Randomized comparison of the effects of endocervical and vaginal prostaglandin E2 gel in women with various degrees of cervical ripeness. Dutch Collaborative Prostaglandin Trialists' Group.

OBJECTIVE: The trail was conducted to obtain an unbiased comparison of the relative merits of endocervical and vaginal prostaglandin E2 gel in a weighted case mix of parous and nulliparous women with favorable and unfavorable cervical features. STUDY DESIGN: Multicenter randomized trial with 285 participants, (three exclusions) was performed with sealed envelopes stratified for parity and Bishop score. RESULTS: Outcomes of labor and delivery were clearly related to the cervical score at trial entry, especially in nulliparous women. Endocervical prostaglandin E2 had a more marked effect on cervical ripeness than did vaginal prostaglandin E2, but this did not result in any differences in more substantive outcomes. Frequencies of delivery within 12 (50%) and 24 hours (77.7%), cesarean section (7.3%), instrumental vaginal delivery (11.7%), and poor infant outcomes were similar with both preparations. CONCLUSION: Because differences in effectiveness between endocervical and vaginal prostaglandin E2 in triacetin gel are marginal, preferences of women and clinicians can determine the choice between them.

A study in patients with erectile dysfunction comparing different formulations of prostaglandin E1. Alprostadil Study Group.

PURPOSE: Prostaglandin E1 sterile powder and sterile solution are 2 new formulations of exogenous prostaglandin E1 that are more convenient for auto-injection therapy for erectile dysfunction than the presently used pediatric sterile solution. Therefore, the pharmacodynamic profiles of intracavernous prostaglandin E1 sterile powder and nonalcohol sterile solution were compared with the pediatric sterile solution in men with erectile dysfunction who were known to be stable responders to intracavernous prostaglandin E1. MATERIALS AND METHODS: Based on the dose used at home, patients were randomized to 1 of 5 dose groups: 0 microgram. (placebo), 2.5 micrograms., 5 micrograms., 10 micrograms. or 20 micrograms. Each patient received a single injection of the same dose of each of the 3 formulations. The primary pharmacodynamic end points were clinical evaluation of erectile response, RigiScan real-time evaluation of erectile response and patient evaluation of erectile response. RESULTS: No significant differences were identified among the formulations for any of these end points, either by comparison among all active doses or by comparison at each prostaglandin E1 dose level. There was also little or no intra-patient variation in dose response and the inter-dose variation in response between patients was not significant. Pharmacodynamic end points were well intercorrelated, although assessment of erectile response by the patients tended to be more positive than that by RigiScan or clinical evaluation. There were no major side effects. Penile pain on injection and/or during erection occurred in 9 to 17% of the patients according to the formulations. However, penile pain was also reported by 11% of the placebo-treated patients. CONCLUSIONS;: The 3 formulations of prostaglandin E1 showed equivalence and were safe for the treatment of erectile dysfunction with respect to side effects.

Effectiveness of low-dose lovastatin combined with low-dose colestipol in moderate to severe primary hypercholesterolaemia.

The effect of the combination of low-dose lovastatin and low-dose colestipol was studied among 57 subjects with moderate to severe primary hypercholesterolaemia (total cholesterol > or = 7.0 mmol l-1). Following an 8-week dietary phase, participants were randomized to treatment with 20 mg of lovastatin combined with 5 g or with 10 g of colestipol, or to matching placebo. Baseline total cholesterol was 7.7 +/- 0.9 mmol l-1 after dietary stabilization. Total cholesterol levels were reduced to 5.6 +/- 0.7 mmol l-1 and 5.8 +/- 0.7 mmol l-1 after 4 and 8 weeks of treatment in the lovastatin 5 g-1 colestipol group, and 74% of the subjects achieved the goal of low density lipoprotein (LDL) cholesterol levels of > or = 4.0 mmol l-1. Among the lovastatin 10 g-1 colestipol group, total cholesterol was reduced to 5.4 +/- 0.5 mmol l-1 and 5.5 +/- 0.9 mmol l-1 following 4 and 8 weeks, and 80% of subjects achieved the LDL cholesterol goal. No change was seen in the placebo group. Thus, low-dose combination therapy with lovastatin and colestipol, in conjunction with dietary treatment, is effective in moderate to severe primary hypercholesterolaemia, and is well tolerated.

Immunohistochemical study of the distribution of secretory component and IgA in the normal and diseased uterine mucosa.

The distribution of secretory component (SC) and IgA in the normal and diseased uterine mucosa was studied by means of an immunoperoxidase method. Both substances could not be demonstrated in ectocervical epithelium, whereas in endocervical epithelium both were present and staining intensity appeared to be related to the degree of inflammatory activity in the underlying stroma. Local IgA-containing plasma cells most likely are the source of epithelial IgA. Well-differentiated adenocarcinomas of the endocervix were shown to display SC immunoreactivity. In endometrial glands SC was observed in the postovulatory phase of the menstrual cycle, in increasing quantities toward menstruation. Hyperplastic conditions of the endometrium showed a weak focal staining for SC. In contrast, in most well-differentiated adenocarcinomas of the endometrium, SC and IgA could be detected in most neoplastic elements, whereas poorly differentiated carcinomas were largely negative. It is concluded that: (a) in contrast to the endometrium, in the endocervix a local secretory immune system operates similar to that of the gastrointestinal tract; (b) the ability of the endometrium to synthesize SC is at least partly regulated by hormonal factors and, as such, is confined to the progestagen-dominated phase of the menstrual cycle; and (c) immunohistochemical detection of SC may be of help in the grading of adenocarcinomas of the endometrium.

Radioimmunoassays for prostaglandins. I. Technical validation of prostaglandin F2alpha measurements in human plasma using sephadex G-25 gelfiltration.

Human plasma samples of 1 ml were processed according to three different procedures prior to Radioimmunoassay (RIA) of Prostaglandin F2alpha (PGF2alpha). Serial dilutions of ethyl acetate extracts as such, or combined with either silicic acid or Sephadex G-25 chromatography were assessed for linearity, homogeneity and parallelism with the corresponding standard dose response line. For plasma extracts used as such, non-parallelism is observed. Subsequent chromatography on silicic acid of such extracts gave only a limited linear and parallel portion upon serial dilution. However, purification of the extracts by gelfiltration on Sephadex G-25 results in linear and parallel lines over the full range of the standard dose response line (B/BO 0.9-0.2). Upon comparison of separation by Polyethylene glycol (PEG) and Dextran coated charcoal (DCC) in these systems, PEG proved to give the best results. It was found that in the Sephadex G-25 procedure, separation by PEG is essential. The method of gelfiltration on Sephadex G-25 is simple and reliable. Intra- and inter-assay coefficients of variation are 6% and 12%, respectively. Accuracy, as measured by recovery of added known amounts of PGF2alpha is 97.6%.

Intermittent low-dose administration of prostaglandins intraamniotically in pathological pregnancies. A comparison with oxytocin and ergometrine.

The effects of prostaglandin F2 alpha on uterine contractility were compared with the effects of oxytocin and ergometrine. All patients had an intrauterine death. 5 patients were induced with prostaglandin F2 alpha, given intraamniotically in low doses, starting with 125 micrograms. Doses were increased in relation to uterine activity. 5 other patients were induced by intravenous administration of oxytocin and ergometrine. Uterine pressure was monitored by a transabdominal open-tip catheter system. Results were quantitated in tonus (mm Hg), amplitude (mm Hg), frequency (number of contractions per 10 min), Montevideo units, active and total pressure areas per 20 min. Possible biochemical and coagulation changes were controlled before, during and after induction. Changes did not occur. Intermittent increasing small doses of PGF2 alpha increased uterine activity exponentially. Hypertonia persisting longer than 5 min was seldom seen with oxytocin or with PGF2 alpha. Ergometrine increased frequency of uterine contractions, without influencing tonus, probably due to a specific effect on the 'archemyometrium'. The induction-delivery interval was shorter in the PGF2 alpha group (range: 6-15 h) than in the oxytocin group (range: 7-24 h). In the latter group more inductions were necessary to complete delivery. Using PGF2 alpha in these small doses did not cause any side effects. With the intraamniotic injections, starting with 125 micrograms PGF2 alpha, clinical results are the same as those reported in the literature for high doses.