Marshal P. Fichman

Diuretic-Induced Hyponatremia

Abstract Severe hyponatremia (serum Na, 91 to 120 mEq/liter) secondary to the use of diuretics was observed in 25 nonedematous patients with clinically normal hydration and creatinine clearances; i...

Role of prostaglandins in the pathogenesis of Bartter's syndrome

Increased renal prostaglandins activated by beta-catecholamines could produce renal tubular sodium wasting and angiotensin pressor resistance observed in Bartters syndrome. We therefore measured plasma renin activity (PRA), aldosterone and prostaglandin A (PGA) by radioimmunoassay, and body composition by isotope dilution prior to and following beta-adrenergic blockade with propranolol (200 mg/day for 4 days) and prostaglandin synthesis inhibition by indomethacin (200 mg/day for 4 days) in a patient with Bartters syndrome on a 250 meq sodium diet. After the administration of propranolol, body weight increased 3 kg, daily urine sodium decreased within 24 hours from 230 to 64 meq, and urine potassium from 102 to 45 meq, but PRA and the aldosterone level remained elevated. With the administration of indomethacin, body weight increased 5 kg, daily urinary sodium decreased within 24 hours to 11meq and urine potassium to 16 meq, PRA (normal less than 3 ng/100 ml/hour) decreased from 55 to 4.3 ng/ml/hour, plasma aldosterone (normal less than 8 ng/100 ml) from 74.1 to 3.6 ng/100 ml, and whole blood PGA (normal 546 +/- 307 pg/ml) decreased from 1,390 and 945 to 86 pg/ml. After the administration of propranolol or indomethacin, exchangeable sodium, total body water, extracellular volume and plasma volume all increased from less than to greater than predicted, and pressor resistance to angiotensin was normalized. These results suggest that Bartters syndrome results from beta adrenergic and prostaglandin-mediated proximal tubular rejection of sodium leading to increased distal sodium-potassium exchange.

Lupus in the 1980s: III. Influence of clinical variables, biopsy,and treatment on the outcome in 150 patients with lupus nephritis seen at a single center

Of 500 patients with systemic lupus erythematosus observed at our center, 150 fulfilled criteria for lupus nephritis. Of these 150 patients, 91% were female, and 67% were white. The mean age of onset was 26.2 years, and the mean follow-up duration was 11.7 years. Biopsies (n = 142) performed on 107 patients showed the following World Health Organization (WHO) class distribution: class I, n = 1; class II, n = 13; class III, n = 19; class IV, n = 69; class V, n = 17; class VI, n = 8; and class not determinable, n = 15. Ninety-five patients were nephrotic. Therapeutic intervention courses given to all patients (n = 356) included parenteral (IV) cyclophosphamide (n = 58), high-dose oral steroids (n = 126), pulse steroids (n = 49), apheresis (n = 39), azathioprine (n = 43), oral cyclophosphamide (n = 5), nitrogen mustard (n = 27), and chlorambucil (n = 6). In addition to examining the course of disease for various subsets, various predictors for fatality and end-stage renal disease (ESRD) were analyzed. Descriptive data for the short-term response to five therapies are provided for the complete patient sample, proliferative disease, and nephrotic syndrome. Twenty patients died, primarily from cardiovascular complications and sepsis, with 97% and 92% 5- and 10-year survival rates, respectively. Twenty-nine were dialyzed, and 11 were transplanted. Risk of ESRD by WHO class at 5 years was as follows: class III, 0%; IV, 9%; V, 16% (P = .04 for class V v other patterns).(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary cyclic AMP analyzed as a function of the serum calcium and parathyroid hormone in the idfferential diagnosis of hypercalcemia.

Urinary cyclic AMP (UcAMP) appropriate for the serum calcium concentration was determined in normal subjects during the base-line state and during alteration in their serum calcium concentrations by saline and calcium infusions. This was compared to the UcAMP in 76 patients with hypercalcemia and 5 patients with hypocalcemia. In 54 of 56 patients with primary hyperparathyroidism, the UcAMP was inappropriately high for their serum calcium concentration, the 2 exceptions having renal failure. In four patients with vitamin D intoxication, sarcoidosis, milkalkali syndrome, and thiazide-induced hypercalcemia and in five patients with hypocalcemia due to hypoparathyroidism, the UcAMP was appropriately low for their serum calcium concentration. In 16 patients with nonparathyroid neoplasms, 10 had UcAMP levels that were inappropriately high suggesting ectopic parathyroid hormone (PTH)-mediated hypercalcemia and 6 had UcAMP levels that were appropriately low suggesting that their hypercalcemia was due to osteolytic factors other than PTH. Correlations between UcAMP, serum calcium concentration, and carboxyl-terminal immunoreactive PTH suggest that random UcAMP is a sensitive accurate reflection of circulating biologically active PTH. If there is adequate renal function (serum creatinine concentration less than 2.0 mg/dl), a random UcAMP expressed as mumol/g creatinine and analyzed as a function of the serum calcium concentration completely separates patients with PTH and non-PTH-mediated hypercalcemia.

Chlorpropamide and tolbutamide inhibition of adenosine 3′5′ cyclic monophosphate phosphodiesterase☆

Abstract These sulfonylurea agents inhibit the cyclic AMP phosphodiesterase, and thereby could increase the steady state level of cyclic AMP in various tissues, depending upon the tissue concentrations achieved after oral or parental administration.

The Role of Adrenocorticoids in the Inappropriate Antidiuretic Hormone Syndrome

Abstract Twenty patients with all of the characteristics of the inappropriate antidiuretic hormone (ADH) syndrome were observed at the Los Angeles County General Hospital in the past 2 years. The v...

Regulation of urinary prostaglandins in Bartter's syndrome

Abstract Enhanced prostaglandin production, possibly stimulated by hypokalemia, may mediate the manifestations of Bartters syndrome. To investigate the cause of increased urinary prostaglandin excretion, we measured urinary immunoreactive prostaglandin E (iPGE) during the oral administration of potassium and the parenteral administration of magnesium, and during water restriction and oral water loading in two subjects with Bartters syndrome. In one patient (Case 1), iPGE was 0.91 μg/day (normal 0.50 ± 0.20 μg/day, SD). Following the administration of indomethacin, 200 mg/day, iPGE, plasma renin activity (PRA), plasma aldosterone and angiotensin pressor sensitivity returned to normal but serum potassium did not. The oral administration of potassium citrate, acetate, bicarbonate, (Potassium Triplex), 240 meq/day for four days, increased iPGE to 2:3 μg/day and PRA from 47 to 73 ng/ml/hour (normal 1 to 3 ng/ml/hour). In the second patient (Case 2), iPGE was 1.4 μg/day. Therapy with ibuprofen, 1,600 mg/day, and indomethacin, 200 mg/day, again resulted in the return of iPGE, PRA, plasma aldosterone and angiotensin pressor sensitivity to normal, but serum potassium increased only transiently from 2.1 to 3.1 meq/liter. The oral administration of potassium chloride, 240 meq/day for four days, increased potassium to 3.0 meq/liter and increased iPGE to 8.0 μg/day. The administration of potassium triplex, 240 meq/day for four more days, further increased potassium to 3.4 meq/liter and iPGE to 9.3 μg/day, and PRA increased from 7.1 to 13.8 ng/ml/hour. This patient (Case 2) was hypomagnesemic (1.0 meq/liter, normal 1.5 to 2.4 meq/liter), and the intravenous administration of magnesium transiently increased iPGE by 15-fold. Following water restriction iPGE returned to normal (0.35 μg/day), and water loading increased iPGE to 3.0 μg/day, but neither maneuver altered PRA, aldosterone or serum electrolytes. The findings that potassium administration failed to reduce iPGE excretion and that water restriction renormalized iPGE excretion suggest that hypokalemia is not the primary stimulus to prostaglandin excretion.