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1. A new antimetabolite, 6-mercaptopurine, has been shown to produce good clinical and hematologic remissions in fifteen out of forty-five children with acute leukemia. Another ten showed partial remissions and clinical improvement. 2. Remissions in adults with acute leukemia have occasionally been brought about by 6-mercaptopurine, and in a few cases it has produced temporary remissions in both the early and the late stages of chronic myelocytic leukemia. 3. The compound has been effective in some children whose disease was resistant to the folic acid antagonists, as shown by the fact that out of twenty-four children with acute leukemia whose disease had been proved to be resistant to amethopterin, five had good clinical and hematologic remissions and five had partial remissions with some marrow and clinical improvement. Some benefit was seen in eight out of eighteen patients whose disease was resistant to ACTH and cortisone. 4. In children the daily oral administration of 2.5 mg./Kg. rarely caused toxic manifestations, but continued therapy at this dose in adults or at higher levels in children occasionally produced bone marrow depression or gastrointestinal symptoms. 5. There is evidence that the therapeutic resistance of the acute leukemias to 6MP develops somewhat more rapidly than it does to the folic acid antagonists but there is, as yet, no laboratory or clinical evidence of cross resistance between these two types of antimetabolites. 6. In a total of thirty-five patients with lymphomas and miscellaneous carcinomas and sarcomas, 6MP did not produce any definite clinical improvement at doses which produced hematologic toxicity. 7. Although 6-mercaptopurine acts as a purine antagonist in certain forms of bacteria, the exact mechanism of its action in leukemia is at present unknown. Since its mode of action appears to differ from that of other agents previously employed clinically in the treatment of leukemia, this compound would appear to be of fundamental as well as practical interest.

THE NITROGEN mustards were introduced into medical practice in 1946 for the palliative treatment of the lymphomas, leukemias and other types of neoplastic disease.1 The most commonly administered nitrogen mustard is methyl-bis (2-chloroethyl) amine hydrochloride (HN2), and, since 1946, much experience has been gained from its use throughout the world.2 This nitrogen mustard has found a useful place as a temporary palliative agent in the management of certain types and stages of neoplastic disease. It must be injected intravenously, and it frequently produces severe nausea and vomiting; consequently, its administration, in most cases, has been regarded as a hospital procedure. Extravasation of the injected solution will produce a prolonged and painful local reaction, and, in patients receiving repeated courses of treatment, venous thromboses and difficulty in finding suitable veins for injection may occur. The dosage must be carefully controlled, since an excessive dose will produce serious, prolonged

The effective treatment of sprue is a problem of considerable practical importance in spite of the fact that therapeutic methods which are occasionally successful have been at hand for many years. One serious difficulty lies in the fact that different individuals, presenting an apparently identical clinical picture, manifest wide variations in the amount of specific therapy that they require to effect clinical cure. Moreover, the available information regarding the treatment of sprue is confusing, since the various therapeutic procedures in use appear to be so unrelated and the clinical results obtained from them have been so inconstant that it has seemed impossible to draw up a general rule of treatment that would be applicable to all cases.More detailed analysis of the existing therapeutic methods in the light of present knowledge makes it clear that a general rule of treatment can be formulated and, furthermore, that from the therapeutic results

In a previous paper1 the fact that mice, rabbits and guinea-pigs are susceptible to psittacosis was reported. No description, however, of the pathologic changes observed or of the work on immunity was given, nor was any mention made concerning experimental psittacosis in monkeys. Furthermore, the portal of entry and exit of the virus was not discussed. The occurrence of a laboratory infection2 in one of the workers (G. P. B.) made feasible certain experiments on immunity and also furnished a series of roentgenograms of the lung involvement to be used for comparison with those obtained of the experimental disease in monkeys. Therefore, in view of the general interest in psittacosis, it seems advisable at this time to record briefly the results of some of our work.NEUTRALIZATION OF PSITTACOSIS VIRUS WITH CONVALESCENT SERUMAlthough serum from recovered individuals has been used in the treatment of psittacosis, no one

It is common clinical experience that patients with gastric carcinoma sooner or later develop anemia. The nature of this anemia, however, is not uniform, and variations from the macrocytic hyperchromic to the microcytic hypochromic disorders have been described. Indeed, it is not unusual to find that even in the same person the anemia may change its characteristics from month to month.It is, of course, obvious that the existence of anemia preoperatively in these patients adds to the hazards of their operative and postoperative periods. There now is good evidence that anemia in patients submitted to prolonged surgical procedures may increase their tendency to shock states1 and their susceptibility to infections, aggravate their usual hypoproteinemia,2 impair wound healing and induce wound disruption.3 Although it is possible to repair this anemic state preoperatively by whole blood transfusions, this is only a transitory measure and its frequent repetition is

An ulcerative stomatitis associated with leucopenia and granulopenia can be induced in dogs by means of a diet causing black tongue. The decrease of circulating leucocytes is due to a suppression of maturation of the erythropoietic elements of the bone marrow. The changes as a whole have a resemblance to those occurring in human beings with acute agranulocytosis.

On feeding to splenectomized dogs a diet producing black tongue, severe anemia developed associated with the presence of small bodies in or on the erythrocytes. The bodies were morphologically similar to Bartonella muris and Bartonella canis. The addition of lean beef to the diet, a material prophylactic against its effects, was followed by improvement of the blood levels, the presence of increased numbers of reticulocytes in the circulating blood, and the disappearance of the bodies. When the blood containing Bartonella-like bodies was injected into other splenectomized dogs fed a normal or a black tongue-producing diet, anemia developed in them and the bodies appeared in large numbers. Similar injections into non-splenectomized animals fed in the same way had anemia alone as its result. Injections into normal animals fed a normal diet caused not even anemia.

1. Under ordinary conditions of hydrogen ion concentration the virus of poliomyelitis, as such, or associated with particles in fine suspension, migrates in an electrical field to the anode. It follows that the virus bears an electronegative charge. 2. By means of cataphoresis, the virus can be recovered from a non-infective mixture of virus and specific immune serum. 3. By the same means it is possible to reveal the presence of virus in the central nervous system of a monkey which has recovered from the active stage of experimental poliomyelitis.

1. The introduction of considerable amounts of living, active poliomyelitis virus into the skin and subcutaneous tissue of monkeys protects the animals against intracerebral inoculations of similar virus material. 2. The degree of protection conferred by intradermal is greater than by subcutaneous injection. 3. During intradermal and subcutaneous inoculations, no local or general pathological signs were observed. 4. The degree of protection produced by the immunization methods used is not absolute, since a percentage of the inoculated monkeys respond to intracerebral injections of highly potent virus. 5. The sera of the animals inoculated intradermally or subcutaneously neutralized poliomyelitis virus in vitro, irrespective of the result of intracerebral inoculation, in all except one instance. 6. The power of the serum of treated monkeys to neutralize virus in vitro is a more delicate test of immunity than is the intracerebral inoculation.

1. An instance of successful inoculation of poliomyelitis virus after preservation for 8 years in 50 per cent glycerol is reported. 2. The virulence of the material injected remained essentially unchanged during this period. 3. The fact that poliomyelitis virus will survive in glycerol for so great a period may be taken as further indication of the improbability of streptococci as the inciting organisms. 4. Poliomyelitis virus would seem to vary in its resistance to glycerolation. 5. The remarkable persistence of active virus outside of the body may have a bearing on the epidemiology of poliomyelitis.

1. The intratracheal injection of egg albumin or pneumococcus protein induces an inflammatory reaction in the lungs of rabbits previously inoculated with the respective antigen. 2. A similar reaction occurs following intratracheal injection of pneumococcus protein into the lungs of rabbits previously inoculated with heat-killed suspensions of the bacteria. 3. This reaction appears to be related to the presence of circulating antibody and to have the nature of the Arthus reaction. 4. A study of the reaction of the lung of rabbits to infection caused by intravenous injections of Pneumococcus reveals that (a) reactions occur irregularly in the lung; (b) in the lungs in which reactions do occur, the histological changes are not different in normal rabbits and in rabbits made resistant by previous intravenous or intracutaneous injections of pneumococci. 5. Intratracheal injection of pneumococcus protein followed by intravenous injection of virulent pneumococci on the next day does not alter the course and character of the infection in resistant rabbits. 6. The experiments reported in this paper bring no evidences to support the view that the lesions in the lungs of rabbits following the intravenous injection of pneumococci are modified by any previous state of sensitivity.

1. Vaccine virus and specific immune serum mixed in such proportions as to produce no lesion when inoculated intradermally induce immunity when instilled into the nasal cavities of rabbits. 2. The mixture is also effective when inoculated subcutaneously. 3. Immunity is brought about with a minimum of systemic reaction and no local one. 4. When the mixtures are incompletely neutralized generalized vaccinia results.

Through the kindness of Dr. W. H. Park we have been enabled to study a horse antipoliomyelitic serum. This preparation has been supplied us in three forms: citrated blood plasma, serum, and globulin concentrate. We have tested these preparations in vitro and in vivo for inactivating or neutralizing or, to use perhaps a better term, antiviral effects against a constant, potent, filtrate virus of poliomyelitis. The preparations exhibited these effects when combined in vitro. Their action in this respect appears to be greater and more constant than that found by Stewart and Haselbauer for the Pettit antipoliomyelitic horse serum. On the other hand, in vivo tests carried out by us were less successful. In comparison with the constancy of action, under given conditions, of convalescent monkey and human sera, the antipoliomyelitic horse serum displayed striking irregularity, and certain preparations were devoid of protective power. The precise nature of the inactivating substances in the horse antiserum and their relation to the corresponding substances in convalescent sera have still, to be determined. As far as one absorption test carried out by us indicates, precipitin does not play a major rôle in the inactivating process. When an active globulin concentrate was filtered through Berkefeld candles, it lost its in vitro inactivating power. This is not true of convalescent sera in the native state. No tests have, however, been made with globulin concentrates from such sera. The experiments described in this paper raise the question whether, therapeutically considered, the antipoliomyelitic horse serum should be regarded as an exact equivalent of, and hence employed as a perfect substitute for, convalescent serum. This question can only be answered by further experiment and observation.

1. Experiments are reported on the use of poliomyelitis virus neutralized by specific antiserum as an agent to induce active immunity against the experimental disease in monkeys. 2. The results indicate that protection can be conferred upon a certain number of the treated animals. 3. The neutralized material gave rise in no instance to symptoms of disease in the treated monkeys. 4. Active poliomyelitis virus, suitably neutralized by admixture with convalescent serum, was without pathogenic effect when given by repeated nasal instillations.

A comparison has been made of the neutralizing value of pooled convalescent monkey serum for the filtered virus of poliomyelitis, before and after a series of reinforcement injections of the same virus strain. The strength of the pooled convalescent serum is increased by the reinforcing procedure. The original monkey convalescent serum had a neutralization value much below that of a pooled human convalescent serum. By reinforcement the neutralization value of the monkey serum was brought approximately to that of the human serum. One sample of serum from a supposedly normal child of 8 years exhibited a neutralizing value approximately equal to that of a pooled human convalescent serum and the reinforced pooled monkey serum.

The study here reported concerns attempts at bacteriological cultivations with fragments of brain or cord, or with Berkefeld V filtrates of the nervous tissues, from seven monkeys successfully inoculated with poliomyelitic virus. With these materials, 315 tubes were inoculated, of which thirty-six showed minute bodies resembling the globoid bodies described by Flexner and Noguchi. However, a study of subplants from these minute, morphological particles did not convince us that we had in hand actual cultures of the globoid bodies, or indeed of any living microorganism. Nevertheless, when washed sediments from subplants of one of the strains, representing the seventh, eighth, ninth, and tenth transfers, were inoculated into monkeys, the clinical signs and pathological effects characteristic of experimental poliomyelitis could be induced. The virulence of the "cultures" could not be ascribed to carrying over the original material into these remote subplants since the seventh transfer represented a dilution of the original cultivated material to about 1.5 x 10–12, and the tenth, to about 1.3 x 10–18 if one assume, as the transfer technic justifies, a thorough mixing of the contents of each tube. On the contrary, it appears as if the poliomyelitic virus had multiplied in vitro, and had increased as a consequence of being in a medium of a modified living tissue-cell culture. For in practically all specimens we observed many well-preserved kidney tissue cells and leucocytes, the latter probably derived from human ascitic fluid, a component of the Smith-Noguchi medium. In this connection, it should be mentioned that the several lots of ascitic fluid used in the cultivation tests were recently obtained from patients and employed from a week to a month after their collection. There remains for consideration the problem of the selective pathogenicity of the "cultures:" only the material of those tubes of the ninth and tenth transfers which showed the "globoid bodies" proved pathogenic; those respective tubes of the same transfers which were free from the minute bodies but apparently identical in all other respects, were avirulent. It may be that the virus was adsorbed to the particular bodies which we have found in the "cultures" and which resemble closely the globoid bodies of Flexner and Noguchi. Further elaboration of this study would be necessary, however, before such an inference could be regarded as a definite hypothesis.

1. By means of a single large dose of poliomyelitis virus, distributed at a number of intradermal sites, active immunity has been produced in Macacus rhesus monkeys, as shown by skin neutralization and intracisternal tests. 2. In the small series (four animals) of monkeys so treated, neither abortive nor paralytic signs of experimental poliomyelitis appeared.

1. The decreased concentrations of vitamin A in the livers of rats given dibenzanthracene probably are due to a particular effect of the carcinogen on the ability of the liver to store the vitamin and not to the production of general hepatic dysfunction. 2. The administration of dibenzanthracene to normal rats does not (a) increase significantly their hepatic content of total fat nor decrease that of phospholipid; (b) impair the ability of their livers to fabricate serum albumin; (c) impair the capacity of their livers to esterify cholesterol or phenol; (d) interfere with the hepatic synthesis and conjugation of glucuronic acid; or (e) interfere with the hepatic storage of riboflavin. 3. The simultaneous ingestion of yeast by the dibenzanthracene-treated rats further depletes their hepatic stores of vitamin A. This depletion conceivably is due to the fact that yeast alone also might deplete the liver of its vitamin A and thus a summation of two similar effects is attained. 4. The results suggest a competition between vitamin A and dibenzanthracene for some substance, possibly a protein, to which vitamin A may be bound in the liver.

The low plasma levels of vitamin A of patients with cancer of the gastrointestinal tract probably are not due to a decreased capacity of the livers of those patients to store the vitamin.

1. By feeding dogs a black tongue diet and at the same time administering amidopyrine, acute stomatitis and anemia may be produced. 2. Both stomatitis and anemia occur some time before they could be expected to appear as result of the diet feeding alone. 3. The anemia is associated with suppression of maturation of the hematopoietic bone marrow elements.

1. An anemia characterized by increased size of the red blood cells and a high color index was produced in rabbits by repeated bleeding and by the subcutaneous injection of stroma-free hemoglobin solution. 2. The bone marrow of these rabbits reverted to a more primitive stage than did the marrows of rabbits rendered anemic in the same manner but not treated with hemoglobin.

1. Liver extract powder, No. 343 Lilly, and the same material prepared for parenteral use, when administered daily by mouth in amounts derived from 2.5 gm. of fresh whole liver, to rats weighing from 40 to 50 gm., contain sufficient vitamin B1 to support normal growth, provided the animals receive in addition an adequate amount of vitamin B2 G. Moreover, liver extract in the forms mentioned, administered in the same amounts, does not contain sufficient vitamin B2 G to maintain normal growth of similar rate when all other necessary constituents of the diet are provided. 2. Liver extract (Lilly) in the form prepared for parenteral use, when administered daily by intraperitoneal injections, in amounts derived from 2.5 gm. of fresh whole liver, to rats under standard experimental conditions, does not contain sufficient vitamin B2 G to maintain normal growth. Furthermore, the amount of vitamin B1 present in liver extract in this form is not as effective in supporting normal growth when given by intraperitoneal injection as it is when given by mouth. 3. Vegex, when administered daily in amounts of 50, 150, and 250 mg. to rats of 40 to 50 gm. in weight contains sufficient vitamin B1 to maintain normal growth of the rats, provided the animals receive in addition an adequate amount of vitamin B2 G. However, vegex in the same amounts does not contain sufficient vitamin B2 G to support normal growth of similar rats when all other necessary constituents of the diet are provided. 4. These experiments indicate that the extrinsic, anti-anemic factor of Castle and the thermostable growth-promoting food constituent, commonly known as vitamin B2 G, are not identical.

1. By the feeding of a particular diet, apparently lacking a substance closely associated with vitamin B2 G, a chronic disease may be produced irregularly in dogs. 2. The disease is characterized by atrophic glossitis, diarrhea, loss of weight, and anemia. 3. The disease can be prevented and relieved by materials rich in vitamin B2 G.