Christine Waterhouse

Reduced Red Cell Glycolysis, 2,3-Diphosphoglycerate and Adenosine Triphosphate Concentration, and Increased Hemoglobin-Oxygen Affinity Caused by Hypophosphatemia

Abstract A marked reduction in red cell glucose utilization, lactate production, and 2,3-diphosphoglycerate and adenosine triphosphate concentration occurred in a patient with intractable diarrhea ...

Lactate metabolism in patients with cancer

Tracer studies of pyruvate and lactate recycling to glucose have been carried out in patients with metastatic carcinoma. The experimental approach of determining the time course radioactivity curve of blood glucose after single injections of pyruvate‐3‐14C and glucose‐6‐14C on separate days allowed definition of the transfer function of lactate and pyruvate to blood glucose. Nine such experiments were done in eight patients. In six of the eight subjects, an increased fraction of the pyruvate and lactate turnover was recycled to glucose (.24 to.54 as compared to an average of.17 in normal subjects). The two subjects with normal Cori cycle activity, though debilitated from the localization site of their metastatic tumors, did not have widespread rapidly growing neoplasms. The subjects with increased Cori cycle activity had a high total turnover of glucose, but normal or only slightly elevated new glucose production rates. Thus, we postulate abnormally high lactate production in these subjects, perhaps related to the metabolism of the cancer itself. One subject studied during the presence of lactic acidosis, and again later when the lactate level was less, showed about twice as much recycling after acidosis was alleviated, suggesting inhibition of hepatic glucose production from lactate during acidosis. It is suggested that the potential for lactic acidosis exists in patients with widespread progressive tumor growth.

Metabolic observations during the forced feeding of patients with cancer

Abstract 1.1. Nine patients with growing malignancies were studied on a metabolism ward while nutritional rehabilitation was attempted by forced feeding. Balances of nitrogen, phosphorus, calcium, potassium, sodium and chloride were conducted before, during and after such treatment and repeated determinations of basal metabolic rate and calculations of caloric expenditures were made. 2.2. Characteristically, large gains in body weight were produced during forced feeding but weight loss was rapid when this was discontinued. An analysis of the weight gain in terms of body compartments revealed that the increase was predominantly due to an accumulation of large quantities of intracellular fluid. 3.3. Although there was initial retention of a significant quantity of nitrogen and phosphorus during forced feeding, there was a tendency for the nitrogen balance to approach equilibrium rapidly, and during the subsequent control periods a negative balance was uniformly observed. This suggests that in these patients a host repletion process could not be sustained. 4.4. Transient clinical benefit occurred in a few of the patients studied, while caloric expenditure determinations, basal metabolic and clinical data indicated that in about half the patients forced feeding had a detrimental effect. 5.5. The significance of the observed changes in nitrogen balance, the basis for the increased caloric expenditure in cancer, and the possible factors responsible for the different responses observed during forced feeding are discussed.

Cushing's syndrome with hypertensive crisis and mixed adrenal cortical adenoma-pheochromocytoma (Corticomedullary adenoma)

Abstract Hypertensive crisis developed unexpectedly during removal of an adrenal tumor in a patient with Cushings syndrome. Preoperative plasma cortisol levels and urinary excretion of 17-hydroxycorticoids, epinephrine and norepinephrine were elevated. Postoperatively, the patient required only adrenal cortical replacement therapy. Histopathologic examination of the tumor disclosed mixed adrenal cortical and medullary cells. States of combined adrenal cortical and medullary dysfunction and their pathophysiologic mechanisms are discussed.

Citrate Excretion in Renal Tubular Acidosis

Excerpt Metabolic and respiratory acidosis has been shown to decrease the urinary citrate excretion in man (1). Conversely, metabolic or respiratory alkalosis will increase this parameter, without ...

HYPERCALCEMIA OF MALIGNANT DISEASE: CASE REPORT AND A PROPOSED MECHANISM OF ETIOLOGY

Excerpt Hypercalcemia, as one of the manifestations of malignant disease, has become a well recognized phenomenon during recent years. In 1953 Woodard1reported that about nine per cent of patients ...

Cori cycle activity in man

12 subjects have been studied after an overnight fast with trace amounts of pyruvate-3-(14)C and glucose-6-(14)C. Blood disappearance curves and incorporation of the pyruvate-3-(14)C label into blood glucose have been determined. By the use of transfer functions which allow processes with many different chemical steps to be examined as a unit, we have determined the per cent of pyruvate and presumably lactate which is regenerated into glucose. 8 of the 12 subjects showed that 7-23 mg/kg per hr are recycled, while 4 subjects fell well outside this range. Correlation of increased activity was not good with any demonstrated metabolic abnormality (diabetes or obesity), and it is suggested from clinical observation of the subjects that anxiety may play a role.

Transfer times across the human body

The radioactivity disappearance curves of glucose-6-14C albumin-I131 after a single injection of tracer into a human subject have been determined in detail, particularly at early time intervals. The curves, expressed as sums of exponentials, have been analyzed as the infinite sum of convolutions of single passage time densities. The resultant transfer time distribution of a single circulatory pass allows examination of all delays in the system no matter how long they take. The structural detail evident by this means and the long mean time of a single pass of glucose (>5 min) supports the thesis that factors other than rapid and uniform diffusion play a role in the extravascular movements of glucose molecules.

Autoimmune Hemolytic Disease and Cryoglobulinemia Associated with Chronic Lymphocytic Leukemia* Hematologic and Metabolic Studies

Abstract 1.1. Hematologic and metabolic studies were made before, during and after administration of ACTH in a case of chronic lymphocytic leukemia complicated by autoimmune hemolytic disease and cryoglobulinemia. 2.2. Reduction in the number of circulating lymphocytes, in the size of the peripheral lymph nodes and in the rate of red cell destruction was sustained for nine months following administration of 1,250 mg. of ACTH over a period of fifteen days. Response following a second series of injections of ACTH was less dramatic but was again well sustained. The possible mode of action of ACTH in this case is briefly discussed, with particular reference to effects on lymphoid tissue and on production or reactivity of autoantibody. 3.3. During ACTH therapy the expected loss of nitrogen, phosphorus and potassium occurred. The quantitative exchange of these substances, however, was believed to have been influenced by the destruction of malignant tissue as well as by the other known metabolic effects of this hormone.

The Genesis of Hyponatremia Associated with Marked Overhydration and Water Intoxication

Prolonged overhydration and hyponatremia have been produced in 10 patients with use of Pitressin Tannate in Oil. Balance studies have shown that in patients who developed moderate hyponatremia, the drop in serum sodium could be explained by water retention. In patients who developed severe water intoxication, the very low levels of serum sodium (100-114 mEq./L.) could not be entirely accounted for by changes in salt and water balance. Certain patients failed to develop severe water intoxication although an equivalent degree of overhydration was achieved. In these subjects, further overhydration was limited by intermittent episodes of low solute diuresis. This diuretic escape from Pitressin effect has been evaluated by measurement of U/P osmolar ratio on 24-hour urine specimens as well as TcH2O during hypertonic mannitol infusion. Defects in both aspects of renal concentration were observed, although they were not necessarily coexistent.