Serum LH and FSH responses to the repetitive administration of gonadotropin-releasing hormone in patients with idiopathic hypogonadotropic hypogonadism.

The serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to the repetitive administration of synthetic gonadotropin-releasing hormone (GnRH) were studied in six male patients with idiopathic hypogonadotropic hypogonadism. Each patient received 50 mug of GnRH intravenously every four hours for 43 consecutive doses, i.e., for one week. Five of the six patients had substantially greater maximum serum LH concentrations in response to the 43rd dose than to the first dose. The mean (+/- SE) maximum serum LH concentration of all six patients following the 43rd dose (14.6 +/- 3.0 mIU/ml) was significantly (P less than 0.01) greater than that to the first dose (8.3 +/- 2.6 mIU/ml. These results suggest that the LH response of the human gonadotroph to GnRH depends on the prior exposure of the gonadotroph to GnRH. All six patients had substantially higher basal serum FSH levels prior to the 43rd dose (13.6 +/- 2.6 mIU/ml) than prior to the first dose (2.8 +/- 0.4; P less than 0.01). Four patients had increases in basal FSH level to within the normal adult male range (5-15 mIU/ml), and two had increases to above it. This uniform elevation of the serum FSH level to normal or above normal suggests that GnRH may be the primary FSH-releasing hormone as well as the primary LH-releasing hormone.

Serum LH and FSH responses to synthetic gonadotropin-releasing hormone in normal men.

The effects of dose and of age on the serum LH and FSH responses to synthetic gonadotropin-releasing hormone (GnRH) were determined in normal men. GnRH was given as in iv bolus in doses from 2 to 500 mug to each of nine normal men, 20-39 years old. The mean (+/- SE) maximum delta LH (maximum increment above the basal concentration) in response to each dose of GnRH was 2 mug, 7.2 +/- 1.7 mIU/ml; 10 mug, 15.7 +/- 3.4 mIU/ml; 50 mug, 37.7 +/- 9.6 mIU/ml; 250 mug, 47.8 +/- 11.2 mIU/ml; and 500 mug, 49.3 +/- 11.2 mIU/ml. The mean delta FSH in response to each dose was 2 mug, 0.5 +/- 0.2 mIU/ml; 10 mug, 0.8 +/- 0.2 mIU/ml; 50 mug, 1.2 +/- 0.3 mIU/ml; 250 mug, 2.0 +/- 0.3 mIU/ml; and 500 mug, 2.4 +/- 0.4 mIU/ml. Since both the LH and FSH responses to the 250 mug dose were significantly greater than those to smaller doses, but the responses to the 500 mug dose were not still larger, 250 mug was used as the standard test done for subsequent studies. The effect of age was tested by administering a 250 mug dose of GnRH as an iv bolus to 42 carefully selected normal men, 14 in each of three age groups, 20-39, 40-59, and 60-79 years old. Dialyzable serum testosterone levels decreased with increasing age, from 21.7 +/- 4.6 to 16.0 +/- 4.9 to 14.3 +/- 3.8 ng/dl (mean +/- SD), and the basal serum LH levels increased slightly, from 7.4 +/- 3.4 to 9.6 +/- 3.1 to 10.8 +/- 3.2 mIU/ml, suggesting that a slight degree of primary Leydig cell failure occurs with increasing age. There was no corresponding increase in mean maximum delta LH in response to GnRH with increasing age, despite the elevation in mean basal LH levels. The maximum delta LH/basal LH ratio, in fact, declined from 6.8 to 5.1 to 3.3 in the three age groups. The basal serum FSH levels did not change with increasing age, but the mean delta FSH values decreased from 3.0 +/- 0.5 to 2.9 +/- 1.1 +/- 0.3 mIU/ml. These data demonstrate decreased LH and FSH responses to synthetic GnRH, as well as some primary Leydig cell failure, in the male senescence.

Clonidine in neuroleptic-induced akathisia.

Six hospitalized patients with neuroleptic-induced akathisia were treated with clonidine under single-blind conditions. Akathisia and anxiety at maximum clonidine dose were significantly lower than at baseline, although it was difficult to differentiate specific therapeutic effects from sedation.

Predictive value of clinical and exercise variables for detection of coronary artery disease in men with diabetes mellitus.

Sixty-eight men with diabetes mellitus (mean age 53 +/- 10 years) and no symptoms of cardiac dysfunction enrolled in a long-range study for detection of latent coronary artery disease. The testing included maximal treadmill stress with thallium-201 scintigraphy and echocardiography. Radionuclide angiography was available in 35 men (52%), and 24 (35%) had gated scanning with exercise. Of the 68 patients, 14 (21%) had a mild (9 patients) or moderate (5 patients) decrease in ejection fraction on radionuclide angiography, echocardiography or both. Fifty-two men agreed to remain in the study and have been followed for 12 to 18 months (mean 41 +/- 19). Ten coronary events have occurred. Four of the men died (2 suddenly) and 6 have angina pectoris. Three patients have had vascular complications. Of the clinical and exercise variables studied, exercise duration effectively predicted an adverse outcome, while the odds ratio in favor of a coronary event increased by 36 times in those with thallium-201 defects and 7 times in those with ST-segment changes on exercise. Radionuclide angiographic responses during exercise were abnormal in 5 of 6 patients with events, but were also abnormal in 12 of 29 men (41%) who did not have coronary artery disease. Clinical variables such as blood pressure, cholesterol level and family history were not predictive of outcome, nor was maximal heart rate during exercise. Thus, diabetic mean who can exercise for 440 seconds on a treadmill using a bruce protocol are at low risk of a coronary event.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial abscess due to Klebsiella pneumoniae complicating acute infarction.

A case is described in which Klebsiella pneumoniae urosepsis associated with acute myocardial infarction resulted in myocardial abscess and papillary muscle rupture. The diagnosis was made during surgery for mitral valve replacement. The patient improved after therapy with cefotaxime; however, cardiac rupture occurred on the sixth postoperative day. The pathogenesis of myocardial abscess and the use of non-invasive techniques for diagnosis are discussed.

Preliminary studies of clonidine in psychotic patients.

Twelve psychotic patients received a mean dose of 3.3 mg/day of clonidine. In four clonidine was the only treatment and in the remaining eight clonidine was superadded to a neuroleptic regimen after symptomatology was stable. Clonidine caused reduction of scores for both productive psychotic symptoms and anxiety. Negative symptoms were unaffected. These findings are discussed with respect to the small magnitude of the effects, questions as to specificity of the effects and methodologic limitations of this pilot study.

The role of aortic valve calcium in the detection of aortic stenosis: an echocardiographic study.

One hundred fifty-three men (mean age 67.0 +/- 10.0 years) with basal systolic murmurs and aortic valve calcium on the echocardiogram (group II) were studied to assess the relationship between the grade of calcium and severity of aortic valve obstruction. Patients were subdivided into group IIA (hypertension, no coronary artery disease), group IIB (coronary artery disease, no hypertension), group IIC (hypertension and coronary artery disease) and group IID (neither hypertension nor coronary artery disease). Group I consisted of 21 normal age-matched men (mean age 60.5 +/- 10.9 years). Aortic valve calcium was graded as 1+ (63 patients), 2+ (54 patients), or 3+ (36 patients) according to the degree of involvement. Left ventricular wall thickness was greater in group II than in group I, and close correlation between wall thickness parameters and grade of aortic valve calcium was observed for group IID. Of 31 catheterized patients, none of seven with 1+ aortic calcium and 11 of 14 with 3+ calcium had gradients greater than or equal to 50 mm Hg. With 3+ calcium the valve area was 0.8 +/- 0.4 cm2, and with 1+ calcium it was 2.8 +/- 0.7 cm2 (f = 0.0006). The presence of 3+ calcium or grade 2+ calcium combined with a left ventricular ejection time index greater than 433 msec and a left ventricular mass greater than 300 gm was highly suggestive of severe aortic stenosis and could be used to separate patients to be considered for invasive studies from those with benign aortic valve sclerosis.

In vitro metabolism of vitamin D3 by isolated liver cells.

Liver cells were prepared from rats fed a rachitogenic diet to investigate the hepatic metabolism of [alpha-1,2-3H2] vitamin D3. Rat hepatocytes suspended in Hanks medium rapidly took up labeled vitamin D3 from the incubation medium and converted this sterol to various metabolites, including 25-hydroxy vitamin D3 (25-OH-D3). There was steady increment in the cellular production of 25-OH-D3 and of the more polar metabolites of vitamin D3 over 3 hr of incubation as determined by thin layer chromatography. Neither the addition of cyclic nucleotides or dexamethasone to, nor the removal of calcium or phosphate from the medium resulted in changes in the rate of conversion of vitamin D3 to its products. Rats pretreated with sodium diphenylhydantoin converted labeled vitamin D3 to its metabolites at the same rate as control rats. These data indicate that isolated liver cells retain the capacity for vitamin D3 hydroxylation, but suggest that the rate of this process does not undergo rapid changes in response to metabolic stimulation.