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We have entered into a new era of medical achievement with the development of successful transplantation of human organs. The transplantation of the heart has aroused the greatest scientific interest and at the same time created serious new problems of an ethical and legal nature. It has been necessary to develop new criteria to determine the "moment of death" of the donor in order to ensure continued life for the recipient. The decision of the moment of death should be made by a small team of skilled physicians interested in furthering this important development, but not as emotionally involved as are the surgeons awaiting the chance to prolong their patient's life with a new heart. Available and suitable hearts will probably always be in very short supply, and the selection of recipients will therefore become critical if the procedure proves to be widely acceptable.New laws will be essential before this process can be adopted in many states and countries. The cost in terms of total resources is so large that careful evaluation of the long-term results must be undertaken after a reasonable number of patients have been operated on and observed, perhaps at the end of the second year following the first procedure. Since the cost of each operation of this type approximates that of the education of several young physicians who could care for thousands of patients during their life span, a good hard look at the potential benefits and ultimate values is in order. At this point in time it is extremely important that this type of surgery be encouraged but limited to those prepared to undertake it with maximum skill and minimal risk. At present it must be recognized as a great experiment rather than a therapeutic triumph for general application.

Conclusions1. Cevitamic acid, properly buffered, may be administered intramuscularly without discomfort or damage to tissue. 2. Studies of the urinary excretion and the blood content of vitamin C following the administration of cevitamic acid intramuscularly demonstrated that it is used by the body when administered by this route. 3. The height of increase in the blood level following the intramuscular injection of cevitamic acid is reached more slowly and is maintained for a longer time than after intravenous injections. 4. In cases of vitamin C deficiency, where cevitamic acid is improperly absorbed through the gastro-intestinal tract, or where the intravenous mode of administration is not feasible, the intramuscular route may be used.

An evaluation of the comparative actions of Tromexan and dicumarol is herein reported. Five hundred fourteen patients were studied; a total experience of 6,642 days of Tromexan therapy and 5,006 days of dicumarol therapy were reviewed and analyzed. Previous reports of the more rapid initial prolongation of the prothrombin times and more rapid return to normal following cessation of therapy with Tromexan were confirmed. During adequate therapy the protection against thromboembolism was approximately equal for the two drugs. In other respects and with minor variations Tromexan and dicumarol were found to be quite comparable. The general advantages of anticoagulant therapy in the prevention of deaths and thromboembolic complications in myocardial infarction were comfirmed.

1. The factors influencing blood conductivity have been noted. 2. An accurate apparatus has been designed to measure blood and plasma conductivity. 3. A new cell has been designed to measure conductivity of blood. 4. Through studies on normal blood before and after dilution, a correlation has been shown to exist between blood conductivity and the red cell count. 5. The form factor for normal human red cells has been determined to be 1.393. 6. A mathematical equation is presented relating red cell count with conductivity for normal blood. See PDF for Equation 7. The factor C on the basis of 33 determinations has been calculated to be 10.80.

SummaryCerebral vascular diseases are of major importance but unfortunately their study has been greatly neglected until recent years.There are serious gaps in our basic knowledge regarding their pathogenesis and therapy. The differential diagnoses of thrombosis, embolism, hemorrhage and tumor have been outlined. Intermittent neurological signs due to cerebral vascular diseases have been discussed. The distinctions between intermittent and permanent occlusion of the basilar artery, carotid artery and cerebral artery have been elaborated.Long term anticoagulant therapy is of value in the prevention of recurrent thromboses and emboli wherever they may occur in the carotid, basilar or cerebral arterial tree.Anticoagulants are indicated as a prophylactic measure before mitral com-misurotomy when the patient has had previous emboli or when his heart is in atrial fibrillation. They should also be continued after this surgery. The question whether the patient should be carried through the operation at therapeutic levels of anticoagulant therapy is at present under study in several clinics, but the evidence suggests that this is feasible and improves the chances of avoiding emboli.It appears logical to use anticoagulants in the treatment of acute episodes of thrombosis and embolism but this is under further study at present.Other forms of therapy including the stellate sympathetic ganglion block, and the inhalation of CO2 have been evaluated. Thus far the evidence suggests that while the inhalation of CO2 may be helpful theoretically the others are of doubtful value.This is a challenging field which should attract the attention of many workers during the next several decades.

1.1. A study of the problem of specific hypersensitiveness of the skin to tobacco in 35 typical cases of thromboangiitis obliterans and 35 controls was made. 2.2. The patients with thromboangiitis obliterans did not show a higher evidence of positive skin reactions than the control group. 3.3. The high incidence of positive skin reactions to tobacco tests reported by other investigators and interpreted as allergic reactions is considered due to some of the many nonspecific reactions from chemical irritation. 4.4. Thrombo-angiitis obliterans is not caused by an allergic type of tobacco hypersensitiveness.

The use of heparin and dicumarol has provided important information regarding the effectiveness and the difficulties of anticoagulant therapy. Neither, however, is an ideal anticoagulant; therefore a search for new substances with advantages over them must be continued. Tromexan, which is administered orally, appears to have the advantages of more rapid utilization and more rapid cessation of action than dicumarol, although the mode of action is similar in that it produces a hypoprothrombinemia. It does require accurate prothrombin tests for satisfactory clinical use. It appears to be less prone to producing hemorrhagic complications. Animal and clinical experiences with Tromexan are herewith presented.

DURING THE COURSE of our experiments on the effect of testosterone on the vascular system, it was noted that testosterone propionate caused an increase in the siz,e of the kidneys of normal rats (1). Korenchevsky, Dennison and Kohn-Speyer (2, 3, 4) had reported a decrease in the weight of the kidneys of male rats following castration and an increase in kidney weights following injections of androgenic urine extracts. More recently, Selye (5) had reported kidney enlargement in normal female mice after the injection of large doses of testosterone propionate. While our experiments were in progress, Selye (6) reported increases in the kidney weight of normal male and female rats injected with testosterone propionate, estradiol, desoxycorticosterone acetate and progesterone, and Korenchevsky and Ross (7) described hypertrophy of the kidneys of normal and ovariectomized female and of castrated male rats following the administration of testosterone esters and androsterone; they did not consider the enlargement i...

1. 1. The chemical formula and the method of preparation of a new solution for the study of the circulation time to various points throughout the vascular tree are presented. We have designated it Circulation Time Test Formula No. 87, or C.T.T. No. 87. 2. 2. The technic of administration and of recording results is outlined. 3. 3. Normal figures for the circulation time to the tongue and throat, perineum, right and left hands, and right and left feet are presented. 4. 4. Figures on a small series of patients with the Raynaud's syndrome show no marked deviation from normal except that the time to the feet is prolonged. 5. 5. Figures on a small series of patients with thrombo-angiitis obliterans show a tendency to a more prolonged circulation time than that of normals. 6. 6. Figures on a small series of patients with arteriosclerosis show a tendency to a more prolonged circulation time than that of normals. 7. 7. Figures on a series of patients with hyperthyroidism showed a definite decrease in the circulation time, with this method as with others previously reported. The circulation time is prolonged after thyroidectomy. 8. 8. This paper represents a preliminary study and will be followed by a more detailed paper, covering work now in progress.

The case of a patient with thromboangiitis obliterans who had quadrilateral gangrene of the digits was reported in 1937. His disease became quiescent after cessation of smoking and intravenous typhoid vaccine. During the interim of 27 years, he has abstained from smoking, and there has been no reactivation of his disease. Clinically, there has been a regression of his vascular lesions during this time. He represents the ideal in terms of treatment and response. In 1937, as part of the preliminary examination, he received at least four intra-arterial injections of thorium dioxide sol for visualization studies, and in 1964, this material was visualized as deposited in the liver and spleen. There was, however, no evidence of liver or spleen dysfunction or disease. Our experience with this patient and many others leads us to the conclusion that thromboangiitis obliterans is a distinct disease, although it is sometimes wrongly diagnosed. The reasons for this conclusion and for the confusion of this disease with atherosclerosis obliterans have been discussed.

There is considerable interest and some difference of opinion about the relative clinical usefulness of many oral anticoagulant agents. In this study the more commonly used agents are evaluated with respect to their action on the clotting process as measured by thrombelastography. This test does not necessarily provide an evaluation of all aspects of the clinical action of an anticoagulant.

Studies of tissue temperature have been made by means of fairly accurate instruments since the work of Becquerel and Breschet.1 Interest in recording the temperature of the circulating blood in humans has been secondary to the development of scientifically accurate apparatus which has been devised on thermo-electric principles. Clark2 developed a galvanometer deflection method of measurement. Harris and Marvin,3 and Bradburn and Blalock4 studied changes in the temperature of the venous blood of the hand after immersion in water at various temperatures—by means of direct measurement. Foged5, 6 reported observations on 116 patients concluding that the temperature in the ulnar vein averaged 2.6 lower than the rectal temperature. He noted, in the presence of fever, an increase in this difference and also that the temperature of the surrounding medium affected the temperature of the venous blood. Other of Foged's observations will be discussed in reference to our findings.Our observations made on humans were r...

The case history of a patient suffering from thrombo-angiitis obliterans with acute simultaneous quadrilateral gangrenous lesions is presented. A search of the literature and inquiry among a number of the major vascular clinics in the United States has failed to reveal a record of any preceding example of this disease with quadrilateral simultaneous lesions. An outline of what we consider to be the most satisfactory form of therapy for thrombo-angiitis obliterans is included. After considerable experience we have not been impressed with the results from new forms of mechanical apparatus, despite the broad claims which have been made for them.

Marcumar [3-(1'-phenyl-propyl)-4-hydroxycoumarin] is a new anticoagulant. Marcumar acts more rapidly than Dicumarol, but not quite as rapidly as Tromexan. The action is more prolonged than Dicumarol. As with other anticoagulants, the administration of Marcumar requires conscientious observation and accurate prothrombin complex determinations.

The purpose in the presentation of this problem is to emphasize the need for a universal standardization of the methods used in the measurement of blood pressure. We have made and effort to determine what variations ordinarily occur in the making of blood pressure observations by interns, attending physicians, and postgraduate medical students in a large postgraduate institution; second, to ascertain how this procedure is taught by medical schools; and third, how it is prescribed by other (medical) institutions which are vitally interested in this subject, such as the life insurance companies. No attempt is made to recommend a standardized method of procedure. Throughout the country, the most widely accepted and practiced method of measuring blood pressure is the auscultatory method described by Korotkoff in 1905, with the use of a rubber cuff, attached either to a mercury or aneroid manometer, and a stethoscope. In a critical study of blood pressure readings as recorded in various hospital charts by different attending and house physicians, many discrepancies were found. In fact, there was greater variation than the regular limits of error would allow. This latter finding provided the stimulus for this investigation. It was decided to test the methods employed in taking blood pressure readings by various members of a large general hospital. The New York Post-Graduate Hospital was considered suitable because it is abundantly supplied with physicians from all parts of the world and from many different medical schools. It was decided to make the experiment among three groups: (1) interns, (2) postgraduate students, and (3) attending physicians.

Coronary thrombosis with myocardial infarction is an extremely serious disease to the individual and to the nation. It kills at least 200,000 persons a year and cripples unknown numbers. The modern treatment is herein outlined. Established therapy is reviewed and evaluated. The use and technics for the control of anticoagulant therapy are discussed.

1. There was no outpouring of mucinous, alkaline gastric secretion in 6 rabbits after subcutaneous injections of 2 and 4 mgm. of mecholyl chloride. 2. There is no marked change in the free and total acid of the gastric contents in rabbits after these dosages but because of large amounts of solid gastric residue these figures are not wholly accurate. 3. In 3 cats no free hydrochloric acid was present in the fasting gastric specimen nor did any appear after subcutaneous injections of 2, 4 and 10 mgm. of mecholyl chloride. 4. When proper care is taken to prevent the swallowing of saliva there is no marked change in character in the gastric secretions in human subjects following the subcutaneous injection of 25 mgm. of mecholyl chloride. 5. There is in most instances a slight to marked rise in free and total acidity following such an injection. 6. There is a marked increase in flow of saliva which becomes mucinous and more alkaline. 7. The accidental swallowing of less than one-half of the saliva more than neutralizes the rise in gastric acidity and the purposeful swallowing of the entire amount is suggested as a possible therapeutic measure in cases of hyperacidity.

1.1. During the past decade the indications for anticoagulant therapy have been clarified. They are listed herein. 2.2. In view of the reduction in both death rate and in the incidence of thromboembolic complications following coronary thrombosis with myocardial infarction with the use of anticoagulants in mild and moderately severe cases, the position that their use should be reserved solely for those patients who are severely ill at onset does not appear justified. This because, despite apparent mildness during the first day or two of the disease, the future course is difficult or impossible to predict with certainty and because the first complication may produce death, more serious illness or permanent disability. 3.3. Recent evidence favors the increased use of anticoagulants during more severe periods o congestive heart failure. 4.4. Newer anticoagulants are now rapidly being developed which generally can be classified as acting similarly to heparin or to dicumarol. 5.5. The clinical facts regarding each of the better known anticoagulants, including their advantages and disadvantages, have been outlined. 6.6. More complete experimental studies should be carried out before crystalline trypsin should be released for general clinical use. 7.7. The final decision whether to use anticoagulants or not, and which ones to use in a specific patient, must rest with the physician responsible for his care. 8.8. Among the important factors to be considered in making this decision are: (1) The diagnosis and condition of the patient; (2) the presence of any coincidental problem requiring caution or contraindicating their use; (3) the sound evidence indicating anticoagulant therapy under these particular circumstances; (4) the qualities of the specific anticoagulants under consideration; (5) the availability of accurate prothrombin and coagulation time tests; (6) the availability of vitamin K and K 1 , and transfusions for emergency use; and, perhaps of greatest importance, (7) the conscientiousness, and skill in this particular field, of the physician who is responsible for their use.

To the ten published cases of surreptitious takers of oral anticoagulants, ten are added by this report. These patients were identified at Cornell Medical College or at the Mayo Clinic. They consisted of four men and six women. Five patients were nurses and two others had a medical background: a fraudulent physician attempting to escape military service and the mother of a veterinarian. All the others had a history of thromboembolism or previous anticoagulant treatment. The differential diagnosis of "Dicumarol-eaters" is that of a lengthened prothrombin time. It includes a congenital deficiency of factors I, II, V, VII or X, or acquired deficiencies of one or more of these factors based on a lack of vitamin K or on liver damage. The simple vitamin K deficiency states can be distinguished readily by the effect on the prothrombin time of the parenteral administration of a small dose of a water-soluble analog of menadione. Definitive diagnosis of this malingering syndrome requires identification of the oral anticoagulant in the blood.

The effectiveness of papaverine hydrochloride intravenously as a vasodilator was studied in a series of eighteen subjects, which included thirteen who suffered from thromboangiitis obliterans, three who had arteriosclerosis obliterans, and two normals. Four patients with Raynaud's syndrome were also observed, but are not included in the statistical analysis. Compared with the simple water immersion procedure for securing vasodilatation, papaverine hydrochloride is ineffective and uncertain in action.

(1) We have described an apparatus to measure claudication time. (2) Following one injection of deproteinated pancreatic extract, twenty-three of a series of twenty-seven patients with arteriosclerosis obliterans showed an improvement (prolongation) of their claudication time. This initial response was in most instances temporary. (3) Following ten or more injections of deproteinated pancreatic extract, nineteen patients showed improvement in their claudication time. (4) After a series of ten or more treatments, the claudication time was, in this series, prolonged to an average of more than three times that of the control tests. (5) Physiologic saline failed to produce an increase in claudication time under identical conditions (6) Further studies will be necessary to determine the extent to which improvement may be advanced, and the duration of the favorable effects after cessation of the treatment.

Although research of the past five years has contributed greatly to the knowledge of the diagnosis and treatment of strokes, there is much still to be learned. Atherosclerosis and embolization have been determined the most common causes of strokes; therefore, solution of this problem depends on prevention, reversal and control of these conditions. Anticoagulant therapy has proved effective in preventing recurrent strokes, but its value in acute attacks is less clear. Surgery and constructive rehabilitation are challenging approaches receiving critical study.

SummaryA case has been presented, which has been diagnosed as a familial deficiency of Factor XI (PTA).The patient with Factor XI deficiency has a gross coagulation defect as demonstrated by numerous in vitro tests. However, to date neither the proband, his mother, nor his sister, who share the same deficiency, has shown any evidence of an abnormal bleeding tendency, even when subjected to repeated surgical procedures. These patients have a minor PTA deficiency and are heterozygous for the deficiency, which is transmitted as an autosomal recessive.

There have been conflicting reports as to whether the ingestion of fat increases the tendency for the blood to clot, and hence, by implication, the risk of thromboembolic complications in man. In this study the effect of a single meal containing a large amount of fat was compared with that of a practically purely carbohydrate isocaloric meal. Under carefully controlled conditions the clotting time varied widely under fasting conditions, and after both fat and carbohydrate meals the clotting time became longer, shorter, or remain unchanged. The results were unpredictable and although a slight trend toward shortened clotting times was evidenced after the fat meals, the results did not reach accepted statistical standards of probability.

1. 1. The general reactions produced by large subcutaneous or oral doses of the more active choline compounds can be reproduced by iontophoresis, using the same drugs. In addition, there are certain local manifestations which appear at the site of application. 2. 2. On the basis of our experiments there is no consistent, marked change in the basal metabolic rate resulting from the use of the choline compounds in the dosages indicated. 3. 3. Although it is possible to produce a marked drop in blood pressure by the use of several of these compounds, this is a transient effect. We have not seen a single patient who has maintained a lowered blood pressure from the use of these drugs. 4. 4. Iontophoresis with mecholyl has proved to be a palliative method for the treatment of arthritis. 5. 5. In peripheral vascular disease, where organic occlusion has been the major factor, the choline compounds have not been of marked value. 6. 6. In vascular disease in which spasm is the major factor, the use of the choline compounds, as outlined, has proved helpful. 7. 7. A preliminary report on the successful treatment of long-standing chronic varicose ulcers in presented.

Evidence has been presented that pernio is a vascular disease, affecting the smaller vessels of the skin, causing anoxemia of the supplied tissue, and resulting in necrosis and ulceration. Later, a definite sclerodermic-like change in the skin may occur. It is precipitated by a downward change in temperature, not necessarily freezing, but by mere cooling. This may occur at a temperature which, under ordinary circumstances, would not cause an appreciable change in normal skin, but which causes definite changes in susceptible persons. Characteristically, exacerbations of this condition occur in the fall and winter, and regression in the summer. In long-standing cases, however, complete recovery may not occur in the summer. We believe that this is due to the extensive vascular changes in the tissues. We have been able to demonstrate giant cells in our sections, but we have found no evidence of tuberculosis. We have very carefully checked our patients clinically with this in mind, so that we can make the definite statement that our patients were free from clinical and roentgenologic evidence of active tuberculosis at the time their leg lesions were active. The following tentative criteria are suggested for the diagnosis of pernio. 1. 1. It may occur in both sexes, predominantly in females. 2. 2. It usually commences in adolescence or early adulthood. 3. 3. It is associated with cool or cold weather and may show spontaneous recovery in warm weather. 4. 4. The lesions have a predilection for exposed areas, particularly the lower third of the leg, around the internal malleolus and calf. They may extend down to the dorsum of the foot and toes, and up the legs to below the knees. 5. 5. The clinical course of these lesions may be characterized briefly as (a) the formation of a reddened area which later becomes elevated, hard, and very painful; (b) this becomes violaceous and fluctuating; (c) it opens, producing an ulcer; (d) this oozes, drains, and heals, becoming less painful; (e) a violaceous scar remains; and (f) the following winter ulceration tends to recur in the same area. 6. 6. There is a definite pathologic picture. Most characteristic is, first, an angiitis of the smaller vessels; secondly, necrosis of the fat; and, thirdly, the presence of giant cells. This pathologic picture, while characteristic of all our cases, must not be considered morphologically specific, for a number of other vascular conditions present similar histologic changes. They all represent a chronic irritative process in the subepidermal tissue. Wherther the irritative phenomenon is secondary or primary cannot be definitely stated. Treatment of this condition is not specific, but the best results in our hands have been achieved by triweekly treatments with acetyl-betamethylcholine chloride (mecholyl) by iontophoresis, and by protection of the legs with proper clothing from undue exposure. Living in a warm climate should minimize the occurrence of the lesions. Early recognition of this syndrome, and treatment as suggested, will help to prevent permanent disfigurement and long periods of incapacitation.

Conclusions1. The intravenous test dose method for the determination of Vitamin C saturation in the body by the study of the urinary excretion eliminates the factor of uncertain absorption of the ascorbic acid from the gastro-intestinal tract, but the problem of faulty kidney elimination remains. 2. In order to properly evaluate this factor a study of the blood curve for possible renal retention is essential. 3. A test is outlined which permits a more complete study of Vitamin C saturation. 4. Results illustrating certain types of curves obtained with and without renal retention are presented and interpreted. Thus far retention of Vitamin C has been noted in patients with marked nitrogenous retention only. 5 . All patients with nitrogenous retention do not have Vitamin C retention, but renal retention of Vitamin C may occur. To our knowledge this has not been demonstrated before.