Khalil G. Wakim

Separation of 2 Glutamic-Oxalacetic Transaminases by Paper Electrophoresis.

Summary By use of paper electrophoresis of crude extracts of heart and liver, 2 fractions with GOT activity were obtained, one of which migrated toward the anode and showed the known characteristics of serum GOT, while the other migrated toward the cathode and exhibited different affinities for both α-ketoglutarate and L-aspartate.

The Effect of Local Application of Glyceryl Trinitrate (Nitroglycerine) on Raynaud's Disease and Raynaud's Phenomenon Studies on Blood Flow and Clinical Manifestations

The authors investigated the effect of repeated inunction with 2 per cent glyceryl trinitrate in lanolin on the blood flow and skin temperature of the extremities in 14 cases of Raynauds disease and in 8 cases in which Raynauds phenomenon was associated with such vascular diseases as acrosclerosis (3 cases), chronic occlusive disease of the arteries (3 cases), occupational disease of the arteries (1 case) and livedo reticularis (1 case). The inunction almost invariably caused an increase in the blood flow and in the skin temperature of the digits in the 14 cases of Raynauds disease.

Variations in the peripheral circulation during pregnancy.

Abstract 1. A large series of determinations made with three different methods of evaluating peripheral blood flow demonstrate a progressive increase in the peripheral circulation during the development of normal pregnancy. 2. A definite mechanical effect of the enlarging gravid uterus on blood flow to the lower extremities was demonstrated coincidentally with the fixation of the fetal head deep in the maternal pelvis, and during gross fetal movements. 3. Within 6 to 10 weeks following delivery values observed in the peripheral circulation had returned to prepregnancy levels.

Role of tryptophan metabolites in the hypoglycemia associated with neoplasia

Three patients who had hypoglycemia associated with neoplasia were studied. In one, total tryptophan and protein‐free metabolites of tryptophan in blood and tryptophan metabolites in urine were increased during hypoglycemia. In another, total tryptophan and protein‐free tryptophan metabolites in serum were increased markedly and tryptophan metabolites in urine were increased mostly during hypoglycemia; during normoglycemia, however, concentration of both total tryptophan and protein‐free tryptophan metabolites in serum and of protein‐free tryptophan metabolites in urine was mostly normal. In the third, during normoglycemia, concentrations of total tryptophan and protein‐free tryptophan metabolites in serum and of protein‐free tryptophan metabolites in urine were normal or nearly so. Thus, patients with hypoglycemia associated with neoplasia seemingly have increased concentrations of tryptophan and tryptophan metabolites in serum and urine during hypoglycemic periods. Intraperitoneal administration of indole‐3‐propionic acid, indole‐3‐butyric acid, and indole‐3‐aretic acid caused profound hypoglycemia in normal and alloxandiabetic mice while L‐tryptophan and kynurenic acid had no effect.

Inhibition of Binding of Tritiated Digoxin to Myocardium by Sodium Depletion in Dogs

Ten intact dogs were subjected to hemodialysis against a solution of low-sodium content to determine the influence of sodium depletion on myocardial binding of digoxin-3H. Serial determinations of serum sodium, potassium, chloride, bicarbonate, pH, and osmolality, of cardiac output, and of cardiac rhythm were obtained in these and in 10 control dogs dialyzed against the standard solution. A dose of digoxin-3H (0.05 mg/kg) was given intravenously after start of the dialysis and the animals were killed 1 hour afterward for measurement of myocardial radioactivity, potassium, and sodium. Significant depletion of serum sodium and chloride and myocardial sodium (P < 0.001) occurred in all animals dialyzed against the low-sodium solution. No significant changes occurred in other serum electrolytes or pH; osmolality was maintained constant by a slow intravenous drip of 25% urea or mannitol. Myocardial radioactivity was reduced in sodium-depleted animals by 50% (P < 0.001). The Na-K ratio was 0.40 in the myocardium of control animals and 0.26 in sodium-depleted animals. It was concluded that depletion of body sodium inhibits binding of digitalis glycosides to the myocardium during the first hour after injection of the dose.

A hypoglycemic factor in leukemic tumors.

Summary A fall in blood sugar was observed in AKR mice inoculated with leukemic tumor BW5147. Marked amelioration of diabetes resulted from inoculation of alloxanized AKR mice with lymphatic leukemic tumor. Growth of this tumor was studied in normal and diabetic mice. Rate of tumor growth and blood sugar values were correlated. Increase in mass of tumor alone did not seem to explain hypoglycemia in these mice. Consequently, 3 extracts of tumor were made and tested for presence of a hypoglycemic factor. Blood sugar values of diabetic mice were determined before and after injection of tumor extracts. A saline extract did not show a hypoglycemic effect, nor did an extract made by insulin-extraction procedure. An acetone extract, however, exhibited moderate hypoglycemic activity. Time-response curves demonstrated that acetone-extractable material derived from 1 g of fresh tumor produced a fall in blood sugar of 7% at 15 minutes, 30% at 30 minutes, 25% at 1 hour, and 7% at 2 hours.

Presence of two glutamic-oxalacetic transaminases in serum of dogs following acute injury of the liver.

Summary Serums of dogs poisoned with carbon tetrachloride exhibited high activities of GOT I and GOT II with maxima 48 hours after administration of the toxic agent. At no time, however, did GOT II contribute to total activity more than 16%. In control serums the presence of GOT II could not be established with certainty. Disappearance rates of intravenously administered purified preparations of transaminase also were studied in dogs. Activity of GOT II decreased very much faster than that of GOT I. This difference may explain the uneven distribution of the 2 serum transaminases in carbon tetrachloride poisoning.

Effect of Anticoagulants on Experimental Cerebral Infarction: Clinical Implications

Cerebral infarction is attended by extravasation of blood in varying degrees. The present study was undertaken to learn whether anticoagulant therapy increases the extravasation and thereby diminishes or negates possibly favorable therapeutic effects. A series of experiments on dogs is described and the clinical implications are discussed.

Tryptophan metabolites in hypoglycemia associated with neoplasia

Studies on tryptophan metabolites in the blood and urine of 5 additional patients having symptoms of hypoglycemia associated with neoplasia are reported. Three patients having islet cell tumors and hypoglycemia had normal levels of tryptophan metabolites in the blood and urine during hypoglycemia. A patient with metastatic carcinoma of the breast and a patient with metastatic adrenal carcinoma also had normal values for tryptophan metabolites in the blood and urine during hypoglycemia. These patients are compared with 2 previously reported patients who had extrapancreatic neoplasms, hypoglycemia and high levels of tryptophan metabolites in the blood and urine. The findings suggest that, when a patient has high levels of tryptophan metabolites in the blood and urine during hypoglycemia, a diligent search for extrapancreatic neoplasm should be undertaken. When tryptophan metabolites in the blood and urine are normal during hypoglycemia, a careful search for an islet cell neoplasm is indicated.

Immune mechanisms in chronic pancreatic disease

SUMMARYThe presence of precipitins to pancreatic antigens was investigated by gel diffusion in two experimental conditions in dogs: pancreatic-duct ligation, and ethionine-induced pancreatitis. Precipitins to the pancreas were not demonstrable after pancreatic-duct ligation, but were demonstrable in other dogs, after small doses of ethionine had been administered for a short time, and in the absence of clinical or other laboratory evidence of pancreatic damage.Histologic study of the pancreases of dogs that were sacrificed after ethionine administration showed disruption of acini and focal inflammation. The pancreas from a dog that was kept alive for 10 weeks following ethionine administration was found to be histologically normal-even though circulating precipitins to its own pancreas had been demonstrated in this animal.The administration of dog-pancreas antisera to normal dogs did not produce any appreciable damage to their pancreases.Our data suggest that, in dogs, certain forms of pancreatic damage may result in the production of circulating precipitating antibodies. Their significance in the production or perpetuation of pancreatic disease is unknown, but it is possible that they have no pathogenetic significance.