Irwin Singer

Superiority of demeclocycline over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone.

We evaluated demeclocycline and lithium therapy in 10 patients with the syndrome of inappropriate secretion of antidiuretic hormone. Despite severe water restriction, all patients had hyponatremia (mean +/- S.E.M. serum sodium of 122 +/- 1.1 meq per liter) and elevated urine osmolality (744 +/- 59 mOsm per kilogram) before treatment. Demeclocycline (600 to 1200 mg daily) restored serum sodium concentration to 139 +/- 1.1 meq per liter within five to 14 days, permitting unrestricted water intake in all patients. In three patients given lithium carbonate (900 mg daily) the serum sodium concentration, urine osmolality and urine volume were unchanged; since two patients had adverse central-nervous-system symptoms during lithium therapy, further study of this agent was abandoned. A patient with an unusual 22-year history of the syndrome was unresponsive to lithium, whereas long-term treatment with demeclocyline was markedly effective. Demeclocycline is superior to lithium in the treatment of the syndrome and may obviate the need for severe water restriction.

Acute Hyperkalemia Induced by Hyperglycemia: Hormonal Mechanisms

Two insulin-requiring diabetics with isolated hyporeninemic hypoaldosteronism cpontaneously developed hyperkalemia that was aggravated whenever blood glucose concentration rose. Acute glucose infusions raised the serum potassium concentration in these patients with combined insulin and aldosterone deficiency but lowered, or did not change, the serum potassium concentration in normal subjects and in patients with either aldosterone or insulin deficiency alone. The paradoxical hyperkalemic response to glucose in patients with combined hormonal deficiency was blunted by prior administration of desoxycorticosterone acetate and abolished by prior administration of insulin. Our studies emphasize the crucial roles played by insulin and aldosterone in regulating the serum potassium concentration in man, and the need to avoid hyperglycemia in patients with combined insulin and aldosterone deficiency.

Guidelines for Drug Therapy in Renal Failure

Five tables are presented that provide guidelines for drug usage in patients with renal insufficiency. The data are derived from the current medical literature. If specific information about a drug is unavailable, emphasis is given to normal pharmacokinetic variables in arriving at recommendations for therapy. Nephrotoxicity of adverse effects in patients with renal disease are noted and adjustments for dialysis suggested.

Demeclocycline Treatment in the Syndrome of Inappropriate Antidiuretic Hormone Secretion

We have studied the effects of demeclocycline on the water metabolism of a patient with the syndrome of inappropriate antidiuretic hormone (ADH) secretion who presented with a serum sodium concentration of 110 meq/litre. Free water clearance was studied before, during, and after treatment with demeclocycline. This study shows that demeclocycline (900 mg/day) can at least partially inhibit the action of ADH in the setting of tumor-induced ADH secretion, with the production of a reversible, partial nephrogenic diabetes insipidus, and with few or no side effects. Demeclocycline may be useful in the treatment of chronic inappropriate ADH secretion.

Profound Hyperkalemia Without Electrocardiographic Manifestations

Although the electrocardiogram (ECG) is not considered a reliable indicator of mild to moderate hyperkalemia, profound elevations of serum potassium concentration generally produce classic ECG manifestations. We report two cases of severe hyperkalemia (greater than 9.0 mEq/L) in which the ECGs did not reveal the expected manifestations of hyperkalemia. Thus, even with profound serum potassium elevations, the ECG cannot reliably be used to exclude the presence of hyperkalemia or to monitor therapy designed to lower the serum potassium concentration.

Drug Therapy in Renal Failure: Dosing Guidelines for Adults: Part I: Antimicrobial Agents, Analgesics

Data are presented in tabular form that provide guidelines for drug use in adult patients with renal insufficiency. The data are derived from the current medical literature. If specific information about a drug is unavailable or conflicting, emphasis is given to normal pharmacokinetic variables in arriving at recommendations for therapy. Nephrotoxicity or adverse effects in patients with renal disease are noted and adjustments for dialysis suggested.

Aldosterone-Induced Protein in Toad Urinary Bladder

Simultaneous electrophysiological and biochemical experiments demonstrated a specific aldosterone-induced protein in paired urinary hemibladders isolated from the toad Bufo marinus. Whenever aldosterone stinlmulated short-circuit current, aldosterone specifically increased [35S] methionine incorporation into a low-molecular-weight protein (about 12,000). Comparative studies with dexamethasone and insulin and inhibitory studies with spironolactone and actinomycin D suggest mineralocorticoid specificity.

Drug Therapy in Renal Failure: Dosing Guidelines for Adults: Part II: Sedatives, Hypnotics, and Tranquilizers; Cardiovascular, Antihypertensive, and Diuretic Agents; Miscellaneous Agents

Data providing guidelines for drug use in adult patients with renal insufficiency are presented in tabular form with supporting references. The data are derived from the current medical literature. If specific information about a drug is unavailable or conflicting, emphasis is given to normal pharmacokinetic variables in arriving at recommendations for therapy. Nephrotoxicity or adverse effects in patients with renal disease are noted and adjustments for dialysis suggested.

Hypouricemia in Hodgkin's disease.

Abstract Two patients with advanced Hodgkins disease had persistent hypouricemia. Renal clearance studies showed elevated uric acid clearances of 35 and 23 ml/min, respectively. Only minimal abnor...

Effect of insulin on the phosphorylation of adipose tissue protein

Abstract Although insulin has profound metabolic effects, only some of these may be explained by modulation of adenosine 3′:5′-cyclic monophosphate (cyclic AMP) levels. Therefore, the effects of insulin on fat cell protein metabolism were studied under conditions which are not associated with changes in cyclic AMP levels. Both rat epididymal fat pad and isolated fat cells were used to study insulin-induced [ 32 P]orthophosphate or [ 35 S]methionine incorporation into sodium dodecyl sulfate-soluble proteins and/or polypeptides isolated by acrylamide slab gel electrophoresis and high resolution autoradiography. Insulin specifically increased the incorporation of [ 32 P]orthophosphate into a high molecular weight protein (about 140 000 mol.wt). This phosphorylation occurred: (1) in both fat pads and isolated fat cells; (2) at physiological insulin concentrations (40 μunits/ml); (3) within 15 min after insulin addition; (4) in the absence of glucose; and (5) was partially antagonized by epinephrine (10 −5 M). Thus, physiological insulin concentrations specifically induced the in vitro phosphorylation of a high molecular weight protein, in a manner consistent with the physiological action of insulin in vivo, and under conditions not associated with changes in cyclic AMP levels.