amount of albumin was -never excessive, and very often was little more than a faint trace. -On the other hand, we have had a few patients where a previous -kidney lesion was known to be present, and naturally in these -cases a heavy cloud of albumin was met with. The albuminuria -was almost always a transient affair, lasting only during the -acute part of the illness, and would rightly come under the class -of febrile albuminuria. We regard it as being more the evidence -of nephrosis than a nephritis. As a rule, the time for the -appearance of albumin was after the fever had been present for -at least two or three days. One rarely met with it in the short -attacks of influenza where the temperature came to normal in -less than 72 hours. A certain time factor appeared to be necessary -in order for the nephrosis to develop. Another point of -interest is the presence of red and white blood cells seen relatively -frequently during the early days of the illness. One -wonders if this finding is analogous to the bleeding from the -nose and lung so often met with at the onset of the disease. The -red blood cells were seen microscopically, and only very rarely -did we encounter a smoky urine.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div><span class='pageno' id='Page_67'>67</span>TABLE I</div> - <div class='c004'>URINE ANALYSIS IN CASES OF UNCOMPLICATED INFLUENZA AT THE MERCY HOSPITAL</div> - </div> -</div> - -<table class='table1' summary='URINE ANALYSIS'> - <tr> - <th class='btt bbt brt c012' rowspan='2'>Day of Disease</th> - <th class='btt bbt brt c012' rowspan='2'>Total No. of Specimens</th> - <th class='btt bbt brt c012' colspan='4'><span class='sc'>Specific Gravity</span></th> - <th class='btt bbt brt c012' rowspan='2'>Alb.</th> - <th class='btt bbt brt c012' rowspan='2'>R.B.C.</th> - <th class='btt bbt c012' rowspan='2'>Casts</th> - </tr> - <tr> - - - <th class='bbt brt c012'>1001–10</th> - <th class='bbt brt c012'>1011–20</th> - <th class='bbt brt c012'>1021–30</th> - <th class='bbt brt c012'>1031–40</th> - - - - </tr> - <tr> - <td class='brt c013'>2</td> - <td class='brt c013'>118</td> - <td class='brt c013'>8</td> - <td class='brt c013'>31</td> - <td class='brt c013'>61</td> - <td class='brt c013'>18</td> - <td class='brt c013'>29</td> - <td class='brt c013'>17</td> - <td class='c013'>8</td> - </tr> - <tr> - <td class='brt c013'>3</td> - <td class='brt c013'>97</td> - <td class='brt c013'>8</td> - <td class='brt c013'>15</td> - <td class='brt c013'>62</td> - <td class='brt c013'>12</td> - <td class='brt c013'>23</td> - <td class='brt c013'>10</td> - <td class='c013'>11</td> - </tr> - <tr> - <td class='brt c013'>4</td> - <td class='brt c013'>51</td> - <td class='brt c013'>9</td> - <td class='brt c013'>22</td> - <td class='brt c013'>17</td> - <td class='brt c013'>3</td> - <td class='brt c013'>11</td> - <td class='brt c013'>7</td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>5</td> - <td class='brt c013'>24</td> - <td class='brt c013'>4</td> - <td class='brt c013'>2</td> - <td class='brt c013'>14</td> - <td class='brt c013'>4</td> - <td class='brt c013'>5</td> - <td class='brt c013'>3</td> - <td class='c013'>4</td> - </tr> - <tr> - <td class='brt c013'>6</td> - <td class='brt c013'>11</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>8</td> - <td class='brt c013'>3</td> - <td class='brt c013'>4</td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>7</td> - <td class='brt c013'>25</td> - <td class='brt c013'> </td> - <td class='brt c013'>10</td> - <td class='brt c013'>14</td> - <td class='brt c013'>1</td> - <td class='brt c013'>8</td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>8</td> - <td class='brt c013'>12</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'>8</td> - <td class='brt c013'>2</td> - <td class='brt c013'>6</td> - <td class='brt c013'> </td> - <td class='c013'>3</td> - </tr> - <tr> - <td class='brt c013'>9</td> - <td class='brt c013'>4</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'>1</td> - <td class='brt c013'>1</td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='bbt brt c013'>18</td> - <td class='bbt brt c013'>2</td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'>1</td> - <td class='bbt brt c013'>1</td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'> </td> - <td class='bbt c013'> </td> - </tr> - <tr> - <td class='bbt brt c012'>Totals</td> - <td class='bbt brt c013'>344</td> - <td class='bbt brt c013'>29</td> - <td class='bbt brt c013'>95</td> - <td class='bbt brt c013'>186</td> - <td class='bbt brt c013'>44</td> - <td class='bbt brt c013'>88</td> - <td class='bbt brt c013'>37</td> - <td class='bbt c013'>26</td> - </tr> -</table> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE II</div> - <div class='c004'>URINE ANALYSIS IN CASES OF UNCOMPLICATED INFLUENZA AT THE MAGEE HOSPITAL</div> - </div> -</div> - -<table class='table1' summary='URINE ANALYSIS'> - <tr> - <th class='btt bbt brt c012' rowspan='2'>Day of Disease</th> - <th class='btt bbt brt c012' rowspan='2'>Total No. of Specimens</th> - <th class='btt bbt brt c012' colspan='4'><span class='sc'>Specific Gravity</span></th> - <th class='btt bbt brt c012' rowspan='2'>Alb.</th> - <th class='btt bbt brt c012' rowspan='2'>R.B.C.</th> - <th class='btt bbt c012' rowspan='2'>Casts</th> - </tr> - <tr> - - - <th class='bbt brt c012'>1001–10</th> - <th class='bbt brt c012'>1011–20</th> - <th class='bbt brt c012'>1021–30</th> - <th class='bbt brt c012'>1031–40</th> - - - - </tr> - <tr> - <td class='brt c013'>1</td> - <td class='brt c013'>101</td> - <td class='brt c013'>6</td> - <td class='brt c013'>22</td> - <td class='brt c013'>49</td> - <td class='brt c013'>24</td> - <td class='brt c013'>5</td> - <td class='brt c013'> </td> - <td class='c013'>3</td> - </tr> - <tr> - <td class='brt c013'>2</td> - <td class='brt c013'>127</td> - <td class='brt c013'>1</td> - <td class='brt c013'>17</td> - <td class='brt c013'>75</td> - <td class='brt c013'>34</td> - <td class='brt c013'>13</td> - <td class='brt c013'> </td> - <td class='c013'>3</td> - </tr> - <tr> - <td class='brt c013'>3</td> - <td class='brt c013'>82</td> - <td class='brt c013'>3</td> - <td class='brt c013'>13</td> - <td class='brt c013'>55</td> - <td class='brt c013'>11</td> - <td class='brt c013'>13</td> - <td class='brt c013'>1</td> - <td class='c013'>4</td> - </tr> - <tr> - <td class='brt c013'>4</td> - <td class='brt c013'>36</td> - <td class='brt c013'>1</td> - <td class='brt c013'>14</td> - <td class='brt c013'>18</td> - <td class='brt c013'>3</td> - <td class='brt c013'>4</td> - <td class='brt c013'> </td> - <td class='c013'>2</td> - </tr> - <tr> - <td class='brt c013'>5</td> - <td class='brt c013'>40</td> - <td class='brt c013'>2</td> - <td class='brt c013'>9</td> - <td class='brt c013'>24</td> - <td class='brt c013'>5</td> - <td class='brt c013'>6</td> - <td class='brt c013'>1</td> - <td class='c013'>2</td> - </tr> - <tr> - <td class='brt c013'>6</td> - <td class='brt c013'>23</td> - <td class='brt c013'>1</td> - <td class='brt c013'>5</td> - <td class='brt c013'>15</td> - <td class='brt c013'>2</td> - <td class='brt c013'>7</td> - <td class='brt c013'>1</td> - <td class='c013'>3</td> - </tr> - <tr> - <td class='brt c013'>7</td> - <td class='brt c013'>5</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>4</td> - <td class='brt c013'> </td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='c013'>2</td> - </tr> - <tr> - <td class='brt c013'>8</td> - <td class='brt c013'>5</td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'>4</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>9</td> - <td class='brt c013'>2</td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>10</td> - <td class='brt c013'>10</td> - <td class='brt c013'>1</td> - <td class='brt c013'>3</td> - <td class='brt c013'>5</td> - <td class='brt c013'>1</td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='c013'>1</td> - </tr> - <tr> - <td class='brt c013'>11</td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='c013'>1</td> - </tr> - <tr> - <td class='brt c013'>12</td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'>1</td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>13</td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>14</td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='bbt brt c013'>15</td> - <td class='bbt brt c013'>5</td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'>1</td> - <td class='bbt brt c013'>4</td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'> </td> - <td class='bbt c013'> </td> - </tr> - <tr> - <td class='bbt brt c012'>Totals</td> - <td class='bbt brt c013'>447</td> - <td class='bbt brt c013'>17</td> - <td class='bbt brt c013'>87</td> - <td class='bbt brt c013'>263</td> - <td class='bbt brt c013'>80</td> - <td class='bbt brt c013'>57</td> - <td class='bbt brt c013'>4</td> - <td class='bbt c013'>21</td> - </tr> -</table> - -<p class='c009'>The results shown in Table II illustrate the urinary findings -at the Magee Hospital, and, as in the previous table, include cases -of influenza which did not develop pneumonia. The specimens -examined were obtained from young, healthy men, between the -<span class='pageno' id='Page_68'>68</span>ages of 20 and 32, and showed albumin in 13 per cent. of the -cases. This age factor probably accounts for the lower incidence -of albuminuria for this group.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE III</div> - <div class='c004'>URINE ANALYSIS IN CASES OF PNEUMONIA (INFLUENZAL) AT THE MERCY HOSPITAL</div> - </div> -</div> - -<table class='table1' summary='URINE ANALYSIS'> - <tr> - <th class='btt bbt brt c012' rowspan='2'>Day of Disease</th> - <th class='btt bbt brt c012' rowspan='2'>Total No. of Specimens</th> - <th class='btt bbt brt c012' colspan='4'><span class='sc'>Specific Gravity</span></th> - <th class='btt bbt brt c012' rowspan='2'>Alb.</th> - <th class='btt bbt brt c012' rowspan='2'>R.B.C.</th> - <th class='btt bbt c012' rowspan='2'>Casts</th> - </tr> - <tr> - - - <th class='bbt brt c012'>1001–10</th> - <th class='bbt brt c012'>1011–20</th> - <th class='bbt brt c012'>1021–30</th> - <th class='bbt brt c012'>1031–40</th> - - - - </tr> - <tr> - <td class='brt c013'>1</td> - <td class='brt c013'>47</td> - <td class='brt c013'>4</td> - <td class='brt c013'>14</td> - <td class='brt c013'>25</td> - <td class='brt c013'>2</td> - <td class='brt c013'>36</td> - <td class='brt c013'>7</td> - <td class='c013'>6</td> - </tr> - <tr> - <td class='brt c013'>2</td> - <td class='brt c013'>22</td> - <td class='brt c013'>1</td> - <td class='brt c013'>8</td> - <td class='brt c013'>9</td> - <td class='brt c013'>4</td> - <td class='brt c013'>19</td> - <td class='brt c013'>1</td> - <td class='c013'>4</td> - </tr> - <tr> - <td class='brt c013'>3</td> - <td class='brt c013'>9</td> - <td class='brt c013'>2</td> - <td class='brt c013'>3</td> - <td class='brt c013'>3</td> - <td class='brt c013'>1</td> - <td class='brt c013'>7</td> - <td class='brt c013'>1</td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>4</td> - <td class='brt c013'>6</td> - <td class='brt c013'>1</td> - <td class='brt c013'>3</td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='brt c013'>4</td> - <td class='brt c013'>1</td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>5</td> - <td class='brt c013'>6</td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'>5</td> - <td class='brt c013'> </td> - <td class='brt c013'>5</td> - <td class='brt c013'> </td> - <td class='c013'>1</td> - </tr> - <tr> - <td class='brt c013'>6</td> - <td class='brt c013'>16</td> - <td class='brt c013'>2</td> - <td class='brt c013'>7</td> - <td class='brt c013'>7</td> - <td class='brt c013'> </td> - <td class='brt c013'>13</td> - <td class='brt c013'>2</td> - <td class='c013'>7</td> - </tr> - <tr> - <td class='brt c013'>7</td> - <td class='brt c013'>9</td> - <td class='brt c013'> </td> - <td class='brt c013'>5</td> - <td class='brt c013'>3</td> - <td class='brt c013'>1</td> - <td class='brt c013'>8</td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>8</td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>9</td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>10</td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>11</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>12</td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>13</td> - <td class='brt c013'>4</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='c013'>1</td> - </tr> - <tr> - <td class='brt c013'>14</td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>15</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>16</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>17</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>18</td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>19</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='bbt brt c013'>20</td> - <td class='bbt brt c013'>1</td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'>1</td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'> </td> - <td class='bbt c013'> </td> - </tr> - <tr> - <td class='bbt brt c012'>Totals</td> - <td class='bbt brt c013'>133</td> - <td class='bbt brt c013'>11</td> - <td class='bbt brt c013'>47</td> - <td class='bbt brt c013'>63</td> - <td class='bbt brt c013'>8</td> - <td class='bbt brt c013'>106</td> - <td class='bbt brt c013'>13</td> - <td class='bbt c013'>19</td> - </tr> -</table> - -<p class='c009'>Table III includes the urinary findings of patients diagnosed -as influenzal pneumonia. In this table the term “Day of Disease” -indicates the day on which the physical signs of pneumonia could -be demonstrated, and not the day on which the patient was taken -ill with influenza. The incidence of albuminuria—79 per cent.—is -very high, while the presence of casts and red blood cells is -low. These results are really what one would expect. As we -have noticed in the late stages of uncomplicated influenza a -greater tendency for urinary changes to become apparent, one -would, therefore, most likely find considerable urinary disturbance -in the pneumonia immediately following the epidemic disease. -Pneumococcic pneumonia is prone to be accompanied by -<span class='pageno' id='Page_69'>69</span>an albuminuria. So when we have both influenzal and pneumococcic -etiological factors involved, it is but natural to have -most of the patients showing signs of kidney disturbance. The -amount of albumin present, although generally greater than in -uncomplicated influenza, was not excessive. At times there was -little more than a trace. We noted the relative scarcity of casts—a -condition which differs greatly from our past experience in the -ordinary lobar pneumococcic pneumonia. On the transient nature -of this kidney involvement we have considerable positive evidence, -but there is no question that the time required for the -urine to return to normal is longer after pneumonia than uncomplicated -influenza. We have observed but one or two cases which -afterward returned to us presenting clinical signs of acute -nephritis. In fact, in going over our hospital records of the -winter and spring we noted that an unusually small number of -acute nephritics have been admitted. This would seem to be -evidence that, as has been noted in the past, the kidney is not a -vulnerable organ in this epidemic disease.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE IV</div> - <div class='c004'>URINE ANALYSIS IN CASES OF PNEUMONIA (INFLUENZAL) AT THE MAGEE HOSPITAL</div> - </div> -</div> - -<table class='table1' summary='URINE ANALYSIS'> - <tr> - <th class='btt bbt brt c012' rowspan='2'>Day of Disease</th> - <th class='btt bbt brt c012' rowspan='2'>Total No. of Specimens</th> - <th class='btt bbt brt c012' colspan='4'><span class='sc'>Specific Gravity</span></th> - <th class='btt bbt brt c012' rowspan='2'>Alb.</th> - <th class='btt bbt brt c012' rowspan='2'>R.B.C.</th> - <th class='btt bbt c012' rowspan='2'>Casts</th> - </tr> - <tr> - - - <th class='bbt brt c012'>1001–10</th> - <th class='bbt brt c012'>1011–20</th> - <th class='bbt brt c012'>1021–30</th> - <th class='bbt brt c012'>1031–40</th> - - - - </tr> - <tr> - <td class='brt c013'>1</td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'>1</td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='c013'>1</td> - </tr> - <tr> - <td class='brt c013'>2</td> - <td class='brt c013'>12</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>10</td> - <td class='brt c013'>1</td> - <td class='brt c013'>8</td> - <td class='brt c013'> </td> - <td class='c013'>6</td> - </tr> - <tr> - <td class='brt c013'>3</td> - <td class='brt c013'>4</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>4</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>1</td> - <td class='c013'>1</td> - </tr> - <tr> - <td class='brt c013'>4</td> - <td class='brt c013'>9</td> - <td class='brt c013'>1</td> - <td class='brt c013'>2</td> - <td class='brt c013'>4</td> - <td class='brt c013'>2</td> - <td class='brt c013'>6</td> - <td class='brt c013'> </td> - <td class='c013'>6</td> - </tr> - <tr> - <td class='brt c013'>5</td> - <td class='brt c013'>8</td> - <td class='brt c013'> </td> - <td class='brt c013'>4</td> - <td class='brt c013'>4</td> - <td class='brt c013'> </td> - <td class='brt c013'>6</td> - <td class='brt c013'> </td> - <td class='c013'>5</td> - </tr> - <tr> - <td class='brt c013'>6</td> - <td class='brt c013'>8</td> - <td class='brt c013'> </td> - <td class='brt c013'>5</td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='brt c013'>7</td> - <td class='brt c013'>2</td> - <td class='c013'>6</td> - </tr> - <tr> - <td class='brt c013'>7</td> - <td class='brt c013'>4</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='brt c013'>3</td> - <td class='brt c013'> </td> - <td class='c013'>2</td> - </tr> - <tr> - <td class='brt c013'>8</td> - <td class='brt c013'>10</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'>8</td> - <td class='brt c013'> </td> - <td class='brt c013'>5</td> - <td class='brt c013'>2</td> - <td class='c013'>5</td> - </tr> - <tr> - <td class='brt c013'>9</td> - <td class='brt c013'>4</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='brt c013'>4</td> - <td class='brt c013'>3</td> - <td class='c013'>4</td> - </tr> - <tr> - <td class='brt c013'>10</td> - <td class='brt c013'>6</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>5</td> - <td class='brt c013'> </td> - <td class='brt c013'>6</td> - <td class='brt c013'>3</td> - <td class='c013'>5</td> - </tr> - <tr> - <td class='brt c013'>11</td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='c013'>1</td> - </tr> - <tr> - <td class='brt c013'>12</td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>13</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>14</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='bbt brt c013'>15</td> - <td class='bbt brt c013'>2</td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'>2</td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'>1</td> - <td class='bbt brt c013'> </td> - <td class='bbt c013'>1</td> - </tr> - <tr> - <td class='bbt brt c012'>Totals</td> - <td class='bbt brt c013'>70</td> - <td class='bbt brt c013'>1</td> - <td class='bbt brt c013'>20</td> - <td class='bbt brt c013'>45</td> - <td class='bbt brt c013'>4</td> - <td class='bbt brt c013'>49</td> - <td class='bbt brt c013'>11</td> - <td class='bbt c013'>40</td> - </tr> -</table> - -<p class='c009'><span class='pageno' id='Page_70'>70</span>Table IV includes specimens obtained at the Magee Hospital -from patients diagnosed as pneumonia. The results among -these young students were very similar to those of the previous -chart, where all ages were included. However, casts and red -blood cells were more regularly noted.</p> - -<p class='c009'>From the four tables, we are able to note one or two common -facts. In acute uncomplicated influenza albuminuria occurred 57 -times in 447 specimens, or 13 per cent., at the Magee Hospital. -Here we dealt entirely with the young adult. At the Mercy Hospital -88 positive results of albumin in 344 specimens, or 26 per -cent., from patients of all types were recorded. The common -total would be 781 specimens examined, and 141, or 17 per cent., -showing albumin.</p> - -<p class='c009'>With the advent of pneumonia the incidence of albuminuria -was increased. At the Magee Hospital it was seen 49 times in -70 examinations, or 70 per cent.; while at the Mercy Hospital 106 -positive results were found in 133 specimens examined, a percentage -of 79. The combined figures, therefore, would show 155 -out of 203, or 76 per cent.</p> - -<p class='c009'>The incidence of albuminuria for the epidemic in all its phases -would be, from our figures, 400 in 994 specimens, or 40 per cent.</p> - -<p class='c009'>Red blood cells were present in 5 per cent. of the influenza -cases, and in 11 per cent. of the pneumonias. This was always -a microscopic observation, save in the case of a slightly smoky -urine. Even microscopically the red cells were not numerous. -We noted them at times quite early in the disease in some of the -severe cases which presented epistaxis and hematemesis. Possibly -one might consider the early presence of red blood cells in -the urine as a condition analogous to those just mentioned, -although we never saw anything suggesting free hemorrhage -from the kidney. It is probably better to regard the red cells -as a manifestation of an acute nephrosis of toxic origin.</p> - -<p class='c009'>Casts were found in 35 per cent. of the cases showing albuminuria. -We are inclined to feel that this observation is somewhat -low, but at the same time we have noted that in uncomplicated -influenza one frequently sees albumin without casts. -We were also impressed with the fact that casts were not as -prominent a feature in the influenzal pneumonias as they are in -frank lobar pneumonia of essentially pneumococcic origin.</p> - -<p class='c009'><span class='pageno' id='Page_71'>71</span>During the course of routine examinations several transient -glycosurias were seen. Their transient character was the outstanding -feature. The quantity of sugar was very moderate—our -figures were never above 1 per cent.—and the daily amount -of urine was always within normal limits. Acetone and diacetic -acid were absent. A few observations on the blood sugar showed -a rise (.2 to .25), which readily came to normal with treatment. -Clinically these cases were not classed as diabetes mellitus, but -rather as a nervous complication of influenza, involving in some -way the carbohydrate metabolism, probably through the central -nervous system. One case of special interest, which is mentioned -elsewhere, was the association of glycosuria with almost total -blindness from a very intense optic œdema. Sugar (1 per cent.) -was present on the day of admission, while only a trace was noted -on the two following days, and from then on the urine was free -from sugar. How many days the sugar had been present before -admission to the hospital we cannot say, but we could trace the -failure of vision back to almost the day of its onset, which was -three weeks previous to our first examination. The eye symptoms -were the only complaints. The patient had had a moderately -sharp attack of influenza a little over two weeks before -the first sign of failure of vision had appeared. We may add -that the vision returned slowly to normal several weeks after -admission. The urine and blood sugar were normal, on a general -diet, over a period of one month while in the hospital. Unfortunately, -we have had no further record of this patient regarding -the urine, but her vision still remains normal. Cases of this type -were observed in England after the 1890 epidemic, and are referred -to in Allbutt’s “System of Medicine,” vol. i, on influenza. -Our other glycosuria cases did not present changes in the fundus -of the eye. The glycosuria and glycæmia were transient, and we -feel that they do not represent diabetes mellitus. Most of the -patients of this class had long since recovered from an attack of -influenza, and came to the hospital usually for treatment of -various nervous conditions, which at times simulated neuritis, or -otherwise one saw manifestations of general nervousness, not -unlike hyperthyroidism. In all probability, we were dealing with -a hyperglycæmia associated with a hyperactive thyroid gland. -So, after all, the glycosuria, even though rare, is not bewildering. -Symptoms and signs of toxic goitre in direct relation to the -<span class='pageno' id='Page_72'>72</span>epidemic we claim to have seen, and one is justified, temporarily -at least, in having the thyroid gland father our transient -glycosuria.</p> - -<p class='c009'>In relation to the positive sugar findings, we have had numerous -negative examples of almost equal interest. Furunculosis is -a very common sequel of the epidemic. It is well known that -in furunculosis there is a hyperglycæmia, but no glycosuria and -no acetone or diacetic acid in the urine. All our blood sugar -readings were above the normal, and at times unusually high. -They varied from .2 to .41. This last unusually high amount was -in a young physician with recurrent furunculosis following -influenza. There was no glycosuria at any time. Elimination -of carbohydrates not only brought the blood sugar to normal -limits in the course of a week, but also assisted in the cure of the -furunculosis, but in a longer time. In all of this group we saw no -incidence of polyuria or glycosuria.</p> - -<h3 class='c010'><em>Hematology</em></h3> - -<p class='c011'>There is very little evidence, as shown in the literature, that -special study on the blood during past influenzal epidemics has -been made. A few references to alterations in the count of cells -have been reported for the last epidemic (1890), but they are, -as a rule, very brief statements. Cabot notes a normal leucocyte -count in two-thirds of the cases, and a moderate increase in the -rest. Several observers call attention to the leucopenia during -the height of the disease, with a subsequent rise after the temperature -has fallen to normal. According to Rieder and Herman -(American Journal of Medical Science, 1893, cv. 696), the leucocytes -were not increased in simple influenza, and only very -slightly in the pneumonia following this disease. Herman also -noticed a decline in the leucocytes in pneumonia as a fatal ending -ensued. This finding was one of the few recorded for the 1890 -epidemic. Emerson (Emerson Clinic Diagnosis, 1911, 558) found -in influenza almost one-half of the cases showing more than -10,000 leucocytes, some even reaching 25,000. He further notes -that early in the disease the count may be low, 3,000 to 5,000, but -it usually rose sharply, to fall again when the temperature comes -to normal. He lays stress on obtaining a leucocyte curve for each -case in order to get a true picture of what changes occur. The -past epidemic has brought out many observations on this subject. -<span class='pageno' id='Page_73'>73</span>They vary somewhat, as is to be expected, but a common -factor seems to be more or less basic—namely, a leucopenia or -a normal count is the most significant single blood picture we -have of uncomplicated influenza. Further, a leucocytosis is fairly -generally, and we believe correctly, interpreted as evidence of a -secondary bacterial invasion in this particular epidemic, and -usually of the respiratory system. The leucopenia is as much a -part of the clinical picture of influenza as it is of typhoid -fever. Leucocytosis always means secondary invasion by other -organisms.</p> - -<p class='c009'>During the recent epidemic the clinical laboratory department -of the School of Medicine, University of Pittsburgh, has made -747 blood counts on influenza cases. In most of the cases blood -counts were made as a routine, while repeated counts were done -only on selected patients.</p> - -<p class='c009'>The following table indicates the leucocyte count for our series, -comprising the epidemic in all of its phases. There are a few -general points which appear striking that we may refer to at this -time, and leave until later the discussion of the minor details. -One-third of the counts, including, as they do, many cases of -pneumonia, showed a leucopenia, while 70 per cent. of the total -number fell under 10,000. This last group contains more pneumonias -and other complications than simple influenza. But 5 per -cent. of the cases counted showed more than 20,000. All of these -undoubtedly had pneumonia or some other complication. Comparing -this finding with our experience in the past before the -epidemic with the pneumococcic lobar pneumonia, one sees at -once that, as far as this type of clinical observation is concerned, -the two pneumonias are totally different. The writer remembers -but one case of lobar pneumonia which showed a persistent white -count falling below 10,000. Certainly in this community lobar -pneumonia and low leucocyte counts were unusual combinations -until the present epidemic. Further, the evident depression of -leucocytosis even where there was an actual increase is indicated -by 95 per cent. of our counts being below 20,000. This leads us -to state that the pneumococcus, although present in practically -all of our pneumonias, produced in only a small percentage of the -bloods we examined its characteristic increase. The toxic factor -of this influenzal epidemic certainly causes a marked change in -the white cells of the blood.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div><span class='pageno' id='Page_74'>74</span>TABLE V</div> - </div> -</div> - -<table class='table1' summary=''> - <tr> - <th class='bbt brt c012' colspan='6'>MERCY HOSPITAL</th> - <th class='bbt c012' colspan='4'>MAGEE HOSPITAL</th> - </tr> - <tr> - <th class='bbt brt c012'>Leucocyte Count.</th> - <th class='bbt brt c012'>Influ.</th> - <th class='bbt brt c012'>Influ. Pn.</th> - <th class='bbt brt c012'>Influ. Compl.</th> - <th class='bbt brt c012'>Total</th> - <th class='bbt brt c012'>%</th> - <th class='bbt brt c012'>Influ.<br />Influ. Pn.<br />Influ. Compl.</th> - <th class='bbt brt c012'>%</th> - <th class='bbt brt c012'>Total</th> - <th class='bbt c012'>%</th> - </tr> - <tr> - <td class='brt c013'>2000 or less</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - <td class='brt c013' rowspan='5'>38</td> - <td class='brt c013'>1</td> - <td class='brt c013' rowspan='5'>28</td> - <td class='brt c013'>3</td> - <td class='c013' rowspan='5'>32</td> - </tr> - <tr> - <td class='brt c013'>2000–3000</td> - <td class='brt c013'>3</td> - <td class='brt c013'>3</td> - <td class='brt c013'>1</td> - <td class='brt c013'>7</td> - - <td class='brt c013'>13</td> - - <td class='brt c013'>20</td> - - </tr> - <tr> - <td class='brt c013'>3000–4000</td> - <td class='brt c013'>7</td> - <td class='brt c013'>12</td> - <td class='brt c013'>4</td> - <td class='brt c013'>23</td> - - <td class='brt c013'>34</td> - - <td class='brt c013'>57</td> - - </tr> - <tr> - <td class='brt c013'>4000–5000</td> - <td class='brt c013'>14</td> - <td class='brt c013'>13</td> - <td class='brt c013'>9</td> - <td class='brt c013'>36</td> - - <td class='brt c013'>41</td> - - <td class='brt c013'>77</td> - - </tr> - <tr> - <td class='brt c013'>5000–6000</td> - <td class='brt c013'>17</td> - <td class='brt c013'>16</td> - <td class='brt c013'>6</td> - <td class='brt c013'>39</td> - - <td class='brt c013'>42</td> - - <td class='brt c013'>81</td> - - </tr> - <tr> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>6000–7000</td> - <td class='brt c013'>15</td> - <td class='brt c013'>13</td> - <td class='brt c013'>6</td> - <td class='brt c013'>34</td> - <td class='brt c013' rowspan='4'>40</td> - <td class='brt c013'>59</td> - <td class='brt c013' rowspan='4'>37</td> - <td class='brt c013'>93</td> - <td class='c013' rowspan='4'>38</td> - </tr> - <tr> - <td class='brt c013'>7000–8000</td> - <td class='brt c013'>7</td> - <td class='brt c013'>8</td> - <td class='brt c013'>5</td> - <td class='brt c013'>20</td> - - <td class='brt c013'>36</td> - - <td class='brt c013'>56</td> - - </tr> - <tr> - <td class='brt c013'>8000–9000</td> - <td class='brt c013'>8</td> - <td class='brt c013'>14</td> - <td class='brt c013'>8</td> - <td class='brt c013'>30</td> - - <td class='brt c013'>37</td> - - <td class='brt c013'>67</td> - - </tr> - <tr> - <td class='brt c013'>9000–10000</td> - <td class='brt c013'>15</td> - <td class='brt c013'>9</td> - <td class='brt c013'>8</td> - <td class='brt c013'>32</td> - - <td class='brt c013'>39</td> - - <td class='brt c013'>71</td> - - </tr> - <tr> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>10000–12000</td> - <td class='brt c013'>4</td> - <td class='brt c013'>12</td> - <td class='brt c013'>9</td> - <td class='brt c013'>25</td> - <td class='brt c013' rowspan='5'>20</td> - <td class='brt c013'>44</td> - <td class='brt c013' rowspan='5'>27</td> - <td class='brt c013'>69</td> - <td class='c013' rowspan='5'>25</td> - </tr> - <tr> - <td class='brt c013'>12000–14000</td> - <td class='brt c013'>1</td> - <td class='brt c013'>1</td> - <td class='brt c013'>8</td> - <td class='brt c013'>10</td> - - <td class='brt c013'>28</td> - - <td class='brt c013'>38</td> - - </tr> - <tr> - <td class='brt c013'>14000–16000</td> - <td class='brt c013'>5</td> - <td class='brt c013'>3</td> - <td class='brt c013'>2</td> - <td class='brt c013'>10</td> - - <td class='brt c013'>22</td> - - <td class='brt c013'>33</td> - - </tr> - <tr> - <td class='brt c013'>16000–18000</td> - <td class='brt c013'>3</td> - <td class='brt c013'>2</td> - <td class='brt c013'>2</td> - <td class='brt c013'>7</td> - - <td class='brt c013'>16</td> - - <td class='brt c013'>23</td> - - </tr> - <tr> - <td class='brt c013'>18000–20000</td> - <td class='brt c013'>2</td> - <td class='brt c013'>2</td> - <td class='brt c013'>2</td> - <td class='brt c013'>6</td> - - <td class='brt c013'>15</td> - - <td class='brt c013'>21</td> - - </tr> - <tr> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>20000–22000</td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>1</td> - <td class='brt c013'>2</td> - <td class='brt c013' rowspan='5'>2</td> - <td class='brt c013'>4</td> - <td class='brt c013' rowspan='5'>5</td> - <td class='brt c013'>6</td> - <td class='c013' rowspan='5'>3</td> - </tr> - <tr> - <td class='brt c013'>22000–24000</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>1</td> - - <td class='brt c013'>8</td> - - <td class='brt c013'>9</td> - - </tr> - <tr> - <td class='brt c013'>24000–26000</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>1</td> - - <td class='brt c013'>4</td> - - <td class='brt c013'>5</td> - - </tr> - <tr> - <td class='brt c013'>26000–28000</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - - <td class='brt c013'>2</td> - - <td class='brt c013'>2</td> - - </tr> - <tr> - <td class='brt c013'>28000–30000</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - <td class='brt c013'>1</td> - - <td class='brt c013'>3</td> - - <td class='brt c013'>4</td> - - </tr> - <tr> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='c013'> </td> - </tr> - <tr> - <td class='brt c013'>30000–32000</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>3</td> - <td class='brt c013' rowspan='6'>3</td> - <td class='brt c013'>3</td> - <td class='c013' rowspan='6'>2</td> - </tr> - <tr> - <td class='brt c013'>32000–34000</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>3</td> - - <td class='brt c013'>3</td> - - </tr> - <tr> - <td class='brt c013'>34000–36000</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>3</td> - - <td class='brt c013'>3</td> - - </tr> - <tr> - <td class='brt c013'>36000–38000</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - - <td class='brt c013'> </td> - - </tr> - <tr> - <td class='brt c013'>38000–40000</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>1</td> - - <td class='brt c013'>1</td> - - </tr> - <tr> - <td class='brt c013'>40000–42000</td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'>2</td> - - <td class='brt c013'>2</td> - - </tr> - <tr> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'> </td> - <td class='brt c013'><hr /></td> - <td class='brt c013'> </td> - <td class='brt c013'><hr /></td> - <td class='brt c013'> </td> - <td class='brt c013'><hr /></td> - <td class='c013'> </td> - </tr> - <tr> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'>287</td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'>460</td> - <td class='bbt brt c013'> </td> - <td class='bbt brt c013'>747</td> - <td class='bbt c013'> </td> - </tr> -</table> - -<p class='c009'>The blood picture in uncomplicated influenza is a normal one -for the red cells and the hæmoglobin, but the white cells are -characteristically altered. We have made many observations on -the red blood cells, and from all aspects the picture appears to be -normal. Similarly, there is nothing significant about the hæmoglobin -estimations. Where we have slight alteration in the red -count and in the hæmoglobin it is probably safer not to attribute -the change to the epidemic. We have no records showing a -secondary anæmia due to the initial epistaxis.</p> - -<p class='c009'><span class='pageno' id='Page_75'>75</span>A leucopenia or a normal count is what one should see in most -of the uncomplicated influenzal cases. We are almost ready to -say that any estimation above normal limits means secondary -bacterial invasion. The count may remain low throughout the -illness, rising to the normal rapidly as the temperature falls. We -do not regard a leucocytosis at the end of an epidemic case as -part of the blood picture. Our experience is that with convalescence -the normal count returns and remains within normal -bounds. Very often hidden sinus infection is responsible for -some of the post-influenzal leucocytoses. The leucopenia may -vary from a slightly subnormal count to a point well below -2,000. Most of the simple epidemic cases showed some degree -of leucopenia. As far as we have been able to estimate, we are -led to believe that one should not lay any special stress on the -grade of leucopenia as being of prognostic significance in uncomplicated -influenza. Many of the mildest clinical types showed -very low counts, and <i><span lang="la" xml:lang="la">vice versa</span></i>. There is, however, a prognostic -relation to be noted with reference to a falling white count in the -pneumonia, but this we shall mention again later. The onset of -the leucopenia corresponds to the onset of the disease. It was -present with the earliest cases we examined, and remained fairly -stationary, although we have records of its fluctuating slightly -one way or the other. But one must remember in this regard -the personal error in blood counting, and also particularly the -error of the apparatus. For careful work only those counting -chambers and pipettes should be used that have a Bureau of -Standards certificate. The duration of the leucopenia was fairly -close to the duration of the disease.</p> - -<p class='c009'>How many cases of influenza of several days’ illness having -about 12,000 leucocytes, a few sticky râles in the chest, but no -signs of definite consolidation, have been observed by the clinicians? -These cases recover without further change, and the -diagnosis is handed in as influenza without a complication being -mentioned. In collecting the blood reports from this group the -12,000 cells accordingly must be considered as having occurred -in a simple influenza. We hold that this is not a case of uncomplicated -epidemic disease. There is undoubted evidence, as is -acknowledged by the clinician, of a bronchiolitis; and how many -lungs showing a bronchiolitis at autopsy fail to have a broncho-pneumonia? -True it may not be demonstrable by our physical -<span class='pageno' id='Page_76'>76</span>examination. This is often the origin of many high counts in -what apparently is considered uncomplicated influenza.</p> - -<p class='c009'>The blood picture of the pneumonia following the epidemic -was more or less constant, although at the same time the features -of the count may be quite different. One could roughly -divide the results into three groups: (1) leucocytosis, (2) leucopenia, -(3) intermediate or normal. Some pneumonias could be -followed during their course through all of these classes. Before -discussing the white count we can briefly dismiss the other -phases of the blood examination by stating that the red blood -cells and hæmoglobin presented nothing by the usual examinations -which was of special significance, or in any way characteristic.</p> - -<p class='c009'>As an example of the group showing a leucocytosis let us -follow a patient through an acute influenzal attack, followed by -a pneumonia with a subsequent recovery. An initial leucopenia, -gradually or suddenly changing into a very moderate leucocytosis -(10,000–15,000), was noted at the onset of the pneumonia. During -the course of the complication the number of cells in the -majority of cases increased, but rarely advanced beyond 20,000. -With lysis or crisis the count dropped toward normal, and by the -time the lung signs had disappeared the white cells were at the -usual number, or very slightly increased. The point which -seemed to us to be of importance was that, even although we had -a leucocytosis, it was nothing like the count that one would expect -for a lobar pneumonia. Of course, there were a few high counts, -but looking at the group as a whole they were relatively low. -There are a number of variations to this form of blood picture -which we might briefly consider. We have observed secondary -rises in the leucocyte count concurrent with a new lung involvement. -This type was the one so prone to develop into a condition -of non-resolution, fibrosis and ultimate death, with a continuous -moderately high leucocytosis to the end. Another variation -which we learned to fear was the fall of leucocytes to normal or -subnormal after a primary rise, when the clinical course of the -case in no way indicated a crisis or lysis pending. Seemingly, -the longer the primary leucocytosis had been present the more -serious was the subsequent leucopenia. We regard this form of -secondary leucopenia, if one may use such a term, as a prognostic -sign of some value. As in lobar pneumonia, a high leucocyte -count has been, as a rule, a favorable feature.</p> - -<p class='c009'><span class='pageno' id='Page_77'>77</span>The second group, or those showing a leucopenia throughout -their course, was by no means an unusual thing. This is a cardinal -point—in fact, one of the most striking clinical features of -the epidemic. The leucopenia here does not have the prognostic -value that it seems to have in the group just referred to previously. -We have observed cases go through a pneumonia with -4,000–5,000 white cells in a relatively easy manner. When, however, -the leucocytes fall to 3,000 or under, one may be reasonably -sure that the outcome is doubtful, even with the general condition -of the patient at the time favorable. In the pneumonias of this -group which died the leucocytes have always fallen to about 2,000 -cells. We have a number of observations taken from one-half -to four hours before death showing counts in the immediate -neighborhood of 2,000, but never below this number. Where -recovery has taken place the cells go forward to the normal, -more or less keeping pace with the general clinical picture.</p> - -<p class='c009'>Of group three there is not much to say, except that on one -hand it tends toward a leucocytosis, and on the other to a leucopenia. -This group comprises a considerable number of the pneumonias. -We are not in a position to say anything regarding the -relative mortality of this group. The development of a leucopenia -from these cases after a period of some stability in the -leucocytic curve is of bad prognostic import. Not infrequently -we have noticed rather wild abrupt rises to 20,000 in the leucocytes -toward the late half of the disease. This curve was nearly -always sustained until the end, which, as a rule, was recovery.</p> - -<p class='c009'>We do not need to consider at any length the effect on the -leucocyte count of complications not of lung origin. Acute sinuses -in head, otitis media and meningitis always produced a variable -moderate leucocytosis. The change was not so marked in meningitis, -as our cases were all preceded by a pneumonia which had -independently invoked a slight leucocytic response. As a complication -of the pneumonia we have noted an abrupt rise following -an acute pleuritis with effusion, and similarly after the onset -of an empyema. These complications seemed to be able to induce -a leucocytosis with more certainty and ease than the more -serious pneumonic condition. Possibly, as they occurred toward -the end of the infection, the toxic factor of the epidemic influenza -was more or less spent, and the secondary invader had a freer -hand to act in its normal way.</p> - -<p class='c009'><span class='pageno' id='Page_78'>78</span>Differential counts were made in 194 cases, including influenza, -influenzal pneumonia and influenzal complications. We have -taken the average percentage of each type of cell for the groups, -which are purely numerical divisions based on the leucocytic -count. No differentiation is made for the various clinical divisions -of the epidemic in the following table:</p> - -<table class='table2' summary=''> - <tr><td class='c014' colspan='6'><span class='sc'>Leucocytes</span> 2,000–8,000.</td></tr> - <tr> - <td class='c015'> </td> - <td class='c016'>P.</td> - <td class='c016'>E.</td> - <td class='c016'>L.M.</td> - <td class='c016'>S.M.</td> - <td class='c017'>Trans.</td> - </tr> - <tr> - <td class='c015'>Total counts 86</td> - <td class='c018'>66%</td> - <td class='c018'>1%</td> - <td class='c018'>13%</td> - <td class='c018'>17%</td> - <td class='c019'>3%</td> - </tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='6'><span class='sc'>Leucocytes</span> 8,000–10,000.</td></tr> - <tr> - <td class='c015'> </td> - <td class='c016'>P.</td> - <td class='c016'>E.</td> - <td class='c016'>L.M.</td> - <td class='c016'>S.M.</td> - <td class='c017'>Trans.</td> - </tr> - <tr> - <td class='c015'>Total counts 33</td> - <td class='c018'>69%</td> - <td class='c018'>1%</td> - <td class='c018'>11%</td> - <td class='c018'>16%</td> - <td class='c019'>3%</td> - </tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='6'><span class='sc'>Leucocytes</span> 10,000–20,000.</td></tr> - <tr> - <td class='c015'> </td> - <td class='c016'>P.</td> - <td class='c016'>E.</td> - <td class='c016'>L.M.</td> - <td class='c016'>S.M.</td> - <td class='c017'>Trans.</td> - </tr> - <tr> - <td class='c015'>Total counts 45</td> - <td class='c018'>76%</td> - <td class='c018'>2%</td> - <td class='c018'>10%</td> - <td class='c018'>19%</td> - <td class='c019'>3%</td> - </tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='6'><span class='sc'>Leucocytes</span> 20,000–30,000.</td></tr> - <tr> - <td class='c015'> </td> - <td class='c016'>P.</td> - <td class='c016'>E.</td> - <td class='c016'>L.M.</td> - <td class='c016'>S.M.</td> - <td class='c017'>Trans.</td> - </tr> - <tr> - <td class='c015'>Total counts 17</td> - <td class='c018'>79%</td> - <td class='c018'>2%</td> - <td class='c018'>8%</td> - <td class='c018'>7%</td> - <td class='c019'>4%</td> - </tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='6'><span class='sc'>Leucocytes</span> 30,000–40,000.</td></tr> - <tr> - <td class='c015'> </td> - <td class='c016'>P.</td> - <td class='c016'>E.</td> - <td class='c016'>L.M.</td> - <td class='c016'>S.M.</td> - <td class='c017'>Trans.</td> - </tr> - <tr> - <td class='c015'>Total counts 13</td> - <td class='c018'>85%</td> - <td class='c018'>1%</td> - <td class='c018'>5%</td> - <td class='c018'>6%</td> - <td class='c019'>3%</td> - </tr> -</table> - -<p class='c009'>The differential count in general indicates an increase in the -polymorphonuclear leucocytes as the total leucocytic number -increases. This is really what one would expect. There also -seems to be an increase of the large mononuclear cells, with a -slight diminution in the small mononuclear elements, particularly -in the count below 10,000. Abnormal cells were encountered -very seldom. One can hardly say that the epidemic has a -characteristic differential blood picture, except, perhaps, that an -increase of the large mononuclears is present in the low counts. -This, however, may hold true for any leucopenia.</p> - -<h3 class='c010'><em>Conclusions</em></h3> - -<p class='c011'>1. Epidemic influenza is often accompanied by a transient -slight albuminuria with a few red blood cells and casts. Acute -nephritis as a clinical entity does not appear to be other than a -rare sequel.</p> - -<p class='c009'><span class='pageno' id='Page_79'>79</span>2. Epidemic influenza tends to produce a leucopenia.</p> - -<p class='c009'>3. A leucocytosis in influenza, as a rule, indicates a secondary -infection.</p> - -<p class='c009'>4. The pneumonia following influenza shows, as a rule, but a -very moderate leucocytosis, while, on the other hand, the presence -of a leucopenia is by no means infrequent.</p> - -<p class='c009'>We are greatly indebted to Miss R. Thompson, Messrs. Mock, -Frost, Marshall and Scott for their assistance in this work at -the Magee Hospital.</p> - -<div class='chapter'> - <span class='pageno' id='Page_81'>81</span> - <h2 class='c005'>THE TREATMENT OF INFLUENZA</h2> -</div> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>By <span class='sc'>W. W. G. Maclachlan, M. D.</span></div> - </div> -</div> - -<p class='c008'>One may frankly say there is no specific treatment for influenza. -Possibly we are in error in introducing the discussion, -particularly on treatment with such a definite and unsatisfactory -conclusion. The same statement has been made after all the -previous pandemics, and one wonders whether a like remark is -going to apply to the next similar scourge. The past two or three -months should bring to the medical profession a certain humility -which should stimulate a keener sense of research, especially as -we now have at our disposal highly organized laboratories where -unsolved problems can be viewed from almost any angle. Yet -we are really, save here and there, putting our forces together -in the study of the disease. It is obvious that a fleeting epidemic -makes a most difficult subject for study, especially during a time -when there is a paucity of physicians. May we not hope, however, -that some researches on the disease may be forthcoming, -so that we may safely feel that at least preventive or protective -measures will be possible?</p> - -<p class='c009'>There is no one who is able to say that this or that drug has -not been thoroughly tried. The alkalies, salicylates, antipyretics, -quinine and the sedatives have all been freely used in the last as -well as the present epidemic. Each group of drugs has its following, -although it appears to be a general rule in this epidemic -to use the antipyretics (coal tar products) as little as possible. -From the distant past we have numerous records of treatment. -Willis (1658) emphasized the value of sweating and the use of -diaphoretics, but at the same time he states that in mild cases -the cure is left to nature; Sydenham (1675) claimed considerable -value in fresh air. He also paid more attention to restricting the -diet, and was not favorable to the use of anodynes. One certainly -obtains the impression from the records of past epidemics -that many of the general principles in treatment were similar to -what are now in vogue. Medicinal remedies, of course, varied -greatly, but to enumerate them would be merely giving a résumé -<span class='pageno' id='Page_82'>82</span>of the progress of therapeutics. Sufficient is it to say that influenza -has certainly, since the earliest days, given therapeutists an -ample opportunity to test their wares.</p> - -<p class='c009'>The outstanding respiratory complication, pneumonia, has -added a very undesirable phase to the disease. In fact, the -greater part of the mortality was due to this serious sequela. -Some interesting points have been brought out in serum and -blood therapy for this type of pneumonia. The use of whole -blood or serum from convalescent patients in cases of pneumonia -opens up a new and not unlikely fruitful means of treatment. -The method of treatment possibly may be applicable as an emergency -measure in other diseases, as has been shown in the case -of scarlet fever and poliomyelitis. We also have the anti-pneumococcic -sera available for therapeutic use. The drugs and the -general treatment of the pneumonia are virtually the same for -the last two epidemics.</p> - -<p class='c009'>The protean manifestations of the 1890 epidemic, with its -unusual nervous sequelæ, have not been seen to any extent, as -far as we yet know. In fact, the present epidemic appears to be -relatively free from complications other than those occurring in -the lung during the acute course of the disease. Hence, in all -likelihood, there will be less of the nervous after effects to be -treated. It is, however, too early to hope that the nervous system -is going to escape.</p> - -<p class='c009'>In another part of this volume the vaccine therapy is discussed -in detail, so that we shall not repeat what has been brought out -in that article. We would, however, emphasize the value of -honest and accurate clinical reports of the use of vaccines, in -order to establish their present status in epidemic influenza. -Overestimation and commercialism are very likely to ruin a -method of treatment, even when it may be of value in a certain -phase of the disease. If we do not carefully weigh the pros and -cons of the vaccine treatment in this epidemic from a purely -scientific and coldly neutral attitude, we are simply doing the -public and ourselves an injustice.</p> - -<p class='c009'>The treatment of influenza as the disease presented itself -to us in this community will be considered under three divisions—acute -influenza, pneumonia, and other complications.</p> - -<div> - <span class='pageno' id='Page_83'>83</span> - <h3 class='c010'><em>Acute Influenza</em></h3> -</div> - -<p class='c011'>There is one important thing to be done in the treatment of -influenza, whether the infection be mild or severe. Have the -patient go to bed as soon as possible. In most of the acute -attacks the individual went to bed of his own accord; but there -were, unfortunately, too many instances where the patient refused -to surrender, trying, as we say, to fight the attack. Some -appeared to be able to accomplish this feat. But how many of -our cases of fatal pneumonia can be clearly linked up with this -group of the mild or subacute preliminary course? No matter -how light the attack may appear to be, the patient should be told -of the necessity of remaining in bed until the pulse, respiration -and temperature have returned to the normal and remained normal -for at least five days. At the onset a hot bath, with care to -avoid chilling, followed by a drink of hot lemonade and a Dover’s -powder, gave considerable relief to the patient.</p> - -<p class='c009'>The value of good nursing cannot be overestimated. The nurse -must see that the patient is always well covered and kept warm, -not even permitting him to rise in bed to reach for a drink; also -the regulation of the temperature of the room should be carefully -watched. The main point is to have plenty of fresh air. We -have noticed that the patient appeared more comfortable if the -air was slightly warmed. Water should be given at regular intervals. -Under no consideration should an acute influenza case be -allowed to get up to go to the toilet.</p> - -<p class='c009'>At the onset, and while the febrile attack is still present, there -is little desire for food—but one does not need to worry about the -question of nourishment in such an acute illness. Milk, cream, -cocoa, gruels and fruit juices may be given at first, and as the -fever subsides the diet increased. We have found that the appetite -returned to normal very readily. In view of the urinary -findings indicating a slight transient nephritis, meat broths are to -be avoided until the convalescent stage is reached. We have been -very guarded in recommending cold sponging in acute influenza. -As a rule, it was not necessary. The icebag to the head is often -of great value in the intense headache, which is so frequent. It -is our opinion that in the treatment of uncomplicated influenza -what has just been mentioned constitutes the important part. -Most physicians would agree with this. However, when we -<span class='pageno' id='Page_84'>84</span>advance to drug therapy, we come into the personal realm of -likes and dislikes of drugs and methods of usage.</p> - -<p class='c009'>We do not intend in any way to give our views in a dogmatic -manner, nor to touch upon all of the remedies that have been -advanced. At the onset of the disease a moderate calomel purge, -followed by a saline, was given in all cases. We were practically -free from the so-called intestinal type of influenza which was -seen in some other communities, consequently we did not hesitate -to use calomel. Castor oil or magnesium sulphate was given -afterward, as was found necessary. Abdominal distention was -rarely seen, and when it occurred a plain soapsuds enema with -turpentine was administered.</p> - -<p class='c009'>Quinine sulphate (gr. iii-v, three times a day) combined with -phenyl-salicylate (gr. v) was a routine measure. We often noticed -deafness after a very few doses of quinine. It was then discontinued. -Acetyl-salicylic acid (gr. v, three to six times a day) -seemed to have a palliative effect on the severe headaches, -although during the height of the disease the general muscular -aching did not appear to be relieved by its use. It was not used -routinely. These drugs possibly made the patients more comfortable, -but we were very skeptical as to their influence on the -general infection. The raising of the leucocyte count by quinine -in influenza appears very unlikely. The use of alkaline salts has -been a general procedure, particularly as we are now on the -alkaline wave of therapeutics. Sodium bicarbonate was added -to the drinking water of all patients (two drams to the quart). -We gave this salt for its diuretic effect. In a few cases more active -diuresis by the alkalines was readily and easily produced by the -use of “imperial drink” three or four times a day. We felt that -good kidney elimination was of considerable importance.</p> - -<p class='c009'>The use of tartrates and citrates, as in “imperial drink” in -a condition where we know some kidney impairment is present, -is possibly flying in the face of danger—especially in view of the -fact that these salts are so available in the production of experimental -nephritis. But we have only to see their application in -the human in mercury bichloride poisoning, where an intense -nephrosis usually develops, to fully realize that these salts may -be given without danger to the kidney. We do not suggest that -the kidney lesions of influenza and mercury bichloride poisoning -<span class='pageno' id='Page_85'>85</span>are the same. We are merely bringing out this point of analogy -in support of their use in certain desirable cases.</p> - -<p class='c009'>The respiratory symptoms gave us more concern than any -other phase of the uncomplicated case. The irritating, distressing, -non-productive cough suggested both a sedative and -expectorant. Ammonium chloride (gr. iii-v, t. i. d.) was the usual -expectorant. It seemed to increase in value with the more chronic -type of case. It is our impression with those acute hacking -coughs that the sedatives produced more gratifying results. -Elixir terpin hydrate with heroin, codeine and occasionally morphine -were preferred. When good results were noted sedatives -were given liberally. Steam inhalations combined with tr. benzoin -co., followed by spraying the throat with medicated liquid -petroleum, gave some relief. The tendency to œdema, however, -as we saw it in the cases complicated by pneumonia made us -hesitate to use inhalations. Possibly the fear was groundless. -Morphine (grs. ⅙) was given for sleeplessness, and it was -repeated if necessary.</p> - -<p class='c009'>Cardiac stimulants were rarely needed. The tincture of digitalis -was the choice, but in the uncomplicated cases was very -seldom used.</p> - -<p class='c009'>At the beginning of the epidemic we prescribed whisky in -almost every case. Our idea was that it would have a sedative -action. At the present time we are very doubtful of its value. -Toward the end of the epidemic we used it very moderately. The -results obtained possibly depended for the most part upon the -type of patient. Some of the soldiers asked to have it discontinued, -not from any moral point of view, while others wished -more frequent doses. The elderly patients seemed to appreciate -this remedial agent to a fuller extent.</p> - -<h3 class='c010'><em>Pneumonia</em></h3> - -<p class='c011'>The pneumonia following the original infection was, from the -standpoint of physical diagnosis, often difficult of diagnosis in its -early stages. The infection commencing as an influenza would -at times pass imperceptibly into pneumonia, and obviously the -points brought out in the previous paragraphs on treatment were -applied until the diagnosis of pneumonia had been established. -<span class='pageno' id='Page_86'>86</span>Some new factors were peculiar to the pneumonia and demanded -further changes in the handling of the cases.</p> - -<p class='c009'>We would again emphasize the value of careful nursing to -conserve the patients’ strength. They should be kept warm, well -covered, with plenty of fresh air. Water should be given regularly -and abundantly. The diet should be light, one depending -a good deal upon the severity of the case. We believe it is safer -to limit the diet to fluids while the infection is still pronounced, -but as soon as the crisis has passed one may increase the diet -freely and fairly rapidly.</p> - -<p class='c009'>Regular elimination from the bowel should be helped by the -use of castor oil every other day, the dosage made to comply with -the patient. We noticed much less abdominal distention in this -form of pneumonia than one is accustomed to see in the ordinary -lobar pneumonia. If distention were present, plain soap enemas -with turpentine gave very satisfactory results. Turpentine -stupes also are of considerable value. Rest at night is needed. -When a hypnotic was necessary we gave morphine (gr. ⅙), and -repeated if the desired results were not obtained.</p> - -<p class='c009'>The day is coming when we are going to isolate our pneumonia -cases. This was almost an impossibility during the stress of the -past epidemic, but we know that temporary and fairly satisfactory -methods can be applied. Many hospitals provided for a type -of isolation. In a pneumonia ward sheets stretched between the -beds keep the fine spray which a heavy cough always produces -from spreading over the next two or three beds. This method is -simple and can be easily carried out. We feel almost certain of -having seen convalescent influenza cases develop pneumonia from -the adjacent pneumonia patients. As much as is physically possible, -the uncomplicated influenza and the pneumonia cases should -be separated. Further, it is to be kept in mind that reinfection -by another group of pneumococcus is quite possible, even in a -ward containing only pneumonia patients.</p> - -<p class='c009'>We did not observe any special effect of quinine, salol, salicylates -after the pneumonia had developed and, therefore, these -drugs were discontinued. Digitalis in the form of the tincture -was at first made a routine measure, but toward the middle of -the epidemic we stopped this routine usage and gave it only as it -appeared to be indicated. Our impression was that the heart -<span class='pageno' id='Page_87'>87</span>was not involved as it is in ordinary pneumonia. A slow, full -pulse, as was so often the rule, did not seem to require digitalis. -For more rapid action of the drug one of the hypodermic digitalis -preparations or strophanthin was given.</p> - -<p class='c009'>Caffein sodium benzoate or salicylate seemed to be of considerable -value given hypodermically every two or three hours, the -last dose at 4 P. M. Its action as a respiratory stimulant and also -as a diuretic was what we desired to obtain. The drug was used -fairly early in the pneumonia, and although it was never prescribed -routinely we gave it frequently.</p> - -<p class='c009'>Atropine was indicated whenever signs of œdema were evident. -Its action was not always successful, but in certain severe cases -we believe that large repeated doses of atropine saved a few lives. -One-fiftieth (<span class='fraction'>1<br /><span class='vincula'>50</span></span> gr.) grain hypodermically, repeated every hour -for several doses, was usually well borne. We noticed twice in -each of two cases after using small doses (<span class='fraction'>1<br /><span class='vincula'>100</span></span> every four hours) -a peculiar rapid cyanosis not associated with dyspnœa develop. -This reaction remained, however, for only a short time, about 15 -to 20 minutes, but it was rather alarming while it lasted.</p> - -<p class='c009'>The drug therapy is not very satisfactory in lobar pneumonia, -and it is less so in the form of pneumonia which follows influenza. -There is practically nothing essentially new in the drug -and general treatment of this serious complication over what was -shown in 1890, or even in the earlier epidemics, save that our -nursing and hygienic measures are undoubtedly better.</p> - -<p class='c009'>The addition of an immune serum (anti-pneumococcus serum -No. 1) to the treatment of pneumonia is a milestone in the history -of the handling of this disease, but we must keep in mind -that the pneumonia of the past epidemic was not the usual pneumococcic -lobar pneumonia. That the pneumococcus was present -in a great many cases is shown in another article of this series, -but we also know that the B. influenzæ was present in many, and -that it played an active part in the disease is evidenced by the -constant low blood count or actual leucopenia. A leucopenia in -true lobar pneumonia is most unusual in the United States. The -rarity of Type I pneumococcus was noteworthy. We were practically -unable to get any anti-pneumococcic serum which was -known to be of value at the time of the epidemic, so naturally -could not apply this method of treatment as was desired. About -<span class='pageno' id='Page_88'>88</span>half a dozen 50 cc. bottles were in possession of the army medical -officers here, but they unfortunately could get no further supply -after this was used. We would have liked very much to have -combined the anti-pneumococcic serum in Type I cases with the -citrated convalescent blood, as was used by us during the epidemic. -The anti-pneumococcic chicken serum of Kyes should also -be considered. This serum has had but a very localized trial, -but from competent observers who have given it to a considerable -extent in some of the army camps we are led to believe that it -has a very definite value. Major Lawrence Litchfield informed -the writer that he had observed excellent results with Kyes -chicken serum during the past epidemic in the treatment of pneumonia. -This serum was not available for our use. It is to be -hoped that further experience with Kyes serum will be favorable, -because from the practical standpoint in the treatment of pneumonia -it has many commendable features. Again, we desire to -point out that the use of anti-pneumococcus sera in influenzal -pneumonia may not be a fair test of their true value.</p> - -<p class='c009'>Very early in the epidemic we realized that the pneumonia was -of unusual severity and most difficult to treat satisfactorily. We -were at once impressed by our helplessness, particularly in those -patients showing cyanosis. Nothing we did seemed to vary the -course of the pneumonia after this sign was evident.</p> - -<p class='c009'>Our work in the epidemic began about October 10 on receiving -a large batch of soldiers, about 100, from the Student Army -Training Corps of the University of Pittsburgh. At the end of -the first week several points were impressed on our mind. -Firstly, in the severe cases of pneumonia; and in the early part -of the epidemic most of the pneumonia was severe, the mortality -was excessive, much higher than we have been accustomed to -experience in Pittsburgh, where, as a rule, our hospital ward -pneumonia is a very severe infection. Secondly, the wide variation -in the severity of the epidemic as presented in the student -soldiers coming from identical surroundings and conditions, the -mildness on the one hand and the malignant character of the -influenza on the other, was a very striking feature. This led to -our adopting a form of treatment which was quite successful.</p> - -<p class='c009'>We worked purely on the hypothesis that those individuals -recovering from a mild or moderate influenza infection developed -<span class='pageno' id='Page_89'>89</span>a higher grade of immunity than those in whom the disease was -more severe or fatal, and this immunity could be transferred to -another. This, of course, was merely inference. If the mild -cases did present a higher immunity, one would naturally think -that immune bodies would be present in the blood, and that in -transfusion from cases which had recovered one might have a -measure of therapeutic value for this epidemic. Recently -Spooner, Scott and Heath and others have demonstrated specific -agglutins in the serum of patients convalescing from the epidemic. -On October 17 we gave whole citrated blood from a convalescent -case of uncomplicated influenza to an influenzal pneumonia -patient. The result in this case was strikingly good, and -for the following five or six weeks this method was frequently -used. We decided to give the whole blood instead of the serum, -as we were able to treat the cases more readily and rapidly in this -way. Our method of transfusion was, fortunately, very simple.</p> - -<p class='c009'>We had treated but a few cases when the report of McGuire -and Redden appeared. These observers working in the Naval -Hospital at Chelsea, Mass., presented very excellent results in -the use of immune serum from convalescent influenza cases in -the treatment of pneumonia. They reported 30 recoveries out of -37 cases, with 1 death, and 6 cases still under treatment at the -time of their report. This form of treatment began at Chelsea -on September 28, 1919. In Texas, on October 15, Brown and -Sweet gave two cases of influenzal pneumonia citrated blood from -convalescent influenza patients. Their two cases recovered. Our -published results, although not showing such excellent figures -as from the Chelsea observers, agree very well with their work.</p> - -<p class='c009'>Since that time a number of confirmatory reports have been -brought forward. Ross and Hund have shown that this method -has been of value in their hands, and recently a further statement -from McGuire and Redden tends to confirm their first views -as to the value of immune serum from convalescent patients. -Their last report giving a mortality of 6 in 151 cases of pneumonia -cannot be other than positive proof of the value of this -method of treatment.</p> - -<p class='c009'>As the technical side of the work has been given in several -articles, we hardly think it necessary to again review it in detail. -A few phases should, however, be recalled. It would seem that -<span class='pageno' id='Page_90'>90</span>either serum or the whole citrated blood may be used. Solis-Cohen -and his group of workers believe that whole blood has -stronger bactericidal properties than defibrinated blood or the -plasma. But yet one cannot complain, even on a theoretical basis, -against the results obtained with serum by McGuire and Redden. -The use of whole blood increases the detail of the procedure, in -that the agglutination reactions must be estimated. Unfavorable -results in this regard also naturally cut down the supply of -available donors. In a military hospital a dearth of donors does -not arise, but in civilian practice the problem is very different. -In our work we never gave more than 100 cc. of whole blood; -usually the amount varied between 50 cc. and 75 cc. On account -of the small amount we felt that isoagglutination would not be -a serious factor, and in more than 200 injections we failed to see -any evidence of ill results from this source. Giving up to 500 cc., -as was done by Ross and Hund, is probably a different affair, and -accurate agglutination tests are essential. We feel that if the -case is treated sufficiently early in the disease as much good can -be shown to occur after 50 cc. as after 100 cc. of blood. We do -believe, however, that the pooling of sera, where one is able to -carry out this method, as it means a liberal supply of donors, is -really the method of choice. Syphilis must be ruled out, both -clinically and serologically.</p> - -<p class='c009'>As we emphasized previously, the problem presented in the -army hospital and in civilian practice is a little different. We -have had some experience with both sides. Fortunately, the -greater part of our work was with the Student Army Training -Corps, where army conditions were more or less carried out. -There was never any difficulty in getting donors. In fact, the -idea of giving blood appealed to these young fellows. In civilian -life it is, in our experience, a more difficult problem. The usual -personnel of the public ward has always its fair percentage of -positive Wassermann reactors, and the type of individual is quite -different from the young soldier. For a relative or friend we -could easily get a donor, but this group would cover only a small -percentage of the cases one wished to treat. The technique of -giving blood can be reduced to a very simple procedure, and -by no means should be regarded as a difficult surgical undertaking. -Combining the receiving apparatus of Ross and Hund -<span class='pageno' id='Page_91'>91</span>(J. A. M. A., 72, 1919, p. 642) with the syringe method for giving -the blood which we suggested in our previous article makes an -ideal arrangement.</p> - -<p class='c009'>The results depend upon the time of treatment. The earlier -the pneumonia is recognized the better are the chances of recovery. -It is our belief that the majority of influenza cases -which kept a fairly high temperature for more than four days -had a lung lesion, even if we could not make out definite consolidation. -As the convalescent influenza serum may have value only -for the influenza infection, it would, therefore, appear but logical -that a late pneumonia which almost always has other organisms -present would not react as favorably. We have seen very few of -the deeply cyanotic type recover even with serum. The essential -rule is to treat them before this stage develops.</p> - -<p class='c009'>We have observed little or no change in the leucocyte count, -even after successful treatment, and taking our group as a whole -we are rather surprised at this result. Other observers have -noticed a marked increase in the leucocytes as the case reacted -favorably to the injections. We agree with McGuire and Redden -that the patients with counts below 10,000, as a rule, show the -best results. This possibly indicates that the influenza infection -is predominating, and that the usual secondary invaders (pneumococcus -and streptococcus) are at this time playing but a little -part. Hence the value of early treatment is apparent.</p> - -<p class='c009'>From the published results of different workers and our own -experience, we feel that influenza immune serum or whole citrated -blood given early in the pneumonia is of undoubted value—in fact, -almost specific. If the epidemic reappears next year, unless some -other better method is forthcoming, we would advise its more -general use, and would suggest the collection of pooled serum as -early as possible in the epidemic.</p> - -<p class='c009'>At the end of this article there is appended a series of our ward -record charts of patients who developed pneumonia following the -influenza. These charts are shown to indicate the results of -giving immune convalescent citrated blood in pneumonia. The -ones presented are from some of the group which recovered. We -have, of course, the charts from the fatal cases, but as they do -not bring out any special point, save that there was little or no -change after treatment, we are omitting them. It is not our -<span class='pageno' id='Page_92'>92</span>idea, however, to give the impression that we have had nothing -but success with this method of treatment. It might be well to -emphasize some of the salient points which are brought out.</p> - -<p class='c009'>(1) The regularity of the drop in temperature after the injection -is almost generally demonstrated.</p> - -<p class='c009'>(2) The occasional chill following the injection seemed to have -no untoward results.</p> - -<p class='c009'>(3) The leucocytes show, as a rule, little or no variation after -transfusion. Our work agrees with McGuire and Redden’s statement -that the cases with a leucocyte count under 10,000 give -the best results with immune serum.</p> - -<p class='c009'>(4) The time of injection in many of the cases was by no -means ideal, in that the disease was advanced; and again in many -the injection should have been repeated sooner. This, however, is -no fault of ours.</p> - -<p class='c009'>(5) One injection of 50 cc. of citrated blood from a good donor, -if given early enough, may be all that is necessary. Several -charts bear out this statement.</p> - -<p class='c009'>(6) The day of disease is dated from the onset of the influenza. -The demonstrable signs of pneumonia correspond roughly to the -initial rise in temperature following the influenza. The day of -disease of the pneumonia is not indicated on the chart, as this -information we have obtained from the daily notes.</p> - -<h3 class='c010'><em>Complications</em></h3> - -<p class='c011'>The epidemic was well spent before we observed many complications, -save those referable to the lung. Later various forms -of sequelæ have been appearing. One must guard, however, -against the danger of attributing all of our ills to the past epidemic. -We are not going to give in detail the treatment of these -various conditions, nor even mention all of the many complications. -The main points, however, we desire to emphasize.</p> - -<p class='c009'>We have previously considered pneumonia, which is the principal -complication with simple influenza, and the two are closely -allied. As an end result of the pneumonia, non-resolution and -fibrosis of the lung are of first importance. We cannot say very -much on the treatment of this condition. The duration varied -from a few to several weeks, and recovery was infrequent. Our -treatment aimed at supplying as much nourishment as was possible -<span class='pageno' id='Page_93'>93</span>to give, with, in addition, good nursing. The treatment -otherwise was purely of a general hygienic type. Tepid sponging -appeared to give considerable relief from the profuse sweating -these patients so often had. Drugs were of value only for some -local effect. We wonder if carefully handled vaccine therapy at -the onset of such a complication might not prove of some value. -The autogenous would be the one of choice.</p> - -<p class='c009'>Empyema was not found to be as prevalent as one would -imagine. With so much non-resolution of lung following the -pneumonia we were surprised to see so little empyema. All -delayed resolutions we explored with the needle, so we feel that -the condition, if present, would have been recognized. The treatment -of empyema need not be given any special emphasis. It is, -as of old, a surgical affair. One or two new points in the technique -have been brought out in the way of drainage, but possibly -they have not been sufficiently tried to lay any stress upon them -at present. Dakin’s solution in certain chronic cases appeared -of value. Our empyema cases did well.</p> - -<p class='c009'>Pleurisy with effusion was observed a number of times, although -it has been our experience to find a very few large -effusions. Pleural puncture often gave negative results, even -when the signs did appear to indicate the condition. We aspirated -the fluid when present. The end results were always good. In -only one case did we have to repeat the aspiration for reaccumulation -of fluid.</p> - -<p class='c009'>Chronic bronchitis, accompanied at times with considerable -dyspnœa, has been seen on several occasions. There is very -likely associated with this condition some fibrosis of lung, and -probably some organization of small bronchioles themselves. -Expectoration has been variable, profuse or scanty, mucoid or -purulent. We consider rest in bed, with as full a diet as possible -to build up the general condition of the patient, the best form of -treatment. These cases had little or no temperature, and consequently -at first absolute rest was not considered necessary, but -we now regard it as the essential part of the treatment. Atropine -and heroin are of value at certain times. We confess to have -seen very little benefit from the expectorants. We are rather -surprised that this sequela is not of more frequent occurrence.</p> - -<p class='c009'><span class='pageno' id='Page_94'>94</span>Phlebitis, in our series usually of the formal vein, occurred -about as often as it does in typhoid fever. The end result, however, -is much better than in typhoid. We have seen only one -case where “the milk leg” has resulted. Rest and elevation of -the limb were all that we required. In the acute stage, if pain was -present, a light, carefully applied icebag was added. It is important -to rest the limb for at least two or three weeks, and to -caution the patient against remaining on the feet too long for -some weeks after recovery.</p> - -<p class='c009'>We saw a great deal of acute sinus infection, often occurring -even while the attack of influenza was present, but, as a rule, -this complication followed the attack. At times several weeks -intervened. The ethmoidal sinuses are most susceptible, but a -considerable number of acute frontal sinus infections were noted, -the latter often immediately following or occurring during the -acute period of the influenza attack. The majority of these -infections appeared transient, and disappeared with a little local -treatment. In fact, in frontal sinusitis cold applications seemed -to be all that was necessary. With some of the more chronic -infections nose and throat surgery has been followed by relief of -symptoms. Acute suppurative otitis media, considering the number -of influenza patients, was not common. Ear drum puncture -was done if necessary. We saw one case of acute mastoiditis -develop. The mastoid process was opened and drained.</p> - -<p class='c009'>Acute suppurative meningitis, following or associated with -pneumonia, appeared on three occasions. The pneumococcus was -cultured from the spinal fluid in all cases. Anti-pneumococcus sera -intraspinally (Type I or the Kyes serum) should be given. The -Type I serum is of value in a similar group infection. We have -had no experience with this method, but some recoveries from -pneumococcus meningitis have been reported after the early use -of serum given into the spinal canal.</p> - -<p class='c009'>Following the 1890 epidemic cases complaining of blindness -or partial loss of vision, with optic œdema or neuritis and a -glycosuria, were occasionally observed. We have seen one of this -type, and several transient glycosurias without eye signs or -symptoms. The glycosuria may be of nervous origin. Our -method of treatment was one of elimination and rest. The gastro-intestinal -tract was emptied with calomel, and afterward a -morning saline was given for a few days. Hot packs were -<span class='pageno' id='Page_95'>95</span>administered, one a day for about two weeks. The patient was -instructed to drink as much water as possible, and we eliminated -sugar, bread and the 20 per cent. vegetables from the diet. The -glycosuria lasted for three days, while the vision, although beginning -to improve at once after treatment, took five weeks to -return to normal. The patient was kept in bed for three weeks. -How long the glycosuria had been present before admission to -the hospital we do not know. The transient glycosuria group -without the eye manifestations required very little treatment. -They also showed a transient hyperglycemia. A carbohydrate -free diet very rapidly cleared up these cases. After a time we -decided to watch the course of this group on a non-restricted -diet, even with sugar, and we found that they all returned to -normal (blood and urine), in a few days clearly indicating their -transient nature. We do not regard this process as a diabetes -mellitus. We do not give the hot packs, although free elimination -by bowel was attained in all. These cases were recognized -only through routine urine examination.</p> - -<p class='c009'>Furunculosis with a high blood sugar, in one case 0.41, without -glycosuria was a very interesting complication. We saw a great -deal of furunculosis, always with the increased blood sugar from -0.2 to 0.3, but never with glycosuria. Reducing the carbohydrates, -or even a fast day with good intestinal elimination, had -excellent results.</p> - -<p class='c009'>Neuritis and general debility have often been associated with -nasal or tonsilar infection, which when surgically corrected led -to the disappearance of symptoms and improvement of health.</p> - -<p class='c009'>Finally, we wish to refer to an isolated case of acute osteomyelitis -which was incised, and from the purulent fluid present in the -bone B. influenzæ was grown in pure culture. This is a very -unusual complication, and is of particular interest on account -of the positive bacteriological finding. The patient made an -uneventful recovery.</p> - -<table class='table2' summary=''> - <tr> - <td class='c006'>McGuire and Redden</td> - <td class='c020'>Jour. A. M. A., 1918; lxxi, p. 1311.</td> - </tr> - <tr> - <td class='c006'>McGuire and Redden</td> - <td class='c020'>Jour. A. M. A., 1919; lxxii, p. 709.</td> - </tr> - <tr> - <td class='c006'>Brown and Sweet</td> - <td class='c020'>Jour. A. M. A., 1918; lxxi, p. 1565.</td> - </tr> - <tr> - <td class='c006'>Ross and Hund</td> - <td class='c020'>Jour. A. M. A., 1919; lxxii, p. 640.</td> - </tr> - <tr> - <td class='c006'>Spooner, Scott and Heath</td> - <td class='c020'>Jour. A. M. A., 1919; lxxii, p. 155.</td> - </tr> - <tr> - <td class='c006'>Maclachlan and Fetter</td> - <td class='c020'>Jour. A. M. A., 1918; lxxi, p. 2053.</td> - </tr> - <tr> - <td class='c006'>Heist and Cohen</td> - <td class='c020'>Jour. Immunol., 1918; iii, p. 261.</td> - </tr> - <tr> - <td class='c006'>Kyes</td> - <td class='c020'>Jour. Med. Res., 1918; xxxviii, p. 495.</td> - </tr> -</table> - -<div class='nf-center-c0'> - <div class='nf-center'> - <div><span class='pageno' id='Page_96'>96</span>[Click on image for larger version]</div> - </div> -</div> - -<div class='figcenter id003'> -<a href='images/i_095a_full.jpg'><img src='images/i_095a.jpg' alt='' class='ig001' /></a> -</div> - -<div class='chapter'> - <span class='pageno' id='Page_97'>97</span> - <h2 class='c005'>THE PREVENTION OF EPIDEMIC INFLUENZA WITH SPECIAL REFERENCE TO VACCINE PROPHYLAXIS</h2> -</div> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>By <span class='sc'>Samuel R. Haythorn, M. D.</span></div> - </div> -</div> - -<h3 class='c010'>INTRODUCTION</h3> - -<p class='c011'>In developing practical measures for the prevention or control -of influenza epidemics, preventive medicine faces one of the most -difficult problems of modern times. By means of quarantine, -protective vaccination and instructions in personal hygiene many -of the diseases which formerly ravaged the world have been -brought under control. At first glance it would seem to be a -simple matter to apply the principles which we have found successful -against these diseases to influenza and let it go at that, -but in the recent epidemic many of the formerly successful -measures were tried and found to be either inefficient, inapplicable, -or at least of doubtful value.</p> - -<p class='c009'>During the pandemic there was little time to think collectedly, -and no time to analyze procedures, and even now it is far from -easy to determine what things were done wisely and what things -were of no practical value. There exists the greatest difference -of opinion as to what measures should again be used when the -need arises, and what ones should be discarded. For instance, -there are confirmed exponents of prophylactic vaccines, and -equally able men who are convinced of their uselessness; enthusiastic -advocates of the face mask, and almost as many objectors; -those who would close schools, churches, theatres, etc., and those -who claim that such measures serve only to prolong the epidemic. -One naval officer is said to have stated that he had accumulated -figures either to prove or to disprove the usefulness of any preventive -measure yet recommended. There is, in short, a chaos -of opinions with followers who vary from the one extreme of -believing there is “virtue in all things” to those of the other -extreme who state that every susceptible person develops the -<span class='pageno' id='Page_98'>98</span>disease in the degree of his susceptibility, regardless of any and -all preventive measures used. While there remain so many -points on which definite, concrete knowledge is lacking, and so -much controversy over the relative value of various measures, -this paper can do little more than state the facts and discuss -their bearing on prevention as impartially as possible.</p> - -<p class='c009'>Great progress has been made in controlling contagious diseases -in recent years—a fact which can be easily verified by -anyone who will compare the sick reports of the Great World War -with those of any war previous to the beginning of the present -century. The diseases which have been most easily controlled -have been those against which prophylactic vaccines or prophylactic -sera have been developed. Smallpox, dysentery and -typhoid fever have lent themselves readily to control by protective -vaccination, while reliable temporary immunity can be -afforded by the administration of sera for protection against -diphtheria and tetanus. These are by no means all, but are -probably the most striking illustrations; and with such examples -before us, the greatest hope for the prevention of influenza -apparently lies in the development of a prophylactic vaccine -against it.</p> - -<h3 class='c010'><em>History of Prophylactic Vaccination in General</em></h3> - -<p class='c011'>The name vaccine came from “vacca,” or cow, and was originally -applied by Jenner (1796) to the virus taken from cowpox -pustules for prophylactic inoculation against smallpox. It -has come to be loosely applied to all forms of preventive inoculations -except sera. We have, therefore, a variety of vaccines -which differ in their nature and method of preparation. Some -are produced by growing the virus in insusceptible animals, some -are composed of attenuated viruses, and most common of all are -the bacterial vaccines, sometimes called “bacterins,” which are -prepared from killed cultures of bacteria. Sera are used in -prophylaxis, as well as treatment, and are made by bleeding and -separating off the serum from animals which have been immunized -against the cause of the disease in question. Sera and -vaccines are wholly different products, and the distinction should -be made in discussing them, although there is a common tendency, -particularly among lay writers, to use the words interchangeably. -<span class='pageno' id='Page_99'>99</span>Smallpox is the classical example of a disease which -can be completely controlled by universal vaccination. The parasite -causing smallpox has never been certainly demonstrated, but -over a century ago Jenner showed that cowpox, a localized, non-fatal -disease, protected against smallpox. Modern methods have -proven that a cow inoculated with smallpox virus develops cowpox, -and that thereafter the virus loses its power to produce -smallpox when it is returned to man. Instead, it causes a local -pustule, and confers immunity to smallpox over a considerable -length of time. Rabies is another example in which the exact -cause of the disease is still in doubt, and in which a protective -vaccine has proven of great value. Rabies vaccine was developed -by Pasteur, and is prepared by drying the spinal cords of rabbits -that have been killed by a highly virulent rabies virus. Typhoid, -dysentery, pneumonia and several other diseases of known etiology -have been more or less controlled by the use of vaccines -made from their respective bacterial causes. These vaccines are -of the “killed bacteria” type of vaccines, and credit for their -application to human disease belongs to Sir Almroth Wright -(1896). The preparation of bacterial vaccines is very simple. -Bacteria which are known to cause a certain disease are isolated -in pure culture, grown on artificial media, killed either by chemicals -or heat, standardized either by counting, or drying and -weighing, and suspended in salt solution for subcutaneous injection. -Salt suspension vaccines are usually given in three or four -increasing doses, about one week apart. Le Moignic and Pinoy -(58) first elaborated a lipovaccine for triple typhoid vaccination, -which was used extensively in France during the war. -Whitmore, Fennel and Peterson have recently also advised the -drying of killed bacteria and the suspension of them in oil. This -method makes it possible to give a single massive dose of bacteria -which is sufficiently large to completely immunize the -individual against the disease, and which prolongs the immunizing -period by allowing slow absorption over a period of several -weeks. These vaccines are called lipovaccines, have been adopted -in the United States Army as the standard typhoid vaccine, and -promise in time to supersede the salt suspensions entirely from a -commercial standpoint. Many other modifications in the preparation -of bacterial vaccines have been advised, notably the class -known as sensitized vaccines. These are prepared by incubating -<span class='pageno' id='Page_100'>100</span>bacterial vaccines for a time with the serum taken from animals -already immunized against them. The serum apparently absorbs -many of the toxic substances, and permits the injection of more -efficient doses. Besredka advised the use of living cultures which -had been incubated with immune sera, on the basis that vaccines -so prepared were very active and non-toxic. The sensitizing -treatment, however, does not stop the growing powers of the -bacteria, and vaccines of the Besredka type are generally considered -dangerous and so are little used. Sensitized killed bacterial -vaccines, on the other hand, are quite popular.</p> - -<p class='c009'>When a sufficiently large dose of vaccine is given to an individual -there is usually a transient rise in temperature for from -12 to 48 hours; the local focus of injection becomes sore and -inflamed, and a white count often shows an actual increase in the -number of polymorphonuclear leucocytes in the general circulation. -A series of doses are usually given. If after a few days -blood is withdrawn from the patient and immuniological tests -made, it will generally be found that the patient’s leucocytes take -up bacteria, and particularly the type of bacteria of which the -vaccine was composed, more readily and in greater numbers than -the leucocytes of the ordinary individual. Wright and Douglas -(52) and Neufeld and Rimpau (53) have shown that this effect -of increased phagocytosis is brought about by the vaccine through -the production of substances which act specifically on the bacteria -and render them more susceptible to inclusion within the -white cells. These substances belong to the group of antibodies, -and are known as “opsonins” or “bacteriotropins,” and are -specific for any given bacteria. Moreover, the serum of the -patient will, as a rule, be found to have developed the faculty -of agglutinating and bacteriolysing suspensions of the specific -organism injected and of fixing complement in the presence of -an antigen prepared from that organism. In animal work it has -been possible to go still farther, for it can be shown that the -resistance of the animal can be raised until it is no longer possible -to kill it with the same dose which is found to be fatal for -the unimmunized animals. Not only has animal work made it -possible to determine the protective powers of vaccines, but it -has also served to show the specific nature of the protective -power and the relative extent to which “group” or “crossed” -protection can be conferred by vaccinating with closely allied -<span class='pageno' id='Page_101'>101</span>organisms—as, for instance, paratyphoid bacilli in typhoid fever. -The non-toxic nature of vaccines is also determined by animal -experiment before such preparations are injected into humans.</p> - -<p class='c009'>The most successful prophylactic bacterial vaccine which has -been developed so far is that for typhoid fever. A comparison -of the occurrence of typhoid fever in the United States Army -before and since the use of anti-typhoid vaccine is all that need -be cited to convince one of its value. At the time of the Spanish -War there was no vaccination against typhoid fever, and there -were 20,738 cases, with 1,580 deaths, among 107,973 men who -remained in the camps in the United States during the war (54).</p> - -<p class='c009'>During the summer of 1911, the maneuver division of the -United States Army, having 12,801 men, all of whom had been -vaccinated against typhoid fever, were stationed at San Antonio, -Texas. Two cases of typhoid fever developed among them, and -neither case died. Among the civilian population of the city, -living under usual conditions during the same time, there were -49 cases of typhoid fever, with 19 deaths. Since 1912, typhoid -vaccination has been compulsory in the United States Army, and -the largest epidemic of typhoid fever which I have found reported -so far during the late war was that at Camp Greene (55), Charlotte, -N. C., where 18 cases developed. Only 12 of these men -had received the complete series of immunizing doses. For a -complete discussion of the value of typhoid vaccine the interested -reader is referred to Gay’s Monograph (56) on typhoid fever.</p> - -<h3 class='c010'><em>Prophylactic Vaccination Against Influenza</em></h3> - -<p class='c011'>The hope of finding an early solution to the vaccine problem -in influenza appeared to be in the development of a prophylactic -“bacterial vaccine” similar to that which proved so efficient for -typhoid. In his discussion of the vaccine problem in pneumonia, -Fennel pointed out that, theoretically, any disease of microbic -origin in which spontaneous recovery is at all possible should -yield to specific prophylactic measures. The difficulty, however, -of preparing a bacterial vaccine for influenza comparable to that -for typhoid fever is that the unquestioned cause of influenza has -yet to be determined. The probable cause of influenza is the -Pfeiffer bacillus, but its relationship has not been proven beyond -question. On the other hand, the innocence has likewise not been -proven, as Dr. Holman in his article of this series has ably shown. -<span class='pageno' id='Page_102'>102</span>It is not my intention to go deeply into the question of etiology, -but simply to bring out a few points which <i><span lang="la" xml:lang="la">a priori</span></i> seemed to -indicate that the reasonable solution of vaccine prophylaxis was -in the preparation of a pure Pfeiffer bacillus suspension.</p> - -<p class='c009'>The experiments in man lead to very surprising results. Rosenau, -Keegan, Goldberger and Lake, at Gallops Island, Boston, -Mass., (1) inoculated volunteers with pure culture of B. Pfeiffer, -with secretions of the upper air passages and with blood from -typical cases of influenza. Sixteen men, of whom 13 were supposedly -non-immune, had Pfeiffer bacilli installed into their nasal -passages, and none of them developed the disease. Secretions -filtered and unfiltered also gave negative results. Contact with -well-developed early cases also failed. McCoy and Richey (1a) -conducted similar experiments in San Francisco, with negative -results. The men of the latter group had been vaccinated with a -mixed streptococcic vaccine, which may have played some part. -Had the experiments with the Pfeiffer bacillus been negative -and the other experiments positive, they would have shown that -the bacillus of Pfeiffer was not the cause of influenza; but since -all attempts were negative, it merely brought out the fact that -there had been a change, due probably to some immune factor, -which seemed to have acted alike on the Pfeiffer bacillus and all -other types of virus present, and to have made them all innocuous. -These experiments still leave the cause of influenza in question.</p> - -<p class='c009'>Those who are opposed to the Pfeiffer bacillus being the cause -of influenza in its epidemic form base their position on the -points that the common finding of the bacillus might be accounted -for on the grounds of its being a secondary rather than a primary -invader; that while it is not so common at ordinary times, it -does occur with other organisms in whooping cough and sometimes -in chronic diseases of the air passages, and that the rules -of Koch have not been complied with in that the organism -has not been found in every case of the disease; that where it -has been grown in pure culture and inoculated into man and animals, -it has either produced no disease, or the lesions which followed -have not been typical of epidemic influenza. On the side -of those who believe that the Pfeiffer bacillus is the chief cause, -or, at any rate, that it is partly responsible for epidemic influenza, -are the facts of its fairly constant presence in the purulent -bronchial secretion of patients suffering from epidemic influenza; -<span class='pageno' id='Page_103'>103</span>its relatively uncommon occurrence at other times; its known -pathogenicity in occasional cases of meningitis, and in the inflammation -of the bony sinuses of the head and face; the relative -immunity of nearly all common laboratory animals and the fact -that the attempts to transfer epidemic influenza from man to -man failed not only when Pfeiffer bacilli were used, but also when -direct contact and direct coughing by the patient into the face -of the volunteer were tried. The argument that many cantonment -laboratories failed to find the organisms loses weight when -we find that the percentage of positives increased where the -material examined was removed directly from the lungs at -autopsy, where special cultural methods were in use and where -the laboratory personnel was large enough to devote a sufficient -amount of time to each individual culture. All of these points -indicate that the organism was overlooked in a great many -instances. In our laboratory we found the examination of sputa -very unsatisfactory because of the great amount of contamination, -and because the bacillus seemed to lose its ability to grow -after a relatively short time in the sputum in vitro. Moreover, -I am convinced that the bacillus changes its morphology to such -an extent under varying conditions as to make it impossible of -identification when present among other organisms in sputum -smears. The failure of animal inoculations is also not conclusive -evidence against the Pfeiffer organism, because guinea pigs, -rats and mice have a natural immunity for them. Rabbits are -only slightly susceptible, and then only to intravenous injections. -The mixture of the Pfeiffer bacillus with any one of several other -pathogenic organisms will increase the pathogenicity of both. -Monkeys inoculated intracranially develop a typical Pfeiffer bacillus -meningitis.</p> - -<p class='c009'>Whatever the ultimate outcome of the investigations as to -the parasitic cause of epidemic influenza, the Pfeiffer bacillus -was the generally accepted cause at the beginning of the 1918 -epidemic, though it was at once realized that most of the deaths -were due to complicating pneumonias and to secondary infections -with other organisms. Under the circumstances, one of two -courses was open: (a) the acceptance of the Pfeiffer bacillus as -the presumptive cause of influenza and the preparation of a -specific prophylactic vaccine against infections with that organism; -or (b) the use of a mixed bacterial vaccine containing the -<span class='pageno' id='Page_104'>104</span>common and most deadly secondary infecting organisms, designed -to increase the patient’s general resistance by decreasing his -susceptibility to the allied, collateral and secondary infecting -agents. Attempts were made along both lines, with more or less -unsatisfactory results.</p> - -<h3 class='c010'><em>The Attempt to Develop a Specific Prophylactic Vaccine by the Use of Pure Pfeiffer Strains</em></h3> - -<p class='c011'>By a specific prophylactic vaccine for any given disease, we -mean a material which when inoculated into an individual will -actively protect that individual against the given disease. In -infectious diseases, the immunizing material is usually of microparasitic -origin (in contrast to desensitizing substances used in -pollen diseases and those due to unusual sensitiveness to foreign -proteins), and is specific only for the disease caused by the microparasite -from which the material was prepared. With the knowledge -in hand during the epidemic, the logical plan seemed to be -to prepare a pure Pfeiffer bacillus vaccine, the object of which -was to eliminate primary infection with that organism and thus -prevent the secondary invaders from obtaining a fertile soil.</p> - -<p class='c009'>While specific Pfeiffer bacillus vaccines had been tried in treatment, -the field was a comparatively new one so far as prevention -was concerned. Many of the biological products companies had -so-called influenza vaccines on the market for treatment purposes, -and many of these contained Pfeiffer bacilli. A few preparations -of pure strains of the bacilli were also available, but I -was unable to find any records of their use for prophylaxis. -Lacy (2) reported two cases of sinusitis treated with autogenous -vaccines made from pure Pfeiffer strains—one patient improved -rapidly and the other showed no change. Investigation of several -of the other references on influenza vaccines showed that mixed -vaccines had been used in each instance. The work of Flexner -and Wolstein (3, 4 and 5) indicated that active immunizing substances -could be prepared from the Pfeiffer bacillus, although -they worked with serum instead of vaccines. They prepared an -anti-influenza-meningitis serum by immunizing goats and horses. -These sera cured monkeys of experimentally produced influenzal -meningitis. The sera showed agglutinins and bacteriotropins -for Pfeiffer bacilli, as well as positive fixation tests in dilutions -of 1 in 100, but they contained no lysins. The serum was offered -<span class='pageno' id='Page_105'>105</span>for intradural use in treating influenzal meningitis, but was -found to have no value when used in human cases.</p> - -<p class='c009'>The first references which we have found on the use of pure -Pfeiffer bacillus vaccines for the prevention of epidemic influenza -were those of Leary (6), (7), and of Rosenau (8). Shortly after -the appearance of the first influenza cases in Boston, Leary used -a vaccine prepared from several strains of Pfeiffer bacilli both -for the treatment of influenza and for its prevention. The vaccine -for the latter purpose was given to medical students and -nurses, and the first results were apparently very encouraging. -Continued use has not been convincing. Barnes (9) reported an -attempt to protect the employees and patients of an institution -near Woonsocket. On October 9 a case of influenza developed in -the female ward, and was followed five days later by another. -On October 22 the disease appeared in the male ward, and the -same day 172 employees and patients were given their first inoculation -with Leary’s vaccine. Doses of 400, 800 and 1,200 million -bacilli were given at 24–hour intervals. All persons who had -developed influenza before the three doses had been completed -were excluded from the computation of the disease incidence, -which was found to be 20 per cent. both among vaccinated and unvaccinated -individuals. The mortality rate was 16 per cent. for -the 25 cases among the vaccinated, and 15.8 per cent. among 57 -unvaccinated patients. The result failed to show any protective -qualities for the vaccine.</p> - -<p class='c009'>The best controlled vaccine experiment in which Leary’s vaccine -was used was that reported by Hinton and Kane (10), and -was carried out at the Monson State Hospital for epileptics. The -hospital had a population of 979 inmates, ranging from 4 years -of age to senility; of these 461 were vaccinated and 518 were not. -Vaccination was begun on October 6, and three doses of 400, 800 -and 1,200 million were given at 24–hour intervals. The first case -of influenza developed a few hours after vaccination was completed, -but there were no more cases before October 12, when five -cases developed. The table shows the result of the work, and -that the vaccine failed to protect.</p> - -<table class='table2' summary=''> - <tr> - <th class='c015'></th> - <th class='c016'>Population.</th> - <th class='c016'>No. of Cases.</th> - <th class='c016'>% of Cases.</th> - <th class='c016'>No. of Deaths.</th> - <th class='c017'>% of Deaths.</th> - </tr> - <tr> - <td class='c015'>Vaccinated</td> - <td class='c018'>461</td> - <td class='c018'>163</td> - <td class='c018'>35.4%</td> - <td class='c018'>28</td> - <td class='c019'>17.1%</td> - </tr> - <tr> - <td class='c015'>Unvaccinated</td> - <td class='c018'>518</td> - <td class='c018'>178</td> - <td class='c018'>32.4%</td> - <td class='c018'>24</td> - <td class='c019'>13.4%</td> - </tr> -</table> - -<p class='c009'><span class='pageno' id='Page_106'>106</span>Attempts to protect by the use of Leary’s influenza vaccine -were made in 11 other Massachusetts institutions, but the results -cannot be used to compare the incidence and mortality rates -between the vaccinated and unvaccinated, because the epidemic -was either on the wane, or at least well advanced when the vaccinations -were begun. The reports are of great interest in -showing the large number of vaccinations which failed to protect.</p> - -<p class='c009'>In the Taunton State Hospital about 800 were vaccinated, and -among them there were 81 cases of influenza and 17 deaths from -pneumonia, even though the epidemic was on the wane when -vaccinations were begun.</p> - -<p class='c009'>In the Gardner State Colony 834 were vaccinated after the -peak of the epidemic had passed. This number included all but -15 of the inmates who had not contracted influenza up to that -time. Out of this group, 62 vaccinated individuals developed the -disease.</p> - -<p class='c009'>At the Massachusetts School for Feeble-Minded 457 inmates -were selected for vaccination and controls. Of the 234 vaccinated, -56 developed influenza. Of the 223 unvaccinated, 185 -developed influenza, with 16 pneumonias and 12 deaths. The vaccinated -group, however, were a more vigorous group of individuals -to begin with, and represented a higher mental grade -than the unvaccinated group, so that the evidence was considered -of questionable value.</p> - -<p class='c009'>At the Wrentham State School the influenza epidemic was -well under way before vaccinations were begun, and hence the -susceptible individuals were in a large part either affected or -infected with the disease. Of 1,198 unvaccinated persons, 758 -developed influenza, giving a morbidity rate of 63 per cent. Of -128 vaccinated, 13 developed influenza and 1 died. Physicians in -this institution believe that the vaccinated were not as ill as the -unvaccinated patients.</p> - -<p class='c009'>In the Medfield State Hospital, having a total population of -1,940,421 cases of influenza, with 63 deaths, had occurred before -vaccinations were begun. Of the remaining unattacked inmates -902 were vaccinated. After the completion of vaccination one -new case appeared among the unvaccinated, and there were none -among the vaccinated.</p> - -<p class='c009'><span class='pageno' id='Page_107'>107</span>At the North Hampton State Hospital there were 9 cases of -influenza, 4 of whom died, among 444 unvaccinated individuals, -and 9 cases, with 1 death, among 563 vaccinated patients.</p> - -<p class='c009'>Among 506 patients vaccinated at the Westborough State Hospital -there developed 15 cases of influenza, 2 of which terminated -fatally. Of the 415 unvaccinated controls, 25 developed influenza -and there were no deaths. At the time vaccinations were completed -only 13 had developed influenza.</p> - -<p class='c009'>In the Worcester State Hospital vaccination was carried out -after the epidemic had entirely subsided.</p> - -<p class='c009'>At the Bridgewater State Hospital no vaccines were used, but -the morbidity rate was 29.9 per cent., as contrasted with 32.9 -per cent. among the unvaccinated at Monson.</p> - -<p class='c009'>At the Danvers State Hospital the population of 853 adults -was divided into three sections. One section was vaccinated with -the Leary vaccine, one section with an unheated influenza vaccine -prepared by Dr. Rosenau at the Chelsea Naval Hospital, and one -section held as controls. The epidemic had, however, reached its -height before vaccination was begun, and no information as to -the relative value of the vaccines could be determined.</p> - -<p class='c009'>In Hinton’s (11) report the analysis covered the studies on -about 6,000 vaccinated individuals, which represented slightly -less than half of the population of 12 Massachusetts State institutions. -Hinton’s conclusions were as follows: “The heated suspension -of influenza bacilli used as a prophylactic vaccine did not -prevent influenza, lessen its severity nor its complications, and, as -far as could be ascertained, resulted in no harm.”</p> - -<p class='c009'>About the same time that Leary was working on his vaccine, -Rosenau prepared an unheated suspension of Pfeiffer bacilli, -isolated from cases of influenza of the existing epidemic, which -he used at the Chelsea Naval Hospital and in an experiment at -the Pelham Bay Naval Training Station. The writer is indebted -to Surgeon-General of the Navy W. C. Braisted for the data -from which this report was compiled—the report of the Sanitary -Officer of the station not having been completed at the time the -information was furnished. The vaccine experiment was made -in the isolation regiment, which had remained practically free of -influenza. Inoculations were begun on September 30, when 638 -men were given the first dose of vaccine, 833 men being held as -controls. On October 4 the second dose was given to 589 men, -<span class='pageno' id='Page_108'>108</span>and vaccination was completed on October 8, when 565 men were -inoculated. This group comprised the total number who received -three inoculations. On October 14 practically all of these men -were transferred, so that it was very difficult to get a complete -record. Those cases which developed influenza prior to October -10 have been omitted by the writer, both from the control and -vaccinated groups, because it is unfair to consider the incidence -of influenza among controls which developed prior to the time -the inoculations were completed in the vaccinated group. Between -October 10 and October 24 there were 27 cases of influenza -which developed among the vaccinated, and 30 among the controls, -giving a morbidity rate of 3.6 per cent. among the 833 -controls, as compared to 4.7 per cent. among the 565 vaccinated -men. Emphasis is laid on the fact that these morbidity rates -were calculated for both groups on the number of cases that -appeared after vaccination had been completed. The result failed -to show protective qualities in the vaccine.</p> - -<p class='c009'>Influenza vaccines for prophylaxis were also prepared in great -quantities by the New York City Board of Health, and were made -under the direction of W. H. Parke. No reports on the value of -their vaccines have as yet appeared, and the writer has been -unsuccessful in obtaining any data on the matter. The Parke -vaccine was made in the following way: A large number of -strains of Pfeiffer bacilli were isolated from cases of influenza -during the epidemic. These were grown on a veal infusion agar -containing 1 per cent. peptone, 0.5 per cent. of sodium chloride, -5 per cent. chemically pure glycerin, and the reaction of which -was made neutral to phenolthalein in the cold. The agar was -melted, and from 3 per cent. to 5 per cent. of citrated horse blood -was added to it at a temperature above 95° C. The media was -then slanted and cooled in 6 × 1 inch test tubes. Most of the -vaccines contained about 17 different strains of Pfeiffer bacilli. -The strains were inoculated separately on a series of slants, and -at the end of 24 hours the cultures were washed off with sterile -water and the washings from each series were placed in a separate -bottle. Smears were then made to determine whether or -not gram positive organisms were present, and as soon as each -bottle was found to be free from contamination the contents -were pipetted off into a 1,000 c.c. flask, and the dilution with -sterile salt solution containing 0.25 per cent. phenol made. All -<span class='pageno' id='Page_109'>109</span>of the strains were mixed together in the large flask. A sample -was then removed for standardization by Wright’s method, and -the flask was submerged for one hour in water at 53° C. Transplants -for sterility were made and watched for 48 hours. The -vaccine was then diluted so that each cubic centimeter contained -1,000,000,000 Pfeiffer bacilli. Prophylactic vaccination was carried -out by giving ½ c.c., 1 c.c. and 1½ c.c. doses at seven-day -intervals.</p> - -<h3 class='c010'><em>Author’s Vaccine</em></h3> - -<p class='c011'>At the request of the Department of Public Health of the city -of Pittsburgh, the writer undertook to prepare Parke’s vaccine -in large quantities. The vaccine was to be prepared under the -direction of a committee consisting of Drs. Oskar Klotz, W. L. -Holman, E. W. Willetts, George L. Hoffman and the writer, and -the vaccine was to be turned over to the City Health authorities -for distribution in the community. The work was carried out -at the Singer Memorial Laboratory, and was begun the same day -that the committee was appointed. Thirteen strains of Pfeiffer -bacilli were used. Holman contributed six strains, isolated at -autopsies done by Klotz at the Magee Hospital. Other fresh -cultures were furnished by Willetts; Wiese, of the City Laboratory, -and by the Singer Laboratory. The media used was that -recommended by the New York Board of Health, save that -sheep’s blood was used instead of horse blood because of convenience. -The same technique was employed, with the exception -that a modification of the Hopkins method of standardization -was used instead of the Wright method. This was done -because Pfeiffer bacilli are extremely small, tend to form unbreakable -clumps and tangles, and so increase the difficulties of -making satisfactory counts, either by means of the Wright -method or with the Helber-Glynn counting chamber, that the -methods are independable. Opalescent standards permit of such -enormous variations that it was decided to use the Hopkins -method, or a slight modification which we found so satisfactory -that we will give our method here in detail.</p> - -<h3 class='c010'><em>Method of Standardization</em></h3> - -<p class='c011'>When the sample was removed for standardization it contained -not only a thick suspension of Pfeiffer bacilli, but also bits of -<span class='pageno' id='Page_110'>110</span>agar and blood-stained debris. It was necessary to rid the suspension -of the gross contamination, and this was done at first by -filtering it through sterile glass wool filters, and later by centrifuging -it at slow speed for about 10 minutes. The suspension -then contained little but the Pfeiffer bacilli, and was placed -in the Hopkins tube and centrifuged for ½ hour on the sixth -contact of the rheostat. This gave the per cent. of Pfeiffer -bacilli in the suspension, and the necessary dilutions to make -1,000,000,000 per cubic centimeter were readily determined. The -Hopkins tube consists of a centrifuge tube, with a capillary tube -sealed on at the smaller end. The centrifuge tube is graduated -in 10 c.c., 5 c.c. and 1 c.c. amounts, and the capillary portion is -graduated in 0.01, 0.02, 0.03, 0.04 and 0.05 c.c. amounts. To -standardize the vaccine, 10 c.c. of the sample was centrifuged in -the tube and the amount of sediment read on the capillary scale. -If the amount of bacilli fell between the graduations, an additional -amount of sample was added, so that the sediment reached -one of the graduated lines, the exact amount of sample added -being noted. The percentage of the suspension could thus be -determined by dividing the number of c.c. of sample used into -the amount of the sediment obtained, and the number of bacteria -calculated according to Hopkins table. The table available to -us did not list the Pfeiffer bacillus, but according to it a 1 per -cent. suspension of staphylococcus contains 10 billion organisms -to the cubic centimeter, and we estimated that Pfeiffer bacilli -were about half the size of staphylococci. This assumption was -borne out by a number of Wright’s method counts on standardized -suspension of bacilli. We, therefore, calculated that a 1 -per cent. suspension of Pfeiffer bacilli should contain about 20 -million organisms. Then, if 10 c.c. contain 0.02 c.c. of bacterial -sediment, the per cent. was calculated by taking <span class='fraction'>0.02<br /><span class='vincula'>10</span></span> = 0.2 per -cent., the strength of the suspension. If 1 per cent. contains -20 billion, then 0.2 per cent. contains 4 billion per c.c. In order -to get a 100 million per c.c. suspension, it would be necessary to -dilute the original suspension 40 times.</p> - -<p class='c009'>Every method of standardization is more or less inaccurate, -but the above described method gave a fairly uniform product. -Drying and weighing is claimed by many to be more accurate, -but even with this procedure a fair amount of non-bacterial sediment -is present in the material to be weighed.</p> - -<p class='c009'><span class='pageno' id='Page_111'>111</span>After the vaccine was completed, cultures were made from -the final dilutions and were watched for 48 hours. Mice and -guinea pigs were injected with the first samples to make certain -that the material was non-toxic. Two laboratory employees also -volunteered and received full doses before the first batch of vaccine -was released. The first five litres were turned over to the -Red Cross on October 31, one week from the day the work was -begun. In three more days the laboratory reached a capacity -of 10 litres a day, and on the fifth day the order was received to -discontinue preparation of the vaccine.</p> - -<p class='c009'>Relatively little of our vaccine was given out, and in the rush -it was not possible to determine which physicians had been given -our vaccine and which had received commercial mixed products, -so there is no data on its protective powers.</p> - -<p class='c009'>As soon as we found that there was no call for prophylactic -vaccines, we planned some animal experiments; but inasmuch as -we were unable to get our cultures of Pfeiffer bacilli virulent -enough to kill mice or guinea pigs, the minimum lethal dose could -not be determined, and without it it was impossible to determine -the protective value of the vaccine. Mr. Purwin, in our laboratory, -injected a 25–gram mouse intravenously with 2 c.c. of a -milk thick suspension of Pfeiffer bacilli without killing the animal. -He was successful in getting a small needle into the tail -vein and in slowly injecting the whole amount. The mouse was -sick for about 36 hours, but entirely recovered. Guinea pigs -were insusceptible to very large doses. Had we succeeded by -means of a vaccine in completely immunizing a man against -Pfeiffer bacilli, we still would have been uncertain that he was -immune to influenza in its “epidemic” form.</p> - -<p class='c009'>The absence of virulence in our laboratory strains may not -mean that the cultures were non-virulent when first isolated, but -it suggests the uselessness of attempting to make active vaccines -from strains kept on artificial media for months or years, such -as those commonly offered for sale by commercial houses.</p> - -<p class='c009'>The loss of virulence in strains that have been isolated for -some time is interesting in the light of Parker’s (12) work upon -toxine production by Pfeiffer bacilli. She found that toxic filtrates -appeared in infusion broth cultures in from 6 to 8 hours, -and that 2 c.c. of a 20–hour filtrate would kill a medium-sized -rabbit in from 1 to 3 hours. It was also found that the poison -<span class='pageno' id='Page_112'>112</span>deteriorated so rapidly that, in order to determine its toxicity, -the tests had to be made on the same day that the filtrate was -obtained. Parker succeeded in making an anti-serum against the -poison, which appeared to be antitoxic for it both in vitro and -in vivo. This work is interesting, and may be a step toward the -development of a practical prophylactic serum.</p> - -<h3 class='c010'><em>Conclusion</em></h3> - -<p class='c011'>From the above data, it is apparent that there is very little to -indicate that an immunity to epidemic influenza is conferred by -the use of a prophylactic vaccine composed of inert Pfeiffer -bacilli alone. If a desirable vaccine is to be obtained through -the use of these organisms, there must be radical changes in the -mode of preparation of the vaccine or in the size of the doses -given.</p> - -<h3 class='c010'><em>The Attempt to Protect Against Epidemic Influenza by the Use of Mixed Vaccines</em></h3> - -<p class='c011'>For some years commercial houses have been carrying mixed -vaccines for the treatment of colds, which they called influenza -vaccines. These preparations were made up usually of six or -more different varieties of bacteria, and all of them were of -similar composition. There was more or less variation in the -doses, both as far as the total number of bacteria and the relative -number of the different types were concerned. A typical example -of a so-called “mixed influenza vaccine” may be given about as -follows:</p> - -<table class='table2' summary=''> - <tr> - <td class='c015'>B. Influenza (Pfeiffer)</td> - <td class='c018'>25</td> - <td class='c016'>to</td> - <td class='c018'>400</td> - <td class='c021'>million per c.c.</td> - </tr> - <tr> - <td class='c015'>M. Catarrhalis</td> - <td class='c018'>25</td> - <td class='c016'>to</td> - <td class='c018'>400</td> - <td class='c021'>million per c.c.</td> - </tr> - <tr> - <td class='c015'>B. Friedlander</td> - <td class='c018'>25</td> - <td class='c016'>to</td> - <td class='c018'>400</td> - <td class='c021'>million per c.c.</td> - </tr> - <tr> - <td class='c015'>Pneumococci</td> - <td class='c018'>25</td> - <td class='c016'>to</td> - <td class='c018'>400</td> - <td class='c021'>million per c.c.</td> - </tr> - <tr> - <td class='c015'>Streptococci</td> - <td class='c018'>25</td> - <td class='c016'>to</td> - <td class='c018'>400</td> - <td class='c021'>million per c.c.</td> - </tr> - <tr> - <td class='c015'>Staph. Albus-Aureus</td> - <td class='c018'>50</td> - <td class='c016'>to</td> - <td class='c018'>800</td> - <td class='c021'>million per c.c.</td> - </tr> - <tr> - <td class='c015'> </td> - <td class='c018'><hr /></td> - <td class='c016'> </td> - <td class='c018'><hr /></td> - <td class='c021'> </td> - </tr> - <tr> - <td class='c016'>Totals</td> - <td class='c018'>175</td> - <td class='c016'>to</td> - <td class='c018'>2800</td> - <td class='c021'>million per c.c.</td> - </tr> -</table> - -<p class='c009'>These vaccines were recommended in the various catalogues -for use either alone or together with other vaccines in the prophylaxis -and treatment of common colds, and in acute and chronic -diseases of the respiratory tract. As a matter of fact, they had -<span class='pageno' id='Page_113'>113</span>been used very little in prophylaxis, and had failed to show very -much value in treatment. In discussing these vaccines from the -standpoint of treatment, R. M. Pearce (13) had the following to -say: “A mixed vaccine for common ‘colds’ containing several -organisms (staphylococcus, streptococcus, pneumococcus, micrococcus -catarrhalis group, bacillus of Friedlander group, diphtheroid -group, bacillus influenza) is one of the most recent -bacterial ‘shotgun’ mixtures, which takes the chance of one lucky -bull’s-eye in seven shots.” “No one can claim a scientific or even -a common-sense basis for the treatment of a cold by such a -mixture.” Catarrhal mixed vaccines of a similar kind were -refused acceptance by the committee on “New and Non-efficial -Remedies” of the American Medical Association, in June, 1918 -(14), on the grounds that insufficient evidence of their therapeutic -value had been furnished by their manufacturers.</p> - -<p class='c009'>While the above illustrates the status of “mixed vaccine” for -therapeutic purposes, it is a well-recognized fact that it is possible -to produce an immunity for most of the bacteria composing -such vaccines, if killed cultures of the various strains are injected -in sufficiently large doses. Again referring to Pearce’s article, -we find the statement: “Prophylactic vaccination rests on a sound, -scientific basis of experimental studies and clinical observation.”</p> - -<p class='c009'>The attempt to protect against epidemic influenza by the use -of mixed vaccines was based largely on the following points. The -medical profession was confronted by a rapidly approaching -deadly epidemic, against which ordinary measures of control had -failed. The epidemic was supposed to be due to a primary infection -with Pfeiffer’s bacillus, but all of the fatal cases were found -to have profound secondary or symbiotic infections, with one or -more of the strains contained in the “mixed vaccines.” It was -known that mixed bacterial proteins, even though they were not -actually specific, possessed certain qualities of producing reactions -unfavorable to infections in general, which were characterized -by a temporary rise in temperature, by an increase in the -number of leucocytes, and by a more or less demonstrable amount -of active immunity against each one of the contained bacterial -toxins. The artificial production of a leucocytosis was especially -desirable, because a characteristic of epidemic influenza was the -failure of leucocytosis on the part of the infected individual. In -other words, mixed vaccines were used because they were the -<span class='pageno' id='Page_114'>114</span>only available substances which offered the hope of creating a -reaction against the secondary invaders which were so commonly -the cause of death in influenza.</p> - -<p class='c009'>Since Pittsburgh’s experience with prophylactic vaccination -had chiefly to do with the use of commercially prepared mixed -vaccines, a brief history of the local experience with them may -be of interest.</p> - -<p class='c009'>About the time that the first cases of influenza were being -reported from the Pittsburgh district, articles on preventive -vaccines as used in Boston and at some of the camps began to -appear in the daily papers, shortly after which came the -announcement that the Carnegie Steel Company was offering -free vaccination to their employees and to the families of their -employees. Dr. W. O. Sherman, chief surgeon for the company, -advocated the use of the vaccine because he hoped to increase -the immunity to secondary infection and to produce an active -leucocytosis in the vaccinated individuals, and at the same time -to allay panic among the employees at a time when an interruption -of manufacturing and mining pursuits might be disastrous -to the entire country; and he did it with the assurance that if -the vaccine did no good, it would at least do no harm. He took -steps to arrange for the collection of data by which he hoped -to determine whether or not the vaccine as used by their company -did any good. His report has not yet appeared. Other -large corporations at once instituted prophylactic vaccinations -with commercial “mixed vaccines.”</p> - -<p class='c009'>In contrast to the altogether laudable efforts of these companies -to protect their employees, a complete history of the -vaccine episode in this community necessitates the recounting of -a very different phase in the matter. When it became known -that corporations were vaccinating their employees, people in -general naturally began to investigate. Physicians’ offices were -besieged by persons who either demanded vaccination at once or -wanted to know whether or not there was “anything in it.” -Conscientious physicians in their turn called up the offices of the -medical societies, the various laboratories, and telegraphed everywhere -trying to get some definite data before recommending the -vaccine to their patients. It was impossible to answer the question -definitely, because it was a new procedure and purely in the -experimental stage. On the whole, the medical profession -<span class='pageno' id='Page_115'>115</span>handled the situation in a competent and dignified manner, for -the great majority gave vaccines only after a full explanation -to the effect that its value was in doubt, or else refused to give -it altogether. There were some, however, who were not conscientious, -and the unscrupulous practitioner seldom had a better -chance to impose upon the public. The demand for vaccine soon -exceeded the supply, and it is claimed that there were doctors -who gave any type of vaccine they could obtain without regard -to its bacterial make-up or intended purpose. Anti-diphtheritic -serum was given in many instances, and it is said that even -normal salt was used. Statements to the effect that exorbitant -sums were being charged and that guarantees of prevention -were being made resulted in the Red Cross Society undertaking -the distribution of the vaccine. To protect itself, the Medical -Society issued the following notice in the weekly bulletin for -October 26, 1918:</p> - -<p class='c022'>The Society wishes it understood that at present there is no -vaccine, serum or inoculation which will secure anyone against -influenza. It is desirable that everyone should avoid hysteria and -consider only the reports which are officially given out by the -Health Department, since of late various methods of prophylaxis -and treatment have found their way into the daily newspapers, -and these may prove harmful rather than do good.</p> - -<p class='c009'>Almost simultaneously the daily papers published the report of -Surgeon-General Blue, of the United States Bureau of Public -Health, which expressed practically the same opinion. It was not -the intention of either of these articles to criticise the practice -of vaccination, but merely to warn the public against profiteering -and fraudulent guarantees. They had the unexpected effect, -however, of causing people to completely lose faith in prophylactic -vaccines, and in many instances to become actually antagonistic -to them. It was during this period that the preparation -of vaccines from pure influenza strains was undertaken, under -supervision of the County Society and for distribution through -the Department of Public Health. Two days after the first supply -of this vaccine was ready the Red Cross authorities telephoned -that there was no further call for vaccine. The man in -charge of the distribution stated concretely that “the bottom -had dropped out of the vaccine business.” A few days later the -<span class='pageno' id='Page_116'>116</span>Department of Health issued an order to stop the preparation of -the vaccine.</p> - -<p class='c009'>Many pharmacies, having small supplies of vaccines, realized -the great call for it and the difficulty of obtaining a new supply, -and were also guilty of commercialism. Certain of the large -biological product companies were no exception. One house -issued a hand-bill, printed in red on a yellow background, which -stated: “Epidemic influenza is due to the influenza bacillus. The -present epidemic of influenza has a tendency to develop pneumonia. -The use of our influenza bacillus vaccine No. —— -will abort the influenza and avoid pneumonia and other sequelæ. -When pneumonia has developed, it can be reduced to less than -one-third the mortality and duration usual with other methods of -treatment,” etc. Practically all of the above statements are still -unproven, and probably will never be shown to be true. Such a -bulletin undoubtedly lays this firm of vaccine manufacturers -open to prosecution under the law protecting against false and -fraudulent advertising. Several fairly well-authenticated incidents -occurred in which the representatives of vaccine houses -offered factory managers and others share and share alike in the -profits, if the brand of vaccine made by them was used. It is -on such happenings as the above that the writer advocates legal -measures, allowing Boards of Health to control the advertising -of remedies and distribution of biological products during epidemics.</p> - -<p class='c009'>How much Pittsburgh will learn from the experience with -vaccines will depend on the numerous analyses of data which -were acquired during the epidemic.</p> - -<h3 class='c010'><em>Data on the Prophylactic Value of Mixed Vaccines</em></h3> - -<p class='c011'>Proof of the prophylactic value of mixed vaccines for epidemic -influenza depends entirely upon the results of its practical -application to human subjects in times when the disease is -prevalent. Animal determinations are out of the question, because -it has not been possible to produce the epidemic form of -influenza experimentally. If all people were equally susceptible -and were equally exposed, it would be a simple matter to compare -the number of vaccinated persons who developed the disease -with the number of unvaccinated persons who contracted it; but -since many thousands were vaccinated and some of them contracted -<span class='pageno' id='Page_117'>117</span>the disease in spite of it, and a greater number of persons -who were not vaccinated entirely escaped, the analysis is -extremely difficult.</p> - -<p class='c009'>The time element is a big factor. In instances where vaccination -was completed in a community before the epidemic appeared -there, the figures are worth more than those in which vaccination -was undertaken after the epidemic had become established. -This is true, because the most susceptible persons in a community -developed the disease as soon as they were exposed, the less susceptible -ones were not attacked until later, and the insusceptible -ones escaped altogether. Whenever vaccination is begun during an -epidemic, the persons vaccinated for prophylactic purposes are -necessarily chosen from those who have not yet developed an -attack. The later in the epidemic that vaccination is begun, the -greater will be the number of persons selected for vaccination -from among those more or less naturally immune. Then, if the -total number of cases among the vaccinated is compared with -the total number of cases among the unvaccinated, the apparent -value of the vaccine is increased; but the estimation is not a fair -one, because the vaccinated group is unavoidably selected from -among relatively immune persons, while the controls include all -of the very susceptible people who were suffering from the disease -at the time vaccination was begun. Where vaccination is -begun after the epidemic is advanced, the only figures worth -while are those obtained by a day-by-day or a week-by-week comparison -between the number of cases developing among controls -and the number of cases appearing among those vaccinated, and -by beginning that comparison at a time subsequent to the day on -which the prophylactic inoculations were completed.</p> - -<p class='c009'>Aside from the interpretation of the results there is possibly -a more serious reason for objecting to the beginning of vaccination -during an epidemic. This lies in the danger of producing -a temporary negative phase in the patient, which makes him -somewhat more susceptible to natural infection for a few hours -immediately following each administration.</p> - -<p class='c009'>McCoy (15) outlined the requirements necessary for an ideal -vaccine experiment as follows: 1. The community should be as -large as possible, and should number at least 10,000 persons. -2. The conditions under which they live should be as nearly equal -as possible. 3. The turnover, or rather the change in population, -<span class='pageno' id='Page_118'>118</span>should be as small as possible. 4. The social service should be -efficient and reliable, so that it can be definitely ascertained when -anyone becomes sick and what the disease is from which he -is suffering. 5. Fifty per cent. should be vaccinated before the -epidemic arrives, and the other 50 per cent. should be held as -controls.</p> - -<p class='c009'>No examples were found which came up to the above requirements, -but there were some instances in which vaccination was -completed before the epidemic appeared, and some in which we -were able to get a week-by-week comparison between vaccinated -and unvaccinated groups. Most of the data which has been -reported shows that vaccination was begun about the last of the -second or the first of the third week of the epidemic, and in some -instances not until after the peak was passed. Add to this the -fact that the vaccine was given in from three to four doses, at -from three to seven day intervals—a course which required in -the neighborhood of two weeks for completion—and it is obvious -that the full protective powers of the vaccine were not acquired -by the individual until the worst of the epidemic was over and -the number of cases were rapidly subsiding.</p> - -<p class='c009'>In order to get the best understanding from these experiments, -the data will be presented in three series: I. Those instances in -which vaccination was completed before the epidemic appeared. -II. Those instances in which it is possible to compare the relative -occurrence of influenza in both the vaccinated and unvaccinated -groups after vaccination was completed. III. Those instances in -which vaccination was begun after the epidemic appeared and -in which comparisons of total figures only are available.</p> - -<h3 class='c010'><em>Series I. Those Instances in Which Vaccination Was Completed Before the Epidemic Appeared</em></h3> - -<p class='c011'>1. The only instance in the Pittsburgh community in which -vaccination was completed before the epidemic appeared is that -reported from the Dixmont Hospital, Dixmont, Pa., and furnished -me through the courtesy of Dr. Hutchinson (16). The institution -had a population of about 1,000 patients and 300 employees. -Prophylactic vaccination was begun on October 20, and was completed -about November 6. Each c.c. of the vaccine used contained -200,000,000 each of B. Pfeiffer, Micrococcus Catarrhalis, B. Friedlander, -<span class='pageno' id='Page_119'>119</span>Pneumococci, Streptococci and Staphylococci, both Aureus -and Albus. Four doses were given of 4 minims, 8 minims, 12 -minims and 16 minims, respectively. Inoculations were carried -out at four-day intervals. Owing to the isolation of the institution -from the general community, the first case did not appear -until two weeks later—namely, on November 20. The results are -shown by the table.</p> - -<table class='table2' summary=''> - <tr> - <th class='c015'></th> - <th class='c016'>Population.</th> - <th class='c016'>No. of Cases.</th> - <th class='c016'>% of Cases.</th> - <th class='c016'>No. of Deaths.</th> - <th class='c017'>% of Deaths.</th> - </tr> - <tr> - <td class='c015'>Vaccinated</td> - <td class='c018'>600</td> - <td class='c018'>44</td> - <td class='c018'>7.3%</td> - <td class='c018'>0</td> - <td class='c019'>0%</td> - </tr> - <tr> - <td class='c015'>Unvaccinated</td> - <td class='c018'>700</td> - <td class='c018'>69</td> - <td class='c018'>9.8%</td> - <td class='c018'>9</td> - <td class='c019'>1.2%</td> - </tr> -</table> - -<p class='c009'>None of the vaccinated patients developed pneumonia, though -there were 15 cases among the unvaccinated.</p> - -<p class='c009'>This experiment shows a slight percentage in favor of vaccination, -and indicates that there was some decrease in the severity -of the secondary infections.</p> - -<p class='c009'>2. The experiment reported by McCoy, Murray and Teeter (17) -showed quite opposite results from the above, and was an excellent -example of a small though completely controlled test. In -an asylum for the insane in San Francisco all of the patients -under 41 years of age were divided into two groups—one group -was kept as controls and the other was given a vaccine furnished -by F. O. Tonney, of the Chicago Health Department. The vaccine -contained 500,000,000 each of B. Influenza, Pneumococcus -I, II and III, 1,500,000,000 Pneumococcus IV, 1,000,000,000 Streptococcus -Hæmolyticus and 500,000,000 Staphylococci. Doses of -0.5 c.c., 1 c.c. and 1½ c.c., which were given at 48–hour intervals. -Inoculation was completed on November 15, and the first case of -influenza appeared on November 26. The table shows the result.</p> - -<table class='table2' summary=''> - <tr> - <th class='c015'></th> - <th class='c016'>Vaccinated.</th> - <th class='c017'>Not Vaccinated.</th> - </tr> - <tr> - <td class='c015'>Persons in group</td> - <td class='c018'>390</td> - <td class='c019'>390</td> - </tr> - <tr> - <td class='c015'>Cases of influenza</td> - <td class='c018'>119</td> - <td class='c019'>103</td> - </tr> - <tr> - <td class='c015'>Cases of pneumonia</td> - <td class='c018'>23</td> - <td class='c019'>17</td> - </tr> - <tr> - <td class='c015'>Number of deaths</td> - <td class='c018'>10</td> - <td class='c019'>7</td> - </tr> -</table> - -<p class='c009'>3. The report of Minaker and Irvine (18) included several -groups of men, the first two of which apparently belonged in our -first series. They used a vaccine, each c.c. of which contained -5,000,000,000 B. Pfeiffer, 3,000,000,000 each of Pneumococcus I -<span class='pageno' id='Page_120'>120</span>and II, 1,000,000,000 Pneumococcus III, 100,000,000 Streptococcus -Hæmolyticus. In all, they vaccinated 11,179 persons.</p> - -<p class='c009'>(a) Their first group numbered 4,950 persons in quarantine at -the Naval Training Station. The quarantine was maintained for -24 days, and no influenza appeared during that time. Three -thousand five hundred and fourteen of them were released at a -time when there were still 200 to 300 cases of influenza being -reported daily in San Francisco. Out of the 3,514 men, 15 had -influenza, and there were no deaths.</p> - -<p class='c009'>(b) At the Mare Island Navy Yards 1,950 marines were released -immediately after completion of the inoculation. They -were turned into Valejo and San Francisco, where influenza was -at its height. Only 35 cases, with 1 death, occurred, and these -developed shortly after the men were released in San Francisco. -This group was controlled with an unvaccinated group of 8,232 -persons who remained at Mare Island, and 1,296 cases of influenza, -with 65 deaths, occurred among the controls.</p> - -<p class='c009'>(c) At San Pedro 3,100 were vaccinated, and of these 53 had -influenza, and there were no deaths. The occurrence among these -was compared with the prevalence of the disease in Los Angeles, -but this part of the report leaves much to be desired in the way -of the relative dates, etc.</p> - -<p class='c009'>(d) The fourth group, consisting of 1,080 civilians, developed -14 cases, with no deaths. However, vaccination of this group -was not completed until 21 days after the pandemic had appeared -in the community. Minaker’s and Irvine’s analyses show a favorable -percentage for vaccination in the first two groups, but their -groups three and four were not sufficiently well controlled to be -of much help.</p> - -<p class='c009'>4. In a report which appeared during October, 1918, Eyer and -Lowe (29) published the results of prophylactic inoculation of -1,000 New Zealand troops with a mixed catarrhal vaccine. They -controlled their experiments with 19,000 New Zealand troops -who were not inoculated. A comparison of the incidence of acute -respiratory disease and influenza during the primary wave of -the epidemic as it appeared during June and July, gave two cases -among the vaccinated troops and an average of 43.2 cases per -thousand among the controls.</p> - -<p class='c009'>Later they reported (58) the results of much larger experiments -as carried out at 17 different camps and hospitals. The -vaccine which they used was a typical “mixed” vaccine, save that -<span class='pageno' id='Page_121'>121</span>the authors emphasized the advantage of using strains not more -than three generations removed from the body. At some of the -camps their reports were unfavorable, but upon the whole their -results, as summarized below, were most encouraging. In most -instances inoculations were completed just prior to the arrival -of the autumn epidemic.</p> - -<p class='c009'>Out of a total average strength of 21,759, approximately -16,104 men received full prophylactic vaccination, and approximately -5,700 were uninoculated, or had received only 1 dose; -3,366 cases of influenza developed—15 per cent.; 1.3 per cent. -occurred among the vaccinated, while 4.1 per cent. developed in -the uninoculated; 8 per cent. of the severe cases among the protected -died, as compared to 23 per cent. among the uninoculated. -The death rate for all infected cases was 0.26 per cent. among the -inoculated and 2.2 per cent. among the uninoculated.</p> - -<p class='c009'><span class='sc'>Notanda.</span>—All of the above reports, comprising the “Series I” -experiments, indicate that mixed vaccines reduced the number of -severe illnesses and lowered the death rate to some extent.</p> - -<h3 class='c010'><em>Series II. Those Instances in Which It Is Possible to Compare the Relative Occurrence in Both Vaccinated and Unvaccinated Groups After Vaccination Was Completed</em></h3> - -<p class='c011'>1. The report on prophylactic vaccination at the Hospital for -the Insane at Retreat, Pa., was very kindly furnished by Dr. -Charles B. Maberry (20). When the epidemic approached, the -institution was placed in quarantine and remained free from -influenza until October 28, when two cases appeared in nurses -who had broken quarantine. Influenza spread in the male ward, -but the female wards were kept free during the whole of the -epidemic. There were 370 male patients, but 60 were in the -infirmary and were not included in the calculation. Out of 310 -patients, 210 received vaccines. Ordinary commercial mixed -vaccine was used, and vaccination was begun two days after -influenza appeared. During the first week there were 40 cases -of influenza, 6 of which occurred among those who had received -a single dose of the vaccine. After the first week there were -38 cases of influenza, with 10 pneumonias and 5 deaths, among -the unvaccinated, giving a morbidity rate of 38 per cent. and a -<span class='pageno' id='Page_122'>122</span>mortality rate of 5 per cent. In the vaccinated group there were -no cases after vaccination was completed. Maberry states -further that in ward III the only cases which appeared subsequent -to vaccination were in six patients who refused preventive -inoculations. This appears to be the most favorable of any of the -reports.</p> - -<p class='c009'>2. Nurses on duty in hospitals everywhere suffered greatly -from influenza, and those of Pittsburgh were no exception. Some -of the hospitals vaccinated the nurses during the epidemic and -some did not, and it was hoped that by getting a week-by-week -comparison of the number of cases among vaccinated and non-vaccinated -nurses some reliable data would be obtained. A circular -letter sent to all of the hospitals in the community contained -a blank asking for the number of nurses, date of appearance -of the epidemic, use of vaccine, dates of inoculations, and -for a week-by-week occurrence of influenza in each group. Only -7 hospitals complied with the request, and of them only 5 sent -complete data. Complete reports were received from the Allegheny -General, Columbia, Presbyterian, South Side and St. Francis -Hospitals. Of a total of 336 nurses in these 5 institutions, -38 developed influenza in the first week, 48 in the second, 39 in -the third, 43 in the fourth, and 45 subsequent to the fourth week, -making a total of 213—a morbidity of 63 per cent. The Mercy -and St. Margaret’s Hospitals reported the total number of nurses -and the occurrence of influenza among them, and adding in their -reports there were 521 nurses on duty in 7 hospitals, with 257 -cases of influenza, giving a morbidity rate of 50 per cent.; 28 -cases of pneumonia and 11 deaths, giving a 2 per cent. mortality -rate. The total figures from hospitals where vaccines were used -are against vaccination, due partly to the fact that vaccination -was started late. In these hospitals the morbidity was 66 per -cent. and the death rate 3 per cent. In the hospitals where -vaccines were not used the morbidity rate was 20 per cent. and the -death rate 1.2 per cent. No dependable data was obtained, but -the report from the South Side Hospital was interesting. Of 60 -nurses on duty, 36 had influenza and 2 died. Of this number -19 were stricken the first week. Three days after the first cases -were admitted to the hospital vaccination was begun, and was -given to most of the nurses still on duty. Of those taking vaccines -20 developed influenza and 1 died during the period of -<span class='pageno' id='Page_123'>123</span>immunization, but after the inoculations were completed there -were no more cases in either group.</p> - -<p class='c009'>During the epidemic it was said that benefit was derived from -the use of vaccines on nurses at the West Penn Hospital, but -the writer was unable to obtain a report from this institution. -The collected data on nurses was useless, though it is interesting, -in that it shows the possibility of making figures prove almost -anything you want them to prove.</p> - -<h3 class='c010'><em>Series III. Those Instances in Which Vaccination Was Begun After the Epidemic Appeared, and in Which Comparisons of Total Figures Only Are Available</em></h3> - -<p class='c011'>Undoubtedly the largest attempt at prophylaxis against epidemic -influenza through the use of “mixed vaccines” was that -made under the direction of Dr. W. O. Sherman for the Carnegie -Steel and H. C. Frick Coke Companies. The results which Dr. -Sherman hoped to attain when he planned using the vaccine and -collecting the data have already been given. Commercial mixed -vaccines similar to those described under the “Series I” experiment -were used, and four doses, three days apart, were given. -Inoculations were begun on October 20, 1918, and were completed -during the first week of November. Vaccine was administered -to the employees and their families without charge. Later cards -were given to all employees, and they were made to fill them out -and return them. On the cards were blanks calling for the -name, age, sex, color, number of inoculations, whether or not -the employee himself or any member of his family had had -influenza, and how many days the sick individuals had been in -bed. Each mill and mine was then supplied with a set of blank -forms providing for a complete statistical record of the number -of inoculations and the total incidence of influenza, pneumonia -and death. From the reports of the respective mills and mines -the total figures given in the charts were compiled.</p> - -<p class='c009'>Difficulties were encountered in every part of the work. The -vaccine demand was so great that the products of three different -firms were used. So many doctors were in service that most of -the vaccine had to be given by carefully coached nurses. The -bulletins of the United States Bureau of Public Health and of -the Allegheny County Medical Society, with their warnings about -influenza vaccines being only in the experimental stage, appeared -<span class='pageno' id='Page_124'>124</span>just at the time the work was begun and caused a great many -to refuse to complete vaccination after one or two doses had been -given. So few medical men were left that it was impossible to -have them see all cases and so determine the nature of many of -the illnesses which were occurring. It was assumed, therefore, -that any employee who had fever and was sick for a period of -three days had influenza, and that any who were confined to bed -for seven days or more had pneumonia. The figures of the central -offices were made up from the reports of 14 steel mills, 1 -cement factory, 4 warehouses and 57 mining districts. The accuracy -of data depended on the careful work of a great many local -statistical workers, which made individual variations hard to -control. The greatest difficulty of all, however, lay in finding a -common basis for comparisons of the incidence of influenza, -pneumonia and death in the vaccinated and non-vaccinated -groups, since the data on the former group included the occurrence -only after the peak of the epidemic had been passed, and -that of the latter group included the occurrence for the entire -epidemic.</p> - -<p class='c009'>The total figures are given in the three charts.</p> - -<table class='table0' summary='Inoculation'> - <tr><th class='c014' colspan='4'>CHART I.</th></tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='4'><span class='sc'>Carnegie Steel Company.</span></td></tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='4'>All Works Except Homestead, City Mills, Columbus, Lucy and Isabella.</td></tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='4'><span class='sc'>Statistical Report on Inoculation Against Influenza.</span></td></tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>1. Number of employees who had influenza</td> - <td class='c023'>5,728</td> - <td class='c007'>18%</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>2. Number of employees who did not have influenza</td> - <td class='c023'>24,956</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c016'>Total number of employees</td> - <td class='c024'> </td> - <td class='c023'>30,684</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'>3. Total number of persons inoculated</td> - <td class='c024'>One inoculation</td> - <td class='c023'>2,983</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>3,675</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>4,626</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>10,053</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>21,337</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'>4. Cases influenza developed after</td> - <td class='c024'>No inoculations</td> - <td class='c023'>2,133</td> - <td class='c007'>23%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>One inoculation</td> - <td class='c023'>745</td> - <td class='c007'>25%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>776</td> - <td class='c007'>21%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>794</td> - <td class='c007'>17%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>1,280</td> - <td class='c007'>12%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>5,728</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'><span class='pageno' id='Page_125'>125</span>5. Cases influenza pneumonia developed after</td> - <td class='c024'>No inoculations</td> - <td class='c023'>804</td> - <td class='c007'>37%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>One inoculation</td> - <td class='c023'>356</td> - <td class='c007'>48%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>403</td> - <td class='c007'>52%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>321</td> - <td class='c007'>40%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>459</td> - <td class='c007'>36%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>2,343</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'>6. Deaths from influenza and “flu Pneumonia” after</td> - <td class='c024'>No inoculations</td> - <td class='c023'>104</td> - <td class='c007'>4.7%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>One inoculation</td> - <td class='c023'>32</td> - <td class='c007'>4.3%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>33</td> - <td class='c007'>4.2%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>21</td> - <td class='c007'>2.6%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>33</td> - <td class='c007'>2.5%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>223</td> - <td class='c007'>3.9%</td> - </tr> - <tr><td> </td></tr> - <tr><td> </td></tr> - <tr><th class='c014' colspan='4'>CHART II.</th></tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='4'><span class='sc'>H. C. Frick Coke Company.</span></td></tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='4'><span class='sc'>Statistical Report on Inoculation Against Influenza.</span></td></tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>1. Number of employees who had influenza</td> - <td class='c023'>5,248</td> - <td class='c007'>31.4%</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>2. Number of employees who did not have influenza</td> - <td class='c023'>11,464</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c016'>Total number of employees</td> - <td class='c024'> </td> - <td class='c023'>16,712</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'> </td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'>3. Total number of persons inoculated</td> - <td class='c024'>No inoculations</td> - <td class='c023'>3,122</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>One inoculation</td> - <td class='c023'>2,483</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>2,548</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>3,550</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>5,009</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>13,590</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'>4. Cases influenza developed after</td> - <td class='c024'>No inoculations</td> - <td class='c023'>1,495</td> - <td class='c007'>47.9%<br /> of (3</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>One inoculation</td> - <td class='c023'>634</td> - <td class='c007'>25.5%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>770</td> - <td class='c007'>30.2%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>1,078</td> - <td class='c007'>30.4%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>1,271</td> - <td class='c007'>25.0%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>5,248</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'><span class='pageno' id='Page_126'>126</span>5. Cases influenza pneumonia developed after</td> - <td class='c024'>No inoculations</td> - <td class='c023'>94</td> - <td class='c007'>6.3%<br />of (4</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>One inoculation</td> - <td class='c023'>33</td> - <td class='c007'>5.2%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>42</td> - <td class='c007'>5.4%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>69</td> - <td class='c007'>6.4%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>85</td> - <td class='c007'>6.7%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>323</td> - <td class='c007'>6.1%<br />of (4 total</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'> </td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'>6. Deaths from influenza and “flu</td> - <td class='c024'>No inoculations</td> - <td class='c023'>30</td> - <td class='c007'>2.0%<br />of (4</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>One inoculation</td> - <td class='c023'>13</td> - <td class='c007'>2.0%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>21</td> - <td class='c007'>2.9%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>16</td> - <td class='c007'>1.5%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>37</td> - <td class='c007'>2.9%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>117</td> - <td class='c007'>2.2%<br />of (4</td> - </tr> - <tr><td> </td></tr> - <tr><td> </td></tr> - <tr><th class='c014' colspan='4'>CHART III.</th></tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='4'><span class='sc'>Bessemer & Lake Erie Railroad.</span></td></tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='4'><span class='sc'>Statistical Report on Inoculation Against Influenza.</span></td></tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>1. Number of employees who had influenza</td> - <td class='c023'>1,275</td> - <td class='c007'>24%</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006' colspan='2'>2. Number of employees who did not have influenza</td> - <td class='c023'>3,986</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c016'>Total number of employees</td> - <td class='c024'> </td> - <td class='c023'>5,261</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'>3. Total number of persons inoculated</td> - <td class='c024'>No inoculations</td> - <td class='c023'>3,091</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>One inoculation</td> - <td class='c023'>232</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>249</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>479</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>1,210</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>2,170</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'>4. Cases influenza developed after</td> - <td class='c024'>No inoculations</td> - <td class='c023'>705</td> - <td class='c007'>55%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>One inoculation</td> - <td class='c023'>111</td> - <td class='c007'>48%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>91</td> - <td class='c007'>36%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>129</td> - <td class='c007'>27%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>239</td> - <td class='c007'>19%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>1,275</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'><span class='pageno' id='Page_127'>127</span>5. Cases influenza pneumonia developed after</td> - <td class='c024'>No inoculations</td> - <td class='c023'>283</td> - <td class='c007'>40%<br />of (4</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>One inoculation</td> - <td class='c023'>75</td> - <td class='c007'>67%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>59</td> - <td class='c007'>64%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>51</td> - <td class='c007'>42%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>69</td> - <td class='c007'>28%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>537</td> - <td class='c007'> </td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c006'>6. Deaths from influenza and “flu Pneumonia” after</td> - <td class='c024'>No inoculations</td> - <td class='c023'>40</td> - <td class='c007'>5.6%<br />of (4</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>One inoculation</td> - <td class='c023'>5</td> - <td class='c007'>4.5%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Two inoculations</td> - <td class='c023'>0</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Three inoculations</td> - <td class='c023'>0</td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'>Four inoculations</td> - <td class='c023'>3</td> - <td class='c007'>4.3%</td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c024'> </td> - <td class='c023'><hr /></td> - <td class='c007'> </td> - </tr> - <tr> - <td class='c006'> </td> - <td class='c025'>Total</td> - <td class='c023'>48</td> - <td class='c007'> </td> - </tr> -</table> - -<p class='c009'>Charts I and III show a decrease in the incidence of influenza -in direct proportion to the number of inoculations given. This -finding would have been very important had vaccination been -completed before the epidemic appeared. There is, however, no -convincing evidence in either of these charts that the vaccine cut -down the relative number of pneumonias, or decreased the death -rate to any appreciable extent. Chart I also shows the interesting -fact that influenza occurred slightly more often among those -who had one inoculation than among those who were not vaccinated -at all.</p> - -<p class='c009'>Chart II would indicate that influenza occurred much less frequently -in the vaccinated than in the control group, but a closer -analysis brings out the contradictory finding that influenza -occurred at the same rate in the group of 634 persons who had -only 1 dose that it did in the group of 1,271 who completed the -course.</p> - -<p class='c009'>The reports from the separate communities were so conflicting -that to attempt to analyze them leads only to confusion.</p> - -<p class='c009'>No reports of harmful effects from the use of the vaccine were -received, and several physicians who attended sick employees -say that, even though the figures do not show it, they feel certain -that the vaccinated persons in general were not as sick as -those who were not vaccinated.</p> - -<p class='c009'>On account of the conditions under which the vaccinations -were done and the reports compiled, Dr. Sherman has not felt -<span class='pageno' id='Page_128'>128</span>justified in making a report, fearing that erroneous conclusions -might be drawn from the data. We are greatly indebted to him -for the use of his reports, without which our account of the -influenza epidemic in Pittsburgh would have been very incomplete.</p> - -<p class='c009'>2. Another large steel corporation who used vaccine but -asked that their names be withheld furnished the following -report. During the epidemic the company offered free vaccination -to its 27,000 employees and their families. Commercial -mixed vaccines were used, three injections given, and vaccination -begun on October 19, which was about the time of the peak of the -epidemic in Pittsburgh. The results include a record of all -employees who lost over six days between October 1 and November -30.</p> - -<table class='table1' summary=''> - <tr> - <th class='btt bbt brt c012' colspan='2' rowspan='2'>EMPLOYEES</th> - <th class='btt bbt brt c012' colspan='2'><span class='sc'>Morbidity</span></th> - <th class='btt bbt brt c012' colspan='2'><span class='sc'>Pneumonia</span></th> - <th class='btt bbt c012' colspan='2'><span class='sc'>Mortality</span></th> - </tr> - <tr> - - <th class='bbt brt c012'>No.</th> - <th class='bbt brt c012'>%</th> - <th class='bbt brt c012'>No.</th> - <th class='bbt brt c012'>%</th> - <th class='bbt brt c012'>No.</th> - <th class='bbt c012'>%</th> - </tr> - <tr> - <td class='c026'>Received only one dose</td> - <td class='brt c013'>3,895</td> - <td class='brt c013'>511</td> - <td class='brt c013'>13.13</td> - <td class='brt c013'>31</td> - <td class='brt c013'>0.8</td> - <td class='brt c013'>28</td> - <td class='c013'>0.72</td> - </tr> - <tr> - <td class='c026'>Received only two doses</td> - <td class='brt c013'>3,329</td> - <td class='brt c013'>414</td> - <td class='brt c013'>12.44</td> - <td class='brt c013'>40</td> - <td class='brt c013'>1.2</td> - <td class='brt c013'>19</td> - <td class='c013'>0.57</td> - </tr> - <tr> - <td class='bbt c026'>Received all three doses</td> - <td class='bbt brt c013'>9,897</td> - <td class='bbt brt c013'>468</td> - <td class='bbt brt c013'>4.75</td> - <td class='bbt brt c013'>46</td> - <td class='bbt brt c013'>0.46</td> - <td class='bbt brt c013'>32</td> - <td class='bbt c013'>0.32</td> - </tr> - <tr> - <td class='c026'>Total of above</td> - <td class='brt c013'>17,119</td> - <td class='brt c013'>1393</td> - <td class='brt c013'>8.14</td> - <td class='brt c013'>117</td> - <td class='brt c013'>0.68</td> - <td class='brt c013'>79</td> - <td class='c013'>0.46</td> - </tr> - <tr> - <td class='bbt c026'>Received no doses</td> - <td class='bbt brt c013'>10,036</td> - <td class='bbt brt c013'>1522</td> - <td class='bbt brt c013'>15.17</td> - <td class='bbt brt c013'>154</td> - <td class='bbt brt c013'>1.53</td> - <td class='bbt brt c013'>106</td> - <td class='bbt c013'>1.06</td> - </tr> - <tr> - <td class='bbt c026'>Total for both groups</td> - <td class='bbt brt c013'>27,155</td> - <td class='bbt brt c013'>2915</td> - <td class='bbt brt c013'>11.66</td> - <td class='bbt brt c013'>271</td> - <td class='bbt brt c013'>1.10</td> - <td class='bbt brt c013'>185</td> - <td class='bbt c013'>0.76</td> - </tr> -</table> - -<p class='c009'>Before satisfactory conclusions can be drawn from these -figures it is necessary to know how many of the 10,036 persons -became sick before vaccination, and whether or not the rate of -decrease in this group was not similar to that shown by the -number of patients who developed influenza during the intervals -between their doses of vaccine. The relatively high percentage -of cases following the first and second doses are capable of -explanation on one, or perhaps on all, of the three following -grounds: (a) the general subsidence of the epidemic, which -showed a rapid decrease by the time the third dose was given; -(b) the increased protection afforded by the three doses of vaccine, -and (c) the broken resistance of the patient following sudden -sensitization by the vaccine.</p> - -<p class='c009'>3. Rosenow (21) prepared a mixed vaccine by growing the -various bacteria in glucose broth, for from 18 hours to 36 hours, -<span class='pageno' id='Page_129'>129</span>centrifuging and suspending the sediment in salt solution and -making up the vaccine on a percentage basis.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>FORMULA OF VACCINE</div> - </div> -</div> - -<table class='table2' summary=''> - <tr> - <td class='c006'>Pneumococci, Types I (10 per cent.), II (14 per cent.) and III (6 per cent.)</td> - <td class='c007'>30 per cent.</td> - </tr> - <tr> - <td class='c006'>Pneumococci Group IV and the allied green-producingdiplostreptococci described</td> - <td class='c007'>30 per cent.</td> - </tr> - <tr> - <td class='c006'>Hemolytic Streptococci</td> - <td class='c007'>20 per cent.</td> - </tr> - <tr> - <td class='c006'>Staphylococcus Aureus</td> - <td class='c007'>10 per cent.</td> - </tr> - <tr> - <td class='c006'>Influenza bacillus</td> - <td class='c007'>10 per cent.</td> - </tr> -</table> - -<p class='c009'>Most of the vaccine was distributed within a radius of 200 -miles of Rochester, Minn., but samples were furnished to physicians -all over the country, who agreed to return statistics on its -use. No evidence was found that this vaccine caused a temporary -break in the resistance of the user. Out of a total of 20,972 -persons vaccinated, 14.6 cases of influenza, 1.8 cases of pneumonia, -with 1.8 mortality, occurred per thousand in the six weeks -following vaccination. As controls, he took “such persons in -institutions, colleges, factories and communities where vaccine -was used, and included only those reports which contained accurate -data as to the incidence and mortality among them.” Among -61,753 such controls he found 229 cases of influenza, 15.7 cases of -pneumonia and 3.4 deaths per thousand. He concluded from his -results that “it appears possible to afford a definite degree of -immunity by prophylactic inoculations to persons against the -more serious respiratory infections during the present epidemic.” -It is quite difficult to agree with Rosenow in his interpretation -of the figures as presented by him, inasmuch as he made no -allowance for the stage of the epidemic at which vaccination was -carried out, either among the vaccinated or the non-vaccinated. -Such a comparison would be well nigh impossible where the vaccine -was sent in varying quantities to such a large number of -places.</p> - -<p class='c009'>4. League Island Report (22). Vaccines were used as a preventive -in 50 persons, most of whom were hospital apprentices -and in the wards 12 to 15 hours a day. Other precautions were -used, such as masks, but not a single case developed in the group. -The vaccine was used as a curative agent in 50 uncomplicated -cases; none of the patients injected early developed pneumonia.</p> - -<p class='c009'><span class='pageno' id='Page_130'>130</span>5. Puget Sound Navy Yards Report (23). The vaccine used -at this station was made from hæmolytic streptococci, no other -organisms being used; 4,212 men were vaccinated, and not one -died from influenza. Among 111 Philippinos isolated and vaccinated -there occurred only 2 cases. Among 361 marines vaccinated -early there occurred 2 cases. Among 62 marines at the -ammunition depot who were vaccinated early there occurred -3 cases, only 1 of which occurred after completion of vaccination. -Among 662 bluejackets at Seattle Training Camp only 10 men -developed the disease. Among 83 at the aviation corps there were -32 cases—31 of them developed the disease within a few hours -after the first injection. There were no deaths in any of the -above groups. The period of observation was closed on October -21, and so few cases of influenza appeared subsequent to that -date that it seemed that the epidemic was practically over at the -time the data was obtained.</p> - -<p class='c009'>6. Kitano (24) used a vaccine for prophylaxis containing -0.2 m.g. of Pfeiffer bacilli per c.c. on 10,300 persons with encouraging -results. He used vaccine for treatment on 87 patients, -without any deaths. In the same group were 270 cases treated in -the usual way, with 23 per cent. mortality. The vaccine lessened -the severity, shortened the period of illness, and lowered the -mortality.</p> - -<p class='c009'>7. Wynn (25) used mixed vaccines in the treatment of influenza, -and believed they aborted the disease if given early.</p> - -<p class='c009'>8. Norman White (26) states that vaccination in India would -be impractical, because the disease is so brief and severe that -it would be over before innumerable doctors could complete -inoculations.</p> - -<p class='c009'>9. Whitingham and Sims (27) reported the use of a mixed -vaccine in an institution where 156 were inoculated and 149 -were not. The case incidence was 5 per cent. among the vaccinated -and 12 per cent. among the controls. No statement of -the stage of the epidemic at which vaccination was done is mentioned -in the report.</p> - -<p class='c009'>10. Cadham (28) reported on inoculations in a military hospital -and in the civilian population near Winnipeg. Of 282 vaccinated -soldiers admitted to the hospital, 17 had pneumonia and -5 died. Of 238 not vaccinated, 41 had pneumonia and 17 died. -Among 24,184 civilians given two doses, 9.7 per cent. had influenza -<span class='pageno' id='Page_131'>131</span>and 0.5 per cent. had pneumonia and 0.09 per cent. died. -Among 85,941 controls, 24.8 per cent. had influenza, 2.2 per cent. -pneumonia and 0.66 per cent. died. Cadham states that most of -the inoculations were made early in the epidemic, but no accurate -statistics were kept on the point.</p> - -<p class='c009'>11. A conference was held at the British War Office on October -14, 1918 (30), to discuss prophylactic vaccination and vaccines -for treatment of influenza. Elaborate plans regarding dosage -and gathering of statistics were made.</p> - -<p class='c009'><span class='sc'>Notanda.</span>—For reasons already given, the reports in Series III -fail to give very reliable data on which to base a knowledge of the -value of preventive vaccination against epidemic influenza.</p> - -<h3 class='c010'><em>The Attempt to Prevent Pneumonia as a Complication of Influenza Through the Use of Lipovaccine</em></h3> - -<p class='c011'>Whitmore, Fennel and Peterson (31) developed a method of -preparing an oily suspension of killed bacteria which they called -“lipovaccine.” The method was used at first in making typhoid -and dysentery vaccines. The advantages of lipovaccines (32) -over salt suspensions are: the prevention of autolysis of the -bacteria, thus increasing the length of time during which the -vaccine remains active; the slow absorption of the dose, allowing -the patient to continue to absorb immunity-producing substances -over a period of days or weeks; the administration of a single -massive dose, which does away with the three doses necessary -when salt suspensions are used; and perhaps, also, the direct -reduction in the toxicity of the dose by the lipoid material.</p> - -<p class='c009'>Based upon the classification of pneumococci by Dochez and -Gillespie (33) in this country, and by Lister (34), (35), (36) in -South Africa, and upon the latter’s successful use of anti-pneumonia -vaccine on the Rand, an anti-pneumonia lipovaccine was -prepared at the Army Medical School which contained approximately -10,000,000,000 each of types I, II and III pneumococci. -The vaccine was made by growing the pneumococci in dextrose -broth, centrifuging them out of the broth with a sharpless milk -centrifuge, drying the sediment at 55° C., weighing it out so -that each cubic centimeter of the finished vaccine contains -0.83 m.g. of each type, and making a suspension of them in olive -oil. More recently cotton-seed oil has been used.</p> - -<p class='c009'><span class='pageno' id='Page_132'>132</span>The result of the use of a salt suspension pneumococcus vaccine -at Camp Upton was published by Cecil and Austin (37). A study -of the agglutination and protective power of the serum of 42 persons -vaccinated against pneumococcus types I, II and III demonstrated -that a definite immune response could be secured to types -I and II but not to type III. Twelve thousand five hundred and -nineteen men were vaccinated at the camp, and most of the men -received three or four inoculations at intervals of from five to -seven days. The men were under observation for ten weeks, and -during that time no cases of pneumonia of the three fixed types -occurred among those who had received two or more injections. -In a control of approximately 20,000 men there were 26 cases of -pneumonia of types I, II and III. The incidence of pneumococcus -type IV pneumonia was less among the vaccinated than among -the unvaccinated groups. There were, however, 17 cases of pneumonia -among the vaccinated men, compared to 173 cases of pneumonia -among the controls. The annual pneumonia death rate for -vaccinated groups in the army was 0.83 per one thousand, and for -unvaccinated groups was 12.8.</p> - -<p class='c009'>Fennell reported the use of pneumo-lipovaccine in Washington -during the influenza epidemic, but the number of cases cited by -him were too small to permit of definite conclusions. His results -appeared favorable.</p> - -<p class='c009'>Cecil and Vaughan (37a) reported on the results of vaccination -with pneumo-lipovaccine at Camp Wheeler; 13,460 men, comprising -80 per cent. of the camp, were inoculated. Most of these -men were under observation for 2 or 3 months after vaccination, -and there occurred among them 32 cases of pneumococcus types -I, II and III pneumonia. In one-fifth of the camp which was not -vaccinated there occurred 43 cases of pneumonia. They observed -that influenza caused a marked reduction in the resistance to -pneumonia among vaccinated as well as non-vaccinated men. Of -155 cases of pneumonia of all types, which developed one week -or more after vaccination, 133 were secondary to influenza. The -death rate among vaccinated men one week or more after vaccination -was 12.2 per cent., whereas the death rate for 327 cases -of all types of pneumonia which occurred among unvaccinated -groups was 22.3 per cent. The death rate for primary pneumonia -among vaccinated groups was 11.9 per cent., and among unvaccinated -31.8 per cent. It was found that protective bodies do not -<span class='pageno' id='Page_133'>133</span>begin to appear in the serum after lipovaccines are given until -the eighth day after the injection. Twenty-four cases of pneumonia -occurred in the first week after vaccination. In their conclusions -Cecil and Vaughan state that there was no evidence -whatever that pneumococcus vaccine predisposed the individual, -even temporarily, toward either pneumococcus or streptococcus -pneumonia. Most of the reactions after vaccination were mild, -but one disagreeable feature was that in a certain percentage -there persisted a small fluctuating mass at the site of the injection. -Lacy saw a number of these cysts aspirated, and the -contents were found to be a sterile, oily fluid, with many leucocytes -present. In one instance the primary reaction disappeared -within a few days after vaccination, but recurred after four -months and persisted for several weeks.</p> - -<p class='c009'><span class='sc'>Notanda.</span>—The army lipovaccine apparently offers a certain -definite amount of protection against pneumonia, which was the -most dangerous complication of influenza. The protective substances -do not appear in the serum until eight days have elapsed -after the vaccination, and while no definite evidence has appeared -to show that there is a temporary increase in susceptibility -immediately after vaccination, the best results would undoubtedly -be obtained where the dose is given something more than eight -days before the appearance of the epidemic. The indications are -that the vaccine will not protect against influenza, but that the -complication of pneumonia is less likely to occur in the vaccinated -than in the unvaccinated individual.</p> - -<h3 class='c010'><em>Summary</em></h3> - -<p class='c011'>Records of attempts to confer immunity to influenza by the -use of vaccines have been separated into related groups and -studied. Those where pure Pfeiffer strains were used have been -considered in one group. Those where mixed vaccines were used -have been analyzed in three sub-groups or series, depending on -the relation between the times of vaccination and of the advent -of the epidemic, upon whether or not a week-by-week comparison -of the occurrence of influenza among vaccinated and unvaccinated -groups was made, and upon whether or not statistics for total -comparison alone were available. The third group included the -reports of the use of army pneumo-lipovaccines for the prevention -of the secondary pneumonia complications of influenza.</p> - -<div> - <span class='pageno' id='Page_134'>134</span> - <h3 class='c010'><em>Conclusions</em></h3> -</div> - -<p class='c011'>From our statistics we conclude that:</p> - -<p class='c009'>1. There is as yet no evidence that vaccines composed purely -of strains of Pfeiffer bacilli will confer immunity to epidemic -influenza.</p> - -<p class='c009'>2. The only data which can be used as a basis for estimating -the value of mixed vaccines as a preventive for epidemic influenza -must be obtained from experiments in which vaccination was -either completed before the epidemic appeared, or in which week-by-week -comparisons between the number of cases occurring in -the vaccinated and unvaccinated groups can be made.</p> - -<p class='c009'>3. Data obtained from experiments conducted under the above -qualifications is inconclusive, but presents little evidence of the -value of mixed vaccines in protecting against influenza. There -is, however, an indication that mixed vaccines used prior to the -arrival of the epidemic will lessen the number and the severity -of secondary pneumonias, and will probably lower the death rate -to a small degree.</p> - -<p class='c009'>4. The army pneumo-lipovaccine apparently offers some protection -against primary infections with types I, II and III pneumococci, -and a somewhat lesser amount of protection against -secondary pneumococcic infections with these strains following -influenza.</p> - -<p class='c009'>5. While it is impossible to say that the large number of -influenza cases developing almost immediately after vaccination -would not have occurred anyway, it is at least suggestive that a -temporary break occurs in the resistance after the inoculation, -and that unusual care should be taken by persons who have been -recently vaccinated, particularly when they are in the midst of -an epidemic disease.</p> - -<h3 class='c010'><span class='sc'>Part II. General Prophylactic Measures</span></h3> - -<p class='c011'>One of the most remarkable things about the 1918 pandemic -was the great rapidity with which it spread to all parts of the -world. From the report of the first cases which landed in Boston -until the epidemic arrived in San Francisco the time consumed -was less than two months, and the peaks of the two epidemics -were just about one month apart. Apparently no part of the -world escaped. Asia, Europe, Africa, North and South America, -<span class='pageno' id='Page_135'>135</span>and some of the remote islands of the Pacific, all reported large -epidemics, with high mortality and great suffering. The deplorable -failure of precautionary measures in controlling the spread, -or at least in limiting the disease, may be offset in a measure -by the unusual conditions under which almost everybody had -been living. Vast numbers from all over the world were gathered -together because of the war. Thousands of men were housed -together in army camps or in training cantonments. Other -thousands were doing relief work or engaged in the manufacture -of munitions. Most of those at home were doing double duty, -and were on a severe nervous strain. Everyone everywhere was -working to the limit and was consequently fatigued. The necessities -of war had cut down the amounts of food generally, and -sugar and fat rations particularly. Traffic, both between nations -and at home, had never been so great nor accommodations so -insufficient. So that it is likely that all of these and many more -changes in the daily routine of individuals led to a condition of -lowered resistance, and at the same time increased their chances -of exposure. One point, at least, stands out prominently, and -that is that “influenza as it occurred clinically during the first -great wave was different from those cases which appeared later.” -This was seen in the acuteness of the onset, in the severity of -symptoms, and in the high mortality rate. Therefore, any -measure which afforded protection, if only for the time being, is -worthy of retrial.</p> - -<p class='c009'>In view of the fact that recurrences have followed closely in -the wake of all former influenza epidemics, and with the hope of -stimulating concerted investigation of preventive measures, the -American Public Health Association (57), at its meeting in -Chicago in December, 1918, appointed a committee to outline -“a provisional working formula, based on the facts and opinions -brought out at the meeting.” A summary of the opinions as -taken from the report of the committee is given here. They -reported that the disease was probably due to some micro-organism -or virus as not yet identified; that while it was known -as “influenza,” it was not known to be identical with the disease -generally known under that name; that there was no known -laboratory method of differentiating it from ordinary colds, -bronchitis, etc.; that there was no known laboratory method of -determining when a patient ceased to be infective; and that the -<span class='pageno' id='Page_136'>136</span>deaths from influenza were due to secondary pneumonia resulting -from an invasion by one or more forms of streptococci, or by -one or more forms of pneumococci, or by the so-called influenza -bacillus or bacillus of Pfeiffer. Because of the clear and concise -manner in which this report brings out the opinions held, at the -time, by a majority of the medical profession a portion of the -report is given here <i><span lang="la" xml:lang="la">verbatim</span></i>.</p> - -<p class='c009'>“Evidence seems conclusive that the infective micro-organisms -or virus of influenza is given off from the noses and mouths of -infected persons. It seems equally conclusive that it is taken -in through the mouth or nose of the person who contracts the -disease, and in no other way except as a bare possibility through -the eyes by way of the conjunctivæ or tear ducts.</p> - -<p class='c009'>“If it be admitted that influenza is spread solely through discharges -from the nose and throats of infected persons, finding -their way into the noses and throats of other persons susceptible -to the disease, then, no matter what the causative organism or -virus may ultimately be determined to be, preventive action -logically follows the principles named below, and, therefore, it -is not necessary to wait for the discovery of the specific micro-organism -or virus before taking such action.</p> - -<p class='c009'>“1. Break the channels of communication by which the infective -agent passes from one person to another.</p> - -<p class='c009'>“2. Render persons exposed to infection immune, or at least -more resistant, by the use of vaccines.</p> - -<p class='c009'>“3. Increase the natural resistance of persons exposed to the -disease by augmented healthfulness.”</p> - -<p class='c009'>The ways and means of carrying out these principles are many -and varied, and it is merely the intention of this paper to put -together a sort of digest of some of the more important arguments -for and against some of the seemingly more important -measures proposed.</p> - -<h3 class='c010'><em>Methods Proposed for Breaking the Channels of Communication</em></h3> - -<p class='c011'>(a) Rigid quarantine for all persons suffering from the disease -and all contacts. During the epidemic quarantine was advocated -by many people. It was pointed out that the disease spread most -rapidly in camps, in ships, and in quarters generally where large -numbers of persons were closely associated; that it was quite as -<span class='pageno' id='Page_137'>137</span>contagious and more rapidly fatal than most diseases which are -regularly quarantined; that while it was admitted that there is -no laboratory method to make certain the diagnosis, and no -method of telling how long convalescents are capable of transmitting -the disease, as there is, for instance, in diphtheria, still -there is no question of the value of the arbitrary quarantine used -in measles, scarlet fever and smallpox, all of which are diseases -in which the parasitic causes are not known. Further, the -opinion was expressed that complete isolation and quarantine -would not only protect the community from influenza, but that -it would also in a measure protect the patient from contact with -numerous outside strains of pneumococci and streptococci, and -so lessen secondary infection and reduce the general mortality.</p> - -<p class='c009'>There are many reasons why quarantine is not applicable -in epidemic influenza. Most important of all is probably the -inability to make certain the diagnosis, especially during the -early stages in light cases. This would work detrimentally in -several ways. Really ill patients would delay calling a physician -until late, for fear of unnecessary quarantine. Many needless -and unjust quarantines would result when the diagnosis was -uncertain and the physician anxious to carry out quarantine -measures efficiently. Many patients would have contacts running -about and infecting their neighborhoods while a delayed diagnosis -was being made. Influenza was so contagious during the -epidemic that it would have necessitated general quarantine -not only of all infected persons but also of all contacts to have -obtained any favorable results, and since nearly everyone was -either a patient or a contact, all lines of business would literally -have been paralyzed by the procedure. If it is true that the -infected person is most dangerous to others before he has developed -symptoms himself, he is a carrier impossible of detection -and control. Points in favor of the hypothesis that infected -persons spread the disease before they develop symptoms are -found in the following facts. As the disease passed from community -to community officials became alert for the appearance -of the first case. In army barracks and in large institutions it -was often possible to determine the first case at its development. -The case was, in many instances, removed at once and isolated, -but I have seen no instance in which such a measure was successful -in curbing the disease. As subsequent cases appeared they -<span class='pageno' id='Page_138'>138</span>were likewise immediately removed, but the cases continued to -spread just the same. Bloomfield (38) cited the incident of a -student who spent a few hours visiting his sister in a part of the -country where there had been no influenza. He appeared well at -the time, but six hours after his return to school he developed -influenza. Two days after the contact the sister came down with -the disease. On the other hand, he told of a student who did not -contract the disease, though he slept for two nights in the same -bed with his roommate, who had returned to school with a well-developed -case of influenza. The unsuccessful attempts to transmit -influenza in the experiments of Rosenau (37), McCoy (37a) -and others already cited would indicate that the cases from whom -the material was taken were no longer infectious, although some -of them had been showing symptoms for only about 12 hours. -Bloomfield observed that the general use of face masks in the -wards did not alter the course of the epidemic, and stated that if -face masks are protective, infection from early unisolated cases -must be assumed.</p> - -<p class='c009'>Provided influenza is generally transmitted during the period -of incubation, a theory which seems consistent with the facts, -rigid quarantine for epidemic influenza is impracticable and probably -useless.</p> - -<h3 class='c010'><em>Partial Isolation by Means of the Cubicle System</em></h3> - -<p class='c011'>The so-called cubicle system consists in the dividing of rooms, -or more particularly of wards, into small compartments by means -of suspending sheets from wires so that each bed is separated -from its neighbor. Capps (39) reported favorably on the method -as used at Camp Grant, where sheets or halves of tents were -suspended from wires or from the mosquito netting frames -which were a part of the standard beds. Doctors, nurses and -attendants were forced to wear masks in the wards, and patients -were not allowed out of the cubicles without them. In discussing -this paper Thayer emphasized the value of screening, masking -and the wearing of gowns, and also recommended thorough washing -of the hands between the examination of each two patients; -and Emerson called attention to the fact that the first demonstration -of the cubicle system as an adequate means of preventing -acute respiratory diseases was made at the Pasteur Institute of -<span class='pageno' id='Page_139'>139</span>Paris, where it had been in operation for 10 years. The latter -stated that the system had been used in various hospitals in -America and was essential for the care of diphtheria, measles and -scarlet fever. He further indicated that if the technique of personal -cleanliness of nurses, doctors and attendants could be perfected, -it was probable that the height of the cubicle partition -could be reduced to that of a “red string.” The method certainly -seems worthy of consideration and trial, particularly in large -general hospitals and public institutions.</p> - -<h3 class='c010'><em>The Use of the Face Mask</em></h3> - -<p class='c011'>The question of the value of wearing a gauze mask over the -mouth and nostrils during an influenza epidemic is still an open -one. Masks, however, have been found useful in protecting -against some other diseases of respiratory origin. In December, -1917, Weaver (40) reported favorably on the use of gauze masks -in the Durand Hospital of Infectious Diseases. The masks were -used by nurses in attendance upon patients with contagious diseases, -and also by patients who were convalescing from diphtheria, -meningitis or pneumonia and who were in the same wards -with those having other respiratory diseases. In a later article -Weaver (41) stated that by the use of masks they had been able -to reduce the percentage of diphtheria carriers among their -nurses in the diphtheria wards to 5.2 per cent., as compared -to the average of 23.25 per cent. during the 20 months immediately -preceding their adoption of their use. He recommended -the general use of masks for physicians when in contact with all -types of respiratory diseases. In March, 1918, Capps (39a) -reported encouraging results in the control of infections through -the masking of all patients at Camp Grant. During the epidemic -the wearing of masks became quite general, and was very popular -in many sections.</p> - -<p class='c009'>Several sets of laboratory experiments have been carried out -recently to determine whether the masks are of practical value -or not. The experiments have generally consisted in spraying -cultures of living bacteria over sterile bacterial plates which were -protected by one or more layers of gauze. A number of variations -were made in the manner in which this was done: (a) the -distance between the nozzle of the spray and the mask was -<span class='pageno' id='Page_140'>140</span>varied, and the distance between the plate and the mask kept constant; -(b) the distance between the plate and the mask varied, -and the distance between the nozzle and the mask kept constant; -(c) the use of masks both over the nozzle of the spray and over -the plate being kept constant, and the distance between the two -masks varied. In a somewhat different set of experiments the -mask was placed over the mouth of a person, who was told to -talk or cough over an agar plate, and the bacterial plate being -held at various measured distances from the face. By counting -the number of colonies which developed upon the plates it was -possible to get fairly reliable data as to the efficiency with which -the bacteria were intercepted by the gauze. Weaver (42) found -that if enough gauze was used, it would filter out all of the bacteria -passing from the spray in the direction of the plate. The -efficiency of the mask being in direct proportion to the fineness -of the mesh and the number of layers employed. Doust and Lyon -(43) made a series of experiments to determine the distance -through which droplets are carried when expelled under different -circumstances. They found that in ordinary speech infected -material is projected for about four feet, and that during coughing -the material is carried about ten feet. They demonstrated -that masks of medium meshed gauze, two to ten layers thick, -worn by the person coughing did not prevent the passage of -infectious material into the air, but that a three-layer buttercloth -mask was much more efficient. Haller and Colwell (44) -used three distinct sets of experiments—one with the mask over -the mouth of the patient, one with the mask over the plate, and -the third with masks over both—and concluded that a five-layer -mask made up of 24 × 20 mesh protected the plate in the second -series of experiments. They suggested marking one side of the -mask, so that it would always be worn with the same side out. -Leete (45), in England, by a similar series of experiments concluded -that a dry mask of six to eight layers of butter muslin -worn by a contact would protect him against droplet-carried -infections. Dannenberg (46) suggested making the gauze mask -over a copper screen wire frame to give it shape and keep it away -from the mouth, thus keeping it relatively dry. All observers -agree that masks while dry are more efficient than they are after -they have become moist.</p> - -<p class='c009'><span class='pageno' id='Page_141'>141</span>The efficiency of the mask has also been widely discussed from -the clinical standpoint. Mink (47) in discussing their use at the -Great Lakes Training Station said that he had no objection to the -mask as it is “intended to be worn,” but that as it “was worn” by -the medical corps men at the station 8 per cent. of those who -used the mask developed influenza, as compared to 7.75 per cent. -of those who did not; 30 per cent. of the dental officers at the -station developed the disease in spite of the fact that they were -all accustomed to wear masks during their work. In discussing -the mask Vaughan (48) said: “With reference to the mask, I -am strongly of the opinion that we have overestimated its -value. * * * When I went to Camp Devens they were not -using the mask. I called the doctors together and told them its -use was not compulsory, but I said: ‘Every doctor who took care -of cases of pneumonic plague and did not wear a mask died from -it, and every man who cared for pneumonic plague cases and -didn’t wear a mask did contract it.’” They were then allowed -to choose for themselves. It has been pointed out that the epidemic -dropped off at once in San Francisco with the universal -compulsory use of the mask on the street, but it is also said that -the epidemic in Los Angeles, which ran a course parallel to that -in San Francisco and in which masks were only indiscriminately -used, began to drop off simultaneously. While it is difficult to -get at the facts, it seems that, provided epidemic influenza is -carried through the air or by means of droplets, the universal -use of masks should decrease the number of exposures. The -claim has been made that masks merely tend to prolong the epidemic, -and that susceptible persons develop the disease after -the epidemic proper has passed. If the mask will protect the -susceptible individual until the virulence of the disease has -decreased, it will better that individual’s chances for recovery, -and so is worth the trouble.</p> - -<h3 class='c010'><em>General Closing Orders</em></h3> - -<p class='c011'>In most large cities orders were issued closing churches and -theatres and prohibiting public gatherings of all kinds. In New -York these places of public gathering were not closed, and it has -been pointed out, as an argument against closing orders in the -future, that the death rate there was less than in Boston, Philadelphia, -<span class='pageno' id='Page_142'>142</span>Pittsburgh, etc. Copeland (49), of the New York Board -of Health, stated that the unventilated picture shows were closed, -but that the theatres were used as places of public instruction. -New York’s relatively low death rate was difficult of explanation, -but it is very certain that it had nothing to do with the fact that -closing orders were not in vogue. If it were possible to obtain -the figures, it would be interesting, indeed, to compare the death -rate from influenza among New York’s theatre-attending public -during the epidemic with the death rate of the community in -general.</p> - -<p class='c009'>Generally speaking, any unnecessary public gatherings are -inadvisable during any epidemic. While our exact knowledge of -the mode of transmission of influenza is incomplete, it is unquestionably -a contact disease. People who have been exposed and who -have not yet contracted the disease are known to have transmitted -it to a third person. A certain number of people from -infected homes will attend public gatherings as long as they are -able, for it is impossible to get together any large group of persons -all of whom are going to play fair. It is true that these -meeting places may be used in a measure to allay panic and to -instruct the public in health measures, but there are many efficient -and far less dangerous methods of accomplishing the same -results. Vaughan in discussing assemblies in large halls mentioned -that in a hall at Camp Forest, which held 9,000 people, -the individuals had a space of about 16 inches laterally between -their noses. He pointed out that if many of them were talking, -coughing or sneezing, the air contamination would soon become so -great that it could make little difference whether there was a -roof over the building or not. He emphasized the fact that it is -just as possible to crowd men in the open as it is indoors. Ventilation -is undoubtedly an important factor, but it cannot correct -overcrowding. As far as the educational value of the public -gatherings was concerned, it may be observed that regular -attendants of theatres and moving-picture houses during the -year of 1918 had become quite accustomed to appeals regarding -all sorts of public movements from speakers who appeared -between the acts, or pictures, but that the closing of these places -threw a wholesome scare into them which made them pay far -closer attention to prophylactic measures than almost anything -<span class='pageno' id='Page_143'>143</span>that could have happened. “Object-lessons are always superior -to didactic teaching.” In Chicago a new argument for the closing -of theatres was advanced. It was said that with no place to go -many people retired earlier and obtained more than their accustomed -amount of rest. It was believed that this aided in increasing -their natural resistance. The argument that the closing of -these places served only to delay the epidemic is an argument -in favor of the measure, because the virulence of the disease -decreased rapidly as the epidemic progressed.</p> - -<h3 class='c010'><em>The Closing of Schools</em></h3> - -<p class='c011'>Boards of Health generally were opposed to the closing of the -public schools. This position gave rise to innumerable clashes -with anxious parents. The health authorities took the position -that children were relatively insusceptible to influenza; that while -they were quiet in a well-ventilated schoolroom they were little -exposed; that those who coughed or sneezed could be examined -at once, and that daily school inspection would lead to early discoveries -of all cases, so that doctors and nurses could take -immediate steps to treat the patients and to protect the families -from which they came. Copeland advocated the continuance of -the schools in New York, and based his position on the fact that -out of 1,000,000 children in New York City 700,000 came from -tenement homes. He believed these children were far better off -in school, where they received daily medical attention, than upon -the streets or in unhygienic homes.</p> - -<p class='c009'>In Pittsburgh the school children were quizzed as to the number -of sick at home, and this gave valuable information on the -stage of the epidemic. They were sent home with printed warnings -against sneezing, coughing and spitting, and were thus used -as a means of instructing their parents. The Pittsburgh schools -were kept open until the sickness of a number of teachers and -the withdrawal of many scholars made it advisable to close.</p> - -<p class='c009'>Three very potent arguments have been brought forward in -favor of closing the schools: (1) As long as the schools are open -children from infected homes are forced into contact with children -from uninfected homes, and we are at present unaware of -the extent to which the disease may be carried by a third person. -(2) Children in as yet uninfected homes which are comfortable -<span class='pageno' id='Page_144'>144</span>and hygienic are far better off than they are in school, and can -hardly be considered in the same class with children from unclean -tenements. (3) If the period of greatest contagion is before -symptoms develop, inspection, while valuable for the institution -of treatment, cannot hope to aid in curbing the epidemic. It is -evident that different measures must be employed in applying -closing orders to crowded cities, moderately large towns and -rural districts. The difficulty lies in determining the best means -for serving each community.</p> - -<h3 class='c010'><em>The Closing of Public Dance Halls</em></h3> - -<p class='c011'>Public dances should undoubtedly be prohibited during epidemics. -They not only present all the bad features of other -public gatherings, but during the dancing people are brought in -very close contact and often breathe directly into each other’s -faces. In addition, air currents are stirred up and a certain -amount of dust is raised. During the exercise the dancers -breathe more rapidly and deeply, thus inhaling unusually large -amounts of dust, droplets and contaminated air. Another feature -is found in the “resistance-breaking” element of alternate overheating -and rapid cooling of the body.</p> - -<h3 class='c010'><em>Regulation of Public Eating and Drinking Places</em></h3> - -<p class='c011'>Public eating places are a necessity and cannot be closed. -People should be cautioned against using them as places of -amusement and of congregation during epidemics. Boards of -Health should feel it just as much their duty to see to the -sterilization of dishes and eating utensils as they do to the -enforcing of any other public health functions, and they should -also insist on the daily inspection of the employees of such -establishments. The beer saloon question may be passed over -for the present, but the soda-water fountain as conducted during -the 1918 epidemic was undoubtedly a great menace. Ice cream, -syrupy mixtures, etc., of various kinds are readily contaminated -by pathogenic organisms which may serve as secondary infectors, -if in no other capacity. The syrups, moreover, adhere to the -spoons and glasses, which are rarely thoroughly washed and are -practically never sterilized between customers. The use of paper -<span class='pageno' id='Page_145'>145</span>dishes and glasses is probably a step in the right direction, but -the spoons should be thoroughly washed and sterilized. The fact -that soda-water employees are not always selected for high-grade -intelligence, and are generally left largely to their own -hygienic procedures, makes the chances of transferring infections -at these places enormous. If soda fountains are allowed -to continue business at all during the epidemics, it should be only -under the very strictest supervision by Boards of Health. The -scalding of all utensils should be enforced by law.</p> - -<p class='c009'>People generally should be cautioned to use exceptional cleanliness -in the preparation of all foods in the home. In discussing -the recent epidemic Lynch and Cummings (50) stated that “the -mess-kit wash water proved the major route of transmission -from sick to well in the army.” Vaughan said: “I am pretty -certain, not convinced, that hand-to-mouth infection is of more -importance than droplet infection.”</p> - -<h3 class='c010'><em>Regulation of Traffic</em></h3> - -<p class='c011'>Business must be conducted in epidemic as well as in normal -time, and employees must go to and from their places of occupation. -In cities where the distance from the residence to the -business districts is great, street cars and other public conveyances -must be used. Their use undoubtedly increases the number -of contacts and leads to a wider distribution of the disease, -but, like eating in public restaurants, it is a chance which many -have to take. Few places offer better opportunities for exposure -than street cars—where people of all grades of intelligence, representing -all states of health and degrees of cleanliness and -uncleanliness, are crowded closely together, breathe into each -other’s faces, and handle the same straps and supports.</p> - -<p class='c009'>In Pittsburgh the cars have a seating capacity for from 30 -to 50 persons, but during the morning and evening hours they -are crowded to capacity, and are commonly seen to carry more -than 100 passengers at a time. Here, too, the unkempt, indifferent -foreign element is conspicuous, and these people are known -to disregard all hygienic teachings. A few days after the -appearance of the epidemic the street cars were placarded with -warnings against coughing, spitting and sneezing. The cards -instructed people who became ill to go home, to go to bed and -<span class='pageno' id='Page_146'>146</span>to remain there until they were well. Later a second order -appeared which gave notice that all windows in street cars were -to be kept raised six inches and that no heat was to be allowed -in the car. The order was intended to improve ventilation, and, -for a wonder, it was enforced. During the first few days the -weather was fine, warm and clear, and the draught caused by -the open windows brought no discomfort; but later the weather -became cold and several days of drizzling rain set in. The cars -with open windows became very uncomfortable, but the streetcar -employees insisted upon obeying the order to the letter. No -judgment was exercised by them, and the windows were kept -open night and day, cold or warm, crowded or empty, in fair -and rainy weather alike, and no heat was allowed to be turned -on. Many people preferred standing to exposing their backs and -necks to the cold draughts, and it is more than likely that such -use of open windows did far more harm than good. As above -quoted, Vaughan pointed out that crowding is just as dangerous -out of doors as indoors, and it is certain that crowding in cold, -draughty cars is dangerous, both from the close contact and -because of the added danger of lowering bodily resistance.</p> - -<p class='c009'>In an attempt to decrease the crowding on public conveyances -the so-called “stagger-hour” system was adopted in New York. -Under this arrangement manufacturers and business houses -changed their working hours in such a way that the morning and -evening travel was spread out and the average number of people -carried per hour was proportionately decreased.</p> - -<p class='c009'>Looking backward over the methods used to decrease the spread -through the use of public conveyances, it seems that the following -procedures have the best claims for retrial: (1) Placarding the -cars. This appeared to reduce the amount of coughing and -sneezing, even in face of the fact that the cars were unusually -draughty and chilly. (2) The adoption of the “stagger-hour” -system where the practice is feasible. (3) The instruction of the -people to use the street cars as little as possible.</p> - -<h3 class='c010'><em>Enforcement of Anti-Spitting Ordinances</em></h3> - -<p class='c011'>All street cars and trains carry anti-spitting notices either -to the effect that spitting will be prohibited on penalty and fine -and imprisonment, or giving stated amounts of the fine. Yet -<span class='pageno' id='Page_147'>147</span>spitting is constantly indulged in in these places and one -rarely sees or hears of the enforcement of the law. If the ordinance -was worth making a law, it is certainly worth enforcing, -and yet there is probably no law so flagrantly broken. Ordinary -police officers pay no attention to the enforcement of the spitting -ordinance and have been known to refuse to even reprimand -spitters. The incident of a sanitary officer wearing a uniform and -a cap, indicating to the public his official position, who was seen -sitting in the smoking car in a local suburban train and spitting -profusely on the floor has been recounted on very reliable authority. -Another incident is known in which a street car conductor -was asked by one passenger to stop another who was expectorating -abundant mucoid sputum upon the floor. The conductor -replied that he had orders not to notice such things. It is no -wonder that people are indifferent to such impotent measures. -Whether it is possible to convey epidemic influenza or not by -means of sputum, it is certain that tuberculosis is spread in this -way, and that influenza predisposes to tuberculosis and causes old -healed tuberculous foci to become active. People should be made -to understand that they may have tuberculosis without knowing -it themselves, and that by spitting it may be transmitted to other -persons. Spitting by persons aware that they have tuberculosis -is criminal negligence and such persons should undoubtedly be -prosecuted. If a person knows that he has tuberculosis and -deliberately spreads about the infection so that other persons -contract the disease and die from it, he is directly responsible for -the deaths. It would be hard to imagine trying to control manslaughter -committed in any other way by merely putting up signs -in conspicuous places forbidding the act. The average boy -acquires the spitting habit between the ages of 8 and 12 years, -and in many instances carries it to the grave. The one possible -way of stopping spitting seems to lie in teaching the dangers of -it to children, beginning in the kindergarten and emphasizing it -throughout the child’s education. It is possible that in this way -spitting may become obsolete in two or more generations.</p> - -<h3 class='c010'><em>Increasing Natural Resistance by Augmented Healthfulness</em></h3> - -<p class='c011'>If there is any way of increasing the natural resistance against -epidemic influenza, it is a most desirable goal toward which to -work, but it must first be determined along what lines the effort -<span class='pageno' id='Page_148'>148</span>is to be directed. It was not the aged, the unconditioned nor the -physically unfit who suffered most from influenza, but was rather -the best trained, most healthful and most robust young persons -we had. Those in the army had been selected because of their -physical fitness and they had further received excellent physical -training in the various camps and cantonments. It would not be -possible to bring any large percentage of the general public up to -such a stage of “augmented healthfulness” as healthfulness is -generally understood. It has been said that men in the military -camps were more commonly infected because they were more -active, went about more and were, therefore, more frequently -exposed. In one particular this statement is true, for men marching -rapidly and exercising violently breathe more deeply and at -a faster rate than they do under ordinary conditions, so that they -naturally draw greater quantities of air into their lungs. It was -an obvious fact that those persons given to sedentary lives were -less often affected than the active and vigorous. Practically -speaking, it would seem that during influenza epidemics people -should be instructed to take more than the usual amount of sleep -and rest, to indulge only in mild exercises, to eat good, wholesome -food, to wear warm clothing, to seek mental and physical relaxation -at home, and, above all, to avoid crowds and public gatherings.</p> - -<p class='c009'>In some instances the constant use of oils in the nose and throat -was advised, the theory being that the oil served the double purpose -of preserving the healthy condition of the mucous membranes -by lessening crusting, crevicing and drying, and of mechanically -protecting from infection by the presence of the layer of oil. -Many of the different liquid paraffins, both medicated and in the -natural state, were used. It is probably advisable to apply such -oils either with a swab or from a medicine dropper, rather than to -attempt to spray them, since in the latter method there is some -danger of blowing infectious material down into the trachea and -larynx.</p> - -<p class='c009'>It is hardly necessary to point out the importance of augmented -cleanliness of the mouth, teeth and throat by means of mild antiseptic -washes and tooth-cleansing materials during an epidemic.</p> - -<h3 class='c010'><span class='sc'>General Measures</span></h3> - -<h4 class='c027'><em>Public Health Administration</em></h4> - -<p class='c011'>Unless one had had a wide experience in the administrative -<span class='pageno' id='Page_149'>149</span>side of public health matters, it would be useless for him to try -to discuss the details of handling any sort of an epidemic, and -even then local conditions vary so much in different cities and -States that each administrator’s experience must differ greatly. -The difficulty with reports of epidemics by public health officials -is usually found in the fact that the reports are impersonal compilations -and convey no idea to the reader, or rather to the -student (for no mere reader is attracted to them), of what situations -were faced, of what difficulties were in the way, of how the -conditions were met, or what the administrator after due reflection -would advise doing next time under similar circumstances. -In the face of inexperience the writer ventures the following suggestions -for improvement, though no originality is claimed for -the ideas.</p> - -<p class='c009'>The administrative powers should be centralized in one individual, -or in an executive officer acting for a competent board of -advisers, who should be endowed with the powers to carry out the -measures which seem best suited to meet the situation at hand, -and who should be beyond the pale of political interference and -in position to prevent political fiascos, built more or less directly -on health regulations.</p> - -<p class='c009'>The United States Public Health Service should work toward -standardizing health laws and penalties for all States.</p> - -<p class='c009'>Thorough enforcement of ordinances requiring the reporting -of all cases and all deaths as now demanded by public health -rulings should be insisted upon. These reports are so important -to a knowledge of the progress of the epidemic that the section on -preventive medicine of the American Medical Association (51) -has just advised the consideration of eliminating from membership -in the Association any physician who willfully fails or refuses -to comply with the regulations requiring the reporting of communicable -diseases. Additional information can be obtained by -daily canvasses of the schools, when open, of the large industries, -and of the daily admissions to hospitals. Data on the daily -facilities for the handling of additional cases in hospitals should -be on file in the office of the administrator of health.</p> - -<p class='c009'>Printed instructions giving in detail the proper procedures for -isolation of the patient and the protection of the family should be -supplied to physicians for distribution at the first visit to suspected -cases.</p> - -<div> - <span class='pageno' id='Page_150'>150</span> - <h4 class='c027'><em>Desirable Laws</em></h4> -</div> - -<p class='c011'>Some specific laws governing the following points would be of -great advantage during the progress of an epidemic: (a) A law -providing for the commandeering by boards of health of vaccines, -sera or other substances for which a sudden unusual demand -may occur, and for the distribution of such substances by the -authorities to the public at the prices ordinarily asked. (b) A -law permitting the exclusion from the daily papers by boards of -health of advertisements containing obviously false and fraudulent -statements relative to the epidemic. (c) A law permitting -the health authorities to go into public eating places and demand -proper sterilization of dishes and eating utensils with the alternative -of closing the establishment. (d) A set of laws making -the penalties sufficient to prevent violations of the regulations.</p> - -<h4 class='c027'><em>Education of the Public</em></h4> - -<p class='c011'>From the beginning to the end of an epidemic the health -authorities, aided by the medical profession, should take the -public wholly into their confidence. At the first news of the -approach of the disease a general bulletin should be issued giving -all of the main facts that are available. This was done in a way -by the American Public Health Service, but the bulletin reached -only a small fraction of the people, and although parts of it -appeared later in the daily papers, it was pretty generally -missed. The papers should be used freely and the space paid for -when necessary, so that the news of the epidemic is featured -emphatically. The establishment of a question and answer -department or a bureau of information would take care of a -great deal in the way of denying misinformation. The public -should be encouraged to report helpful facts of all kinds, but -with the understanding that no rumors would be published without -investigation and confirmation. In this way it would be -possible to prevent articles advising harmful and useless remedies -from reaching the press, and aid in suppressing some of the -“Sure Cures,” so many of which appeared to abuse the confidence -of the unwary during the 1918 epidemic. Several such -cures have been most interestingly discussed in a recent bulletin -of the United States Public Health Service. The bulletin divides -the “Sure Cures” into three different classes, as follows: “First -<span class='pageno' id='Page_151'>151</span>comes the individual who has a specific remedy, the formula of -which he will sell for a price * * *; next comes the person -with a pseudo-scientific treatment, e. g., isotonic sea water, -‘orzono therapy,’ ‘harmonic vibrations.’ * * * Still another -type, who gives freely of his advice that humanity may be -spared from pestilence.” Among the latter are found advice for -placing sulphur in the shoes, wearing of amulets, inhaling of -alcohol, chloroform, etc., as well as numerous religious and mental -science treatments, etc. A frank statement of facts and a discussion -of the ridiculous side of many of these claims would -undoubtedly benefit the entire public. The placarding of the cars -and the warnings posted in conspicuous places no doubt helped -greatly, and this method undoubtedly should be continued. As -long as theatres are allowed to remain open, speakers may be -used to advantage to emphasize important points. The County -Medical Societies should be asked to appoint committees for -supplying information or for seeing that the information given -to the public is authoritative. In large cities committees may -be organized among hospital superintendents, so that the heartiest -co-operation between health authorities and hospitals will -be available. The ever-ready aid of the Red Cross and of every -other auxiliary body should be employed to the fullest extent to -allay apprehension and relieve suffering.</p> - -<h3 class='c010'><em>Summary</em></h3> - -<p class='c011'>The exact knowledge of the mode of transmission of epidemic -influenza is still wanting, but it is known to be spread by contact. -Attention should be directed toward every practical means of -decreasing the number and intimacy of contacts. Publicity campaigns -and other educational measures should be pushed strongly. -Health Departments should adopt a policy of preparedness during -inter-epidemic times, should make every effort to centralize and -standardize their work, and should take steps to obtain sufficient -legal backing, so that upon the appearance of the epidemic they -can take the lead, speak with authority and enforce their ordinances -and measures. The physician’s duty is to inform himself -on the value of the various measures, and if he is at odds with -the public health methods, he should settle them between epidemics, -so that when he is called upon to carry out public health -<span class='pageno' id='Page_152'>152</span>orders he can do it to the letter and without criticism. Laymen -should learn that quiet living without violent exercise, the keeping -of good hours, the avoidance of public gatherings and of -unnecessary exposure is the best policy to pursue during influenza -epidemics. They should strictly obey the orders of those who -have specialized in the control of epidemics, and all business men -must stand ready to help in every possible way and to make their -business interests subservient to the public good.</p> - -<h3 class='c010'>BIBLIOGRAPHY</h3> - -<table class='table3' summary=''> - <tr> - <td class='c018'>1.</td> - <td class='c006'>Rosenau, Keegan, Goldberger and Lake</td> - <td class='c028'>Public Health Report, 1919; xxxiv, No. 2, p. 33.</td> - </tr> - <tr> - <td class='c018'>1a.</td> - <td class='c006'>McCoy and Richey</td> - <td class='c028'>Public Health Report, 1919; xxxiv, No. 2, p. 34.</td> - </tr> - <tr> - <td class='c018'>2.</td> - <td class='c006'>Lacy</td> - <td class='c028'>Jour. Lab. and Clin. Med., 1918; iv, p. 55.</td> - </tr> - <tr> - <td class='c018'>3.</td> - <td class='c006'>Wollstein</td> - <td class='c028'>Jour. Exper. Med., 1911; xiv, p. 73.</td> - </tr> - <tr> - <td class='c018'>4.</td> - <td class='c006'>Flexner</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1913; lxi, p. 1872.</td> - </tr> - <tr> - <td class='c018'>5.</td> - <td class='c006'>Park and Williams</td> - <td class='c028'>Bacteriology, 1914 Edition; p. 437.</td> - </tr> - <tr> - <td class='c018'>6.</td> - <td class='c006'>Leary</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxxi, p. 2098.</td> - </tr> - <tr> - <td class='c018'>7.</td> - <td class='c006'>Leary</td> - <td class='c028'>Amer. Jour. Public Health, 1918; viii, p. 755.</td> - </tr> - <tr> - <td class='c018'>8.</td> - <td class='c006'>Rosenau</td> - <td class='c028'>Preliminary report furnished through Surgeon-General of the Navy W. C. Braisted.</td> - </tr> - <tr> - <td class='c018'>9.</td> - <td class='c006'>Barnes</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxxi, p. 1849.</td> - </tr> - <tr> - <td class='c018'>10.</td> - <td class='c006'>Hinton and Kane</td> - <td class='c028'>The Commonwealth Mass. State Dept. Health, 1918; vi, Nos. 1 and 2, p. 28.</td> - </tr> - <tr> - <td class='c018'>11.</td> - <td class='c006'>Hinton and Kane</td> - <td class='c028'>Hinton’s Report.</td> - </tr> - <tr> - <td class='c018'>12.</td> - <td class='c006'>Parker</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1919; lxxii, p. 476.</td> - </tr> - <tr> - <td class='c018'>13.</td> - <td class='c006'>Pearce</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1913; lxi, p. 2115.</td> - </tr> - <tr> - <td class='c018'>14.</td> - <td class='c006'>Committee on New and Non-Official Remedies</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxx, p. 1967.</td> - </tr> - <tr> - <td class='c018'>15.</td> - <td class='c006'>McCoy</td> - <td class='c028'>Personal Communication.</td> - </tr> - <tr> - <td class='c018'>16.</td> - <td class='c006'>Hutchinson</td> - <td class='c028'>Dixmont Hospital Report.</td> - </tr> - <tr> - <td class='c018'>17.</td> - <td class='c006'>McCoy, Murray and Teeter</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxxi, p. 1997.</td> - </tr> - <tr> - <td class='c018'>18.</td> - <td class='c006'>Minaker and Irvine</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1919; lxxii, p. 847.</td> - </tr> - <tr> - <td class='c018'>19.</td> - <td class='c006'>Sherman</td> - <td class='c028'>Report.</td> - </tr> - <tr> - <td class='c018'>20.</td> - <td class='c006'>Maberry</td> - <td class='c028'>Report from Hospital for Insane, Retreat, Pa.</td> - </tr> - <tr> - <td class='c018'>21.</td> - <td class='c006'>Rosenow</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1919; lxxii, p. 31.</td> - </tr> - <tr> - <td class='c018'>22.</td> - <td class='c006'>Beaver, Boles and Case</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1919; lxxii, p. 265.</td> - </tr> - <tr> - <td class='c018'>23.</td> - <td class='c006'>Ely, Lloyd, Hitchcock and Nickson</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1919; lxxii, p. 24</td> - </tr> - <tr> - <td class='c018'>24.</td> - <td class='c006'>Kitano</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1919; lxxii, p. 1575.</td> - </tr> - <tr> - <td class='c018'>25.</td> - <td class='c006'>Wynn</td> - <td class='c028'>Pract. London, 1919; cii, p. 77.</td> - </tr> - <tr> - <td class='c018'>26.</td> - <td class='c006'>Norman White</td> - <td class='c028'>Lancet., 1919; i, p. 707.</td> - </tr> - <tr> - <td class='c018'>27.</td> - <td class='c006'>Whitingham and Sims</td> - <td class='c028'>Lancet., 1918; ii, p. 865.</td> - </tr> - <tr> - <td class='c018'><span class='pageno' id='Page_153'>153</span>28.</td> - <td class='c006'>Cadham</td> - <td class='c028'>Lancet., 1919; ii, p. 885.</td> - </tr> - <tr> - <td class='c018'>29.</td> - <td class='c006'>Eyre and Lowe</td> - <td class='c028'>Lancet., 1918; ii, p. 485.</td> - </tr> - <tr> - <td class='c018'>30.</td> - <td class='c006'>Conference British War Office</td> - <td class='c028'> </td> - </tr> - <tr> - <td class='c018'>31.</td> - <td class='c006'>Whitmore, Fennel and Peterson</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxx, p. 427; also p. 902.</td> - </tr> - <tr> - <td class='c018'>32.</td> - <td class='c006'>Fennel</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxxi, p. 2115.</td> - </tr> - <tr> - <td class='c018'>33.</td> - <td class='c006'>Dochez and Gillespie</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1913; lxi, p. 727.</td> - </tr> - <tr> - <td class='c018'>34.</td> - <td class='c006'>Lister</td> - <td class='c028'>Publications of the South African Institute for Medical Research, No. 2, 1913.</td> - </tr> - <tr> - <td class='c018'>35.</td> - <td class='c006'>Lister</td> - <td class='c028'>Publications of the South African Institute for Medical Research, No. 8, 1916.</td> - </tr> - <tr> - <td class='c018'>36.</td> - <td class='c006'>Lister</td> - <td class='c028'>Publications of the South African Institute for Medical Research, No. 10, 1917.</td> - </tr> - <tr> - <td class='c018'>37.</td> - <td class='c006'>Cecil and Austin</td> - <td class='c028'>Jour. Exper. Med., 1918; xxviii, p. 19.</td> - </tr> - <tr> - <td class='c018'>37a.</td> - <td class='c006'>Cecil and Vaughan</td> - <td class='c028'>Jour. Exper. Med., 1919; xxix, p. 457.</td> - </tr> - <tr> - <td class='c018'>38.</td> - <td class='c006'>Bloomfield</td> - <td class='c028'>Johns Hopkins Bull., 1919; xxx, p. 1.</td> - </tr> - <tr> - <td class='c018'>39.</td> - <td class='c006'>Capps</td> - <td class='c028'>War Med., Vol. ii, p. 371.</td> - </tr> - <tr> - <td class='c018'>39a.</td> - <td class='c006'>Capps</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxx, p. 910.</td> - </tr> - <tr> - <td class='c018'>40.</td> - <td class='c006'>Weaver</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxx, p. 76.</td> - </tr> - <tr> - <td class='c018'>41.</td> - <td class='c006'>Weaver</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxxi, p. 1405.</td> - </tr> - <tr> - <td class='c018'>42.</td> - <td class='c006'>Weaver</td> - <td class='c028'>Jour. Infect. Dis., 1919; xxiv, p. 218.</td> - </tr> - <tr> - <td class='c018'>43.</td> - <td class='c006'>Doust and Lyon</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxxi, p. 1216.</td> - </tr> - <tr> - <td class='c018'>44.</td> - <td class='c006'>Haller and Colwell</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxxi, p. 1213.</td> - </tr> - <tr> - <td class='c018'>45.</td> - <td class='c006'>Leete</td> - <td class='c028'>Lancet., 1919; i, p. 392.</td> - </tr> - <tr> - <td class='c018'>46.</td> - <td class='c006'>Dannenberg</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxx, p. 99.</td> - </tr> - <tr> - <td class='c018'>47.</td> - <td class='c006'>Mink</td> - <td class='c028'>Jour. Amer. Med. Assoc. 1918; lxxi, p. 2175.</td> - </tr> - <tr> - <td class='c018'>48.</td> - <td class='c006'>Vaughan</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxxi, p. 2100.</td> - </tr> - <tr> - <td class='c018'>49.</td> - <td class='c006'>Copeland</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxxi, p. 2173.</td> - </tr> - <tr> - <td class='c018'>50.</td> - <td class='c006'>Lynch and Cummings</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1918; lxxi, p. 2174.</td> - </tr> - <tr> - <td class='c018'>51.</td> - <td class='c006'>Amer. Med. Association</td> - <td class='c028'>Public Health Report, 1919; xxxiv, p. 1413.</td> - </tr> - <tr> - <td class='c018'>52.</td> - <td class='c006'>Le Moignie and Pinoy</td> - <td class='c028'>Compt. rendu. Soc. Biol., 1916; lxxix, pp. 201 and 352.</td> - </tr> - <tr> - <td class='c018'>52a.</td> - <td class='c006'>Wright and Douglas</td> - <td class='c028'>Proc. Royal Soc. Med., 1904; lxxiii, p. 128, and lxxiv, p. 147.</td> - </tr> - <tr> - <td class='c018'>53.</td> - <td class='c006'>Neufeld and Rimpau</td> - <td class='c028'>Zeitschr. f. Hyg., 1905; li, p. 283.</td> - </tr> - <tr> - <td class='c018'>54.</td> - <td class='c006'>Rosenau</td> - <td class='c028'>Prevent. Med. and Hyg., 1918.</td> - </tr> - <tr> - <td class='c018'>55.</td> - <td class='c006'>Brown, Palfrey and Hart</td> - <td class='c028'>Jour. Amer. Med. Assoc., 1919; lxxii, p. 463.</td> - </tr> - <tr> - <td class='c018'>56.</td> - <td class='c006'>Gay</td> - <td class='c028'>Typhoid fever. (Published by Macmillan Co., 1918.)</td> - </tr> - <tr> - <td class='c018'>57.</td> - <td class='c006'>Eyre and Low</td> - <td class='c028'>Lancet. I, April 5, 1919; p. 557.</td> - </tr> -</table> - -<div class='chapter'> - <span class='pageno' id='Page_155'>155</span> - <h2 class='c005'>PHYSIOLOGICAL AND PHYSIOLOGICAL CHEMICAL OBSERVATIONS IN EPIDEMIC INFLUENZA</h2> -</div> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>By <span class='sc'>C. C. Guthrie, Ph. D., M. D.</span></div> - </div> -</div> - -<p class='c008'>The material consisted of cases in the acute stage of epidemic -influenza with and without clinical pulmonary involvement -(alveolar); of convalescents, and of normal individuals without -influenzal history.</p> - -<p class='c009'>It was hoped that it would be possible to follow selected cases -over considerable time periods, observation to compromise coordinated -clinical as well as laboratory data, but the exigencies of -the situation rendered this impossible. Unfortunately, this limits -the value of the studies. But since similar observations were -made on cases ranging from normal to the gravest severity—in -fact, preceding death but a few hours in some instances—and -from the nature of the findings, certain conclusions are clearly -warranted.</p> - -<p class='c009'>It is regrettable that the data on certain points is not more -extensive, and particularly that other methods of observation -were not employed. As an example of the latter, measurements -and analyses of expired air may be given, as this was planned -from the beginning and unsuccessful efforts made to provide the -required apparatus. In view, however, of the circumstances of -the investigation, it is felt that the studies made are, on the -whole, reasonably comprehensive and complete. And it is only -fair here to acknowledge that this was rendered possible by the -cordial and practical support of the Medical School, the military -authorities, the director of the laboratories, clinical colleagues, -particularly Dr. W. W. G. Maclachlan, and last, but not of less -importance, of the members of the department who made the -studies.</p> - -<p class='c009'>In presenting the results, it is deemed most expedient and -practical to omit extensive tabulations and to summarize the data -under each subject.</p> - -<p class='c009'>From the report it will be obvious that certain studies were in -preliminary stages at the termination of the investigation. This -<span class='pageno' id='Page_156'>156</span>was due in certain instances to the lateness of their undertaking, -or time consumed in providing essential equipment and methods; -or to disappearance of suitable cases due to waning of the -epidemic.</p> - -<h3 class='c010'><span class='sc'>Results</span></h3> - -<h3 class='c010'><em>Circulation</em></h3> - -<p class='c011'>For the most part, cases showing marked clinical symptoms -were studied. The pulse in severe cases frequently was weak -and rapid but regular. In some cases it was less rapid than the -clinical state would seem to indicate.</p> - -<p class='c009'><em>Arterial Blood Pressure</em> was low; systolic pressure in severe -cases ranging downward from 95, and diastolic down to 40 or -under. In patients in early stages of convalescence the pressure -showed a marked advance toward normal levels. Arterial blood -pressure seemed a reliable general index of the condition of the -patient.</p> - -<p class='c009'><em>Venous Blood Pressure.</em>—The observations included patients -who a few hours later expired. The Von Recklinghausen method -was used. No marked abnormality was observed, so other -methods of observation were deemed superfluous.</p> - -<h3 class='c010'><em>Respiration</em></h3> - -<p class='c011'>In severe cases, frequently it was rapid and of shallow character; -but, like the pulse, often it was less rapid than the clinical -state would seem to indicate.</p> - -<p class='c009'><em>Cyanosis</em> of dark hue and marked degree was prevalent in the -earlier severe cases, and in some cases appeared entirely out of -proportion to the state of circulation and respiration and to the -post-mortem findings as reported by Dr. Klotz.</p> - -<h3 class='c010'><em>Blood</em></h3> - -<p class='c011'>Hemorrhage being not uncommon, the blood was tested for -coagulability, but in this respect no marked departure from the -normal range was noted.</p> - -<p class='c009'><em>Coagulation.</em>—Coagulation time was observed by stirring blood -in a test tube with a wire and noting the time of the appearance -of fibrin and by means of a Biffi-Brooks coagulimeter. The -extreme ranges observed were from 2½ to 5½ minutes. The -<span class='pageno' id='Page_157'>157</span>average by defibrination was 3 minutes and 36 seconds, and by -the Biffi-Brooks method 4 minutes and 38 seconds.</p> - -<p class='c009'><em>Red Corpuscles.</em>—Osmotic resistance. A number of bloods -were examined by observing their resistance to osmotic laking -by exposure to a series of hypotonic sodium chloride solutions. -Though some differences were observed, from the evidence -obtained, it is not permissible to conclude that such variations -were constant or of a significant magnitude.</p> - -<p class='c009'><em>Color</em> on exposure to air. It was early observed that venous -blood from cyanotic patients was very slow to take on arterial -hue on exposure to air.</p> - -<p class='c009'><em>Plasma Bicarbonate.</em>—The plasma bicarbonate was determined -in seven cases by Miss Waddell by the method of Van Slyke and -Cullen. In all except one of these the results were within the -normal range as given by Van Slyke. Three were in the lower -normal range, being 54.1, 55.1 and 60.5 respectively, expressed -in terms of cubic centimeters of CO<sub>2</sub> reduced to 0°, 760 mm. Hg. -pressure, bound as bicarbonate by 100 c.cm. of plasma. Three -were in the median range, being 64, 65.5 and 71 c.cm. In one case -the bicarbonate CO<sub>2</sub> was reduced to 46.6 c.cm.</p> - -<p class='c009'>There seemed to be no constant relation between the apparent -severity of the clinical condition of the patient and the bicarbonate -reading. In the one case in which this was found to be -reduced below Van Slyke’s lower normal limit the blood was taken -only a few hours before death.</p> - -<p class='c009'><em>Hemoglobin Per Cent.</em>—As determined by the Sahli hemoglobinometer -(by Miss Lee) and as estimated by the total oxygen -capacity (Van Slyke method) (by Dr. Rohde and Mrs. Macklin), -the hemoglobin content ranged within normal levels.</p> - -<p class='c009'><em>Relative Volume of Corpuscles.</em>—A limited number of hematokrit -tests on severe cases gave results in normal levels.</p> - -<p class='c009'><em>Spectroscopic Studies.</em>—Sera obtained from 20 post-mortem -bloods were examined spectroscopically. In eight an absorption -band in the red was observed. In some instances such a band -was observed in blood obtained shortly after death and before -coagulation had occurred, while other similar bloods, as well as -bloods obtained at longer intervals after death, exhibited no -such band. A similar band was observed in one case from blood -obtained from a patient about 12 hours before death from pneumonia -following influenza. Medication was not a causative -<span class='pageno' id='Page_158'>158</span>factor. To ammonium sulphide the band in the red reacted as -methemoglobin and the position (as estimated by Dr. Menten) -corresponded with methemoglobin. Oxyhemoglobin bands in -such bloods occupied normal positions as determined by Dr. -Menten. On diluting such bloods with water no abnormality in -character or position bands was observed, save in one instance -(No. 778 below). This does not, however, disprove the possibility -of such abnormality in the hemoglobin within the cells, for -moderate dilution only of serum rendered the band in the red -invisible, presumably by dilution.</p> - -<blockquote> -<p class='c009'>Detailed examination of the absorption bands was made with a direct reading wave-length -Hilger Spectroscope (which was calibrated by line spectra derived from salts added to an -alcohol flame) by Dr. Menten. This spectroscope had an accuracy of about two Angstroms. -In all, seven post-mortem bloods were examined, viz. autopsy numbers 756, 761, 763, 773, -778, 784, and 787. In five of these, sufficient serum was obtained to make readings. All -gave the two characteristic oxyhemoglobin bands in the blue-green with centers of the bands at -<span lang="grc" xml:lang="grc">λ</span> 758<span lang="grc" xml:lang="grc">μμ</span> <span lang="grc" xml:lang="grc">λ</span> and 542<span lang="grc" xml:lang="grc">μμ</span>. The second oxyhemoglobin band varied slightly in width in the different -samples. In addition to the two oxyhemoglobin bands in each of four of the above sera, viz: -Nos. 756, 763, 767 and 787, an absorption band in the red was found with the center of the -band as follows: Number 756 at <span lang="grc" xml:lang="grc">λ</span> 627<span lang="grc" xml:lang="grc">μμ</span>, number 761 at <span lang="grc" xml:lang="grc">λ</span> 634<span lang="grc" xml:lang="grc">μμ</span>, number 763 at <span lang="grc" xml:lang="grc">λ</span> 625<span lang="grc" xml:lang="grc">μμ</span>, and -number 787 at <span lang="grc" xml:lang="grc">λ</span> 634<span lang="grc" xml:lang="grc">μμ</span>. These bands varied considerably in intensity and could only be -identified when the two oxyhemoglobin bands were merged and appeared as one broad band. -As controls for the position of the oxyhemoglobin bands two normal bands were examined, -which showed two bands with centers also at <span lang="grc" xml:lang="grc">λ</span> 758<span lang="grc" xml:lang="grc">μμ</span> and <span lang="grc" xml:lang="grc">λ</span> 543<span lang="grc" xml:lang="grc">μμ</span>. For comparison of the -methemoglobin bands of the above post-mortem bloods, a sample of this hemoglobin compound -was made by adding potassium ferricyanide to normal blood until the solution became brownish -in color. The center of this methemoglobin band was found at <span lang="grc" xml:lang="grc">λ</span> 634<span lang="grc" xml:lang="grc">μμ</span>. In blood from -autopsies number 773 and number 778 sufficient serum could not be obtained to make a reading. -To each of these bloods distilled water was added. The laked blood of 778 gave a -methemoglobin band with the center at <span lang="grc" xml:lang="grc">λ</span> 632<span lang="grc" xml:lang="grc">μμ</span> on examination 24 hours after autopsy. -Similar treatment of corpuscles five days subsequently gave no indication of the presence of -any methemoglobin spectroscopically.</p> - -<p class='c009'>From the serum and from the laked corpuscles of number 784 no trace of methemoglobin -was found when the blood was examined a few hours after removal at autopsy.</p> -</blockquote> - -<p class='c009'><em>Oxygen Capacity.</em>—The total oxygen capacity was determined -by the Van Slyke method (by Dr. Rohde and Mrs. Macklin). At -this stage the more pronounced type of influenza had subsided, -but in early convalescence the capacity was within normal ranges.</p> - -<p class='c009'>Other studies using different technique gave concordant results, -but there were indications that oxygen was more slowly -absorbed than normally.</p> - -<p class='c009'><em>Oxygen Content of Venous Blood</em> measured by the Van Slyke -method (by Dr. Rohde and Mrs. Macklin) on the same bloods -examined for total oxygen capacity seemed to indicate a mild -deficiency as compared to normal bloods.</p> - -<p class='c009'><span class='pageno' id='Page_159'>159</span><em>Gases, Kinds, Quantity and Rate Yielded to Vacuum.</em>—In general -it may be said that quantitative differences observed are not -considered fundamental, but that the studies indicate abnormal -slowness in oxygen absorption.</p> - -<p class='c009'><em>Gases, Quantity and Rate of Absorption on Exposure to Air -After Extraction by Pump.</em>—The results emphasize slowness of -oxygen absorption as compared to normal blood.</p> - -<blockquote> -<p class='c009'>The material to be examined was exhausted for three minutes in the receiver of the Van -Slyke apparatus. One c.cm. was then transferred, with as little exposure to air as possible, -to a small empty bottle, which was then closed and placed in communication with a calibrated, -horizontal tube, containing a segment of alcohol, which served the dual purpose of a seal -and an air volume change indicator. (See Fig. 1.) The apparatus was made in duplicate and -mounted on a common base, so that simultaneous readings on different samples could be -made. After establishing the zero position of the alcohol segment, the base on which the -bottles were mounted was vigorously shaken in a uniform manner. Ten seconds after the -period of shaking, the volume readings were taken. Successive periods of shaking and -reading were conducted at 30-second intervals, until the test was completed. Actual volume -changes were then calculated, tabulated and plotted.</p> - -<p class='c009'>The greater confidence is placed on the results obtained by observing the color of the blood, -as described below; but since then the method has been checked up and the results indicate -that the findings were of sufficient accuracy to warrant their inclusion in this report.<a id='r1' /><a href='#f1' class='c029'><sup>[1]</sup></a></p> -</blockquote> - -<div class='footnote' id='f1'> -<p class='c009'><a href='#r1'>1</a>. Studies along this line are being made with improved apparatus, the results of which, -together with the description of the apparatus, will be published elsewhere. (See Am. Gr. -Physiol., 1920, li, 195.)</p> -</div> - -<div class='figcenter id002'> -<img src='images/i_159.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>FIG. 1.</p> -</div> -</div> - -<p class='c009'><em>Effect of Addition of Serum on Behavior on Exposure to Air.</em>—The -persistence of venous hue of blood exposed to air was noted -above. It was observed that the addition of serum from the -same blood conspicuously shortened the time required for such -blood to acquire an arterial hue. The addition of normal serum -was more effective in this respect than pathological serum. -Measurements of the rate of absorption of such blood after the -addition of serum indicated acceleration of oxygen absorption. -<span class='pageno' id='Page_160'>160</span>From this it would seem that the oxygen transmitting capacity -of the serum was diminished.</p> - -<p class='c009'><em>Effect of Addition of Dry Sodium Bicarbonate on Behavior on -Exposure to Air.</em>—The addition of a small quantity of dry sodium -bicarbonate to a blood refractory to arterialization on exposure -to air enormously accelerated the process, as judged by the color. -To what extent the change in color may have been due to causes -other than oxygen absorption was not determined.</p> - -<h3 class='c010'><em>Comment</em></h3> - -<p class='c011'>The most significant positive findings were evidence of deficiency -of serum oxygen transmitting capacity or rate, and the -detection in serum of an absorption band in the red corresponding -to methemoglobin. The presence of the abnormal substance -giving rise to the absorption band is considered of special interest -as indicating abnormal chemical conditions in the blood, rather -than material change in hemoglobin oxygen capacity.</p> - -<div class='chapter'> - <span class='pageno' id='Page_161'>161</span> - <h2 class='c005'>THE BACTERIOLOGY OF EPIDEMIC INFLUENZA WITH A DISCUSSION OF B. INFLUENZÆ AS THE CAUSE OF THIS AND OTHER INFECTIVE PROCESSES</h2> -</div> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>By <span class='sc'>W. L. Holman</span>, B. A., M. D.</div> - </div> -</div> - -<h3 class='c010'><em>Introduction</em></h3> - -<p class='c011'>In a study of the bacteriology of a respiratory disease such as -influenza, the technical difficulties encountered are very great -and must be overcome before we can draw useful conclusions -from the results obtained or attempt to determine the etiological -factors. The important methods of attacking such a problem -include: (1) the study of stained smears and cultures from the -various available materials, along with the demonstration of the -bacteria in the lesions found in the disease by a study of sections; -(2) tests with the various materials to determine the presence -of the causative agent, which includes experiments on man and -animals and is more inclusive than the mere study of the bacteria -isolated; (3) immunological studies of man suffering from -the disease, or of man and animals treated with the materials -from the disease; (4) pathological, clinical and epidemiological -studies linked with the above.</p> - -<p class='c009'>Many of the difficulties and sources of error in these methods -are manifest to all, but certain points may be indicated as more -important in the phases of the work on which I am to report.</p> - -<h3 class='c010'><em>General Methods of Investigation</em></h3> - -<p class='c011'>Stained smears from the material available. The choice of the -material is of first importance. Sputum to be of any real value -must be obtained from the deeper portions of the respiratory -tract, should be as free as possible from the secretions of the -buccal cavity, and should be washed in saline before it is used. -These are considered among the first requirements in the study -of lung infections by the pneumococci and are equally important -in influenza. Swabs from the nasopharynx should be obtained -with the same precautions as are demanded in meningococcal -<span class='pageno' id='Page_162'>162</span>work. The other available material—such as blood, lung puncture -fluid, pleural fluid and spinal fluid—must be collected with -the greatest care.</p> - -<p class='c009'>The staining methods should, naturally, include those which -will bring out the various types of bacteria, and must include -the Gram method, using dilute alcoholic fuchsin (1-20) as the -counterstain. The varying morphology of the B. influenzæ and -its frequent minute size make it difficult to detect. It is not the -only Gram negative small bacillus seen in smears from the -throat, but when it occurs in the typical schools, or where there -are numerous bacilli to be seen, its characteristics are quite -definite. I have recently isolated an anærobic Gram negative -bacillus from a series of swabs from the buccal cavity which -suggests in many ways the morphology of the B. influenzæ, which -will indicate one of the many difficulties to be met with in the -study of stained smears. They are, nevertheless, of great use as -a control on cultures, and most helpful in the study of the -material from sources other than the respiratory tract.</p> - -<p class='c009'>Cultures of the bacteria from the various materials. Here we -have the greatest difficulty of all. The medium chosen determines -the bacteria which will appear to predominate, and there is -no single medium that will answer all purposes. Streptococci -will appear to be in excess when serum broth is used, as I have -previously shown; pneumococci with Avery’s pneumococcus -medium; and staphylococci, the Gram negative cocci, and the diphtheria -group with Loeffler’s serum. Ordinary blood agar is perhaps -the best general medium for direct and secondary plating. -There have been many special media devised for growing the -B. influenzæ, but the one I have used most and found particularly -helpful is heated blood agar made after the general method of -Voges.</p> - -<p class='c009'>The extremely tiny colony of B. influenzæ on ordinary blood -agar makes it particularly difficult to detect, and one is apt to -get the wrong impression of its numbers from the macroscopic -appearance of the plate. In attempts at isolation there must be a -liberal use of media in picking colonies, as many suspicious ones -will turn out to be immature growths of B. xerosis, M. pharyngis -(or M. catarrhalis), streptococci, or more rarely pneumococci and -other organisms. Replating from such picks is frequently necessary, -<span class='pageno' id='Page_163'>163</span>and further plates, from the original culture on heated blood -agar, must often be made before the B. influenzæ can be isolated. -The care required in all stages of the isolation of this organism, -the unstinted use of media for plating and for picks, the number -of stained smears to be studied, and the further transfers necessary -to verify results, all these limit the amount of material -which can be studied with any degree of accuracy. If further -the streptococci, the pneumococci, the Gram negative cocci, the -capsulated Gram negative bacilli and many others are to receive -any attention, it can readily be appreciated that a few cases -carefully studied are of far more value than a large number -hurriedly examined in an uncertain routine.</p> - -<p class='c009'>The pathological study of the same cases on which I have done -the bacteriology will be found in Dr. Klotz’s paper in these communications, -and I will merely refer to some of the bacterial findings -in the sections of the lungs and bronchi. The more inclusive -methods which have been used in attempts to determine the -etiological factor in influenza we have been unable to attempt, -but I will refer later in this paper to the findings of the investigations -of others. Immunological studies have been limited to -a few investigations on the presence of agglutinins, complement -binding substance, skin reactions and the amount of complement -present in the sera of certain patients. The epidemiological and -clinical studies are reported by Drs. Johnston and Lichty in this -series of reports.</p> - -<h3 class='c010'><em>Material Studied</em></h3> - -<p class='c011'>The material used in the study I am reporting included swabs -from the large bronchi and fluid from the lungs and pleural -cavities of 32 autopsies, as well as blood cultures from 22 -patients and swabs from the nasopharynx of 31 individuals. -Fifteen sera were tested for fixation of complement with an -antigen made from several strains of B. influenzæ. Fourteen -other sera were tested for agglutinins. Complement content -was determined in the sera of 25 patients. Skin tests after the -Von Pirquet method were done on 14 convalescents, and carefully -stained nasopharyngeal smears without cultures were -studied from 48 patients.</p> - -<p class='c009'><span class='pageno' id='Page_164'>164</span>The chief attention was given to the study of the autopsy -material and we concentrated on the isolation of B. influenzæ. -At the same time we did not neglect the other bacteria making -up the flora of the bronchi, lungs and pleural cavity in these -cases. The various types were isolated and most of them fully -identified.</p> - -<h3 class='c010'><em>Technique</em></h3> - -<p class='c011'>Direct smears were made on sterile slides of all material -studied and stained by Gram’s method. The counterstain was -always alcoholic fuchsin diluted 1-20 in distilled water. Direct -cultures were made on a human blood agar plate containing 5 -per cent. blood, which was further smeared just before use with -defibrinated blood. This latter procedure was later discarded, -as it did not appear to assist to any marked extent the growth of -B. influenzæ. Blood broth containing a few drops of defibrinated -blood and blood agar slants smeared with blood were also used. -Heated blood agar (2-3 c.cm. of defibrinated human blood added -to 100 c.cm. of ordinary agar at a temperature of from 90 to -100° C., or as the agar comes from the sterilizer) was used in the -last nine cases to replace the blood agar slant in the direct cultures -and as the medium of choice for transfers of the B. influenzæ.</p> - -<p class='c009'>I prefer the ordinary blood agar plate to the heated blood plate -because the former gives readings which are very helpful in -distinguishing colonies of various types. B. influenzæ appears as -clear, tiny, pinpoint, inert colonies. B. xerosis or the pseudodiphtheria -group gives more opaque but often rather similar -colonies. Gram negative cocci as M. pharyngis siccus have dry, -raised, soon becoming wrinkled, inert colonies, varying greatly -in size; M. catarrhalis, more moist, inert colonies. The cocci of -the streptococcus viridans group appear as very small colonies -with greening, or are not infrequently inert, while thin, flattened -colonies with central thickening may sometimes be noted. Those -of the streptococcus hemolyticus group occur as small, frequently -nipple-like colonies with clear, wide zones of hemolysis; pneumococci -as moderately small, moist, dewdrop-like colonies with -center collapsing early and with greening; streptococcus or -pneumococcus mucosus as larger, watery, sticky colonies with -greening and frequently an early clearing near the colonies.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE I.</div> - <div class='c004'>BACTERIOLOGY OF THIRTY-TWO AUTOPSIES FROM INFLUENZA CASES.</div> - </div> -</div> - -<div class='overflow'> - -<table class='table1' summary='BACTERIOLOGY'> - <tr> - <th class='bttd bbt brt c030' rowspan='2'><span class='sc'>Autopsy Number.</span></th> - <th class='bttd bbt brt c030' rowspan='2'><span class='sc'>Date.</span></th> - <th class='bttd bbt brt c030' rowspan='2'><span class='sc'>Day of Disease.</span></th> - <th class='bttd bbt brt c030' rowspan='2'><span class='sc'>Hours P.M.</span></th> - <th class='bttd bbt brt c030' rowspan='2'>DIRECT SMEAR—GRAM’S METHOD.</th> - <th class='bttd bbt brt c030' colspan='3'><span class='sc'>B. Influenzæ</span></th> - <th class='bttd bbt c030' rowspan='2'><span class='sc'>Pneumcocci.</span></th> - <th class='bttd bbt blt brt c030' rowspan='2'><span class='sc'>Strept. Mococci.</span></th> - <th class='bttd bbt brt c030' rowspan='2'><span class='sc'>Hemolytic Strept.</span></th> - <th class='bttd bbt brt c030' rowspan='2'><span class='fss'>S.P.A.</span></th> - <th class='bttd bbt brt c030' rowspan='2'><span class='sc'>Other Cocci.</span></th> - <th class='bttd bbt brt c030' rowspan='2'><span class='sc'>Other G—B.</span></th> - <th class='bttd bbt brt c030' rowspan='2'><span class='sc'>Other Bacteria.</span></th> - <th class='bttd bbt c030' rowspan='2'>NOTES.</th> - </tr> - <tr> - - - - - - <th class='bbt brt c030'><span class='sc'>Bronch.</span></th> - <th class='bbt brt c030'><span class='sc'>Lung.</span></th> - <th class='bbt brt c030'><span class='sc'>Pleural Fluid.</span></th> - - - - - - - - <th class='bbt c033'> </th> - </tr> - <tr> - <td class='bbt brt c030'>741</td> - <td class='bbt brt c031'>1918 Oct. 9</td> - <td class='bbt brt c031'>3</td> - <td class='bbt brt c031'>16</td> - <td class='bbt brt c032'>G +staph. Few pneumo-like. Few chains of elong. cocci.</td> - <td class='bbt brt c030'>0</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>+</td> - <td class='bbt brt c033'>G+ diploc.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>Nine plates used to isolate B.I. Sp.a. overgrew all cultures. B.I. seen in blood smear agar in 24 hours.</td> - </tr> - <tr> - <td class='bbt brt c030'>743</td> - <td class='bbt brt c031'>11</td> - <td class='bbt brt c031'>5</td> - <td class='bbt brt c031'>8</td> - <td class='bbt brt c032'>Br. G—bac. from coccoid to short threads. Mostly scattered. Some phagocyted. Fewer G +cooci in short chains.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>0</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'>Pleural fluid and seen as diplos in direct smear.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Br. G + diploc. not like pneumo.</td> - <td class='bbt brt c033'>Br. lux. white almost coccoid.</td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>Pericard, fluid and liver juice, no growth.</td> - </tr> - <tr> - <td class='bbt brt c030'>744</td> - <td class='bbt brt c031'>11</td> - <td class='bbt brt c031'>7</td> - <td class='bbt brt c031'>11</td> - <td class='bbt brt c032'>Br. G—bac. moderately stout about in small groups and scattered. G+diploc (pneumo) also G— threads. Phago. of both in a few cells.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Lung +</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>M. tetrag. in Br. M. pharyng. in Br.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>Pneumococcus from lung. No attempt after first plate to isolate B.I.</td> - </tr> - <tr> - <td class='bbt brt c030'>745</td> - <td class='bbt brt c031'>12</td> - <td class='bbt brt c031'>10</td> - <td class='bbt brt c031'>6</td> - <td class='bbt brt c032'>Br. G +–large bac., strept. short, G—B, few, very short, no threads.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>0</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'>Pleural fluid, also seen in smear.</td> - <td class='bbt brt c033'>Pl. fluid, also seen in smears.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>Swab from ruptured rectus. Sterile. No material from lung.</td> - </tr> - <tr> - <td class='bbt brt c030'>746</td> - <td class='bbt brt c031'>12</td> - <td class='bbt brt c031'>5</td> - <td class='bbt brt c031'>½</td> - <td class='bbt brt c032'>Br. G—B very short, no threads. Irregularly scattered. More seen in left bronchus. A few cells phagocyted.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Strept. viridans from bronchus.</td> - <td class='bbt brt c033'>B. coli from bronchi and lung.</td> - <td class='bbt brt c033'>B. xerosis from bronchus.</td> - <td class='bbt c033'>The overgrowth of B. coli in lung material prevented further attempts to isolate B.I.</td> - </tr> - <tr> - <td class='bbt brt c030'>747</td> - <td class='bbt brt c031'>13</td> - <td class='bbt brt c031'>6</td> - <td class='bbt brt c031'>3</td> - <td class='bbt brt c032'>Br. G+diploc, fairly numerous. G—B tiny, as diplos and in long threads scattered or in small groups. Pleural fluid and lung no bacteria seen.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Bronchus and pleural fluid.</td> - <td class='bbt brt c033'>Strept. viridans from bronchi and lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>B. subtilis group from pleural fluid.</td> - <td class='bbt c033'>Five picks from blood agar plate failed to recover B.I. from lung.</td> - </tr> - <tr> - <td class='bbt brt c030'>748</td> - <td class='bbt brt c031'>13</td> - <td class='bbt brt c031'>4</td> - <td class='bbt brt c031'>4</td> - <td class='bbt brt c032'>Br. nothing like B. I. seen. G+ small elong. diplo. Numerous G + diploc. in lung. Comparatively few Q-B, very short.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Lung+, not isolated from bronchus.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Strept. viridans from bronchus.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>B.I. not seen nor isolated from the bronchi.</td> - </tr> - <tr> - <td class='bbt brt c030'>749</td> - <td class='bbt brt c031'>14</td> - <td class='bbt brt c031'>4</td> - <td class='bbt brt c031'>15</td> - <td class='bbt brt c032'>Br. G+large pneumo like, many G+large bacilli, single and in pairs. Few G—B very tiny and widely scattered; lung, heavy mixture as in bronchi.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Bronchus Lung?</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Bronchus and lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>B. coli from bronchus and lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>The overgrowth of B. coli prevented any further attempts to isolate B.I.</td> - </tr> - <tr> - <td class='bbt brt c030'>750</td> - <td class='bbt brt c031'>14</td> - <td class='bbt brt c031'>9</td> - <td class='bbt brt c031'>6</td> - <td class='bbt brt c032'>Br. G+B large like B. welchii, G—rather stout coccoid forms, G+C in pairs and short chains. Tiny G—coccoid forms like B. I. Lung G+ pneumo-like and caps, chains; no B. I.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Bronchus? Lung?</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>B. coli from bronchi and lungs.</td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>B. coli again present as in No. 749. Direct smear suggests heavy contamination.</td> - </tr> - <tr> - <td class='bbt brt c030'>751</td> - <td class='bbt brt c031'>14</td> - <td class='bbt brt c031'>7</td> - <td class='bbt brt c031'>6</td> - <td class='bbt brt c032'>Br. G +cocci large elong.? caps, also G +C in flat pairs. G—coccoid forms. Lung, numerous bacteria. G+strept. with flattened cocci. Some G-short forms?</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'>Pleura. Lung. Bronchus.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>M. tetragenous from bronchus.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Spore-bearer with tiny cols, pleur. B. xerosis from bron.</td> - <td class='bbt c033'> </td> - </tr> - <tr> - <td class='bbt brt c030'>752</td> - <td class='bbt brt c031'>15</td> - <td class='bbt brt c031'>13</td> - <td class='bbt brt c031'>15</td> - <td class='bbt brt c032'>Br. G+pneumo-like. G+B smaller than B. welchii, occasionally tiny G -diplobacillus. Lung, G+chains of cocci Gram weak. Few G—tiny bacilli scattered or in groups.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Bronchus and lung.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Strep. viridans from bronchus and lungs.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>B.I. like seen in original culture on blood agar but not isolated from bronchus.</td> - </tr> - <tr> - <td class='bbt brt c030'>756</td> - <td class='bbt brt c031'>16</td> - <td class='bbt brt c031'>8</td> - <td class='bbt brt c031'>18</td> - <td class='bbt brt c032'>Br. numerous G+B. B welchii like. G—B large and few tiny. G+round diploc. Pl. fluid almost pure pneumo-like, few G-forms probably the same.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>0</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Pleural fluid.</td> - <td class='bbt brt c033'>Strep. viridans from bronchus.</td> - <td class='bbt brt c033'>B. coli from bronchus and pleural fluid.</td> - <td class='bbt brt c033'>B. xerosis from bronchus.</td> - <td class='bbt c033'>Compare No. 749 and 750. Fluid from lung not obtained for culture.</td> - </tr> - <tr> - <td class='bbt brt c030'>757</td> - <td class='bbt brt c031'>16</td> - <td class='bbt brt c031'>6</td> - <td class='bbt brt c031'>14</td> - <td class='bbt brt c032'>Br. G—B tiny, to medium. G—like M. catarrhalis. G+cocci, pairs and chains. Few B. W. like. Lung, many G—B like B. I. Some cells filled, also G—cocci. M. catarrhalis like and rare B. welchii like.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Bronchus and lung.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Bronchus and lung.</td> - <td class='bbt brt c033'>M. tetragenous? from lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>B. xerosis from bronchus.</td> - <td class='bbt c033'>This case 14 hours P. M. gave B.I. from all the material.</td> - </tr> - <tr> - <td class='bbt brt c030'>758</td> - <td class='bbt brt c031'>16</td> - <td class='bbt brt c031'>14</td> - <td class='bbt brt c031'>16</td> - <td class='bbt brt c032'>Br. pneumo-like in excess. G—B from tiny to forms stouter than B. I. Few strept. rare M. catarrhalis. Lung, pneumo-like. Phago.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>?</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Bronchus and lung.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>M. catarrhalia-like from lung. Strep. viridans from lung and bronchus.</td> - <td class='bbt brt c033'>B. coli from bronchus.</td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>The B. coli did not prevent the isolation of B.I. like seen in original blood agar cultures of lung.</td> - </tr> - <tr> - <td class='bbt brt c030'>761</td> - <td class='bbt brt c031'>17</td> - <td class='bbt brt c031'>7</td> - <td class='bbt brt c031'>19</td> - <td class='bbt brt c032'>Br. pneumo-like. B. I. like common, M. catarrhalis like. Both B.I. and M. catarrhalis phagocyted. B.I. single or in threads. Some typical groups. Lung, pneumo, caps, rare, M. catarrhalis like.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Bronchus and lung.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Bronchus and lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>B. coli from bronchus.</td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>Even after 19 hours P. M. the B.I. was isolated.</td> - </tr> - <tr> - <td class='bbt brt c030'>762</td> - <td class='bbt brt c031'>17</td> - <td class='bbt brt c031'>10</td> - <td class='bbt brt c031'>12</td> - <td class='bbt brt c032'>Br. numerous B.l. like typical, also many pneumo. and M. catarrh. Lung same. M. catarrh. phagocyted. B.I. smear, many phagocyted, many pneumo.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt c033'>Pleural fluid and bronchus.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>M. catarrh. like from lung and bronchus.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>B. xerosis from lung. B. subtilis from bronchus.</td> - <td class='bbt c033'> </td> - </tr> - <tr> - <td class='bbt brt c030'>763</td> - <td class='bbt brt c031'>17</td> - <td class='bbt brt c031'>11</td> - <td class='bbt brt c031'>13</td> - <td class='bbt brt c032'>Lung, pneumo-like, slight phagocytosis. Pl. fl., pneumo and few strept., slight phagocytosis.</td> - <td class='bbt brt c030'>0</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'>Pleural fluid.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>No growth from lung on plate. B.I. like seen in original culture from pleural fluid. No material from bronchus.</td> - </tr> - <tr> - <td class='bbt brt c030'>764</td> - <td class='bbt brt c031'>17</td> - <td class='bbt brt c031'>9</td> - <td class='bbt brt c031'>6</td> - <td class='bbt brt c032'>Br. B.I. smear. Cells crowded. Pneumo-like fewer, occasional G—stouter thread.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>0</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Bronchus.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Staph, albus from bronchus.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>Material only from bronchi.</td> - </tr> - <tr> - <td class='bbt brt c030'>765</td> - <td class='bbt brt c031'>17</td> - <td class='bbt brt c031'>9</td> - <td class='bbt brt c031'>16</td> - <td class='bbt brt c032'>Br. pneumo. B.I. few scattered. G+flattened diploc. Phago. of B.I. and pneumo. Lung, pneumo-like, rare strept. very questionable G—B free and in cells.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'>Lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>M. catarrh. from bronchus and lung.</td> - <td class='bbt brt c033'>B. coli from bronchus and lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'> </td> - </tr> - <tr> - <td class='bbt brt c030'>767</td> - <td class='bbt brt c031'>18</td> - <td class='bbt brt c031'>10</td> - <td class='bbt brt c031'>14</td> - <td class='bbt brt c032'>Br. rather round pneumo-like with caps. B.I. few. Scattered, also in cells. Lung, few bacteria. G+strep. often phagocyted.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Bronchus.</td> - <td class='bbt blt brt c033'>Lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Bronchus.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>Blood culture <span class='fraction'>15<br /><span class='vincula'>10</span></span> gave pure growth of pneumo. mucosus.</td> - </tr> - <tr> - <td class='bbt brt c030'>770</td> - <td class='bbt brt c031'>19</td> - <td class='bbt brt c031'>11</td> - <td class='bbt brt c031'>9</td> - <td class='bbt brt c032'>Br. crowded with B.I. like. Few G+cocci and fewer M. catarrh. like. Pl. fluid G+flattened pairs, pus cells, phagocyted.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'>Bronchus.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Bronchus, lung, pleural fluid.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'> </td> - </tr> - <tr> - <td class='bbt brt c030'>773</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>20 Recurrence.</td> - <td class='bbt brt c031'>3</td> - <td class='bbt brt c032'>Br. few bacteria G+and G—pneumo-like. Rare G+–thread. Lung, pneumo and rare strept. Pl. fluid, pneumo-oat shapes, etc.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Bronchus.</td> - <td class='bbt brt c033'>Strept. viridans bronchus. Sarcina albus lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>B. xerosis from bronchus. G + B lux. white pleura. fluid.</td> - <td class='bbt c033'>No growth from lung except sarcina. Only 2 colonies from pleural fluid on blood agar plates.</td> - </tr> - <tr> - <td class='bbt brt c030'>778</td> - <td class='bbt brt c031'>24</td> - <td class='bbt brt c031'>23</td> - <td class='bbt brt c031'>17</td> - <td class='bbt brt c032'>Br. B.I. smear. Fewer large pneumo. Lung, G + small diploc. Few B.I. like. Pl. fluid, few cells, no bacteria.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'>Bronchus and lung.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Non-motile, non-fermenting, lux, white from bron.</td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>Ten plates and 30 picks were done for the isolation of B.I.</td> - </tr> - <tr> - <td class='bbt brt c030'>781</td> - <td class='bbt brt c031'>26</td> - <td class='bbt brt c031'>5</td> - <td class='bbt brt c031'>4</td> - <td class='bbt brt c032'>Br. crowded with staph. like. Fewer G—B, larger than B.I., few M. catarrhalis like. Lung G+ small staph. like, caps, cocci in pairs and chains. Few tiny G—B. Pl. fluid pneumo-like and elong. cocci in chains capsulated.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'>Lung and pleural fluid.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Bronchus and lung abscess.</td> - <td class='bbt brt c033'>Staph. albus and sarcina from pleural fluid.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>B.I. like seen from 24 hour Ht. blood agar from bronchi and lung but only isolated from lung on replating. Bl. culture <span class='fraction'>25<br /><span class='vincula'>10</span></span> sterile.</td> - </tr> - <tr> - <td class='bbt brt c030'>782</td> - <td class='bbt brt c031'>26</td> - <td class='bbt brt c031'>8</td> - <td class='bbt brt c031'>3</td> - <td class='bbt brt c032'>Br. numerous B.I. like scattered, some phagocyted. Fewer G+ flat pairs with capsule.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'>Bronchus and lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>No B.I. like on 24-hour Ht. blood agar from lung.</td> - </tr> - <tr> - <td class='bbt brt c030'>783</td> - <td class='bbt brt c031'>26</td> - <td class='bbt brt c031'>8</td> - <td class='bbt brt c031'>1</td> - <td class='bbt brt c032'>Br. G+small caps, pneumo-like. Lung poor smear, occasional pneumo-like.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Lung.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Bronchus.</td> - <td class='bbt brt c033'>M. catarrh. like bronchus.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>No B.I. like on 24-hour Ht. blood agar from lung.</td> - </tr> - <tr> - <td class='bbt brt c030'>784</td> - <td class='bbt brt c031'>28</td> - <td class='bbt brt c031'>8</td> - <td class='bbt brt c031'>6</td> - <td class='bbt brt c032'>Br. capsulated pneumo-like, few strep. Lung, chiefly pneumo-like. few G—B like B.I., also G—pneumo-like.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Bronchus and lung.</td> - <td class='bbt blt brt c033'>Bronchus and lung?</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>M. catarrh. like bronchus.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>Numerous B.I. like on 24-hour Ht. blood agar of bronchi and fewer from lung. Isolated by replating.</td> - </tr> - <tr> - <td class='bbt brt c030'>786</td> - <td class='bbt brt c031'>29</td> - <td class='bbt brt c031'>4</td> - <td class='bbt brt c031'>2</td> - <td class='bbt brt c032'>Br. G+cocci in round pairs and rather flat chains, suggested caps. Tiny G—B very rare. Lung streptococci flattened, often phagocyted.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'>Bronchus.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'>Bronchus and lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Staph, albus from bronchus.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>Pleural fluid not collected sterilly, Haemol. strept. isolated.</td> - </tr> - <tr> - <td class='bbt brt c030'>787</td> - <td class='bbt brt c031'>29</td> - <td class='bbt brt c031'>8</td> - <td class='bbt brt c031'>2</td> - <td class='bbt brt c032'>Br. numerous pneumo-like, bacillary forms. A rare suspicious B.I. like, some of these in cells. Lung, caps, elongated diplos, and chains of elong. cocci.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>0</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Bronchus and lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>B.M.C. from bronchi.</td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>All the bacteria isolated were seen in 24-hour Ht. blood agar cultures from bronchi and lung.</td> - </tr> - <tr> - <td class='bbt brt c030'>791</td> - <td class='bbt brt c031'>Nov. 1</td> - <td class='bbt brt c031'>6</td> - <td class='bbt brt c031'>6</td> - <td class='bbt brt c032'>Br. few bacteria. G+pneumo-like round, G—B and threads, size varies, like B.I. Lung, G + caps, pneumo. G+Large B. few suspicious G—coccoid forms. Pl. fl. caps, pneumo and caps, elong. chains.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'>Bronchus and pleural cavity.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Bronchus and lung.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>Replated from Ht. blood agar to isolate B.I. from lung.</td> - </tr> - <tr> - <td class='bbt brt c030'>792</td> - <td class='bbt brt c031'>2</td> - <td class='bbt brt c031'>6</td> - <td class='bbt brt c031'>3</td> - <td class='bbt brt c032'>Br. caps, pneumo-like bac. forms and chains. G-caps, pneumo-like. Few G—B. questionable. Lung. caps, pairs and chains of elong. cocci, in cells. Pl. fluid, numerous caps, chains of diploc.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'>Bronchus, lung and pleural fluid.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'>Staph. albus, lung, strept. viridans lung, M. catarrh. like lung and bronchi.</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>B.I. like seen on 24-hour Ht. blood agar from bronchi and lung but not pleural fluid.</td> - </tr> - <tr> - <td class='bbt brt c030'>793</td> - <td class='bbt brt c031'>4</td> - <td class='bbt brt c031'>10</td> - <td class='bbt brt c031'><span class='fraction'>3<br /><span class='vincula'>2</span></span></td> - <td class='bbt brt c032'>Br. M. catarrh. and G+cocci, few bacteria, few G—B. Ear, G+cocci.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt c033'>?Throat.</td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'>Bronchus, lung, arm vein, spleen ear.</td> - <td class='bbt brt c033'>Throat, ear and bronchus.</td> - <td class='bbt brt c033'>Strept. viridans from throat.</td> - <td class='bbt brt c033'>B. coli from throat.</td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'>B.I. like never seen except from throat which may have been B. coli.</td> - </tr> - <tr> - <td class='brt c030'> </td> - <td class='brt c031'> </td> - <td class='brt c031'> </td> - <td class='brt c031'> </td> - <td class='brt c030'>Total</td> - <td class='brt c030'>20</td> - <td class='brt c030'>13</td> - <td class='brt c030'>2</td> - <td class='c033'>20</td> - <td class='blt brt c033'>6</td> - <td class='brt c033'>4</td> - <td class='brt c033'>16</td> - <td class='brt c033'> </td> - <td class='brt c033'> </td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c030'> </td> - <td class='brt c031'> </td> - <td class='brt c031'> </td> - <td class='brt c031'> </td> - <td class='brt c032'>B. influenzæ found—Percentage</td> - <td class='brt c030'>66½</td> - <td class='brt c030'>46</td> - <td class='brt c030'>14</td> - <td class='c033'> </td> - <td class='blt brt c033'> </td> - <td class='brt c033'> </td> - <td class='brt c033'> </td> - <td class='brt c033'> </td> - <td class='brt c033'> </td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c030'> </td> - <td class='brt c031'> </td> - <td class='brt c031'> </td> - <td class='brt c031'> </td> - <td class='brt c032'> </td> - <td class='brt c030'><hr /></td> - <td class='brt c030'><hr /></td> - <td class='brt c030'><hr /></td> - <td class='c033'> </td> - <td class='blt brt c033'> </td> - <td class='brt c033'> </td> - <td class='brt c033'> </td> - <td class='brt c033'> </td> - <td class='brt c033'> </td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='bbt brt c030'> </td> - <td class='bbt brt c031'> </td> - <td class='bbt brt c031'> </td> - <td class='bbt brt c031'> </td> - <td class='bbt brt c032'>Total percentage for B. influenzæ</td> - <td class='bbt brt c030'> </td> - <td class='bbt brt c030'>78</td> - <td class='bbt brt c033'>%</td> - <td class='bbt c033'> </td> - <td class='bbt blt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'> </td> - </tr> -</table> - <dl class='dl_1'> - <dt>EXPLANATORY NOTE.</dt> - <dd> - </dd> - <dd>B.I.—B. influenzæ. - </dd> - <dd>S.P.A.—Staphylococcus pyogenes aureus. - </dd> - <dd>M. pharyog—Micrococcus pharyngis siccus. - </dd> - <dd>Br.—Bronchus. - </dd> - <dd>Phago.—phagocytosis. - </dd> - <dd>Ht.-Heated blood agar. - </dd> - <dd>B. W.—B. welchii. - </dd> - </dl> - -</div> -<p class='c009'><span class='pageno' id='Page_165'>165</span>Staphylococci develop opaque, paint-like colonies of varying size, -with or without hemolysis, and so do other less frequently found -bacteria give more or less distinctive colonies. The heated blood -agar does not show these differences.</p> - -<p class='c009'>The colonies most liable to be confused with those of B. influenzæ -are, therefore, those of B. xerosis, immature colonies of -the Gram negative cocci and certain colonies of the streptococcus -viridans group. Transfers should always be made to heated -blood agar of all colonies suggestive of B. influenzæ, or when -the growth of the B. influenzæ has only occurred in the more -crowded portions of the plate, and it is difficult to pick pure -cultures, attempted pickings should be made to this medium for -further platings. It is frequently necessary to make further -blood agar plates from the original blood agar, blood broth or -heated blood agar cultures after longer incubation periods, -depending on the findings in smears from these media. The -heated blood agar is the best of these to encourage the growth -of B. influenzæ. It must, however, be used at once, or within a -very few days of its preparation, and cannot be kept on hand as -a stock medium. I have not found it as useful for plating -because of the difficulty of differentiating colonies. The phenomenon -of the star-like and more luxuriant growth of the colonies -of B. influenzæ about colonies of other bacteria has often been -noted, and will be referred to in a later portion of this report. -Here it may be said that this is at times a marked feature of -certain mixtures and must be recognized in studying the plates. -The finding of B. influenzæ in picks from apparently isolated -colonies of other forms is not uncommon, and is the same type -of difficulty which I have discussed in papers on streptococci. It -is important to recall, in connection with cultures taken from -the lungs at autopsy, the experimental work of Norris and Pappenheimer, -who showed that B. prodigiosus put in the mouth -immediately after death could be recovered from the lungs in -over 50 per cent. of the cases studied.</p> - -<h3 class='c010'><em>Results of the Author</em></h3> - -<p class='c011'>In Table I are shown my results from the 32 cases which came -to autopsy. The B. influenzæ was isolated from one or more -sources in 25, making a total of 78 per cent. Most of the negative -<span class='pageno' id='Page_166'>166</span>cases probably also had this organism, but I did not grow -it from the material which I used for culturing. The work of -others would indicate that it may have been present in other -regions, such as the sinuses of the head or other portions of the -lung and respiratory tract. The positive results show B. influenzæ -present in 20 out of 30 cases from the bronchi; in 13 of 28 -from the lungs; in 2 of 14 from the pleural cavity; in 9 of 26 -from both bronchi and lung where both were cultured; in 8 of -26 from the bronchi with the lung negative; in 3 of 26 from the -lung with the bronchi negative; once of 10 from the pleural -cavity with both the bronchi and the lung negative, and once -from all three sources.</p> - -<p class='c009'>The negative results occurred in seven cases. In three of -these (749, 750, 756) B. coli overgrew the cultures from the -bronchus, in two also from the lung, and in one, without lung -culture, from bronchus and pleural cavity. The mere presence -of B. coli, however, did not preclude the isolation of B. influenzæ, -as is seen in cases 746, 758, 761 and 765. The finding of B. coli -would suggest a post-mortem invasion. The hours after death -before the autopsy was done were in these seven cases, ½, -15, 6, 18, 16, 19, 16, respectively. That delay in performing the -autopsy, as emphasized by Spooner, Scott and Heath, adds -to the difficulty is self-evident, but successful isolations of -B. influenzæ have been obtained after even longer periods than -in the negative cases (761). In the fourth negative case (763) -the bronchus was not cultured. A pneumococcus was grown -from the pleural cavity and no growth was obtained from the -lung. In the original culture from the pleural cavity influenza-like -forms were seen but could not be isolated. In the fifth case -(767) a blood culture three days before death gave a growth of -pneumococcus mucosus which was also grown from the lung at -autopsy. Direct smear from the bronchus showed very few -influenza-like forms. Our sixth negative finding was in a case -of 20 days’ illness, the patient having had a recurrence (773). -Staphylococcus pyogenes aureus, streptococcus viridans and -B. xerosis were grown from the bronchus. Only a sarcina form -grew from the lung, and a further probable air contamination -occurred on the media from the cultures of the pleural cavity. -The B. xerosis colonies were confusing, picked as possible B. influenzæ, -<span class='pageno' id='Page_167'>167</span>and, before this was discovered, the overgrowth prevented -further attempts to isolate the influenza bacilli. The last unsuccessful -case was one with a general infection of a hemolytic -streptococcus from an acute otitis media. The streptococcus was -isolated from the bronchus, lung, spleen, arm vein and the middle -ear at autopsy.</p> - -<p class='c009'>It will be seen that in these seven negative cases technical -difficulties prevented the isolation of the B. influenzæ, even if it -had been present. I would not, therefore, conclude that the -organisms were necessarily absent, but rather that we have -failed either to secure material from the focus of infection or on -account of the other reasons mentioned.</p> - -<p class='c009'>It is very evident that a variety of secondary organisms very -frequently overgrow the field and become numerically predominant. -In our first case staphylococcus pyogenes aureus overgrew -all the other organisms present in cultures from the lung -material. B. influenzæ was, however, seen in the original 24-hour -blood agar culture. It required 9 blood agar plates before the -organism could be isolated. In another case 10 plates were used -for the isolation.</p> - -<p class='c009'>The findings of the bacteria in the lung sections are particularly -interesting and instructive. The entire series of cases have -not been completely studied, so I am unable to tabulate the findings. -In cases 761 and 762 sections of the lung showed influenza-like -bacilli to be almost pure in the earlier stages of the process, -while in areas with purulent foci pneumococcus-like and other -Gram positive cocci were also numerous. In some cases B. influenzæ-like -organisms were to be seen in overwhelming numbers. -In others they were scarce, while in some nothing resembling -B. influenzæ could be found in the sections. Positive cultures -were often independent of whether the influenza-like forms were -to be seen in smears or sections or not, although they were found -in the great majority of the cases. The findings in the direct -smears and the bacteriological results make useful material for -comparison.</p> - -<p class='c009'>Swabs from the nasopharynx were cultured from 31 individuals; -nearly all of these were cases suspected of diphtheria -or as carrying the diphtheria bacillus, and no particular effort -was made to isolate the B. influenzæ. They were seen in the -<span class='pageno' id='Page_168'>168</span>mixed culture occasionally. In the last eight cases the heated -blood agar, ordinary blood agar and Loeffler’s serum were seeded -from the throat swabs. B. influenzæ practically overgrew all -the other bacteria from seven of these cases on the heated blood -agar medium and was isolated without difficulty; all eight showed -M. catarrhalis. The two other media gave little or no evidence -of the presence of B. influenzæ. As I have said above, our attention -was concentrated on the autopsy material. These cultures -from the throat were simply made to demonstrate the usefulness -of the heated blood agar.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE II</div> - <div class='c004'>BACTERIA SEEN IN DIRECT SMEARS FROM NASOPHARYNX</div> - </div> -</div> - -<table class='table1' summary='TABLE II'> - <tr> - <th class='bttd bbt c030'>Type of Disease.</th> - <th class='bttd bbt blt c034'>Number of Patients.</th> - <th class='bttd bbt blt c034'>B. Influenzæ-Like.</th> - <th class='bttd bbt blt c034'>Pneumococcus-Like.</th> - <th class='bttd bbt blt c034'>M. Catarrhalis-Like.</th> - </tr> - <tr> - <td class='c035'>Early</td> - <td class='blt c036'>24</td> - <td class='blt c036'>14</td> - <td class='blt c036'>17</td> - <td class='blt c036'>6</td> - </tr> - <tr> - <td class='c035'>Serious</td> - <td class='blt c036'>13</td> - <td class='blt c036'>13</td> - <td class='blt c036'>13</td> - <td class='blt c036'>9</td> - </tr> - <tr> - <td class='bbt c035'>Convalescent</td> - <td class='bbt blt c036'>11</td> - <td class='bbt blt c036'>8</td> - <td class='bbt blt c036'>11</td> - <td class='bbt blt c036'>6</td> - </tr> - <tr> - <td class='c030'>Total</td> - <td class='blt c036'>48</td> - <td class='blt c036'>35</td> - <td class='blt c036'>41</td> - <td class='blt c036'>21</td> - </tr> - <tr> - <td class='bbt c035'>Percentage of positives</td> - <td class='bbt blt c036'> </td> - <td class='bbt blt c036'>73</td> - <td class='bbt blt c036'>86</td> - <td class='bbt blt c036'>43</td> - </tr> -</table> - -<h3 class='c010'><em>Direct Smears from Nasopharyngeal Swabs</em></h3> - -<p class='c011'>It is recognized by most of the modern investigators that little -reliance can be put on the finding of B. influenzæ-like bacilli in -direct smears. The organism is markedly pleomorphic, occurring -as extremely small coccoid forms up to threads of various lengths. -Notwithstanding these morphological variations the organisms -are usually seen as tiny bacilli, and these are considered as the -typical form. We carried out a series of microscopical examinations -of carefully made smears from the throats of patients with -influenza. Particular attention was given to the occurrence of -organisms resembling in morphology and staining B. influenzæ, -pneumococci and M. catarrhalis. We have divided the cases -roughly into three types—early, serious, and convalescent. Table -II shows our results. The term B. influenzæ-like was used for -the typical morphological picture so often described. Dr. Frost -and Mr. Scott carried out this portion of our work and their -results are interesting.</p> - -<p class='c009'><span class='pageno' id='Page_169'>169</span>Blood cultures were done on 22 cases. Pneumococcus mucosus -was grown from one patient who three days later came to -autopsy (Case 767). In another case pneumococcus-like organisms -were seen in smears from the dextrose broth flask after -24 hours’ incubation. These, for some unknown reason, did not -grow on blood agar plates. After 48 hours smears made on -blood agar from the original flask gave a growth of B. influenzæ -and a M. catarrhalis-like organism. I consider this result a very -unsatisfactory one, being quite unable to explain the failure to -grow the pneumococci-like forms on transfer. Possibly the -acidity developed might account for it.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE III</div> - <div class='c004'>AGGLUTINATION TESTS WITH SERA OF CONVALESCENT INFLUENZA PATIENTS</div> - </div> -</div> - -<table class='table1' summary='TABLE III'> - <tr> - <th class='bttd bbt c012' colspan='2'><span class='sc'>Dilution of Serum</span></th> - <th class='bttd bbt blt c030'>+</th> - <th class='bttd bbt blt c030'>+–</th> - <th class='bttd bbt blt c030'>–</th> - </tr> - <tr> - <td class='c026' rowspan='5'>Convalescents</td> - <td class='blt c033'>1-1</td> - <td class='blt c031'>3</td> - <td class='blt c031'>0</td> - <td class='blt c031'>2</td> - </tr> - <tr> - - <td class='blt c033'>1-10</td> - <td class='blt c031'>5</td> - <td class='blt c031'>2</td> - <td class='blt c031'>7</td> - </tr> - <tr> - - <td class='blt c033'>1-40</td> - <td class='blt c031'>2</td> - <td class='blt c031'>3</td> - <td class='blt c031'>9</td> - </tr> - <tr> - - <td class='blt c033'>1-80</td> - <td class='blt c031'>0</td> - <td class='blt c031'>1</td> - <td class='blt c031'>13</td> - </tr> - <tr> - - <td class='bbt blt c033'>1-160</td> - <td class='bbt blt c031'>0</td> - <td class='bbt blt c031'>0</td> - <td class='bbt blt c031'>14</td> - </tr> - <tr> - <td class='c026' rowspan='2'>Normal Controls</td> - <td class='blt c033'>1-10</td> - <td class='blt c031'>1</td> - <td class='blt c031'>2</td> - <td class='blt c031'>0</td> - </tr> - <tr> - - <td class='bbt blt c033'>1-40</td> - <td class='bbt blt c031'>0</td> - <td class='bbt blt c031'>1</td> - <td class='bbt blt c031'>2</td> - </tr> -</table> - -<blockquote> -<p class='c009'>The complete agglutination as would be indicated by +++ or ++ was -not seen.</p> -</blockquote> - -<p class='c009'>Agglutination tests were carried out with the sera of 14 convalescents -and 3 normal individuals. A polyvalent emulsion of -strains of the influenza bacillus isolated from our cases was used. -The results are shown in Table III. Tubes were incubated at -37.5° C. The results did not indicate anything in the nature of a -specific reaction. Dr. Frost carried out this work during the -height of the epidemic, but we were unable to continue it further. -A short review of the work of others will be found near the end -of this paper. Miss Thompson and Mr. Mock studied complement -fixation, using the sera of 15 convalescents against an antigen -of B. influenzæ. Their results were negative. The antigen -appeared to be slightly more anti-complementary than were -<span class='pageno' id='Page_170'>170</span>emulsions of staphylococcus or B. coli. Huntoon also noted this -anti-complementary character of emulsions of B. influenzæ.</p> - -<p class='c009'>Attempts were made to estimate the amount of complement -present in the fresh blood serum of influenza patients. The -technique was to use a 1-4 dilution of the patient’s serum, adding -measured amounts of this to a 1 per cent. blood emulsion, with -1 unit of amboceptor and determine the smallest amount necessary -to bring about complete hemolysis. This test was carried -out on eight patients ill for only a few days. The average -amount of the dilute serum was 0.181 c.cm. Fifteen patients, convalescent -after a moderate illness, gave an average of 0.276 c.cm. -Two patients seriously ill with temperatures of 104.3° F. and -105° F. required 0.4 c.cm. to bring about complete hemolysis. We -would not like to draw any very definite conclusions where we -are dealing with such small fractional differences. This lessening -of complement has been noted in other infectious diseases and -may be important in the questions of immunity in influenza. -Dr. Frost carried out a number of cutaneous tests after the -method of Von Pirquet, using a polyvalent, weakly alkaline -emulsion of influenza bacilli in 25 per cent. glycerin. Eleven -convalescents were tested and none of them showed any local or -general reaction. The suggestion that these results may indicate -an increase in resistance is discussed in another place. A number -of strains of pneumococci which we had isolated from our -autopsy cases were differentiated by the agglutination method. -Type I was found 3 times; type II, 10 times; type IV, 9 times. -Four showed agglutination with both type I and type II sera. -Type IV pneumococcus was isolated in one case from the right -and left bronchus as well as the lung. In another case the same -type pneumococcus was recovered from the lung and pleural -fluid. These results are similar to those found by numerous -workers.</p> - -<h3 class='c010'><em>The Hemophilic Bacteria</em></h3> - -<p class='c011'>The discovery by Pfeiffer of the hemophilic character of the -bacillus found by him in cases of influenza opened up a new group -of micro-organisms known as the hemophilic bacteria. Davis -(1915) has laid particular stress on the group character of these -bacilli, and the more they are studied the more clear does it -become that there are several distinct members. The B. influenzæ -<span class='pageno' id='Page_171'>171</span>is by far the most important as well as the most frequently -found of the group and is considered as the type organism.</p> - -<p class='c009'>All these bacteria require for their growth the presence of -some form of hemoglobin. The actual amount necessary may -be very small, and Davis suggested that it may have a catalytic -action. A great deal of work has been done in attempts to discover -just what portions of the hemoglobin are necessary to -bring about this phenomenon. In our discussion on media for -the influenza bacillus we will briefly describe some of the various -hemoglobin preparations that have been used successfully. It -must at this point be emphasized that blood is very useful in -many media to stimulate the growth of a great variety of bacteria, -and the transfers made from such luxuriantly growing -cultures may grow very poorly or not at all on ordinary media, -and this might easily lead to erroneous conclusions on the hemophilic -character of the organisms studied. There are certain -bacteria which grow so much better on media containing blood -that such media are sometimes necessary for their isolation, -although after a few transfers they will grow on ordinary media. -This is true for bacillus pertussis, and throughout the literature -a good deal of confusion has arisen in not recognizing this temporary -hemophilic character of certain bacteria. The true hemophilic -bacteria do not grow except in the presence of hemoglobin -in some form or other. The problem becomes almost academic -when we consider the small amounts of hemoglobin that are -necessary. Davis has shown that a dilution of 1 in 180,000 is -sufficient, and in the interesting discussion between Cantani and -Ghon and Preyss it was demonstrated that hematin or other -hemoglobin product was necessary in the agar before B. influenzæ -would grow in the presence of other bacteria, and that this -hematin could be derived from the blood in the meat which was -used in making the basic infusion.</p> - -<p class='c009'><em>Symbiosis.</em>—The fact that other bacteria can bring to growth -the influenza bacillus on media otherwise unsuited to its needs -brings up the interesting problem of symbiosis, which is one of the -most important characters of the influenza bacillus. Not only do -other bacteria make possible the growth of B. influenzæ on media -on which the influenza bacillus will not grow, but they stimulate -a better growth on blood agar and other more or less favorable -media. Grassberger first noted this stimulating character of -<span class='pageno' id='Page_172'>172</span>other bacteria and described and illustrated the very large -colonies of B. influenzæ which develop in the neighborhood of -colonies of staphylococcus and other bacteria. Staphylococci -killed by heat were found to have a similar effect. Meunier -nicely described this phenomenon by using the term satellites -for the circles of B. influenzæ colonies which develop about the -colonies of other bacteria. A great number of workers have -since noted this characteristic relationship between B. influenzæ -and other bacteria, and occasionally have laid stress on its importance -in the problems of the infections by the influenza bacillus. -Allen particularly emphasized the probable importance of this in -discussing the problem of carriers of B. influenzæ as sources of -danger. There seems no doubt that this symbiotic relationship -depends on so altering the hemoglobin products as to render -them more readily available for the influenza bacillus. This is -indicated by the fact that on various media containing hemoglobin, -altered so that it encourages the growth of B. influenzæ, -no such symbiotic stimulation can be demonstrated. This phenomenon -is quite peculiar to this bacillus, distinguishes it from -most of the other members of the group, and should be always -determined before an organism is classed as B. influenzæ.</p> - -<p class='c009'><em>Other Hemophilic Bacteria.</em>—The question of a pseudo-influenza -bacillus was first raised by Pfeiffer and has been studied by many -workers after him. Grassberger, who carefully investigated this -problem, worked more particularly with two strains showing the -extreme of variation between the small characteristic morphology -of the B. influenzæ and the thread forms supposed to be characteristic -of the so-called pseudo-influenza bacillus. The great -majority of workers have agreed with him in concluding that this -morphological variation is not sufficient nor constant enough to -justify separating two such groups. Nevertheless many reports -indicate peculiar tendencies of certain strains toward thread -formation. There seems to be suggestive evidence that the -organism described by Cohen in 1909 under the name B. meningitidis -cerebrospinales septicemicus is different from true -B. influenzæ. Although the cultural characters were apparently -identical, this organism was definitely pathogenic for guinea pigs -and rabbits. The involvement of joints in the cases reported -by Longo and others would suggest a greater pathogenic power -for these strains. Prasek and Zatelli reported a similar bacillus -<span class='pageno' id='Page_173'>173</span>from meningitis, and Davis found that his meningitis strains -were more pathogenic for rabbits than were others. Wollstein -has studied this question very carefully and found a marked -difference between the strains from the meninges and those from -the respiratory tract in their pathogenicity for rabbits. The -strains with a tendency to thread formation were usually also -those grown from the meninges, but she concluded from the -results of serological tests that all strains of B. influenzæ are of -one race, irrespective of their origin or virulence. The question -is still an open one, as Batten and others described strains from -the meninges which are non-pathogenic, and Ritchie found his -strains from meningitis pathogenic for guinea pigs but not for -rabbits. The irregularity and wide divergence in the results of -blood cultures may have a definite relationship to these differences -in the pathogenicity of strains.</p> - -<p class='c009'>Other hemophilic bacteria include the bacillus described by -Friedberger under the name of B. hemoglobinophilus canis. -This organism is to be found in the preputial secretion of dogs. -It does not show the phenomenon of symbiosis, and I have found -that it grows rather more freely and is more resistant to drying -than is the influenza bacillus. Krage has confirmed Friedberger’s -findings growing this bacillus from 60 per cent. of his dogs, -and believed it a pyogenic organism just as B. influenzæ may be.</p> - -<p class='c009'>The hemophilic and hemolytic organisms described by Davis, -which he isolated from pathological urine, were non-symbiotic -and non-pathogenic. Koch has described a similar organism -from puerperal infection. Whether the hemophilic organism -described by Thalhimer from the uterus in a case of puerperal -infection, those found by Cohen in urethral discharge in one -case and the pelvic exudate of another, and the findings of Kretz -in pyelitis, Wright in pyelonephrosis and Klieneberger in cystitis -cases, possibly refer to this same bacillus is, of course, uncertain. -Pritchett and Stillman found a somewhat similar bacillus, which -they called Bacillus X, from the mouths of 24 persons. It was -hemophilic and hemolytic, stouter than B. influenzæ and showed -long tangled threads in blood broth. It was non-pathogenic and -is probably the same as Davis’ organism.</p> - -<p class='c009'>Davis described another hemophilic bacillus from a patient -with purulent foci which was non-hemolytic and non-symbiotic. -It was grown from an abscess of the shoulder joint, the blood -<span class='pageno' id='Page_174'>174</span>and the bronchial secretion of an infant. Cyanosis was a marked -feature of this case. Paranhos described a hemophilic bacillus -from meningitis, which, however, was Gram positive, and Moon -reported an anærobic hemophilic bacillus from an infection of -the ethmoid sinus. The work of Jordan would suggest that there -may be two groups of B. influenzæ based on the indol production.</p> - -<p class='c009'><em>Morphology.</em>—The morphology of B. influenzæ has received -more than usual attention. In what we consider its characteristic -form, it is an extremely small bacillus, usually single but sometimes -in pairs, and not infrequently exhibiting polar staining. In -direct smears, where there are many bacteria present, they are -frequently arranged in the schools so frequently described. The -development of thread forms is today considered quite characteristic -for B. influenzæ. The organisms vary from moderately long -bacillary forms to very long twisted or curled threads suggesting -leptothrix. In such cultures chains of tiny bacilli are also quite -often noted. At the other extreme we have exceedingly tiny -coccoid forms, resembling in size the B. bronchisepticus, which, -as Ferry has shown, are small enough to pass through many -grades of filters.</p> - -<p class='c009'>It is the thread forms, as discussed above, that have received -most attention in relation to the so-called pseudo-influenza bacillus. -The observations of Wollstein, Lacy and many others -showed these forms to be common in meningeal infections and -that, as a rule, they are more pathogenic for animals than other -strains. Another interesting and important observation is that -emphasized by Dick and Murray of the possible confusion of -these forms with Gram negative leptothrix. That this confusion -is liable to occur is illustrated by reports such as Macdonald -finding leptothrix in a meningeal infection, now looked upon as -an example of influenzal meningitis, and the probable B. influenzæ -reported by Dick, and, as quoted by Dick and Murray, the -finding of a Gram negative leptothrix as the cause of broncho-pneumonia -by Kato. The 2 per cent. leptothrix reported by -Nuzum and his co-workers from the recent epidemic may be still -another example. Equally important is the recognition of the -great frequency of this thread development in the majority of -B. influenzæ cultures on ordinary blood agar media, or even in -the water of condensation of fresh blood agar tubes. The delayed -growth of this bacillus on ordinary blood agar would lead to its -<span class='pageno' id='Page_175'>175</span>being frequently overlooked unless smears are made, and the -irregular thread forms are recognized as being the B. influenzæ. -This development of thread forms was particularly noted in my -work before pickings were made to the Voges heated blood agar, -but because I had been forewarned by discussing these morphological -variations with Lacy, I was able to recognize them as -forms of B. influenzæ. Most of my early isolations showed these -predominating, and they were also noticed in cultures sent from -the Public Health Laboratory at Washington. These cultures on -further transfer, however, showed in 24 hours the typical small -form on ordinary blood agar as well as on the Voges medium. -On the latter the development of thread forms was greatly -delayed and frequently did not appear at all, although after long -periods other abnormal, swollen and irregular shapes sometimes -developed.</p> - -<h3 class='c010'><em>Media in Growth of B. Influenzæ</em></h3> - -<p class='c011'>The discovery of the hemophilic character of B. influenzæ has -been confirmed by a long list of investigators. The agar smeared -with pigeon blood as used by Pfeiffer has not, however, been -found fully satisfactory and many modifications have been made. -The fact that hemoglobin in some form is necessary for the -growth of these bacteria has led to a great deal of study in -attempts to discover the chemical part, or parts, essential for -this purpose. Hemoglobin in very small amount, as shown by -Davis and others, is sufficient to make media suitable for growing -B. influenzæ. This fact has led to much confusion, owing -to the difficulty of eliminating all possible sources from which -some form of hemoglobin might enter the media. Kitasato used -a glycerin agar and succeeded in growing the influenza bacillus -for 10 transfers. Pielicke, however, did not consider that Kitasato -was actually dealing with the influenza bacillus, but that -he as well as Babes, Bruschettini and Markel had most probably -streptococci in their cultures. Besson held the same view of -Kitasato’s organism. It would further appear from the illustrations -of Klein that he also grew streptococci and not the B. influenzæ. -The first culture of the influenza bacillus was probably -obtained by Bujiwid in February, 1890. He grew on agar -smeared with the spleen pulp of an influenzal patient a tiny -bacillus which he was unable to grow on blood free medium, but -<span class='pageno' id='Page_176'>176</span>he did not appreciate its importance until Pfeiffer’s article -appeared. Teissier in his book on “L’ Influenza en Russie” mentioned -this culture.</p> - -<p class='c009'>The hemophilic character of these bacteria indicates that they -are rather strict parasites, and despite the researches of Nastjukoff -with various egg media, and Cantani with a number of -supposedly non-hemoglobin additions to the agar, as well as the -studies on symbiosis, with other bacteria, by Cantani, Neisser, -Luerssen and many others, it still remains true that some form -of hemoglobin is necessary for their growth. Fresh blood either -incorporated in the medium or smeared on the surface is not the -best medium for these bacteria. Altered hemoglobin is much -more favorable, and a variety of methods have been devised to -bring about those alterations which stimulate the growth of -B. influenzæ. One of the earliest, as well as one of the very best, -of these is the method of Voges, who added blood to melted -agar at a temperature of about 100° C. I have found this -medium exceptionally suited to growing B. influenzæ, and I consider -it excellent for the primary culture from the original -material, for pickings from plates and to obtain a heavy growth -of B. influenzæ for any purpose. The medium was used by Delius -and Kolle (1897), Grassberger (1898), who spoke very highly -of it, and Paltauf (1899), who said that the use of this medium -made the demonstration of B. influenzæ possible when only a -very few were present. A great many other workers have used -it with success, and during the recent epidemic it has gradually -found its place. Levinthal’s medium (1918) is practically the -same, although he boiled and filtered the agar after the addition -of the blood. The growth of B. influenzæ on the Voges agar can -properly be described as luxuriant, and to anyone only accustomed -to the use of ordinary blood agar it is an agreeable -surprise to see this supposedly delicate bacillus growing so -remarkably well.</p> - -<p class='c009'>Various other methods have been used to bring about this -beneficial change in hemoglobin. Gioelli (1896) used a medium -made up of 1.1 per cent. hemoglobin and 21.5 per cent. malt -extract. This is reddish brown in color, becomes clear when -neutralized with potassium hydrate and remains so on heating. -This added to agar is reported as very favorable in growing this -bacillus. Ghon and Preyss described a medium made up of meat, -<span class='pageno' id='Page_177'>177</span>peptone, salt and agar prepared in the ordinary way, but not -filtered for at least a week, and then only roughly. This medium -is favorable for symbiotic growths. He further used beef blood -heated in a soda solution and blood heated in water as hemoglobin -preparations to be added to agar. Thalhimer found an -amorphous hemoglobin medium to be more favorable than when -a purer hemoglobin was used. W. F. Robertson found a hemoglobin -agar, prepared by allowing sheep’s blood to clot, decanting -off most of the serum, freezing and then thawing what remains -and adding 1 c.c. of this to an agar tube at about 60° C., to be -very favorable for the growth of B. influenzæ. Cantani used a -blood treated with pepsin and hydrochloric acid, digested some -days in the incubator, filtered and made weakly alkaline. This -mixture was heated for a few minutes, refiltered and added to -the medium. He speaks of it as extraordinarily good for B. influenzæ. -Blood treated with trypsin has been used by Matthews, -Averill, Young and Griffiths, Harris, A. Fleming and others. -Fleming further found that this alteration in hemoglobin can be -brought about in a number of other ways. Blood boiled in agar -(suggesting the Voges agar) and the tubes slanted while hot, -blood boiled in water, the clotted blood precipitated and the -clear fluid added to agar, or more rapidly by adding equal quantities -of sulphuric acid to the blood and a similar amount of -potassium hydrate he obtained altered blood suitable for media. -He reported that by any of these methods he could obtain a -medium very stimulating to the growth of B. influenzæ. By the -addition of brilliant green (1 in 500,000) he inhibited the growth -of staphylococcus, streptococcus and pneumococcus. For storing -cultures of B. influenzæ Fleming found a minced meat medium -with the addition of blood to be the best. I have found this -medium without the blood to be an excellent one for keeping -a great variety of cultures. Bernstein and Loewe have reported -the use of gentian violet (1 in 5,000) for the same purpose as the -brilliant green used by Fleming. Avery’s oleate blood agar -medium he reported to be largely selective. It checked the -growth of pneumococci and streptococci, but gave luxuriant -growths of B. influenzæ. Pritchett and Stillman have used it -with excellent results recovering B. influenzæ from a very high -percentage of the cases studied.</p> - -<p class='c009'><span class='pageno' id='Page_178'>178</span>The use of symbiotic bacteria has been extensively studied in -investigations of the biology of B. influenzæ, and it has been -shown, as noted elsewhere, that such accessory bacteria will -bring to growth B. influenzæ on media otherwise quite unsuited -to its needs. It has been further found that on various preparations -of hematin agar, on which B. influenzæ refused to grow, -such media could be rendered favorable for their growth by the -addition of living or freshly killed cultures of staphylococcus and -many other bacteria. And although the method is well known, -it has not been extensively used for the purposes of isolation. -Many of the workers, however, have pointed out the importance -of looking for growth of the influenza bacillus in the neighborhood -of the more easily grown bacteria which almost always -develop in cultures from the respiratory tract. Grassberger has -particularly studied this problem and has made practical application -of the method. Accidental contamination of plates with air -bacteria have made possible, in some instances, the isolation of -B. influenzæ—as, for example, in the finding of Heyrovsky from -a case of empyema of the gall bladder—while other workers have -pointed out the difficulty of demonstrating growth where B. influenzæ -is pure in the material cultured, and the comparative ease -and relative luxuriance of growth where other bacteria are -present. To just what this stimulating effect is due has been -much discussed, and it is generally agreed that the hemoglobin -is markedly changed and rendered more available by the action -of these germs. It is to be noted that on a medium containing -blood altered by heating or by the various methods as described -by Fleming the foreign bacteria no longer show any symbiotic -action on B. influenzæ. Grassberger considered the effect of the -bacteria on the blood to be the same as that of heating. Allen -laid particular stress on this symbiotic character. He used a -staphylococcus, either living or killed, in making his cultures -and noted the difficulty of growing B. influenzæ from material -in which it occurred pure. W. F. Robertson made use of these -facts of symbiosis for both isolation and stimulation of growth. -He employed alternate drills of M. catarrhalis or pneumococcus -with the B. influenzæ, and Brown and Orcutt used strains of -hemolytic streptococci for the same purpose. The latter authors -considered that the beneficial effect of the streptococci was -merely due to the setting free of the hemoglobin. The fact that -<span class='pageno' id='Page_179'>179</span>similar results are to be obtained by the use of non-hemolytic -bacteria as well as forms giving green color changes to the blood -makes this explanation untenable. In my own studies I have -confirmed the results of several previous workers. I have found -that B. influenzæ is stimulated in its growth by the presence -near it of colonies of staphylococcus pyogenes aureus and albus, -pneumococci, streptococcus viridans and hemolyticus and other -bacteria. The largest colonies of the bacillus I have obtained -were those growing near the periphery of a colony of an air -nocardia. I have also noted that emulsions of a staphylococcus -killed by boiling for five minutes, when added to ordinary blood -agar, had a marked stimulating effect, although no evidence of -hemolysis was present. This effect was practically absent if the -emulsion was boiled for 15 minutes, or after being killed was -left at room temperature for several days. There was no evidence -of these stimulating effects by any of these methods when -heated blood agar was used, the colonies on this medium growing -equally large by themselves. Comparative studies of the effect -of different bacteria can be simply carried out as follows: Smear -evenly the surface of an ordinary blood agar plate with an emulsion -of B. influenzæ. Seed this plate at various points with -minimal amounts of the various bacteria. After various periods -of incubation the size of the B. influenzæ colonies about the -other bacterial growths can be estimated, and impression preparations -on cover glasses will give very interesting pictures.</p> - -<p class='c009'>The growth of B. influenzæ in primary cultures from sputa -and similar sources is to be explained by the probable presence -of traces of blood or altered hemoglobin as well as the symbiotic -relationship with other bacteria. Fichtner used fresh heated -sputum (60 to 65° C.) in place of blood, and Richter a medium -made with sterilized pus. Parker, in her study of a filterable -poison produced by the B. influenzæ, found veal infusion broth -with 10 per cent. defibrinated blood heated to 75° C. until the -blood coagulated and settled on standing to be the best for the -purpose. Jordan in his study of indol production by these bacteria -used a meat infusion broth with 5 per cent. sheep’s blood -added at 90° C. or over and filtered through cotton or paper. -Wittingham and Sims noted that in using blood from influenza -cases the bacteria frequently did not grow, more especially -B. influenzæ; and Rivers found human blood poorer than cat or -<span class='pageno' id='Page_180'>180</span>rabbit blood for growing this organism, as did Minaker and -Irvine. It would seem clear from this review of some of the -suggestive work on the methods of growing B. influenzæ that -little attention should be given to the results of many workers, -where ordinary media were used, particularly when the difficulties -of isolation were not appreciated.</p> - -<h3 class='c010'><em>B. Influenzæ as a Pathogenic Bacterium</em></h3> - -<p class='c011'>If B. influenzæ is the causative agent in clinical influenza, -there is certainly ample evidence that it is pathogenic to man. -The symptoms of toxemia, which are so manifest in the pandemic -disease as well as in the sporadic cases, would indicate that the -etiological agent is markedly toxicogenic. Animal experiments -by Pfeiffer, and a long list of investigators following him, would -seem to show that the majority of cultures of B. influenzæ do -not have any power of establishing themselves in the animal -tissue. Killed cultures showed equally as high toxic effects as -the living, and so it was generally concluded that many of the -general effects in influenzal infections were of a toxic nature.</p> - -<p class='c009'>There are many exceptions to the above-mentioned failures to -produce infections in animals. Cantani obtained very constant -positive results by subdural injections. He first clearly showed -that killed cultures were markedly toxic and that virulence could -be raised very definitely by animal passage. By injecting brain -emulsion with a culture he obtained a subcutaneous abscess in -a rabbit which after eight days still contained the living -organism. Nastjukoff found that animals with a lowered resistance, -or definitely ill from, for example, an artificial tuberculosis, -became infected while others did not. Jacobson showed that -B. influenzæ injected with streptococci caused a definite mixed -infection, and that after six passages the influenza bacillus alone -could produce a fatal infection. Saathoff (1907) confirmed -Jacobson’s findings and found pneumococci equally effective. -Davis (1915) also confirmed the principle established by Jacobson -of the symbiotic relation of other bacteria to infection with -B. influenzæ. He used a culture of a non-virulent staphylococcus -pyogenes aureus, and was able to produce death invariably in -guinea pigs after intraperitoneal injection. From the heart’s -blood, as a rule, only the hemophilic bacillus was recovered. He -also found animal passage increased the virulence, and further -<span class='pageno' id='Page_181'>181</span>that M. catarrhalis and an avirulent streptococcus had the same -effect as the staphylococcus. Slatineanu (1901) found that he -could infect animals with B. influenzæ if the cultures were -injected along with weak solutions of lactic acid, and that after -animal passage by this method the bacillus became more virulent -and would eventually kill by itself. It must not be forgotten -in this connection that strains of B. influenzæ from meningitis -cases are frequently definitely pathogenic for animals. The -importance of considering these various factors in a discussion -of infection by this organism is, of course, very evident. Ecker -found his strains pathogenic for mice after subcutaneous injection, -and the bacilli were readily obtained from the heart’s blood. -Spooner and his co-workers from their results of more than a -hundred intraperitoneal injections concluded that the organism -is not pathogenic for mice.</p> - -<p class='c009'>In all animal experiments it is of the greatest importance that -the bacteria be known which may interfere in the experiments -through spontaneous infection (often liable to be induced by the -injection) from the animal’s own flora, as well as the greater -susceptibility of previously diseased animals (Nastjukoff). It -would appear from the results of Bruschettini and Cornil and -Chantemesse in the early days of the influenza bacillus, and -those of Lamb and Brannin in their recent study, that these -authors did not seriously consider the spontaneous infection of -guinea pigs and rabbits with B. bronchisepticus or the bacillus -of rabbit septicæmia, both morphologically, very similar to -B. influenzæ. Rosenow in his experiments with streptococci from -cases of influenza has also apparently failed to realize the importance -of the lung lesions produced by the B. bronchisepticus in -guinea pigs as reported by Theobald Smith, myself and many -others.</p> - -<p class='c009'>Parker has found a filterable poison from the influenza bacillus -which developed rapidly (6 to 8 hours) in a special heated blood -broth medium, deteriorated rapidly even in the cold, and killed -rabbits in quantities of 2 c.c. in from 1 to 3 hours. Rabbits -could further be immunized against this poison, and their sera -protected other rabbits against fatal doses. This is the first time -that a true powerful toxine has been obtained. Couret and -Herbert obtained toxine from B. influenzæ in Avery’s oleate -broth. Huntoon and Ross also clearly demonstrated toxine production -<span class='pageno' id='Page_182'>182</span>by this organism so that it would appear, with this confirmation, -that the B. influenzæ can be definitely classed among -the toxine producers. Toxemia being the most striking clinical -characteristic of influenza, we have in these findings very strong -evidence of the etiological importance of this hemophilic bacillus -to the disease. A very interesting observation was made by -Latapie that the serum of a goat immunized against influenza -bacillus is toxic if it is used shortly after the injection of the -microbes, but that this toxicity is absent three weeks after the -last injection. It would appear to me that the evidence of a -filterable virus from the secretions of the respiratory tract does -not eliminate the very probable toxine from such materials. The -production of toxine by this organism probably depends, as is -the case with very many of our toxine formers, on the most -favorable combinations of conditions. That it is not readily -formed in artificial cultures, or that it is very unstable if formed, -is evidenced by the frequent failures of a great many workers. -It has been suggested that different symbiotic conditions in the -respiratory tract determine the amount of toxine produced. -Huntoon found a high toxine production in mixed cultures with -streptococci. This, however, does not appear to be necessary, -as there is ample evidence of severe toxemia from pure infections -with B. influenzæ in various parts, such as the accessory sinuses -of the head, the meninges, the lungs and other parts of the -respiratory tract.</p> - -<p class='c009'>It is not fundamentally necessary that a toxine producing -organism be present in overwhelming numbers before it can be -accepted as the cause of the toxemia. Nor, on the other hand, -must we have toxemia every time the organism is found. The -prevalent idea among bacteriologists would appear to be the -reverse of what I have just stated. It would, indeed, be extremely -difficult to make bacteriological diagnoses of a great many of our -diseases, where the etiological factor is well established, if these -conditions were required. We do not do so, for example, in -diphtheria, examinations of stools for typhoid, nor in infections -with the tetanus bacillus. We recognize carrier cases of meningococcus, -B. typhosus, hemolytic streptococci and many others, -without detracting seriously from their importance in definite -types of infection. Formerly the specificity of the different -bacteria for definite disease processes was very rigid, but today -<span class='pageno' id='Page_183'>183</span>we interpret more broadly the finding of gonococcus in endocarditis, -the meningococcus in bacteremia, B. typhosus in osteomyelitis, -streptococci and pneumococci in all manner of infections -and many other bacteriological results. True it is that the -various bacteria show predilections for attacking certain tissues, -but the varying susceptibilities bring about the greatest variations -in the manifestations of these infections.</p> - -<p class='c009'>The B. influenzæ is not confined to the causation of severe -pandemic or epidemic influenza, but includes in its field purulent -bronchitis, meningitis, sinusitis, conjunctivitis and many other -pathological processes. It further should be recognized as a -relatively frequent cause of complications in measles and other -diseases.</p> - -<h3 class='c010'><em>Infections of the Respiratory Tract</em></h3> - -<p class='c011'>The disease influenza is primarily an infection of the respiratory -tract. It varies from one of the most acute and fatal -diseases we know of through all grades of severity—from -chronic infections lasting over years to the familiar three or five -day fever. This graduation is to be found more or less marked -in all our bacterial infections, but would seem to be not generally -recognized or appreciated as occurring in infections with the -influenza bacillus. That Pfeiffer was dealing with one phase of -the disease when the influenza bacillus was discovered does not -invalidate the results of numerous workers which have been -added since then.</p> - -<p class='c009'>Probably the greatest confusion in attempts to get a clear -picture of this protean disease has been and is a non-recognition -of influenza as a frequent complication of other diseases, such as -measles (Jochmann, Susswein, Tedesko and very many others). -The second cause for this confusion has been the misinterpretation -of the facts demonstrating the rather frequent occurrence -of carriers. During an epidemic the vast majority of patients -show the disease as an upper respiratory infection of varying -degrees of intensity, but which usually subsides after periods -of from three to five days of fever. Along with this we have -other graded manifestations of further involvement of the tract -with laryngitis, bronchitis, bronchiolitis and all degrees of broncho-pneumonia. -To prevent the severe lung involvement prompt -treatment must be carried out, under which rest in bed is by -<span class='pageno' id='Page_184'>184</span>long odds the most important. This will be discussed in another -paper of this series, and was particularly well demonstrated in -the results at the Naval Hospital as verbally reported to me by -D. G. Richey. The interesting point is that the infection can -be controlled, but this does not indicate the etiological factor as -different from that acting in the more severe cases.</p> - -<p class='c009'>The epidemiological evidence would seem to show very clearly -that the incubation period is approximately two days, and that a -period of six weeks is the usual limit for the severe wave of the -epidemic in different localities. In my opinion, during this period -every exposed individual in a community has received the influenza -bacillus in the respiratory tract, and that all the susceptible -individuals are attacked and show more or less evidence of the -infection. As a consequence of this general distribution we have -great numbers of individuals carrying the organism, and the -aftermath is to be noted in other and later manifestations of -the same infection.</p> - -<p class='c009'>Sporadic cases of influenza appear during inter-epidemic -periods and more or less healthy carriers are frequent. Scheller’s -study in Königsberg showed, if we can rely on his figures, that -the carriers were very numerous during an epidemic year (winter -1906-1907), being 24 to 33 per cent.; that as the epidemic -became less widespread (winter 1907-1908) it fell to 10 to 13 -per cent.; as it was disappearing (summer 1908) he found only -1.5 to 3.3 per cent.; while when the epidemic was completely -over (winter 1908-1909) there were no carriers of B. influenzæ -found. These results are taken from studies of sputa and throat -smears of 138, 218, 155 and 185 cases, respectively, for the -periods mentioned. The monumental work of Tedesko, who reported -the results of 1,479 cultures, covering 11 years (1896-1906), -would indicate that B. influenzæ is continually present -in the population. However, in carefully analyzing his results, -it is very clear that in the great majority of his cases it was of -definite etiological significance. Lobular pneumonia, acute, purulent -and chronic bronchitis, and most frequently clinical influenza, -are the prominent diagnoses in all his tables. He was able to -grow B. influenzæ repeatedly from individual patients for many -months.</p> - -<p class='c009'>Lord in similar studies (1902, 1905, 1908) brought out somewhat -similar facts. He laid particular stress on the cases of -<span class='pageno' id='Page_185'>185</span>chronic bronchitis with numerous B. influenzæ in the sputum -and a probable confusion of these with pulmonary tuberculosis. -He was able to follow a number of his patients for several years. -B. influenzæ was grown in culture from the sputum of one of -these in 1902; in November, 1903; in February, 1904, and in -February, 1905. In other cases the organism was shown to be -present by culture practically continuously for months and even -years. Lord, with Scott and Nye, in a recently published article -(1919) reviewed his former results and showed a relatively high -incidence of B. influenzæ in the respiratory tract of apparently -healthy people. Davis studied 534 cases, further indicating the -prevalence of this organism in the community.</p> - -<p class='c009'>The B. influenzæ has been recovered from the respiratory tract -during the clinically pure influenza, from the sputum and lung -in influenzal pneumonia, and from the purulent sputum in all -grades of bronchitis. These should all be looked upon as true -infections by the influenza bacillus, the varying manifestations -merely differing with the resistance of the individual. In the -epidemic in the fall of 1918 pneumonia was the outstanding -feature. Preceding this in the English publications we have -reports of outbreaks of purulent bronchitis. Macdonald and his -co-workers, finding the B. influenzæ frequently present, considered -the condition as one indication of a virulent infection by -this organism. Hammond, Rolland and Shore reported similar -cases, and Abrahams and his co-workers looked upon the cases -of purulent bronchitis as occupying a position, without any -definite line of demarcation, between those with definite broncho-pneumonia -on the one side and those with simple bronchial -catarrh on the other. H. E. Robertson emphasized the serious -nature of influenzal purulent bronchitis and the almost epidemic -character and rather high mortality of the outbreak in the winter -and spring of 1917-1918. There were also numerous mild outbreaks -of influenza before the overwhelming culmination of the -last three months of 1918, as reported by Orticoni and many -others and noted by Johnston in this series of papers. Greenwood -in an epidemiological study emphasized the point, previously -made evident by Parsons for the pandemic of 1889-1892, -that the mass attack is preceded by numbers of individual cases. -In this country it was noted during the winter of 1917-1918 and -the following spring that the B. influenzæ was rather frequently -<span class='pageno' id='Page_186'>186</span>found in the respiratory infection in our army camps (Soper, -Cole and MacCallum and others).</p> - -<p class='c009'>It is well recognized that when the actual epidemic struck -there were comparatively few bacteriologists familiar with the -B. influenzæ. The real difficulties of isolation, the more favorable -media, the facts of symbiosis, the importance of carriers, -the varying manifestations of the infection and many of the -other vitally important points, although more or less fully reported -in the literature, were nevertheless practically unknown. -It was my own experience, and that of many others. This must -be seriously considered in analyzing many of the reports on bacteriological -findings throughout the period of the severe wave and -even after.</p> - -<h3 class='c010'><em>Results of Others During the Recent Pandemic</em></h3> - -<p class='c011'>It will be impossible to review the numerous reports on the -recent epidemic that have appeared. Many of these can be discounted, -as far as the finding of B. influenzæ is concerned, for -the reasons mentioned above. The often quoted report of Little, -Garofalo and Williams, who did not even use a hemoglobin -medium, will serve as an example. Little attention should be -given to others where the large numbers of cases precluded the -requisite time and media necessary for such a difficult problem. -Friedlander and his co-workers in their report from Camp Sherman -made no mention of the number of sputa, throat swabs or -autopsies which they examined bacteriologically. The incidence -of influenza showed a total of 10,979 cases, 2,001 of pulmonary -œdema or pneumonia and 842 deaths. They recorded one culture -from the sputum with pneumococcus predominating which gave -two colonies of B. influenzæ, and this bacillus was grown from -the lung exudate at one autopsy. Their conclusions that “B. influenzæ -(Pfeiffer) has not been demonstrated as the causative -organism” is certainly true from their results, but that “the -frequency of its detection has not exceeded the frequency of its -existence under normal conditions” can hardly be considered as -established, if we accept the many results mentioned above as -indicating its presence during inter-epidemic times, unless they -mean by normal conditions practically complete freedom from -this organism.</p> - -<p class='c009'><span class='pageno' id='Page_187'>187</span>The prevalence of B. influenzæ in various sections of this -country may be indicated by the following reports chosen from -many available ones. Keegan, from the First Naval District -Hospital, found B. influenzæ 19 times from 23 in cultures grown -from the lungs. In 6 cases these cultures were pure. Medalia -reported from Camp McArthur the following. Out of 2,279 sputa -of influenza suspects, 76.8 per cent. showed “B. influenzæ” in -smears, and 445 sputa from cases of broncho-pneumonia showed -it in 54 per cent. It was found in culture in only 10.6 per cent. -of these last cases. He considered sputum smears of practical -diagnostic help. He further grew B. influenzæ twice from the -blood during life, once with a pneumococcus and once alone. -Necropsy cultures gave B. influenzæ in 2 of 3 cultures from the -brain, 19 of 34 from the heart, 19 of 36 from the spleen, 54 of -65 from both lungs, 50 of 62 from the right pleura and 47 of 62 -from the left pleura. The percentage of positive results ranged -from 53 in the spleen to 83 in the lungs. Nuzum and his associates -only found B. influenzæ in 4 of 100 cases from the bronchial -secretions, but it is interesting to note that he grew it in -practically pure culture from both lungs of one case at autopsy. -Synnott and Clark in Camp Dix found streptococci and pneumococci -predominating, and, although making no particular -effort to study the B. influenzæ or determine its frequency, they -found it in the majority of cases when it was looked for. Blanton -and Irons reported as follows from Camp Custer. From cultures -of the nose and throat of 357 examined before the epidemic -struck, B. influenzæ was found in 5.1 per cent.; in 366 throat -cultures of influenza cases without physical signs of pneumonia -the same organism was grown in 44, or 8 per cent.; sputa typed -for pneumococci 740 times from influenza cases with pneumonia -gave isolations of B. influenzæ 38 times, or 5 per cent.—8 times -alone, but here it should be remarked that these latter isolations -were only attempted after the organism was suspected from the -morphological picture of the smears; from 280 autopsies B. influenzæ -was recovered 8 times from the lung and 3 times from the -heart’s blood. This report covered the period from the outbreak -of the epidemic, October 5 (or as given by Soper, September 30) -to October 22, at the outside a period of 22 days. During this -time 366 throat cultures, 510 blood cultures, 740 sputa typed for -pneumococci, 280 autopsies with cultures from both lung and -<span class='pageno' id='Page_188'>188</span>heart’s blood, made a total of primary cultures of well over 2,000. -The technical difficulties would make it almost impossible to -handle such a mass of material and get reliable results for the -incidence of B. influenzæ.</p> - -<p class='c009'>Brem, Bolling and Casper in Camp Fremont found B. influenzæ -in 259 from 537 selected cases in swabs from the nasopharynx. -It was also noted in a fair number of other examinations. Opie -and his co-workers found B. influenzæ to be very frequent at -Camp Pike. Spooner, Scott and Heath isolated B. influenzæ at -Camp Devens from the sputa of 104 cases, from nasopharyngeal -swabs in 11 out of 18 attempts and from the pleural fluid 8 times -out of 45, twice pure. From 37 autopsies they found B. influenzæ -in 23 and in pure culture in at least 1 lobe of the lung in 16. From -82 blood cultures at autopsy B. influenzæ was recovered twice. -Nichols and Stimmel studied lung punctures during life and grew -the B. influenzæ from 7 out of 10 attempts, 5 times in pure culture. -Stone and Swift at Fort Riley found B. influenzæ in 18.7 -per cent. of 928 sputa and in 5.2 per cent. of 77 sputa from fatal -cases. He recovered it from autopsy material; 21 times from 51 -lungs, once alone; twice from 26 pleural fluids; twice from 30 -heart bloods; 19 times from the sinuses of 40, and 9 times from -the ear and mastoid of 17 cases.</p> - -<p class='c009'>Lamb and Brannin at Camp Cody examined 80 typical cases -early in the epidemic. They found B. influenzæ predominated in -46 per cent. being present with pneumococci on 41 per cent. of the -plates. They also grew the influenza bacillus from a fair number -of other cases.</p> - -<p class='c009'>Wollstein and Goldbloom in the Babies Hospital of the City of -New York found the B. influenzæ in 13 of 17 sputa during life -and in both lungs of all 18 autopsies as well as in the heart’s blood -of one. Kotz found it in half of his 30 cases. Pritchett and Stillman -grew the influenza bacillus from 41 of 49 cases of influenza, -from 40 of 43 cases of influenza with broncho-pneumonia, from all -of six other broncho-pneumonia cases and from 11 of 20 cases of -lobar pneumonia, making a total of 98 positive findings from 118 -or 82 per cent. They further found 25 positives from 54 convalescent -and 74 from 177 normal sputa. Wolbach found this -organism in pure culture in one or more lobes of the lungs of 9 -from 23 cultured cases. It was demonstrated in 23 of 28 either -by culture or in section.</p> - -<p class='c009'><span class='pageno' id='Page_189'>189</span>Similar results are to be found in reports from Great Britain. -Martin noted a great increase in the numbers present as the -sputum became more purulent. Hicks and Gray found B. influenzæ -by culture in 75 per cent. of their cases. They were seen -in direct smears in only 70 per cent. Gotch and Wittingham considered -M. catarrhalis to be the etiological factor as it was found -in all of their 50 cases. B. influenzæ was grown in 8 per cent., -although B. influenzæ-like bacilli, were seen in 62 per cent. of their -smears. Averill, Young and Griffiths studied the sputum from 41 -cases and found B. influenzæ in 32. It is interesting that Macdonald -and Lyth determined the incubation period to be 41 hours -as a minimum in their own experience and that from the posterior -nares of one of them B. influenzæ was obtained.</p> - -<p class='c009'>Schofield and Cynn found the B. influenzæ in Korea. Kraus in -Brazil found it in the sputum in 62 per cent. of his cases of influenza. -It was also found in the organs of 27 who had died, being -in pure culture in five. It has further been found in France, Italy -and practically all parts of the world where investigations have -been made. The German literature is at present only available -in the report of the British Medical Research Committee which -is written in a more or less popular manner with a rather strong -tendency against the importance of B. influenzæ. Dietrich, -Simmonds, Bergmann and others, however, found B. influenzæ -rather frequently. Such quotations as “Uhlenhuth, a diehard of -bacteriologic orthodoxy, has clearly shown signs of uneasiness” -and “one empyema and one throat swab yielded the looked for -growth” will indicate why this review is of little use. It is certainly -necessary to “look for” the B. influenzæ to get results of -any worth.</p> - -<p class='c009'>Secondary, ancillary or symbiotic bacteria are of cardinal importance -in these infections. It has been considered by some -writers as characteristic for the influenza bacillus to be followed -so frequently with such a variety of secondary invaders. Sahli -looked upon the complex of B. influenzæ, pneumococcus and streptococcus -as the true etiological cause of influenza. Abrahams and -his associates discussed the symbiotic effect of the B. influenzæ -in raising the virulence of pneumococci previously present in the -patient and many other investigators lay stress on these symbiotic -relationships.</p> - -<p class='c009'><span class='pageno' id='Page_190'>190</span>Pneumococci appear to be the commonest of these secondary -micro-organisms judging from the various published reports, but -the fact must not be overlooked that, particularly in America, the -typing of pneumococci has drawn a disproportionate attention to -this group. Hemolytic streptococci have received much attention -(Ely and his co-workers and several others). M. catarrhalis -(Gotch and Wittingham and several of the British writers), members -of the B. mucosus capsulatus group (Nichols and Stimmel, -Rucker and Wenner), staphylococcus aureus (Patrick), various -ill-defined streptococci (Rosenow and several British writers), -capsulated cocci apparently different from pneumococci, B. pestislike -forms and many others have been given more or less attention, -often as clearly recognized secondary infections, but not -infrequently as of primary significance.</p> - -<p class='c009'>B. influenzæ, however, is the organism most regularly found in -this pandemic where carefully looked for, and the evidence of its -lowering the general resistance to bacterial invasion is very -strong. The experiments of Ghedini and Fedeli showing the -effect of the toxine on muscular tone and those of Ghedini and -Breccia who found a similar effect on blood vessels are worthy of -note.</p> - -<p class='c009'>The fact that the flora differs so widely in various regions is -what one might expect and many investigators have emphasized -the significance of this. Bacteria in the mouth and throat are -readily transmitted from individual to individual and under the -conditions in the training camps and our modern life, the development -of local flora is not surprising. That it is of very great -importance is recognized by all and it is often a determining -factor in the severity of the infection. Nevertheless, influenza in -this pandemic has been almost equally severe whatever the secondary -organism may have been.</p> - -<p class='c009'>I have discussed in another place the suggestion of the stimulating -effect of various bacteria on the growth and toxine production -of B. influenzæ. Huntoon showed the effect of hemolytic -streptococci in cultures to be helpful in toxine production. An -important point, however, is that no one bacterium has been -shown to be exclusive in thus affecting the growth on media of -the influenza bacillus, and in the animal experiments in raising -the invasive and pathogenic power of this organism the same -appears to be true. The infection in influenza, in the vast -<span class='pageno' id='Page_191'>191</span>majority of cases, rapidly becomes a mixed one. The secondary -organisms at times completely dominating the field, at least as far -as numbers go, most frequently invade the blood stream and it -would appear often play the important role in many of the secondary -conditions.</p> - -<h3 class='c010'><em>Chronic Infections</em></h3> - -<p class='c011'>B. influenzæ is a frequent finding in the sputum of patients with -chronic bronchitis, pulmonary tuberculosis and other chronic conditions -in the respiratory tract. Boggs recovered this bacillus -from two cases of bronchiectasis, Richards and Gurd had a similar -case and Tedesko reported several. The literature is filled -with references to the finding of B. influenzæ in cases of chronic -bronchitis. Those reported by Lord, Madison and Tedesko quoted -above will serve as examples. The frequent positive cultures in -cases of pulmonary tuberculosis so often referred to in reviews -of the literature and the significance of these findings, as pointed -out by Scheller, are important as bearing on the much debated -subject of the effect of influenza on this disease. These types of -chronic infection by the influenza bacillus should be more generally -recognized as they undoubtedly will become more numerous -following this last epidemic if we can judge from the experience -of the past.</p> - -<h3 class='c010'><em>Infections of the Pleura</em></h3> - -<p class='c011'>The recovery of B. influenzæ from the pleural cavity is not -uncommon as is shown in the above review. The findings of -MacCallum, Cole and others during the spring of 1918 are particularly -interesting. Beall in 1906 reported a case of empyema -with large quantities of green pus in which B. influenzæ was -found in pure culture.</p> - -<h3 class='c010'><em>Sinuses of the Head</em></h3> - -<p class='c011'>Infection of the accessory sinuses of the head has long been -recognized as occurring in influenza. Frankel found B. influenzæ -in 4 from 40 infected antra. Lindenthal, who was particularly -interested in the question of sporadic influenza, found the bacillus -in one or more of the head sinuses in six of eight carefully studied -cases. He considered that the B. influenzæ remained in these -<span class='pageno' id='Page_192'>192</span>areas during inter-epidemic times and from hence caused the -sporadic outbreaks of influenza. Howard and Ingersoll reviewed -the literature up to 1898 and grew B. influenzæ from one of three -acute antral diseases. They did not find it, however, in 12 chronic -cases. Clemens believed the influenza bacillus to be present in -the sinuses rather frequently in cases where it was overgrown or -difficult to culture from the lower respiratory secretions. Moszkowski -grew it in one case from the pus of the antrum. Tedesko -recorded several positive results and many others are reported in -the literature.</p> - -<p class='c009'>The two cases reported by Lacy (1918), the findings during the -present epidemic by Stone and Swift of B. influenzæ in 13 of 28 -sphenoidal and 6 of 12 ethmoidal sinuses cultured at necropsy, -those by Spooner, Scott and Heath, of B. influenzæ in four frontal -sinuses and in eight sphenoidal, and the recovery by Wolbach of -B. influenzæ in cultures from the sinuses in certain cases where -the lung cultures were negative, emphasize the importance and -frequency of the infection by this organism in these cavities. -Keegan, who laid particular stress on lung punctures and autopsy -examinations, pointed out that in throat cultures the probability -that the influenza focus is often not in the pharynx but in some -recess of the nasal cavity.</p> - -<p class='c009'>H. E. Robertson in the spring of 1918 reported the infection of -the sinuses in seven cases of tracheo-bronchitis with patches of -broncho-pneumonia and the growth of B. influenzæ from sphenoid, -ethmoid or frontal sinuses of all these cases. He also found this -organism in the sphenoid of six cases dying with various diseases -as well as in two accident cases with death under 24 hours. The -importance of these results was laid stress on by the author, not -only on account of the probable toxic absorption and the general -menace of spread, but, more particularly, because such individuals, -acting as carriers, could furnish foci for the spread of epidemics.</p> - -<h3 class='c010'><em>Eye and Ear</em></h3> - -<p class='c011'>Infections of the eye by the influenza bacillus are quite common. -This subject is fully discussed by Axenfeld (text-book, -“The Bacteriology of the Eye”). Giani and Picchi found it in the -eye in 66 per cent. of influenza cases, in 90 per cent. of epidemic -conjunctivitis, and in the normal eye of 5.8 per cent. Wynekoop, -<span class='pageno' id='Page_193'>193</span>in 1903, reported having found this organism in cases of conjunctivitis -in 1899. Guiral, in the recent epidemic, found influenza -bacillus constantly present in the secretions in cases of -what seemed to be Week’s conjunctivitis. Ulceration of the -cornea was rather common. One such case is mentioned in which -there was no pain in the eyes, but general symptoms of influenza. -The middle ear is also sometimes infected. Between the report -of Kossel in 1893 and that of Stone and Swift in 1918, who found -the middle ear and mastoid to contain B. influenzæ in 8 of 17 -cases, there have been many references in the literature to this -complication by the influenza bacillus. The evidence indicates, -however, that in the middle ear, as in the pleural cavity, the -secondary bacteria are far more often the important ones.</p> - -<h3 class='c010'><em>Meninges</em></h3> - -<p class='c011'>Influenzal meningitis seems to stand by itself as a manifestation -of the pathogenic effects of B. influenzæ. The literature is -too voluminous to review in this place, but the evidence would -seem to point to a more invasive and pathogenic type of this -organism, if not to a separate member of the group.</p> - -<h3 class='c010'><em>Invasion of the Blood Stream</em></h3> - -<p class='c011'>The evidence in clinical influenza would suggest at times a -bacteremia in addition to the severe toxemia, which is such a -constant feature of the disease. Simultaneously with the discovery -of B. influenzæ, Canon reported finding bacilli of similar -morphology in blood smears, but was unable to grow them, and it -would appear at least doubtful that he was dealing with the -influenza bacillus. Meunier is probably the first who grew this -organism from the blood. He recovered it from 8 blood cultures -out of 10 in cases of broncho-pneumonia following measles, and -in one other case of broncho-pneumonia. A very full discussion -of this question is to be found in Canon’s book on “The Bacteriology -of the Blood in Infectious Diseases.” Of particular -interest are the results of Ghedini, who made a careful study of -28 influenza patients. B. influenzæ was grown from the blood in -18 of these at the height of the fever, while in the 10 negative -cases the disease was milder or the blood was taken only after -<span class='pageno' id='Page_194'>194</span>the temperature had fallen. The amount of blood used was -20-30 c.c., and it was cultured in lecithin broth. In practically -all of his cases several cultures were taken, and in a number of -the positive cases negative results were obtained both before and -after the acme of the fever. He also grew the bacillus from 8 of -14 spleen punctures of these patients. Madison (1910) reported -the recovery of this bacillus from the blood of a patient with a -primary broncho-pneumonia who recovered. This author also -used about 30 c.c. of blood. Thursfield, in 1910, also reported -two cases of B. influenzæ bacteremia in which the organisms were -recovered at the height of the temperature. One had influenza, -the other phlebitis, and both recovered. Tedesko and several -others have found it in the heart’s blood in many cases, more -especially in broncho-pneumonia after measles.</p> - -<p class='c009'>During the present epidemic the positive cultures of this -bacillus from the blood have been rather infrequent. J. S. Fleming -had 2; 2 are quoted in the report of the Influenza Committee of -the Advisory Board to the D. G. M. S. (Peters and Cookson); -Medalia had 2 during life and 19 of 34 at autopsy; Orticoni, Barbie -and Leclerc in 5 of 10 blood cultures in one series, and 7 of 19 -in another; Stone and Swift 2 at autopsy; McKeekin, in Australia, -influenza-like bacilli in 4; Blanton and Irons three times in the -heart’s blood, one of these pure; Spooner, Scott and Heath twice -in the heart’s blood at autopsy, and Wollstein and Goldbloom -from the heart’s blood in one child. In the majority of these -findings the bacillus was not found in pure culture. Abrahams -and his associates found the B. influenzæ along with a pneumococcus -and M. catarrhalis from the heart’s blood in one case. -In our positive blood culture there was evidence of the same -mixture being present.</p> - -<p class='c009'>Before drawing sweeping conclusions against the invasion of -the blood by B. influenzæ it must be remembered that the quantity -of blood used has been generally only about 10 c.c., and often -much less, the difficulty of observing growth if the culture is -pure has been largely overlooked, the use of more favorable media -than blood agar and the possible inhibitory action of influenzal -blood, as suggested by Wittingham and Sims, Rivers and others, -has not been considered, and further that sufficient care has -not been exercised to obtain blood at the most favorable period in -the disease. It may be recalled that the problem is quite similar -<span class='pageno' id='Page_195'>195</span>to that of demonstrating the organisms in the blood in patients -with streptococcus viridans bacteremia.</p> - -<p class='c009'>All the available evidence, however, points to the invasion of -the blood in influenzal infections as being a very fleeting one. -Unless this is true, it would be surprising in the many hundreds -of blood cultures which have been taken in the concentrated -study of patients during the recent pandemic, if more successful -cultures had not been obtained. General infections with localization -of B. influenzæ in different parts of the body are here of -interest—such as that reported by Slawyk and others. Whether -the strains causing meningitis, and which apparently more frequently -invade the blood, are really different members of the -hemophilic group or only forms with a higher invasive power is -still, I believe, an open question.</p> - -<h3 class='c010'><em>Endocarditis</em></h3> - -<p class='c011'>In endocarditis the B. influenzæ is probably, after streptococci, -the organism most frequently isolated from the blood. Rosenthal -from heart’s blood at autopsy, Schlangenhaufer, Jehle two cases, -Horder (1907) six cases, and who believed he was the first to -isolate B. influenzæ from the blood, Tedesko in a number at -autopsy, Spat, F. J. Smith, Saathoff, Libman four cases, Sacquepee, -McPhedran, Mann, Rainaford and Warren three cultures -from two patients, and a number of others all bear witness to its -frequency.</p> - -<p class='c009'>Other organs of the body are sometimes found to contain -B. influenzæ. Adrian, Schultes, Basile and Tedesko have all -recovered this organism from the diseased appendix. Several -years ago a bacillus, considered, to be B. influenzæ, was grown -from the pus of an appendix abscess in our laboratories. Wright -found it in pyelonephrosis. Klieneberger found influenza-like -bacilli in cases of cystitis. Menko reported the bacillus from -orchitis, and Cohn found numerous influenza-like bacilli in the -discharge from urethritis. Meunier found it in pure culture in -a case of osteoperiostitis. Huyghe, Besancon and Griffon recovered -it from infected joints, as did Pacchioni in a general infection. -Weil found it in the pus about the hip joint one month -after an attack of influenza. This short review serves to illustrate -that the influenza bacillus, although generally limited to -<span class='pageno' id='Page_196'>196</span>infections in the respiratory tract, is, nevertheless, capable of -infecting other parts.</p> - -<h3 class='c010'><em>Immunity—Phagocytosis</em></h3> - -<p class='c011'>Phagocytosis of the B. influenzæ has been very frequently -noted in the study of sputum smears. It has been observed, -moreover, that this phenomenon occurs most frequently when -the patient is on the road to recovery (Pfeiffer, Martin, and -others), and it may indicate an important reaction on the part -of the body to this organism. Tunnicliff in a recent report, however, -did not find the opsonic index to be raised above the normal -in her patients, and Tunnicliff and Davis had difficulty with a -spontaneous phagocytosis of this bacillus. This difficulty was to -a large extent absent in her later study.</p> - -<h3 class='c010'><em>Agglutination</em></h3> - -<p class='c011'>Agglutination tests have been used by many investigators in -attempts to determine a specific reaction in the sera of persons -suffering from influenza. Such reactions develop, as we know, -against secondary infecting bacteria, so that unqualified conclusions -cannot be drawn that agglutinins in the sera of patients -against B. influenzæ indicate the etiological importance of this -organism. Vagedes using a dilution of 1-50 found 8 positives -among 27 patients tested. Lord found the test most inconstant. -Ghedini obtained useful results by using serum in dilutions 1-20 -to 1-30, and had 17 positives from 28 influenza cases. He found -agglutinins present three to four days after the height of the -infection, and noted that the sera became practically normal after -three to four weeks. Fichtner, although he obtained agglutination -with sera of influenza patients in high dilutions (1-100 and -1-750), found his controls were often agglutinated, and consequently -drew no conclusions. Wollstein (1906) did a series of -agglutination tests, using various strains of B. influenzæ. The -sera of patients she found very unsatisfactory, but by immunizing -rabbits with this organism she obtained sera with titres up to 1 in -400. She could find no differences among the various strains -studied. Somewhat similar results were obtained by her in 1915 -working with strains from the meninges and the respiratory -tract. Odaira carried out a rather extensive series of tests, using -<span class='pageno' id='Page_197'>197</span>immunized rabbit sera and a special method of making his bacterial -emulsions. He was able to distinguish B. influenzæ from -both B. pertussis and the so-called Cohen’s bacillus of meningitis. -Friedberger’s dog bacillus, however, could not be differentiated -from B. influenzæ by this means. A. Fleming during the -recent epidemic had good results with the sera of 21 patients. -He incubated at 50° C. for two hours. He also used sera of -immunized rabbits and got marked agglutination against the -homologous strain, but varying results with other strains. He -noted some strains agglutinated readily, while others did not. -Eyre and Lowe noted an increase in agglutinins in the sera of -people vaccinated against the influenza bacillus. Couret and -Herbert could distinguish two types and a possible third among -their strains. Park and his co-workers found numerous types -by means of agglutination. Absorption of agglutinins was found -helpful by these last two workers. There are so many factors -capable of altering the sensitiveness of bacteria to agglutination, -as in the well-known experiments of Neufeld, that we must -recognize that much work is still to be done before we can properly -interpret the results of these agglutination tests.</p> - -<h3 class='c010'><em>Binding of Complement</em></h3> - -<p class='c011'>Complement fixation tests were carried out by Odaira but his -results were much less satisfactory than those he obtained by -means of agglutination. Rapaport made an extensive study of -this test, using the sera of patients in various stages of convalescence. -Three hundred and fifteen convalescents showed 54.5 -per cent. positive while 300 controls only gave 9.5 per cent. -positive results. Most of the positive cases were in patients -three to five days after their illness, but the reaction was found -in convalescents after from 1 to 45 days. Sera from acutely -ill patients at times showed negative or slightly positive reactions -but these same sera after keeping for some days and retesting -often gave strongly positive results. This would appear to be -a promising field for investigation.</p> - -<h3 class='c010'><em>Anaphylaxis</em></h3> - -<p class='c011'>Hypersensitiveness was noted by W. F. Robertson in chronic -infections with B. influenzæ. Wollacott in a letter to the British -<span class='pageno' id='Page_198'>198</span>Medical Journal suggested that the severity of the recent outbreak -of influenza may possibly be due to the development of a -state of anaphylaxis. There would seem to be at least some -evidence in favor of such a view in the fact that the severe outbreak -was preceded by epidemics of a milder form of influenza -and that the influenza bacillus was probably widely spread during -this time. Greenwood, as quoted above, noted that primary cases -always precede the mass attack. Of course, the term anaphylaxis -has been used to explain almost everything. Nevertheless, -the theory is interesting. The skin tests which we did for hypersensitiveness -were, as I have noted above, negative but there is -a possibility that the failure of the reaction may indicate a higher -resistance or even an antitoxin, now that the bacillus can be -classed as a toxicogenic one. Anti-influenza sera have been produced -by a few investigators (Latapie, Wollstein) but have not -found any practical application during this pandemic. Vaccination -is discussed elsewhere in these studies.</p> - -<h3 class='c010'><em>Experiments on the Human</em></h3> - -<p class='c011'>There has never been in the history of medicine so many experiments -on human beings as have been carried out in the -attempts to discover the etiological factor in the recent pandemic -of influenza. Davis has called attention to a successful human -inoculation with pure cultures of B. influenzæ which he performed -in 1906. During the present investigation at least 200 men have -volunteered as experimental subjects, and the results of many -different methods of attempting to transmit the disease, have -been disappointing and inconclusive. I will not attempt to -review the reports at present available, as a great deal of the -work done has not yet appeared in print. The important point -is that the results do not affect the various views held as to -the causative agent in pandemic influenza nor the massive evidence -for transmission of the disease under natural epidemic -conditions.</p> - -<p class='c009'>It is my opinion, as expressed above, that practically all of -the population are rapidly infected during such a pandemic as -we have had. The resistant have escaped, and it would appear -to be very difficult to break down this resistance. The human -experiment carried out by Pettenkofer on himself and his assistant -<span class='pageno' id='Page_199'>199</span>with vibrion choleræ is an example, but we have numerous -others demonstrating the same kind of phenomena in most of -our diseases of established bacterial origin. In diphtheria we -have an explanation in the varying antitoxic content of the sera, -but we really know very little of what are the actual factors in -preventing or determining infection among exposed individuals -in the natural history of most diseases. The reports of Leonard -Hill and Gregor are well worth reading in this connection, as -well as the editorial in the same number of the British Medical -Journal. We are not in a position to be very dogmatic on the -causes of epidemics. The mere presence of the bacteria or any -other living virus is not in itself sufficient to explain the phenomenon, -and one of the chief objects of this paper is to indicate -from the collected facts, that in the words of Flexner, “the case -against the influenza bacillus is not proved.”</p> - -<h3 class='c010'><em>Conclusions</em></h3> - -<p class='c011'>1. B. influenzæ is one of a group of hemophilic bacteria and -there are probably strains of this organism which may be differentiated -which will lead to further subdivisions of the group.</p> - -<p class='c009'>2. B. influenzæ as we understand it today, is distinguished -by its morphological and staining characters; its requiring hemoglobin -in some form for its development; its showing symbiotic -reactions with other bacteria which stimulate its growth; the -production of a toxine and its usual low pathogenicity for -animals.</p> - -<p class='c009'>3. The media found most favorable for its growth are those -containing blood with the hemoglobin content altered in certain -ways, (1) by heating, (2) the addition of various chemicals, -(3) by the action of other bacteria or their products. The heated -blood agar I have found to be a most efficient and readily prepared -medium.</p> - -<p class='c009'>4. Since B. influenzæ is so difficult to isolate, it is necessary -to be very cautious in interpreting results unless the greatest -effort has been made to demonstrate the presence of this -organism.</p> - -<p class='c009'>5. B. influenzæ should be considered, from the evidence at -hand, as the bacterial causative agent in epidemic influenza, and -it should be recognized that secondary infections following the -<span class='pageno' id='Page_200'>200</span>primary attack by this organism are both frequent and important. -This view I believe the logical one, unless much more -convincing evidence than we have today may demonstrate -another more probable living virus as the cause.</p> - -<p class='c009'>6. B. influenzæ is a frequent etiological factor in purulent -and chronic bronchitis, broncho-pneumonia and other acute and -chronic respiratory infections, in meningitis, endocarditis, sinusitis, -conjunctivitis and other conditions, as well as in complications -of many other diseases.</p> - -<p class='c009'>7. There are many carriers of the bacillus among our population, -both in apparently normal individuals and in those suffering -from chronic infections of bronchi, sinuses or other parts.</p> - -<p class='c009'>8. The problem of what constitutes resistance or susceptibility -to this infection are as far from solution as they are in -most other respiratory diseases, and the attempts to explain the -reasons for epidemics have been as futile as they are for meningitis -and many other respiratory epidemics.</p> - -<p class='c009'>9. It would not appear that the immunological reaction -against this infection has been discovered, but the possibility -of its being of an antitoxic nature opens an interesting field for -investigation.</p> - -<h3 class='c010'>BIBLIOGRAPHY</h3> - -<table class='table3' summary=''> - <tr> - <td class='c006'>Abrahams, Hallows and French</td> - <td class='c028'>Lancet., 1919; i, p. 1.</td> - </tr> - <tr> - <td class='c006'>Abrahams, Hallows, Eyre and French</td> - <td class='c028'>Lancet., 1917; ii, p. 377.</td> - </tr> - <tr> - <td class='c006'>Abstract of Foreign Literature on Influenza</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1573.</td> - </tr> - <tr> - <td class='c006'>Adrian</td> - <td class='c028'>Quoted by Tedesko, q. v.</td> - </tr> - <tr> - <td class='c006'>Allen</td> - <td class='c028'>Lancet., 1910; i, p. 1263.</td> - </tr> - <tr> - <td class='c006'>Averill, Young and Griffiths</td> - <td class='c028'>British Med. Jour., 1918; ii, p. 111.</td> - </tr> - <tr> - <td class='c006'>Avery</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 2050.</td> - </tr> - <tr> - <td class='c006'>Babes</td> - <td class='c028'>Deutsch. Med. Wochen., 1892; xviii, p. 113.</td> - </tr> - <tr> - <td class='c006'>Batten</td> - <td class='c028'>Lancet., 1910; i, p. 16.</td> - </tr> - <tr> - <td class='c006'>Basile</td> - <td class='c028'>Baumgarten Jahresb., 1907; xxiii., p. 284.</td> - </tr> - <tr> - <td class='c006'>Beall</td> - <td class='c028'>Jour. A. M. A., 1906; xlvi, p. 1442.</td> - </tr> - <tr> - <td class='c006'>Bernstein and Loewe</td> - <td class='c028'>Jour. Infect. Dis., 1919; xxiv, p. 78.</td> - </tr> - <tr> - <td class='c006'>Besancon and Griffon</td> - <td class='c028'>Quoted by Scheller, q. v.</td> - </tr> - <tr> - <td class='c006'>Besson</td> - <td class='c028'>Text-book, translated by Hutchens, 1913.</td> - </tr> - <tr> - <td class='c006'>Blanton and Irons</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1988.</td> - </tr> - <tr> - <td class='c006'>Boggs</td> - <td class='c028'>Amer. Jour. Med. Sci., 1905; cxxx, p. 902.</td> - </tr> - <tr> - <td class='c006'>Brem, Bolling and Casper</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 2138.</td> - </tr> - <tr> - <td class='c006'><span class='pageno' id='Page_201'>201</span>Brentz and Frye</td> - <td class='c028'>Woman’s Med. Jour., 1908; xviii, p. 73.</td> - </tr> - <tr> - <td class='c006'>Brown and Orcutt</td> - <td class='c028'>Jour. Exper. Med., 1918; xxviii, p. 659.</td> - </tr> - <tr> - <td class='c006'>Bruschettini</td> - <td class='c028'>Cent. f. Bakt. Abt. i., 1892; xi, p. 412.</td> - </tr> - <tr> - <td class='c006'>Bruschettini</td> - <td class='c028'>Cent. f. Bakt. Abt. i., 1892; xii, p. 34.</td> - </tr> - <tr> - <td class='c006'>Bruschettini</td> - <td class='c028'>Cent. f. Bakt. Abt. i., 1893; xiv, p. 253.</td> - </tr> - <tr> - <td class='c006'>Bujivid</td> - <td class='c028'>Cent. f. Bakt. Abt. i., 1893; xiii, p. 554.</td> - </tr> - <tr> - <td class='c006'>Canon</td> - <td class='c028'>Die Bakteriologie des Blutes bei Infektionskrankheiten Jena, 1905.</td> - </tr> - <tr> - <td class='c006'>Canon</td> - <td class='c028'>Deutsch. Med. Wochen., 1892; xviii, p. 28.</td> - </tr> - <tr> - <td class='c006'>Cantani</td> - <td class='c028'>Zeit. f. Hyg., 1896; xxiii, p. 265.</td> - </tr> - <tr> - <td class='c006'>Cantani</td> - <td class='c028'>Cent. f. Bakt. Abt. i., 1897; xxii, p. 601.</td> - </tr> - <tr> - <td class='c006'>Cantani</td> - <td class='c028'>Cent. f. Bakt. Abt. i., 1900; xxviii, p. 743.</td> - </tr> - <tr> - <td class='c006'>Cantani</td> - <td class='c028'>Zeit. f. Hyg., 1901; xxxvi, p. 29.</td> - </tr> - <tr> - <td class='c006'>Cantani</td> - <td class='c028'>Cent. f. Bakt. Abt. i., Orig., 1902; xxxii, p. 692.</td> - </tr> - <tr> - <td class='c006'>Cantani</td> - <td class='c028'>Zeit. f. Hyg., 1903; xlii, p. 505.</td> - </tr> - <tr> - <td class='c006'>Capaldi</td> - <td class='c028'>Cent. f. Bakt. Abt. i., 1896; xx, p. 800.</td> - </tr> - <tr> - <td class='c006'>Clemens</td> - <td class='c028'>Munchen. Med. Wochen., 1900; p. 925.</td> - </tr> - <tr> - <td class='c006'>Cohen</td> - <td class='c028'>Annales de l’Instit. Pasteur., 1909; xxiii, p. 273.</td> - </tr> - <tr> - <td class='c006'>Cohen and Fitzgerald</td> - <td class='c028'>Cent. f. Bakt. Abt. i., Orig., 1910; lvi, p. 464.</td> - </tr> - <tr> - <td class='c006'>Cohn</td> - <td class='c028'>Arch. f. Gyn., 1907; lxxxii, p. 695.</td> - </tr> - <tr> - <td class='c006'>Cohn</td> - <td class='c028'>Cent. f. Bakt. Abt. i., ref., 1906; xxxviii, p. 23.</td> - </tr> - <tr> - <td class='c006'>Cole and MacCallum</td> - <td class='c028'>Jour. A. M. A., 1918; lxx, p. 1146.</td> - </tr> - <tr> - <td class='c006'>Cornil and Chantemesse</td> - <td class='c028'>Cent. f. Bakt. Abt., i., 1893; xiii, p. 489.</td> - </tr> - <tr> - <td class='c006'>Couret and Herbert</td> - <td class='c028'>Report at meeting of Amer. Assoc. Path. and Bact., 1919.</td> - </tr> - <tr> - <td class='c006'>Coutant</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1566.</td> - </tr> - <tr> - <td class='c006'>Davis, D. J.</td> - <td class='c028'>Jour. Infect. Dis., 1907; iv, p. 73.</td> - </tr> - <tr> - <td class='c006'>Davis, D. J.</td> - <td class='c028'>Arch. Int. Med., 1908; ii, p. 124.</td> - </tr> - <tr> - <td class='c006'>Davis, D. J.</td> - <td class='c028'>Jour. Infect. Dis., 1910; vii, p. 599.</td> - </tr> - <tr> - <td class='c006'>Davis, D. J.</td> - <td class='c028'>Amer. Jour. Dis. Child., 1911; i, p. 249.</td> - </tr> - <tr> - <td class='c006'>Davis, D. J.</td> - <td class='c028'>Jour. A. M. A., 1915; lxiv, 1814.</td> - </tr> - <tr> - <td class='c006'>Davis, D. J.</td> - <td class='c028'>Jour. Infect. Dis., 1917; xxi, p. 392.</td> - </tr> - <tr> - <td class='c006'>Delius and Kolle</td> - <td class='c028'>Zeit. f. Hyg., 1897; xxiv, p. 327.</td> - </tr> - <tr> - <td class='c006'>Dever, Boles and Case</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 265.</td> - </tr> - <tr> - <td class='c006'>Dick, G. F.</td> - <td class='c028'>Jour. A. M. A., 1918; lxx, p. 1529.</td> - </tr> - <tr> - <td class='c006'>Dick, G. H. and Murray</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1568.</td> - </tr> - <tr> - <td class='c006'>Dujarric de la Riviere</td> - <td class='c028'>Jour. Med. Res., 1918; xxxix, p. 39, review.</td> - </tr> - <tr> - <td class='c006'>Dunn</td> - <td class='c028'>Jour. A. M. A., 1919; lxxi, p. 2128.</td> - </tr> - <tr> - <td class='c006'>Ecker</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1482.</td> - </tr> - <tr> - <td class='c006'>Ely, Lloyd, Hitchcock and Nickson</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 24.</td> - </tr> - <tr> - <td class='c006'>Eyre</td> - <td class='c028'>Jour. Path. and Bact., 1909; xiv, p. 160.</td> - </tr> - <tr> - <td class='c006'>Eyre and Lowe</td> - <td class='c028'>Lancet., 1918; ii, p. 484.</td> - </tr> - <tr> - <td class='c006'>Ferry</td> - <td class='c028'>Jour. Path. and Bact., 1915; xix, p. 488.</td> - </tr> - <tr> - <td class='c006'>Fichtner</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1904; xxxv, p. 374.</td> - </tr> - <tr> - <td class='c006'>Fichtner</td> - <td class='c028'>Baumgarten’s Jahresb., 1906; xxii, p. 207.</td> - </tr> - <tr> - <td class='c006'>Finkler</td> - <td class='c028'>Cent. f. Bakt. Abt., i, 1896; xx, p. 807.</td> - </tr> - <tr> - <td class='c006'>Fleming, A.</td> - <td class='c028'>Lancet., 1919; i, p. 138.</td> - </tr> - <tr> - <td class='c006'><span class='pageno' id='Page_202'>202</span>Fleming, J. S.</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 2137.</td> - </tr> - <tr> - <td class='c006'>Fraenkel</td> - <td class='c028'>Quoted by Howard, q. v.</td> - </tr> - <tr> - <td class='c006'>Friedberger</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1903; xxxiii, p. 401.</td> - </tr> - <tr> - <td class='c006'>Friedlander, McCord, Sladen and Wheeler</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1652.</td> - </tr> - <tr> - <td class='c006'>Ghedini and Breccia</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Ref., 1911; lvii, p. 567.</td> - </tr> - <tr> - <td class='c006'>Ghedini and Fedeli</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Ref., 1910; xlvii, p. 358.</td> - </tr> - <tr> - <td class='c006'>Ghedini</td> - <td class='c028'>Baumgarten’s Jahresb., 1906; xxii, p. 207.</td> - </tr> - <tr> - <td class='c006'>Ghedini</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1907; xliii, p. 407.</td> - </tr> - <tr> - <td class='c006'>Ghon and Preyss</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1902; xxxii, p. 90.</td> - </tr> - <tr> - <td class='c006'>Ghon and Preyss</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1904; xxxv, p. 531.</td> - </tr> - <tr> - <td class='c006'>Giani and Picchi</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Ref., 1906; xxxvii, p. 239.</td> - </tr> - <tr> - <td class='c006'>Gioelli</td> - <td class='c028'>Cent. f. Bakt. Abt., i, 1898; xxii, p. 853.</td> - </tr> - <tr> - <td class='c006'>Goodpasture</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 724.</td> - </tr> - <tr> - <td class='c006'>Gotch and Wittingham</td> - <td class='c028'>British Med. Jour., 1918; ii, p. 82.</td> - </tr> - <tr> - <td class='c006'>Grassberger</td> - <td class='c028'>Zeit. f. Hyg., 1897; xxv, p. 453.</td> - </tr> - <tr> - <td class='c006'>Grassberger</td> - <td class='c028'>Cent. f. Bakt. Abt., i, 1898; xxiii, p. 353.</td> - </tr> - <tr> - <td class='c006'>Greenwood</td> - <td class='c028'>British Med. Jour., 1918; ii, p. 563.</td> - </tr> - <tr> - <td class='c006'>Gregor</td> - <td class='c028'>British Med. Jour., 1919; i, p. 242.</td> - </tr> - <tr> - <td class='c006'>Guiral</td> - <td class='c028'>Reviewed Jour. A. M. A., 1919; lxxii, p. 80.</td> - </tr> - <tr> - <td class='c006'>Guizzetti</td> - <td class='c028'>Reviewed Jour. A. M. A., 1919; lxxii, p. 1111.</td> - </tr> - <tr> - <td class='c006'>Hammond, Rowland and Shore</td> - <td class='c028'>Lancet., 1917; ii, p. 41.</td> - </tr> - <tr> - <td class='c006'>Harris</td> - <td class='c028'>Lancet., 1918; ii, p. 877.</td> - </tr> - <tr> - <td class='c006'>Heyrovsky</td> - <td class='c028'>Wien, Klin. Woch., 1904; xvii, p. 644.</td> - </tr> - <tr> - <td class='c006'>Hicks and Gray</td> - <td class='c028'>Lancet., 1919; i, p. 419.</td> - </tr> - <tr> - <td class='c006'>Hill, Leonard</td> - <td class='c028'>British Med. Jour., 1919; i, p. 238.</td> - </tr> - <tr> - <td class='c006'>Holman</td> - <td class='c028'>Jour. Infect. Dis., 1914; xv, p. 293.</td> - </tr> - <tr> - <td class='c006'>Holman</td> - <td class='c028'>Jour. Med. Res., 1916; xxxv, p. 151.</td> - </tr> - <tr> - <td class='c006'>Horder</td> - <td class='c028'>Lancet., 1918; ii, p. 871.</td> - </tr> - <tr> - <td class='c006'>Horder</td> - <td class='c028'>36th An. Rep. Loc. Govt. Bd., 1906; p. 279.</td> - </tr> - <tr> - <td class='c006'>Howard and Ingersoll</td> - <td class='c028'>Amer. Jour. Med. Sci., 1898; cxv, p. 520.</td> - </tr> - <tr> - <td class='c006'>Huntoon</td> - <td class='c028'>Report at meeting of Amer. Assoc. Path. and Bact., 1919.</td> - </tr> - <tr> - <td class='c006'>Hurley</td> - <td class='c028'>Letter. Boston Med. Surg. Jour., 1918; clxxix, p. 691.</td> - </tr> - <tr> - <td class='c006'>Huyghe</td> - <td class='c028'>Quoted by Scheller, q. v.</td> - </tr> - <tr> - <td class='c006'>Influenza Committee Advis. Bd. to the D. G. M. S.</td> - <td class='c028'>British Med. Jour., 1918; ii, p. 509.</td> - </tr> - <tr> - <td class='c006'>Jacobsohn</td> - <td class='c028'>C. r. Soc. Biol., 1901; xix, p. 553.</td> - </tr> - <tr> - <td class='c006'>Jehle</td> - <td class='c028'>Quoted by Madison, q. v.</td> - </tr> - <tr> - <td class='c006'>Jochmann</td> - <td class='c028'>Cent. f. Bakt. Abt. i, Ref., 1906; xxxviii, p. 661, and quoted by Scheller, q. v.</td> - </tr> - <tr> - <td class='c006'>Jordan</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 1542.</td> - </tr> - <tr> - <td class='c006'>Keegan</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1051.</td> - </tr> - <tr> - <td class='c006'>Keeton and Cushman</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1962.</td> - </tr> - <tr> - <td class='c006'>Kinsella</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 717.</td> - </tr> - <tr> - <td class='c006'>Kitasato</td> - <td class='c028'>Deutsch. Med. Wochen., 1892; xviii, p. 28.</td> - </tr> - <tr> - <td class='c006'><span class='pageno' id='Page_203'>203</span>Klein</td> - <td class='c028'>British Med. Jour., 1892; p. 170.</td> - </tr> - <tr> - <td class='c006'>Klieneberger</td> - <td class='c028'>Quoted by Scheller, q. v.</td> - </tr> - <tr> - <td class='c006'>Koch</td> - <td class='c028'>Quoted by Davis, 1915; q. v.</td> - </tr> - <tr> - <td class='c006'>Kossel</td> - <td class='c028'>Quoted by Ritchie, q. v.</td> - </tr> - <tr> - <td class='c006'>Kotz</td> - <td class='c028'>Jour. Lab. Clin. Med., 1919; iv, p. 424.</td> - </tr> - <tr> - <td class='c006'>Krage</td> - <td class='c028'>Baumgarten’s Jahresb., 1910; xxvi, p. 1063.</td> - </tr> - <tr> - <td class='c006'>Kraus</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 292. Medical News.</td> - </tr> - <tr> - <td class='c006'>Kretz</td> - <td class='c028'>Cent. f. Bakt. Abt., i, 1898; xxiii, p. 24.</td> - </tr> - <tr> - <td class='c006'>Krumbhaar</td> - <td class='c028'>Lancet., 1918; ii, p. 123.</td> - </tr> - <tr> - <td class='c006'>Lacy</td> - <td class='c028'>Jour. Lab. and Clin. Med., 1918; iv, p. 55.</td> - </tr> - <tr> - <td class='c006'>Lamb and Brannin</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 1056.</td> - </tr> - <tr> - <td class='c006'>Latapie</td> - <td class='c028'>C. r. Soc. Biol., 1904; lv, p. 1272.</td> - </tr> - <tr> - <td class='c006'>Latapie</td> - <td class='c028'>Jour. Med. Res., 1918; xxxix, review.</td> - </tr> - <tr> - <td class='c006'>Levinthal</td> - <td class='c028'>Zeit. f. Hyg., 1918; lxxxvi, p. 1.</td> - </tr> - <tr> - <td class='c006'>Libman</td> - <td class='c028'>Trans. Assoc. Amer. Phys., 1912; xxvii, p. 157.</td> - </tr> - <tr> - <td class='c006'>Lindenthal</td> - <td class='c028'>Wien. Klin. Wochen., 1897; x, p. 353.</td> - </tr> - <tr> - <td class='c006'>Little, Garofalo and Williams</td> - <td class='c028'>Lancet., 1912; ii, p. 34.</td> - </tr> - <tr> - <td class='c006'>Longo</td> - <td class='c028'>Baumgarten’s Jahresb., 1908; xxiv, p. 660.</td> - </tr> - <tr> - <td class='c006'>Lord</td> - <td class='c028'>Boston Med. and Surg. Jour., 1902; cxlvii, p. 662.</td> - </tr> - <tr> - <td class='c006'>Lord</td> - <td class='c028'>Boston Med. and Surg. Jour., 1905; clii, pp. 537 and 574.</td> - </tr> - <tr> - <td class='c006'>Lord</td> - <td class='c028'>Jour. Med. Res., 1908; xix, p. 295.</td> - </tr> - <tr> - <td class='c006'>Lord, Scott and Nye</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 188.</td> - </tr> - <tr> - <td class='c006'>Luerssen</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1904; xxv, p. 434.</td> - </tr> - <tr> - <td class='c006'>MacCallum</td> - <td class='c028'>Monog. of Rockefeller Instit. for Med. Res., 1919; No. 10.</td> - </tr> - <tr> - <td class='c006'>Macdonald and Lyth</td> - <td class='c028'>British Med. Jour., 1918; ii, p. 488.</td> - </tr> - <tr> - <td class='c006'>Macdonald, Ritchie, Fox and White</td> - <td class='c028'>British Med. Jour., 1918; ii, p. 481.</td> - </tr> - <tr> - <td class='c006'>Madison</td> - <td class='c028'>Amer. Jour. Med. Sci., 1910; cxxxix, p. 527.</td> - </tr> - <tr> - <td class='c006'>Madison</td> - <td class='c028'>Jour. A. M. A., 1910; lv, p. 477.</td> - </tr> - <tr> - <td class='c006'>Mann, Rainaford and Warren</td> - <td class='c028'>Med. Surg. Rep. of Roosevelt Hosp., 1915.</td> - </tr> - <tr> - <td class='c006'>Martin, C. J. .</td> - <td class='c028'>British Med. Jour., 1918; ii, p. 281.</td> - </tr> - <tr> - <td class='c006'>Matthews</td> - <td class='c028'>Lancet., 1918; ii, p. 104.</td> - </tr> - <tr> - <td class='c006'>Medalia</td> - <td class='c028'>Boston Med. Surg. Jour., 1919; clxxx, p. 323.</td> - </tr> - <tr> - <td class='c006'>Menko</td> - <td class='c028'>Quoted by Scheller.</td> - </tr> - <tr> - <td class='c006'>Menschikow</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Ref., 1906; xxxvii, p. 490.</td> - </tr> - <tr> - <td class='c006'>Meunier</td> - <td class='c028'>Cent. f. Bakt. Abt., i, 1897; xxi, p. 689.</td> - </tr> - <tr> - <td class='c006'>Meunier</td> - <td class='c028'>La Sam. Med., 1898. Quoted by Lord and Scheller, q. v.</td> - </tr> - <tr> - <td class='c006'>Minaker and Irvine</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 847.</td> - </tr> - <tr> - <td class='c006'>Mix</td> - <td class='c028'>New York Med. Jour., 1918; cviii, p. 709.</td> - </tr> - <tr> - <td class='c006'>Moon</td> - <td class='c028'>Quoted by Davis, 1915; q. v.</td> - </tr> - <tr> - <td class='c006'>Moszkowski</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Ref., 1902; xxxii, p. 272.</td> - </tr> - <tr> - <td class='c006'>Munro</td> - <td class='c028'>British Med. Jour., 1919; i, p. 338.</td> - </tr> - <tr> - <td class='c006'>Muir and Wilson</td> - <td class='c028'>British Med. Jour., 1919; i, p. 3.</td> - </tr> - <tr> - <td class='c006'>McMeekin</td> - <td class='c028'>Reviewed Jour. A. M. A., 1919; lxxii.</td> - </tr> - <tr> - <td class='c006'><span class='pageno' id='Page_204'>204</span>McPhedran</td> - <td class='c028'>Canadian Med. Assoc. Jour., 1913; iii, p. 548</td> - </tr> - <tr> - <td class='c006'>Nastjukoff</td> - <td class='c028'>Cent. f. Bakt. Abt., i, 1895; xvii, p. 492.</td> - </tr> - <tr> - <td class='c006'>Nichols and Stimmel</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 174.</td> - </tr> - <tr> - <td class='c006'>Norris and Pappenheimer</td> - <td class='c028'>Jour. Exper. Med., 1905; vii, p. 450.</td> - </tr> - <tr> - <td class='c006'>Nuzum, Pilot, Stangl and Bonar</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1562.</td> - </tr> - <tr> - <td class='c006'>Odaira</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1911; lxi, p. 289.</td> - </tr> - <tr> - <td class='c006'>Oertel</td> - <td class='c028'>Canadian Med. Surg. Jour., 1919; ix, p. 339.</td> - </tr> - <tr> - <td class='c006'>Opie, Freeman, Blake, Small and Rivers</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, pp. 108 and 556.</td> - </tr> - <tr> - <td class='c006'>Orticoni and Barbie</td> - <td class='c028'>Reviewed Jour. A. M. A., 1919; lxxii, p. 228.</td> - </tr> - <tr> - <td class='c006'>Orticoni, Barbie and Leclerc</td> - <td class='c028'>New York Med. Jour., 1918; cviii, p. 730.</td> - </tr> - <tr> - <td class='c006'>Paltauf</td> - <td class='c028'>Wien. Klin. Wochen., 1899; xii, p. 576.</td> - </tr> - <tr> - <td class='c006'>Paranhos</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1909; l, p. 607.</td> - </tr> - <tr> - <td class='c006'>Park</td> - <td class='c028'>Reported at Meeting of Amer. Assoc. Path. and Bact., 1919.</td> - </tr> - <tr> - <td class='c006'>Parker</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 476.</td> - </tr> - <tr> - <td class='c006'>Patrick</td> - <td class='c028'>Lancet., 1919; i, p. 137.</td> - </tr> - <tr> - <td class='c006'>Pfeiffer</td> - <td class='c028'>Deutsch. Med. Wochen., 1892; xviii, p. 28.</td> - </tr> - <tr> - <td class='c006'>Pfeiffer</td> - <td class='c028'>Zeit. f. Hyg., 1893; xiii, p. 357.</td> - </tr> - <tr> - <td class='c006'>Pfeiffer and Beck</td> - <td class='c028'>Deutsch. Med. Wochen., 1893; xviii, p. 465.</td> - </tr> - <tr> - <td class='c006'>Pieliche</td> - <td class='c028'>Berl. Klin. Wochen., 1894; xxxi, p. 534.</td> - </tr> - <tr> - <td class='c006'>Poliak</td> - <td class='c028'>Wien. Klin. Wochen., 1908; xxi, p. 973.</td> - </tr> - <tr> - <td class='c006'>Pritchett and Stillman</td> - <td class='c028'>Jour. Exper. Med., 1919; xxix, p. 259.</td> - </tr> - <tr> - <td class='c006'>Rapaport</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 633.</td> - </tr> - <tr> - <td class='c006'>Richards and Gurd</td> - <td class='c028'>Montreal Med. Jour., 1907; xxxv, p. 541.</td> - </tr> - <tr> - <td class='c006'>Richter</td> - <td class='c028'>Cent. f. Bakt. Abt., i, 1894; xxxi, p. 832.</td> - </tr> - <tr> - <td class='c006'>Ritchie</td> - <td class='c028'>Jour. Path. and Bact., 1911; xiv, p. 615.</td> - </tr> - <tr> - <td class='c006'>Rivers</td> - <td class='c028'>Bull. Johns Hopkins Hosp., 1919; xxx, p. 129.</td> - </tr> - <tr> - <td class='c006'>Robertson, H. E.</td> - <td class='c028'>Jour. A. M. A., 1918; lxx, p. 1533.</td> - </tr> - <tr> - <td class='c006'>Robertson, W. F.</td> - <td class='c028'>British Med. Jour., 1918; ii, p. 680.</td> - </tr> - <tr> - <td class='c006'>Rosenow</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 1604.</td> - </tr> - <tr> - <td class='c006'>Rosenthal</td> - <td class='c028'>These. Paris., 1900.</td> - </tr> - <tr> - <td class='c006'>Rucker and Wenner</td> - <td class='c028'>New York Med. Jour., 1918; cviii, p. 1066.</td> - </tr> - <tr> - <td class='c006'>Saathoff</td> - <td class='c028'>Munch. Med. Wochen., 1907; p. 2220.</td> - </tr> - <tr> - <td class='c006'>Sacquepee</td> - <td class='c028'>Paris Med., 1913; xxxv, p. 208.</td> - </tr> - <tr> - <td class='c006'>Sahli</td> - <td class='c028'>Reviewed Jour. A. M. A., 1919; lxxii, pp. 686 and 111.</td> - </tr> - <tr> - <td class='c006'>Scheller</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1909; l, p. 503.</td> - </tr> - <tr> - <td class='c006'>Scheller</td> - <td class='c028'>Kolle and Wassermann, 1912; v, p. 1257.</td> - </tr> - <tr> - <td class='c006'>Schlagenhaufer</td> - <td class='c028'>Quoted by Scheller, q. v.</td> - </tr> - <tr> - <td class='c006'>Schofield and Cynn</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 981.</td> - </tr> - <tr> - <td class='c006'>Schultes</td> - <td class='c028'>Quoted by Scheller, q. v.</td> - </tr> - <tr> - <td class='c006'>Slatineanu</td> - <td class='c028'>C. r. Soc. Biol., 1901; xxix, p. 850.</td> - </tr> - <tr> - <td class='c006'>Slatineanu</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1906; xli, p. 185.</td> - </tr> - <tr> - <td class='c006'>Slawyk</td> - <td class='c028'>Zeit. f. Hyg., 1899; xxxii, p. 443.</td> - </tr> - <tr> - <td class='c006'>Smith, F. J.</td> - <td class='c028'>Lancet., 1908; i, p. 1201.</td> - </tr> - <tr> - <td class='c006'>Smith, W. H.</td> - <td class='c028'>Jour. Boston Soc. Med. Sci., 1899; iii, p. 274.</td> - </tr> - <tr> - <td class='c006'><span class='pageno' id='Page_205'>205</span>Smith, Theobald</td> - <td class='c028'>Jour. Med. Res., 1913; xxix, p. 291.</td> - </tr> - <tr> - <td class='c006'>Soper</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1899.</td> - </tr> - <tr> - <td class='c006'>Soper</td> - <td class='c028'>Jour. Lab. Clin. Med., 1918; iii, pp. 560-567.</td> - </tr> - <tr> - <td class='c006'>Spat</td> - <td class='c028'>Berl. Klin. Wochen., 1907; xliv, p. 1173.</td> - </tr> - <tr> - <td class='c006'>Spooner, Scott and Heath</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 155.</td> - </tr> - <tr> - <td class='c006'>Stone and Swif</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 487.</td> - </tr> - <tr> - <td class='c006'>Strause and Bloch</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1568.</td> - </tr> - <tr> - <td class='c006'>Susswein</td> - <td class='c028'>Wien. Klin. Wochen., 1901; xiv, p. 1149.</td> - </tr> - <tr> - <td class='c006'>Synnott and Clark</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1816.</td> - </tr> - <tr> - <td class='c006'>Tedesko</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1907; xliii, pp. 322, 432, 548.</td> - </tr> - <tr> - <td class='c006'>Thalhimer</td> - <td class='c028'>Bull. Johns Hopkins Hosp., 1911; xxii, p. 293.</td> - </tr> - <tr> - <td class='c006'>Thalhimer</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Orig., 1914; lxxiv, p. 189.</td> - </tr> - <tr> - <td class='c006'>Thursfield</td> - <td class='c028'>Quart. Jour. Med., 1910; iv, p. 7.</td> - </tr> - <tr> - <td class='c006'>Tunnicliff</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1733.</td> - </tr> - <tr> - <td class='c006'>Tunnicliff and Davis</td> - <td class='c028'>Jour. Infect. Dis., 1907; iv, p. 66.</td> - </tr> - <tr> - <td class='c006'>Vagede</td> - <td class='c028'>Baumgarten’s Jahresb., 1903; xix, p. 244.</td> - </tr> - <tr> - <td class='c006'>Voges</td> - <td class='c028'>Berl. Klin. Wochen., 1894; xxxi, p. 868.</td> - </tr> - <tr> - <td class='c006'>Weil</td> - <td class='c028'>Cent. f. Bakt. Abt., i, Ref., 1910; xlvii, p. 359.</td> - </tr> - <tr> - <td class='c006'>Wittingham and Sims</td> - <td class='c028'>Lancet., 1918; ii, p. 865.</td> - </tr> - <tr> - <td class='c006'>Wolbach</td> - <td class='c028'>Bull. Johns Hopkins Hosp., 1919; xxx, p. 104.</td> - </tr> - <tr> - <td class='c006'>Wollstein</td> - <td class='c028'>Jour. Exper. Med., 1906; viii, p. 681.</td> - </tr> - <tr> - <td class='c006'>Wollstein</td> - <td class='c028'>Jour. Exper. Med., 1911; xiv, p. 73.</td> - </tr> - <tr> - <td class='c006'>Wollstein</td> - <td class='c028'>Jour. Exper. Med., 1915; xxii, p. 445.</td> - </tr> - <tr> - <td class='c006'>Wollstein and Goldbloom</td> - <td class='c028'>Amer. Jour. Dis. Child., 1919; xvii, p. 165.</td> - </tr> - <tr> - <td class='c006'>Woollacott</td> - <td class='c028'>British Med. Jour., 1918; ii, p. 530.</td> - </tr> - <tr> - <td class='c006'>Wright, J. H.</td> - <td class='c028'>Boston Med. Surg. Jour., 1905; clii, p. 496.</td> - </tr> - <tr> - <td class='c006'>Wynekoop</td> - <td class='c028'>Jour. A. M. A., 1903; xl, p. 574.</td> - </tr> -</table> - -<div class='chapter'> - <span class='pageno' id='Page_207'>207</span> - <h2 class='c005'>THE PATHOLOGY OF EPIDEMIC INFLUENZA</h2> -</div> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>By <span class='sc'>Oskar Klotz</span>, M. D., C. M.</div> - </div> -</div> - -<p class='c008'>The discussion to be entered into in this report will be limited -to an experience dealing with epidemic influenza as it was met -with in the emergency Military Hospital in Pittsburgh. We -shall largely confine our attention to the observations which -came directly under our supervision, and in as much as this -investigation was continued during the epidemic as it swept -over this district, the intensive study was limited to a time period -of about five weeks. During this period much material was -collected, which since then, has taken us a considerable time to -analyze. We have thought it more valuable to restrict our discussion -to this material in that it illustrates the pathological -lesions as they occurred during the acute stage of the disease. -We have not entered upon a discussion of the sequelæ or the -chronic lesions which are not uncommonly found following in the -wake of an acute epidemic nor do we deal with the lesions arising -in cases of sporadic influenza, such as are always with us. As -is so well illustrated in the literature, there is probably no disease -which has so many late complications and sequelæ as influenza. -The investigations upon the protean lesions have been fully reported -in numerous papers during the intervals between epidemics. -A comprehensive bibliography upon influenza will be -found at the end of the extensive report by Leichtenstern (1905). -There is very much less accurate information available upon the -actual lesions present during the acute disease when present in -epidemic or pandemic form, than upon the many clinical complications -in various systems and organs. In fact, our knowledge -of the pathology of influenza lies more largely in the field of -associated lesions such as the late events in the bronchi, the -sinuses of the head, abscesses, meningitis and other conditions, -rather to be viewed as complications than as portions of the -disease. There are relatively few thorough pathological analyses -of the influenza lesions as they are found in the acute epidemic -disease.</p> - -<p class='c009'><span class='pageno' id='Page_208'>208</span>A fair literature has already appeared upon epidemic influenza -from the many countries and regions over which the present -pandemic (1918) has swept. These reports by various authors -are offered from different viewpoints, some investigators being -impressed with certain features which they bring into marked -prominence in their reports. It thus happens that up to the -present there is a decided lack of uniformity in the opinions -expressed upon different phases of the subject. The nature of -the pathology of the past epidemic has given rise to many expressions -of opinion as well as dogmatic statements, which are found -to differ from those of others. It seems to us that this apparent -confusion arises partly through the somewhat different characteristics -of the disease as it has made its appearance in different -centers. We hear it repeatedly stated that the types found -in different military camps and urban communities were quite -unlike those of other regions. It is evident that such differences -in the clinical course actually did exist and that the epidemic -though having a common foundation upon which the disease process -was built differed in what might be looked upon as symbiotic -complications during the early and acute stages. Differences in -the nature of the findings in various communities also probably -lay in the fact that the bacterial flora associated with the causative -agent of influenza was quite different in different regions. -We mention this here so that a full appreciation will be obtained -for the differences in the pathological characters of the disease -as they are found in one region or another. We appreciate, of -course, that if the concomitant bacterial flora associated with the -underlying cause of influenza, differs in different regions, so, too, -will the bodily reactions differ within certain degrees. We are -becoming more familiar with different types of bacteria, and the -resulting inflammatory reaction which is often unique or at least -particular, and that not uncommonly the nature of the inflammatory -process suggests the type of bacterium involved. This -argument, of course, must not be driven too far, for we well -know that the same micro-organisms under different conditions -can cause types of inflammatory reactions wholly divergent.</p> - -<p class='c009'>In as much as our observations are confined to a particular -group of cases and the study of these was undertaken during -the five weeks of the acute epidemic, these results are not to be -compared with the collected statistics on influenza as they shall -<span class='pageno' id='Page_209'>209</span>be made over a period beginning with the onset of the epidemic -and ending with the last vestiges remaining after months or it -may be years of time. Our observations are to be considered -only in the light of the events taking place during the height of -an epidemic wave. In as much as influenza presents itself -during an epidemic in different forms, we shall again mainly -limit the report upon our investigations of those cases having -respiratory lesions. Our acute observations were made upon -the tissues of those who had died of this disease. It is impossible, -or nearly so, to fully study the tissues of those with lesser -lesions and who recover. Hence, if we divide the influenza cases -into those (1) without pulmonary lesions and (2) those with -pulmonary lesions, we must state that all of our cases coming -to autopsy fall in the second group. It is true that one of these -having pulmonary lesions was not brought to his fatal termination -by them but by a septicæmia arising in the middle ear. He -had distinct lesions in his lungs. In other words, our autopsy -material represents epidemic influenza in which the lung was -definitely involved in an inflammatory state. In all but one of -these the pulmonary lesion was the cause of death.</p> - -<p class='c009'>No doubt, if opportunity had presented itself to follow a large -epidemic through months of its progress, during which late complications -in various portions of the body would make their -appearance, our analysis would give a different picture and the -pulmonary factor for the fatal termination would not be in such -prominence.</p> - -<p class='c009'>Of the first group, those cases of epidemic influenza not showing -pulmonary lesions, we will have very little to say, in as much -as the pathological investigations of them is impossible, or nearly -so, during the height of the disease.</p> - -<p class='c009'>Such cases apparently do not die at this period. I am willing -to admit that individuals without pulmonary involvement may -succumb, but I question whether their death has been due to -the result of the influenzal lesions, be it in nose, pharynx, larynx -or trachea, or be it in the intestine, but rather that the fatal -termination occurred later in the course of this complex disease, -when distant vital organs became involved or incapacitated in a -toxemia or secondary bacterial invasion. We must clearly distinguish -these cases from the clear-cut ones of epidemic influenza, -looking upon the new circumstances as complications aside from -<span class='pageno' id='Page_210'>210</span>the original disease. Such, for example, is the case we have -mentioned where a fatal streptococcus bacteriæmia followed in -the wake of an otitis media. In our experience we have not had -a fatal case of the acute epidemic disease in which the lung was -not involved.</p> - -<p class='c009'>In types of epidemic disease such as we have just had, where -the epidemic wave has passed over in a period of four or five -weeks, there is always much to be regretted which has been left -undone. We tried as far as possible to gain all the information -available at the time of collecting our materials and of laying -aside such of the work which could be accomplished at a subsequent -date. The materials were collected from divergent sources -in the cadaver, and the more perishable substances were analyzed -immediately. During the period of the epidemic 32 autopsies -were performed and as much use as possible was made of each -for a thorough comprehension of the lesions.</p> - -<h3 class='c010'><em>Materials</em></h3> - -<p class='c011'>During the period of our work 639 patients were admitted to -the hospital suffering from clinical influenza. The cases varied -in type from the very mild to the extremely ill. The majority -of the cases were of the type of “three-day fever.” Clinically -81 cases developed pneumonia, and of these, 35 died. It would, -of course, be impossible to say how many other individuals had -a pulmonary involvement which could not be recognized clinically. -In fact, some of the cases which did come to autopsy were only -recognized as having a pulmonary involvement when the lungs -were examined outside of the body. The physicians freely admitted -that the physical signs were quite unusual and unlike those -of the ordinary forms of pneumonia. In fact, except for the -fact that we were living in the midst of an epidemic of respiratory -infections, there was nothing to make the clinician suspect -that many of these cases had a pulmonary involvement. -Obviously, when the recognized signs of different types of pneumonia -made their appearance, the clinician did not fail to make -proper interpretation of the lung involvement. This, as we shall -discuss later, is an event superadded to a lung condition which -pathologically must be recognized as pneumonia (inflammation) -and which differs so decidedly from what we know of as croupous -or lobar pneumonia, as well as ordinary broncho-pneumonia that -<span class='pageno' id='Page_211'>211</span>it would be incorrect to include them under this heading, although -the distribution of the lesion may have lobar, bronchial or lobular -characters.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE I</div> - </div> -</div> - -<table class='table2' summary='TABLE I'> - <tr> - <th class='bttd bbt c016' colspan='2'><span class='sc'>Date 1918</span></th> - <th class='bttd bbt c016'><span class='sc'>Patients Admitted</span></th> - <th class='bttd bbt c016'><span class='sc'>Patients Discharged</span></th> - <th class='bttd bbt c016'><span class='sc'>Cases in Hospital</span></th> - <th class='bttd bbt c017'><span class='sc'>Deaths</span></th> - </tr> - <tr> - <td class='c015'>October</td> - <td class='c018'>5</td> - <td class='c018'>65</td> - <td class='c018'>0</td> - <td class='c018'>65</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>6</td> - <td class='c018'>23</td> - <td class='c018'>0</td> - <td class='c018'>88</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>7</td> - <td class='c018'>61</td> - <td class='c018'>0</td> - <td class='c018'>149</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>8</td> - <td class='c018'>77</td> - <td class='c018'>0</td> - <td class='c018'>225</td> - <td class='c019'>1</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>9</td> - <td class='c018'>42</td> - <td class='c018'>1</td> - <td class='c018'>266</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>10</td> - <td class='c018'>35</td> - <td class='c018'>1</td> - <td class='c018'>300</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>11</td> - <td class='c018'>9</td> - <td class='c018'>0</td> - <td class='c018'>307</td> - <td class='c019'>2</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>12</td> - <td class='c018'>2</td> - <td class='c018'>16</td> - <td class='c018'>290</td> - <td class='c019'>3</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>13</td> - <td class='c018'>10</td> - <td class='c018'>0</td> - <td class='c018'>298</td> - <td class='c019'>2</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>14</td> - <td class='c018'>1</td> - <td class='c018'>18</td> - <td class='c018'>278</td> - <td class='c019'>3</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>15</td> - <td class='c018'>4</td> - <td class='c018'>13</td> - <td class='c018'>266</td> - <td class='c019'>3</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>16</td> - <td class='c018'>9</td> - <td class='c018'>23</td> - <td class='c018'>248</td> - <td class='c019'>4</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>17</td> - <td class='c018'>10</td> - <td class='c018'>19</td> - <td class='c018'>235</td> - <td class='c019'>4</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>18</td> - <td class='c018'>16</td> - <td class='c018'>34</td> - <td class='c018'>217</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>19</td> - <td class='c018'>38</td> - <td class='c018'>29</td> - <td class='c018'>225</td> - <td class='c019'>1</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>20</td> - <td class='c018'>27</td> - <td class='c018'>0</td> - <td class='c018'>252</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>21</td> - <td class='c018'>37</td> - <td class='c018'>43</td> - <td class='c018'>245</td> - <td class='c019'>1</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>22</td> - <td class='c018'>33</td> - <td class='c018'>7</td> - <td class='c018'>270</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>23</td> - <td class='c018'>14</td> - <td class='c018'>20</td> - <td class='c018'>263</td> - <td class='c019'>2</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>24</td> - <td class='c018'>20</td> - <td class='c018'>17</td> - <td class='c018'>266</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>25</td> - <td class='c018'>27</td> - <td class='c018'>21</td> - <td class='c018'>272</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>26</td> - <td class='c018'>10</td> - <td class='c018'>29</td> - <td class='c018'>250</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>27</td> - <td class='c018'>18</td> - <td class='c018'>3</td> - <td class='c018'>265</td> - <td class='c019'>1</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>28</td> - <td class='c018'>10</td> - <td class='c018'>31</td> - <td class='c018'>243</td> - <td class='c019'>3</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>29</td> - <td class='c018'>6</td> - <td class='c018'>16</td> - <td class='c018'>231</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>30</td> - <td class='c018'>11</td> - <td class='c018'>27</td> - <td class='c018'>215</td> - <td class='c019'>1</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>31</td> - <td class='c018'>2</td> - <td class='c018'>15</td> - <td class='c018'>202</td> - <td class='c019'>2</td> - </tr> - <tr> - <td class='c015'>November</td> - <td class='c018'>1</td> - <td class='c018'>2</td> - <td class='c018'>18</td> - <td class='c018'>185</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>2</td> - <td class='c018'>4</td> - <td class='c018'>18</td> - <td class='c018'>170</td> - <td class='c019'>1</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>3</td> - <td class='c018'>5</td> - <td class='c018'>1</td> - <td class='c018'>174</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>4</td> - <td class='c018'>2</td> - <td class='c018'>19</td> - <td class='c018'>156</td> - <td class='c019'>1</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>5</td> - <td class='c018'>5</td> - <td class='c018'>0</td> - <td class='c018'>161</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c016'>〃</td> - <td class='c018'>6</td> - <td class='c018'>4</td> - <td class='c018'>16</td> - <td class='c018'>149</td> - <td class='c019'>0</td> - </tr> - <tr> - <td class='c015'> </td> - <td class='c018'> </td> - <td class='c018'><hr /></td> - <td class='c018'> </td> - <td class='c018'> </td> - <td class='c019'><hr /></td> - </tr> - <tr> - <td class='bbt c018' colspan='2'>Admissions.</td> - <td class='bbt c018'>639</td> - <td class='bbt c018'> </td> - <td class='bbt c018'> </td> - <td class='bbt c019'>35</td> - </tr> -</table> - -<p class='c009'>The individuals admitted to this hospital were obtained from -the two military camps at the University of Pittsburgh and the -Carnegie School of Technology. All of them were enrolled in -<span class='pageno' id='Page_212'>212</span>the army service and ranged from the ages of 18 to 30. They -were vigorous individuals, who had passed their physical examinations -for the army. The epidemic made its appearance in -these camps on October 2, rapidly ascending from a report of -two ill on October 2, four on October 3, eight on October 4, to -65 on October 5. On October 11 there were 307 cases in the -hospital.</p> - -<p class='c009'>Of these cases 35 died, the day of death being indicated in the -following table.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE II</div> - </div> -</div> - -<table class='table1' summary='TABLE II'> - <tr> - <th class='bttd bbt c030'><span class='sc'>Day of Disease on Which Death Occurred</span></th> - <th class='bttd bbt blt c030'><span class='sc'>Number of Cases</span></th> - </tr> - <tr> - <td class='c033'>Third</td> - <td class='blt c030'>1</td> - </tr> - <tr> - <td class='c033'>Fourth</td> - <td class='blt c030'>3</td> - </tr> - <tr> - <td class='c033'>Fifth</td> - <td class='blt c030'>4</td> - </tr> - <tr> - <td class='c033'>Sixth</td> - <td class='blt c030'>4</td> - </tr> - <tr> - <td class='c033'>Seventh</td> - <td class='blt c030'>4</td> - </tr> - <tr> - <td class='c033'>Eighth</td> - <td class='blt c030'>5</td> - </tr> - <tr> - <td class='c033'>Ninth</td> - <td class='blt c030'>3</td> - </tr> - <tr> - <td class='c033'>Tenth</td> - <td class='blt c030'>4</td> - </tr> - <tr> - <td class='c033'>Eleventh</td> - <td class='blt c030'>3</td> - </tr> - <tr> - <td class='c033'>Thirteenth</td> - <td class='blt c030'>1</td> - </tr> - <tr> - <td class='c033'>Fourteenth</td> - <td class='blt c030'>1</td> - </tr> - <tr> - <td class='c033'>Twentieth</td> - <td class='blt c030'>1</td> - </tr> - <tr> - <td class='bbt c033'>Twenty-third</td> - <td class='bbt blt c030'>1</td> - </tr> -</table> - -<p class='c009'>The time as indicated in the above table has no relation to the -length of time that the patients were ill of pneumonia, but refer -to the period of illness from the beginning of the influenza. The -duration of the pneumonia is indicated in another table.</p> - -<p class='c009'>Of the 35 fatal cases 32 came to autopsy. Facilities were available -to do the work very satisfactorily, in that the hospital was -well provided with a modern post-mortem room and its accessories. -The notes on the autopsies were taken immediately and -fully, and the materials for subsequent study were collected in -different types of preserving fluid. Portions of tissue were collected -from all of the organs for microscopical study, while fluids -from the chest, lungs, bronchi and heart were obtained for bacteriological -investigations and for some chemical analyses.</p> - -<p class='c009'>Added to the above material we also had the opportunity of -reviewing and studying the lesions of 18 autopsies performed by -<span class='pageno' id='Page_213'>213</span>Dr. J. W. McMeans. These cases were very similar to our own -series, in that they were cases of epidemic influenza amongst -soldiers who were being cared for at the St. Francis Hospital. -The disease processes were quite alike in the two series, and the -analyses made by Dr. McMeans are comparable in our own and -serve as a means of checking our results obtained in another -institution. The similarity of the lesions in the lungs and other -organs serve to indicate that what is reported in this paper is an -index of the nature of the lesions of epidemic influenza as it -occurred in the Pittsburgh district. In a few instances the -autopsies performed by Dr. McMeans revealed more advanced -pulmonary lesions with abscess and gangrene than were noted in -the cases autopsied at the Military Hospital. The process, however, -in the two series of autopsies was identical.</p> - -<h3 class='c010'><em>General External Features</em></h3> - -<p class='c011'>There were no external characteristics of the bodies which -were autopsied by us which were constant. Some features were -more commonly present than others. Of these the cyanosis of -the face, head, neck and shoulders, and in a few instances of the -upper extremities, attracted our attention more than any other. -This cyanosis was present in over one-half of the number of -cases, and it was confined almost always to the upper part of -the body. The face, ears and neck were always more affected -than other parts. This cyanosis bore no relation to the length of -time after death when the body was viewed, as we found that -when it was present during life it maintained its prominent -appearance for a long time after death.</p> - -<p class='c009'>The cyanosis differed from the bright hue or flush as it is at -times observed in ordinary pneumonia, the color in these instances -being of a dark purple, or better a purplish blue. The -lips and ears showed the most intense color. The cyanosis was -not associated with any evidence of œdema. The capillaries of -the tissues were filled with blood which was of a very dark character. -Cyanosis could also be seen in the finger tips about the -nails. This was more marked in the upper extremities than in -the lower. The skin of the body rarely showed any cyanosis, -these tissues being quite pale, or at times showing a slightly -yellowish tinge. In one instance the cyanosis of the head and -<span class='pageno' id='Page_214'>214</span>neck was accompanied by a slight purplish rash upon the upper -portion of the chest. This rash was of a petechial kind, there -being slight hemorrhage into the tissues. The lesion, however, -was not of the blotchy purpuric type which has been observed -by others during this and past epidemics (Cole). This single case -is the only one where we had evidence of superficial hemorrhages -into the skin.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE III</div> - </div> -</div> - -<table class='table1' summary='TABLE III'> - <tr> - <td class='bbtd c031'> </td> - <td class='bbtd blt c033'><span class='sc'>Cyanosis</span></td> - <td class='bbtd blt c032'> </td> - <td class='bbtd blt c034'><span class='sc'>No Cyanosis</span></td> - </tr> - <tr> - <td class='bbt c031'><span class='sc'>No.</span></td> - <td class='bbt blt c033'><span class='sc'>Degree</span></td> - <td class='bbt blt c032'><span class='sc'>Distribution</span></td> - <td class='bbt blt c036'> </td> - </tr> - <tr> - <td class='c031'>741</td> - <td class='blt c033'>+</td> - <td class='blt c032'>Chest and upper extremities</td> - <td class='blt c036'>747</td> - </tr> - <tr> - <td class='c031'>743</td> - <td class='blt c033'>+ +</td> - <td class='blt c032'>Face, neck and ears</td> - <td class='blt c036'>748</td> - </tr> - <tr> - <td class='c031'>744</td> - <td class='blt c033'>+ + +</td> - <td class='blt c032'>Head and neck (upper portion of chest and thighs mottled and purple)</td> - <td class='blt c036'>749</td> - </tr> - <tr> - <td class='c031'>745</td> - <td class='blt c033'>+ +</td> - <td class='blt c032'>Head and neck and upper extremities</td> - <td class='blt c036'>751</td> - </tr> - <tr> - <td class='c031'>746</td> - <td class='blt c033'>+ +</td> - <td class='blt c032'>Ears, neck and shoulders</td> - <td class='blt c036'>752</td> - </tr> - <tr> - <td class='c031'>750</td> - <td class='blt c033'>+ +</td> - <td class='blt c032'>Face, ears and neck</td> - <td class='blt c036'>764</td> - </tr> - <tr> - <td class='c031'>756</td> - <td class='blt c033'>+ +</td> - <td class='blt c032'>Neck, jaw, shoulders and upper extremities</td> - <td class='blt c036'>765</td> - </tr> - <tr> - <td class='c031'>757</td> - <td class='blt c033'>+</td> - <td class='blt c032'>Face, neck, shoulders, arms and chest</td> - <td class='blt c036'>778</td> - </tr> - <tr> - <td class='c031'>758</td> - <td class='blt c033'>+ + +</td> - <td class='blt c032'>Face, ears, neck and upper chest</td> - <td class='blt c036'>782</td> - </tr> - <tr> - <td class='c031'>761</td> - <td class='blt c033'>+</td> - <td class='blt c032'>Face, ears, neck and upper chest</td> - <td class='blt c036'>784</td> - </tr> - <tr> - <td class='c031'>762</td> - <td class='blt c033'>+</td> - <td class='blt c032'>Ears, neck and chest</td> - <td class='blt c036'>786</td> - </tr> - <tr> - <td class='c031'>763</td> - <td class='blt c033'>+</td> - <td class='blt c032'>Head and neck</td> - <td class='blt c036'>793</td> - </tr> - <tr> - <td class='c031'>767</td> - <td class='blt c033'>+</td> - <td class='blt c032'>Face, ears and neck</td> - <td class='blt c036'> </td> - </tr> - <tr> - <td class='c031'>773</td> - <td class='blt c033'>+ +</td> - <td class='blt c032'>Neck, ears and cheeks, extending moderately to upper chest. Hemorrhage into conjunctiva</td> - <td class='blt c036'> </td> - </tr> - <tr> - <td class='c031'>781</td> - <td class='blt c033'>+ +</td> - <td class='blt c032'>Eyes, lips, ears and neck</td> - <td class='blt c036'> </td> - </tr> - <tr> - <td class='c031'>783</td> - <td class='blt c033'>+ +</td> - <td class='blt c032'>Face, lips, neck and fingers</td> - <td class='blt c036'> </td> - </tr> - <tr> - <td class='c031'>787</td> - <td class='blt c033'>+ + +</td> - <td class='blt c032'>Ears, neck and shoulders</td> - <td class='blt c036'> </td> - </tr> - <tr> - <td class='c031'>791</td> - <td class='blt c033'>+ +</td> - <td class='blt c032'>Ears, neck and upper chest</td> - <td class='blt c036'> </td> - </tr> - <tr> - <td class='bbt c031'>792</td> - <td class='bbt blt c033'>+ +</td> - <td class='bbt blt c032'>Ears and back of neck</td> - <td class='bbt blt c036'> </td> - </tr> - <tr> - <td class='c031'>19</td> - <td class='blt c033'> </td> - <td class='blt c032'>+ Blotchy or slight 6</td> - <td class='blt c036'>12 or</td> - </tr> - <tr> - <td class='c031'>or</td> - <td class='blt c033'> </td> - <td class='blt c032'>++ Moderate 10</td> - <td class='blt c036'>38.6%</td> - </tr> - <tr> - <td class='bbt c031'>61.4%</td> - <td class='bbt blt c033'> </td> - <td class='bbt blt c032'>+++ Well marked 3</td> - <td class='bbt blt c036'> </td> - </tr> - <tr> - <td class='bbt c031'>770</td> - <td class='bbt blt c033'> </td> - <td class='bbt blt c032'>Fine petechial rash over upper chest.</td> - <td class='bbt blt c036'> </td> - </tr> -</table> - -<p class='c009'>Occasionally we met with small hemorrhages lying in the -upper layers of the subcutaneous tissue. These lesions were -small and could not be seen from the external surface. Nevertheless, -<span class='pageno' id='Page_215'>215</span>some of them seemed to have occurred in direct contact -with the deep cutis and surrounded portions of the deep skin -appendages. From an examination of our cases there was no -reason at the time of autopsy to lay any particular stress upon -the occurrence of these hemorrhages. Subsequently, it has come -to mind, and since learning of the unusual frequency of boils and -deep pustules making their appearance as post-influenzal sequelæ, -that these minute lesions may have a bearing upon the localization -of infection in the skin tissues. We must appreciate, of -course, that other factors of a constitutional nature probably -render the individual more susceptible to the invasion of the -staphylococcus, and that such factors are all-important in allowing -this organism to gain a foothold. Whether the decreased -sugar-tolerance with hyperglycemia, which has been observed -in the late stages of influenza, bears a relation to the increased -susceptibility, as appears to be the case in diabetes mellitus, is an -interesting point for further investigation. Other constitutional -states are also undoubtedly involved in the increased susceptibility -to the infection which the patient suffers. Elsewhere -(Dr. Holman) it is shown that the natural complement content -is considerably depressed during the height of the influenza. -With such factors present and with the available infecting micro-organisms, -it is possible that the minute deep skin hemorrhages -bear a relation to the immediate localization of the infection.</p> - -<p class='c009'>In two instances slight hemorrhages were observed into the -conjunctival tissues. In each case they were unilateral and occupied -the tissues contiguous to the inner canthus. In one case -there was well-marked icterus with yellow coloration of the -scleræ and skin. In this case the icterus was associated with -degenerative changes in the liver, there being no recognizable -obstruction to the bile passages. The icterus had come on quite -acutely and without any special clinical manifestations. In the -epidemic of 1890 jaundice was present in a considerable number -of cases (Medical Record, 1890, xxxvii, 473). Cole made similar -observations in the epidemic of influenza amongst the Canadian -soldiers. Œdema of the skin was not met with in any of our -cases. This point is worthy of comment, inasmuch as some -authors have been impressed with the serious damage taking -place in the kidney and the resulting incapacity of these organs. -<span class='pageno' id='Page_216'>216</span>Although, as we shall point out later, the kidney tissues in these -cases showed a decided toxic degeneration, there was no evidence -that a glomerular damage of serious degree ever occurred. The -urinary excretion, as is pointed out in a report by Dr. Zeedick, -varies considerably with the intensity of the disease. It is unusual -to find derangement of kidney function to a degree to reflect seriously -upon the general bodily state. At least this has been our -experience in the present epidemic. Even where subsequently -we were able to demonstrate a considerable tubular degeneration -in the cortex of the kidney the change in the kidney function -was not of sufficient magnitude to lead to a water-retention to -be recognized in an anasarca. I wish to distinguish clearly at -this point the difference in finding an œdema in certain involved -tissue structures in various parts of the body and arising through -an inflammatory reaction due to the presence of peculiar focal -irritation, as compared with the accumulation of fluid in many -and irregular situations as it occurs through retention and faulty -excretion by the kidneys. Various organs as we have found—as, -for instance, the lung, heart and liver—showed a condition of -œdema which was not to be reconciled with an inadequate circulation -because of a cardiac or renal incompetency. These œdemas, -which we will discuss later, are local and are the result of damaging -influences inducted in and upon the tissues where they are -found.</p> - -<h3 class='c010'><em>Muscle</em></h3> - -<p class='c011'>In all of our cases we have been struck with the excellent -physique of the individuals succumbing to this epidemic. All -were youths in the best of health, of good muscular build and -strong bony frame-work. Post-mortem rigidity set in fairly -rapidly after death. Where this rigidity had “set” for six or -more hours it required much force to change the position of the -muscles. The voluntary muscles of the thorax and abdomen were -always carefully observed, and in a number of instances the -muscles of the thigh were also examined. It was not possible -routinely to dissect the muscles of the extremities, so that we -are unable to give an accurate account of the occurrence of -degenerations in these structures. We have, however, observed -the reactions taking place in the pectorals, psoas and muscles of -<span class='pageno' id='Page_217'>217</span>the abdominal parietes. Changes were observed with greatest -frequency in the recti of the abdomen. Degeneration occurred in -these muscles in 14 instances, while the same tissues suffered -rupture, in part or completely with hemorrhage, in six instances. -It was not uncommon to find marked degeneration in the lower -segment of the rectus muscle on one side, while degeneration -and hemorrhage had occurred in its fellow on the opposite side. -In four cases rupture of the entire belly of the muscle had taken -place, so that a considerable space had occurred between the -broken ends and a large clot of blood filled the intervening space. -This degeneration, which was seen only in the voluntary muscles, -was quite interesting and in its milder degrees was rather difficult -to detect. All gradations of loss of muscle color were seen. In -some instances the muscle simply seemed to have lost its meaty -lustre, while again in the more severe instances the muscle color -had changed from the bright red to an insipid yellow or clay -color. The most marked degeneration occurred in the midportions, -while the ends of the muscle masses at the points of -attachment were less involved. Complete rupture of the rectus -always occurred in the lowermost segment, a short distance above -the insertion into the pubic bone. At times the distribution of -the degeneration within the muscle was quite patchy, and irregular -islands of yellow about 2 cm. in diameter were splashed -through the muscle masses, which in themselves were paler than -normal. Where the muscle degeneration was advanced the tissue -was soft and at times even buttery. It resembled the character -of the degeneration observed in typhoid fever, although I have -no recollection amongst many enteric cases of having seen the -degeneration of the muscle occur so acutely. Recklinghausen -claimed that these hemorrhages were most unusual in influenza. -This is contrary to our findings.</p> - -<p class='c009'>Degenerations of a similar kind as those of the abdominal recti -were found in both pectorals. In the chest region, however, the -degeneration was less frequent and less severe. We observed it -only twice, and in neither instance had the degeneration led to -a rupture and hemorrhage of the muscle bundles. Kuskow -observed a single case of degeneration and hemorrhage of the -pectoral muscles. In the psoas muscle we observed degeneration -on two occasions, in one of which the lesion was associated with -a partial separation of the muscle fibers and hemorrhages into -<span class='pageno' id='Page_218'>218</span>its substance. In one case clinically, but not coming to autopsy, -a lesion, which from its character we presume to have been a -degeneration, occurred in the sterno-mastoid, being accompanied -by hemorrhage and the development of a firm clot the size of a -hazel nut. In the subsequent history of this case the lesion -passed through an aseptic process of organization with contracture -so that the patient has recently been developing a “wryneck.” -Kohts in 1890 reported the finding of muscle degeneration -and abscesses in the arm. The condition arose as a late complication -of influenza.</p> - -<p class='c009'>From our experience at the autopsy table in observing the -relative frequency with which muscle degeneration occurs in the -severe cases of epidemic influenza, we feel convinced that numerous -cases which recover pass undiagnosed of this condition. -Furthermore we have evidence, as illustrated in a case observed -by Dr. McMeans, wherein a lesion which occurred in the gluteal -muscles was followed by a localizing infection at this site that -these muscle degenerations and hemorrhages may have serious -consequences. There are a number of instances in which post-influenzal -complications of the nature of deep-seated abscesses of -the extremities, thorax, and abdomen may have their explanation -for the localization in a primary muscle damage accompanied by -hemorrhage and followed by an infection of variable type. Cole -also comments upon the development of abscess in the deep -muscles where degeneration had taken place. In illustrating -some of our findings to Dr. J. Anderson he immediately recognized -such a condition in the pectoral muscles of a patient in -which he was unable to arrive at a conclusion of the pathological -events which had taken place. It is one of the noteworthy features -in this disease that the voluntary muscles of certain -regions are apt to suffer severe damage, while the heart and the -various unstriped muscular tissues are little if at all affected by -a similar process. It would be interesting to know whether the -lack of response and the delayed functional recovery on the part -of the muscles of the extremities in so many patients who have -suffered influenza is the result of the damaging influence of a -peculiar intoxication present in this disease. One of the features -in influenza is the prostration of the patient, and with it there is -definite muscular weakness. We have been prone to lay the responsibility -of this state entirely at the door of the nervous -<span class='pageno' id='Page_219'>219</span>tissues. Here, however, we are able to offer evidence that quite -aside from the lesions arising in the nervous tissue, there is definite -muscle damage which, as we shall again discuss when -describing the microscopic features, incapacitates even to the -point of complete destruction the muscle elements in various -fields of the body. Before, however, being able to state that the -muscular weakness of the extremities is the result of such damage -by toxins it is necessary to obtain more definite information -regarding the frequency with which these degenerations occur -in the limbs. In our own material we are unable to discuss the -matter with adequate figures. We are, however, impressed with -the changes observed in the muscles which were available to us. -Naturally, too, a certain number of muscle degenerations have -escaped our detection because of our unfamiliarity with the -mildest grades. In fact, we have already discovered in our -microscopic studies that certain cases, which in the macroscopic -had escaped us, showed well-marked lesions under the microscope.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE IV</div> - <div class='c004'>MUSCLE DEGENERATION</div> - </div> -</div> - -<table class='table1' summary=''> - <tr> - <th class='bbtd brt c030' colspan='2'><span class='sc'>Abdominal Recti</span></th> - <th class='bbtd brt c030'><span class='sc'>Pectoral</span></th> - <th class='bbtd c030'><span class='sc'>Psoas</span></th> - </tr> - <tr> - <th class='bbt brt c030'><span class='sc'>Toxic Degeneration</span></th> - <th class='bbt brt c030'><span class='sc'>Hemorrhage Into Rectus</span></th> - <th class='bbt brt c030'><span class='sc'>Toxic Degeneration</span></th> - <th class='bbt c030'><span class='sc'>Toxic Degeneration</span></th> - </tr> - <tr> - <td class='brt c033'>745 on 10th day</td> - <td class='brt c033'>745 both on 10th day</td> - <td class='brt c033'>756 on 8th day</td> - <td class='c033'>756 on 8th day</td> - </tr> - <tr> - <td class='brt c033'>749 on 4th</td> - <td class='brt c033'>752 both on 13th</td> - <td class='brt c033'>770 on 11th</td> - <td class='c033'>792 on 6th</td> - </tr> - <tr> - <td class='brt c033'>752 on 13th</td> - <td class='brt c033'>756 both on 8th</td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c033'>756 on 8th</td> - <td class='brt c033'>764 both on 9th</td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c033'>757 on 6th</td> - <td class='brt c033'>765 both on 9th</td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c033'>762 on 10th</td> - <td class='brt c033'>778 both on 23d</td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c033'>763 on 11th</td> - <td class='brt c033'><hr /></td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c033'>764 on 9th</td> - <td class='brt c030'><span class='sc'>Rupture of</span></td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c033'>765 on 9th</td> - <td class='brt c030'><span class='sc'>Rectus</span></td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c033'>767 on 10th</td> - <td class='brt c033'> </td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c033'>770 on 11th</td> - <td class='brt c033'>745 right on 10th day</td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c033'>778 on 23d</td> - <td class='brt c033'>756 both on 8th day</td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='brt c033'>783 on 8th</td> - <td class='brt c033'>778 right on 23d day</td> - <td class='brt c033'> </td> - <td class='c033'> </td> - </tr> - <tr> - <td class='bbt brt c033'>791 on 6th</td> - <td class='bbt brt c033'> </td> - <td class='bbt brt c033'> </td> - <td class='bbt c033'> </td> - </tr> -</table> - -<p class='c009'>We have convinced ourselves that the marked hemorrhage -taking place in the muscle tissue follows upon a primary degeneration -of this tissue and its spontaneous rupture. The amount -<span class='pageno' id='Page_220'>220</span>of hemorrhage is in proportion to the degeneration and fracture -of the muscle elements. The hemorrhage does not precede the -muscular change, nor does it have any antecedent relation to the -actual tearing of the muscle fibers.</p> - -<p class='c009'>A much better appreciation of the muscle degeneration was -obtained in the <em>microscopic</em> studies of these tissues. The various -gradations of tissue change could be followed, which was not -possible in the naked-eye examinations. Some points respecting -this degeneration were quite noteworthy. Firstly, the process of -degeneration in its early stages and advancing through the acute -destructive periods was not accompanied by any inflammatory -reaction. Evidence of inflammatory exudate was obtained only -when the degeneration had proceeded to a degree permitting of -rupture with hemorrhage, or in the late stages when the areas of -marked muscle dissolution were undergoing repair. We have no -evidence to indicate that bacteria were present during the beginning -of the degenerative process. Bacteria could not be demonstrated -in section. The appearance of the tissue suggested a -purely toxic process which was selective in its action, picking -out voluntary striped muscle tissue and attacking certain muscle -groups in preference to others. It was also interesting to observe -in the early stages of the degeneration that individual fibers lying -amidst healthy and unchanged muscle elements would show -degeneration in many of its stages. This appearance was often -unique, particularly when in the early stages of the process the -involved fiber would still retain its normal position and shape -though markedly altered in its staining and chemical qualities.</p> - -<p class='c009'>The degeneration as observed in these cases showed many of -the characters like that of waxy degeneration seen in typhoid -fever. Similar appearances to these have also been described in -connection with the toxic degenerations which occur in the -vicinity of infections by the gas bacillus. In fact, all the stages -observed in the one can be seen in the other. They differ, -however, only in the degree to which final destruction takes -place and in the speed with which the degeneration is accomplished. -The character of the degeneration is well studied -in sections stained with hematoxylin and eosin, eosin-methylene -blue, and best of all in the phosphotungstic acid hematoxylin. -By the latter method one is able to follow clearly the grade -of degeneration as it effects the muscle striations. On the -<span class='pageno' id='Page_221'>221</span>other hand, the peculiar waxy appearance of the early degenerating -fibers is best seen in sections stained with eosin or -fuchsin, where the striated muscle fibers are found to be -changed to a more intensely staining red body of homogeneous -character and devoid of all evidence of their original internal -architecture. These bland waxy fibers were often of the size and -shape like the normal. On the other hand, the fibers are also -not uncommonly swollen, stretching the sarcolemma to almost the -bursting point. Following this primary bland degeneration the -fiber takes on irregular shapes, becoming constricted and collapsed -at irregular intervals, so that islands of the waxy contents lie -within the sarcolemma, being separated from each other by constricted -areas in which the original myoplasm has undergone decomposition -and sometimes complete absorption. This irregular -destruction of the muscle contents often has a granular stage in -which the original muscle substance has become disintegrated. -The sarcolemma follows the condition within it, stretching when -the fiber is swollen and shrinking, or even becoming collapsed when -the inner substance is becoming liquified and absorbed. The -sarcolemma does not suffer the degenerative changes of the inner -fiber, nor can one observe nuclear changes in this sheath which -are significant.</p> - -<p class='c009'>When first studying this process of degeneration it appeared -to us that the earliest change was a loss of the transverse striations -and the subsequent disappearance of the longitudinal -fibrillæ. We have subsequently found that this is incorrect and -that the changes observed in the markings of the fibers were not -constant. At times the muscle substance would progress through -stages of degeneration up to the point of disintegration and dissolution -while the transverse striæ were still discernible in the -altered fiber. The one constant change that we have observed in -the degenerating fibers was the early loss of staining qualities -as obtained by the phosphotungstic acid hematoxylin. In such -preparations the earliest effect of the intoxication upon the -muscle fiber was a change in reaction to this stain. Sometimes -within a given fiber small irregular and poorly staining blotches -could be observed, while the remaining portion of the fiber was -normal in its appearance. Later these poorly staining areas -became larger, occupying the entire width of the fiber and being -distributed at irregular intervals in its length. Finally the characteristic -<span class='pageno' id='Page_222'>222</span>staining quality was entirely lost, although in the -poorly colored cell transverse striations were still discernible and -a true waxy stage had not yet taken place.</p> - -<p class='c009'>At times the waxy degeneration advanced into the stage of -disintegration by an irregular destruction within the fiber. When -this occurred the fragments of waxy substance took on curious -coiled and grotesque shapes, while a granular destruction was -taking place in their periphery. Neither inflammation, œdema -nor a vascular reaction could be determined in these tissues of -mild or severe change. The reaction as is indicated in the table -occurred quite acutely and was not accompanied by fatty products -commonly seen in the slower forms of degeneration.</p> - -<p class='c009'>Gradually the debris of the degenerated fibers is absorbed and -the sarcolemma shrinks and collapses upon itself. During this -stage a reaction occurs in the sarcolemma with nuclear proliferation. -At times the last vestiges of the muscle fiber are seen to -be surrounded by a crown of nuclei and cells reminding one of -the appearance of the degenerating nerve cells in the Gasserian -ganglion in hydrophobia. The involved area becomes active in -appearance, showing proliferation of fibroblasts and the appearance -of occasional lymphocytes and plasma cells. Scar tissue -continues to develop in proportion to the amount of damage done. -In areas where hemorrhage had taken place the amount of scar -tissue is exaggerated, owing to a process of organization which is -taking place quite apart from the muscle degeneration. Thus -not a few scars scattered through the voluntary striped muscles -are the final outcome of this toxic degeneration occurring in -epidemic influenza. Some of these lesions may account for the -indefinite pains and symptoms of which the patient complains -for so many months after his acute illness. I refer particularly -to lesions occurring in the psoas and muscles of the back as possible -explanations for the partial invaliding of some individuals.</p> - -<p class='c009'>In a certain number of cases of acute influenza the patients -complain of severe abdominal pain, in the absence of any localizing -symptoms or evidence of intestinal derangement. Such was -the case with a number of the above cases coming to autopsy, -and the sole evidence we could offer was muscle degeneration with -or without massive hemorrhage. The abdominal pains complained -of were more of the nature of dull aches with occasional exacerbations -and shooting or lancinating “stitches.” Rarely was the -<span class='pageno' id='Page_223'>223</span>patient able to define the position of the pain, not being able to -state whether it was within the abdomen or in the parietes. -Most frequently they claimed it was internal. We have on no -occasion demonstrated an intra-abdominal lesion which could -account for such pains. None of our cases was of the type of -“intestinal influenza.” We are, therefore, led to the conclusion -that the muscle degenerations of the various degrees, from the -slight with few muscle elements involved to the severe with -rupture and hemorrhage, account for a proportion of the clinical -symptoms of (muscle) pains and aches as well as weakness. -We cannot claim that coughing was a necessary factor in inducing -rupture of the abdominal recti. In some of the cases with rupture -severe coughing had not been observed during the illness.</p> - -<h3 class='c010'><em>Upper Respiratory Tract</em></h3> - -<p class='c011'>The pathological changes found in the nose, pharynx and -larynx were of relatively slight importance and most variable in -their severity and incidence. The majority of individuals had -few clinical manifestations of disease in these parts. Some, however, -complained of dryness of the pharynx with slight feeling -of fullness. An examination of these parts revealed some congestion, -varying from a red injected mucosa to a bluish cyanosis. -In the nose the reaction was rarely as acute as is seen in infectious -coryza, but even where relatively little change was to be -seen in the tissues hemorrhage from the erectile tissue was not -uncommon during the acute stages. No particular lesion was to -be found associated with nose bleed. There was an unusual -absence of excessive secretion from nose and pharynx in the -majority of cases. One was also struck with the infrequency -with which the larynx was involved. A certain number of individuals -complained of hoarseness, and in them injection of the -vocal cords with some swelling was found. In many others, however, -even where an intense infectious process was present in -the lower respiratory tract the larynx was almost without change. -It was from the level below the larynx that the acute reaction -in the respiratory system was found.</p> - -<p class='c009'>In all of our cases the trachea showed definite inflammatory -reaction. Of the 32 cases there were 26 having an acute tracheitis, -5 with an acute mucopurulent inflammation and 1 with a -<span class='pageno' id='Page_224'>224</span>reaction in the subacute stage. In the majority of the cases with -acute tracheitis there was a thin layer of exudate lying upon the -mucosal surface. At times the trachea was filled with a frothy -serous fluid, the greater part of which had its origin in the lung. -Nevertheless, as we shall point out later, we did obtain microscopical -evidence indicating that during the early acute stage -of the tracheitis a considerable serous exudate escapes from its -mucosa. This serous inflammatory reaction is an important one -for all of the mucosal structures upon which the virus of influenza -obtains a footing. This we have found true for the trachea, -bronchi and alveoli of the lungs. In some cases the exudate -was grey and lay in close contact with the injected tissues. At -first sight this grey exudate suggested necrosis, but it was readily -wiped from the underlying structure. Some leucocytes and cell -debris with many bacteria made up the content of this grey -exudate.</p> - -<p class='c009'>The macroscopic appearance of the trachea was that of an -intensely injected structure which had largely lost its normal -lustre. The naked eye could distinguish that anatomical change -had occurred in the surface tissue of the trachea and that there -was unusual evidence of intensely injected vessels lying in the -submucosa. In only one instance was there an appearance of a -true necrotic membrane lying upon the surface of this intensely -inflamed layer. This apparent membrane was found to consist -of a wide patch of desquamated epithelial cells which was lying -as a delicate necrotic plate upon the surface. This thin layer -was devoid of a meshwork of fibrin threads as usually accompanies -a true false membrane of other sources.</p> - -<p class='c009'>The early intense inflammatory reaction of the surface membrane -of the trachea was characteristic, and in our experience -was never exceeded in intensity by other infections. A desquamation -of the lining membrane was also a common finding. -Naturally this intense reaction so commonly found in the trachea -extended without interruption into the main bronchi and their -divisions. The finding of this continuous surface inflammation -is good evidence of the mode of spread of the infectious process -along these membranes, beginning in the upper portions and by -direct continuity involving more and more of the respiratory -tubes toward the lung.</p> - -<p class='c009'><span class='pageno' id='Page_225'>225</span>The varying grades in the intensity of the inflammatory reaction -upon the inner surface of the trachea was well illustrated in -the microscopic sections. Even with the different degrees of the -reaction there was a fairly constant character to the inflammation. -In this way the response was found to differ from that -commonly observed in ordinary infections of the respiratory -tract. The first striking feature is the marked response of the -vascular channels, both blood and lymphatic. The vessels lying -in the submucosa were found intensely engorged so that their -walls were stretched to the point of bursting. In fact, not a few -vessels were seen whose walls, probably under the stress of -intoxication and dilatation, had given way leading to a flooding -of the neighboring tissue with their contents. Where such vessels -lay close underneath the surface the hemorrhage escaped -into the lumen of the trachea. Accompanying this early vascular -response there was found a marked serous exudate leading to a -stretching of the submucosal tissues by distention of the interstitial -spaces. This reaction resembled an acute inflammatory -œdema and occupied the area between the mucosa and the inner -border of the cartilage rings. Beyond this region no response -was found. Thus in the earliest stages, and where the mucosa -was still intact, the main reaction was of the nature of an intense -serous inflammation with congestion of the blood vessels and -frequent interstitial hemorrhages.</p> - -<p class='c009'>Shortly following the development of the serous exudate in the -submucosal tissues, the epithelial lining is found to suffer from -the reaction. The serous exudate does not remain confined to the -interstitial tissues, but is poured out through the mucosa into -the trachea. It would appear that the amount of this clear -exudate may become greater than can be dealt with by the -mucosa, with the result that an accumulation of this serous fluid -takes place between this epithelial layer and its basement membrane. -We have repeatedly seen considerable stretches of the -mucosa lifted from the basement membrane and shed in large -plaques into the lumen. These mucosal cells at the time of their -desquamation retain fairly well their morphological characters, -and do not show evidence of necrosis prior to their removal. -Disintegration of these cells naturally occurs while lying in the -secretion of the trachea, and a variable cellular mass in stages of -disintegration may often be found both in smears and sections. -<span class='pageno' id='Page_226'>226</span>When the epithelial cells are lifted in wide plates, a type of bleb -develops which is easily broken and then disintegrates.</p> - -<p class='c009'>The desquamation of the lining membrane is a fairly constant -occurrence in the cases coming to autopsy. In the majority of -those which we have examined the greater portion of the trachea -was completely denuded, save for small islands lying in the -recesses near the mouths of the mucous ducts. In one case this -lesion was accompanied by a process of ulceration, due in all -probability to the invasion by other micro-organisms. The denuded -tracheal surface usually shows a further inflammatory -reaction in which a cellular exudate then makes its appearance. -This reaction is mainly one in which lymphocytes and plasma -cells infiltrate the spaces previously occupied by the serous fluid. -The reaction is limited to the submucosa and does not extend into -the tissues beyond the cartilages. We have found only occasional -polymorphonuclear leucocytes lying close below the surface. During -this period, however, varying grades of degeneration may -occupy the upper layers. The basement membrane particularly -seems to suffer by losing its characteristic outline and staining -qualities. This membrane becomes swollen, softened and indefinite. -At times a homogeneous precipitate occurs along its free -surface giving rise to an appearance resembling a false membrane. -This deposit is, however, distinctively different from the -diphtheritic membrane of other infections. It is interesting, -however, that where such deposits and degeneration occur in -the basement membrane more or less degeneration and necrosis -also occur in the connective tissues immediately neighboring to it. -These tissues show a peculiar granular destruction and alter -their staining qualities. Moreover, and what is more important, -under these conditions the dilated blood vessels are found to -suffer from the injuries taking place in their neighborhood. -We have repeatedly found partially or completely thrombosed -capillaries, arterioles and venules in these surface layers. These -thromboses took place while the vessel was in its distended state -and thus produced a mold of the dilated vessel. This observation -is of importance in indicating the severity of the effect of the -virus and toxin upon the tissues of the trachea, and it is also of -importance to appreciate that this damaging influence is very -different from that which we encounter in pneumococcus infections, -and we shall point out in our discussion on lung a reaction -<span class='pageno' id='Page_227'>227</span>very similar to that which takes place very superficially in the -trachea may also occur in the alveolar walls of the lung.</p> - -<p class='c009'>Having referred to the intensity of the responses of the blood -vascular system, we must also indicate the part played by the -lymphatics. Simultaneously with the reactions taking place -about the blood vessels of the trachea we observed similar -responses in the lymphatic channels. At first these dilated structures -contained only fluid. Later the migration of the lymphocytes -took place along these routes, and rarely micro-organisms -could be demonstrated either free or within an occasional leucocyte. -The sharp response of the lymphatics during the serous -inflammation is noteworthy, inasmuch as we have found that the -lymph glands lying about the respiratory tubes and lungs were -early in their response to the irritating virus.</p> - -<p class='c009'>Bacteria were demonstrated in the secretions lying upon the -surface of the trachea. In those specimens in which the mucous -membrane was still intact we attempted to demonstrate the -clustering of the micro-organisms about the ciliated cells as was -described by Mallory in whooping cough. Although the organisms, -and particularly small Gram negative bacilli, could be -demonstrated lying about these cells no characteristic arrangement -was found. Furthermore where the mucosa was still -attached to its basement membrane we were never able to demonstrate -organisms below the surface of the epithelial layer. In -several cases where the mucosa was lifted in bleb-like structures -a number of organisms were detected below the epithelial layer -and in contact with the basement membrane of the submucosa. -We have rarely demonstrated bacteria in the interstitial spaces -of the submucosa, even where large numbers of organisms were -lying upon the inner denuded surface.</p> - -<p class='c009'>The distinction which was made by the gross examination of -the trachea between the acute tracheitis with serous exudate, -subacute tracheitis and mucopurulent tracheitis was not so -readily distinguished in the microscopic sections. In the gross -the character of the exudate lying upon the surface was the main -guide suggesting the nature and intensity of the inflammatory -reaction. In the microscopic sections this exudate was largely -wanting, or was not sufficiently characteristic to confirm the -gross findings. On the other hand, differences in the nature of -the injury were to be found mainly in the reaction of the submucosa. -<span class='pageno' id='Page_228'>228</span>As we have indicated above, the early inflammatory -reaction of the trachea is mainly evident in an intense congestion -accompanied by an inflammatory œdema of the submucosal -tissues, hemorrhage sometimes accompanying this response. In -the later stages of the reaction a cellular deposit takes the place -of the inflammatory œdema and usually consists of lymphocytes -and plasma cells. It is only in those cases where the intensity of -the irritant continues to act over a longer period of time that -a superficial necrosis with leucocytic infiltration makes its appearance. -The epithelial layer of the trachea is desquamated early -in the acute reaction, and hence a denudation of the surface is to -be found in all stages of the acute lesion. The mucous glands -have not been found to show any particular involvement in the -inflammatory process, and in the majority of instances they were -found to have escaped entirely the damaging effect of the virus. -Their response in an over-secretion of mucus may be the outcome -of a stimulation by toxins or soluble irritants; but on the -other hand, may also probably be a reflex response to the injury -of the mucosal surface, which being bared of its covering is -highly sensitive. The increased discharge of mucus from the -deep glands may well be a protective response to such injury.</p> - -<h3 class='c010'><em>Bronchi</em></h3> - -<p class='c011'>The lesions in the bronchi were in every way comparable to -those in the trachea. The main bronchial tubes differ in no -material way from the structure of the trachea, and the extension -of the inflammatory process from above downwards leads -to a reaction in their walls similar to what has been above -described. As we follow the subdivisions of the bronchi we -gradually lose some of the characteristics contained in the larger -tubes. The mucous glands gradually become fewer and eventually -disappear. The cartilage rings become smaller and no longer -completely encircle the bronchus, and with the further diminution -in the size of these structures disappear entirely. A relatively -greater amount of muscle tissues takes the place of the -cartilage rings. This change in the anatomy of these structures -has a certain influence in modifying the character and distribution -of the inflammation.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div><span class='pageno' id='Page_229'>229</span>TABLE V</div> - <div class='c004'>BRONCHITIS AND TRACHEITIS</div> - </div> -</div> - -<table class='table2' summary='TABLE V'> - <tr> - <td class='bttd c015'>Acute bronchitis and tracheitis</td> - <td class='bttd c019'>26</td> - </tr> - <tr> - <td class='c015'>Subacute bronchitis and tracheitis</td> - <td class='c019'>1</td> - </tr> - <tr> - <td class='c015'>Acute mucopurulent tracheitis</td> - <td class='c019'>5</td> - </tr> - <tr> - <td class='c015'>Acute purulent bronchitis</td> - <td class='c019'>2</td> - </tr> - <tr> - <td class='c015'>Acute mucopurulent bronchitis</td> - <td class='c019'>7</td> - </tr> - <tr> - <td class='c015'>Ulcers of trachea</td> - <td class='c019'>1</td> - </tr> - <tr> - <td class='bbt c015'>Acute bronchiectasis</td> - <td class='bbt c019'>1</td> - </tr> -</table> - -<p class='c009'>Thus whereas we have indicated that the inflammation of the -trachea and of the large bronchi is of a peculiar kind and remains -confined to the tissue lying inwardly from the cartilage rings, we -found that where these structures give place to a loose muscle -tissue with a more extensive lymphatic drainage the zone of -inflammation is not so limited, but proceeds outwardly into the -neighboring tissues. We often use the terms bronchus and -bronchioles very freely without clearly distinguishing any real -difference. In a study of the inflammatory reactions of the -respiratory tubes in epidemic influenza (as well as in other infections) -it is best to accept the anatomical definition that the -bronchioles not only represent the minute tubules passing to the -alveoli, but also those small air passages which devoid of cartilage, -mucous glands and heavy connective tissue stroma are in -close relation to the parenchymatous tissues of the lung. These -soft muscular tubes possess blood and lymphatic vessels which -freely communicate with the blood vessels of the lung alveoli. -It is in association with these distant tubes that concomitant -inflammatory reactions are found in the alveoli and in the bronchial -tubes.</p> - -<p class='c009'>Desquamation of the epithelial lining is to be found in every -size of bronchial tube where the infection has caused an acute -inflammatory reaction. Throughout the pulmonary tissues where -the lung is found in some stage of influenzal pneumonia the -bronchial tubes, both large and small, are either entirely denuded -of the mucosa or show only remnants attached to irregular -areas. In the smaller passages dense clusters of desquamated -cells are sometimes found within the lumen and indicate the -accumulation of a desquamated epithelium obtained from portions -<span class='pageno' id='Page_230'>230</span>of the tubular system in deeper portions of the lung. In -the early stages, this desquamation is accompanied by a serous -exudate and a certain amount of hemorrhage. Later we find -masses of leucocytes which fill up the tube, and though appearing -to arise from these structures have in fact largely come from -the lung alveoli. Like the larger bronchial tubes the distant -ramifications show relatively little cellular reaction in their walls -in the early period. It is only when the neighboring lung tissues -are extensively implicated in a purulent inflammation that we -find a similar exudate occupying the tissues of the bronchioles. -Polymorphonuclear leucocytes are equally distributed through -the region of the basement membrane, submucosa, muscular coat -and outer connective tissue layer. Some grades of degeneration -may occupy the inner surface wherein the basement membrane -first shows a homogeneous swelling and later a granular degeneration. -In a few instances where the small bronchioles have -communicated with regions with abscess formation an ulcerating -surface occupied the inner boundary.</p> - -<p class='c009'>The evidence in the smaller bronchial tubes, both those with -cartilage and those without, that an inflammatory reaction of -some degree may occupy the muscular coat is of importance. -We have found reactions of inflammation in the muscular coat -varying from a mild œdema and cellular exudate to an intense -polymorphonuclear leucocyte involvement. In the latter the -muscle fibers showed evidence of degenerative change and suggested -an acute weakening of this layer. We lay particular -importance upon this finding as indicating a causative factor in -the development of acute bronchiectasis as was met with in one -of our cases. In this particular instance the bronchi passing to -the lower lobes of each lung were unusually dilated and could be -followed, in the gross, to their distant extremities. The dilatation -was more or less uniform and no large pouches or cavities had -developed. A mucopurulent exudate was found occupying these -dilated tubes. Others have likewise observed the development -of acute bronchiectasis under these conditions. Goodpasture and -Burnett found that as early as the second to the fourth day one -of the striking appearances was the gaping dilated condition of -the infundibula, and the tendency to dilatation of the air passages -was manifested in a bronchiectasis in 4 out of 30 cases. -Boggs as well as Lord have reported upon chronic bronchiectasis -<span class='pageno' id='Page_231'>231</span>associated with the B. influenzæ and there appeared to be evidence -that a certain percentage of cases recovering from influenza -permanently develop irregular dilatations of the bronchial tubes.</p> - -<p class='c009'>The recognition of inflamed bronchi or bronchioles was never -difficult. In the gross the presence of the abnormal exudate and -the intense injection of the mucosal surfaces always attracted -attention to the inflammatory state. Furthermore where the -mucosa had been desquamated the surface of these tubes was -found to be quite granular if closely observed. With moderate -magnification by means of a hand lens the granular appearance -was shown to be due to the engorged vessels. Much easier, of -course, was the recognition of the inflammatory reaction by the -microscope. The importance, however, of the bronchitis and -bronchiolitis lay in the amount of involvement which had -occurred in the neighboring tissues. As we, however, indicated -elsewhere, we do not doubt that many of the cases of three-day -fever have a state of tracheitis and bronchitis equal to that which -we have observed in many of our cases. Whether the inflammatory -reaction progressed beyond the firmer bronchial tubes to the -softer and more vascular structures would be difficult to say -where our evidence rests upon the clinical findings alone. It -is, however, probable that a certain number of the severe and -sharp attacks of influenza not only cause a tracheitis and bronchitis -of the larger tubes, but also extend more deeply into the -smaller ramifications tending to simulate the reactions which we -have above described. When we ask ourselves, however, how -distantly must the infection invade the smaller bronchial tubes -before involving the parenchymatous tissues of the lung we are -at a loss to enunciate a general rule. It is more than probable -that there are modifying influences which determine whether the -bronchitis with a certain amount of its bronchiolitis will progress -to a true pneumonia or will remain localized to these tubular -systems. I can well appreciate that in the event that a bronchitis -has an inflammatory reaction accompanied by much serous -exudate there is great danger of flooding the neighboring alveoli -with this inflammatory fluid and of carrying the large numbers -of the micro-organisms within the tubes to the air sacs of the -lung. Under these conditions the virus has an unusual ability to -develop the disease from one localized in the air passages to that -of a true pneumonia. It is probable that the peculiar early acute -reaction which is present in the air passages in epidemic influenza -is responsible for the extensive involvement of the lung in the -severe and dangerous form of inflammation.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div><span class='pageno' id='Page_232'>232</span>TABLE VI.</div> - <div class='c004'>EXTENT AND DISTRIBUTION OF PNEUMONIA.</div> - </div> -</div> - -<div class='overflow'> - -<table class='table1' summary=''> - <tr> - <th class='bttd bbt brt c030' rowspan='3'><span class='sc'>Autopsy Number.</span></th> - <th class='bttd bbt brt c030' rowspan='3'><span class='sc'>Age.</span></th> - <th class='bttd bbt brt c030' colspan='4'>RIGHT LUNG.</th> - <th class='bttd bbt brt c030' rowspan='3'><span class='sc'>Type of Lesion.</span></th> - <th class='bttd bbt brt c030' colspan='3'>LEFT LUNG.</th> - <th class='bttd bbt brt c030' rowspan='3'><span class='sc'>Type of Lesion.</span></th> - <th class='bttd bbt brt c030' colspan='2' rowspan='2'><span class='sc'>Pleura.</span></th> - <th class='bttd bbt brt c030' rowspan='3'><span class='sc'>Abscess of Lung.</span></th> - <th class='bttd bbt c030' rowspan='3'><span class='sc'>Day of Disease.</span></th> - </tr> - <tr> - - - <th class='bbt brt c030' rowspan='2'><span class='sc'>Weight of Lung.</span></th> - <th class='bbt brt c030' colspan='3'><span class='sc'>Involvement of Lobes.</span></th> - - <th class='bbt brt c030' rowspan='2'><span class='sc'>Weight of Lung.</span></th> - <th class='bbt brt c030' colspan='2'><span class='sc'>Involvement of Lobes.</span></th> - - - - - - </tr> - <tr> - - - - <th class='bbt brt c030'><span class='sc'>Upper.</span></th> - <th class='bbt brt c030'><span class='sc'>Middle.</span></th> - <th class='bbt brt c030'><span class='sc'>Lower.</span></th> - - - <th class='bbt brt c030'><span class='sc'>Upper.</span></th> - <th class='bbt brt c030'><span class='sc'>Lower.</span></th> - - <th class='bbt brt c030'><span class='sc'>Right.</span></th> - <th class='bbt brt c030'><span class='sc'>Left.</span></th> - - - </tr> - <tr> - <td class='bbt brt c030'>741</td> - <td class='bbt brt c031'>18</td> - <td class='bbt brt c031'>720 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c031'>850 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>3d.</td> - </tr> - <tr> - <td class='bbt brt c030'>743</td> - <td class='bbt brt c031'>20</td> - <td class='bbt brt c031'>825 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c032'>Lobular S. & H.</td> - <td class='bbt brt c031'>1375 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. Early P.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>5th</td> - </tr> - <tr> - <td class='bbt brt c030'>744</td> - <td class='bbt brt c031'>30</td> - <td class='bbt brt c031'>900 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar and Lobular S. & H.</td> - <td class='bbt brt c031'>900 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>7th</td> - </tr> - <tr> - <td class='bbt brt c030'>745</td> - <td class='bbt brt c031'>18</td> - <td class='bbt brt c031'>575 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobular S. & H.</td> - <td class='bbt brt c031'>480 G.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>B.P. with Necrosis.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c030'>+</td> - <td class='bbt c030'>10th</td> - </tr> - <tr> - <td class='bbt brt c030'>746</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>900 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c031'>650 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>5th</td> - </tr> - <tr> - <td class='bbt brt c030'>747</td> - <td class='bbt brt c031'>27</td> - <td class='bbt brt c031'>1510 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c031'>1000 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>6th</td> - </tr> - <tr> - <td class='bbt brt c030'>748</td> - <td class='bbt brt c031'>22</td> - <td class='bbt brt c031'>900 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar and Lobular S. & H.</td> - <td class='bbt brt c031'>1250 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. and B.P.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>4th</td> - </tr> - <tr> - <td class='bbt brt c030'>749</td> - <td class='bbt brt c031'>23</td> - <td class='bbt brt c031'>1480 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. Slight Purulent.</td> - <td class='bbt brt c031'>1250 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. Slight P.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>4th</td> - </tr> - <tr> - <td class='bbt brt c030'>750</td> - <td class='bbt brt c031'>24</td> - <td class='bbt brt c031'>1200 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar and Lobular. Early Purulent.</td> - <td class='bbt brt c031'>825 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar and Lobular. Early P.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>9th</td> - </tr> - <tr> - <td class='bbt brt c030'>751</td> - <td class='bbt brt c031'>22</td> - <td class='bbt brt c031'>1250 G.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar Purulent.</td> - <td class='bbt brt c031'>610 G.</td> - <td class='bbt brt c030'>±</td> - <td class='bbt brt c030'>±</td> - <td class='bbt brt c032'>B.P. slight.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>7th</td> - </tr> - <tr> - <td class='bbt brt c030'>752</td> - <td class='bbt brt c031'>27</td> - <td class='bbt brt c031'>1125 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c031'>775 G.</td> - <td class='bbt brt c030'>±</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>B.P. and Lobar P.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>13th</td> - </tr> - <tr> - <td class='bbt brt c030'>756</td> - <td class='bbt brt c031'>22</td> - <td class='bbt brt c031'>1000 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar S. & H. Slight Purulent.</td> - <td class='bbt brt c031'>820 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar and Lobular S. & H.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>8th</td> - </tr> - <tr> - <td class='bbt brt c030'>757</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>815 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobular S. & H.</td> - <td class='bbt brt c031'>1075 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. and Purulent.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>6th</td> - </tr> - <tr> - <td class='bbt brt c030'>758</td> - <td class='bbt brt c031'>22</td> - <td class='bbt brt c031'>1150 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c032'>Lobar Purulent</td> - <td class='bbt brt c031'>1400 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar Purulent.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>14th</td> - </tr> - <tr> - <td class='bbt brt c030'>761</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>1250 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. and Lobular Purulent.</td> - <td class='bbt brt c031'>550 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c032'>Lobular S. & H.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>7th</td> - </tr> - <tr> - <td class='bbt brt c030'>762</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>680 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c032'>Lobular S. & H.</td> - <td class='bbt brt c031'>750 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. and Lobular P.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>10th</td> - </tr> - <tr> - <td class='bbt brt c030'>763</td> - <td class='bbt brt c031'>22</td> - <td class='bbt brt c031'>920 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c032'>B. P. and Lobar S. & H.</td> - <td class='bbt brt c031'>540 G.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c032'>B.P.</td> - <td class='bbt brt c033'>F.P.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>11th</td> - </tr> - <tr> - <td class='bbt brt c030'>764</td> - <td class='bbt brt c031'>23</td> - <td class='bbt brt c031'>725 G.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c032'>Lobular S. & H.</td> - <td class='bbt brt c031'>550 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c032'>B.P.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>9th</td> - </tr> - <tr> - <td class='bbt brt c030'>765</td> - <td class='bbt brt c031'>25</td> - <td class='bbt brt c031'>1100 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c031'>1400 G.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. and Early P.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>9th</td> - </tr> - <tr> - <td class='bbt brt c030'>767</td> - <td class='bbt brt c031'>25</td> - <td class='bbt brt c031'>1075 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar and Lobular S. & H. and Lobular Purulent.</td> - <td class='bbt brt c031'>850 G.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar S. & H. Lobular P.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>10th</td> - </tr> - <tr> - <td class='bbt brt c030'>770</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>900 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar S. & H. and Lobular Purulent.</td> - <td class='bbt brt c031'>750 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar S. & H. Lobular P.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt c030'>11th</td> - </tr> - <tr> - <td class='bbt brt c030'>773</td> - <td class='bbt brt c031'>22</td> - <td class='bbt brt c031'>2050 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. and Purulent.</td> - <td class='bbt brt c031'>780 G.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. Lobular P.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>20th recurrence</td> - </tr> - <tr> - <td class='bbt brt c030'>778</td> - <td class='bbt brt c031'>22</td> - <td class='bbt brt c031'>1100 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Interstitial Pneumonia.</td> - <td class='bbt brt c031'>975 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Interstitial Pneumonia.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>23d</td> - </tr> - <tr> - <td class='bbt brt c030'>781</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>1000 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c031'>540 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. Purulent.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt c030'>5th</td> - </tr> - <tr> - <td class='bbt brt c030'>782</td> - <td class='bbt brt c031'>18</td> - <td class='bbt brt c031'>650 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobular S. & H. Slight Purulent.</td> - <td class='bbt brt c031'>875 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. and Early P.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>8th</td> - </tr> - <tr> - <td class='bbt brt c030'>783</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>1250 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c031'>580 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>8th</td> - </tr> - <tr> - <td class='bbt brt c030'>784</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>1590 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar Purulent.</td> - <td class='bbt brt c031'>1400 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. and Purulent.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>8th</td> - </tr> - <tr> - <td class='bbt brt c030'>786</td> - <td class='bbt brt c031'>20</td> - <td class='bbt brt c031'>1100 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. Slight Lobular Purulent.</td> - <td class='bbt brt c031'>700 G.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar S. & H. and Early P.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>4th</td> - </tr> - <tr> - <td class='bbt brt c030'>787</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>750 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobular S. & H.</td> - <td class='bbt brt c031'>1125 G.</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>8th</td> - </tr> - <tr> - <td class='bbt brt c030'>791</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>775 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobular S. & H. and Purulent.</td> - <td class='bbt brt c031'>1050 G.</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar S. & H. and Slight P.</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>6th</td> - </tr> - <tr> - <td class='bbt brt c030'>792</td> - <td class='bbt brt c031'>21</td> - <td class='bbt brt c031'>1050 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>+++</td> - <td class='bbt brt c032'>Lobar and Lobular S. & H.</td> - <td class='bbt brt c031'>950 G.</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c030'>++</td> - <td class='bbt brt c032'>Lobar and Lobular S. & H.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c033'>S.F.</td> - <td class='bbt brt c030'> </td> - <td class='bbt c030'>6th</td> - </tr> - <tr> - <td class='bbt brt c030'>793</td> - <td class='bbt brt c031'>18</td> - <td class='bbt brt c031'>500 G.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c032'>Slight Lobular S. & H.</td> - <td class='bbt brt c031'>435 G.</td> - <td class='bbt brt c030'>–</td> - <td class='bbt brt c030'>+</td> - <td class='bbt brt c032'>Slight Lobular Purulent.</td> - <td class='bbt brt c033'>–</td> - <td class='bbt brt c033'>F.</td> - <td class='bbt brt c030'>Strep. Bacteriemia.</td> - <td class='bbt c030'>10th</td> - </tr> -</table> - -</div> -<blockquote> -<p class='c009'>S—Serous. H—Hemorrhagic. P—Purulent. B.P.—Broncho-pneumonia. S.F.—Serofibrinous. F.—Fibrinous. -F.P.—Fibrinopurulent.</p> -</blockquote> - -<p class='c009'><span class='pageno' id='Page_234'>234</span>It was very evident that the smaller bronchi and bronchioles -were much more readily involved in a severe inflammatory reaction -than the larger tubes. A purulent inflammation was not -uncommonly found in the bronchioles of the lung when a pneumonic -state with leucocytic infiltration was present. Even where -such purulent infiltration of the walls of the bronchioles was -readily demonstrable the trachea and main bronchi were devoid -of this intense reaction. These purulent inflammations were not -uniformly distributed in the bronchioles of the lung, but only -occurred in those regions where the parenchymatous tissues were -in themselves involved in a purulent reaction. It was difficult to -find the evidence whether the purulent bronchitis preceded or -followed the presence of a purulent pneumonia. The intimacy -of the lung tissues with those of the small bronchioles makes it -impossible for one or other of these structures to escape when -one of them is implicated in a purulent reaction. It is equally -important to appreciate that to a considerable extent the lung -tissue surrounding the small bronchioles becomes involved by a -direct radial extension through the walls of the thin respiratory -tubes. Such extension laterally is assisted by the free lymphatic -communication lying about the bronchioles and stretching into -the lung parenchyma. Purulent processes of the small air tubes -always showed a similar reaction in the interstitial tissues of the -neighboring air sacs.</p> - -<p class='c009'>Our material did not permit of following the bronchial reactions -to their conclusion. In some instances we have found that -where abscesses developed within the lung the contiguous bronchi -and bronchioles either became eroded or suffered intense suppurative -inflammatory lesions on their inner surface. The manner -in which repair of the more common inflammatory processes -of the bronchi is accomplished could not be demonstrated in the -cases dying during the acute stage. In one case an organizing -bronchitis was associated with an organizing lobular pneumonia. -In this instance the connective tissues were proliferating freely -from the inner wall of the bronchi, there being no evidence of a -basement membrane at the point where the connective tissue was -growing. The development of the connective tissue appeared to -<span class='pageno' id='Page_235'>235</span>be spontaneous and was not taking place within an unresolved -fibrinous exudate. In as much as the fibrosing process was -largely scattered through all of the lobes, the numerical involvement -of the respiratory tubes was quite great. In this instance -the amount of obstruction which was imposed upon the respiratory -tissues by the fibrosing pneumonia and bronchitis was sufficient -to cause considerable distress and dyspnœa during the last -few days of the patient’s life. The amount of dyspnœa was out -of proportion to the clinical manifestations of pulmonary involvement, -and from a clinical point of view it was difficult to arrive -at a conclusion of the nature of the lung lesion.</p> - -<p class='c009'>Undoubtedly during the subsidence of the inflammatory process -within the bronchi the gradual restitution of the tissues -with little or no fibrosis is accompanied by a reproduction of -the lining membrane arising from the epithelial remnants in the -small mucous crypts. In a few cases lately coming to autopsy -where the patients had suffered an influenza five or six weeks -previously, the mucosa of the trachea and bronchi had assumed -its normal appearance and was fully clothed by a normal epithelial -covering.</p> - -<h3 class='c010'><em>Lung—Early Stage</em></h3> - -<p class='c011'>We have just discussed the importance of the inflammation of -the trachea and bronchi in the cases of influenza. It is our belief -that every case of influenza has some tracheitis, and a great -many have both tracheitis and bronchitis. This is true in the -absence of localizing signs and symptoms, as was evident even -in these cases in which the simple influenza passed into its more -severe type with its pulmonary lesions. In many of these -instances clinical evidences of an inflammatory reaction in the -respiratory tubes were wanting, while the reactions observed at -autopsy were often astounding.</p> - -<p class='c009'>Just as we feel that simple influenza and inflammation of the -respiratory tubes go hand in hand, or better that these respiratory -localizations are the all-important ones in every case of -simple influenza, so, too, we are of the belief that the pulmonary -lesions bear the same relation to all cases of severe and fatal -epidemic influenza. We hold that no case comes to his death -through acute epidemic influenza without having a lesion in the -lung. The pulmonary condition, therefore, is of first importance -<span class='pageno' id='Page_236'>236</span>and its analysis is imperative for a proper understanding of this -disease. There has been divided opinion as to the part played -by the pulmonary lesion in epidemic influenza, some holding that -it is to be looked upon as a part of the disease and others that -it must be viewed as a complicating lesion. Complications of -various kinds are very common, and there are a number of conditions -arising in the lung (abscess, gangrene, necrosis) which -must be viewed as complications. There is, however, a type of -pneumonia, and here I use the term in its broad sense, which is -not in truth a complication but merely a wider extent of involvement -of the respiratory tract by the same virus which is always -present to cause lesions in the respiratory tubes. The reaction -within the lungs is distinctive and differs from the pneumonias -which are met with under other conditions and with various -bacterial agencies. Nor are our findings in this matter unique -for this epidemic. They have been described and discussed in -the past. True it is that, like in the epidemic which has just -passed us, the incidence of clinical and pathological pneumonia -varied quite widely in different communities, so, too, the reports -of past epidemics do not give a uniform description of a pulmonary -lesion. Where, however, the analysis has been made -during the four weeks’ period of the acute epidemic and where -the descriptions have been recorded by painstaking observers, the -similarity with our present findings is very striking. I would -refer in particular to one report made in 1893 in Petrograd by -Kuskow. His report deals with 40 carefully studied cases in -which records both macroscopic and microscopic were accurately -made.</p> - -<p class='c009'>One of the great difficulties in placing an accurate interpretation -upon the pulmonary findings lies in the fact that true pneumonia -as seen in epidemic influenza in man has not been reproduced -in animals. Furthermore, as the majority of the fatal -human cases of epidemic influenza with their associated pneumonias -present a mixed infection of the lung tissues, it is difficult, -if not impossible, to indicate the lesions which have resulted -through the activity of one of these as against those induced by -the other bacteria present. In our own carefully studied cases -wherein bacteriological cultures were taken from every lung -there was not a single instance in which the influenza bacillus -was present in pure culture. This is more fully commented upon -<span class='pageno' id='Page_237'>237</span>in the studies by Dr. Holman, but the point we wish to make -here is the difficulty in arriving at a conclusion in our material -as to the actual effects induced by any one type of organism. -As it is fully discussed by Dr. Holman we are convinced of the -importance of the influenza bacillus in this epidemic. We also -appreciate that pneumonia lesions in animals have been induced -by a variety of materials gained from influenza patients, but yet -in view of the abnormal manner of producing such lesions these -are hardly comparable to those in man. We may well expect -severe œdema, inflammation and hemorrhage, if in guinea pigs, -rabbits and monkeys we introduce by intra-tracheal insufflation -large quantities of fluid suspensions of bacteria. And thus we -find positive results obtained by the use of a filtrable virus, -streptococci, influenza bacilli and other organisms. The lung is -a sensitive tissue which quite readily responds to a variety of -irritants. In many respects some of these lesions simulate those -in influenza, but still we are far from the conclusion that the -disease, influenza, with all its manifestations has been actually -reproduced.</p> - -<p class='c009'>The pathology of the pulmonary lesions in acute epidemic -influenza is so distinctive that except for the late purulent stage -which may resemble types of reinfected and unresolved pneumonia -the condition cannot be confused with the stages of frank -lobar pneumonia. We appreciate that this is a very positive -statement, and that opposition will be taken by those who resting -their opinion upon individual factors may claim that a clear -distinction from other forms of pneumonia is not available. We, -however, base our opinion not upon a single feature, but upon -the combined pathological complex observed in many individual -cases. These features are mainly those seen in the type of the -lesion, the character of the distribution, extent of involvement -and the multiple stages so commonly present at one time in -different portions of the lung. The type lesion that has become -so well known in pneumococcus lobar pneumonia has its distinctive -stages which for teaching purposes are divided into the -stage of (1) congestion, (2) red hepatization, (3) gray hepatization -and (4) resolution. In dealing with lobar pneumonia from -the standpoint of illustrating these stages the majority of teachers -annually confess their inability to present for the student’s -study the stage of congestion. The student is impressed that -<span class='pageno' id='Page_238'>238</span>the congestive stage of lobar pneumonia is very transient and -rapidly passes into the stage of red hepatization. Patients do -not die with pneumococcus pneumonia in the stage of congestion. -And this is also largely true of the stage of red hepatization, -which is but rarely seen at the autopsy table. This community -(Pittsburgh) gives its large quota to the mortality statistics of -pneumococcus pneumonia, but it is most unusual to meet with a -specimen of red hepatization except for the borders of the -advancing gray area. And, furthermore, red hepatization even -when found in the unusual cases shows remarkably little of this -character when seen under the microscope. True it is that a -certain number of red blood cells will be found in the alveoli and -a certain degree of congestion will occupy the alveolar walls, but -its extent is far less than what we may have hoped to demonstrate -to others. So that broadly speaking the intensely congested -lung with or without red hepatization is unusual in our -frank lobar pneumonia. This was quite the reverse in our cases -of acute epidemic influenza-pneumonia. Furthermore lobar pneumonia -in the great majority of instances illustrates a distribution -distinctive for the name. Massive lobar, or pneumococcus pneumonia -is found to occupy one or more lobes or parts of lobes. -The involved lobe is fairly uniform in the stage of the inflammatory -process. If it is in the early gray stage, this will be seen -with equal intensity in the different areas of the lobe. Patches -of pneumonia in different stages within the same lobe are not -to be found, while this finding is not uncommon in the pneumonias -of acute epidemic influenza. And lastly, the frequency -with which an inflammatory œdema occupied the lungs in the -cases of influenza was in quite striking contrast with the dry -fibrinous lesion of common pneumonia. This wet state of the -lung was but a stage in the inflammatory process varying in its -extent in the different periods, but nevertheless inducing a character -in the early pulmonary lesions which was quite foreign to -our usual finding. This wet state also assisted in modifying the -subsequent picture so that when the lung assumed its gray -appearance it was rather of a slimy character than of the firm -dry nature. In this late gray stage the slimy lung somewhat -resembled the appearance of unresolved pneumonia where this -condition had been brought about by a new infection upon the -original cause of the pneumonia.</p> - -<p class='c009'><span class='pageno' id='Page_239'>239</span>It is incorrect in influenza pneumonia to speak of the lesions -as lobar pneumonia or broncho-pneumonia if by these terms -we have in mind the pathological characters observed in the -pneumococcic pneumonia with its lobar or bronchial distribution. -Influenza-pneumonia appeared with both lobar and -lobular characteristics. Nearly every case had both types of -lesions present, but the nature of the inflammatory process is -so decidedly different from that of the ordinary endemic pneumonia -that a confusion in the interpretation is likely to arise -and in fact has already raised a considerable polemic. Influenza-pneumonia -is commonly lobar, lobular or bronchial in distribution. -It is, however, not of the characters that are associated -with the lesions designated under these terms. When, therefore, -we here use the word “lobar” we mean lobar <em>in distribution</em> but -not lobar in type. As will be seen from our table, it was usual -to have multiple lobes involved. But the lesions, not only in the -different lobes varied in their character and distribution, but -even within the same lobe a variety of types was present.</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE VII</div> - </div> -</div> - -<table class='table1' summary=''> - <tr> - <th class='bttd bbt c030'>Day of Pneumonia on Which Death Occurred</th> - <th class='bttd bbt blt c030'>No. of Cases</th> - </tr> - <tr> - <td class='c033'>Second</td> - <td class='blt c031'>2</td> - </tr> - <tr> - <td class='c033'>Third</td> - <td class='blt c031'>4</td> - </tr> - <tr> - <td class='c033'>Fourth</td> - <td class='blt c031'>7</td> - </tr> - <tr> - <td class='c033'>Fifth</td> - <td class='blt c031'>6</td> - </tr> - <tr> - <td class='c033'>Sixth</td> - <td class='blt c031'>7</td> - </tr> - <tr> - <td class='c033'>Seventh</td> - <td class='blt c031'>3</td> - </tr> - <tr> - <td class='c033'>Eighth</td> - <td class='blt c031'>1</td> - </tr> - <tr> - <td class='c033'>Tenth</td> - <td class='blt c031'>1</td> - </tr> - <tr> - <td class='bbt c033'>Twentieth</td> - <td class='bbt blt c031'>1</td> - </tr> -</table> - -<p class='c009'>To a certain degree we were able to analyze the types of the -lesions as they occurred in the different stages and progress of -the pulmonary inflammation. Briefly, these were as follows: the -earliest stage of congestion following rapidly upon the infection -from the bronchi was followed by (1) inflammatory œdema, (2) -hemorrhage, (3) cellular exudate (a. mononuclear cells, b. leucocytes, -c. interstitial infiltration) and (4) resolution or organization, -abscess, infarct and gangrene. The majority of our cases -<span class='pageno' id='Page_240'>240</span>died during the stages of congestion, hemorrhage or early purulent -infiltration. In the early stages the amount of fibrin was -small or entirely absent, later, with the appearance of leucocytes, -some fibrin was present.</p> - -<p class='c009'>For the estimation of the time elapsing between the onset of -the pneumonia and death we are dependent upon the clinician. -This is often quite difficult to do, in as much as with a primary -respiratory disease, such as epidemic influenza represents, it is -very difficult to determine the time when there is a transition -from the inflammatory process of the upper respiratory tubes -to that of the pulmonary tissue. In many of the cases where from -the onset there was intense prostration and every evidence of -marked intoxication the clinical manifestations of localized processes -taking place in the respiratory system were very much -in the background and often of insidious progress. In four of -our cases it appeared as if the pulmonary manifestations had -made their appearance with the first sudden and severe onset of -the influenza. On the other hand, also, the clinical signs and -symptoms of lung involvement were different from those of frank -lobar pneumonia. We would, from our experience at the autopsy -table, say that where in the cases of epidemic pneumonia there -are present the signs of pulmonary consolidation like those of -true lobar pneumonia, that there has been an antecedent period -of a pulmonary lesion which passed unrecognized by the clinician. -To more clearly state the case, whereas in lobar pneumonia the -stage of congestion preceding the stage of red hepatization gives -rise to no signs whereby the clinician can indicate the time of -its onset or determine the time when it has passed into the succeeding -stage, and moreover, the stage of congestion is of short -duration to be measured in a period of a few hours, this stage -in epidemic influenza though equally indefinite in its clinical -manifestations is much prolonged, lasting not only a period of -hours but even a period of several days. It is this pulmonary -state which is difficult or even impossible to recognize in the -living. All gradations of it occur and the clinician can only -broadly suggest from all the evidence at hand, the period when -inflammation with definite exudate began in the lung. In as -much as the total length of illness of a number of cases was only -three, four and five days, whereas there was nothing at the onset -to suggest pulmonary involvement, we can estimate approximately, -<span class='pageno' id='Page_241'>241</span>at least, the duration of the lung condition. This makes -it possible to give a relative estimate of the character of the -lesions present at different periods of time. The outstanding -finding, as we will discuss again, was that a distinct and peculiar -pulmonary reaction was primarily imposed upon the lung, which -made its appearance at periods different from those of frank -lobar pneumonia.</p> - -<p class='c009'>We were repeatedly surprised at finding death to have occurred -during the stage of acute congestion with some hemorrhage and -inflammatory œdema of lung and in the absence of any sign of -grey hepatization or purulent infiltration. In many of these -cases the involved areas of lung though heavy and œdematous, -were still partly air-containing and the amount of lung involvement -was insufficient, on the basis of mechanical interference, -in accounting for the severity of the clinical symptoms and the -fatal outcome. This must have impressed everyone dealing with -the autopsies during the acute epidemic. It immediately suggests -that in some cases at least the pulmonary lesion, in as far -as incapacitating the external respiratory system, was not the -sole or even the important cause of death, but that a condition -of intoxication, borne out by the evidence of damage in muscles, -blood and kidney is a large factor of danger in this disease.</p> - -<p class='c009'>We shall briefly describe the important pulmonary findings -as we have met with them in the successive stages of influenza-pneumonia. -This, we hope, will make clear the interpretation -of the pathology of the lung lesion of the epidemic as it came -under our observation.</p> - -<p class='c009'>The earliest pulmonary lesion which we encountered was one -of congestion, inflammatory œdema and hemorrhage. These -three conditions were usually present at the same time and were -found in the height of intensity in all of the cases dying within -the first four days of illness. During this early period these -manifestations of inflammation were not accompanied by definite -red or grey hepatization as might ordinarily be expected. -The lesions varied greatly in their intensity, the œdema always -being very prominent, while the hemorrhage varied from a -diffuse infiltration of the involved lobe or added to this, was -localized in massive collections four or five cm. in diameter and -commonly occupying the central portions of the lobes. We have -seen several hemorrhages lying in close proximity to each other -<span class='pageno' id='Page_242'>242</span>with their borders coalescing and leading to a larger central -involvement. In the regions where the hemorrhage and inflammatory -œdema were diffuse, air was still present within the lung -tissue, sometimes to an extent permitting the lung tissue to float -on water but more often in quantity sufficient only to suspend -the tissue at various depths. On pressure the fine air bubbles -were recognized amidst the blood-stained fluid. Acute compensatory -emphysema often occupied the anterior borders of -the lobes or formed interstitial blebs beneath the pleura. The -quantity of fluid, inflammatory œdema and hemorrhage, contained -within these bulky lobes was often very surprising. A -lobe when compressed would leak fluid with the ease that it could -be obtained from a sponge. Out of the lower lobe on one occasion -we pressed 700 c.c. of limpid blood-stained exudate. The -acute emphysema which may make its appearance suddenly, is</p> - -<div class='nf-center-c0'> -<div class='nf-center c003'> - <div>TABLE VIII</div> - <div class='c004'><span class='sc'>Distribution of Pneumonic Lesions and Grades of Severity</span></div> - </div> -</div> - -<table class='table2' summary=''> - <tr> - <th class='bttd c016'><span class='sc'>Degree of Involvement</span></th> - <th class='bttd c016'>+</th> - <th class='bttd c016'>++</th> - <th class='bttd c016'>+++</th> - <th class='bttd c017'>Total</th> - </tr> - <tr> - <td class='c015'>Left upper lobe</td> - <td class='c018'>10</td> - <td class='c018'>6</td> - <td class='c018'>7</td> - <td class='c019'>23</td> - </tr> - <tr> - <td class='c015'>Left lower lobe</td> - <td class='c018'>4</td> - <td class='c018'>10</td> - <td class='c018'>17</td> - <td class='c019'>31</td> - </tr> - <tr> - <td class='c015'>Right upper lobe</td> - <td class='c018'>12</td> - <td class='c018'>8</td> - <td class='c018'>9</td> - <td class='c019'>29</td> - </tr> - <tr> - <td class='c015'>Right middle lobe</td> - <td class='c018'>10</td> - <td class='c018'>9</td> - <td class='c018'>4</td> - <td class='c019'>23</td> - </tr> - <tr> - <td class='bbt c015'>Right lower lobe</td> - <td class='bbt c018'>5</td> - <td class='bbt c018'>9</td> - <td class='bbt c018'>18</td> - <td class='bbt c019'>3</td> - </tr> - <tr><td> </td></tr> - <tr><td class='c014' colspan='5'>All lobes were simultaneously involved in some grade of pneumonia in 18 cases—56 per cent.</td></tr> -</table> - -<p class='c009'>at times quite remarkable. It may appear very early in disease. -We have not met with a single case where the emphysema of -the lung led to a rupture of the air sacs and an interstitial infiltration -of air through lung, mediastinum, neck and subcutaneous -tissues. Some very remarkable cases are reported by different -authors where this emphysema was of astounding grade leading -to a crepitating infiltration throughout the mediastinum, neck -and the subcutaneous tissues over the thorax and abdomen as -low as the pubis. The milder grade of emphysema consisted -mainly of an abnormal expansion of the air sacs which were not -infiltrated by exudate and which probably had some effect in preventing -the diffusion of the inflammatory fluid from entering -<span class='pageno' id='Page_243'>243</span>certain regions. These emphysematous areas could be readily -recognized by the naked eye along the anterior borders of the -lung as well as between the involved pneumonic patches within -the lung.</p> - -<p class='c009'>These lungs, involved in this early serous and hemorrhagic -exudate varied considerably in their appearance according to the -regional and quantitative involvement. As is seen from Table -viii, the lower lobes were more commonly occupied by massive -exudate than the upper, and the involvement of multiple lobes -was the usual. Still more remarkable is the fact that all lobes -were simultaneously involved in some grade of reaction (pneumonia) -in 56 per cent. of cases. In complicated influenza-pneumonia -Goodpasture and Burnett found the inflammatory reaction -in both lungs and involving to a greater or less degree the lobes -on each side. Most commonly this involvement consisted of a -lobar distribution in one or two lobes with a lobular or patchy -disposition of exudate in one or more of the remaining lobes. -Where the distribution was lobar the involved lobe was distended -to its fullest and the pleura tightly stretched over the -lung tissue which, heavy with fluid, was not solid but flabby. -The lung could be moulded under the finger and could be compressed -into various shapes. At first sight this flabby, heavy -lung tissue suggested the appearance of the waterlogged lung -which one encounters in renal disease or failing circulation. A -closer analysis, and particularly when the lung was sliced, showed -an entirely different character.</p> - -<p class='c009'>Where the inflammatory œdema was accompanied by much -focal hemorrhage the distribution was nodular and suggested -the appearance of the hemorrhagic lung of plague pneumonia. -It was this appearance which led to the suggestion that the -pandemic was not one of influenza but possibly of an infection -related to the eastern plague. The nodular masses of hemorrhage -at times occupied areas varying from the size of a walnut to -that of a golf ball and were localized amidst a relatively mildly -involved lung tissue making a sharp contrast between the involved -and relatively normal tissue. With the removal of the -lung from the body and the partial collapse of the aerated tissues -these nodules became still more prominent. The greater -the amount of hemorrhage within these areas the more solid -became the occupied tissue. Such sporadic distribution of hemorrhagic -<span class='pageno' id='Page_244'>244</span>lesions occurred in the two most intense and rapidly -fatal cases. Both of these individuals died within 48 hours of -the time of onset of the lung conditions. In these two cases we -do not believe that the pulmonary lesions had been prolonged -over a time even as long as 36 hours but with the difficulty of -estimating the onset of the lung involvement we are giving a -liberal estimate of this time.</p> - -<p class='c009'>Besides meeting with the stages of congestion, œdema and -hemorrhage during the earliest days of the pulmonary lesions -we have found that they are to be encountered virtually through -all the stages of the fatal cases either as remnants of the original -reactions which had not been entirely obliterated by the succeeding -purulent process or as was so commonly found, new reactions -occurred in other regions of the lung so that, in the same individual, -inflammatory reactions of different stages of development -could be defined. I do not recollect a single autopsy of a -case dying during the acute period which did not show evidence -of some areas in the stages of this early acute reaction. Naturally -where resolution is well advanced within the lung all trace of -inflammatory exudate of various kinds is removed and where -such individuals with their resolved pneumonia are brought to -death through succeeding complications the above finding will -not be borne out. We limit, however, our statement to the findings -in the acute deaths.</p> - -<p class='c009'>We have previously intimated that the œdema present in the -early stages of the reaction is to be looked upon as an inflammatory -œdema or better as a true serous exudate, and must not -be confused with the transudation of fluids in non-inflammatory -conditions. We have on several occasions collected the fluid -expressed from the soggy lungs and have made some determinations -of their chemical qualities. The difficulty immediately -arises in separating the materials arising from cellular degeneration -from the natural constituents of the serous exudate. We -were unable to obtain specimens in which laked blood was not -present, so that even though the cellular constituents and fibrin -were removed, decomposition products could not be separated. -The analyses, however, gave a differentiation from the transudate -seen in renal and cardiac conditions.</p> - -<p class='c009'>During the period of the accumulation of this inflammatory -fluid the clinician could often recognize a profuse watery exudate -<span class='pageno' id='Page_245'>245</span>within the lung or even observed an abundant serous discharge -arising in bronchi and trachea. At times the quantity of expectoration -was great. Frothy serous fluid accumulated in the air -passages and would periodically be expectorated. At other times -the hemorrhage was of quite serious extent and the patient -would suddenly bring up several mouthfuls or more of bright -blood. This pulmonary hemorrhage was without manifestations -different from the acute illness with cyanosis of other individuals. -The two most acute cases, which we have referred to -above, were of this kind, both of them having marked hæmoptysis -with the loss of upwards of a pint of blood at a time.</p> - -<p class='c009'>The early pulmonary lesion which we have described, we have -called acute serous pneumonia and acute hemorrhagic pneumonia -(or we might speak of it as an acute sero-hemorrhagic pneumonia) -and is one which is distinctive for epidemic influenza. -The cut surface of a lobe involved in this reaction is wet, glassy, -meaty and oozes much blood-stained fluid. It contains no visible -fibrin and presents no characters of a “cellular consolidation.” -As a serous inflammation of the lung it is unique. The further -remarkable character to the pulmonary lesion is that in advancing -through the other stages, it never passes through a stage -of “red hepatization.” Here again we have a distinctive difference -from the pneumococcus-pneumonia. From what we have -previously said about the nature of this early acute inflammation -of the lung in this disease it is apparent that red hepatization -has no place in its process. The stage of red hepatization -is attained only when the inflammatory reaction is accompanied -by certain constituents in the exudate, which upon coagulation -(separation out of the fibrin) renders the lobe dry and solid, -while there is a sufficient abundance of red blood cells and congestion -to maintain a dark red color. The hepatized lung on section -is dry, more or less granular, containing fibrin, red cells and -leucocytes within the alveoli. Extensive œdema is unusual except -in the cases of hypostatic pneumonia, which in well marked -cases bears some resemblance to the gross appearance of the -early influenza pneumonia. We have not encountered a single -case of the red meaty lung of influenza which showed evidence -of true red hepatization in the gross.</p> - -<p class='c009'>The <em>microscopical</em> examination of the lung tissue confirmed -the observations which were made in the gross. In the early -<span class='pageno' id='Page_246'>246</span>stages of congestion the reaction was much more extensive than -what could be spoken of as a broncho-pneumonia. The capillary -dilatation in the alveolar walls occupied diffuse areas varying -from multiple lobules and areas several cm. in size to the -common diffuse congestion of an entire lobe. Capillaries were -distended to their full capacity and often this engorgement was -associated with the leakage of blood or a serous fluid. Not uncommonly -a clear serous fluid was exuded into the interstitial -tissues of the alveolar wall and collected within the air sacs. -The high albuminous content of this fluid was seen in the homogeneous -coagulation which occurred when the tissues were placed -in fixatives. The microscopical sections of such parts demonstrated -the coagulum occupying the alveoli as a clear homogeneous -substance containing relatively few cells and looking not unlike -the colloid deposit of the thyroid. The alveolar walls, themselves, -were infiltrated with fluid so that the distended tissues and vessels -made these structures thick and bulky. In our own observations -we were impressed by the differences of the early inflammatory -reaction from those ordinarily seen in pneumonia. Amongst -these differences was the quantity of fluid extruded into the lung -with a relative absence of fibrin. In some instances fibrin was -completely wanting, although small quantities could be demonstrated -in isolated areas. This observation upon the quantity of -fibrin can be made only during the early stage of the disease in -as much as after secondary infection of various kinds has become -implanted the presence of fibrin has become a variable -quantity often exceeding that seen in the early stages. This is -one of the points upon which the older authors have laid stress -in differentiating influenza pneumonia from others. In this we -fully concur. Whether this lack of fibrin in the inflammatory -exudate is a characteristic to be associated with the infection -by the B. influenzæ alone is hard to say, but in as much as it was -such a prominent finding we are led to lay some stress upon it. -It is, of course, to be realized, as with all other micro-organisms -that under certain conditions fibrin will form an important part -of the exudate even when the B. influenzæ is present. This -is true in the inflammatory reactions of the meninges present in -infections due to this bacillus. Under the conditions of epidemic -influenza where the lung lesion is the prominent and unique -<span class='pageno' id='Page_247'>247</span>reaction this micro-organism fails by itself to bring out this -quality in the exudate.</p> - -<p class='c009'>Not uncommonly this stage of inflammatory œdema was accompanied -by various grades of hemorrhage, varying from the -presence of small aggregations of red cells to a complete flooding -of the lung tissue making it look not unlike a red infarct of lung, -save that the alveolar walls still showed an active circulation and -living cells. It was remarkable that even though there was such -an intense reaction taking place in the lung tissue there was -little or no evidence of a cellular exudate during this stage of -the process. Where much blood was extruded into the alveoli -occasional fibrin threads were found in the coagulum. In these -early cases the bronchicles and small bronchi were found to contain -an exudate similar to that in the alveoli. Not uncommonly -the vessels from which the red blood was escaping, could be -demonstrated in sections. The appearance of the vascular wall -suggested that a definite opening had occurred in the side of the -capillary from which the blood escaped. We were not able to -demonstrate a fatty or other type of degeneration in the cells of -the capillary walls. It is probable that the process of injury was -much too acute to permit of the demonstration of the products -of degeneration within the surviving cells.</p> - -<p class='c009'>The hemorrhagic lesions which had existed for a longer period -of time gradually showed a varying infiltration by wandering -cells. The earliest cells not belonging to those of the hemorrhage -or œdema appearing within the alveoli were mononuclear elements -partly arising from the alveolar walls and partly coming -from the circulation. Numerous mononuclear cells of epithelial -type desquamating from the inner surface of the alveoli accumulated -in the œdematous fluid and the hemorrhage within a short -time after their occurrence. These cells either appeared in -clusters or as single elements. Accompanying this were also large -mononuclear cells loaded with different quantities of pigment -which had apparently escaped from the lymphatic channels within -the alveolar walls. These latter cells belong to the wandering -endothelial type which are active in phagocytosis for foreign -material and which assist so largely in inducing the deposit of -carbon in the lungs and lymph glands. A third mononuclear cell -appearing early in the reaction was the lymphocyte. The numbers -and extent of distribution of this cell were not constant. We -<span class='pageno' id='Page_248'>248</span>have seen it in some of the reactions where very few leucocytes -were to be seen, and where it constituted the main infiltrating cell -of the alveolar wall or the air sacs. We have previously mentioned -its presence in the inflammatory reactions of the bronchi. -Here we find it in the early response within the lung tissue and -appearing amidst a reaction which is intensely acute. It is not -long after the finding of these various cell elements that the -polymorphonuclear leucocyte wanders in large droves to numerically -overshadow the mononuclear cells. Nevertheless, the three -types above mentioned can be recognized in the exudate through -the succeeding stages of reactions in the lung. The large macrophage -shows its phagocytic properties in taking up numerous red -blood cells, lymphocytes and occasional leucocytes.</p> - -<p class='c009'>It is not difficult to demonstrate that the inflammatory reaction -within the bronchi and bronchioles precedes the responses within -the alveoli. Quite often one may find an acute bronchiolitis with -desquamation of the lining epithelium and the early serous exudate -lying amidst the lung parenchyma unaffected by any irritant -and reaction. There is every evidence that the bacteria reach the -lung tissue by extending along the walls of the respiratory tubes -and eventually reaching the air sacs either in the distant extremities -of the bronchioles or when they have arrived at the thin-walled -structures extend through them into the neighboring air -sacs.</p> - -<p class='c009'>It is during this early period that we are able to observe the -characteristics of the initial inflammatory exudate as we have -described it above. The serous exudate and the infiltration by -mononuclear cells appear early while the absence of fibrin also -attracts attention. In place of fibrin there appeared in a certain -number of cases a peculiar material of a hyaline nature which -becomes plastered against the borders of the air sacs forming -a fairly thick laminated structure and within which thread-formation -is not to be seen. Occasionally a few cells lie within -this hyaline substance. Some have referred to this as a type -of fibrin. We have found, however, that it does not give the -staining reactions for fibrin and does not appear to be of the -same composition. These masses are tightly welded to the alveolar -walls and the borders are often indistinguishable. In part -this material appeared to be made up of necrotic cells of the -septum which previously had suffered œdema and circulatory -<span class='pageno' id='Page_249'>249</span>interference. We have found in a number of cases hyaline -thromboses of the fine capillaries with more or less necrosis of the -alveolar septum. At times the septum was entirely destroyed so -that a thick hyaline mass alone separated neighboring air sacs. -This hyaline necrosis resembles in part the superficial necrosis -which was observed along the borders of the denuded bronchi. -There is, however, more than necrosis of cells constituting this -deposit for the bulk of material eventually deposited is much -greater than could arise from tissue cells alone. These hyaline -masses have never been found to lie upon the alveolar wall with an -intact lining, but it is always accompanied by a loss of the lining -cells and more or less destruction of the wall itself. As to the -nature of the hyaline deposit which is laid down in lamellae we do -not know. Fibrin threads occasionally appear to arise from these -hyaline deposits and extend amidst the exudate in the air sac. -One cannot assume, however, that the fibrin and the hyaline -material have any relation to each other as their chemical characteristics -(and mode of deposition) appear to be quite different. -It has been suggested by some that this hyaline material represents -an imperfectly formed fibrin which has formed a jelly-like -clot, not having the property of developing the usual threads.</p> - -<p class='c009'>It is of importance to appreciate that the deposition of these -hyaline structures indicates a severe injury of the alveolar walls -not commonly observed in ordinary pneumonias.</p> - -<p class='c009'>In different areas of the same lung these constituents of the -early exudate may be observed in all proportions of admixture. -Each one of the elements of the exudate may largely overshadow -the others and prominently modify the appearance of the lesions. -Broadly speaking, however, the inflammatory œdema and hemorrhage -occupying the greatest part of the exudate in the lungs and -the absence of marked leucocytic response as well as the absence -of the characteristic fibrinous meshwork in the alveoli give to the -early influenza-pneumonia a character different from those which -we ordinarily see.</p> - -<p class='c009'>It is during this early phase of the reaction that the influenza -bacilli can be shown within the lung structures. The distribution -of bacteria is not uniform. Clusters of these minute bacilli -are found in the alveoli at irregular intervals, many of the air sacs -containing much exudate being quite free from organisms. When -present the bacteria appeared in tightly aggregated schools lying -<span class='pageno' id='Page_250'>250</span>free amongst cells of the exudate, but also certain numbers being -incorporated within the large mononuclear cells. In some regions -organisms of the type of the influenza bacilli were alone seen, -while elsewhere again, and particularly where the exudate was -assuming purulent characters other bacteria of the nature of -streptococci, staphylococci and micrococcus catarrhalis, were also -found.</p> - -<h3 class='c010'><em>Lung—Secondary Stage</em></h3> - -<p class='c011'>Following upon the primary reaction in the lung as above -described, a secondary reaction makes its appearance at variable -periods. This reaction is one in which the inflammatory exudate -resembles more closely but is not identical with the responses -which are observed in ordinary lobar, lobular and pneumococcus-pneumonia. -Whereas in the earlier period, the reaction is largely -one of a serous and hemorrhagic exudate accompanied by peculiar -hyaline deposits along the inner borders of the alveoli, later there -is seen a change in the quality of the exudate with the accumulation -of more cellular elements and some fibrin. The naked eye -appearance of the involved tissue changes considerably. The lung -tissue loses in weight but becomes more solid. The lung contains -less fluid and the cut surfaces are drier and the color of the reaction -changes from the dark congested appearance to one showing -all varieties of red and gray. This change from the flabby and -soggy pneumonia to the more definite type of consolidation occurs -in the regions which have been previously involved and is not to -be found in the lung areas which have escaped the early reaction. -The gray consolidation appears to be either a stage of the influenza-pneumonia -or is a new reaction superadded to those pulmonary -lesions induced by the primary infection.</p> - -<p class='c009'>It is sometimes difficult to recognize the beginning of this pneumonic -stage inasmuch as the gray color does not make its appearance -even with the presence of fairly large quantities of cellular -exudate. The amount of hemorrhage that originally lay in the -affected areas for a long time overshadows the presence of the -color of the cellular exudate. This is also true of the characters -that may be impressed by the presence of fibrin. Small quantities -of fibrin scattered through the congested and œdematous lung are -not readily recognized and the beginning of this secondary reaction -is also easily overlooked if one relies upon evidence of consolidation. -<span class='pageno' id='Page_251'>251</span>More or less solid exudate may occupy a flabby lung -without permitting one to appreciate its presence in the gross -specimen. When, however, the deposit is of sufficient quantity to -change the color of the involved lobe and to alter its consistency, -one has little difficulty in recognizing the changes now taking -place. The earliest development of this change in the inflammatory -reaction was on the fourth day. In the majority of instances -the gray color and the consolidation made its appearance about -the sixth day. We have, however, on several occasions observed -hemorrhagic lesions as late as the seventh and eighth day, at -which time it was impossible to recognize a gray hue to the -exudate or the character of granular consolidation to the involved -lung.</p> - -<p class='c009'>The reaction naturally suggests the stage of gray hepatization -as we so well appreciate it in ordinary pneumococcus-pneumonia -and from the standpoint of its color and the greater solidification -of the lung tissue we might speak of it as such. Here, however, -it must be clearly distinguished from the gray hepatization of -ordinary pneumonia. This secondary lesion of influenza-pneumonia -has but little in common other than its color and the -development of a consolidation with true lobar pneumonia. It is -never as clear cut as we see it in the latter and the degree of the -“gray hepatization” is not uniformly distributed through the involved -lobe. One portion of the lobe will show a diffuse gray hue -while in other parts more decided lobular or patchy areas are -picked out in the advanced reaction. There is not the uniformity -of lobar involvement nor is the distribution as regular as one -obtains it in broncho-pneumonia. Furthermore, the character of -the consolidation differs very decidedly in showing such a variety -of hues in reds and grays and the cut surface is not the picture -of the dry granular consolidation of our endemic disease. The -gray areas are in all states of wetness and ooze a slimy fluid on -the cut surface. In the later stages this exudate is most profuse -resembling a sticky pus. In its appearance we were reminded of -the character seen in unresolved pneumonia as well as in the -pneumonias produced by the pneumococcus mucosus, and the B. -mucosus capsulatus. We would, therefore, avoid the use of the -term gray hepatization and in place of it, as the evidence with the -microscope confirms, use the term <em>purulent pneumonia</em>.</p> - -<p class='c009'><span class='pageno' id='Page_252'>252</span>There are three other characters which differentiate this gray -stage from those of ordinary pneumonias—(1) the irregular distribution, -(2) the friability of the involved tissue and (3) the -interstitial reaction. We have never observed such an irregularity -in the distribution of a gray stage of pneumonia as we have -seen it develop in acute influenza-pneumonia. All types of involvement -of the lobes are found in different cases and even sometimes -in the same case. The least frequent type has been the -broncho-pneumonia in its true form. Broncho-pneumonia as we -see it in children and the cases following measles is usually fairly -uniformly seeded through several lobes and the size of the individual -patches is about that of a split pea. The small bronchus -can be recognized about the center of the involvement. In those -instances one has studded through the lung tissue numerous small -swollen areas which are granular, dry and gray. Differing from -this the patchy distribution of the gray stage of influenza-pneumonia -had no regularity either in the size of the areas nor the distribution. -A lobe may show one or more patches. The patches -may be distributed toward one portion of the lobe more than -another. Furthermore the areas do not always encircle the small -bronchi but involve the terminal portion so that an entire lobule -is more commonly affected. The lobular type rather than the -peribronchial type is most commonly seen and it is often remarkable -how sharply the gray lobule is demarcated from the surrounding -congested lung tissue. On several occasions we observed -a single lobule in the gray stage while the remaining portion of -the lobe was in the serous and hemorrhagic condition. However, -multiple lobules are commonly seen closely associated in the -advancing inflammatory process. Such lobules show peculiar -geographical patches or leaflet-like configuration. Varying with -the number of lobules involved the extent of the gray change in -the lobes assumed more or less a lobar distribution. There was -no uniform position to this pneumonic state sometimes appearing -in the peripheral tissues of the lung, at other times lying centrally -with less involved or less advanced inflammatory reactions surrounding -it. Nevertheless, the gray stage made its appearance -more rapidly in the lower lobe than the upper and it was not -uncommon to find this condition appearing quite early in the -upper posterior portion of the lower lobes. This latter position -is the one which is recognized during life by the clinician as one -<span class='pageno' id='Page_253'>253</span>of the earliest localizations of the demonstrable pneumonia. It is -reported by many that the first physical signs of consolidation are -to be obtained close to the lower angles of the scapulae.</p> - -<p class='c009'>There is no doubt that the character of the pneumonic process -in the epidemic influenza was not the same in all localities. There -have been not a few who have reported a large proportion of their -pulmonary lesions as a definite broncho-pneumonia with an interstitial -purulent involvement. The prominent reaction was a small -circumscribed yellow focus about the bronchioles from which a -bead of pus could be expressed. These pea-sized foci were scattered -through several or all lobes. It is this type of reaction -which appears to develop by a direct extension through the -bronchial walls and to remain quite localized in the alveoli -about these tubes. This reaction seems to be purulent from -its very beginning and does not pass through the stages as -we have described them above. There is more or less fibrin -present in the exudate, but usually not in the quantity observed -in lobar pneumonia. These lesions closely resemble those observed -in the post-measles pneumonia, and it is claimed are the result of -the same agent; the hemolytic streptococcus. In only one case did -we observe a lesion of this kind. The small areas of broncho-pneumonia -were confined to the left lower lobe and in the lower -portion of the upper lobe. Each area was about the size of a split -pea, was quite yellow and in fairly sharp contrast to the background -of an acute sero-hemorrhagic pneumonia. The subsequent -history of these interstitial purulent broncho-pneumonias -is like that in measles, where the tendency toward an organizing -pneumonia has been shown. The importance of the hemolytic -streptococcus in inducing purulent interstitial lesions of the lung -(and also of other organs) cannot be over-impressed. It is not -so much the type of the reaction during its acute stage which -attracts our attention, but the manner of the healing process. It -is more than probable that the organizing pneumonias of influenza, -not only of this distinct bronchial type, but also the lobular, -confluent and lobar variety have had an associated streptococcus -infection. The more intimate discussion of this type of pneumonia -has been given by MacCallum.</p> - -<p class='c009'>Our autopsy experience has led us to believe that the definite -clinical signs of pneumonia are associated with the development -of this gray consolidation of the lung. The lung tissue develops -<span class='pageno' id='Page_254'>254</span>characters which permit the physical signs to be recognized. The -tissue is more solid and more readily transmits the bronchial -sounds. This is not true of the earlier stages where the inflammatory -process is contained within a lung tissue which still is -partially crepitant and when the so-called consolidation is due to -an inflammatory œdema and not to the more solid fibrinous and -cellular exudate. With the protean distribution of the gray lesion -one does not wonder at the clinical difficulties in mapping out or -even finding the consolidated tissues.</p> - -<p class='c009'>As soon as the lobes show this gray character and with the -progressive development of an acute interstitial purulent pneumonia, -the lung tissue becomes friable. All gradations of flabbiness -may still be obtained and in the early stages while the -cellular exudate is accumulating to change the color of the lung, -little variation from the tough character of the pulmonary tissues -can be recognized. When, however, a true gray character is -assumed by a portion of the lobe, the tissue becomes so soft that -it is handled with difficulty without rupture. The thumb can be -pressed into the gray mass and pus will well up around the invading -phalanx. The consistency in the late stages reminds one -of the pulpy tissues in acute splenitis. In cutting such lobes it is -almost impossible to obtain slices of the tissues, their own weight -often breaking such a segment. When allowed to rest on the -table for a few moments, the cut surface becomes coated with a -dirty yellow slime representing pus and products of disintegration -arising from the lung. The stroma and alveolar tissues are themselves -involved in the inflammatory process and many of them -have suffered complete or partial destruction so that they offer -but little resistance to pressure and serve as a poor supporting -stroma to the pulmonary tissues. The reaction which has taken -place within the lung producing both the gray color and the -destruction of the tissues is, indeed, an active suppurative one. -One would not be surprised to obtain not only a purulent lesion -wherein the cellular exudate occupies the air sacs and their walls -but also a further stage leading to a destruction of the tissues to -the extent that abscess cavities are produced. These we have met -with in several instances, some of them being small while others -were several centimeters in diameter. An abscess of larger extent -and having a destructive process which involved the surrounding -tissues so that one would speak of it as a process of gangrene, was -<span class='pageno' id='Page_255'>255</span>observed by Dr. McMeans in one of his cases. A lobar distribution -of the purulent lesion takes place where multiple involved -lobules have fused in their periphery or where a suppurative flooding -of the tissues in this violent late reaction has taken place.</p> - -<p class='c009'>The question at once comes to mind whether this gray stage is -but the late event of what we have previously spoken of as influenza-pneumonia -or whether this condition is superadded to what -may begin as an influenza-pneumonia but end in a pulmonary -inflammation with a mixed infection. Dr. Holman was not able -to demonstrate a sufficient difference in the bacteriology of the -lobes in the gray stages from those in the early acute stage to be -able to say that the flora changes at a certain time during the -progress of the disease in the individuals. It is possible, and -there is some evidence in support of this, that the earlier stages -of the pneumonic process represent the reaction to the influenza -bacillus and that during this period the response is fairly uniform -and similar owing to the fact that this infection has but a short -incubation period and a high pathogenicity. In such an event the -particular micro-organism may bring about a peculiar response -of its own before the other organisms with which it is associated -have the opportunity of producing damage. Subsequently, however, -these secondary organisms impose their peculiar reactions -upon an altered lung, thus inducing an inflammatory lesion which -differs from the preceding reaction and also differs from the reaction -usually induced by those organisms upon relatively healthy -tissues. It is difficult to account for the very irregular distribution -of the gray lesions by an explanation concerning the influenza -bacillus alone, or by the characters peculiar to the secondary -infection. There is an entire want of character to these gray -lesions which makes them differ from other types of pneumonia -known to us.</p> - -<p class='c009'>It is well to lay particular stress upon this peculiarity in the -distribution and extent of the lesions within the lobes; and it is -also important to appreciate the difference in the appearance of -these gray areas from those of true lobar or broncho-pneumonia.</p> - -<p class='c009'>Finally there is another point in which this stage of the pneumonic -process differs from that of pneumococcus lobar pneumonia. -In frank lobar pneumonia the reactions taking place in -the involved portion of the lung are fairly uniform in all its parts. -The stage of red hepatization occupies about that amount of lung -<span class='pageno' id='Page_256'>256</span>which subsequently shows itself in the state of gray hepatization. -In other words, all of those areas which appear gray are preceded -by this peculiar red consolidation, and all of the area occupied by -the red hepatization will pass through the phases of gray hepatization -before entering upon the final stage of resolution.</p> - -<p class='c009'>In influenza-pneumonia, on the other hand, the events taking -place in a given lobe are not uniform and various stages and -grades of the inflammatory reaction may be recognized at the -same time, some appearing red, some congested, some flooded -with blood in hemorrhage and others showing the purulent infiltration -by the appearance of gray patches upon the background -of red. Not only do the various reactions within the same lobe -fail to show similar grades of intensity and similar stages or time -of involvement, but we find that all of the red and hemorrhagic -areas are not destined to pass through the gray stages. At times -it is true an entire lung will enter into the purulent phase and if -this becomes extreme abscess and gangrene are almost certain to -develop. But often the purulent infiltration occupies only a few -or scattered lobules and resolution may take place in a lung where -the greater part of the lobes is occupied by the inflammatory -œdema and hemorrhage and has never become truly consolidated -by cellular and fibrinous exudate. This feature that the involved -lung tissues need not pass through the sequence of events which -is usually observed in frank lobar pneumonia is so distinctive -that it differentiates the character of the inflammatory reaction -very clearly. It may be that this is an indication of the unequal -distribution of the micro-organism and that the first infection -presumably by the <em>bacillus influenzæ</em> has been much more diffuse -and of wider extent than the secondary invading bacteria which -being distributed through the bronchial tree are more or less -localized to those lobules most severely involved. It is impossible -to claim for influenza-pneumonia as clear and sharp-cut stages as -we obtain them in the pneumococcus lobar pneumonia.</p> - -<p class='c009'>During the period of the intense purulent reaction in certain -portions of the lung, the intrinsic structures within the area also -partake in the damage and response. The suppurative infiltration -not only occupies the alveolar walls but also extends through the -tissues of the bronchioles, the arteries and the veins. The polymorphonuclear -leucocytes seem to migrate into all of the parenchyma -indicating some damage by bacterial invasion. On more -<span class='pageno' id='Page_257'>257</span>than one occasion have we observed partial or incomplete thrombosis -of arterioles and capillaries whose walls showed an acute -suppurative reaction. Some of these thromboses are of importance, -being associated with the interference with a blood supply -not compensated by adequate anastomosis. Necrosis and small -areas of gangrene and abscess are to be found in the region of -the circulatory disturbances. It is also during this period of the -disease when the bronchi and their ramifications contain pus or -muco-pus, that the exudate from the alveoli readily finds its way -into the air passages and becoming mixed with the mucus from -these tracts forms a tenacious discharge.</p> - -<p class='c009'>The presence of large amounts of exudate within the bronchi -brought these structures into unusual prominence. This was particularly -true in the purulent stage of the reaction when beads of -sticky pus would well up from the cut bronchioles. We were -tempted on a number of occasions to speak of this in terms of -bronchiectasis but with the intense inflammatory reaction occupying -the bronchial wall and modifying its contour on this account -we avoided this diagnosis. In one instance, however, the lesion -was unmistakable. This was a case of purulent pneumonia (764) -dying on the ninth day of the disease. The distribution of his -pulmonary lesions was distinctly lobular, apparently following the -course of the bronchial distribution. The bronchi were followed -longitudinally and irregular pouchings of the lumen were very -apparent. The bronchi had suffered marked inflammatory reaction -which had also infiltrated the muscular tissues of the tubes. -Goodpasture and Burnett report finding two cases of acute bronchiectasis -associated with abscess and ulceration of the bronchi. -In our case the bronchiectasis was found bilateral but was more -marked in the lower lobes than the upper.</p> - -<p class='c009'>The lymphatic channels within the lung tissue are found active -in establishing an internal drainage to the neighboring thoracic -glands. The lymph vessels were often found filled with leucocytes -and variable amounts of serum. During this late stage only a few -of the endothelial leucocytes were observed wandering to or from -the lung with a load of pigment or cell debris. These wandering -endothelial cells, however, appeared to become loosened from their -normal situations and in the vicinity of lymphatic nodes or communicating -channels where these cells are prone to localize with -their carbon pigment, again assumed their spherical form and -<span class='pageno' id='Page_258'>258</span>took on migratory properties entering into the nearby tissues and -scattering themselves in the looser structures. It is an interesting -point to note that these pigment carrying cells, ordinarily -assuming a latent existence when their cytoplasm has been -crowded with foreign particles will assume all the activities of -migrating cells when the œdema of the tissues alters the physical -properties not conducive to a stationary existence. These cells -will then be found to enter the lung alveoli, often appearing as -cells which have only recently picked up their carbon load. -When, however, the conditions of the experiment, that is, the -production of an inflammatory œdema in the lung, are produced -in the tissues of an individual with much anthracosis, he will, -during the period of his pneumonia and for some time during -convalescence, bring up a greater number of these cells in his -sputum than are ever obtained during the times when the lung is -not involved. We are convinced that inflammatory conditions of -the lung tend to reduce the total number of latent pigment bearing -cells present in the involved tissues, and in this way somewhat -reduce the grade of anthracosis.</p> - -<p class='c009'>A considerable discussion has arisen concerning the proper -nomenclature for the pneumonia or pneumonias found in epidemic -influenza. From some quarters have come the reports of a true -lobar pneumonia, from others a lobular or broncho-pneumonia -and others again claim that the reaction is an interstitial pneumonia -of varying distribution. It appeared to us that the gross -distribution of the lesions is not alone the criterion for a proper -appreciation of the inflammatory states which may arise within -the lung. I believe it has been amply demonstrated that the pneumonic -reactions appearing in different regions of the United -States as well as in different countries are not of a constant kind -when viewed alone in the light of the gross picture nor are they -constant from the standpoint of their bacteriology. We are of the -opinion that the earlier phases of the pulmonary reaction are -fairly constant in different places and that this constancy is -dependent upon the common virus which initiates the respiratory -lesion and which then permits a variety of micro-organisms invading -as secondary agents. The secondary agents vary with the -community and depending upon their nature the character of the -reaction differs from that in other places. It has been well -demonstrated that in some regions the hemolytic streptococcus -<span class='pageno' id='Page_259'>259</span>is the important organism following the primary injury by the -initial virus. In other places the pneumococcus or the staphylococcus -or the M. catarrhalis is found to be of primary importance. -Up to the present it has not been shown that the influenza -bacillus is not the important organism causing the initial reaction -and being responsible for the opportunity of secondary invaders -leading to such diverse reactions in the lung. In our series we -have met with lobar, lobular, interstitial and broncho-pneumonic -types. We have not observed a case of the miliary bronchial reaction -as described and illustrated by Goodpasture and Burnett and -fully investigated by MacCallum. Moreover we have not met -with the type of purulent bronchitis as a characteristic lesion -preceding pulmonary involvement. The occurrence of pus within -the bronchi occurred not early in the pulmonary lesion but later -after the bronchi and bronchioles had passed through their stages -of acute, serous and hemorrhagic pneumonia and were entering -upon their secondary stage with pus production. The pulmonary -lesion had long preceded the appearance of pus in the bronchi. -We do not hold, however, that such relations between the pulmonary -lesion and the purulent bronchitis do not exist for there -is evidence that in particular regions this sequence of events was -closely observed.</p> - -<p class='c009'>We cannot, however, correlate our findings with the classification -of pneumonias as given by MacCallum. His claim for specific -types of pneumonia as a sequel to influenza is based upon his -statement that “no satisfactory evidence has been brought forward -to show that the epidemic influenza is a bacterial infection. -It is evidently a general or systematic infection not especially -affecting the respiratory tract and analogous in many respects, -as Bloomfield has pointed out, to the acute exanthematic diseases.” -Thus we are confronted by two schools concerning the nature of -influenza. The one claiming that epidemic influenza is essentially -a disease of the respiratory system and the other completely denying -this.</p> - -<p class='c009'>I am unable to understand the claims which are put forward -to substantiate the second view.</p> - -<p class='c009'>The classification of the pneumonias as suggested by MacCallum -would be valuable if it could be applied in a practical -manner. We find, however, that his description for the pneumococcus-pneumonia -hardly coincides with common observations on -<span class='pageno' id='Page_260'>260</span>endemic pneumonia and if the description is to apply only to the -pneumonias associated with influenza wherein pneumococcus -alone is isolated we find that our own observations do not coincide -with this. The picture offered by MacCallum under this heading -was reproduced when the bacteriological findings illustrated the -presence of organisms other than the pneumococcus or combinations -of these. The most characteristic of his description is the -one for the streptococcus-pneumonia which when present alone -gives quite a unique picture. The picture, however, is to a certain -degree modified by the reactions which precede the streptococcus -in the lung. Furthermore to offer as a characteristic picture for -the influenza infection of the bronchi the presence of a thick -yellow pus is hardly complete inasmuch as this exudate appeared -only as a stage in the inflammatory process. The intense serous -and hemorrhagic response observed early in this type of infection -is more unique than the presence of pus which appears somewhat -later and which may occur with infections other than the B. -influenzæ. It has long been the hope in pathology to be able to -establish by the character of the tissue reaction, the nature of the -infecting agent. Up to the present this has been possible only -with a very few types of bacteria.</p> - -<h3 class='c010'><em>Lung—Stage of Resolution</em></h3> - -<p class='c011'>The removal of the infection and the inflammatory exudate -from the lung tissue is accomplished slowly. Clinically the pulmonary -process clears up by lysis, and it is quite unusual to have -a crisis with the rapid disappearance of the serious manifestations. -It is difficult to obtain a clear conception of what takes -place in any individual case recovering from an influenza-pneumonia, -but if we have an understanding of what may occur in -the inflamed lung tissue in any one of the stages or varieties of -kind, we may visualize the changing character of the lung condition -tending toward the final restoration.</p> - -<p class='c009'>We have previously pointed out that the early stage of influenza-pneumonia -is one of congestion, œdema, hemorrhage and -more or less leucocytic infiltration, and that this reaction differs -materially from that observed in pneumococcus lobar pneumonia. -There being no stage of true red hepatization, it has also become -apparent that this peculiar primary reaction need not pass into -the stage of gray consolidation. Scattered areas in the lung pass -<span class='pageno' id='Page_261'>261</span>from the condition of acute serous and hemorrhagic pneumonia -to a type of purulent pneumonia while much of the remaining -tissue continues in the state as seen in the early reaction. A certain -amount of cellular exudate makes its appearance but not -sufficient to lead to a true consolidation. This variety of reaction -is present from the fifth day of the pneumonia onwards and may -continue with all of its varieties through until the tenth or twelfth -day or even longer when recovery from the infection is beginning. -Thus the stage of resolution makes its appearance before the -inflammatory reaction in the involved lobes has assumed a common -character and where we are able to recognize different grades -of severity and different stages of inflammation within the same -lobe. Resolution taking place in such a lobe has responses occurring -in the different parts determined by the nature of the antecedent -reaction. We have found that those portions which have -not advanced beyond the stage of œdema and hemorrhage may -clear up with the disappearance of this early exudate and its -infection. In a neighboring portion the purulent inflammation -passes through phases differing somewhat from the preceding -but also tending toward the restoration of the parenchyma and -the disappearance of the inflammation. It would be incorrect to -consider the resolution of the early type of inflammatory reaction -as an abortive process inasmuch as it is not yet clear whether -this serous and hemorrhagic process is not the characteristic -inflammation of a peculiar micro-organism or organisms and that -when acting alone these bacteria do not in themselves stimulate -a further inflammatory response. Hence if it is true that there -is a peculiar inflammatory reaction of a non-suppurative and non-fibrinous -kind the manner of resolution will differ somewhat from -that where these other constituents of the exudate are present. -It becomes clear, therefore, that in influenza-pneumonia all of the -lung involved in the early peculiar inflammatory reaction need not -pass through those stages and reactions as we recognize them in -pneumococcus lobar pneumonia.</p> - -<p class='c009'>The resolution taking place in the areas of serous and hemorrhagic -pneumonia is accomplished largely by a reabsorption of -the fluid, autolytic disintegration of the red blood cells and a -certain amount of phagocytosis of red blood cells and their -debris. This resolution is quite rapidly accomplished, and the -clearing up of such an area may take place in a remarkably short -<span class='pageno' id='Page_262'>262</span>period of time. The leucocytes and endothelial cells which are -present with every such reaction become active in phagocytosis -of bacteria, and we have repeatedly observed them crowded with -small Gram negative bacilli, whose morphology is similar to that -of the B. influenzæ. These areas contain but few bacteria of -other kinds. The exudate in the alveolar walls is also simple in -character and is readily removed. Slight suffusion of blood, -serous fluid, and migrating cells may occupy portions of the -alveolar walls during the acute reaction, but these, too, are easily -removed and the tissue rapidly resumes its normal character. -The vascular and lymphatic congestion again disappear and the -tissues which once were soggy return to a normal state without -leaving behind evidence of the pulmonary incapacity. The lining -epithelium of trachea, bronchi and alveoli is restored by proliferation -from the neighboring less injured parts.</p> - -<p class='c009'>If this early stage in influenza-pneumonia is to be compared -with the early reactions of endemic pneumonia, it is interesting -to note with what ease the resolution may be accomplished in -the former, whereas in the latter a further sequence of stages -must apparently be passed through before the lung is cleared -of its inflammatory products. As we have intimated before, the -early exudate in these two types of pneumonia differs very essentially, -the one being accompanied by much fibrin and leucocytes -which are present only in small quantities in the pulmonary -lesion of influenza.</p> - -<p class='c009'>Resolution of the other portions of the involved lobes in influenza -is not so easily accomplished. Where a progressive lesion -with its development of pus occupying both the air sacs and the -tissue of the lung, the outcome of attempts at repair are uncertain. -Complete resolution with complete disappearance of the -purulent exudate may take place as we see it in many other -regions occupied by a similar reaction; and where the purulent -response is not accompanied by material damage to the tissue the -restoration of the lung is so complete that upon its recovery no -evidence is left behind of the former injury, but in as much as -the presence of a purulent reaction in the lung is often of more -severe grade than this, a certain amount of tissue destruction -having been accomplished, the repair does not completely restore -the tissue to its former normal state. The purulent lesion, however, -is not uncommonly accompanied by minute capillary thromboses, -<span class='pageno' id='Page_263'>263</span>tissue derangement, organic destruction, with even tissue -alteration amounting to abscess or gangrene, and it is too much -to hope that the lung may be completely restored. Minute -abscesses varying from microscopic size to large cavities, several -centimeters in diameter, were not unusual in the tissues severely -involved in the purulent reaction. Thus in these areas, resolution -can be accomplished only by a process of slow organization of -the damaged parts with the final production of fibrosis. These -fibroses are of variable extent depending upon the initial damage. -We have been very much struck with the speed with which this -process of organization may take place and the extent of the -lung tissue which may become involved in this late lesion. In -one of our cases we have evidence of marked fibrosis present on -the twenty-third day of his illness. Patches of organization varying -from one to four centimeters in diameter occupied the different -lobes of the lung. The new fibrous tissue was well developed -and the purulent reaction had largely disappeared. The fibrosis -obliterated the normal architecture of alveoli and bronchioles, -leaving only irregular islands of epithelium which assumed -grotesque glandular shapes and looked not unlike a new growth. -One of the interesting features of these late fibroses which -come to occupy various extents of the lung and bronchial tissues -is that the individual after recovering from his acute influenzal -lesions again passes, in about his third week, into a stage of -dyspnœa with manifestations out of proportion to the physical -signs or constitutional derangements which can be determined. -The dyspnœa is often the outstanding sign and the patient may -die in a state of asphyxia.</p> - -<p class='c009'>We have observed evidence of organization in its earlier reactions -taking place in the patches of gray consolidation. This -organization of the lung tissue takes place as an interstitial -fibrosis and as an alveolar organization. Masses of granulation -tissue grow out into and come to occupy the lumen of the air -sacs, while in other instances the new growth of tissue takes -place mainly in the alveolar walls converting them from thin -partitions to thickened and tough structures. In the cases in -which a purulent pneumonia was present for some time, and -where some of these tended towards repair, this type of restoration -with the new development of connective tissue was found. -The amount of fibrosis varied very much, and in many instances -<span class='pageno' id='Page_264'>264</span>there was no evidence that obstruction to the bronchioles -occurred to a material degree. Hence, although we believe that -more or less organization occurs in all of those cases which have -passed through a purulent pneumonia, and that a permanent -mark is left upon the lung tissue, it is not probable that the -amount of involvement and final damage by fibrosis is sufficient -to seriously influence the pulmonary respiration. There is, however, -a certain percentage of cases in which this organization -and fibrosis does involve sufficient of the lung parenchyma and -bronchioles to interfere with the pulmonary ventilation.</p> - -<p class='c009'>Where the purulent pneumonia has markedly involved the -parenchyma, and particularly where vascular channels both large -and small have suffered, some of them by thrombosis, others by -a sclerotic thickening, the circulatory disturbance may be sufficiently -interfered with to infarct the area. The infarction usually -occupies the purulent area itself, and with the complete occlusion -of the circulation the resulting necrosis gives rise to an appearance -different from that usually seen in pulmonary infarcts. The -area may lie in the peripheral portion of the lobe or may occupy -deeper parts. The infarct is of a cream-white color, quite homogeneous, -and resembles the appearance of a local area of caseous -pneumonia. This appearance is brought about through the local -purulent consolidation undergoing necrosis. Some of these areas -rapidly develop a cavity through liquefaction of the exudate.</p> - -<p class='c009'>The localization of the inflammatory products not only upon -the surface of the air sacs but also in the stroma of the alveoli; -the interlobular trabeculæ, and about the vascular channels indicates -the intense effect of the virus of this disease. The exudate -is largely an indication of the point of action of the irritant upon -the tissues, and in influenza with its variety of bacteria in the -lung this is not limited to the surface membrane of the air sacs. -During this second stage of the reaction the purulent exudate -was found occupying all structures of the involved area. Damage -upon the component tissues was to be seen in the endothelium -of the capillaries, the muscle tissue of the bronchioles and arterioles, -the connective tissues and the epithelium. It was seldom -that bacteria were demonstrated in the interstitial parts, and it -would appear that the damage was the result of their toxins.</p> - -<p class='c009'>Hence, broadly speaking, the end result of the pneumonic -process in influenza is far more complex and indefinite than that -<span class='pageno' id='Page_265'>265</span>in lobar pneumonia. Resolution may take place early with the -clearing up of the first products of the exudate; or it may be -delayed in association with the secondary purulent process which -not uncommonly occupies multiple lobes. Where the resolution -begins in purulent regions the final outcome is most variable, -depending upon the amount of damage which has been imposed -upon the lung tissue during the suppurative inflammation, ending -either in complete restoration or slight fibrosis of the lung, or -passing on to focal scarring of various degrees, sufficient to alter -the pulmonary capacity. In other instances the resolution is -delayed by the development of abscess, infarct and gangrene. -Here the final outcome is determined by the amount of tissue -involved in the destructive process, and the persistency with -which the infecting micro-organisms attack the local tissues and -the constitutional resistance of the individual. Those individuals -in whom resolution begins before there is much purulent pneumonia -stand the best chance of having the lung return to its -normal characteristics.</p> - -<h3 class='c010'><em>Pleura</em></h3> - -<p class='c011'>Inflammation of the pleura was a complication which varied -in its extent and appearance. It appeared to us that a definite -interval lapsed between the development of the lesions in the -lung and the appearance of an inflammatory reaction upon the -pleural surfaces. Although we have recorded evidence of a -pleural reaction in 27 cases, this does not indicate that we have -met with that number of pleurisies of clinical severity. In this -group we include all gradations of pleural reaction from the -merest evidence of irritation and slight dulling of the surface to -the cases in which definite and marked inflammatory exudate -accumulated within the cavity. In many cases we observed a -slight increase in the amount of the fluid present in one or other -pleural cavity, while there was little or no macroscopic evidence -of a cellular or fibrinous exudate. An examination of the fluid -showed the presence of lymphocytes and endothelial cells in small -numbers, and sections of the pleural surface at points where a -slight dulling of the serous membrane was seen at autopsy -showed the presence of a very thin layer of a hyaline fibrin. By -taking these reactions as indicative of pleurisy we have recorded -<span class='pageno' id='Page_266'>266</span>6 cases of acute fibrinous pleurisy, 20 of acute serofibrinous -pleurisy, and 1 of acute fibrino-purulent pleurisy.</p> - -<p class='c009'>An increase in the quantity of fluid in the pleural sacs was the -most common indication of pleural irritation. The quantity -varied from 50 to 500 c.c. of a clear or slightly turbid fluid. Not -uncommonly this fluid was blood stained and evidence of superficial -extravasation of blood could be recognized directly beneath -the pleural membrane. These serous reactions accompanied the -early acute stage, while hemorrhage was the accompaniment of -the early period of the influenzal pneumonia when similar hemorrhages -were found in the lung substance. The pleural reactions -were almost entirely confined to the visceral pleura, and only -in the very severe responses did we obtain a marked inflammatory -reaction with hemorrhage upon the chest wall. Goodpasture -and Burnett state that “there is commonly a moderate serous -effusion in one or both pleural cavities amounting to 50 or 250 -cubic centimeters. The fluid is clear and has the color of blood-stained -serum. The pleural surfaces are smooth, shiny and wet, -though occasionally a thin, granular fibrinous exudate may be -seen by reflected light over limited areas. Often numerous small, -red, discrete, or confluent pleural hemorrhages are present over -consolidated portions, especially posteriorly on the surface of the -lower lobes.” Where organisms other than the influenza bacillus -had invaded the pleural sac and had been present for a sufficient -time to obtain a reaction, the serous type of exudate observed -in the early lesions changed to the turbid type of fluid accompanied -by more or less fibrin deposit. There was one case where -the intense reaction with fibrin and leucocytes gave rise to a new -character to the pleural exudate, a fibrino-purulent pleurisy or -empyema.</p> - -<p class='c009'>As we have subsequently learned the pleurisies developing late -in the course of the influenza and those which persist after the -pulmonary inflammation has passed are prone to be of a purulent -kind. There have been a fair number of cases of empyema -brought to our attention by the surgical department in the bacteriological -laboratory of the hospital, subsequent to the wave -of epidemic influenza. If one were to base his finding alone upon -observations obtained in the operating room, he would be impressed -by the fact that the pleurisy accompanying the epidemic -of influenza is of a purulent type. On the other hand, if one were -<span class='pageno' id='Page_267'>267</span>alone to consider the findings at the autopsy table during the -five weeks of the epidemic, one would be of the opinion that the -pleurisy is of very minor consequence and of a serous type. It -is this changing picture which is particularly to be kept in mind. -And our experience indicates that during the height of the influenzal -lesions of the lung when the pulmonary lesions develop so -rapidly that we obtain a pleural reaction closely resembling the -inflammatory conditions in the lung and also containing bacteria -not unlike the pulmonary flora. Dr. Holman has obtained the -influenza bacillus and other varieties from the pleura during -these early periods of the pulmonary inflammation. It is more -than probable that just as in the infection of the lung tissue -where there is a change in the type of the bacteria present, so, -too, the flora of the pleura alters in the succeeding stages of the -pulmonary reaction. In the late event of empyema we have not -observed the influenza bacillus. The majority of the empyemas -possess hemolytic streptococci and occasionally pneumococci.</p> - -<h3 class='c010'><em>Heart</em></h3> - -<p class='c011'>During the acute epidemic and while the disease was at its -height it was remarkable how few cases showed involvement of -the heart. It was the common observation that even during -intense illness the heart action remained fairly stable and did not -indicate an effect by intoxication as might be expected from the -severity of the illness. In as much as the majority of deaths -occurred within relatively few days of the onset of the severe -infection, the type of lesion that would be looked for in the heart -would be either bacterial inflammatory products within the pericardium, -myocardium or endocardium or toxic lesions of musculature -alone.</p> - -<p class='c009'>In our series we have encountered no cases of pericarditis. -This lesion in the experience of others has also been unusual, -and it would appear that bacterial invasion of this sac is accomplished -mainly in the presence of secondary infections localizing -in the neighboring pleura. It was not uncommon to find a slight -increase in the serous fluid in the sac, but this on no occasion -amounted to a hydropericardium. The fluid was always clear -and with no evidence of fibrin or cellular exudate. Petechial -hemorrhages scattered over the epicardium were noted in seven -<span class='pageno' id='Page_268'>268</span>cases. In the majority of instances these minute hemorrhages -were scattered in small numbers over the ventricular walls. In -one instance these petechial hemorrhages were also present -through the myocardium, suggesting the influence of an intoxication -not upon the tissues of the heart as much as upon the -finer structures of the vascular channels. This is furthermore -borne out in the presence of petechial hemorrhages confined not -to one organ, but to various tissues and structures in the body.</p> - -<p class='c009'>More or less cloudy swelling or granular degeneration of the -muscle elements of the heart was not uncommon. It was sufficiently -pronounced in 12 cases to be readily detected by the -naked eye. A lesser amount was also observed in other cases -on microscopical examination. In only one instances was the -myocardial degeneration of such extent to lead to a definite and -recognizable weakening of the musculature. In this instance the -autopsy showed a flabby myocardium which was relatively soft -and easily broken and in which all the chambers of the heart -were decidedly dilated. This was the only case in which we were -convinced of a sufficient influence of the toxic effects upon the -musculature to permit a stretching of the walls, with failure of -function.</p> - -<p class='c009'>In a number of other instances, however, in which there was -more or less granular degeneration and cloudy swelling we found -that the right ventricle ceased in diastole without, however, the -capacity of the chamber being enlarged. We would make this -differentiation in speaking of dilatation of the heart. We have -met with 11 cases in which the right heart died in diastole, but -in which there was no evidence that the right ventricle had been -unduly expanded. In four cases there was evidence of an old -compensatory hypertrophy of the left ventricle in which the -cavity of this chamber was also slightly larger than normal. The -lesions in these four cases, however, bore no direct relation to -the results from the influenza infection. The appearance of the -musculature with moderate grade of cloudy swelling suggested -some œdema of the tissues. In the myocardium, œdema is difficult -to recognize, and we would not place great stress upon its -presence in mild degree.</p> - -<p class='c009'>The microscopic examination of the myocardium showing -cloudy swelling gave the usual picture as is seen with a variety -of infections. The muscle fibers showed a fine granular deposit -<span class='pageno' id='Page_269'>269</span>in their cytoplasm and the staining quality of the tissue was -somewhat altered. The transverse striæ were less distinct than -normal, while not uncommonly the longitudinal fibrils became -more evident. Fatty degeneration was not encountered.</p> - -<p class='c009'>In the single case showing a definite and acute dilatation of the -ventricles the cause of the myocardial lesion could not be placed -at the door of the influenzal infection. This was the case suffering -from a secondary streptococcal bacteriæmia arising in the -middle ear. It is more than probable that the streptococcus was -the immediate cause of the acute muscle change and weakening. -In a number of cases we have studied the tissues of the bundle of -His, but we were unable to note any definite change.</p> - -<p class='c009'>It is interesting that the intoxication associated with acute -influenza is selective in localizing in certain muscle tissues. We -have previously indicated the intensity of muscle degenerations -occurring in the abdominal recti. Even in these cases where -these striped voluntary muscles were markedly affected the myocardium -showed nothing more than a mild or moderate grade of -cloudy swelling. We can only account for this in a difference -in the constitution of these muscular structures, some being of -such composition permitting of the localizing and damage by -the unknown intoxicant. It does not appear that the reason for -localization in certain tissues is in any way related to the character -of the blood supply, nor is it related to the activity of the -part.</p> - -<p class='c009'>In three cases we have found an inflammatory lesion of the -endocardial tissues. In all of them this consisted of a slight -acute verrucose mitral endocarditis. The lesions were very small, -consisting only of a fine granular deposit looking like grains -of sand localized along the border of the mitral leaflets. In no -instance was the leaflet injured or incapacitated. Unfortunately -the lesion not being suspected was encountered after the heart -had been removed and opened and when it was too late to make -bacteriological analyses. This point is greatly to be regretted, -in as much as it is of great importance to know whether some -distant lesions are induced through the influenza bacillus or its -symbiotic flora.</p> - -<p class='c009'>The majority of authors report but little upon the heart lesions -in influenza. Many deny that a heart involvement is to be found, -a few report an occasional endocarditis. Wallis and Kuskow -<span class='pageno' id='Page_270'>270</span>found more or less myocardial change similar to what is usually -described as cloudy swelling. This reaction they point out differs -in no way from the degenerations arising from other types of -intoxications. Keegan in a series of about 23 autopsies found -only a single case with acute dilatation.</p> - -<p class='c009'>Abrahams, Hallows and French had an opportunity of observing -over 400 autopsies upon the influenza patients, and they comment -upon the infrequency of cardiac dilatation. A slight dilatation -of the right ventricle was seen in a few cases, and in no -instance did they find pericarditis or endocarditis. They comment -upon the heart condition as follows: “The most remarkable -feature about the heart is the general absence of dilatation. In -quite a large proportion of cases there has been no trace of dilatation; -in a fair number of others there has been some dilatation -of the right side, but this has seldom been extreme, perhaps -enough to cause the apex of the heart to be formed about equally -by right and left ventricles. Most often the heart has appeared -of normal dimensions and the apex has been formed entirely by -the left ventricle. This absence of dilatation accounts for the -clinical absence of orthopnœa.” In direct contradiction to the -above findings, the Advisory Board to the D. G. M. S., France, -report the findings in 30 autopsies of clinical influenza. Twenty-nine -of these 30 cases showed dilatation of the heart, chiefly of -the right side, but very commonly of the left side as well. -Twenty-one showed myocarditis and two endocarditis. In this -report it is stated that these patients showed evidence of obsolete -tuberculosis. It is possible that the condition of the patients -and the presence of an unusual complicating infection led to the -high incidence of cardiac involvement. The figures in this last -series are much too high when compared with the frequency of -heart involvement as found by the majority of other investigators.</p> - -<p class='c009'>A number of heart lesions not resulting from influenza were -observed. For none of them was there an antecedent history, -but in some cases the condition may have had an influence in -causing accessory cardiac embarrassment. One case had a -chronic interstitial myocarditis of the rheumatic type, three had -mild grades of chronic sclerotic mitral endocarditis, one a bicuspid -pulmonary valve and three showed old pericardial adhesions, one -<span class='pageno' id='Page_271'>271</span>of them having a complete obliteration of the sac. The foramen -ovale was patent in six of the hearts.</p> - -<h3 class='c010'><em>Arteries</em></h3> - -<p class='c011'>The arteries in these young adults were remarkably healthy, -and in none of them did we observe the characters of arteriosclerosis -or leutic lesions. On the other hand, evidence of superficial -fatty streaks lying in the intima of the aorta and some of -its large branches were not uncommon and are believed to have -had a relation to the acute infection of which they died. In only -four cases in the series of 32 autopsies was evidence of these -fatty streaks wanting. In about one-half of the remaining number -these fatty streaks were only slight or moderate in extent, -while in the rest of them these lesions were particularly prominent -and striking. They formed linear markings on the posterior -wall of the aorta, aggregating with particular prominence about -the intercostal arteries. The anterior wall was quite free from -them. The greater extent of these lesions lay in the descending -thoracic and was less marked in the arch and the abdominal -aorta. At times these fatty streaks were found to extend into -the large vessels of the neck and into the intercostal arteries, and -they were also found in the coronaries of the heart. It was -uncommon to observe their presence in the arteries of the -abdominal viscera.</p> - -<p class='c009'>This type of lesion has been discussed from the standpoint of -its etiology and its possible bearing upon true arteriosclerosis. -Some believe that the frequency of its finding in autopsy -material suggests the non-importance of its presence. This we -can hardly agree with. It is true that the presence of these -lesions does not materially incapacitate the aorta in acting as -the main channel for the distribution of blood. The lesions are -quite superficial in the intima and cause but little elevation on -the surface. The amount of roughening which the intima presents -to the blood is not great. Nevertheless, the presence of -these fatty streaks is an index of the disturbed metabolism of -the cholesterin products of the body. Under certain conditions -they make their appearance when there is a true hypercholesterinemia -such as is readily produced in the animal experiments -by feeding cholesterin. Under these circumstances the various -<span class='pageno' id='Page_272'>272</span>tissues of the body, including the adrenal, the corpus luteum, the -spleen, liver and arteries, all participate in localizing cholesterin -in the form of cholesterin-ester in peculiar cells which have been -termed cholesterin-ester phagocytes. It has been shown that -cholesterin metabolism is quite readily altered in the human and -that the blood content will vary from the normal. In chronic -kidney disease, pregnancy, diabetes, chronic heart disease and -arteriosclerosis the blood cholesterin rises, while in many of the -acute infectious diseases the cholesterin in the blood is materially -diminished. It is particularly in these latter cases where fatty -streaks of the intima are prone to occur. Hence in human -pathology we more often meet with the development of fatty -streaks of the intima associated with a hypocholesterinemia than -with a hypercholesterinemia.</p> - -<p class='c009'>The fatty streaks of the intima of the aorta to which we are -referring are lesions quite aside from true endarteritis as well as -atheroma. In naked eye appearance the lesion is of a fatty -nature and suggests atheroma, but it differs from this well-known -lesion in the fact that the fatty materials, cholesterin-esters, -are contained within cells which are of uniform type and -have no reaction in their immediate vicinity. True atheroma -may occur in definite levels of the intima, most commonly in the -deepest portion, and is characterized by the fact that we are -dealing with a variety of fatty materials, neutral fat, fatty acids, -soap, cholesterin-ester and free cholesterin which lie between the -tissue cells forming a detritus following a process of true degeneration. -It is possible that some of the superficial fatty streaks -do give rise to a small atheromatous area by death of the cells -which primarily contain the fatty substances. Most commonly, -however, the fatty streaks do not progress directly to atheroma -but may entirely disappear, as we have seen it occur in our -experimental animals. At other times these fatty streaks are -followed by a slight thickening of the surface of the intima so -that the resemblance to early endarteritis is obtained. We do -not believe that these fatty streaks in themselves lead to the -chronic nodular thickening of the aorta, but that other factors -giving rise to a low grade inflammatory reaction must be present.</p> - -<p class='c009'>There appears to be a relation between the development of -these fatty streaks and the altered cholesterin metabolism, -brought about by pathological change in the blood, adrenal cortex -<span class='pageno' id='Page_273'>273</span>and it may be in the liver. It is under these conditions where -these tissues are altered particularly by bacterial toxins in a -process of marked cloudy swelling that these intimal fatty -streaks arise. Analyses in other diseases have shown that such -organic changes lead to a diminution in the cholesterin content -of the blood, while at the same time there is neither an increased -intake nor an excessive output. It would appear that certain -types of tissues and cells are stimulated into activity to become -depots for the cholesterin which is not being properly handled -by the adrenal and other organs. These cells in the intima which -become active in taking up cholesterin-esters are types of endothelial -cells whose origin is not entirely clear. In these lesions -it is observed that the most superficial cells of the intima do not -show an overloading with the fatty compound, but that the cells -active in absorption lie at a level slightly beneath the endothelial -lining and form colonies as if arising through active division of -cells which are present in these parts. Active migration on the -part of these cells is not to be observed. They do not appear -to wander far from the location where they are found during the -acute process. The plaque may enlarge by proliferation and thus -enlarge the extent of the involved area. We have failed to find, -however, that these cells migrate into the lowermost portion of -the intima or into the media. The possibility that these cells -do arise from the endothelium lining the blood vessels has, up -to the present, not been excluded. If such is the case, the cells -appear to adopt a function which is not commonly observed in -normal arteries nor present in the endothelial cells lying immediately -above the fatty plaque.</p> - -<p class='c009'>We have searched various arterial systems in the cases of acute -epidemic influenza for inflammatory lesions lying in the adventitia -and media. These, up to the present, we have not discovered. -Some years ago a number of French authors reported the -development of acute non-suppurative influenza lesions in the -outer coats of arteries which at times had aneurysm as the outcome. -These cases, however, occurred during non-epidemic -periods, when the type of influenza of which the patient suffered -was quite different from that seen in pandemics. As far as we -know none of the reported cases of arteritis and aneurysm occurring -under these conditions has shown the presence of the influenza -bacilli in the arterial lesion. It is possible that sporadic -<span class='pageno' id='Page_274'>274</span>influenza has complicating secondary infections which are of -importance in localizing in the arterial wall.</p> - -<p class='c009'>Occasional reports have been made upon the occurrence of -thrombosis immediately following an attack of influenza. These -thromboses have occurred in diverse regions, the brachial, -femoral, the mesenteric, and other arteries. It is possible that -the development of the deep hemorrhagic lesions of muscles in -the extremities are associated with thrombosis. It is impossible, -however, to demonstrate within such blood masses the presence -of thrombosed vessels which had preceded the hemorrhagic state. -It was, however, possible to demonstrate capillary thromboses -through the lung and in the submucosa of bronchi and trachea. -In these instances the damage to the vascular walls was brought -about by the action of the infection immediately surrounding -them, and was not associated with a process beginning within -the lumen of the channel. The type of thrombosis within the -lung to which we have referred in a previous discussion is interesting -in that it does not show the usual type of fibrin clotting, -but in place of fibrin threads a gummy homogeneous material is -deposited upon the vessel walls within which the red blood cells -soon undergo dissolution. It would appear that these thromboses -within the lung are dependent upon a toxic action on the -vessel wall and its plasma content.</p> - -<p class='c009'>Thromboses within venous channels are met with more often -than in arteries. The veins of the lower extremities are most -frequently affected, and yet amidst the many cases of influenza -it is an unusual occurrence. The various thromboses of larger -vessels usually occur as post-influenzal complications rather than -as accompaniments of the acute disease. It is possible that factors -other than those present during the acute stage play an -important part, and that the virus of influenza is not directly -the cause of the thrombosis.</p> - -<h3 class='c010'><em>Lymphatics of Lung and Mediastinum</em></h3> - -<p class='c011'>One of the prominent reactions which was almost constantly -present as the inflammatory reaction involving the lymphatic -system of the chest. The lymph glands within the chest responded -to a marked degree in hyperplasia and commonly showed -enlargement quite out of proportion to what is usually observed in -<span class='pageno' id='Page_275'>275</span>lobar pneumonia. These reactions were in direct relation to the -inflammatory processes of the lung and appeared to be involved -in proportion to the inflammation occupying the tissues drained -by them. Elsewhere in the body the lymph glands responded but -slightly, and often no change was observed in the lymphatics -of the abdomen, axilla and lower extremities. The systemic -intoxication thus had no effect upon distant lymph glands, and -even the presence of micro-organisms in the circulation did not -appear to cause responses in these tissues other than in the -neighborhood of the chest. Within the chest the lymphatic system -became involved through the presence of the various bacteria -migrating along the lymphatic channels as well as through its -activity in removing products of inflammation.</p> - -<p class='c009'>The response of the thoracic lymphatics, including those within -the lung and mediastinum, is observed in all stages of pneumonia. -But in epidemic influenza the reaction was much more prompt, -appearing in the early stages and rapidly developing tissue -changes along the channels and in the lymph nodes. The lymph -channels during the period of the early serous pneumonia became -dilated and filled with fluid with relatively few cells. The stroma -immediately surrounding became œdematous, so that in the gross -specimen the connective tissue between the lobules of lung were -sometimes easily seen as gray strands. At this time this tissue -was not increased in quantity and did not project above the level -of the cut lung. The fibrous tissue remained soft and pliable, but -formed quite wide strands. When the pulmonary reaction became -hemorrhagic, red blood cells, leucocytes and large mononuclears -were found mixed with the fluid in the lymphatics. We -had no way of determining the direction of the lymph flow from -the pulmonary tissues, but it was assumed that as there was no -excessive loss of serous fluid from the lung and the lymphatics -beneath pleura into the chest cavities that the fluid was draining -through the channels lying about the bronchi and vessels. -The further evidence of the direction of flow was seen in the -rapid and comparable responses which occurred in the lymph -glands along these routes. The glands about the bronchi and -at the hilus became enlarged, red and succulent. The glands were -often two and one-half centimeters in diameter. Their capsule -was thin and stretched and the gland was quite soft. Many of -them when cut open were almost diffluent.</p> - -<p class='c009'><span class='pageno' id='Page_276'>276</span>This acute lymph hyperplasia occurred in 30 of our cases. It -is impossible to indicate any particular type of infection as being -responsible for these lymphatic lesions. The nature of the bacteria -present in these 30 cases differed quite considerably: 25 -showed influenza bacilli, 15 pneumococci, 18 streptococci, 8 -M. catarrhalis and 17 staphylococci. In as much as the pulmonary -reaction was fairly constant in certain characteristics in -all of our cases, and as we believe that the influenza bacilli were the -very important factor in these reactions, it would appear that the -lymphatic responses are only a part of the general inflammation -of the respiratory organs. Comparison can also be made of the -character of the lymphatic changes with that occurring within -the pulmonary tissues. The lymphatics were filled with fluid -which dilated all the available sinuses; the lymph nodes were -œdematous and within them the reaction often had numerous -small hemorrhages.</p> - -<p class='c009'>The lesion within the lymph nodes following the early serous -inflammation was of a non-suppurative kind. The lymph follicles -lost their outline, and the lymphocytes were diffused through the -stroma so that no recognition of the germinal centers could be -found. The dilated sinuses within the lymph nodes were filled -with large mononuclear cells, of the type of endothelial cells, -along with some lymphocytes and leucocytes. Subsequently the -leucocytes increased very materially so that the lymphatic fluid -became purulent. Smears obtained from larger lymphatics -showed leucocytes and varieties of bacteria. This was particularly -true in those cases where the pulmonary lesion had itself -become purulent either localized in a patchy pneumonia or with -lobar involvement. Under these circumstances focal areas of -purulent infiltration were found within the tissues of the gland -occupying the regions of the former follicles and leading to -necrosis or abscess. Where such purulent reaction and abscess -formation were found within the lymph nodes there was remarkably -little reaction in the tissues of the immediate vicinity. No -attempt at the development of a pyogenic membrane or granulation -tissue was observed, though this probably does take place in -the cases recovering.</p> - -<p class='c009'>In only one instance did we observe the development of the -peculiar fibrosis along the lymphatic channels where the freshly -cut section of lung reveals prominent and raised demarcation -<span class='pageno' id='Page_277'>277</span>between the lobules. This response has been described by MacCallum -as unique for the streptococcus inflammation of the lung. -The character of the exudate within the lymphatics with many -mononuclear cells and blood is not to be considered singular for -the influenza pneumonia. It has been found that in ordinary -lobar pneumonia, as well as in the pneumonia following measles, -the early pulmonary reaction is accompanied by the dilatation -of the lymphatic channels along the bronchi, containing serous -fluid, mononuclear cells, blood and leucocytes, while occasionally -thrombosis entangling bacteria is also encountered. It would -seem, however, that the lymphatics in epidemic influenza can -more readily recover their normal character when a streptococcus -infection is wanting.</p> - -<p class='c009'>In the late purulent lesions of the lung we have encountered -dilated lymphatic channels whose yellow contents could be recognized -by the naked eye. At times this could be followed for short -distances along the bronchi as narrow yellow cords, or when cut -transversely appeared as small dots close to the bronchi or vessels. -On pressure small droplets of pus may be evacuated, or -again where fibrin has led to a coagulation of the exudate a -yellow plug can be withdrawn from the channel. These small -plugs resembled the thick exudate seen within the bronchi and -often were misleading when first viewed. The distribution of the -purulent lymphatic masses was most irregular occupying only -local or patchy fields in the lung, particularly associated with -the purulent confluent pneumonia. In one instance such a lymphatic -appeared to be associated with the development of a small -abscess lying close to the bronchus.</p> - -<p class='c009'>Too much stress cannot be placed upon the importance of the -lymphatics in all forms of pneumonia. They play an important -role in the drainage of the lung during inflammation. In the -normal lung we hardly appreciate the lymphatic distribution -except in our observations upon anthracosis. But even under -these conditions when much carbon is deposited in conjunction -with the lymphatic system we do not gain a true appreciation of -the activity of the lymph channels and nodes during an acute process. -Bacteria may be demonstrated in acute infections of the -lung within the fluid and cells of the lymph channels. Less -easily may we demonstrate bacteria in the lymph nodes under -similar conditions, although when abscess has occurred their -<span class='pageno' id='Page_278'>278</span>presence is readily recognized. The transport of bacteria is -accomplished not only by a passive migration of micro-organisms -in the fluid as it drains from the lung, but organisms are also -found within the leucocytes as they travel with the current. -Only occasionally have we demonstrated bacteria within the -wandering large mononuclear cells, although we have observed -them in a few instances within the cells lining the sinuses of -the nodes.</p> - -<p class='c009'>Whether the inflammation of the pleura is directly related to -the involvement of the pleural lymphatics we have not been able -to determine. In our series of cases pleurisy has not been a -prominent feature of the disease, and in many instances the -grade of involvement was so slight that it was not easily recognized -by the naked eye and showed only a slight reaction microscopically. -That the presence of bacteria within the intricate -plexus of lymphatics beneath the pleura may be responsible for -the development of an inflammation of this membrane may well -be the case, and in this way simulate the mode of transmission -of the infection as seen in lobar pneumococcus pneumonia and in -the streptococcus type of infection.</p> - -<h3 class='c010'><em>Abdominal Viscera</em></h3> - -<p class='c011'>The lesions occurring in the abdominal viscera were of less -importance than those within the thorax. In none of the cases -of the epidemic was the intestinal type of the disease, described -in previous years, encountered. The changes found in the various -viscera were concomitant with evidences of intoxication as -observed clinically or at autopsy in other regions of the body. -We found no evidence that the bacteria of the disease localized in -the tissues of the abdominal viscera, and we were led to believe -that the alterations in morphology and function were the result -of diffusible toxins. The action of these toxins was either upon -the parenchymatous cells of the organs, as in the liver and kidney, -resulting in granular degeneration, or upon the capillaries -with the development of petechial or diffuse hemorrhage as was -encountered in the stomach, intestines and bladder. The absence -of definite localized inflammatory processes in these distant -tissues, including the abdominal lymphatics, speaks against the -probability of a bacteriæmia playing an important role in the -<span class='pageno' id='Page_279'>279</span>disease. That transient bacteriæmias by the influenza bacillus -do occur has been repeatedly demonstrated, and that the organisms -associated with this bacillus may also enter the blood stream -has likewise been found. But these states are accessory to the -disease, and must be viewed as complications rather than the -rule. Hence the occasional observations by some, of bacterial -inflammatory reactions in liver and kidney must not be considered -a part of epidemic influenza, for in many cases it is wanting. -The majority of lesions of the abdominal viscera probably arise -through the action of the unknown toxin in the blood.</p> - -<p class='c009'>In the <em>stomach</em> and <em>intestines</em> the lesions were of two kinds, -(1) hemorrhage and (2) erosions. Petechial hemorrhages were -present in the stomach 15 times, in the intestines 4 times. These -small dots of blood extravasation, lying in the mucosa and submucosa, -differ in no way from those observed in other acute -infections and intoxications, save that the tendency for the leakage -of blood into the lumen of the viscera was more pronounced. -Often we could observe the presence of free and more or less -altered blood in the stomach and intestines, and in 12 cases the -amount was considerable, sufficient to be spoken of as melena. -It is probable that the oozing of blood takes place not only from -the areas visible to the eye as petechial hemorrhages, but also -from the more normal-looking mucosa of stomach and bowel. -The tendency to hemorrhage was not necessarily accompanied by -visible alterations in the epithelial layer of the mucosa, though -at times erosions were found. When hemorrhage could be -observed, the extravasation of blood occupied the superficial -layers of stroma, causing a separation of the tissues beneath the -epithelial layer. At times the submucosa was also infiltrated, -and in one instance the musculature. The lesions were isolated -and sporadic, but always about small capillary loops. It appeared -to us that the damage was primarily upon the vascular tissues -and particularly upon the endothelial walls of the fine channels. -Inflammation was not present, and the hemorrhage was more or -less passive—that is, a slow oozing rather than acute hemorrhage -by rhexis.</p> - -<p class='c009'>The second type of lesion of the gastro-intestinal canal was -erosion. This was of the nature of a defect in the mucosa, -usually multiple, small and well circumscribed. The tissue loss -was superficial. In their appearance these lesions were similar -<span class='pageno' id='Page_280'>280</span>to those encountered in these parts in other infections, and also -as described by McMeans in experimental infections of animals. -The erosions appear to arise in a process of bland necrosis, limited -in the periphery by healthy tissue and not tending to enlarge. It -is probable that these erosions are associated in their development -with the petechial hemorrhages, being a sequel to the vascular -disturbance of the mucosa and subsequent digestion of the -injured tissue. Multiple lesions of the stomach were found 10 -times and twice in the intestine. The largest was 1.25 cm. in -diameter. They are more common on the posterior than anterior -wall, and usually toward the lesser curvature. It is probable that -these defects are limited in their progress and heal readily.</p> - -<p class='c009'>The changes occurring in the <em>liver</em> were not of striking account. -Cloudy swelling was observed 13 times, usually of moderate -grade. The usual appearances with enlargement of the organ, -bulging of the parenchyma on section and a dull gray cut surface -were all that could be found. The one case with icterus was the -only one in which the natural discharge of bile from the liver -was interfered with through the swelling. Even in this case the -obstruction to the outflow of bile in the small channels was not -demonstrable in the microscopic sections, nor was there evidence -of unusual bile staining of the liver-points suggesting the possible -origin of the icterus in an unusual hemolysis. On no occasion -did we meet with recent inflammatory reactions in the gall -bladder or bile ducts, and we have no evidence that the organisms -of the infection are discharged from the body by these routes. -The cloudy swelling of the liver was accompanied by slight -œdema of these tissues in seven cases; and in six instances focal -necroses were observed. These focal necroses were similar in -appearance to those seen in typhoid fever, but were much less -frequent in the tissue. Only careful search revealed isolated pinhead -gray dots with depressed centers. They were most commonly -in the mid-zone of the lobule, and in the early stage were -without inflammatory reaction. Subsequently, leucocytes infiltrated -the area, but not in an amount to form pus. Bacteria -were never demonstrated in the areas of focal necrosis. Four -cases showed old adhesions about the gall bladder and in one a -gall stone was present.</p> - -<p class='c009'><span class='pageno' id='Page_281'>281</span>Lesions of the <em>pancreas</em> were not encountered. In a few cases -the lymph glands about the head of the pancreas were slightly -enlarged.</p> - -<p class='c009'>The <em>spleen</em> showed relatively little reaction and in only two -cases was it enlarged. Fourteen times a diagnosis of acute -splenitis was made on examination of the gross specimen. This -diagnosis rested upon the finding of a swollen spleen with tense -capsule and with a dark bulging pulp. The Malpighian bodies -were usually in part or completely obliterated, though in a few -instances these grayish nodules seemed even larger than normal. -These spleens contained an excess of blood within the pulp. In -one case several isolated areas appeared hemorrhagic as if a local -rupture of the tissues had occurred. The microscopic examination -of these specimens showed mainly a marked congestion of -the sinusoids, a diminution in the size of the lymphoid corpuscles -and some increase in the number of leucocytes within the blood -spaces and reticulum. Only occasionally did we observe a proliferative -reaction of the large mononuclear cells lying in the -reticulum. This proliferation was not sufficiently marked nor -uniformly present to be considered as characteristic. We did not -find abnormal deposition of blood pigment indicating an unusual -destruction of red blood cells within the spleen. It is interesting -to note that 5 of the 32 cases showed obsolete miliary tubercles -in the spleen.</p> - -<p class='c009'>Our analysis of the changes occurring in the <em>kidney</em> bore out -the clinical findings observed in the wards. Like in so many -acute infectious diseases urinary changes were commonly present. -These are in part dependent upon systemic changes in the metabolism -of tissues and not entirely the result of renal lesions. In -acute epidemic influenza there was no common characteristic in -the urinary output. The amount excreted in 24 hours was usually -diminished to a small extent, the color was darker, the specific -gravity slightly increased, as well as the total solids. There was -no marked change in the total quantity of output of any one of the -constituents as far as they were analyzed by us. Albumin was -present in the urine in variable amounts and in the more severe -cases casts were also present. There was only one case in which -the quantitative output was much diminished and where some fear -was entertained of development of acute uremic manifestations. -This individual, however, died before these made their appearance -<span class='pageno' id='Page_282'>282</span>and before there was any evidence that the retention of -waste products was causing definite clinical symptoms.</p> - -<p class='c009'>In 30 cases coming to autopsy more or less cloudy swelling -was to be observed in the kidney. This reaction varied from a -very mild swelling and granular degeneration of the tubules of -the cortex to a decided parenchymatous degeneration with loss -of nuclear structure and erosion of some of the cells lining the -tubules. The convoluted tubules were always most markedly -involved. Occasionally this tubular degeneration was accompanied -by a desquamation of the lining cells of the glomerular -capsules. We were, however, unable to recognize an acute inflammatory -reaction in the interstitial tissue or in the glomeruli in -any of the cases, except the one which had developed a streptococcus -bacteriæmia as a sequel to an otitis media. The kidney -lesion reminded one very much of the toxic lesion which is -observed in the kidney in typhoid fever. Differing, however, -from the latter there was a variable congestion of the fine vessels -associated with the cyanosis which was present in a certain percentage -of these cases. At times the kidneys were quite wet -with blood from the venous engorgement.</p> - -<p class='c009'>The lesions in the kidney were of a toxic type and did not -resemble reactions following the presence of the bacteria in the -stroma of the organ. In the majority of instances in other diseases -where bacteria themselves locate in tissues we are able to -recognize focal lesions of acute necrosis or inflammation. In -epidemic influenza where a variety of micro-organisms within -the lung are able to reach distant structures in a bacteriæmia, -we would, because of their type, expect to find inflammatory -reactions of a definite kind. The absence of such reactions is -very suggestive that the bacteria do not commonly localize in the -kidney, but that their toxins alone affect it during its elimination. -We have also entirely missed the finding of any vascular -lesions in the renal system. Neither degeneration nor inflammatory -reactions of any of the coats of the blood vessels could be -distinguished.</p> - -<p class='c009'>The partial incapacity on the part of the kidneys must, therefore, -be viewed as a complication resulting from the effect of a -diffusible toxin reaching them by the blood stream. The damage -performed in this manner may be quite extensive upon the -secreting tissues of the tubules leading to an increased or decreased -<span class='pageno' id='Page_283'>283</span>output of the urinary constituents. Because of the nature -of the lesion, it is probable that the kidney damage incurred -during the acute epidemic influenza is only temporary and not -permanent. Tubular degeneration is readily repaired, and in the -absence of an inflammatory reaction in the interstitial tissue -or the glomeruli avoids the development of a permanent mark or -derangement in the system. This is as we find it in typhoid -fever.</p> - -<p class='c009'>In two cases we observed very interesting lesions in the <em>bladder</em>. -These two individuals during life had been excreting -markedly blood-stained urine for some days preceding death. -In the one case the hemorrhage was so marked that on standing, -about one-tenth of the urine was composed of sedimented red -blood cells. It was assumed that the hemorrhage was of kidney -origin until the autopsy revealed a simple cloudy swelling of the -kidney associated with a hemorrhagic state of the submucosa -of the bladder. In both cases the posterior wall of the bladder -was heavily infiltrated with blood so that the mucosa was raised -from the surface and the prominent folds showed a superficial -erosion with small points of greenish necrosis. This bladder -hemorrhage was concomitant with hemorrhagic foci elsewhere -in the body, pericardium, pleura, stomach and intestine. Alone -in the bladder however, the hemorrhage formed a distinct mass -and allowed a considerable escape from the lesions on the surface. -These areas of hemorrhage were not infected and showed no -local inflammatory reaction. They also appeared to be toxic in -origin and resembled the hemorrhages occurring in the muscles -of the abdomen.</p> - -<p class='c009'>Changes in the <em>adrenal</em> gland were noted in 14 instances. In -all of these there was the picture of what is commonly known -as cloudy swelling of the cortex and, in addition to this, in three -cases small petechial hemorrhages were observed. The so-called -cloudy swelling of the adrenal consists largely in a loss of the -bright golden appearance of the cortical tissues accompanied by -soft œdematous swelling. The tissues change color to a brown or -clay color, and it is not uncommon to observe that the inner -zone of pigmentation is more diffuse. There is no sharp demarcation -between the layers of the cortex. With this alteration in -the outer structure of the adrenal, the medulla not uncommonly -<span class='pageno' id='Page_284'>284</span>appears smaller. This change is more apparent than real, and -we have not been able to observe any definite lesion in the nervous -portion. At times we believed that the inner tissue appeared -more cellular, but it was not possible to determine any specific -alteration in the cells.</p> - -<p class='c009'>The changes in the adrenal cortex are comparable to those -observed in typhoid fever. The analyses of these tissues showed -that the cells were almost devoid of cholesterin bodies and few -doubly refractile globules could be demonstrated. This change -in the adrenal is by no means specific for any acute disease, it -being found in many of the severe infections. We regret that -systematic analysis of the blood serum in these cases was not -made to determine the cholesterin content. If the comparison -bears out with typhoid fever, we would expect to find that the -quantitative cholesterin of the blood is diminished. Some importance -attaches itself to the study of the cholesterin metabolism, -particularly in regard to the development of the peculiar fatty -streaks which develop in the aorta and other arteries during -these acute infections. It has been claimed that in the human -these streaks bear an analogy to those produced in the experimental -animals and that the arterial lesions are associated with -an altered activity on the part of the adrenal cortex in handling -the cholesterin compounds. In influenza there is evidence that -the adrenal does not function in a normal fashion and that the -storage of cholesterin-esters does not take place. From this, -however, we cannot conclude that the blood content is increased, -and, in fact, it is more than probable in comparing the other -reactions of the disease that it follows the changes as seen in -typhoid fever where the blood content of cholesterin is lowered. -In this way comparison with the experimentally produced arterial -lesions in animals is not clear, in as much as in the experimental -work a true hypercholesterinemia was induced. Nevertheless it -is possible that with the abnormal function on the part of the -adrenal the cholesterin materials are made more available for -absorption by other tissues and that a true hypercholesterinemia -is not necessarily a constant factor, even with the abnormal -accumulation of these substances in the intima. It may well be -that the normal activity of the adrenal is related to the presence -<span class='pageno' id='Page_285'>285</span>of toxins in the circulation and an attempt by mobilizing cholesterin -to diminish the activity of these harmful substances.</p> - -<h3 class='c010'>OBSERVATIONS UPON THE PATHOLOGY OF EIGHTEEN CASES OF INFLUENZA</h3> - -<div class='nf-center-c0'> -<div class='nf-center c004'> - <div>By <span class='sc'>J. W. McMeans</span></div> - </div> -</div> - -<p class='c009'>The recent epidemic of influenza has afforded a series of interesting -autopsies in view of the very extensive and peculiar -involvement that occurred in the lungs of the cases examined. -Ordinary lobar pneumonia, as we know it, was not observed, -although it must be said that the lungs many times exhibited a -consolidation of a lobar distribution. The usual dry granular -lung of the more common pneumonia was absent, and in its stead -a most unusual series of pictures was observed in the several -cases. A common feature of all cases was the œdema of the -lung tissue, which in the majority of instances contained such -an amount of fluid that it ran freely from the cut surface in -almost unlimited quantity. This fluid varied in its color and -consistence depending upon the age of the process. In the very -early cases the lungs were boggy, very congested, and a thin -serosanguinous fluid poured forth from the cut surface. It -actually appeared as though the fluid within the tissue was under -considerable pressure. At times blotchy deep red hemorrhages -occurred in the lung substance, and hemorrhages of a bright red -color were not infrequent in the pleura. That the circulation of -the lungs was much embarrassed was often prettily demonstrated -by the dilatation of the fine capillaries and lymphatics beneath -the pleura. These small vessels stood out prominently as a -meshwork more or less outlining the areas supplied by them. -Not only was the peculiar consolidation in lobar arrangement, -but also in many cases was there evidence of a lobular distribution. -Even in some cases where the entire lobe was consolidated -the cut surface presented a peculiar lobulation with patches of -lung tissue projecting above the general surface. The wet -trabeculated structure of the lung in this stage did not give the -impression of true red hepatization, but rather a structure -resembling spleen and at times a meaty, compact, glassy picture -not unlike thyroid.</p> - -<p class='c009'><span class='pageno' id='Page_286'>286</span>As the process advanced the appearance of the lung changed -from deep red to yellowish red and finally to a quite yellowish -gray color, still retaining, however, the very moist characters. -The fluid found in the lung changed its consistency from the -thin red type to a sticky, glairy variety which could be pulled -out in long strings. It was noted that the change in the character -of the fluid was accompanied by similar changes in the lung -structure, advancing in two cases to abscess formation of a -grape-bunch type. Here there was a rather extensive necrosis -and cavitation of lung substance in communication with the -bronchioles. However, there was also marked softening and -necrosis of lung in a number of cases where abscesses did not -develop, but the lesion was so advanced that the lung substance -was almost diffluent. An accompaniment of these advanced cases -were irregular yellow islands which appeared beneath the pleura. -At times they reached the size of a circle 2 cm. in diameter and -were slightly raised above the surrounding pleural surface. When -these were opened they were found to be areas of softened lung -substance. This reaction was so extensive in some lungs that -it resembled to a degree the appearance of a caseous pneumonia. -However, the former process appeared to be brought about by the -interference with the lymphatic drainage, as it was not uncommon -to see engorged yellow channels beneath the pleura as well -as enlarged lymph nodes at some distance from the hilus. -Another feature of the advanced cases were the plugs of ropy -yellow material which were contained within the bronchioles, -while in the early cases the bronchi and bronchioles showed -intense congestion of the mucosa with blood-stained fluid in their -lumina.</p> - -<p class='c009'>Of the more unusual reactions observed in the lungs an infarct -was found occupying a considerable part of the lower left lobe -in one case. There was a marked softening of the lung tissue -with reddish, mucky-looking lung substance arranged about small -irregular cavities. This reaction extended into the lung for a -distance of 4.5 cm. Bordering close on these softened areas -there was a dry mottled yellowish gray and deep red lung tissue. -Surrounding this area again were noted a number of small blood -vessels in which there were found yellowish granular plugs. One -plug in a vessel was found at a distance of 3 cm. from the base -<span class='pageno' id='Page_287'>287</span>of the lobe, and another was found at a distance of 8 cm. from -the apex of the lobe. On further examination it was observed -that the base of this softened area was situated on the pleural -surface and that the apex was directed inward about a distance -of 6 cm. from the pleura. Bathing the cut surface there was a -glairy and very sticky material of a reddish yellow color. Near -the apex of this softened area in the lung there was found a -vessel about the size of a goose-quill in which there was a grayish -yellow granular plug. This plug was adherent to the vessel. -Within the small bronchioles there were plugs of a soft yellowish -brown material. The striking feature in addition to the softening -of the lung in a number of places was the glairy material of a -sticky nature which bathed the cut surface. A white infarct was -present in the spleen. The lung described above as well as -another showed gangrenous change. In the second of these two -abscesses had formed, and there was a communication between -the lung and pleural cavity in which there was a large amount of -sanguino-purulent fluid and a pyopneumothorax.</p> - -<p class='c009'>In a description of these reactions it must be added that the -early and late changes were not always observed independently, -but in most cases occurred together, giving the lung a peculiar -mottled red and yellow glassy appearance. More frequently the -congested œdematous reaction was observed singly, while the -purulent alteration usually was in combination with the former -type. The acute serous pneumonia was noted 13 times, 6 times -in combination with the purulent reaction and 7 times alone, -while the acute purulent pneumonia was found in 9 cases, 3 times -alone and 6 times with an acute serous process. In all but -3 of 18 cases there was evidence of a bronchial distribution. Two -of these three cases showed a massive œdematous lung with in -one case an extensive hemorrhage, while the third presented an -advanced purulent reaction with marked necrosis and softening. -An acute bronchitis which varied in character from a hemorrhagic -to a purulent one was present in all the cases. The reaction -observed within the bronchi in the individual cases corresponded -closely to the picture found in the lungs.</p> - -<p class='c009'>In all cases except one there was an exudate in one or both -pleural cavities. A serofibrinous pleurisy was noted in 11 cases -with, in 2 of this number, a fibrino-purulent reaction present -<span class='pageno' id='Page_288'>288</span>in the opposite pleural cavity, while fibrino-purulent pleurisy -occurred alone in 6. In 6 cases pleurisy occurred on one side -only with the incidence equally divided in each cavity. Both -pleurae were involved in 9 cases. Seventeen of the 18 cases -showed both lungs involved. One case was an individual who had -had clinical influenza and during convalescence developed gangrenous -colitis and acute ascending myelitis which terminated -fatally. B. influenzæ was isolated from the bronchioles in the -lung of this individual.</p> - -<p class='c009'>The reaction of the body generally was evidenced by a widespread -distribution of petechial hemorrhages over serosal and -mucosal surfaces. However, certain other important lesions -were noted such as one acute vegetative mitral endocarditis, -two acute serofibrinous pericarditis, three cases in which focal -necroses were prominent in the liver and two examples of infarct -of spleen. Further, there were four cases of slight dilatation of -the right heart. The liver was usually swollen and œdematous -and the spleen presented evidence of an acute reaction, softening -and reddening of its pulp with at times slight enlargement.</p> - -<p class='c009'>As evidence of the virulent character of the infection from -which these patients suffered, there was not only present in the -lung a peculiar hemorrhage and purulent process, but also a -more or less widespread distribution of hemorrhages in other -parts of the body. The gastro-intestinal tract was most affected -with the stomach showing petechial hemorrhages in 17 of 18 -cases and the small intestine in 15 of the same number. In the -gastric mucosa of three cases there were definite erosions, while -in two instances the duodenum presented an intense œdematous -and hemorrhagic appearance of its mucosa. Further hemorrhages -were observed on one occasion each in the mesentery and -in the mesenteric and retroperitoneal lymph nodes. In the latter -the mesenteric glands were so distended with hemorrhages that -a soft pulp spurted out when the glands were sectioned. Next -in order of frequency, hemorrhages were noted 9 times in the -pleura, 8 in the pelvis of the kidney, 6 in heart muscle and 3 -each in pericardium and bladder. In one case of widespread distribution -of petechial hemorrhages there was a massive loose -hemorrhage into the lower recti abdominis. Further another -<span class='pageno' id='Page_289'>289</span>case showed a large amount of a blood-stained fluid in the peritoneal -cavity.</p> - -<h3 class='c010'><em>Summary</em></h3> - -<p class='c011'>In the analysis of the cases of acute epidemic influenza two -important features of the disease present themselves, (1) a -marked systemic intoxication with localized manifestations in -certain organs, and (2) inflammatory lesions of the respiratory -tract. These manifestations present themselves both to the -clinician and to the pathologist, and to each they have demonstrated -their importance in the disease. The pathologist not in -touch with the clinical manifestations of the toxæmia has more -closely linked the occurrence of these two factors with the actual -findings in the cadaver. But there are those who look upon -these factors as separate and distinct, viewing the toxæmia as -an individual process and as illustrating the uninvolved influenza, -while the inflammatory reaction of the respiratory tract is taken -to be a complication arising through the activity of secondary -invading organisms. This is the view held by MacCallum, who -compares influenza with the acute exanthemata wherein the -respiratory lesions are but secondary to the production of a -lowered resistance and an invasion by a variety of bacteria. Such -confusion presupposes an undetermined virus for influenza. In -confirmation to such views we have the reports upon a filterable -virus. Up to the present, however, the latter has been on insecure -grounds.</p> - -<p class='c009'>It would appear to us that, as has been discussed by Dr. Holman, -the case against the B. influenzæ not being the important -causative agent has not been proved. The demonstration by -others of a potent toxin from the B. influenzæ cannot be overlooked, -and although the actual disease has not been reproduced -in animals, there is evidence that this toxin will induce acute -degenerations in various tissues. Furthermore, the in vitro -symbiotic relation demonstrated for the B. influenzæ with other -organisms, as the pneumococcus, streptococcus, staphylococcus -pyogenes aureus and M. catarrhalis, gives ample support to the -claim for a similar symbiosis in the human tissues. The evidence -for the important primary relation of the B. influenzæ to epidemic -influenza is such that we cannot disregard it—at least, -<span class='pageno' id='Page_290'>290</span>not before we can produce some definite positive evidence that -another demonstrable virus precedes it and produces those constitutional -effects which initiate the remaining sequelæ.</p> - -<p class='c009'>We must agree with Christian in the statement that all cases -dying during the acute stage of epidemic influenza have inflammatory -lesions in the respiratory tract and largely in the lung -(pneumonia). It is difficult to conceive of a disease comparable -to the acute exanthemata, which beginning as a separate and distinct -process ends fatally within 48 hours with a pneumonia -which is claimed to be secondary.</p> - -<p class='c009'>Epidemic influenza is an acute infectious process of the respiratory -tract, usually localizing in the upper respiratory system, but -often and in a fairly constant percentage of cases extending into -the lower portion of the same system and causing a type of broncho-pneumonia. -Accompanying the initial invasion there is a -marked systemic intoxication with lesions of degeneration arising -in a variety of tissues. These lesions of degeneration are to be -seen both locally in the respiratory system as well as in distant -parts, as in the muscles, kidney and liver. The primary damage -arising in the respiratory organs, and which we believe to be the -result of infection by the B. influenzæ, facilitates attacks by such -other bacteria as are available and pathogenic to man. The -secondary invaders are not constant in type, but we find variations -according to the localities where the epidemic takes place. -Just as there is a difference in the bacterial flora which constitutes -the secondary invasion, so, too, there is a variation in the -picture of the inflammatory process which appears in the lungs. -The occurrence of the miliary streptococcal broncho-pneumonia -has been met with in certain localities much more frequently than -in others; lobular and confluent pneumonia has been the prevailing -type in certain regions, while a lobar purulent pneumonia with -abscess and gangrene was most frequent with others. There -does not appear to be an individual and constant character in the -mode of distribution of the pneumonia in the lungs. That the -pneumonias were not the usual type otherwise seen, is fairly -agreed upon by all. The most astonishing feature presenting -itself to us was the frequency of death occurring in the early -stages of the inflammatory process and before the gray stage -had definitely developed. The gray stage of influenza pneumonia -<span class='pageno' id='Page_291'>291</span>is a purulent pneumonia which often also constitutes an acute -interstitial pneumonia.</p> - -<p class='c009'>The extensive hemorrhage and inflammatory œdema of the -lung are striking during the early stages of the lung involvement. -The mononuclear infiltration which appears early and remains -for a variable time, until the purulent process is well under way, -is also unique. The hyaline deposit in the lung alveoli; the capillary -thrombosis and necrosis of the alveolar walls and bronchi -are important; while the tendency to abscess, infarct, gangrene -and incomplete resolution with fibrosis differentiates this type of -pneumonia from the common lobar variety.</p> - -<p class='c009'>As an organic evidence of the acute intoxication, none stands -out more prominently than the degeneration of the voluntary -muscles. These resemble the waxy degeneration of other bacterial -intoxications, and particularly that of typhoid fever. The -finding of these acute degenerations does not assist us in arriving -at a conclusion as to the nature of the poisonous body, whether -a true exotoxin. The presence, however, of such widespread -degenerative lesions in cases showing no naked eye change suggests, -at least, that the peculiar muscle weakness associated with -pain has its origin in this definite process and not in primary -nerve lesions.</p> - -<p class='c009'>Very interesting it is that the different muscular structures -are not equally affected by the intoxication. This is particularly -noteworthy in the heart and intestine. In neither of these structures -have we met with lesions comparable to those in the voluntary -muscles. Wherein this immunity resides we cannot state. -In our own series, as well as in the majority of others, there was -an unusual absence of evidence of myocardial weakness. In most -of those dying during the acute illness, the heart muscle was -found firm and the cavities not dilated. This finding was in -striking contrast to that found in acute lobar pneumonia where -dilatation of the right ventricle and auricle, along with muscle -degeneration, is almost the rule. In but one case of the present -series did we find myocardial degeneration leading to dilatation -of the cavities and causing death. And in this particular case -the intoxication was due to a streptococcus septicæmia arising -as a late sequel from the middle ear. The heart in influenza -withstands remarkably well the effects of an intoxication from -<span class='pageno' id='Page_292'>292</span>the disease and carries the extra load imposed upon it by the -involved lung with little evidence of fatigue.</p> - -<p class='c009'>It is also worthy of attention to note that the kidney suffers -so little in this severe disease. Bacterial localization with inflammatory -concomitants does not occur, and there is no lasting -damage upon its structure. As in so many conditions of bacterial -poisoning, tubular degeneration, varying from a cloudy swelling -to a more acute damage, is to be found in a percentage of cases, -but complete restoration is rapidly obtained in convalescence. -It is unusual to find such severe renal damage to incapacitate -function to a degree to endanger life.</p> - -<p class='c009'>Finally we can add our evidence, gained from a study of the -pathology of epidemic influenza, that the primary disease induced -by the invasion of the B. influenzæ opens the way for secondary -infections of a variety of kinds, whose subsequent effect may be -more serious than initial lesions. The many late complications -which arise in this manner we have not investigated.</p> - -<h3 class='c010'>BIBLIOGRAPHY</h3> - -<table class='table3' summary=''> - <tr> - <td class='c006'>Abrahams, Hallows and French</td> - <td class='c028'>Lancet., 1919; i, p. 1.</td> - </tr> - <tr> - <td class='c006'>Advisory Board to the D. G. M. S</td> - <td class='c028'>Brit. Med. Jour., 1918; ii, p. 505.</td> - </tr> - <tr> - <td class='c006'>Blanton and Irons</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1988.</td> - </tr> - <tr> - <td class='c006'>Boggs</td> - <td class='c028'>Johns Hop. Bull., 1905; xvi, p. 288.</td> - </tr> - <tr> - <td class='c006'>Brooks and Cecil</td> - <td class='c028'>Brit. Med. Jour., 1918; ii, p. 496.</td> - </tr> - <tr> - <td class='c006'>Chickering and Park</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 617.</td> - </tr> - <tr> - <td class='c006'>Christian</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1565.</td> - </tr> - <tr> - <td class='c006'>Cole</td> - <td class='c028'>Brit. Med. Jour., 1918; ii, p. 566.</td> - </tr> - <tr> - <td class='c006'>Cole</td> - <td class='c028'>Canadian Med. Assoc. Jour., 1919; ix, p. 41.</td> - </tr> - <tr> - <td class='c006'>Dever, Boles and Case</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 265.</td> - </tr> - <tr> - <td class='c006'>Fildes, Baker and Thompson</td> - <td class='c028'>Lancet., 1918; ii, p. 697.</td> - </tr> - <tr> - <td class='c006'>Fletcher</td> - <td class='c028'>Lancet., 1919; i, p. 104.</td> - </tr> - <tr> - <td class='c006'>Friedlander, McCord, Sladen and Wheeler</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1652.</td> - </tr> - <tr> - <td class='c006'>Goodpasture and Burnett</td> - <td class='c028'>U. S. Naval Med. Bull., 1919; xiii, No. 1.</td> - </tr> - <tr> - <td class='c006'>Hall, Stone and Simpson</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1986.</td> - </tr> - <tr> - <td class='c006'>Hunt</td> - <td class='c028'>Lancet., 1918; ii, p. 419.</td> - </tr> - <tr> - <td class='c006'>Keegan</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1051.</td> - </tr> - <tr> - <td class='c006'>Kuskow</td> - <td class='c028'>Virchows Archiv., 1895; cxxxix, p. 406.</td> - </tr> - <tr> - <td class='c006'>Le Count</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 650.</td> - </tr> - <tr> - <td class='c006'>Lord</td> - <td class='c028'>Boston Med. and Surg. Jour., 1905; cl, p. 537.</td> - </tr> - <tr> - <td class='c006'>Lyon</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 924.</td> - </tr> - <tr> - <td class='c006'><span class='pageno' id='Page_293'>293</span>MacCallum</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 720.</td> - </tr> - <tr> - <td class='c006'>MacCallum</td> - <td class='c028'>Monog. Rock. Inst. for Med. Res., 1919; No. 10.</td> - </tr> - <tr> - <td class='c006'>Muir and Wilson</td> - <td class='c028'>Brit. Med. Jour., 1919; i, p. 3.</td> - </tr> - <tr> - <td class='c006'>McMeans</td> - <td class='c028'>Archives of Int. Med., 1917; xix, p. 709.</td> - </tr> - <tr> - <td class='c006'>Nuzum, Pilot, Stangl and Bonar</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1562.</td> - </tr> - <tr> - <td class='c006'>Oertel</td> - <td class='c028'>Canadian Med. Assoc. Jour., 1919; ix, p. 339.</td> - </tr> - <tr> - <td class='c006'>Opie, Freeman, Blake, Small and Rivers</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 556.</td> - </tr> - <tr> - <td class='c006'>Speares</td> - <td class='c028'>Boston Med. and Surg. Jour., 1919; clxxx, p. 212.</td> - </tr> - <tr> - <td class='c006'>Stone and Swift</td> - <td class='c028'>Jour. A. M. A., 1919; lxxii, p. 487.</td> - </tr> - <tr> - <td class='c006'>Symmers</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1482.</td> - </tr> - <tr> - <td class='c006'>Synnott and Clark</td> - <td class='c028'>Jour. A. M. A., 1918; lxxi, p. 1816.</td> - </tr> - <tr> - <td class='c006'>Torrey and Grosh</td> - <td class='c028'>Amer. Jour. Med. Sci., 1919; clvii, p. 170.</td> - </tr> - <tr> - <td class='c006'>Weber</td> - <td class='c028'>British Med. Jour., 1919; i, p. 8.</td> - </tr> - <tr> - <td class='c006'>Wittingham and Sims</td> - <td class='c028'>Lancet., 1918; ii, p. 865.</td> - </tr> -</table> - -<div class='chapter'> - <span class='pageno' id='Page_294'>294</span> - <h2 class='c005'>EXPLANATION OF PLATES</h2> -</div> - -<table class='table0' summary='EXPLANATION OF PLATES'> - <tr> - <td class='c015'>Fig. i.</td> - <td class='c020'>Cyanosis of head and neck.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. ii.</td> - <td class='c020'>Acute tracheitis with desquamation of epithelium and superficial necrosis.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. iii.</td> - <td class='c020'>Acute serous and hemorrhagic pneumonia.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. iv.</td> - <td class='c020'>Acute serous pneumonia with massive hemorrhage.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. v.</td> - <td class='c020'>Acute hemorrhagic and purulent lobular pneumonia. The purulent process is seen to be advancing from the focal type to the more diffuse lobar by fusion of the neighboring lobules.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. vi.</td> - <td class='c020'>Acute purulent pneumonia.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. vii.</td> - <td class='c020'>Lobular fibrosing pneumonia. In this specimen the patches of new scar tissue formed irregular islands. The final stage of contraction of the scar had not taken place.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. viii.</td> - <td class='c020'>Acute serous pneumonia with some infiltration by mononuclear cells.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. ix.</td> - <td class='c020'>Acute hemorrhagic pneumonia.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. x.</td> - <td class='c020'>Hyaline deposits upon alveolar walls. In some areas the wall itself has suffered necrosis.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. xi.</td> - <td class='c020'>Acute purulent pneumonia. In other areas of the same lung the interstitial infiltration by leucocytes was more intense.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. xii.</td> - <td class='c020'>Acute lymph adenitis, showing the unusual numbers of endothelial cells while leucocytes are relatively infrequent.</td> - </tr> - <tr><td> </td></tr> - <tr> - <td class='c015'>Fig. xiii.</td> - <td class='c020'>Rupture of abdominal rectus muscle with hemorrhage. The degeneration antecedent to the rupture is shown in the belly of the muscle.</td> - </tr> -</table> - -<div class='figcenter id002'> -<img src='images/fig_01.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. i</p> -</div> -</div> - -<div class='figcenter id004'> -<img src='images/fig_02.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. ii</p> -</div> -</div> - -<div class='figcenter id004'> -<img src='images/fig_03.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. iii</p> -</div> -</div> - -<div class='figcenter id004'> -<img src='images/fig_04.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. iv</p> -</div> -</div> - -<div class='figcenter id004'> -<img src='images/fig_05.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. v</p> -</div> -</div> - -<div class='figcenter id004'> -<img src='images/fig_06.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. vi</p> -</div> -</div> - -<div class='figcenter id004'> -<img src='images/fig_07.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. vii</p> -</div> -</div> - -<div class='figcenter id004'> -<img src='images/fig_08.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. viii</p> -</div> -</div> - -<div class='figcenter id004'> -<img src='images/fig_09.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. ix</p> -</div> -</div> - -<div class='figcenter id004'> -<img src='images/fig_10.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. x</p> -</div> -</div> - -<div class='figcenter id004'> -<img src='images/fig_11.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. xi</p> -</div> -</div> - -<div class='figcenter id004'> -<img src='images/fig_12.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. xii</p> -</div> -</div> - -<div class='figcenter id003'> -<img src='images/fig_13.jpg' alt='' class='ig001' /> -<div class='ic002'> -<p>Fig. xiii</p> -</div> -</div> - -<div class='pbb'> - <hr class='pb c004' /> -</div> -<div class='tnotes'> - -<div class='chapter'> - <h2 class='c005'>TRANSCRIBER’S NOTES</h2> -</div> - <ol class='ol_1 c003'> - <li>Silently corrected typographical errors and variations in spelling. - - </li> - <li>Anachronistic, non-standard, and uncertain spellings retained as printed. - - </li> - <li>Footnotes have been re-indexed using numbers. - </li> - </ol> - -</div> - - - - - - - - -<pre> - - - - - -End of the Project Gutenberg EBook of Studies on Epidemic Influenza, by -University of Pittsburgh School of Medicine - -*** END OF THIS PROJECT GUTENBERG EBOOK STUDIES ON EPIDEMIC INFLUENZA *** - -***** This file should be named 60822-h.htm or 60822-h.zip ***** -This and all associated files of various formats will be found in: - http://www.gutenberg.org/6/0/8/2/60822/ - -Produced by Richard Tonsing and the Online Distributed -Proofreading Team at http://www.pgdp.net (This file was -produced from images generously made available by The -Internet Archive) - - -Updated editions will replace the previous one--the old editions will -be renamed. - -Creating the works from print editions not protected by U.S. copyright -law means that no one owns a United States copyright in these works, -so the Foundation (and you!) can copy and distribute it in the United -States without permission and without paying copyright -royalties. 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