Background: Pharmacological and postmortem investigations suggest that patients with major depressive disorder have alterations in function or density of brain serotonin 1A (5-HT 1A ) receptors. The aim of the present study was to use positron emission tomography with the selective 5-HT 1A receptor antagonist [11 C]WAY-100635 to measure 5-HT 1A receptor binding in depressed patients before and during treatment with selective serotonin reuptake inhibitors.

To describe the age at menarche and the prevalence of menstrual disturbances in an unselected group of women with insulin-dependent diabetes mellitus compared to controls, we identified all women having debut of diabetes mellitus before the age of 30 yr and living in the County of Funen, Denmark on July 1, 1987 and being between 18 and 49 yr old. The women received a structured questionnaire inquiring information concerning menstrual conditions. An age comparable group of nondiabetic women was used as controls; 245 (94%) diabetic women and 253 (88%) controls answered the questionnaire. Among women with debut of diabetes before the age of 10 yr, the age at menarche was delayed 1 yr when comparing to controls (P less than 0.0001). During the past 6 months before answering the questionnaire, 8.2% of the diabetic women and 2.8% of the controls had experienced episodes of secondary amenorrhea (P less than 0.01). Corresponding figures for oligomenorrhea were 10.6% and 4.8% (P less than 0.02), for polymenorrhea 7.3% and 5.2% (NS), and for all types of menstrual disturbances 21.6% and 10.8%, respectively (P less than 0.005). Episodes of secondary amenorrhea occurring more than 6 months before answering the questionnaire had been experienced by 10.7% of the diabetic population vs. 4.8% of the controls (P less than 0.05); corresponding figures for primary amenorrhea were 4.9% and 1.2%, respectively (P less than 0.05). We conclude that the age at menarche among women having developed insulin-dependent diabetes mellitus before the age of 10 yr was delayed by 1 yr when compared to controls. The overall prevalence of menstrual disturbances is increased in diabetic women compared to nondiabetic controls.

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Our study demonstrates that diabetic women are not sufficiently advised concerning use of contraception.

Verapamil has been shown to reduce total-body digoxin clearance by 35% due to impairments of both renal and extrarenal clearances. Our study was undertaken to evaluate the influence of the related calcium antagonist nifedipine on single-dose kinetics. Nifedipine increased extrarenal clearance of digoxin from 1.09 +/- 0.30(SD) to 1.45 +/- 0.23 ml/min/kg (P less than 0.05) and reduced the total urinary recovery of the drug from 69.2% +/- 5.9(SD) to 64.3% +/- 5.2 (P less than 0.05). There were no significant changes in renal digoxin clearance, distribution, or biological half-life or in digoxin distribution volumes during nifedipine coadministration.

Plasma digoxin concentration and renal digoxin clearance were determined during 2 hr of normal physical activity and during 2 hr of complete immobilization in eight healthy subjects on steady-state digoxin dosing. Mean plasma digoxin concentration rose from 0.64 +/- 0.13 ng/ml during physical activity to 1.04 +/- 0.19 ng/ml (63%) after 2 hr of rest. Resumption of physical activity resulted in gradual decline of plasma digoxin, and subsequent strenuous exercise reduced the value to preimmobilization level. Mean renal digoxin clearance was reduced from 168.4 +/- 18.7 ml/min during physical activity to 137.2 +/- 32.7 ml/min during rest whereas creatinine clearance was unchanged. The rise in plasma digoxin during rest is presumed to be due to changes in the binding of the drug to tissues such as skeletal muscles. Our findings indicate that attention should be given to the state of physical activity when kinetic studies are performed or when digoxin therapy is monitored by means of plasma digoxin analysis.

The effect of captopril has been investigated in four patients with Bartter's syndrome treated for 12 weeks. Baseline biochemistry showed normal serum aldosterone (mean 347 pmol.l-1) and a mean serum renin of 217 mU-l-1, and a considerable increase in serum renin during captopril treatment. Serum aldosterone decreased gradually during the study period to about half its initial value. The patients presented with a mean serum potassium of 2.5 mmol.l-1, which rose to 3.4 mmol.l-1 on captopril. Lymphocytes showed a substantial captopril-induced increase in intracellular sodium (from 15 to 22.5 mmol.l-1 on average), but no change in the potassium content. Captopril was well-tolerated. It may be an alternative to potassium-sparing diuretics for maintaining normal serum potassium levels in patients with Bartter's syndrome.

Verapamil increases plasma digoxin concentration by about 60% to 80%. To explore the clinical consequences of this interaction, we evaluated single-dose digoxin kinetics along with repeated measurements of intraerythrocytic sodium concentration in eight healthy subjects before and during verapamil coadministration. Verapamil reduced mean total body clearance of digoxin from 4.68 +/- 0.41 to 3.29 +/- 0.26 ml/min/kg and prolonged digoxin biologic t1/2 from 33.5 +/- 2.4 to 41.4 +/- 2.3 hr. These kinetic changes were associated with a greater elevation of intraerythrocytic sodium concentration than controls. Verapamil had no effect on intraerythrocytic sodium content. In vitro experiments revealed no influence of verapamil on the number of glycoside receptors on human lymphocytes. Since intracellular sodium concentration has proved to correlate closely with clinical signs of digoxin toxicity, our indicate that verapamil is likely to increase the risk of digoxin-induced arrhythmias.