Studies on Epidemic Influenza: Comprising Clinical and Laboratory Investigations
Part 15
The United States Public Health Service should work toward standardizing health laws and penalties for all States.
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.
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.
_Desirable Laws_
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.
_Education of the Public_
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 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.
_Summary_
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 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.
BIBLIOGRAPHY
1. Rosenau, Keegan, Public Health Report, 1919; xxxiv, No. 2, Goldberger and Lake p. 33. 1a. McCoy and Richey Public Health Report, 1919; xxxiv, No. 2, p. 34. 2. Lacy Jour. Lab. and Clin. Med., 1918; iv, p. 55. 3. Wollstein Jour. Exper. Med., 1911; xiv, p. 73. 4. Flexner Jour. Amer. Med. Assoc., 1913; lxi, p. 1872. 5. Park and Williams Bacteriology, 1914 Edition; p. 437. 6. Leary Jour. Amer. Med. Assoc., 1918; lxxi, p. 2098. 7. Leary Amer. Jour. Public Health, 1918; viii, p. 755. 8. Rosenau Preliminary report furnished through Surgeon-General of the Navy W. C. Braisted. 9. Barnes Jour. Amer. Med. Assoc., 1918; lxxi, p. 1849. 10. Hinton and Kane The Commonwealth Mass. State Dept. Health, 1918; vi, Nos. 1 and 2, p. 28. 11. Hinton and Kane Hinton’s Report. 12. Parker Jour. Amer. Med. Assoc., 1919; lxxii, p. 476. 13. Pearce Jour. Amer. Med. Assoc., 1913; lxi, p. 2115. 14. Committee on New and Non-Official Jour. Amer. Med. Assoc., 1918; lxx, p. Remedies 1967. 15. McCoy Personal Communication. 16. Hutchinson Dixmont Hospital Report. 17. McCoy, Murray and Jour. Amer. Med. Assoc., 1918; lxxi, p. Teeter 1997. 18. Minaker and Irvine Jour. Amer. Med. Assoc., 1919; lxxii, p. 847. 19. Sherman Report. 20. Maberry Report from Hospital for Insane, Retreat, Pa. 21. Rosenow Jour. Amer. Med. Assoc., 1919; lxxii, p. 31. 22. Beaver, Boles and Case Jour. Amer. Med. Assoc., 1919; lxxii, p. 265. 23. Ely, Lloyd, Hitchcock and Nickson Jour. Amer. Med. Assoc., 1919; lxxii, p. 24 24. Kitano Jour. Amer. Med. Assoc., 1919; lxxii, p. 1575. 25. Wynn Pract. London, 1919; cii, p. 77. 26. Norman White Lancet., 1919; i, p. 707. 27. Whitingham and Sims Lancet., 1918; ii, p. 865. 28. Cadham Lancet., 1919; ii, p. 885. 29. Eyre and Lowe Lancet., 1918; ii, p. 485. 30. Conference British War Office 31. Whitmore, Fennel and Jour. Amer. Med. Assoc., 1918; lxx, p. 427; Peterson also p. 902. 32. Fennel Jour. Amer. Med. Assoc., 1918; lxxi, p. 2115. 33. Dochez and Gillespie Jour. Amer. Med. Assoc., 1913; lxi, p. 727. 34. Lister Publications of the South African Institute for Medical Research, No. 2, 1913. 35. Lister Publications of the South African Institute for Medical Research, No. 8, 1916. 36. Lister Publications of the South African Institute for Medical Research, No. 10, 1917. 37. Cecil and Austin Jour. Exper. Med., 1918; xxviii, p. 19. 37a. Cecil and Vaughan Jour. Exper. Med., 1919; xxix, p. 457. 38. Bloomfield Johns Hopkins Bull., 1919; xxx, p. 1. 39. Capps War Med., Vol. ii, p. 371. 39a. Capps Jour. Amer. Med. Assoc., 1918; lxx, p. 910. 40. Weaver Jour. Amer. Med. Assoc., 1918; lxx, p. 76. 41. Weaver Jour. Amer. Med. Assoc., 1918; lxxi, p. 1405. 42. Weaver Jour. Infect. Dis., 1919; xxiv, p. 218. 43. Doust and Lyon Jour. Amer. Med. Assoc., 1918; lxxi, p. 1216. 44. Haller and Colwell Jour. Amer. Med. Assoc., 1918; lxxi, p. 1213. 45. Leete Lancet., 1919; i, p. 392. 46. Dannenberg Jour. Amer. Med. Assoc., 1918; lxx, p. 99. 47. Mink Jour. Amer. Med. Assoc. 1918; lxxi, p. 2175. 48. Vaughan Jour. Amer. Med. Assoc., 1918; lxxi, p. 2100. 49. Copeland Jour. Amer. Med. Assoc., 1918; lxxi, p. 2173. 50. Lynch and Cummings Jour. Amer. Med. Assoc., 1918; lxxi, p. 2174. 51. Amer. Med. Association Public Health Report, 1919; xxxiv, p. 1413. 52. Le Moignie and Pinoy Compt. rendu. Soc. Biol., 1916; lxxix, pp. 201 and 352. 52a. Wright and Douglas Proc. Royal Soc. Med., 1904; lxxiii, p. 128, and lxxiv, p. 147. 53. Neufeld and Rimpau Zeitschr. f. Hyg., 1905; li, p. 283. 54. Rosenau Prevent. Med. and Hyg., 1918. 55. Brown, Palfrey and Jour. Amer. Med. Assoc., 1919; lxxii, p. Hart 463. 56. Gay Typhoid fever. (Published by Macmillan Co., 1918.) 57. Eyre and Low Lancet. I, April 5, 1919; p. 557.
PHYSIOLOGICAL AND PHYSIOLOGICAL CHEMICAL OBSERVATIONS IN EPIDEMIC INFLUENZA
By C. C. GUTHRIE, PH. D., M. D.
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.
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.
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.
In presenting the results, it is deemed most expedient and practical to omit extensive tabulations and to summarize the data under each subject.
From the report it will be obvious that certain studies were in preliminary stages at the termination of the investigation. This 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.
RESULTS
_Circulation_
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.
_Arterial Blood Pressure_ 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.
_Venous Blood Pressure._—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.
_Respiration_
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.
_Cyanosis_ 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.
_Blood_
Hemorrhage being not uncommon, the blood was tested for coagulability, but in this respect no marked departure from the normal range was noted.
_Coagulation._—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 average by defibrination was 3 minutes and 36 seconds, and by the Biffi-Brooks method 4 minutes and 38 seconds.
_Red Corpuscles._—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.
_Color_ 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.
_Plasma Bicarbonate._—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_{2} 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_{2} was reduced to 46.6 c.cm.
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.
_Hemoglobin Per Cent._—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.
_Relative Volume of Corpuscles._—A limited number of hematokrit tests on severe cases gave results in normal levels.
_Spectroscopic Studies._—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 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.
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 λ 758μμ λ and 542μμ. 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 λ 627μμ, number 761 at λ 634μμ, number 763 at λ 625μμ, and number 787 at λ 634μμ. 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 λ 758μμ and λ 543μμ. 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 λ 634μμ. 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 λ 632μμ on examination 24 hours after autopsy. Similar treatment of corpuscles five days subsequently gave no indication of the presence of any methemoglobin spectroscopically.
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.
_Oxygen Capacity._—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.
Other studies using different technique gave concordant results, but there were indications that oxygen was more slowly absorbed than normally.
_Oxygen Content of Venous Blood_ 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.
_Gases, Kinds, Quantity and Rate Yielded to Vacuum._—In general it may be said that quantitative differences observed are not considered fundamental, but that the studies indicate abnormal slowness in oxygen absorption.
_Gases, Quantity and Rate of Absorption on Exposure to Air After Extraction by Pump._—The results emphasize slowness of oxygen absorption as compared to normal blood.
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.
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.[1]
Footnote 1:
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.)
_Effect of Addition of Serum on Behavior on Exposure to Air._—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. From this it would seem that the oxygen transmitting capacity of the serum was diminished.