Prostaglandin (PTG) E and F receptors in the porcine corpus luteum; effect of tumor necrosis factor-α.

The porcine corpus luteum (CL) is NOT sensitive to the luteolytic effects of PGF-2α until days 12-13 of cycle. The control of "luteolytic sensitivity" (LS) of the pig CL to PGF-2α is unknown, but it is temporally associated with macrophage infiltration into the CL. Since macrophages are the predominant source of TNF-α in the porcine CL, in other studies we examined the effects of TNF-α on porcine luteal cells in culture and showed that TNF-α induces LS in vitro. In Experiment 1 of this study possible mechanisms involved in the control of LS were examined, and involved measurement of the protein levels of PTGER2/EP-2, and PTGER3/EP-3 in porcine CL collected before (days 7-10), versus after (day 13), the onset of the LS. In Experiment 2, an examination of potential mechanisms involved in the control of LS by TNF-α, was carried out in which the effects of TNF-α on mRNA and protein expression of EP-2, EP-3 and FP in cultured luteal cells, were examined. The results of Experiment 1 showed that PTGER-3/EP-3 (but not PTGER-2/EP-2) levels decreased in porcine CLs after (day 13) compared to before (day 7-10) LS. In Experiment 2, the data obtained showed that TNF-α decreased PTGER-3/EP-3 and increased PTGFR/FP protein (in EARLY stage CL). In conclusion, these studies suggest a role for PTGER-3/EP-3 in the acquisition of LS, and support the hypothesis that TNF-α from CL macrophages plays a critical role in the control of LS in the porcine CL, by increasing PTGFR/FP, and decreasing PTGER-3/EP-3 protein.

Efficacy of misoprostol before diagnostic hysteroscopy in postmenopausal women: a randomized clinical trial.

OBJECTIVE: To evaluate pain and determine the efficacy of misoprostol, compared with placebo, for postmenopausal women before diagnostic hysteroscopy. METHODS: This randomized, double-blind, placebo-controlled clinical trial included 158 postmenopausal women who received either 200 µg of misoprostol or placebo through the vaginal route before diagnostic hysteroscopy (79 women/group). The primary outcome was pain assessment (presence and intensity) during the four steps of hysteroscopy: cervical grasping with a Pozzi tenaculum forceps immediately before hysteroscopy, during hysteroscopy, during performance of the endometrial biopsy, and postprocedure. The secondary outcomes were duration of the procedure, need for additional cervical dilatation, complications, and adverse effects. RESULTS: Mean ages of the women were 62 ±â€Š8.2 years and 60 ±â€Š7.3 years in the misoprostol and placebo groups, respectively. Abnormal bleeding (misoprostol group, 45.6%; placebo, 43%) and endometrial thickening (54.4% in the misoprostol group and 57% in the placebo group) were the most common indications for the examination in both groups (P = 0.49). There was no significant difference between groups in the pain intensity of the four steps of the procedure. The duration of hysteroscopy was similar in both groups (misoprostol group, 2.5 ±â€Š2.7 minutes; placebo, 2.1 ±â€Š1.6 minutes; P = 0.43). Additional cervical dilatation was needed in 11 women in the misoprostol group versus 9 in the placebo group (P = 0.63). In both groups, there was no significant difference in terms of complications. Adverse effects were reported by 25.3% of women using misoprostol (vaginal bleeding, 11.3%; cramping, 12.6%; diarrhea, 2.5%; 1 woman reported both vaginal bleeding and cramping). In the placebo group, only 2.5% of women developed adverse effects (P < 0.0001). CONCLUSION: Misoprostol does not reduce pain intensity, the duration of the procedure, or need for additional cervical dilatation, and causes more adverse effects when used in postmenopausal women before diagnostic hysteroscopy.

Palliative Therapies for Congenital Heart Disease with Ductus Dependent Pulmonary Circulation.

In neonates, the management of ductus dependent pulmonary circulation is challenging. There have been three palliative therapies for this lesion: the modified Blalock-Taussig shunt, ductal stenting and prostaglandin E infusions, for maintaining the ductal patency before definite operations. Debates remain with regard to the indications and disadvantages of three palliative therapies. The aim of this article is to give a brief review of these three palliative therapies.

Reactive gamma-ketoaldehydes as novel activators of hepatic stellate cells in vitro.

AIMS: Products of lipid oxidation, such as 4-hydroxynonenal (4-HNE), are key activators of hepatic stellate cells (HSC) to a pro-fibrogenic phenotype. Isolevuglandins (IsoLG) are a family of acyclic γ-ketoaldehydes formed through oxidation of arachidonic acid or as by-products of the cyclooxygenase pathway. IsoLGs are highly reactive aldehydes which are efficient at forming protein adducts and cross-links at concentrations 100-fold lower than 4-hydroxynonenal. Since the contribution of IsoLGs to liver injury has not been studied, we synthesized 15-E2-IsoLG and used it to investigate whether IsoLG could induce activation of HSC. RESULTS: Primary human HSC were exposed to 15-E2-IsoLG for up to 48h. Exposure to 5µM 15-E2-IsoLG in HSCs promoted cytotoxicity and apoptosis. At non-cytotoxic doses (50 pM-500nM) 15-E2-IsoLG promoted HSC activation, indicated by increased expression of α-SMA, sustained activation of ERK and JNK signaling pathways, and increased mRNA and/or protein expression of cytokines and chemokines, which was blocked by inhibitors of JNK and NF-kB. In addition, IsoLG promoted formation of reactive oxygen species, and induced an early activation of ER stress, followed by autophagy. Inhibition of autophagy partially reduced the pro-inflammatory effects of IsoLG, suggesting that it might serve as a cytoprotective response. INNOVATION: This study is the first to describe the biological effects of IsoLG in primary HSC, the main drivers of hepatic fibrosis. CONCLUSIONS: IsoLGs represent a newly identified class of activators of HSC in vitro, which are biologically active at concentrations as low as 500 pM, and are particularly effective at promoting a pro-inflammatory response and autophagy.

Prostaglandins before caesarean section for preventing neonatal respiratory distress.

BACKGROUND: Respiratory distress (RD) can occur in both preterm and term neonates born through normal vaginal delivery or caesarean section (CS). It accounts for about 30% of neonatal deaths and can occur at any time following birth. Respiratory distress syndrome (RDS), transient tachypnoea (rapid breathing) of the newborn and persistent pulmonary hypertension (increased blood pressure of pulmonary vessels) of the newborn are the most frequent clinical presentations of neonatal RD. Prostaglandins are used in routine obstetric practice to ripen the uterine cervix and to trigger labour, with those of the E series being preferred over others due to the fact that they are more uteroselective. Administration of prostaglandins to an expectant mother before delivery causes reabsorption of lung fluid from the fetal lung and promotes surfactant secretion by inducing a catecholamine surge. As a result, significant reduction in neonatal respiratory morbidity following a CS could be obtained, leading to reduced long-term complications such as bronchopulmonary dysplasia (chronic lung disease with lung tissue modification) and asthma. OBJECTIVES: The objective of this review was to determine if administration of prostaglandins before CS can improve respiratory outcomes of newborns. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). We also searched three clinical trial registries; ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry and the WHO Clinical Trials Registry Platform (ICTRP), for ongoing studies (24 June 2013). SELECTION CRITERIA: We included all published and unpublished randomised controlled trials comparing the use of prostaglandins with other treatments (including placebo) to reduce neonatal respiratory morbidity. Participants were pregnant women with an indication for a CS, and we compared administration of prostaglandins prior to CS with no treatment, placebo or another treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and assessed trial quality, with the third review author referred to for settling any disagreements. Two review authors extracted data. Data were checked for accuracy. We used the Cochrane tool for assessing risk of bias in the included study and contacted the study authors to request additional information where appropriate. MAIN RESULTS: We found one randomised controlled trial with a low risk of bias which was carried out in a tertiary neonatal care centre in Australia. The study involved 36 women (18 received intravaginal prostaglandin E 2 gel and 18 received placebo).There was one case of neonatal respiratory distress in the control group, which the trialist reported as transient tachypnoea of the newborn (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.01 to 7.68, one study, n = 36).None of the neonates required mechanical ventilation and the trial authors reported median Apgar scores at one and five minutes as being similar in both groups.There were no treatment-related side effects in either group. Noradrenaline concentrations (median values (range)) were reported as being significantly higher in the cord blood samples of the intervention group compared to the control group. AUTHORS' CONCLUSIONS: Although the trial authors reported a significant increase in catecholamine levels in the intervention group, there was no significant difference in the respiratory outcomes between intervention and control groups. The quality of evidence was graded as low because the sample size was small and there were few events. No definite conclusions can thus be drawn on the effects of prostaglandins on neonatal respiratory outcomes from this review.

Low-dose but not high-dose prostaglandin E(1) improves the histological outcome of severe forebrain ischemia in rats.

PURPOSE: Prostaglandin E(1) (PGE(1)) has been shown to provide short-term neuroprotection against various types of brain ischemia in a dose-dependent manner in mice. However, these findings were obtained from experiments performed without any control over physiological parameters. We performed an outcome study where physiological parameters were controlled in an attempt to confirm the dose-dependant neuroprotective effects of PGE(1). METHODS: A rat model of severe forebrain ischemia was used. Two doses of PGE(1) were administered during the pre-ischemic period, a low dose (LowPG group) and a high dose (HighPG group). Normotension was maintained in the LowPG group, while hypotension was induced in the HighPG group. In separate groups, normal saline (Control) or sodium nitroprusside (SNP) were infused to compare outcomes under similar blood pressure conditions. Histological outcomes in the hippocampal CA1 and entorhinal cortex were evaluated 5 days post-ischemia. RESULTS: HighPG resulted in hyperglycemia. The percentage of dead neurons in the hippocampal CA1 and entorhinal cortex were similar in the Control, SNP, and HighPG groups, the percentage being significantly attenuated in the LowPG group (CA1: Control = 92.8 +/- 2.4%, LowPG = 85.0 +/- 8.5%, HighPG = 95.3 +/- 2.4%, and SNP = 96.4 +/- 0.7%, P < 0.01; entorhinal cortex: Control = 73.8 +/- 4.0%, LowPG = 53.2 +/- 12.3%, HighPG = 72.1 +/- 12.6%, and SNP = 76.5 +/- 4.1%, P < 0.01). CONCLUSION: Pre-ischemic administration of low-dose PGE(1) in rats provided neuroprotection against severe forebrain ischemia. A dose dependency was not observed with PGE(1) dose and outcome.

Effects of centrally administered prostaglandin E(3) and thromboxane A(3) on plasma noradrenaline and adrenaline in rats: comparison with prostaglandin E(2) and thromboxane A(2).

Previously, we reported the involvement of brain omega-6 prostanoids, especially prostaglandin E(2) and thromboxane A(2), in the activation of central sympatho-adrenomedullary outflow in rats. omega-3 Prostanoids, including prostaglandin E(3) and thromboxane A(3), are believed to be less bioactive than omega-6 prostanoids, although studies on the functions of omega-3 prostanoids in the central nervous system have not been reported. In the present study, therefore, we compared the effects of centrally administered omega-3 prostanoids, prostaglandin E(3) and thromboxane A(3), with those of omega-6 prostanoids, prostaglandin E(2) and thromboxane A(2), on the plasma catecholamines in anesthetized rats. Intracerebroventricularly (i.c.v.) administered prostaglandin E(2) (0.15, 0.3 and 1.5 nmol/animal) and prostaglandin E(3) (0.3 and 3 nmol/animal) predominantly elevated plasma noradrenaline but not adrenaline, but the latter was less efficient than the former. On the other hand, U-46619 (an analog of thromboxane A(2)) (30, 100 and 300 nmol/animal, i.c.v.) and Delta(17)-U-46619 (an analog of thromboxane A(3)) (100 and 300 nmol/animal, i.c.v.) both elevated plasma catecholamines (adrenaline>>noradrenaline) to the same degree. These results suggest that centrally administered prostaglandin E(3) is less effective than prostaglandin E(2) to elevate plasma noradrenaline, and that thromboxane A(3) is almost as equipotent as thromboxane A(2) to elevate plasma catecholamines in rats.

Psychosocial interventions for erectile dysfunction.

BACKGROUND: Normal sexual function is a biopsychosocial process and relies on the coordination of psychological, endocrine, vascular, and neurological factors. Recent data show that psychological factors are involved in a substantial number of cases of erectile dysfunction (ED) alone or in combination with organic causes. However, in contrast to the advances in somatic research of erectile dysfunction, scientific literature shows contradictory reports on the results of psychotherapy for the treatment of ED. OBJECTIVES: To evaluate the effectiveness of psychosocial interventions for the treatment of ED compared to oral drugs, local injection, vacuum devices and other psychosocial interventions, that may include any psycho-educative methods and psychotherapy, or both, of any kind. SEARCH STRATEGY: The following databases were searched to identify randomised or quasi-randomised controlled trials: MEDLINE (1966 to 2007), EMBASE (1980 to 2007), psycINFO (1974 to 2007), LILACS (1980 to 2007), DISSERTATION ABSTRACTS (2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2007). Besides this electronic search cross checking the references of all identified trials, contact with the first author of all included trials was performed in order to obtain data on other published or unpublished trials. Handsearch of the International Journal of Impotence Research and Journal of Sex and Marital Therapy since its first issue and contact with scientific societies for ED completed the search strategy. SELECTION CRITERIA: All relevant randomised and quasi-randomised controlled trials evaluating psychosocial interventions for ED. DATA COLLECTION AND ANALYSIS: Authors of the review independently selected trials found with the search strategy, extracted data, assessed trial quality, and analysed results. For categorical outcomes the pooled relative risks (RR) were calculated, and for continuous outcomes mean differences between interventions were calculated as well. Statistical heterogeneity was addressed. MAIN RESULTS: Nine randomised (Banner 2000; Baum 2000; Goldman 1990; Kilmann 1987; Kockott 1975; Melnik 2005; Munjack 1984; Price 1981; Wylie 2003) and two quasi-randomised trials (Ansari 1976; Van Der Windt 2002), involving 398 men with ED (141 in psychotherapy group, 109 received medication, 68 psychotherapy plus medication, 20 vacuum devices and 59 control group) met the inclusion criteria. In data pooled from five randomised trials (Kockott 1975; Ansari 1976; Price 1981; Munjack 1984; Kilmann 1987), group psychotherapy was more likely than the control group (waiting list - a group of participants who did not receive any active intervention) to reduce the number of men with "persistence of erectile dysfunction" at post-treatment (RR 0.40, 95% CI 0.17 to 0.98, N = 100; NNT 1.61, 95% CI 0.97 to 4.76). At six months follow up there was continued maintenance of reduction of men with "persistence of ED" in favour of group psychotherapy (RR 0.43, 95% CI 0.26 to 0.72, N = 37; NNT 1.58, 95% CI 1.17 to 2.43). In data pooled from two randomised trials (Price 1981; Kilmann 1987), sex-group psychotherapy reduced the number of men with "persistence of erectile dysfunction" in post-treatment (RR 0.13, 95% CI 0.04 to 0.43, N = 37), with a 95% response rate for sex therapy and 0% for the control group (waiting list - no treatment) (NNT 1.07, 95% CI 0.86 to 1.44). Treatment response appeared to vary between patient subgroups, although there was no significant difference in improvement in erectile function according to mean group age, type of relationship, and severity of ED. In two trials (Melnik 2005; Banner 2000) that compared group therapy plus sildenafil citrate versus sildenafil, men randomised to receive group therapy plus sildenafil showed significant reduction of "persistence of ED" (RR 0.46, 95% CI 0.24 to 0.88; NNT 3.57, 95% CI 2 to 16.7, N = 71), and were less likely than those receiving only sildenafil to drop out (RR 0.29, 95% CI 0.09 to 0.93). One small trial (Melnik 2005) directly compared group therapy and sildenafil citrate. It found a significant difference favouring group therapy versus sildenafil in the mean difference of the IIEF (WMD -12.40, 95% CI -20.81 to -3.99, N = 20). No differences in effectiveness were found between psychosocial interventions versus local injection and vacuum devices. AUTHORS' CONCLUSIONS: There was evidence that group psychotherapy may improve erectile function. Treatment response varied between patient subgroups, but focused sex-group therapy showed greater efficacy than control group (no treatment). In a meta-analysis that compared group therapy plus sildenafil citrate versus sildenafil, men randomised to receive group therapy plus sildenafil showed significant improvement of successful intercourse, and were less likely than those receiving only sildenafil to drop out. Group psychotherapy also significantly improved ED compared to sildenafil citrate alone. Regarding the effectiveness of psychosocial interventions for the treatment of ED compared to local injection, vacuum devices and other psychosocial techniques, no differences were found.

Components in seminal plasma regulating sperm transport and elimination.

Seminal plasma has been suggested to be involved in sperm transport, and as a modulator of sperm-induced inflammation, which is thought to be an important part of sperm elimination from the female reproductive tract. This article reports on recent experiments on the importance of seminal plasma components in sperm transport and elimination. In Experiment 1, hysteroscopic insemination in the presence (n = 3) or absence (n = 3) of 2 ng/mL PGE showed an increased portion of spermatozoa crossing the utero-tubal junction in the presence of PGE in two mares, while no difference was observed between treatments in a third mare. In Experiment 2, whole seminal plasma, heat-treated seminal plasma (90 degrees C for 45 min), and charcoal-treated seminal plasma were added to: (1) sperm samples during opsonization prior to polymorphonuclear neutrophil(s) (PMN)-phagocytosis assays (n = 5); or to (2) phagocytosis assays (n = 5). Opsonization of spermatozoa was suppressed in the presence of whole seminal plasma, compared with samples without seminal plasma (p < 0.05). Charcoal treatment did not remove the suppressive effect of seminal plasma on opsonization, but heat treatment of seminal plasma reduced its suppressive properties (p < 0.05). The addition of whole seminal plasma to opsonized spermatozoa almost completely blocked phagocytosis (p < 0.05). Charcoal treatment did not remove the suppressive effect of seminal plasma. However, heat-treated fractions of seminal plasma removed the suppressive effect of seminal plasma on phagocytosis (p < 0.05). In Experiment 3, viable and non-viable (snap-frozen/thawed) spermatozoa were subjected to in vitro assays for PMN binding and phagocytosis with the following treatments (n = 3): (1) seminal plasma (SP), (2) extender; (3) ammonium sulfate precipitated seminal plasma proteins with protease inhibitor (SPP+); or (4) ammonium sulfate precipitated seminal plasma proteins without protease inhibitor (SPP-). Treatment was observed to impact binding and phagocytosis of viable and non-viable spermatozoa (p < 0.05). SP and SPP+ suppressed PMN-binding and phagocytosis of viable sperm. This effect was also seen, but to a lesser degree, in SPP- treated samples. Non-viable spermatozoa showed less PMN-binding and phagocytosis than live sperm in the absence of SP. The addition of SP promoted PMN-binding and phagocytosis of non-viable spermatozoa. SPP- treated samples also restored PMN-binding of non-viable spermatozoa. The addition of protease inhibitors removed this effect. In Experiment 4, seminal plasma proteins were fractionated based on MW by Sephacryl S200 HR columns (range 5000-250,000 kDa). Fractionated proteins were submitted to sperm-PMN binding assays. A protein fraction <35 kDa suppressed PMN-binding to live and snap-frozen spermatozoa. A greater MW protein fraction appeared to promote binding between PMNs and snap-frozen spermatozoa. While the addition of protease inhibitors was necessary to maintain the protective effect of seminal plasma proteins on viable spermatozoa, the promotive effect of seminal plasma on non-viable spermatozoa appeared to require some protease activity. It was concluded from these experiments that components of seminal plasma play active roles in transportation and survival of viable spermatozoa in the female reproductive tract and in the elimination of non-viable spermatozoa from the uterus.

Síndrome de exceso de prostaglandina E, en conejos / Hyperprostaglandin E syndrome in rabbits

No disponible

A prospective evaluation of efficacy and compliance with a multistep treatment approach for erectile dysfunction in patients after non-nerve sparing radical prostatectomy.

OBJECTIVE: To assess the response rate to different erectile aids in a consecutive series of patients treated with non-nerve sparing radical prostatectomy (NNSRP). PATIENTS AND METHODS: Ninety-four potent men were counselled about the different treatment options to restore an assisted erection before they had NNSRP. They were invited to participate in a multiphase protocol involving the sequential use of different erectile aids which aimed at restoring erectile function after surgery. The first proposed treatment was oral apomorphine sublingual. Patients with a positive response to the 1-item overall efficacy question and a minimum score of 3 in both question 3 and 4 of the International Index of Erectile Function were considered responders to oral pharmacotherapy. Treatment with sildenafil was then suggested to those not responding. If patients did not respond to oral pharmacotherapy a trial with a vacuum erectile device was offered; those not responding to this were then offered intracavernosal injection therapy with prostaglandin-E alone as the first option, followed by a mixture of vasoactive agents if needed. In those in whom injections also failed, a penile implant was recommended. At the 1-year follow-up visit all patients were offered a second trial with oral therapy regardless of the treatment currently in use. RESULTS: Seventy-six patients entered the protocol; there was no response to apomorphine. Five of 59 (8%) patients responded to sildenafil when they first used it at a mean of 7 months after NNSRP, while there were three additional responders in 22 patients who tried it for a second time a year later. Of patients achieving at least a complete tumescence sufficient for vaginal penetration, 52% and 60% were considered responders to the vacuum device and intracavernosal injections, respectively. Overall, 44% of patients enrolled in the protocol chose to use an erectile aid for at-home use. At the 1-year follow-up, only 20% of patients were still using an erectile aid, including two who had had a penile implant. CONCLUSIONS: Up to 10% of patients may achieve a clinically significant erection with sildenafil after NNSRP, but 80% will not be using any erectile aid at 1 year after surgery. In the present study protocol the proposed erectile aids were largely inadequate for treating the permanent erectile dysfunction that follows NNSRP.

Prostaglandin E--a powerful anabolic agent for generalized or site-specific bone formation.

Prostaglandins are locally secreted, rapidly metabolized, biologically active fatty acids first identified in the prostate. The role of prostaglandins in the inflammatory response has been widely studied. However, some prostaglandins, particularly those of the E series (PGEs), can suppress inflammation, making it difficult to understand the local events and their sequence. This bimodal potential of the PGEs has been poorly understood in skeletal biology, causing the initial report of PGEs as mediators of bone resorption to persist for more than two decades, despite ample evidence to the contrary. This resulted in part from the power of any initial report to overrule subsequent conflicting views and in part on the exclusive reliance on in vitro data to explain in vivo phenomena. Over a decade ago, the potential of PGEs as authentic anabolic skeletal agents was demonstrated convincingly in vivo by both systemic and local delivery. The potential clinical applications of the PGEs in skeletal biology have not yet been developed. Our purpose is to review the reasons for the delayed discovery of the true skeletal effects of the PGEs and to describe applications for this technology. With the development of appropriate delivery systems, one can anticipate widespread clinical applications of the PGEs to accelerate skeletal repair, and to treat skeletal pathologies and trauma.

[Comparative morpho-functional assessment of the impact produced by prolonged infusions of prostaglandins E and F on the course of genetically preconditioned arterial hypertension]. / Sravnitel'naia morfofunktsional'naia otsenka vliianiia prolongirovannykh infuzii prostaglandinov E i F na techenie geneticheski obuslovlennoi arterial'noi gipertonii.

The administration of prolonged intravenous infusions of prostaglandins is defined; the method provided for specifying a long-term impact produced by prostaglandins on a nature of the course of genetically preconditioned arterial hypertension (AHT) in rats. Infusions of PGE-2 bring about a prolonged and stable reduction of mean arterial presser (AP) by 10% versus its original value; they intensify 2-fold the depressor baroreflectory regulation and stimulate the urinary excretion of endogenous renal PGF-2 alpha; besides, they contribute to a better blood supply to organs, i.e. an increased perfusion of the cortical and medullary layers of the kidneys and of the brain substances; and dilatation of the intramural branches of the coronary arteries, due to which the AP becomes milder. Infusions of PGF-2 alpha contribute to a prolonged and stable elevation of mean AP by 12% versus the original value; they inhibit the depressor baroreflectory regulation and intensify the pressor baroreflectory regulation; they, additionally, induce the urinary excretion of endogenous renal PGF-2 alpha and correct the lesions in the blood supply to organs, i.e. pathological microcirculation, anemia and spasm of the renal parenchyma, ischemic foci in the myocardium, spastic contraction of small cerebral arteries, edema and destructive changes (of the local necrosis variation) in the cerebral substance microvessels concomitant with a commencing diapedetic hemorrhages. Finally, all above listed lesions are signs of the malignant AP course.

Methylene blue as a means of treatment for priapism caused by intracavernous injection to combat erectile dysfunction.

OBJECTIVE: The authors observed priapism as a side effect occuring during the intracavernous treatment of erectile dysfunction. Earlier priapism had been treated with an intracavernous injection of sympatomimetics; unfortunately several complications and contraindications were found. PATIENTS AND METHODS: Methylene blue was applied in the treatment of five patients. First a corpus cavernosum punction was performed and some blood was aspirated from the penis. Finally 100 mg of Methylthionin Chlorati was injected into the corpus cavernosum. RESULTS: A sufficient detumescence was observed in all of these cases. There were no complications. The method was applied effectively in two cases after an unsuccessful punction. CONCLUSION: The autors recommend intravenous methylene blue for the treatment of priapism. According to their experience this method is free of complications and as effective as a sympathomimetics treatment. As they think, it can be recommended in any manifestations of priapism because its force of action appears to be both chemically and biologically clear.

Active management of term prelabour rupture of membranes with oral misoprostol.

OBJECTIVE: To compare the active management of term prelabour rupture of membranes with oral misoprostol with conservative management for 24 hours followed by induction with oxytocin or prostaglandin E(2) (PGE(2)) gel. DESIGN: A non-blinded randomised controlled trial. SETTING: Induction and labour wards, Aberdeen Maternity Hospital. POPULATION: Sixty-one women with confirmed prelabour rupture of the membranes at > or =36 weeks of gestation. METHODS: The women were randomised to 50 microg of oral misoprostol repeated every 4 hours, if required, to a maximum of five doses (active group), or to induction of labour with PGE(2) gel or oxytocin only if not in spontaneous labour 24 hours after prelabour rupture of membranes (conservative group). MAIN OUTCOME MEASURES: Number of women in active labour within 24 hours of the prelabour rupture of membranes, preference of women for any one particular method of management in any subsequent pregnancy with prelabour rupture of membranes. RESULTS: 93.3% of the active group and 54.8% of the conservative group were in spontaneous labour within 24 hours of the prelabour rupture of membranes (RR 1.7, 95% CI 1.2 to 2.4). Of those achieving a vaginal delivery, 72% of the active group did so within 24 hours of the prelabour rupture of membranes as compared with 26.9% of the conservative group (RR 2.7, 95% CI 1.4 to 5.3, P = 0.002). There were no significant differences in the neonatal or maternal outcomes. In the active group, 78% felt they would have the same method of induction as compared with 40% in the conservative group (RR 1.9, 95% CI 1.1 to 3.3, P = 0.03). CONCLUSIONS: Active management with oral misoprostol resulted in more women going into labour and delivering within 24 hours of the prelabour rupture of membranes with no increase in maternal or neonatal complications. Women tended to view active management of prelabour rupture of membranes more positively. Oral misoprostol might be an option to consider in those wishing active management.

Short report: penile lymphoma following local injections for erectile dysfunction.

We report a case of high grade lymphoma which appeared at the site of prior injections of medications into the shaft of the penis for erectile dysfunction. We discuss the possible mechanisms of causation for this unusual form of lymphoma.

Impact of prenatal diagnosis on survival and early neurologic morbidity in neonates with the hypoplastic left heart syndrome.

BACKGROUND: Prenatal echocardiography can identify the fetus that has complex congenital heart disease and may improve early management and surgical outcome. Prenatal diagnosis may be particularly beneficial to patients who have hypoplastic left heart syndrome (HLHS) and who are at risk for hypoxic-ischemic insult at presentation. OBJECTIVES: We sought to determine whether prenatal diagnosis reduces neurologic morbidity and operative mortality in patients who undergo palliative surgery for the HLHS. METHODS: Data from all patients who had HLHS, except for those with lethal genetic anomalies, and who were admitted to our institution between July 1992 and September 1997 were analyzed to assess the impact of prenatal diagnosis on preoperative management, neurologic morbidity, and surgical mortality. The primary outcome measures were hospital mortality and the incidence of adverse neurologic events (seizure or coma). RESULTS: There were 216 patients who had HLHS and were referred for surgical palliation, 79 (36.6%) of whom had been diagnosed prenatally. All patients who had been diagnosed prenatally were delivered in an advanced nursery and were started on prostaglandin E(1) on the first day of life. Patients whose HLHS was diagnosed postnatally were begun on prostaglandin E(1) later in life (median = day 2 [range = 1-28 days]). There were 4 preoperative deaths and 53 operative or postoperative deaths. Overall hospital mortality was 26.4% and did not differ between patients whose HLHS had been diagnosed prenatally and those whose HLHS had been diagnosed postnatally. With the use of multivariable analysis, prenatal diagnosis was associated with fewer adverse perioperative neurologic events in the patients whose HLHS had been diagnosed prenatally than in those whose HLHS had been diagnosed postnatally (odds ratio = 0.46). CONCLUSIONS: These data suggest that prenatal diagnosis has a favorable impact on treatment of patients who have HLHS and are undergoing staged palliation and reduces early neurologic morbidity. Prenatal diagnosis was not associated with reduced hospital mortality. It is possible that prenatal diagnosis may improve long-term neurologic outcome.

Necrotizing enterocolitis in neonates with congenital heart disease: risk factors and outcomes.

OBJECTIVE: Necrotizing enterocolitis (NEC) is primarily a disease of the premature infant. Among children born at term, however, congenital heart disease may be an important predisposing factor for this condition. To determine risk factors for NEC in patients with congenital heart disease, we conducted a case-control study of neonates with cardiac disease admitted to the cardiac intensive care unit at our center during the 4-year period from January 1995 to December 1998. METHODS: Cardiac diagnosis and age at admission were analyzed for association with NEC among the 643-patient inception cohort. Demographic, preoperative, and operative variables were recorded retrospectively in 21 neonates with congenital heart disease who developed NEC and 70 control neonates matched by diagnosis and age at admission. Using parametric and nonparametric analysis, cases and controls were compared with respect to previously identified risk factors for NEC. RESULTS: Among the entire cohort of 643 neonates with heart disease admitted to the cardiac intensive care unit, diagnoses of hypoplastic left heart syndrome (odds ratio [OR] = 3.8 [1.6-9.1]) and truncus arteriosus or aortopulmonary window (OR = 6.3 [1.7-23.6]) were independently associated with development of NEC by multivariable analysis. In the case-control analysis, earlier gestational age at birth (36.7 +/- 2. 7 weeks vs 38.1 +/- 2.3 weeks), prematurity (OR = 3.9 [1.2-12.5]), highest dose of prostaglandin >0.05 microg/kg/minute (OR = 3.9 [1. 2-12.5]), and episodes of low cardiac output (meeting specific laboratory criteria) or clinical shock (OR = 6.5 [1.8-23.5]) correlated with the development of NEC. Earlier gestational age and episodes of low output were the only factors that remained significantly associated with NEC by multivariable analysis. Although there was no difference in hospital mortality between patients with and without NEC, mean hospital stay was significantly longer in those who developed NEC (36 +/- 22 days vs 19 +/- 14 days). CONCLUSIONS: The risk of NEC in neonates with congenital heart disease is substantial. Factors associated with an elevated risk of NEC in infants with heart disease include premature birth, hypoplastic left heart syndrome, truncus arteriosus, and episodes of poor systemic perfusion or shock. Heightened suspicion is warranted in newborns with these risk factors.