1942: Medicine

Industrial Accident Prevention.

The National Safety Council has been designated by President Roosevelt to lead an attack on the accident menace. In 1941 no less than 18,000 men were killed by accidents while working at their jobs and over 1,500,000 were maimed or hurt. These figures do not include over 30,000 workers who were killed and nearly 2,500,000 hurt in off-job accidents.

Many of our great factories have been introducing measures that are already proving effective in prevention of these accidents. In one factory, 32 per cent of all medical claim cases were eye injuries during one month whereas four months later the number of such cases was only 15 per cent because of the introduction of a goggles and face-shield campaign.

The dangers of magnesium in factories that make airplane engines are being markedly reduced by the use of special garments and by the provision of quickly accessible shower baths.

Acute Anterior Poliomyelitis.

Flies as Carriers of the Virus.

For some time it has been known that acute poliomyelitis virus is present in the faeces of patients convalescent from the disease. The virus may linger for months in the intestines of patients who have recovered from the disease, even when the attack has been so mild as to be regarded as a slight influenzal infection. It was recently shown that flies that feed on infected sewage may carry the virus. Since it is now certain that flies may be carriers of the virus, it will be necessary to bring the proof of how patients become inoculated — whether by fly bites or by other routes.

Angina Pectoris.

Patients who suffer from angina pectoris usually have disease of the coronary arteries and reduction of the blood supply to the heart. Recently to increase the blood supply to the heart muscle a surgical method has been introduced. It consists of opening the pericardial cavity into which 2 teaspoonfuls of sterile talcum powder are sprinkled, the powder being distributed about the pericardial cavity. Inflammation develops and causes extensive adhesions of the parietal and visceral layers of the pericardium. In this way the arteries of the pericardium become connected with the heart and provide a much better blood supply (S. A. Thompson & M. J. Raisbeck, Annals of Internal Medicine, 1942, 16: 495-520).

Arsenical Poisoning and Mees' Band on the Finger Nails.

An interesting case of exfoliative dermatitis with paralyses of all four distal extremities and with glove and stocking anaesthesia is reported in the Urologic and Cutaneous Review, August 1942. The patient had been accidentally poisoned by arsenic and the appearance of a peculiar dull band (Mees' band) across the breadth of the whole of each finger nail confirmed the etiological diagnosis. On reviewing the history one can tell the exact week, perhaps even the exact day, when the arsenical poisoning occurred, for a latent period of eight weeks follows the poisoning before the Mees' band appears. The importance for legal medicine is obvious in relation to suicidal or murderous attempts.

Asthmatic Patients as Surgical Risks.

The risks of development of some form of pulmonary complication after operation upon asthmatics have been studied by Gaarde, Prickman and Raszkowski at the Mayo Clinic (J. A. M. A., 1942, 120: 431-433). They conclude that the risks are not great since 86.7 per cent of their patients underwent major operations without developing significant pulmonary complications, though the necessity of adequate preoperative and postoperative care is emphasized. Of the postoperative pulmonary complications that did occur, pneumonia, bronchitis or severe asthma were most common.

The authors avoid ether anesthesia wherever possible. They suggest that, carefully administered, the sulfonamide drugs given before operations on asthmatics not only should increase the safety of the operations but may make surgical treatment possible in cases in which it might otherwise be contraindicated by asthmatic bronchitis.

Dicoumarin as an Anti-coagulant.

In diseases in which there is an abnormal tendency to coagulation of the blood and to thrombus formation, the physician's only resource until recently was heparin, made from the liver of the horse, an expensive substance, somewhat difficult to administer and to control (see studies of W. H. Howell).

A new substance known as dicoumarin obtained from sweet clover and also made synthetically by Link and his associates at the Wisconsin Agricultural Experimental Station has been shown to be an ideal anti-coagulant. It is much superior to costly heparin and available at one-tenth the price of the latter (see Journal of Biological Chemistry, 1942, 142: 941-955).

Blood Typing by a Rapid Method.

When a blood transfusion is necessary one must make sure that the blood of the donor is not incompatible with that of the patient, for otherwise death may result from clotting of the patient's blood.

The ordinary methods of blood typing require some little time but the types A and B (which make up about 50 per cent of the bloods of all adults) can now be distinguished very quickly.

Concentrates of the A and B types are prepared and a drop of each of these is placed in one of the squares printed on a card and next to each is placed a drop of the blood to be tested. The adjacent drops are then mixed with a tooth pick. In less than 60 seconds one can make sure whether the bloods are compatible or incompatible. The properly matched blood and serum will look smooth and even, whereas if the types do not match, clotting will result and the surface will be lumpy and uneven (see W. Thalheimer and S. A. Myron, J. A. M. A., 1942).

Cancer; Results of Recent Researches.

The more important recent contributions to the study of cancer have been analyzed and briefly summarized by James B. Murphy, one of the most distinguished American investigators of malignant growths (see J. A. M. A., 1942, 120: 107-111). Experimental studies support the view that malignancy is a universal cell potentiality since any cell of the body has inherent in its make-up the potentiality for unlimited or uncontrolled growth, the degree of such potentiality being variable in degree depending either upon heredity or predisposing factors. This malignancy potentiality of a cell may be developed in the more sensitive groups by the strain of normal physiological processes, while in more resistant groups it may be set off by a variety of inciting agents.

The change from a normal cell to a malignant cell involves an alteration in the cell itself through which proliferation becomes an automatic process that is independent of a continuously acting provocative agent. This change seems to develop suddenly in the cell and becomes a fixed character that is transmitted to all its descendents. It has been suggested that this change may represent a 'somatic mutation.'

A more comprehensive formulation of the fundamental cancer problem must await further knowledge.

At the Memorial Hospital in New York, the effects of chemicals upon cancer cells are being studied. Some seventy different substances have been used and those that seem to have an anti-cancer effect are characterized by a common chemical structure. This empirical study may lead to some important discovery before long.

Fuso-spirochetal Infections.

Vincent's disease (due to mixed infection with fusiform bacilli and spirochetae) was prevalent in the First World War and was commonly known as 'trench mouth.' It is still widespread in many countries. Most cases can now be quickly cured but some are very resistant to treatment. Tonsillar and gingival infections are often associated in this disease and the odor of the breath is foul and characteristic (described as 'the odor of rotten meat').

During the war the patients were isolated, and a mixture of equal parts of wine of ipecac, liquor arsenicalis and glycerin was applied locally on a tooth brush and on cotton applicators. Many still regard this as the best form of local treatment.

In later years, intramuscular injection of a bismuth preparation in oil has become popular and is usually effective, but one should be cautious to avoid bismuth poisoning especially in children and in patients suffering from renal disease.

In England good effects have been reported from the daily administration of 250 mg. of nicotinic acid (J. D. King).

The sulfonamide group of drugs does not seem to have been very helpful in the treatment of Vincent's disease though in one severe case a good response followed the administration of neoprontosil.

Last year Dr. S. L. Rosenthal of Philadelphia reported marked benefit from the local application of 10 per cent solution of sodium carbonate. After thorough cleansing of the mouth the solution was applied beneath the free margin of the gums with a glass syringe and a blunt curved platinum needle so as to make the solution reach the bottom of all pockets. The tissues were kept moist with the solution for ten minutes. Afterwards, a mouthwash of 1 per cent solution of sodium carbonate was used (see Journal of the American Dental Association, 1941, 28: 972-974).

Influenza; Prevention of Epidemics.

Two types of epidemic influenza are now known: (1) Type A, common in alternate years (1935, 1937, 1939, 1941), and Type B, that so far seems to have occurred in small and scattered epidemics. Both types appear to be due to filtrable viruses; when streptococci or other bacteria are present, they are to be regarded as secondary invaders.

According to Philadelphia observers (Stokes and Henle) prevention of influenza depends upon the measures for the control of air-borne infection, vaccination procedures and the use of immune serum.

To prevent air-borne infection in hospital wards or homes two methods have been used: (1) ultraviolet irradiation of the air and (2) propylene glycol vapor. Both have been of value but the second method seems to be the more efficient.

Vaccination procedures, first used on mice, are now applicable to human beings. For Type A, inhalations of the active virus have prevented severe infections though mild or subclinical attacks sometimes followed. For Type B, immunization with the inactive virus reported by Eaton and his co-workers seems to be promising. A combination of a concentrated virus vaccine containing both viruses A and B is now on trial.

Life Expectancy.

The average expectancy of life in this country is now about 64 years in contrast with 30 years in India and 55 years in Italy. In New Zealand and Australia life expectancy is still a little better than in this country.

L. I. Dublin, in a recent article (Am. Mercury, July, 1942) has discussed the possibility of further increasing life expectancy. He believes that before long the average length of life for man will be 71 years, but even this age does not set the limit for the future. If the cancer problem could be solved an additional year could be added and if satisfactory control of the impairments of the heart and blood vessels in middle life could be achieved still another year could be added. The growing knowledge of nutrition promises still further prolongation. Proper attention to vitamin deficiencies, hormone deficiencies, and mineral deficiencies could add still further to life expectancy.

Malaria and Its Treatment with Quinacrine (Identical with Atabrine).

Up to 1932 we had to depend upon quinine as a preventive and for the treatment of malaria. In that year a new drug, atabrine, was prepared in this country from imported intermediate substances obtained from Germany.

When the Netherlands East Indies were overcome by Japan, quinine was no longer available. Germany also cut off the supply of the substances from which atabrine was made. Fortunately, however, American chemists have found the way to synthesize atabrine from substances still available here and the National Research Council has made it fairly certain that the atabrine manufactured in this country under the nonproprietary name quinacrine is comparable in every respect with the atabrine produced in other countries. This is a chemical achievement of very great importance for the incidence of malaria is still very great in certain local areas of the United States and in Panama.

It is generally conceded that malaria is the most prevalent disease afflicting the populations of the world as a whole. It has been estimated that as many as 800,000,000 cases occur yearly (J.A.M.A., 1942, 120: 842).

Medical Education and the War.

Because of the immediate needs of the armed forces of the United States extensive changes in medical education have been instituted to meet the special conditions created.

Most medical schools have adopted an accelerated program whereby the medical course is shortened from four to three calendar years by means of continuous instruction throughout the summer months. The total number of hours devoted to instruction in the medical sciences has not been reduced.

Medical graduates under the new system will be eligible for service in the Army or Navy Medical Corps after they have completed a hospital internship of from nine to twelve months.

Changes in the medical teaching are required in order to prepare graduates properly for work in traumatic surgery and tropical diseases.

Neurocirculatory Asthenia; Recognition of Potential Cases in Draftees.

During the Great War many of the soldiers became incapacitated because of neurocirculatory asthenia, so many indeed that the malady came to be known as 'soldier's heart' or as 'effort syndrome.' Dr. John T. King has emphasized the importance of the cooperation of internists and psychiatrists to prevent the acceptance of men with potential neurocirculatory asthenia into the armed forces of the present war.

The psychiatrist would be suspicious of the potentiality in men who have shown unstable reactions to authority (parental or other), symptoms of chronic invalid reactions (cardiovascular, emotional), sense of inferiority, or fears of various sorts. The internist will study carefully men with abnormally small hearts (especially asthenics) and men who give a history of unusual sensitiveness to coffee, tobacco, or alcohol. The behavior of the pulse rate on exercise should be observed. In doubtful cases, an injection of 0.5 cc. of a 1:1000 solution of epinephrine may be administered and if the blood pressure rises more than 10 mm. or the pulse rate more than 10 beats per minute, along with tremor, palpitation, sweating and nervousness, the candidate should be rejected for he will be a poor subject for military service (see Annals of Internal Medicine, 1942, 16: 941-949).

Psychosurgery.

Although a few operations upon the brain for the purpose of relieving mental symptoms were performed about fifty years ago by G. Burckhardt of Switzerland, psychosurgery did not make much progress until about 1936 when Moniz and Lima published a paper reporting their first twenty cases of treatment of psychotic patients by surgical interruption of the nerve pathways connecting the frontal lobes with other parts of the brain.

In this country prefrontal lobotomy for mental disorders has been practiced by Walter Freeman and James W. Watts (see their Psychosurgery, 1942). Apparently the best results have been obtained in the involutional depressions whereas those in the schizophrenias have been less satisfactory. Prefrontal lobotomy does seem to offer something of importance in the handling of certain intractable neuroses and psychoses by alteration of the personality of the individual.

Chronic Seasickness.

Statistical studies have shown that about 40 per cent of any population group will become seasick on sudden exposure to rough weather at sea but most will recover after two or three days exposure to such weather. About 5 per cent of the general population are, however, subject to severe or chronic seasickness. Of this chronic form two types can be distinguished: (1) The constitutionally intractable seasickness in patients who have had previous histories of car, train, swing, elevator or other forms of motion sickness. These patients did not improve even after months on the same vessel. They were completely incapacitated while seasick and lost 20 or 30 pounds in weight while at sea. They also manifested chronic acidosis. More than half of them showed strong neurotic traits and were subject to attacks of dizziness or fainting. (2) The second form of chronic seasickness occurred in persons who developed severe illness only during duty on destroyer or patrol craft in extremely rough weather though they could get along adequately on larger vessels. They gave no history of car, train, or other forms of motion sickness and their neurotic traits were less marked. Moreover they did not tend to lose weight, could do their work and were up and about most of the time, though efficiency was partially impaired. The whole subject has been discussed by R. S. Schwab of the Medical Corps, United States Navy Reserves (Archives of Neurology and Psychiatry, 1942, 48: 496-500).

Tetany; Danger of Precipitating Attacks Attending Administration of Adrenaline to Hypocalcemic Patients.

The danger of injecting adrenaline in patients with low blood calcium has recently been stressed by A. M. Harvey and J. L. Lilienthal, Jr. (Bulletin of the Johns Hopkins Hospital, 1942, 71: 163-173). If it should be necessary to administer adrenaline to patients with latent tetany due to hypocalcemia, it is recommended that the serum calcium first be increased by intravenous injection of calcium salts.

Thyroid Gland; Its Functions and Diseases.

A vast amount of work upon this subject has been done in recent years and the general practitioner of medicine will be grateful for the recent careful summary of progress in this field supplied by Dr. J. H. Means (New England Journal of Medicine, 1942, 227: 594-602).

The thyreotropic hormone of the pituitary, TSH (thyroid stimulating hormone) continues to be a center of interest. Evidence favors the view that the action of TSH on the thyroid is chemical rather than nervous; it drives the thyroid cells to increased activity and can cause symptoms of thyrotoxicosis faster than thyroxine and therefore is probably not merely a liberator of thyroxine.

There is some evidence that the thyrotoxicosis of Graves's disease may be due not to an increased secretion of TSH but rather to an increased sensitivity of the thyroid cells to TSH and that the latter may depend upon an excessive production of adrenalin.

Iodine, as is well known, inhibits or counteracts the thyrotoxicosis induced by TSH much as it does the spontaneous thyrotoxicosis of Graves's disease.

Recently it has been shown that cyanides and vegetables (like cabbage) containing them may cause goitre and hypothyroidism and that when high blood pressure is treated with sulfocyanates an acute thyreoiditis may develop. It would appear also that the sulfonamide drugs and other substances containing sulfur may cause hyperplasia of the thyroid.

Determination of the iodine levels of the blood (though rather difficult and expensive) may sometimes yield a better yardstick of function than that afforded by the basal metabolic rate.

It is important to know that there are certain patients with Graves's disease in whom thyroidectomy is contraindicated. These are to be recognized by the fact that their eye complaints and signs are more striking than their thyrotoxic ones and that they make a superstandard response to iodine. They are best treated by iodine alone, or by x-ray treatment in addition, rather than by surgery.

Virus Pneumonia.

Just as physicians were congratulating one another upon the victory over pneumonia due to pneumococcus and other cocci through treatment by the sulfa drugs, another form of pneumonia due to a filtrable virus has made its appearance to plague them. This disease is as a rule not fatal but its course may be prolonged and as yet no specific treatment for it has been discovered. Good accounts of it will be found in recent articles (see W. T. Longcope, Practitioner, 1942, 148: 1-8; and J. M. Adams, Jour. Of Ped., 1942, 20: 405-420).

Though virus pneumonia does not respond to chemotherapy with the sulfonamide drugs, much can be done for it by means of physiologically directed therapy, including application of positive pressure with oxygen or with helium-oxygen mixtures and inhalation of vaporized solutions of epinephrine and neosynephrine, etc. (see A. L. Barach, Annals of Internal Medicine, 1942, 17: 812-819).

War; Its Psychological Effects on Citizen and Soldier.

Dealing with this subject, Dr. R. D. Gillespie, of Guy's Hospital, London, delivered the Salmon Memorial Lectures of the New York Academy of Medicine and published them in a volume of 251 pages (New York, 1942).

In war time, the author has been surprised at the relative rarity of pathological mental and nervous disturbances among civilians exposed to air raids. In the bombed areas, very few cases of neuroses attributable to war conditions were observed, despite the many tragedies and heartbreaks that occurred. It is interesting that in the development of pathological psychological reactions to bombing, male cases outnumbered the females in the ratio of 30 to 18.

BACTERIOLOGY

As may have been expected, scientific activities in the field of microbiology during 1942 were markedly influenced by the War and the demands of war-time medicine upon research connected with the control of infectious diseases. However, even though many efforts were focused on problems of a predominantly practical nature, the past year has seen a number of contributions of basic importance to microbiologists, especially among the virus diseases. This review will present the available material in the following divisions: I. Bacteriology; II. Immunology; III. Virus Diseases. The customary review of chemotherapy will be omitted because the field has become too large for consideration in a short article.

I. Bacteriology.

A study of the distribution of color variants in aging cultures of Serratia marcescens, by Bunting and Ingraham, showed that the bacterial populations changed in a reproducible manner, in so far as the predominance of red, pink or white colonies was concerned. The fact that dissociation occurred in accordance with a definite numerical pattern lends new impetus to the genetic approach in this problem.

In an attempt to localize the site of formation of diphtheria toxin, Morton and Gonzales found that this toxin, one of the classical examples of an exotoxin, was present within the cells of the diphtheria bacillus whence it could be liberated by breaking up the bacillary bodies by means of sonic vibration.

The pleuropneumonia group of organisms was newly investigated by Preston. Animals infected with this organism frequently show arthritis, as a complication or a primary manifestation. A suppurative arthritis which occurs spontaneously in rats has been shown to be caused by an organism of this group, the L4 type of Klieneberger. This arthritis resembles suppurative arthritis of humans rather than rheumatoid arthritis. As yet it has not been possible to incriminate organisms of this group in the etiology of human rheumatism.

In a similar study Beeuwkes and Collier found no difference between two strains of microorganisms of the pleuropneumonia-like group, one isolated from spontaneous polyarthritis in a rat, the other from rats which had been inoculated with material from a patient with acute rheumatic fever. Continuing their investigation of the growth requirements of the Brucella group, Koser and Wright could demonstrate that biotin is needed by certain strains. Extremely small amounts of pure biotin supported growth, i.e., 0.001 mg. per cc. of medium produced about 90 per cent of maximum growth, 0.00001 mg. supported approximately half maximum and 0.000003 mg. was sufficient for light growth.

II. Immunology.

Antibacterial Factors of Human Saliva.

Van Kesteren et al. investigated the antibacterial factors of human saliva which is known to affect a wide variety of microorganisms. By subjecting saliva to heating, ultraviolet radiation, storage, freezing and thawing, filtration, adsorption and chemical fractionation, the conclusion was reached that saliva contains at least two antibacterial principles, the one resembling lysozyme, the other apparently being distinct from it.

Antibody Production.

Cannon has formulated a general theory on the mechanism of antibody production which is based on the supposition that antibodies are specifically modified globulins which are formed intracellularly during the synthesis of globulin. Since globulin production depends upon the intake of amino acids and is impaired by an inadequate intake of dietary proteins, antibody production in turn must similarly depend upon protein intake. The relationship of this theory to problems related to fluctuation in resistance to infection and to the capacity to produce antibodies, in general to the conservation of an adequate antibody-matrix (protein reserves) is discussed.

Evidence bearing on the molecular valence of antigen and antibody is presented and discussed by Hooker and Boyd, the conclusion being that antigenic proteins of a molecular weight of about 35,500 seem to have a minimal functional valence of 5, with an upper limit of less than 30. The experimental data are as yet insufficient to indicate whether ordinary antibody is univalent, or perhaps divalent.

The first manufacture of antibodies in vitro was reported by Pauling and Campbell. A protein solution with the properties of a specific antiserum to methylene blue was made by treating a solution of bovine globulin and the dye with alkali and then slowly neutralizing the alkali; also, by heating solutions of globulin and antigen to 57° C. for several days, antisera homologous to the antigen were prepared. This latter method was used successfully with the azo dye 1,3-dihydroxy-2,4,6-tri (p-azo phenylarsonic acid) benzene and with pneumococcus polysaccharide Type III.

III. Virus Diseases.

Electron Microscope Photography.

Sharp and associates published an electron micrograph with a final magnification of 52,000 fold which shows that the Western strain of equine encephalomyelitis is a spherical or disc-shaped particle of approximately 40 mu in diameter. The images suggest some internal structure characterized by a round or oval region of relatively high density surrounded by an enveloping material of lesser density.

Green, Anderson and Smadel who obtained remarkably clear electron micrographs of vaccinia virus conclude that the elementary bodies have a regular morphology of their own. The particles looked like dice and showed an internal structure as well as some sort of limiting membrane. In other words, a complex organization was found which approaches the structure of bacteria and differs from that of the smaller viruses. It should be borne in mind in this connection that the agent of variola-vaccinia is a relatively large unit in the dimensional scale of the viruses.

Relation between Hydration of Tissues and Virus Spread.

Sprunt has published interesting data bearing on the effect of the nutritional state of an animal on the extent of viral lesions. It was found that in rabbits which had been deprived of food the lesions resulting from the injection of vaccinia virus were fewer and smaller. The state of hydration seemed to be closely correlated with this phenomenon. Thus, if the amount of interstitial fluid was increased by permitting the animals to drink, the lesions were even less numerous; if, on the other hand, the tissues were dehydrated by withholding water the lesions were more numerous. It appears therefore that virus is less able to multiply in the poorly nourished cell than in a well nourished one and that hydration of the tissues increases resistance while dehydration has the opposite effect.

Similar findings of collateral interest were reported by King who observed that previous injection of glycerin or of concentrated sodium chloride greatly enhanced the activity of Eastern equine encephalomyelitis virus in mice injected by the intramuscular route. The increase in virulence was up to 100 fold. This effect seems to have been caused by a sudden dehydration of the nervous system. For, while gradual withdrawal of body fluids, induced by depriving animals of drinking water, leads to a sharp concentration of the blood, equal to that produced by glycerin or salt, no increased peripheral virus activity is observed. Since glycerin does not enhance infection produced by the ocular or nasal routes, it seems that the latter two routes involve a mechanism of pathogenesis fundamentally different from that implicated in intramuscular injection.

Interference Phenomenon.

It has long been known that a plant infected with one virus will, upon reinfection with another related virus, fail to develop the symptoms characteristic of the superimposed infection. In other words, the second virus is inhibited in its multiplication by the effects produced as the result of infection with the first virus. Similar interference among animal viruses has previously been described by Hoskins (pantropic against neurotropic yellow fever virus), by Findlay and MacCallum (Rift Valley fever virus against yellow fever virus) and by Dalldorf (lymphocytic choriomeningitis virus against poliomyelitis virus).

Further progress in this field has recently been made by the discovery of three additional interfering viral systems. Thus, Delbrueck and Luria found that mixed infection of a bacterium with two strains of bacteriophage, feeding on the same substrate, resulted in complete suppression of the growth of one phage, whereas the other phage grew normally. Moreover, Andrewes described a mutual suppression in tissue culture of a lung strain and of a neurotropic strain of influenza virus, depending upon which virus was first in the field. Finally, Jungeblut and Sanders reported interference in monkeys between poliomyelitis virus and a murine variant of poliomyelitis virus. The features common to all these interference phenomena are, first, the fact that the strain which is more potent, or which arrives first in the field, suppresses the weaker or secondary infecting strain, second that interference occurs between related viruses (or between variants or mutants of the same virus), and, third, that the antagonistic interaction is based on certain quantitative relationships between the two interfering agents. The most reasonable explanation offered for this highly interesting phenomenon is that one virus exhausts a cellular metabolite, present only in measured amounts, which is an indispensable factor in a successive series of enzyme systems necessary for the multiplication of both viruses. Since interference is broader than protection induced by immunity, a new approach suggests itself to the control of certain virus diseases in which immunity is either poorly developed or strictly strain-specific. It is also conceivable that interference may be used as a tool to establish fundamental relationships between certain viruses in which such relationship cannot be clearly demonstrated by immunological methods. For unrelated viruses, when growing within the same susceptible cell, do not inhibit each other (Anderson).

Epidemic Kerateconjunctivitis.

In 1941 there occurred in the San Francisco shipyards an outbreak of an acute inflammatory disease of the eyes, apparently derived from a similar earlier outbreak in Hawaii, which soon spread throughout the Pacific coast area and which eventually reached the East coast. Some major epidemics have since been reported from several industrial plants located on the Atlantic Seaboard. The disease appears as an acute follicular conjunctivitis, with swollen and sometimes painful preauricular lymph nodes, and sometimes also leads to an involvement of the cornea. As a possible specific etiological agent for this disease, Sanders identified a filterable virus which was obtained from a typical case. The virus was isolated by intracerebral inoculation of mice with human material and subsequent passages in embryonic mouse brain tissue cultures. Serial subcultivation was possible only at room temperature. The agent was filterable through collodion membranes measuring 75 to 100 millimicrons. The disease could be reproduced in a human volunteer by placing the virus into the conjunctival sac. Definite neutralization of this virus was obtained when it was mixed with sera from convalescent patients; the neutralizing power of such sera varied from 100 to 10,000 lethal mouse doses. The isolation of this virus represents not only the discovery of a new pathogenic virus but may pave the way for better diagnosis and treatment of this important new disease.

Yellow Fever.

At his press conference on July 24, 1942, Secretary of War Henry L. Stimson reported that 25,585 cases of jaundice had developed among army personnel between Jan. 1 and July 4, apparently from the use of vaccination against yellow fever. Of those affected, 24,057 were among troops in the United States and 4,528 among forces abroad. The ratio of deaths was 1 for every 461 cases, or a total of 62 deaths in all. Up to this time 2,000,000 or 2,500,000 men had been inoculated. (Distribution of vaccine-during 1941 by the Rockefeller Foundation shows the following figures: total for U. S. Government, 1,938,300 doses; total for Africa, 1,972,380 doses; miscellaneous, 350,000 doses; grand total: 4,260,680 doses.) In interpreting these data it must be kept in mind that the active principle in yellow fever vaccine is a modified strain of live virus. However the evidence available up to the present, mostly on immunological grounds, seems to exonerate the virus as the cause of the icterus. Moreover, there are various conditions which, from the changes brought about in the liver, may cause confusion with the clinical diagnosis of yellow fever (Smith). It is also possible that the responsible agent was a contaminating virus which gained entrance to the vaccine and which was carried over a series of tissue-culture passages. Such virus might conceivably be the cause of icterus classified as 'catarrhal jaundice' or 'infectious' or 'epidemic hepatitis' (Fox and associates). One of the obvious precautions in the future production of the vaccine is the obtaining of an uncontaminated strain of 17D virus and the complete elimination of human serum.

Influenza.

A study by Hirst of the adsorption of influenza hemagglutinins on chicken red cells showed that the virus could be eluted after contact with the cells. Red cells which had absorbed and then fully eluted the agglutinin were incapable of readsorbing a detectable amount of fresh agglutinin; in addition, such cells would no longer agglutinate when exposed once more to fresh virus suspensions. It could be demonstrated that the infectious agent was absorbed simultaneously with the hemagglutinin. In another paper by Hirst, dealing with a quantitative determination of influenza virus and antibodies by means of red cell agglutination, the agglutinative titer of the virus for chicken red cells was found to be proportional to the potency expressed in mouse lethal doses; however virus preparations inactivated by heat or by storage retained their agglutinating power. An agglutination-inhibition test, using ferret and human sera, was devised which gives qualitative data regarding the titer of influenza antibodies similar to those obtained from neutralization tests. Because of the complexity of the mouse test, the in vitro test holds promise of yielding more accurate data. In a third paper, Hirst et al. studied the antibody response following vaccination with influenza virus by means of this agglutination-inhibition test. Wide individual variations were found to exist among various individuals in response to the same preparation of virus, but, in general, antibody production was proportional to the amount of virus administered. No differences could be detected between various types of vaccines, such as allantoic fluid, active virus, or virus inactivated by formalin, heat or drying. The use of the X strain of distemper virus failed to enhance the antigenicity of the virus as had previously been reported by Horsfall.

New data which demonstrate the limitations in the degree of efficacy obtainable in man with the present vaccines of influenza virus have been supplied by Eaton and Martin. A total of 1,102 persons received vaccine (tissue culture A strain or complex influenza A distemper vaccine) while 7,987 unvaccinated persons served as controls. An epidemic of influenza which occurred shortly after completion of vaccination caused 985 cases of clinical influenza in the control group (12.3 per cent incidence) and 92 cases in the vaccinated group (8.3 per cent incidence). The antibody response produced by the vaccines was not as large as that resulting from infection. Cases of clinical influenza occurred with equal frequency in persons with low, medium or high initial antibody titers.

Viral Pneumonia.

As early as 1938 Francis and Magill reported the discovery of a new virus in ferrets following inoculation with throat-washings from human cases of an influenza-like respiratory infection: it was not clear whether this virus was derived from the original human material or from the ferrets. When inoculated into mice this virus caused fatal meningitis after intracerebral injection and a fatal pneumonia after nasal instillation, reasons for which it was called the virus of meningopneumonitis. In certain respects this virus resembled the virus of psittacosis. Two years later (1940), Pinkerton and Swank described the recovery of a virus, morphologically identical with psittacosis, from pigeons on a thiamin-deficient diet. This agent, like the virus of meningopneumonitis, also produced either pneumonia or a fatal meningoencephalomyelitis in mice, depending upon the route of injection. Finally, Eaton et al., in 1941, isolated from four human cases of a typical pneumonia a third virus which behaved in mice very much like the two other viruses and which also showed immunological similarity with psittacosis. In 1942 a careful comparison of the viruses which fall into this group was made by Pinkerton. The conclusion was reached that all viruses are morphologically identical with psittacosis and probably represent modified strains of the psittacosis virus. Since psittacosis virus shows some relation to the virus of Q fever and that of lymphogranuloma venereum it would seem that there may exist a large group of individual viral agents all of which are similar in particle size, shape of elementary bodies, and type of cellular inclusions, even though they cause different disease entities in man.

An infectious agent, presumably a filterable virus, which differs from the psittacosis-like viruses previously described, was isolated by Eaton, Meikeljohn, van Herick and Talbot from cases of atypical pneumonia by intranasal inoculation of cotton rats with human sputum. The strains adapted to cotton rats were obviously related to the etiological agent in human material as shown by cross-infection experiments. However the available evidence is still considered as incomplete by the authors because of irregularities which occurred in neutralization tests with human convalescent sera.

Encephalitis Group.

In 1940 Smithburn had isolated from the blood of a native in Uganda, Africa, a neurotropic virus which was called West Nile virus; no unusual illness was reported in the region where this agent had been isolated. This virus behaved in mice somewhat like the viruses of St. Louis encephalitis, Japanese encephalitis and louping ill, approximated in size the virus of St. Louis encephalitis, and gave evidence of cross-neutralization with the three viruses mentioned above. In attempting to obtain data on the geographical distribution of the West Nile virus, Smithburn and Jacobs made an epidemiological survey of certain regions of the Western Province of Uganda, including the area from which the virus had originally been isolated, to determine the incidence of humoral immunity against this and the related neurotropic viruses. The results showed that antibodies against this group of viruses were present in the serum of residents of every country included in the survey, except Spanish Guinea. The West Nile virus was apparently active in the Sudan, Uganda, Kenya and in the Congo, the St. Louis virus in Kenya and the Congo and possibly also in the Sudan, and Japanese B virus in the Sudan and the Congo. The serum of 1 to 4 blue monkeys caught in the Kakamega forest neutralized both West Nile and St. Louis virus. In a second communication Smithburn reports the results of a careful study in which the immunological properties of the three viruses, West Nile, St. Louis, Japanese B, were compared with a viewpoint towards some differentiation. It was found that while West Nile antiserum fails to neutralize either St. Louis or Japanese B virus, antisera against St. Louis virus may cross-neutralize the West Nile virus and antisera against Japanese B virus have some power to cross-neutralize both West Nile and St. Louis virus. On the other hand, vaccination with either of the three viruses confers protection only against infection with the homologous strain. The described facts not only point to the antigenic complexity of the agents in question but also indicate the possibility of the existence of a large family of encephalitis-producing viruses which share certain immunological and pathogenic properties. Much new light has been shed on the epidemiology of the viruses belonging to the encephalitis group by the recent work of Hammon and his colleagues, particularly with reference to the transmission of encephalitis in the Yakima Valley, California. Over a period of four months, during the summer of 1941, some 15,000 living arthropods were collected, frozen and inoculated into laboratory animals in an attempt to isolate encephalitis virus; over 1,200 of these were mosquitoes. From Culex tarsalis three strains of St. Louis and five strains of Western equine encephalitis could be isolated, but not from other species of mosquitoes. These studies are complemented by recent investigations of Howitt and van Herick in which the authors recorded a high percentage of specific antibodies against St. Louis and Western equine encephalomyelitis virus (61.6 per cent against both viruses) in the serum of domestic mammals (horses, cows, rabbits) or birds (13 per cent against both viruses) in endemic areas. The finding of these antibodies in the blood stream of wild and domestic animals has greatly extended our views regarding the scope of infection for these two diseases, suggesting the existence of a very extensive animal reservoir for these viruses whence encephalitis may be transmitted to man through insect vectors.

Poliomyelitis Group.

The dissemination of poliomyelitis virus in monkeys following intrasciatic injection was carefully traced by Sabin and Ward. No virus could be detected in nasal secretions or olfactory bulbs, nasal mucosa, tonsils and adjacent pharyngeal tissue, salivary glands, adrenals, superior cervica, sympathetical ganglia, abdominal celiac ganglia and small intestine. Elimination of virus by any of the routes indicated by the above choice of tissues therefore was obviously not one of the consequences of poliomyelitic infection resulting from virus invasion along a peripheral nerve in monkeys.

From a series of tests covering a continuous local sampling period of 15 months, Trask and Paul recorded another instance of the detection of poliomyelitis virus in urban sewage (New York City system). These results do not necessarily indicate that the disease is transmitted by contact with sewage, but simply emphasize the stability and widespread presence of the virus in extrahuman channels which are presumably reached by contamination with human feces.

In a systematic investigation of the in vitro resistance of poliomyelitis virus to chemical agents Schultz and Robinson found among 112 different agents tested 33 which seemed to inactivate the virus upon direct contact (chrysoidin Y, Congo red 4B, copper sulfate, hexvlresorcinol, mercuric chloride, mercurochrome, methylene blue, hydrogen peroxide, oxyquinoline sulfate, potassium hydroxide, potassium permanganate, and others). Outstanding was also the high degree of resistance which the virus exhibits against a varied array of chemical compounds and its tolerance for a wide range of hydrogen ion concentrations (pH 2.2 — pH 10.4).

In a series of publications on 'rodent poliomyelitis' Jungeblut and his associates have consolidated and amplified their observations on the adaptation of human poliomyelitis virus (SK strain) from the monkey to mice and guinea pigs. A detailed serological analysis revealed no relationship between SK murine virus and lymphocytic choriomeningitis virus; however, some antigenic overlapping could be demonstrated between SK murine virus and Theiler's virus of spontaneous mouse encephalomyelitis, on the one hand, and monkey poliomyelitis virus, on the other. The conditions under which the SK murine virus may be cultivated in vitro were carefully studied. The interesting observation was made that with extended subcultivation the cultured virus shows a loss of infectivity for mice by peripheral injection, whereas intracerebral potency remains unchanged. The establishment of a fixed cavian strain of virus was described by transfer of murine virus from mouse to guinea pig. The potency of the virus was found to be considerably lower in guinea pigs than in mice; moreover, in paralyzed guinea pigs the-virus was present only in the central nervous system and not in extraneural sites. Resistance to reinfection could be demonstrated in convalescent guinea pigs as well as in guinea pigs which had survived a symptomless infection. A detailed histopathological study (Wolf) served to show the marked difference in response to the same virus in two different susceptible hosts. In paralyzed mice, in addition to an involvement of the anterior horns of the spinal cord, the virus showed strong affinity for cerebral tissues, particularly the olfactory area; in paralyzed guinea pigs there was a reversion to a predominant affinity for the-nerve cells of the anterior horn so that the picture approaches the type of lesions found in the human or simian disease. Further light has been shed on the interference in monkeys between murine and monkey polionyelitis virus. The specificity of such interference, its quantitative character, and its effectiveness against three strains of monkey virus could be demonstrated in prophylactic and therapeutic experiments. Bourdillon and Moore, who reported attempts at purification of the SK murine strain by physical and chemical means, obtained virus material in highly purified form. A comparison with analogous data available for monkey poliomyelitis virus and Theiler's-virus of spontaneous mouse encephalomyelitis revealed similar figures for all three strains of virus (sedimentation constant, molecular weight, particle size). It therefore appears that the activity of viruses belonging to the poliomyelitis group, regardless of the strain considered, is always associated with material of very heavy molecular weight. As soon as electron microscope pictures are available it will be of interest to observe whether this analogy extends also to the shape of the respective virus particles.

Rabies.

As the result of long-continued study of the rabies vaccination problem Webster has finally announced the production of a non-virulent, irradiated, single dose (330,000 mouse doses per cc.) rabies vaccine which is highly effective in the immunization of dogs against rabic infection.

Virus Tumors.

Following the original discovery by Berry and Dedrick that fibroma virus may be transformed into myxoma virus by injecting rabbits with suitable mixtures of killed myxoma virus and live fibroma virus, divergent reports have been published by various authors who have tried — successfully and unsuccessfully — to repeat such transformation. Recently Gardner and Hyde were able to accomplish this transformation with 3 or 7 elementary body suspensions of myxoma virus. Confirmation has also come from the current work of Houlihan who obtained the Berry transformation again with combinations of heat-inactivated myxoma virus and active fibroma virus which were passed serially through rabbits. The occurrence of the phenomenon in only one of 21 rabbits, injected with differently prepared virus mixtures, emphasizes the difficulties in obtaining this transformation easily. Duran-Reynals reported an elaborate and most interesting study on the variation of the virus which causes the Rous sarcoma in chickens when the infectious agent is transmitted to ducks. By using ducks within the first 24 hours after hatching it was possible to infect 22 per cent of these animals with the Rous sarcoma. The lesions thus induced in ducks were divided into immediate and late tumors. Extracts from immediate tumors reproduced in chickens the characteristic Rous sarcoma but were wholly ineffective in ducks. In other words, the virus causing the immediate tumors was still a chicken virus producing a heterologous infection in ducks. On the other hand, extracts from the late tumors had entirely lost their power to induce lesions in adult chickens, whereas they were highly pathogenic for ducks. In this case the virus had evidently varied and the resulting disease was a homologous infection in the duck. A similar process of variation was noted when the above sequence was reversed by returning the duck variants to young ducks. The great variability in the infectivity of chicken and duck viruses for heterologous hosts and the great variety of tumors obtained emphasize the inherent instability and capacity for variation of the viruses which induce tumor growth.