Fred H. Katz

Combined Therapy with Vasodilator Drugs and Beta-Adrenergic Blockade in Hypertension: A Comparative Study of Minoxidil and Hydralazine

The hypotensive efficacies of two vasodilators, hydralazine and minoxidil, were assessed as these drugs were used individually in combination with beta-adrenergic blockade and diuretics in 11 hypertensive patients in whom elevated blood pressure had not been adequately controlled previously by other antihypertensive therapy.Control supine blood pressure fell from 191/128 mm Hg on propranolol and hydrochlorothiazide to 169/108 mm Hg on hydralazine, with a significantly greater reduction to 142/92 mm Hg on minoxidil. Although sodium retention and tachycardia were controlled by the use of concomitant diuretics and beta-blockade, an increment in each of these drugs was occasionally required to prevent these complications. Renal function was changed little with the decrease in blood pressure. Plasma renin increased from a standing control of 14.5 mμg/ml/hr to 35.9 and 31.1 mμg/ml/hr, respectively, on hydralazine and minoxidil. These data suggest the role of vasodilators used in combination with beta-blockers and diuretics and indicate the greater therapeutic efficacy of minoxidil.

Troleandomycin: Effectiveness in steroid-dependent asthma and bronchitis

Abstract The steroid dose-reducing capacity of troleandomycin (Tao), a macrolide antibiotic, was substantiated by a double-blind crossover study of 74 corticosteroid-dependent asthmatic and bronchitic subjects. Fifty were marked responders, 13 probable responders, and 11 nonresponders. Responders also improved in their sputum production, pulmonary function measurements, need for aerosolized bronchodilators, and subjective evaluations. Tao was effective when used concomitantly with methylprednisone. At a dose of up to 16 mg. of methylprednisolone per day, along with 250 to 500 mg. of Tao per day, patients could either retain a normal serum cortisol level or increase this to normal values 24 to 48 hours after the last dose. Hepatic function abnormalities were usually mild and transient but 10 had increased alkaline phosphatase levels, prompting discontinuation in some patients. The mechanism of action is not known, but in 11 of 14 marked responders on Tao, the threshold dose of methacholine required to produce a 20 per cent fall in Fev 1 was substantially increased. The antibiotic property of Tao did not explain improvement.

Variations in Arterial Blood Pressure after Kidney Transplantation Relation to Renal Function, Plasma Renin Activity, and the Dose of Prednisone

The course of hypertension within the first 2 months after kidney transplantation was correlated with renal function, plasma renin activity (PRA), and the daily maintenance dose of prednisone in 18 homograft recipients. During acute rejection blood pressure (BP) closely correlated with PRA. Patients with normal homograft function showed an increase in BP early after transplantation which in most returned to normal 3-8 weeks later. In the latter group no correlation could be found between the level of BP and PRA, however the BP correlated closely with the dose of prednisone. These observations suggest that during acute rejection the increase in BP may at least partly be mediated by a renal pressor mechanism, whereas with normal renal function the high dose of glucocorticoids may play an important role in the development of hypertension.

Failure of Medullary Carcinoma of the Thyroid to Respond to Doxorubicin Therapy

We describe 3 patients with metastatic medullary carcinoma of the thyroid who were treated with doxorubicin hydrochloride (Adriamycin). Serum calcitonin was measured before and after doxorubicin therapy. Doxorubicin failed to arrest the progression of the disease in any of the patients. Although serum calcitonin levels dropped in 1 patient during therapy, they remained markedly elevated in all 3 patients. From the present series it appears that medullary thyroid carcinoma often does not have a response to doxorubicin.

The renin-aldosterone system in mother and fetus at term

Umbilical cord plasma aldosterone consistently exceeded that of paired maternal plasma (N=24), although plasma renin activity (N=15) and reinin substrate (N=25) were always higher in the mother. This dissociation of levels of aldosterone and its stimulating hormone renin may be due to (1) a different stimulus for aldosterone secretion in the fetus, (2) increased fetal sensitivity to renin-produced angiotensin II, or (3) altered fetal metabolism of the latter hormone.

Central, renal and adrenal effects of lithium in man

Abstract The effect of lithium on thirst and plasma vasopressin concentration was tested in seven subjects with affective psychiatric disorders. Mean ad libitum fluid intake was liberal but no different before (3,293 ml/day) and three to four weeks after treatment with lithium (3,443 ml/day). After fluid deprivation, plasma vasopressin was 1.5 ± 0.39 pg/ml before and 3.72 ± 0.55 pg/ml after treatment with lithium (p 3 − , HPO 4 = , glucose, amino acid and uric acid excretion). A lower titratable acid excretion (21 ± 5 versus 32 ± 4 μeq/min, p 4 Cl ingestion during lithium therapy as compared to control. In conclusion, three to four weeks of lithium therapy neither stimulates thirst nor suppresses vasopressin release; some of the polyuria in patients with affective disorders may be due to their liberal fluid intakes. Lithium does not alter base line or standing PRA, aldosterone or proximal tubular function. Lithium does, however, induce an incomplete renal tubular acidosis.

Plasma Vasopressin Variation and Renin Activity in Normal Active Humans

Plasma concentrations of vasopressin and plasma renin activity were measured every 30 min for 24 h in 5 normal active humans, in 1 normal woman confined to bed (except for brief periods up to the bathroom), in 2 active patients with primary aldosteronism and in 1 patient with low-renin hypertension. Plasma vasopressin varied markedly over the day and night in a pattern suggesting episodic secretion of the hormone in the normal subjects. Assumption of upright posture was accompanied by a rise in plasma levels from undetectable to 20--50 pg/ml. Episodic secretion, however, also occurred during bed rest and sleep. In contrast, patients with primary aldosteronism and low-renin hypertension had plasma vasopressin levels considerably lower than the normals, and their profiles of plasma concentration lacked the peaks seen in normals. In the normals, although vasopressin and renin secretion often coincided, only 2 of 6 studies showed a significant correlation between the plasma levels of the two hormones. This study, therefore, shows that vasopressin is secreted periodically in normal humans, that upright posture is an important modulator of secretory activity and that the renin-angiotensin system may or may not influence the pattern of secretion. In addition, it underlines the necessity of recumbency in establishing the existence of a circadian rhythm of plasma vasopressin levels.

Testosterone effect on renin system in rats.

Summary Testosterone, 2.5 mg/day, was administered for 21 days to groups of female rats ovariectomized at age 105 days, male rats orchidectomized at age 50 days, and male rats orchidectomized as 26-day-old weanlings. The three groups were sacrificed at 133, 78, and 75 days, respectively, at body weights ranging from 248 to 313 g. In the two male groups there was a significantly greater plasma renin activity in testosterone-treated animals (P < 0.01) than in untreated controls. Plasma renin concentration rose with treatment in all three groups but only in the older males was this increase statistically significant (P < 0.05). RS was unchanged with treatment, however, except in the youngest group of males (P 0.05). This could have been due to conversion of testosterone to estrogens. Plasma aldosterone was not significantly altered by testosterone treatment. These results suggest that testosterone stimulates secretion of renin in at least the young male rat. Since testosterone has previously been shown to stimulate levels of the renin-like enzyme in mouse submaxillary gland, it is unclear from these experiments whether renal or submaxillary renin is involved. Although an indirect mechanism of antagonism by testosterone to action of mineralo-corticoids could be playing a role, this is unlikely because aldosterone was unchanged. The testosterone and sterile vehicle used in this study were kindly supplied by Marvin R. Guthaus, Medical Services, the Upjohn Company, Kalamazoo, Michigan. Evelyn Fitzgerald rendered expert secretarial assistance.

Hypothalamic Sarcoidosis and Hypopituitarism

4 patients with presumed pituitary hypothalamic sarcoidosis are described. 3 had histological diagnoses compatible with sarcoidosis and in the other this diagnosis was strongly suspected from chest X-rays. 2 patients presented with diabetes insipidus. ACTH reserve was diminished in 3 out of 4 and growth hormone reserve was diminished in the 3 who were tested. All 4 patients developed secondary amenorrhea. 3 patients had hypothalamic hypothyroidism. Prolactin dynamics were intact. Tomograms of the sella turcica in all 4 and computerized tomography of the hypothalamic area in 2 patients failed to reveal any abnormality.

“Masked” 21-hydroxylase deficiency of the adrenal presenting with gynecomastia and bilateral testicular masses

An infertile 27 year old man with precocious puberty is described. He presented in adulthood with unilateral and then bilateral gynecomastia, and subsequently testicular tumors developed. An early diagnosis of congenital adrenal hyperplasia would have avoided unnecessary surgery. Initial detailed metabolic evaluation led to the erroneous diagnosis of 11-hydroxylase deficiency because of the presence of an unusual steroid (21-desoxycortisol) in serum which was falsely reported as an increased 11-desoxycortisol (compound S). The observed low urinary pregnanetriol measurements would have supported this diagnosis. Subsequent specific measurements of 21-desoxycortisol established its presence in the serum and its major metabolite, tetrahydro-21-desoxycortisol, in the urine. The unique features in this case of 21-hydroxylase deficiency alert the physician to its unusual clinical presentation and the pitfalls that may be encountered when evaluating adrenal steroidogenesis.