William Jubiz

Thyroid dysfunction in uremia: evidence for thyroid and hypophyseal abnormalities.

Disturbances in thyroid function and a high prevalence of goiter develop in patients on chronic hemodialysis. This study shows that in patients on dialysis, mean serum thyroxine and triiodothyronine levels are lower than normal. Patients with chronic renal failure not on dialysis, have mean serum thyroxine levels similar to normal subjects and low mean serum triiodothyronine levels. However, both serum thyroxine and triiodothyronine concentrations decrease as the renal failure worsens. In addition, both groups of patients with renal failure have a decreased serum thyroxine response to oxogenous thyrotrophin and a diminished serum thyrotrophin response to thyrotrophin-releasing hormone. These data suggest the presence of an intrathyroidal and an hypophyseal defect in uremic patients. Although serum iodide concentrations are elevated, there is no correlation between the level of serum iodide and the degree of renal failure. Therefore, we have no direct evidence that iodide excess is responsible for the abnormalities observed.

Decreased leukotriene B4 synthesis by polymorphonuclear leukocytes from male patients with diabetes mellitus

Leukotriene B4 (LTB4) synthesis and release by polymorphonuclear leukocytes (PMNL) from 17 male patients with type I diabetes mellitus was decreased (407.1 +/- 55.6 vs 709.4 +/- 62.7 ng/30 X 10(6) cells/10 min, mean +/- SE, p less than 0.001) as compared with 17 normal subjects matched for sex and age. There was an inverse correlation (r = -0.50, p less than 0.04) between LTB4 synthesis and plasma glucose concentration in the diabetic patients. The same correlation (r = -0.71, p less than 0.01) was observed in three diabetic patients studied weekly for one month. Because LTB4 is a potent chemoattractant and stimulates PMNL function, the defect in its synthesis may contribute to the predisposition to infections in the diabetic patient.

Potassium-renin-aldosterone relationships during the first year of life

In order to gain insight into factors controlling aldosterone secretion during the first year of life, we studied the relationships between PRA, serum potassium, sodium, and serum aldosterone levels. While we found a dissociation during the early neonatal period, there was a high degree of correlation between serum aldosteron, PRA, and serum potassium by 3 to 12 months of age. This suggests that aldosterone secretion in the 3- to 12-month-old child, as in adults, is regulated by the circulating levels of potassium and angiotensin II.

Circadian variation of prostaglandin E (PGE) production in human gastric juice

Prostaglandin E output in human gastric juice has been determined by radioimmunoassay and correlated with gastric acid secretion in 10 normal subjects and 10 patients with duodenal ulcer. PGE and acid outputs were higher in patients with peptic ulcer. Although not statistically significant these changes were probably secondary to changes in gastric juice volume. A circadian rhythm of gastric PGE production was observed in normal subjects with high output at midday, a spike at midnight, and low output in the early morning, in phase relationship to the circadian rhythm of gastric acid secretion. Disruption of PGE and acid rhythms was found in ulcer patients.Our study does not support the concept that prostaglandin deficiency may be an etiological factor in peptic ulcer disease. Nonetheless, a heretofore unrecognized disruption in gastric PGE rhythm may prove to be of physiologic significance.

Alterations of Glucocorticoid Actions by Other Drugs and Disease States

SummaryGlucocorticoids are used in physiological and pharmacological amounts in the management of a variety of clinical conditions. Concomitant utilisation of other drugs or the presence of some diseases may affect the physiological action of the steroid in the tissues. Phenytoin, phenobarbitone, ephedrine and rifampicin accelerate the metabolism of glucocorticoids thereby decreasing their biological activity. A similar phenomenon occurs in patients with hyperthyroidism. In contrast, glucocorticoid action is enhanced in hypothyroid patients and in those with hepatic damage as the result of a defect in the clearance of the hormone from blood. In turn, glucocorticoids antagonise the effects of Cholinesterase inhibitors and ganglion blocking agents. The above mentioned effects should be kept in mind whenever glucocorticoids are utilised in the diagnosis and management of endocrine or non-endocrine conditions.

The relationship between unbound and total cortisol: Its usefulness in detecting CBG abnormalities

The relationship between unbound and total cortisol has been studied in patients with a variety of clinical conditions. We report on a simple, rapid and reliable method for evaluating the percentage unbound cortisol in serum or plasma which can be used in conjunction with total plasma cortisol to obtain a more complete understanding of the patients adrenal status. Comparison of a patients percentage unbound and total cortisol with a nomogram showing the normal relationship between percentage unbound and total cortisol indicates the patients concentration of cortisol binding globulin. The concentration of unbound cortisol, the biologically active moiety, is the product of the percentage unbound and total cortisol concentration. The following values for the unbound cortisol concentration (microgram/dl) were obtained (mean +/- S.D.). Twenty-four normal subjects, 8--10 a.m., 1.2 +/- 0.4; 14 women receiving an oral contraceptive, 1.4 +/- 0.5; 6 patients with adrenal insufficiency, 0.2 +/- 0.1; 9 hyperthyroid patients, 1.7 +/- 0.8; 5 acute ill patients, 3.8 +/- 2.4; and a patient with Cushings syndrome, 6.1. In normal subjects the values decreased at 4 p.m. (0.4 +/- 0.1) and after dexamethasone administration (0.1 +/- 0.1), and increased following the intravenous injection of adrenocorticotropic hormone (3.6 +/- 0.7). In pregnant women the unbound cortisol increased as the pregnancy progressed, first trimester: 1.2 +/- 0.3, second trimester: 1.6 +/- 0.2, third trimester: 2.4 +/- 0.5.

Enhanced Erythropoietin and Prostaglandin E Production in the Dog following Renal Artery Constriction

Summary Renal artery constriction (RAC) to 30% of normal flow for 12 hr in the unilaterally nephrectomized dog produced a marked increase in both erythropoi-etin titers and prostaglandin E (PGE) levels in the blood. In dogs pretreated prior to RAC with indomethacin, a potent inhibitor of prostaglandin synthetase, there was no significant increase in either PGE or eryth-ropoietin levels as compared to zero-time control values. These data suggested an involvement of renal PGE in the generation of erythropoietin following RAC. The authors gratefully acknowledge the excellent technical assistance of Mr. Jesse Brookins, Ms. Patricia Dargon, Mr. Rene Stiaes, and Mrs. Jacqueline Frailey.

A source of error in equilibrium dialysis

Equilibrium dialysis is often used to study the binding of steroids to proteins. With this technique it is customary to determine the percent bound and unbound steroid in the sample, the affinity constant for the steroid-protein binding reaction, and the concentration of binding sites on the protein. Investigators have used many different ratios of dialysis buffer to sample volumes in their experiments assuming that the equilibrium in the post-dialysis sample was the same as existed before dialysis. Chemical equilibrium expressions for the system before and after dialysis indicate that during dialysis the concentration of steroid in the sample decreases resulting in a new equilibrium in which the percent bound and unbound are different from the original sample. The magnitude of the difference between the pre- and post-dialysis systems is proportional to the ratio of dialysis buffer to sample volumes. Accurate values for the affinity constant and binding site can be obtained only if this change in the equilibrium is considered.

Prostaglandin e generation during storage of plasma samples

Abstract Generation of prostaglandin E (PGE) was found during storage of plasma at 4C for three weeks and in plasma specimens that were kept frozen and then thawed before being assayed. PGE production was greater in the refrigerated than in the frozen samples. The increment in PGE correlated with the number of platelets present in the plasma. Sodium salicylate decreased the amount of PGE generated in the refrigerated but not in the frozen plasma samples. Under the same experimental conditions, PGE generation was not observed in serum samples. Awareness of this phenomenon is important whenever stored plasma samples are used for prostaglandin determinations.

Plasma prostaglandin E concentrations from birth through childhood

The prostaglandins are synthesized in a variety of tissues and participate in an extensive number of physiologic processes. As prostaglandin concentrations have not been reported in infants and children, we measured PGE levels from birth through childhood. PGE levels in cord blood were significantly higher than those in adults. By 48 to 72 hours of age, however, they had fallen to levels that were significantly lower than those in adults. Although PGE concentrations increased with age, they remained significantly lower than did adult levels. These low levels may be related to some of the functional pecularities of the immature kidney.