S-nitrosocaptopril. I. Molecular characterization and effects on the vasculature and on platelets

We have synthesized an S-nitrosylated derivative of captopril, S-nitrosocaptopril, that manifests nitrosovasodilatory activity, inhibits angiotensin converting enzyme activity and inhibits platelet aggregation. The direct vasodilatory effects of S-nitrosocaptopril reflect the effects of the thionitrite bond, the presence of which does not in any way influence S-nitrosocaptopril's ability to inhibit angiotensin converting enzyme. Thionitrite stimulation of both vascular and platelet soluble guanylate cyclase activity leads to increases in intracellular cyclic GMP that are accompanied by vasodilatation and platelet inhibition, respectively. S-nitrosocaptopril is a novel hybrid molecule that has potential use in the treatment of hypertension regardless of renin status, angina pectoris and congestive heart failure.     

Impact of gestrinone on the course of asymptomatic endometriosis

A new drug, gestrinone, was subjected to the first double blind, randomised placebo controlled trial of any treatment of endometriosis. The disease deteriorated in eight (47%) of the 17 patients prescribed placebo (95% confidence limits 23% and 71%) compared with none of the 18 patients prescribed gestrinone (p = 0.002). There was a difference in elimination of the endometriosis in the gestrinone group compared with placebo but this was not statistically significant (p = 0.057). There was a significant difference in improvement of the disease in the gestrinone group compared with placebo (p = 0.004), confirming that gestrinone is an effective treatment of endometriosis. Endometriosis deteriorates in at least 23% of patients; as it is impossible to predict in whom this will happen, treatment appears to be warranted in all cases.     

Diagnosis in Prader-Willi syndrome.

Thirty one patients with the putative diagnosis of Prader-Willi syndrome were reassessed clinically and by DNA analysis. Eleven patients were judged not to have Prader-Willi syndrome and 20 to have the condition. This was confirmed by DNA analysis in all but one case. The diagnosis of Prader-Willi syndrome, especially in early infancy, should be made with caution unless confirmed by molecular genetic studies.     

Primary malignant melanoma of skin in four regions of New Zealand.

AIMS: to describe the incidence and thickness of a representative collection of melanomas occurring in recent years in New Zealand. METHODS: all pathology reports of primary malignant melanoma of the skin, in defined periods in 1987-9, were collated for four regions of New Zealand. RESULTS: nonMaori incidence rates were 52 and 58 melanomas per 100,000 person years for men and women, respectively. These rates are much higher than the 24 per 100,000 person years for melanoma registrations in 1983-4. The age standardised invasive melanoma rate of 35 per 100,000 person years was higher than those of most Australian states and close to the rate for Queensland in 1986. Preinvasive melanomas comprised 26% of all melanomas. Of invasive melanomas, 58% in men and 55% in women were less than 0.76 mm in thickness; 7% of invasive melanomas in men and 5% in women were at least 3.5 mm thick. CONCLUSIONS: increasingly early detection of malignant melanomas in successive years is likely to have contributed to the recent increase in incidence, perhaps to a major degree, but an environmental cause cannot be excluded.     

The endometrial biopsy as a predictive factor of pregnancy rate in women with unexplained infertility.

To investigate whether or not there is any relation between endometrial morphology and subsequent pregnancy rate, 47 couples with unexplained infertility were followed up for 3 years after they had had an endometrial biopsy. Each woman had an LH-timed endometrial biopsy performed in the luteal phase of the cycle. The biopsy was dated chronologically according to the luteinizing hormone (LH) surge and histologically using morphometric criteria. None of the women received any form of treatment in the endometrial biopsy cycle. Of 47 women with unexplained infertility, 36 (76.6%) (Group I) had 'in phase' endometrial development and 11 (23.4%) (Group II) had retarded endometrium. Women with normal endometrial development had a higher pregnancy rate than women with retarded endometrial development (50% vs. 9%; P less than 0.02). The fecundability during treatment cycles was higher in Group I than in Group II (0.051 vs. 0.008; P less than 0.05). In women with 'in phase' endometrium, treatment increased the monthly probability of conception (0.051 vs. 0.006; P less than 0.001). A precisely timed endometrial biopsy should be considered as part of the investigations for women with unexplained reproductive failure, to help determine prognosis.     

Kinetic changes in experimental colonic urinary diversion

An experimental model of colonic urinary diversion was performed on male Wistar rats to see if faeces, urine or a faeces and urine mixture produces tumours. Cell kinetic techniques, including the crypt cell production rate, and cellular DNA measurement were used to examine the effect of urine and of faeces on the colonic mucosa. Urinary diversion into the colon significantly increased colonic crypt activity. Tumours were found at the anastomosis when urine and faeces were mixed at 4 months, and at 6 months with urine alone.     

Effect of exogenous progesterone administration on the morphology of normally developing endometrium in the pre-implantation period

The effects on endometrial morphology of a single, intramuscular dose of 100 mg of progesterone administered in the early luteal phase, between days LH + 1 and LH + 6, were studied in a group (n = 8) of normal, fertile subjects by morphometric techniques and transmission electron microscopy. While the dose of progesterone administered consistently resulted in an increase of salivary progesterone concentration to above the upper limit of the reference range, no significant effect on endometrial development was observed; in particular, endometrial development was not advanced.