Prostanoids in patients with peripheral arterial disease: A meta-analysis of placebo-controlled randomized clinical trials.

AIMS: Prostanoids are indicated in the treatment of peripheral arterial disease (PAD). Available trials suggest that these compounds could reduce the symptoms of intermittent claudication, even though the quality of studies is poor. The present meta-analysis is aimed at verifying the effects of prostanoids on amputation rate and ulcer healing in patients with lower limb PAD. MATERIALS AND METHODS: The review protocol was published on http://www.crd.york.ac.uk/prospero (CRD42015020258). A comprehensive search for published and unpublished trials comparing iloprost, alprostadil, prostaglandin-E1, epoprostenol, or taprostene with placebo/no therapy on amputation rate in patients with PAD and ulcer healing rate in patients with concomitant foot ulcers. Mantel-Haenzel odds ratio (MH-OR) was calculated with random effect models for the chosen endpoints. RESULTS: A total of 18 trials, enrolling 3,077 and 2,763 patients in the prostanoid and comparator groups, respectively were included in the analysis. Only 11 and 10 of those trials reported data on total and major amputations, respectively. Prostanoids were associated with a significantly lower risk of major (MH-OR [95% confidence interval] was 0.77 [0.63; 0.93], p=0.007), but not total, amputations. Healing rate (available only in 7 trials) was not significantly augmented by prostanoid treatment. CONCLUSIONS: Available data are not sufficient to support an extensive use of prostanoids in patients with critical limb ischemia, as an adjunct to revascularization or as an alternative to major amputation in cases which cannot undergo revascularization.

Cervical priming with misoprostol prior to transcervical procedures.

Cervical priming with misoprostol has shown to facilitate transcervical procedures and to reduce side-effects. Cervical priming is recommended by several evidence-based guidelines prior to surgical abortion, dilatation and curettage, hysteroscopy and intrauterine device insertion. It is effective in pregnant as well as in non-pregnant women while the results in post-menopausal women are conflicting. Misoprostol is the best suited prostaglandin for a number of reasons: it has a short half-life, few side effects, it is stable at room temperature, it is relatively cheap and the dosage can easily be adjusted according to the clinical need. Various doses, routes, and time intervals between misoprostol application and the intervention have been evaluated. A single dose of 400 microg given sublingually or vaginally 3h before the intervention has given the best efficacy with the least side effects. Higher doses or longer intervals do not improve the effect on the cervix. Pain is a frequent side effect, but usually responds well to NSAIDs. Other side effects are rare.

[Severe cardiovascular complications relating to Gemeprost therapy]. / Schwere kardiovaskuläre Komplikationen im Zusammenhang mit Gemeprost.

The use of gemeprost vaginal pessaries is generally thought to be a method with little complications used for cervical softening within the first two trimesters of pregnancy. Though in our hospital two cases presented with severe cardiovascular reactions, to be attributed to the effect of prostaglandins. The first patient experienced a severe cardiogenic shock due to vasospasm several hours after primary administration of gemeprost vaginal pessaries and a cerebral stroke some hours later. The second patient suffered of a myocardial infarction ensuing from coronary spasm.

[Reintroduction of medical abortion in Denmark]. / Reintroduktion af medicinsk abort i Danmark.

Medical termination of early pregnancy with mifepristone (RU 486) followed by a prostaglandin analogue (Cervagem) is a fairly new abortion method in surgical and gynaecological departments in Denmark. Sixty-two patients were evaluated during the period December 1, 1997 to the June 10, 1998 at Kalundborg hospital. The success rate was 97%. Side effects were rare. The study illustrates the need for strong analgesics in half of the patients. In conclusion RU 486 followed by a prostaglandin analogue provides an efficient and attractive alternative to surgical abortion methods.

[Vasospastic angina pectoris following abortion induced by prostaglandin analogue]. / Vasospastisk angina pectoris ved medicinsk provokeret abort med prostaglandinanalog.

A case of vasospastic angina pectoris with loss of consciousness, bradycardia and seizures induced by medical abortion following administration of mifepristone and gemeprost is reported. The patient had a history of smoking and migraine, and former treatment with ergot alkaloids or serotonin agonists had also resulted in chest pain and lipothymia. The case underlines the importance of obtaining a detailed history of vasospastic disorders in women referred for medical abortion.

[Retrospective analysis (1996-1998) of the treatment results with PgE2 (3 mg) of pregnant women with induced birth indications because of unsatisfactory cervix condition]. / Retrospektiven analiz ot prilozhenieto na PgE2 (3 mg) pri nezadovolitelno s'stoianie na matochnata shiika pri bremenni s indikatsii za induktsiia na razhdaneto (1996-1998).

The aim of the retrospective analysis is to estimate the results of PGE treatment/or cervical ripening with Bishop score < or = 4--effectiveness and safety. The research includes 60 patients with different induction indications. The comparative analysis has been carried out between 2 groups of patients with premature ruptiere of the ammotic membranes. The first group includes 22 patients treated only with Pg; and the second one includes 18 patients treated only with....

[Acute myocardial infarction following administration of a synthetic analog of prostaglandin E2 in a subject with an intramural course of the anterior intraventricular artery]. / Infarto miocardico acuto dopo somministrazione di un analogo di sintesi della prostaglandina E2 in soggetto con decorso intramurale dell'arteria interventricolare anteriore.

We report a case of acute myocardial infarction which occurred after administration of a synthetic analog of prostaglandin E2 (PGE2) for the voluntary interruption of pregnancy in a 31-year-old woman who had previously been asymptomatic, with myocardial bridging of the left anterior descending artery. The pathogenesis of the severe ischemia causing myocardial infarction and left ventricle aneurysm is quite unclear. The temporal connection is highly indicative of a causal relationship between the pharmacological effects of a synthetic PGE2 analog and coronary spasm responsible for severe ischemia. The hypothesis of endothelial dysfunction proximal to the intramyocardial artery tract and paradoxical vasoconstriction with platelet activation should be taken into consideration. A possible additional effect seems to be a horizontal coronary steal produced by the administration of PGE2 in the myocardium below the intramyocardial artery tract. It cannot be excluded that pharmacological doses of a synthetic analog of PGE2 may have inverted the vasoactive effects of the substance due to direct stimulation on the delivery of constrictive agonist factors.

[A trial of the use pf prostaglandin E1 (Edex, Caverject) for the diagnosis and treatment of erectile dysfunction]. / Opyt primeneniia prostaglandina E1 (edeks, kaverdzhekt) dlia diagnostiki i lecheniia érektil'noi disfunktsii.

The authors have examined 48 patients aged 17-70 years with erectile disorders. In 15 cases sexual adaptation was achieved after teaching them autoinjections. Pharmacological aid with PGE1 (Edex, Caverject) proved effective for sexual adaptation of patients with erectile disorders. In case of well adjusted dose and strict compliance of the autoinjection regimen the number of complications was minimal. In 50-70-year-olds PGE1 do not cause systemic complications due to pharmacokinetics and endogenic nature of PGE1. This prostaglandin is highly effective in some forms of psychogenic erectile dysfunction especially in expecting failure. For such patients 1 or 2 autoinjections of minimal dose are enough to correct erection.

The use of 16.16-dimethyl-PGE1-delta-methyl ester (Cervagem) vaginal pessaries for cervical dilatation prior to evacuation for second trimester termination.

The results of a study of 101 consecutive second trimester terminations by Dilatation and Evacuation (D & E) under ultrasound control is presented. All had a Cervagem pessary inserted into the vagina prior to the procedure. The PGE1 analogue was assessed as 'effective' in 97% of patients. Concomitant ultrasound resulted in no patient leaving the operating table with retained products. The high efficacy of the single pessary associated with a low incidence of side-effects makes this combination the method of choice for nearly all second trimester terminations.

The effect of enprostil on duodeno-jejunal motility in man.

Motor changes could be involved in the pathogenesis of diarrhoea that complicates the treatment of ulcer disease by prostaglandins. Our aim was to assess the effect of enprostil, a synthetic analogue of PGE2, on duodeno-jejunal motility. During this randomized double-blind crossover study, two manometric recordings, each lasting 20 h (12.00-08.00 hours), were carried out during dosing with 35 micrograms enprostil b.d. or placebo (eight volunteers: part 1), or during dosing with 35 or 70 micrograms enprostil b.d. (nine volunteers: part 2). Subjects were only allowed a standard dinner at 18.00 hours. During fasting, in part 1, the number of phase 3 activity patterns (PIIIs) was higher with enprostil than with placebo (P less than 0.01), without any difference in their characteristics; the overall duration of phase 1 activity was longer with enprostil than with placebo (P less than 0.01). In part 2, during fasting the number and characteristics of the PIIIs were not different, but there was a dose-related increase in PI, and decrease in PII activity. Fed motor patterns did not differ between the two doses of enprostil.

Enprostil, a prostaglandin E2 analogue, in the treatment of gastric ulcer--a multicentre comparison with pirenzepine.

In a double-blind, multicentre study 77 patients with benign gastric ulcer were randomly allocated to treatment with either enprostil 35 micrograms bd or pirenzepine 50 mg bd. After four weeks of treatment 13/26 (50 per cent) of evaluable enprostil-treated patients and 9/30 (30 per cent) of evaluable pirenzepine-treated patients were healed. Corresponding healing figures after eight weeks were 20/25 (80 per cent) and 25/31 (81 per cent). Both drugs rapidly reduced the severity of ulcer pain and the need for antacid use. No statistically significant differences were detected between the treatments with respect to healing rate or symptom control. Adverse events were reported by eight patients taking enprostil and by 17 patients taking pirenzepine. Two patients withdrew from each treatment group because of adverse events. None of these was serious. In conclusion, enprostil and pirenzepine were equally effective in healing gastric ulcers and no statistically significant differences in safety and efficacy were detected. There was a tendency for earlier healing and fewer side effects in the enprostil-treated patients.

Ranitidine compared with the dimethylprostaglandin E2 analogue enprostil as adjunct to pancreatic enzyme replacement in adult cystic fibrosis.

In a double-blind cross-over randomized study adjunct therapy with ranitidine (2 x 150 mg) was compared with enprostil (2 x 35 micrograms) in eight adult cystic fibrosis (CF) patients receiving a fixed dose of enteric-coated microsphere capsules of pancreatin (Pancrease). The study consisted of two consecutive 14-day treatment periods. All patients kept a fixed daily fat intake during the last 5 days of each treatment period and performed 72-h faecal collections during the last 3 days of each treatment period. Gastrointestinal complaints were scored at the end of each treatment period. During treatment with ranitidine there was less faecal fat excretion (18.9% versus 25.1%; NS), less faecal weight (263 versus 303 g/day; NS), and a lower gastrointestinal complaints score (5.3 versus 3.1; P less than 0.05) compared with the treatment with enprostil. One patient dropped out during the treatment period with enprostil because of very severe diarrhoea and abdominal discomfort. We conclude from this study that adjunct therapy with ranitidine has significantly less side effects and may give a better reduction of faecal fat excretion and daily faecal weight in CF.