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Much has been written concerning filtration experiments with various types of artificial filters such as the Berkefeld, Chamberlain and collodion membranes. Recently a new type of filter has come upon the market, the Seitz-Werke filter, and for certain types of work is apparently quite efficient. The efficiency of all these types of artificial filters, as far as the mere removal of bacteria is concerned, is beyond question. It is only when investigators attempt to draw fine conclusions from filtration experiments employing such filters that their value is questioned. A substance, for example, which is filterable through a Berkefeld Type N or W filter in the hands of one investigator may not be filterable when presumably the same type of filter in every respect is employed by another. Such results are very confusing and often discouraging. This has been particularly true in the field of filterable viruses and indeed, there are many viruses so classified at the present time upon the sole basis that they hav...

Summary Four types of diets were used in a study of weight gain in undernourishedchildren, viz., the customary diet used in this hospital, designated the “normal” diet, a diet richer in fat called the “fat” diet, and a diet low in both fat and complex carbohydrates, containing its calories as protein and dextrose, the “dextrose” diet. In the fourth diet ripe bananas were substituted for an equivalent amount of dextrose. Weight gains were more rapid with the dextrose and banana dietsthan with either of the other two. Consistent weight gains were obtained with the dextrose and banana diets at lower caloric intake than with the other diets. The fat diet necessitated largest caloric intake in order to maintain consistent weight gain. The rapid early gains in weight observed with banana and dextrosediets, presumably due in large part to water retention, were not subsequently lost, but were apparently replaced by tissue gains without an intervening period of slow or no gain. The psychologic effect of such gains is apparent. The studies of retention of calcium, phosphorus, and nitrogen confirmthe results of the studies of the weight gain and show that diets made up of protein and simple carbohydrates provide intake levels of these substances such that good body tissue can be built rapidly. These studies provide proof that the spectacular weight gains observed are due primarily to sound tissue growth, and that the resulting normal weight is an indication of normal body composition and not due to inordinate amounts of fat or water.

and subsequent experimentation. The same may be said of the streptococcus described by Rosenow.2 The problem of studying this disease in rabbits has been complicated by the appearance of spontaneous encephalitis in these animals which was first described by Bull.3 In recent years, however, this objection has been largely obviated by the work of Wright and Craighead,4 Doerr and Zdansky,5 Levaditi and Nicolou and Schoen,6 Cowdry and Nicholson,7 Goodpasture,8 McCartney 9 and others who have described the microorganism causing this disease. Out of 372 normal rabbits McCartney found as high as 76^ of the animals affected in some groups. The most common lesion histologically consists of focal areas of necrosis near the blood vessels, perivascular infiltration and a layer of mononuclear cells around the focal areas. There are apparently great variations in the lesions and occasionally small areas of epithelial-like cells without mononuclears are found scattered throughout the brain. The histologic lesions in this disease taken together with the clinical course of the disease serves to differentiate it from other forms of encephalitis in rabbits. We have been concerned especially with the form of encephalitis produced in rabbits with the herpes virus. Levaditi and Harvier 10 in 1922 described a form of encephalitis produced in rabbits by an ultramicroscopic virus obtained from a case of encephalitis. Much criticism has been directed against this virus as having anything to do with epidemic encephalitis. Flexner 11 has pointed out that out of thirty sets of specimens from cases of epidemic encephalitis Levaditi succeeded in

Among others Dreyer and Hanssen,1 Kreibich,2 Schmidt-Nielson,3 Burge, Fischer and Neill,4 Vedder,5 and Allen and Ellis6 have exposed ferments, enzymes, proenzymes and hormones to light of short wave length; while Vallet,7 Bayne-Jones and van der Lingen,8 Mayer and Dworski,9 Mayer and Guttmacher,10 , Browning and Russ,11 Cambier,12 Burge,13 Eidenow,14 Weiss and Weiss 15 and several others have exposed living cultures of bacteria and other living cells to the action of ultraviolet rays. Radium too has been employed, for example by Bruynoghe,16 who has reported the absence of lytic principle in the sixth passage of his bacteriophage filtrates when B. typhosus, the sensitive organism used, was previously exposed; and by Brutsaert17 who exposed d'Herelle's P3 to radium emanations equivalent to 0.914 grains of radium for twenty-four hours, and found the lytic property only slightly attenuated. Insulin, according to Ellis and Newton,18 is apparently more active after relatively short exposure to ultraviolet light, losing its ability to produce hypoglycemia only after prolonged irradiation.

The writer visited the laboratory of Dr. E. C. Rosenow in Rochester, Minnesota, in June, 1929, to observe the work of this investigator on epidemic encephalitis and poliomyelitis. Rosenow very kindly demonstrated to me his methods and technique with material taken from cases of epidemic encephalitis which had come to the Mayo clinic. The writer frankly expressed his skepticism of the role of the green streptococcus in epidemic encephalitis and the rather large group of diseases which Rosenow regards as allied conditions. (It should be recalled that Rosenow regards a green streptococcus as etiologically related to a group of 12 or more disease conditions among which are epidemic encephalitis, poliomyelitis, spasmodic torticolis, epidemic hiccup, ulcerative colitis, gastric ulcer, arthritis deformans, rheumatic fever, epidemic influenza, infectious arrythmia, chorea, pulmonary embolism, etc.).Rosenow was able to demonstrate to me that one could take swabs from the tonsils and nasopharynx of encephalitis cas...

Climate and human welfare have long been subjects for discussion. The variables met with in the consideration of this subject are so numerous as to discourage the scientific mind which seeks to establish suitable controls as points of departure for rational reasoning. Man, in his effort to adapt himself to his climatic environment, is dealing with a fundamental situation which determines the expenditure of human energy. As Huxley says, “Changes of climate cause migrations, and migrations bring about not only wars, but the fertilizing intermingling of ideas necessary for rapid advance in civilization.” Climate is usually defined as the temperature and meteorological conditions of a country, or as the effects of the sun, atmosphere and earth upon living objects at a given place on the earth's surface. Thus, radiant energy, is one of the elements of climate, as are also humidity, rain, snow, wind, density, electrification and temperature, all of which determine, with other factors, what the atmosphere shall be.

Metabolic studies of calcium, phosphorus, and nitrogen in children with moderate to severe idiopathic scoliosis have been carried out. The findings demonstrated no clear-cut abnormality in mineral metabolism, but did show a serious disturbance in catabolism of protein with excessive wastage of nitrogen through the urine. The metabolic error also appears to involve derivatives of sulphur-containing amino acids. The scoliotic children tended to excrete a larger number of essential amino acids than did normal children of the same age range.

Since the comprehensive work of Novy, Roehm and Soule1 on microbic respiration appeared in 1925, an effort has been made to devise a simple apparatus for determining CO2 production in cultures which would be simple and available for ordinary laboratory use. It is doubtful if any device known at present will give the fine results which Novy, Roehm and Soule are able to obtain with the compensation manometer.Bronfenbrenner2 described a simple micro-respirometer in 1926 using as a test object a strain of bacteriophage. He was unable to demonstrate that the bacteriophage respired. In a more recent report this author has studied the respiration of the herpes virus and of rabies virus3. In this study in order to differentiate between the respiration of tissue and that of the filterable virus he made use of the Warburg4 respirometer to determine the oxygen uptake and of his closed cell respirometer for the respiration proper.Bertrand5 was perhaps the first to make use of an alkali trap for the absorption of resp...

The results of a fifteen year follow-up of a family with idiopathic Fanconi syndrome without cystinosis have been reviewed and compared with those of similar cases recorded in the literature. The disease in our patients is considered to be of autosomal dominant transmission. The mother and her oldest child, a son, were severely affected with stunting, hypophosphatemia, hypokalemia, acidosis, gross aminoaciduria (including increased excretion of cystine), proteinuria and glycosuria. The son showed hypercalciuria, but the mother's urinary excretion of calcium was within the normal range. The two younger children were small for their ages and showed some increase in aminoaciduria; each finally achieved low normal height and in neither has the disease developed as yet. Of four grandchildren, one is somewhat stunted at one year of age, but otherwise, up to the present, all seem to be normal. Control of the disease in the two affected members became increasingly difficult after each lapse in therapy. Similar findings have been reported by others.

Bordet1 has demonstrated that the intravenous injection of globulins from fresh, normal guinea pig serum into guinea pigs is followed by extreme shock and death of the animal, usually within 3 or 4 minutes. In 1925, together with Bordet, further study was made of this phenomenon.2 In this study it was found that the toxicity of the globulin fraction of guinea pig serum for guinea pigs was destroyed when heated at 70° C. for 1/2 hour; that the toxicity of the globulin fraction remained intact when heated at 60° C. for the same length of time; that the leucocyte count of the animal was decreased to about 1/2 following injection; that the temperature of the animal increased 3 to 4 degrees and there was a delay in the coagulation time of the blood following injection, in some cases as long as 24 hours. At the same time it was shown that injections of globulins intraperitoneally or subcutaneously into guinea pigs were innocuous.Later, in collaboration with Zunz3, it was demonstrated that following the intraven...

Summary The experiments reported describe the actual cultivation of Mycobacterium leprae on artificial culture medium in a gaseous tension of carbon dioxide and oxygen through sixteen generations over a period of eighteen months. Several new mediums have been prepared and inoculated but no growth appeared after six weeks incubation. Organisms from the ninth, tenth and eleventh serial transfers failed to produce experimental tissue changes in older monkeys then were used several months earlier when the culture which was not so distant from the host produced granulomatous lesions by intradermal injection. Guinea pigs and several varieties of mice manifested no pathologic changes when injected intracutaneously with these cultures. Serological data are given as a matter of record. A discussion of the possible mechanism of infection in human leprosy is presented. These studies are being continued.

Recent work on attempts to produce active immunity in monkeys with poliomyelitis virus by McKinley and Larson1 and quite recently by Kramer, Schaeffer and Park,2 Brodie3, 4 and Kolmer and Rule5, 6 has indicated that it is possible to produce such immunity with virus treated with sodium ricinoleate, immune serum or formalin. In addition Park and his group and Kolmer have employed such vaccines without harm in children and adults. Aycock and others have given live virus to monkeys subcutaneously without producing paralysis. Brodie7 has demonstrated that a single sub-infective intracutaneous inoculation of active virus gives rise to an immunity which appears at or soon after the sixth day and reaches its height by the twentieth day. The immunity so produced persists for at least one year. A second injection of the antigen gives rise to considerable additional immunity. These various observations give hope that some method may be found to produce immunity against this disease.We here report briefly a method w...

It is well known that various strains of herpes virus produce encephalitis in rabbits. Some investigators believe that the herpes virus is the etiologic agent in epidemic encephalitis in human beings. At present there is little evidence to support this view. The fact remains, however, that the herpes virus has been recovered from the brain tissue of several cases of epidemic encephalitis and the question naturally arises as to whether the herpes virus is related to the disease process in such cases or whether it is merely present by accident as a contaminating agent. A critical discussion of the question is contained in another publication.1In a previous communication2 we have shown that rabbits may be hyperimmunized with herpes virus attenuated by fresh rabbit serum and that the serums from such rabbits are capable of producing passive immunity in healthy rabbits when injected intravenously. Attempts to immunize sheep were unsuccessful even when fresh virus was administered subcutaneously.The possibility...

The geographic and seasonal incidence and variations of poliomyelitis have been among the most interesting problems in the study of the epidemiology of this disease. Further, the preponderance of cases in children under the age of puberty with also a tendency towards a larger proportion of cases in males than in females is striking. Friedberger, Bock and Furstenheim1 have called attention to antibody rise in relation to age and one may logically inquire what, if any, may be the physiological factors involved which may modify the susceptibility or resistance to infection with the virus of poliomyelitis. The work of Aycock2 and of Shaughnessy, Harmon and Gordon3 indicates that the serums of normal individuals, particularly adults, may in a high percentage of cases neutralize this virus. Aycock has suggested that different reactions to infection with poliomyelitis virus may be due to physiological variations in the host, rather than to variations in the virus itself. Further this author states that evidence ...

Through the kindness of Dr. E. V. Cowdry and Dr. Ralph S. Muckenfuss of the School of Medicine, Washington University, we have been permitted to study brain tissue from 2 fatal cases of the recent epidemic of encephalitis in St. Louis. When received by us, these 2 brains were immediately cultured anaerobically and aerobic-ally in several different mediums to determine the presence or absence of visible microorganisms, such as the streptococcus. All cultures were entirely negative. Emulsions prepared with these 2 brains were then injected intracerebrally into a large number of different animals, including Rhesus and Cebus monkeys, rabbits, guinea pigs, kangaroo rats, white rats and mice, canaries, pigeons, ferrets, dogs, puppies, cats and kittens. None of these animals or fowls inoculated has developed any symptoms definitely characteristic of encephalitis after 47 days. On the twenty-fifth day following inoculation one of the kittens died with what appeared to be cerebral involvement, but upon autopsy, an...

In so far as we have been able to learn epidemics of so-called infectious jaundice have never occurred in the Philippines. Indeed the writer has been unable to find any record in the various hospit...

During the past year Kelser1 has prepared a chloroform-treated tissue-vaccine for rinderpest which is highly efficacious in protecting cattle and carabaos against this disease. Kakisaki, Nakanishi and Nakamura2 in Japan have also prepared a tissue-vaccine for this disease by treating the infected tissues with toluol, ether, etc. The vaccine prepared by the Japanese workers is difficult to administer because of its consistency and is also absorbed very slowly. In the Philippines the Kelser vaccine has now been adopted as the standard method of protection against rinderpest and its efficiency approaches 100%. In more recent work Kelser3 has prepared a chloroform-treated tissue-vaccine for rabies.Briefly the chloroform-treated tissue vaccine for rinderpest as prepared by Kelser consists of finely ground tissues (lymph glands, tonsils, spleen, liver) from animals killed in the acute stages of rinderpest. This tissue is diluted with equal parts of physiological saline and for each 100 cc. of tissue emulsion 0....

We have recently attempted to test the effect of induced fever on the development of myxomatosis and fibroma in rabbits. There are a large number of fever machines1 in use in clinics and in offices of practicing physicians, and the subject of fever therapy in various pathological conditions is growing rapidly in importance. In some of these, notably in the acute pelvic inflammation due to Neisseria gonorrhea the treatment has proved its efficiency and worth. In other conditions fever therapy is employed experimentally, or empirically, as in the case of arthritis. Clinical results are good, bad, and indifferent, depending upon the individual patient and his disease. While this type of therapy has been directed for the most part toward bacterial inflammatory conditions, little has been done with the virus diseases. The authors, therefore, have attempted to set up crucial experiments with the viruses of myxomatosis and fibroma in order to determine if induced fever would affect these virus processes in any w...

The study of the virus of rinderpest has been rendered difficult because of the lack of a suitable experimental animal. The virus of rinderpest is pathogenic for cattle, carabaos, hogs, boars, sheep, goats and camels. With the exception of goats and sheep the other susceptible animals are either too expensive to use for experimental purposes or are unobtainable. That goats are susceptible to the virus of rinderpest has been shown by Kolle and Turner1 and by Topacio.2 In the Philippines where rinderpest has a high incidence among cattle it is possible to obtain goats in large numbers and they are even less expensive than rabbits. As a rule the mortality in goats from this disease is very low. This animal, however, manifests very definite symptoms of the disease. These symptoms consist of a gradual rise in temperature reaching a maximum of 40.2 degrees C. to 40.8 degrees C. on the 5th or 6th day. About this time the animal develops a diarrhoea which persists for some time while the temperature gradually ret...

McKinley and Soule1 reported the successful cultivation of Mycobacterium leprae, obtained from Puerto Rican lepers, on several culture media. Subsequent reports were made by Soule and McKinley2, 3 when their nonchromogenic strain of acid-fast bacilli, believed to be the true Mycobacterium leprae, had been carried through the eighth and sixteenth generations respectively, the latter representing cultivation over a period of 18 months. Experimental protocols were also presented dealing with suggestive experimental lesions produced in 2 species of monkeys. In the cultivation work it was apparent that the leprosy microbe was maintained on artificial media with greater difficulty with each generation or transfer. In the sixteenth generation, so-called, after the organism had been on artificial media for some 18 months, only 2 definitely positive cultures resulted. One of these cultures has been employed in an attempt to ascertain better methods of cultivation.A logical procedure was to attempt cultivation in e...

There has been a great deal of discussion in the literature regarding the production of bacteriophage from bacterial cultures. A classical example of this phenomenon is the B. coli of Lisbonne and Carrere1 which is able to elaborate lytic principle for B. dysentery Shiga. This subject has been treated extensively by one of us (McKinley2) in another publication. More recently Muckenfuss3 has studied these cultures supplied to him by us and he concludes that such organisms as B. coli Lisbonne may be made lysogenic by exposing the organisms to a bacteriophage and that the organisms so exposed then “carry” the lytic principle and antibodies are produced against the bacteriophage when the “phage infected” bacteria are used for immunization. However, this author states that failure of such antibodies to appear on immunization with bacteria does not necessarily indicate that bacteriophage is not present.We have attempted to “contaminate” or “infect” a strain of B. coli with a bacteriophage lytic for Staphylococc...

At a Conference on Tropical Medicine held on February 5th and 6th under the auspices of the National Research Council in Washington the new Academy of Tropical Medicine was formed and incorporated under the laws of the District of Columbia. Delegates to the Conference included: Dr. George C. Shattuck and Dr. Richard P. Strong, Harvard School of Medicine; Dr. Francis W. O'Connor and Dr. James W. Jobling, College of Physicians & Surgeons, Columbia University; Dr. Charles F. Craig, Tulane School of Medicine; Dr. Henry E. Meleney, School of Medicine, Vanderbilt University; Dr. Robert Hegner and Dr. W. W. Cort, School of Hygiene and Public Health, Johns Hopkins University; Dr. Edward B. Vedder and Dean Earl B. McKinley, School of Medicine, George Washington University; Dr. William H. Taliaferro, Chicago University; Dr. Alfred C. Reed, Pacific Institute of Tropical Medicine, University of California; Dr. Thomas T. Mackie, School of Medicine, Cornell University; Dr. Howard T. Karsner, School of Medicine, Western Reserve University; Dr. Henry B. Ward, University of Illinois; Dr. Stanhope Bayne-Jones, School of Medicine, Yale University; Dr. Malcolm N. Soule, University of Michigan Medical School; Dr. Mark F. Boyd, International Health Division, Rockefeller Foundation; Dr. Theobald Smith representing the Rockefeller Institutes of New York and Princeton; Mr. Perry Burgess, President, Leonard Wood Memorial for the Eradication of Leprosy; Dr. George W. Bachman, School of Tropical Medicine, San Juan, Puerto Rico; Dr. Robert Hegner, Gorgas Memorial; Dr. Henry Hanson, State Board of Health of Florida; Dr. R. C. Connor, Medical Department, United Fruit Co., Major James S. Simmons, Medical Corps, United States Army; Lieut. Commander Sterling S. Cook, Medical Department, United States Navy; Dr. L. R. Thompson, United State Health Service; Dr. Bolivar J. Lloyd, Pan American Sanitary Bureau and Maurice C. Hall, Bureau of Animal Industry, Department of Agriculture.

It is well known that bacteriophage may be precipitated from bouillon by alcohol, acetone, and magnesium sulphate. The lytic principle is only slightly impaired by this procedure though length of time of exposure and temperature have been shown to be limiting factors. It is thought that the lytic principle is adsorbed onto protein and hence is naturally carried down with the precipitate. Hauduroy1 has shown that gelatin, as well as other similar substances, such as agar, gum, etc., will arrest the action of the bacteriophage. Bronfenbrenner2 states that the influence of agar or gelatin in inhibiting bacteriophagy depends on the fact that these agents prevent water from entering the bacterial cells. De Necker3 has shown that colloidal metals, bone charcoal, and serum exercise an inhibitory effect upon the bacteriophage and this author thinks that the nature of the adsorption suggests that the lytic principle is a ferment. Angerer4 has shown that killed Flexner dysentery bacilli adsorb about 70% of homologo...

Herpetic encephalitis may be produced in rabbits by inoculating such animals either subdurally, intravenously, subcutaneously, or intraperitoneally. The possibility of inducing herpetic encephalitis in guinea pigs by feeding occurred to us. While there is little evidence to support the view that epidemic encephalitis in man is caused by the herpes virus, any evidence regarding the portals of entry of this virus into the animal body is important. Nothing is known concerning the portal of entry of the true virus of epidemic encephalitis and epidemiological control of the disease is based largely upon speculation. It is known that paralysis follows the inoculation of the virus of poliomyelitis into the stomach and intestines of monkeys and it seemed probable to us that infection might be produced in this way with the herpes virus.Four guinea pigs were fed by catheter 3 cc. of a freshly prepared emulsion of herpetic (Beckley) rabbit brain. One guinea pig received 4 cc. while a 6th received 5 cc. Of the 6 guin...

A very common infection in Porto Rico is caused by a hemolytic Staphylococcus aureus. These infections are exceedingly virulent as a rule and offer a serious problem in our clinics and hospitals. Pomales1 has shown that this organism is present in the throat flora of about 19% of supposedly healthy individuals and in pathological cases it predominated in 24%. This organism proved to be the predominating microbe in the crypts and the interior of 65 pairs of tonsils removed at operation. Because of the severity of infections with this organism we have attempted treatment in a few cases with a bacteriophage which is lytic for a non-hemolytic Staphylococcus aureus. The administration of the bacteriophage has had no effect upon the course of the infection. The bacteriophage employed was supplied to us by Larkum,2 who has reported the efficacious use of this lytic principle in clinical cases.We have attempted to adapt the bacteriophage which is lytic for a non-hemolytic variety of Staphylococcus aureus to 7 str...

We1 have previously reported the cultivation of Mycobacterium leprae in minced chick embryo suspended in Tyrode's solution direct from leprous nodules containing acid-fast organisms. Evidence of growth and multiplication was obtained in as few as 5 days although subsequent experience has shown that better growth occurs in from 10 days to 2 weeks. The leprosy nodules were digested with 3% sodium hydroxide to free the organisms from the tissue and to destroy contaminants and, following neutralization, the tissue medium was inoculated. Human embryonic tissue (spleen, liver, lung) has also been employed and more experience with this tissue leads us to believe that it is a better medium than chick embryo, contrary to our previous report, although it is, of course, more difficult to obtain.Leprosy nodules which have been treated as described above, the acid-fast organisms from which have been seeded in minced embryonic tissue suspended in Tyrode's solution, have been found to contain acid-fast organisms which a...

Since oysters have been shown to be a good source of vitamins A, B, C, and D as well as to contain in considerable amounts the inorganic elements iron, copper, manganese, zinc, lead, arsenic and iodine,1 the possibility of the use of oysters in culture mediums was suggested. It was found that many organisms, including the group of acid-fast bacteria, grow quite luxuriantly on certain of the mediums prepared. Two solid egg-oyster mediums, one made with the yolks and the other with the whites, and a hormone oyster infusion broth have proven to be the most satisfactory of all preparations.Six strains of Mycobacterium tuberculosis (H 37, Ru a virulent human strain obtained from Dr. Novy, a virulent bovine strain, a virulent avian strain and an avirulent strain) and 9 strains of chro-mogenic acid-fast bacteria isolated from lepers by several investigators all give typical growth on both the egg white and egg yolk oyster mediums. The strain of M. leprae isolated by McKinley and Soule2, 3, 4 has been successfull...