Beta-adrenoceptor modulation in a case of pure autonomic failure.

In a patient with pure autonomic failure, exercise did not modify beta-adrenoceptor density, probably due to an insufficient increase in plasma catecholamines. Isoproterenol infusion increased the number of beta-adrenoceptor by only 17%. Since in control subjects an increased beta-adrenoceptor level was found, following both physical stress and isoproterenol infusion, we suggest that the lack of increased beta-adrenoceptor levels may contribute to the poor circulatory adjustments observed in autonomic dysfunction during activities involving the sympathetic nervous system.

Early diastolic time intervals during hypertensive pregnancy.

Early diastolic time intervals have been assessed by means of the echopolycardiographic method in 17 pregnant women who developed hypertension during pregnancy (HP) and in 14 normal pregnant women (N). Systolic time intervals (STI), stroke volume (SV), ejection fraction (EF), and mean velocity of myocardial fiber shortening (VCF) were also evaluated. Recordings were performed in the left lateral decubitus (LLD) and then in the supine decubitus (SD). In LLD, isovolumic relaxation period (IRP) was prolonged in the hypertensive pregnant women compared with normal pregnant women (HP 51 +/- 12.5 ms, N 32.4 +/- 15 ms p less than 0.05), whereas time of the mitral valve maximum opening (DE) was not different in the groups. There was no difference in SV, EF, and mean VCF, whereas STI showed only a significant (p less than 0.05) lengthening of pre-ejection period (PEP) in HP. When the subjects shifted from the left lateral to the supine decubitus position, left ventricular ejection time index (LVETi) and SV decreased significantly (p less than 0.05) in both normotensive hypertensive pregnant women. IRP and PEP lengthened significantly (p less than 0.05) only in normals, whereas they were unchanged in HP. DE time did not vary in either group. In conclusion, hypertension superimposed on pregnancy induces lengthening of IRP, as well as of PEP, and minimizes the effects of the postural changes in preload on the above-mentioned time intervals.

Effect of a combination of ethinylestradiol and desogestrel in adolescents with oligomenorrhea and ovarian hyperandrogenism.

Nine oligomenorrheic adolescent girls with a clinical and hormonal picture of ovarian hyperandrogenism were treated with a monophasic oral contraceptive (OC) containing 0.03 mg ethinylestradiol (EE) plus 0.150 mg desogestrel (DOG) for six months. The same treatment was administered in eight eumenorrheic adolescents. In both groups the treatment induced a decrease in LH, FSH, androstenedione (delta 4-A), testosterone (T) and dehydroepiandrosterone sulphate (DHEA-S) levels associated with a significant sex-hormone-binding globulin (SHBG) increase. In oligomenorrheic adolescents a marked decrease in both the total ovarian volume and the number of cystic follicles was observed. All parameters, except SHBG and ovarian volume in hyperandrogenic girls, returned to pre-treatment values 3 months after treatment. Subjective improvement of skin problems occurred in six of the nine oligomenorrheic girls. Although temporary, the EE + DOG formulation pill is effective in the treatment of ovarian hyperandrogenism in adolescents. It may also be useful for the prevention of the progressive transformation in the 'classical' and 'irreversible' micropolycystic ovary of adult age.

PIP: The hormonal effects of a combined, monophasic oral contraceptive (OC) containing 0.03 mg of ethinyl estradiol and 0.150 mg of desogestrel were compared in 9 adolescents with oligomenorrhea and ovarian hyperandrogenism and 8 controls with regular menstrual periods. All adolescents were treated for 6 consecutive months. Before treatment, the females with irregular periods had significantly higher basal luteinizing hormone (LH), delta 4-androstenedione (A), testosterone (T), and dehydroepiandrosterone sulfate (DHEA-S) levels than controls. In addition, the oligomenorrheic females had significantly lower sex hormone binding globulin (SHBG) levels and greater mean ovarian volume. OC treatment produced a decrease in all hormones (LH, follicle-stimulating hormone, delta-4 A, T, and DHEA-S) in girls in both groups and a significant increase in SHBG levels. Oligomenorrheic subjects further manifested a significant decrease in total ovarian volume, with reduced number or disappearance of all echo-free cystic follicles in both ovaries. With the exception of SHBG and ovarian volume in hyperandrogenic subjects, all parameters returned to pretreatment values 3 months after discontinuation of the OC. 6 of the 9 oligomenorrheic subjects showed subjective improvement of skin problems; in addition, 6 reported a longterm decrease in hair growth. Post-treatment, oligomenorrhea and anovulation persisted in 7 of the 9 subjects. Although the effect of this treatment is temporary, the ethinyl estradiol-desogestrel OC appears to be effective in hyperandrogenic adolescents and may delay the progression of hirsutism and prevent adult micropolycystic ovarian disease.

Efficacy, cycle control and side-effects of two monophasic combination oral contraceptives: gestodene/ethinylestradiol and norgestimate/ethinylestradiol.

Two monophasic oral contraceptives containing gestodene (GTD, 75 micrograms) and ethinylestradiol (EE, 30 micrograms) or norgestimate (NGS, 250 micrograms) and EE (35 micrograms) were compared during the first six cycles of use. The subjects were randomly assigned to receive either type: 97 received GTD/EE and 92 NGS/EE. Six women in the GTD/EE group and nine in the NGS/EE group withdrew from the study; three (3%) and two (2%), respectively, withdrew because of adverse reactions. A total of 562 cycles for GTD/EE and 523 for NGS/EE were available. No woman became pregnant during the study. Overall, 94.4% of cycles in the GTD/EE group and 92.8% in the NGS/EE group were normal. A similar incidence of breakthrough bleeding (0.2% of cycles for GTD and 1.6% for NGS) and spotting (5.4% vs. 5.6%) was observed. Amenorrhea was never reported. Duration of withdrawal bleeding tended to be slightly longer in the NGS/EE group, significantly so for cycles 2 (0.5 days, p = 0.016), 4 (0.5 days, p = 0.031) and 5 (0.4 days, p = 0.045). Cycle 2 was significantly longer in the GTD/EE group (0.3 days, p = 0.027). Side-effects were reported by 12 (12%) women in the GTD/EE group and 13 (14%) in the NGS/EE group. The most common side-effects were headache (five cases (5%) in the GTD/EE group and two (2%) in the NGS/EE group) and breast pain (three (3%) and eight (9%) cases respectively). There were no statistically significant differences between the two groups with respect to change in body weight or changes in blood pressure and in laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet dysfunction in uremia. II. Correction by arachidonic acid of the impaired exposure of fibrinogen receptors by adenosine diphosphate or collagen.

Previous studies showed that platelets from patients with uremia have a marked decrease in their aggregation response to adenosine diphosphate (ADP) and collagen as single agents or as a pair. It is known that small amounts of arachidonic acid can enhance the sensitivity of platelets to concentrations of ADP or collagen that do not cause aggregation when used singly. Stimulation of platelets by certain agonists induces the formation of fibrinogen receptors on the platelet surface. The binding of fibrinogen that follows is essential for platelet aggregation. The platelet membrane glycoprotein IIb-IIIa complex appears to be the site of the fibrinogen receptor. Therefore, we investigated the binding of iodine 125-labeled fibrinogen to uremic platelets exposed to ADP, collagen, or arachidonic acid as single agents and as pairs. When aggregation and binding were studied in response to ADP, collagen, or the combination of ADP with collagen, uremic platelets had reduced aggregation and bound abnormally low amounts of fibrinogen. In contrast, platelets from patients with uremia bound as much 125I-fibrinogen and aggregated as well as controls when ADP or collagen were used in combination with low concentrations of arachidonic acid. Studies with a monoclonal antibody (B 79.7) suggested that the number of glycoprotein IIb-IIa molecules is the same in uremic and normal platelets. We conclude that uremia impairs the exposure of fibrinogen receptors on platelets in response to ADP or collagen without affecting the glycoprotein IIb-IIa complex quantitatively. Correction by arachidonic acid of the impaired aggregation and exposure of fibrinogen receptors by ADP or collagen suggests that abnormal release of endogenous arachidonic acid plays a role in the dysfunction of platelets in uremia.

Observations on the use of purified follicle-stimulating hormone in the treatment of luteal phase defects.

We treated 18 infertile patients affected by histologically confirmed luteal phase deficiency with 75 IU of purified follicle-stimulating hormone (FSH) daily during the first 5 days of the cycle. Patients who were not pregnant after the first cycle of treatment underwent a second cycle. In the second cycle the daily doses of purified FSH were doubled if luteal phase deficiency had persisted during the first cycle. During the two cycles before treatment and during treatment, patients underwent an endometrial biopsy 1-3 days before the expected onset of menses. An assessment of progesterone serum concentrations was also performed on days 8, 6 and 4 before the expected onset of menses. Treatment was administered in a total of 33 cycles resulting in 30 ovulatory cycles. Six pregnancies were achieved. Among non-conception ovulatory cycles, 13 presented delayed endometrial dating and 11 normal endometrium. The mean +/- SD of the sum of the three progesterone determinations was 14.7 +/- 1.4 ng/ml in pretreatment cycles, 14.6 +/- 1.6 ng/ml in cycles with normalization of endometrial dating, 14.8 +/- 1.7 ng/ml in cycles with persistence of luteal phase deficiency and 30.4 +/- 3.0 ng/ml in conception cycles (P < 0.05 versus other groups). We conclude that purified FSH, if effective in the treatment of luteal phase deficiency, does not act through an increase in progesterone concentrations.

[The reduction of beta-adrenoceptor density and the suppression of ectopic ventricular activity with low doses of amiodarone]. / Riduzione della densità beta-adrenocettoriale e soppressione dell'attività ectopica ventricolare con basse dosi di amiodarone.

In 5 patients with frequent premature ventricular ectopic beats, refractory to other antiarrhythmic treatments, amiodarone, given orally at the dose of 200 mg once a day for 4 weeks, reduced beta-adrenoceptor density from 202.9 +/- 62 to 101.1 +/- 33 fmol/mg protein (p < 0.01). Similarly, kd decreased from 21.0 +/- 6 to 3.9 +/- 1 (p < 0.05). Changes in beta-adrenoceptor population were accompanied by a marked reduction in mean premature ventricular complexes (PVC) frequency from the control value of 428.9 +/- 150.3 to 13.4 +/- 10.7 PVC/h (p < 0.05) and by a decrease in heart rate, from 83.8 +/- 4 to 73.9 +/- 4 b/min (p < 0.01). On the contrary, mean arterial pressure remained unchanged. Patients did not show side effects during treatment. Therefore, low dose oral amiodarone has important pharmacologic and therapeutic effects. It significantly reduces lymphocyte beta-adrenoceptor density and is effective in treatment of ventricular arrhythmias. Additional studies were performed in vitro exposing lymphocytes to increasing concentrations of amiodarone. The analysis of variance for repeated measures showed that amiodarone-induced reduction in lymphocyte beta-adrenoceptor density is a dose-depending phenomenon. Accordingly, treatment with doses of amiodarone higher than that used in the present study may induce a major reduction in lymphocyte beta-receptor density and exert a depressant cardiac effect.

Effects of thyroxine therapy on bone metabolism in postmenopausal women with hypothyroidism.

OBJECTIVE: To evaluate whether thyroid stimulating hormone-suppressive thyroxine replacement therapy increases bone loss in postmenopausal women. MATERIALS AND METHOD: The study had a cross-sectional design. Fifty-four postmenopausal women on long-term treatment with thyroxine for primary hypothyroidism, who showed suppressed thyroid stimulating hormone levels were enrolled in our study. In these patients and in a control group of 54 healthy postmenopausal women we evaluated bone mineral density at distal radius and the main biochemical parameters of bone turnover. Student's t test, Wilcoxon signed rank-test, Chi-square test and the univariate linear regression in the statistical analysis of the data were employed. RESULTS: Bone mineral density values, expressed as z-scores, in the treated group were significantly decreased in comparison with the control group (p < 0.01). We did not detect a significant relationship between different L-thyroxine doses administered and bone mineral density z-scores. On the contrary, an inverse correlation was detected between length of treatment and bone mineral density z-scores. Treated patients showed a significantly higher concentration of serum alkaline phosphatase, osteocalcin, urinary calcium/creatinine and hydroxyproline/creatinine in comparison with the controls. CONCLUSIONS: Our study suggests that thyroxine replacement therapy in patients with suppressed thyroid stimulating hormone levels increases postmenopausal bone loss.

Effect of dihydroergocryptine on serum prolactin levels and milk secretion in puerperal women.

The aim of the present study was to evaluate the efficacy and tolerability of the dopamine agonist drug dihydroergocryptine in the suppression of puerperal lactation. A single blind and placebo-controlled study was performed. A total of 90 postpartum women was acutely or repeatedly treated with dihydroergocryptine at different doses in order to investigate the efficacy of this drug in the suppression of puerperal lactation and to find the optimum dose for therapy. Prolactin levels, mammary symptomatology and rebound effects were monitored during the repeated treatment and also 1 and 8 days after drug discontinuation. With acute administration, dihydroergocryptine significantly reduced prolactin levels only at the dose of 10 mg and not at 5 mg. With repeated administration, a daily dose of 15 mg was more effective than 10 mg in reducing prolactin levels and in suppressing puerperal lactation. No side-effects occurred during the treatment. These results suggest that dihydroergocryptine might be considered an effective drug in the suppression of puerperal lactation.