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Interest has recently been revived concerning the efficacy and safety of crystalline trypsin (Enzar) administered intravenously in the treatment of intravascular thrombosis. This has followed reports by Innerfield, Schwartz, and Angrist 1 stating that trypsin intravenously induces lytic effects upon artificially formed intravascular thrombi in rabbits and dogs. They also claim that with certain amounts of trypsin "complete dissolution" of such clots may be obtained "with restoration of circulatory integrity." These observations have led them to administer trypsin intravenously to patients with what they claim to have been gratifying results. 2 As the attempted dissolution of an intravascular protein thrombus with a proteolytic enzyme would appear to be an empiric but rational procedure, further consideration and investigation seemed mandatory. The concomitant possibility that it might activate the profibrinolysin system of the plasma had also to be considered. Reference to the literature, however, revealed that in certain amounts trypsin will, in

Recent investigations of the value of anticoagulants in myocardial infarction have indicated the need for a critical analysis of the blood-clotting mechanism in this disease. 1 Observations have been reported 2 which suggest that there is an increased tendency toward a coagulation associated with coronary thrombosis. Certain studies have yielded evidence that "hyperprothrombinemia" (in reality a summation of factors producing a shortening of the prothrombin time) is one of the factors responsible for the increased clotting tendency. 3 The importance of careful inquiry into whether such a state actually exists in patients with coronary thrombosis becomes obvious when the use of the anticoagulant drugs for both treatment and prophylaxis is being considered. Opportunity to observe daily prothrombin times in patients in whom coronary occlusion with myocardial infarction developed was afforded us during studies of the use of bishydroxycoumarin (dicumarol®) in this syndrome. The data obtained from observations of a group

The effects of using safflower oil and corn oil as supplements to the usual diet were studied in 22 young healthy men. Serum was obtained weekly from each subject by venipuncture, to be analyzed for total cholesterol. Determinations during an initial observation period of five weeks afforded a basis for dividing the subjects into two matched groups with equal mean serum cholesterol levels (221 mg. per 100 cc.). One group thereupon received a supplement of safflower oil for seven weeks followed by corn oil for seven weeks; the other group received corn oil for seven weeks followed by safflower oil for seven weeks. In both groups a consistent decline in the mean cholesterol levels was observed as the experiment progressed, but the changes were not convincing because of the wide individual variations and no differences between safflower and corn oil were revealed under the conditions of this experiment. Significant cholesterol-lowering effect of these two oils can be demonstrated only if they are used as replacements for, rather than additions to, some of the saturated fats in the usual diet.

Among a group of 303 patients having signs and symptoms of cerebral vascular disease 4 were later found to have pathological lesions of other than vascular origin. The histories of these four patients and two others, not of this group but exhibiting a similar situation, are here reviewed. The lesions discovered were subdural hematoma, cerebral abcess, two metastatic brain tumors, and two primary brain neoplasms. To limit errors of diagnosis and to obtain best results from therapeutic measures such as anticoagulation, the author advises that any patient with a stroke should have a complete and careful evaluation. When the medical history is inadequate, when atypical features are noted, or when the patient is younger than the age group in which cerebral thrombosis is usually encountered, both arteriography and pneumoencephalography should be seriously considered.

The possibility of preventing the extension of coronary thromboses and the development of mural thrombi in the presence of myocardial infarction by the use of anticoagulants was suggested by Solandt, Nassim and Best 1 in 1938. These investigators were able to prevent the development of both coronary thrombi and of intracardiac mural thrombi under conditions in which such thrombi are usually produced experimentally in animals, by the use of the anticoagulant, heparin. Their observations were not applied to human beings on any significant scale because of the difficulties and the risk felt to be inherent in the use of heparin clinically. In the years 1945 and 1946, Wright, 2 Nichol and Page 3 and Peters, Guyther and Brambel 4 reported encouraging results following the use of the anticoagulant "dicumarol" in the treatment of coronary thrombosis with myocardial infarction in human beings. These reports were preliminary in nature, since only small

• Series of patients with myocardial infarction treated with anticoagulants have generally shown a decrease in death rate of one-third to one-half that seen in series of such patients on other types of treatment. The incidence of thromboembolic complications has been more strikingly reduced. Contraindications and caution must be observed with anticoagulant therapy is used, and laboratory facilities must be adequate to measure its effect on the blood. For rapid action, 1,200 to 1,500 mg. of ethyl biscoumacetate and 200 to 300 mg. of bishydroxycoumarin are given at the same time by mouth; thereafter the bishydroxycoumarin is given daily in doses, generally of between 25 and 50 mg., that will maintain the prothrombin time between 22 and 35 seconds as determined by the Quick one-stage method. In some patients it is desirable to give heparin, 75 mg. subcutaneously at 12-hour intervals for two or three doses. The anticoagulant effect of the coumarin and indanedione compounds can be terminated promptly if necessary by the use of phytonadione (vitamin K 1 ). It is frequently difficult to classify attacks of myocardial infarction as severe or mild during the early days of the attack. The decision as to which patients should receive any form of therapy must rest on the judgment of the physician.

T IS presently fashionable in scientific circles to regard basic research as the high-priestess of the new era, and certainly no one can challenge this general position. However, the definition as to what basic research really consists of and who is doing it varies, depending on the spokesman. In the medical field the pathologists, the biochemists, and the anatomists consider themselves to be the basic scientists. But in broader scientific circles the physical chemists, the physicists, and the mathematicians, with the many ancillary branches of these disciplines, are not unanimous in accepting the biochemists or the pathologists into their fold as true basic scientists. Even within the medical field, it seems to make a difference whether the investigator works with an electronic computer, test tubes, mice, guinea pigs, or human beings—the implication in some quarters being that man working with man as his subject is in some way a lesser

Cases of purpura haemorrhagica after the use of sedormid (allyl-isopropyl-acetyl-carbamide) have been reported with increasing frequency since 1933. Joekes 1 reviewed the literature on this subject and stated that there were to date thirty-seven reported cases of purpura haemorrhagica due to sedormid. Since the period covered by his recent survey, seven more cases have been added to the literature. 2 It is interesting to note that on March 5, 1938, the Council on Pharmacy and Chemistry of the American Medical Association 3 declared sedormid not acceptable for New and Nonofficial Remedies. Also of the twenty recorded observers, only four are Americans. 4 In view of this we feel that it might be pertinent to describe a recent case of severe purpura haemorrhagica with two separate episodes due to this sedative. REPORT OF CASE A white woman aged 57 complained of multiple subcutaneous hemorrhages, which she had noticed on finishing her

Chronic ulcers, associated either with varicose veins or with the occlusions following phlebitis of the deep veins, constitute one of the most severe and disabling conditions affecting the lower extremities. Despite the numerous forms of treatment, including vein injection, recommended during the past fifty years, certain of these ulcers fail to heal. This is a report of the results of a new method of treatment of these ulcers, which appears to be more satisfactory than any hitherto suggested. The formation of varicose ulcers is now generally accepted as being the result of venous stasis, secondary to the dilatation of the veins and weakening of venous valves. This produces an increasing backpressure into the capillary bed, with the development of pressure edema and the waterlogging of the tissues. With the associated anoxemia, impaired nutrition and accumulation of toxic waste products of metabolism, the resistance of the tissues to trauma and infection

The problems presented by the development of arteriosclerosis are of overwhelming magnitude both medically and socially. Their potential significance is, nevertheless, for the most part hopelessly underestimated. Yet, unless satisfactory solutions are found for the varied facets of this massive loadstone, it may prove too heavy for our present civilization. Once before when our civilization was threatened by the weight of a great problem, a then little known man, Abraham Lincoln, suggested a mental approach which appears equally applicable to the present: "If we could first know where we are and whither we are tending, we could better judge what to do and how to do it." For centuries men have sought the secret of longevity. The alchemists, soothsayers and astrologers flourished in the courts of many dynasties that they might prolong the lives of the rulers. The search for this secret drove men such as Ponce de Leon to

The long-term effects of anticoagulant therapy have been studied in 100 patients with evidence of cerebral vascular thrombosis or embolism. During 2,842 patient-months without anticoagulant therapy there were 229 thromboembolic episodes (67 being cerebral) as compared with 20 thromboembolic episodes (5 being cerebral) that occurred during 2,291 patient-months on anticoagulant therapy. Similar data permitted comparison of continuous with interrupted anticoagulant therapy, and it was found that 48 thromboembolic episodes occurred during 1,311 patient-months on interrupted therapy as compared with 15 episodes during 957 patient-months on continuous therapy. The dosages of anticoagulant (usually bishydroxycoumarin) were aimed to keep the prothrombin time for the undiluted plasma between 20 and 40 seconds. Hemorrhagic complications occurred in 30 of the 100 patients; there were three fatal cerebral hemorrhages, occurring over a period of 2,532 patient-months of anticoagulant therapy. The results are interpreted to mean that anticoagulant therapy is effective in reducing the danger of recurrent thromboembolic episodes if contraindications are observed and prothrombin times are pains-takingly controlled.

It has long been realized by thoughtful teachers and practitioners of medicine that the wide variations noted in blood pressure 1 records of the same individual were due not only to changes in the pressure from time to time under different conditions but also to differences in the methods and interpretation used by the observers. A recent survey 2 revealed a serious lack of agreement among physicians as to the correct technic for taking and interpreting the blood pressure. Equally confusing was the situation among insurance companies as to what they should require of their examiners in this regard. Experiments with multiaural stethoscopes demonstrated that recent years have brought little if any improvement in this situation, since the variations among the recently qualified were as great as those among attending physicians, and the range of error was too great among all groups tested. The committees for the standardization of methods

The effect of safflower oil emulsion given as a supplement to the usual diet was studied in 24 young men, weekly samples of blood being taken and analyzed for total cholesterol. After an initial period of five weeks, the subjects were divided into two groups who received either safflower oil emulsion or a placebo for seven weeks. At the end of that time the two groups were reversed, so that those who had received the placebo now received emulsion and vice versa. Neither the subjects nor the supervising physicians knew which preparation a given subject was receiving at a given time. The emulsion, containing 65% safflower oil, was given in 15-cc. doses five times daily to a total of 75 cc. each day. Used as a supplement to the usual diet under these conditions, it had no demonstrable depressant effect on the total serum cholesterol levels.

The discovery and study of the substances that play a part in the coagulation of the blood have, as in many other areas in science, progressed in a rather strange and irregular manner. Workers in many laboratories have prepared or described the action of what they have considered to be new factors that contribute to this process, and unfortunately have given them names without knowledge or consideration of the work of others who preceded them. Some factors are now known by from 10 to 14 different names. As reports appear from various laboratories, the use of these terms is confusing to the experienced investigator. A scientific Tower of Babel has thus been erected. The situation appears discouraging, if not chaotic, to the physician who is not a specialist in this field, and even more so to the medical student. While there is widespread agreement on the meaning of prothrombin, thrombin

The exact mechanism by which bishydroxycoumarin (dicumarol®) affects the blood coagulation system is still unknown. The similarity in the chemical structure of 3-substituted 4-hydroxycoumarins to vitamin K led the original workers1to suggest that bishydroxycoumarin might act by blocking or competing with vitamin K in maintaining prothrombin activity. This hypothesis was supported by animal experiments which demonstrated the similarity of vitamin K deficiency to the biologic response to bishydroxycoumarin2and the ability of vitamin K to reverse the action of this drug.3However, it was clearly shown that the levels of 2-methyl-1, 4-naphthoquinone necessary to counteract the action of the anticoagulant are considerably larger

The present study was undertaken with the primary objective of developing data which might throw further light on our understanding of the production of arteriosclerosis. It was appreciated that certain other facts of interest might be uncovered as the investigation progressed. Although years of study by numerous workers have been devoted to this great enigma of biology, it can be fairly stated that today it is not known whether arteriosclerosis should be considered as a disease or as a purely degenerative process. The fundamental importance of diet, climate, infection, metabolism, race, heredity and many other factors is yet to be finally evaluated. Age alone does not appear to be responsible, since arteriosclerosis may be present in some persons at 30 years or less, whereas others may show practically none at the age of 70. A popular hypothesis has been that arteriosclerosis is related to prolonged stress and strain on the

Although the capillaries as a group exercise the most profound influence on the functions of the living body, their activity, especially in man, has been susceptible of direct study for only a short era in the history of medical science. A great volume of instructive work has since been produced, much of which has been confined to animals other than man. My purpose in this discussion, however, will be to outline briefly some of the more recent observations concerning the activities of the minor vessels of the skin in man which appear to have some value clinically, either (1) in adding evidence which results in changes in certain conceptions of physiology in normals, or pathologic variations in disease processes, or (2) in giving information of direct value in the study of single patients or groups of patients with similar diseases. It should be clearly stated at the outset that although

One of the most interesting and challenging developments in the field of the biologic sciences in recent years has been the recognition, isolation and, finally, synthesis of the substance causing hemorrhagic sweet clover disease in cattle, the dicoumarin 3,3′-methylene-bis-(4-hydroxycoumarin). We must give full credit for this contribution to two keen students of veterinary medicine, Schofield 1 and Roderick, 2 and to an outstanding agricultural chemist, Karl Paul Link. Schofield in Canada and Roderick at the North Dakota Agricultural Experimental Station studied and quite accurately analyzed the factors responsible for this phenomenon in cattle and rabbits. They pointed out that, whereas normal sweet clover silage produced no damage, spoiled sweet clover resulted in hemorrhagic tendencies and often in death. In 1934 Prof. Karl Paul Link and his associates at the Wisconsin Agricultural Experimental station of the University of Wisconsin undertook thetask of identifying the hemorrhagic factor in spoiled sweet clover.

On the basis of clinical and experimental observations, it has been recorded by many authors 1 that the use of tobacco produces definite effects on the vascular system, which are particularly important in certain disease conditions, such as thrombo-angiitis obliterans and angina pectoris. In spite of this widely recognized association, the available evidence has tended to show that the smoking of tobacco must be looked on as an aggravating rather than an etiologic factor. Following the work of Maddock and Coller, 2 experiments have been reported by Barker, 3 Johnson 4 and Wright, 5 proving that the smoking of cigarets will produce in the great majority of normal individuals, under certain conditions, a marked change in the surface temperature of the extremities. This can be measured at the tips of the fingers and toes. We noted that in many instances slowing and even stoppage of the blood flow occurred in

On the completion of hostilities with Japan it was inevitable that a large number of allied prisoners of war would be released from Japanese prison camps. Approximately one third of these were American. The period of captivity had ranged from three and one-half years to a few days. The conditions under which most of them had lived were those of starvation, filth and lack of suitable clothing, with periods of definite torture. Thousands died as a result of these hardships. It was believed that a careful health survey of those who survived might be of value in helping to determine the best future care for them, the possibility of the prevention of the spread of communicable conditions in their families and communities, and a better understanding of the changes which take place in man after exposure to such living conditions. To achieve these objectives a board was established by the

The state of medical education, as it exists in Germany and Austria today, may appear to have only a remote relation to the health of other portions of the world, and in particular to the problems of medical care in the United States. A moderate degree of reflection, however, will clearly demonstrate that the health of any large nation in the center of the continent reflects quickly on the health of all surrounding countries. Furthermore, those who have been familiar with the problems of medical licensure of foreign physicians during the past two decades will anticipate that this experience will be repeated as soon as it is possible for physicians of Germany and Austria to migrate to the United States. Inevitably, pressure will be brought to bear on the various licensure bodies to pass on the qualifications of the graduates of the German and Austrian medical schools, in order that