Prospective 12 month study of 30 minute decision to delivery intervals for "emergency" caesarean section.
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Cesarean Section↗
Biomedical subjects
I Cooke
Publications and source records attributed to I Cooke.
Infertility: past, present and future -- a personal view.
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Animals↗
Fertility 2000: session reports. Assisted conception.
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Female↗
Antifibrinolytics for heavy menstrual bleeding.
BACKGROUND: Heavy menstrual bleeding (HMB) is an important cause of ill health in women. Medical therapy, with the avoidance of possibly unnecessary surgery, is an attractive treatment option. A wide variety of medications are available to reduce heavy menstrual bleeding but there is considerable variation in practice and uncertainty about the most appropriate therapy. Plasminogen activators are a group of enzymes that cause fibrinolysis (the dissolution of clots). An increase in the levels of plasminogen activators has been found in the endometrium of women with heavy menstrual bleeding compared to those with normal menstrual loss. Plasminogen activator inhibitors (antifibrinolytic agents) have therefore been promoted as a treatment for heavy menstrual bleeding. There has been a reluctance to prescribe tranexamic acid due to possible side effects of the drugs such as an increased risk of thrombogenic disease (deep venous thrombosis). Long term studies in Sweden, however, have shown that the rate of incidence of thrombosis in women treated with tranexamic acid is comparable with the spontaneous frequency of thrombosis in women. OBJECTIVES: To determine the effectiveness of antifibrinolytics in achieving a reduction in heavy menstrual bleeding. SEARCH STRATEGY: All studies which might describe randomised controlled trials of antifibrinolytic therapy for the treatment of heavy menstrual bleeding were obtained by electronic searches of the MEDLINE 1966-1997, EMBASE 1980-1997 and the Cochrane Library. Companies producing antifibrinolytics and experts within the field were contacted for reference lists and information on unpublished trials. SELECTION CRITERIA: Randomised controlled trials in women of reproductive age treated with antifibrinolytic agents versus placebo, no treatment or any other medical (non-surgical) therapy for regular heavy menstrual bleeding within either the primary, family planning or specialist clinic settings. Women with post menopausal bleeding, intermenstrual bleeding, iatrogenic or pathological causes of heavy menstrual bleeding were excluded. DATA COLLECTION AND ANALYSIS: Fifteen eligible trials were assessed by three reviewers and eight of these did not meet with the inclusion criteria. Of the seven remaining trials, four of these could be included within the meta-analysis. The remaining three trials had a crossover design and despite contacting the authors and appropriate companies, we were unable to extract the results in a format suitable to include these within the meta-analysis. However the results are included within the text of the review for discussion. MAIN RESULTS: Antifibrinolytic therapy compared to placebo showed a significant reduction in mean blood loss (WMD -94.0 [-151.4, -36.5]) and significant change in mean reduction of blood loss (WMD -110.2 [-146. 5, -73.8]). This objective improvement was not mirrored by a patient perceived improvement in monthly menstrual blood loss (RR 2.5 [0.9, 7.3]) in the one study which recorded this outcome ( approximately approximately Edlund 1995 approximately approximately ). Antifibrinolytic agents were compared to only three other medical (non-surgical) therapies: mefenamic acid, norethisterone administered in the luteal phase and ethamsylate. In all instances, there was a significant reduction in mean blood loss (WMD -73.0 [-123.4, -22.6], WMD -111.0 [-178.5, -43.5] and (WMD -100 [-143.9, -56.1] respectively) and a strong, although non-significant trend in favour of tranexamic acid in the participants' perception of an improvement in menstrual blood loss. There were no significant differences in the frequency of reported gastrointestinal side effects with tranexamic acid when compared to either NSAIDs (RR 0.9 [0.4, 2.1], oral luteal phase progestagens (RR 0.4 [0.1, 1.2]) or ethamsylate (RR 0.88 [0.3, 2.9]) when these treatments were used for heavy menstrual bleeding. (ABSTRACT TRUNCATED)
Antifibrinolytic Agents↗
Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding.
BACKGROUND: Heavy menstrual bleeding (HMB) or menorrhagia is an important cause of ill health in women. Surgical treatment of HMB often follows failed or ineffective medical therapy and the definitive treatment is hysterectomy but this is a major surgical procedure with significant physical and emotional complications and social and economic costs. A number of less invasive surgical techniques (e.g. endometrial resection and laser ablation) have been developed with the purpose of removing the entire thickness of the endometrium. The benefits claimed for these therapies are reduced trauma and post-operative complications to the woman, reduced need for a general anaesthetic, direct cost savings to the health service due largely to a shift from inpatient to day case treatment and indirect cost savings to society as women return more quickly to their usual activities. However, endometrial hysteroscopic techniques are not always completely successful and additional surgical treatment is required in a proportion of cases. Although initially the resource and patient costs of these techniques are much cheaper than the cost of hysterectomy, the need for re treatment at a later stage may reduce the cost differential. Thus, the effectiveness of these techniques to improve a woman's perception of her own wellbeing long term has yet to be confirmed. OBJECTIVES: The objective of this review is to compare endometrial destruction techniques with hysterectomy by any means for the treatment of heavy menstrual bleeding (HMB). SEARCH STRATEGY: Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Sub fertility Group Register of Trials, MEDLINE, EMBASE, PsychLIT, Current Contents, Biological Abstracts, Social Sciences Index and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles and hand searching. In most cases, the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of endometrial destruction techniques with hysterectomy by any means for the treatment of heavy menstrual bleeding in premenopausal women. DATA COLLECTION AND ANALYSIS: Five RCTs were identified that fulfilled the inclusion criteria for this review. For two trials, a number of publications were identified which assessed different outcomes and different follow up time points for the same patients. The reviewers extracted the data independently and odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data. Outcomes analysed included improvement in menstrual blood loss, satisfaction, change in quality of life, duration of surgery and hospital stay, time to return to work, adverse events and requirement for repeat surgery because of failure of the initial surgical treatment. MAIN RESULTS: There was a significant advantage in favour of hysterectomy in the improvement in HMB and satisfaction rates (up to 4 years post surgery) compared with endometrial destruction techniques. Although many quality of life scales reported no differences between surgery groups, there was some evidence of a greater improvement in general health for hysterectomy patients. Duration of surgery, hospital stay and recovery time were all shorter following endometrial destruction. Most adverse events, both major and minor, were significantly more likely after hysterectomy and before discharge from hospital. After discharge from hospital, the only difference that was reported for this group was a higher rate of infection. Repeat surgery because of failure of the initial treatment, either endometrial ablation or hysterectomy, was more likely after endometrial destruction than hysterectomy. (ABSTRACT TRUNCATED)
Endometrium↗
Progesterone/progestogen releasing intrauterine systems versus either placebo or any other medication for heavy menstrual bleeding.
BACKGROUND: Heavy menstrual bleeding (HMB) is an important cause of ill health in women and it accounts for 12% of all gynaecology referrals in the UK. Heavy menstrual bleeding is clinically defined as greater than, or equal to, 80mls blood loss per menstrual cycle but women may complain of excessive bleeding when their blood loss is less than 80ml. Hysterectomy is often used to treat women with this complaint but medical therapy may be a successful alternative. The intrauterine coil device was originally developed as a contraceptive but the addition of uterine relaxing hormones, or progestogens, to these devices resulted in a large reduction in menstrual blood loss. Case studies of 2 types of progesterone/progestogen releasing systems, Progestasert and Mirena, report reductions of up to 90% and dysmenorrhoea may be improved. Insertion, however, may be regarded as invasive by some women affecting its acceptability as a treatment and frequent intermenstrual bleeding and spotting is likely during the first few months. OBJECTIVES: To determine the effectiveness and acceptability of progesterone/progestogen-releasing intrauterine devices in achieving a reduction in heavy menstrual bleeding. SEARCH STRATEGY: All studies which might describe randomised controlled trials of progesterone/progestagen-releasing intrauterine devices for the treatment of heavy menstrual bleeding were obtained by electronic searches of the MEDLINE 1966-1999, EMBASE 1980-1999 databases and the Cochrane Library. Companies producing progestogen releasing intrauterine devices and experts in the field were contacted for information on published and unpublished trials. SELECTION CRITERIA: Randomised controlled trials in women of reproductive age treated with progesterone/progestogen-releasing intrauterine devices versus no treatment, placebo, or other medical or surgical therapy for heavy menstrual bleeding within either the primary care, family planning or specialist clinic setting were eligible for inclusion. Women with postmenopausal bleeding, intermenstrual or irregular bleeding, or pathological causes of heavy menstrual bleeding were excluded. DATA COLLECTION AND ANALYSIS: Potential trials were independently assessed by three reviewers and five trials met the criteria for inclusion in the review. The reviewers extracted the data independently and data were pooled where appropriate. Odds ratios for dichtomous outcomes and weighted mean differences for continuous outcomes were estimated from the data. The primary outcome was reduction in menstrual blood loss but incidence of side effects, changes in quality of life and satisfaction and acceptability measures were also assessed. MAIN RESULTS: Progesterone/progestogen-releasing intrauterine systems have not been compared to placebo or no treatment. Progestasert has been compared to a number of different medical therapies in one small study but no conclusions can be made about effectiveness. The levonorgestrel-releasing intrauterine device (LNG IUS) has been compared to oral cyclical norethisterone (NET) administered on days 5-26 in one trial and was significantly more effective although there was a large reduction from baseline in both groups and these differences were not perceived by the women undergoing the treatment. Some side effects were more common in the LNG IUS group but a significantly greater proportion of women in this group were satisfied and willing to continue with their treatment. In one trial of women awaiting hysterectomy where the LNG IUS was compared with a control group taking their existing medical therapy, a higher proportion of the women in the former group cancelled their planned surgery after 6 months of treatment. The levonorgestrel-releasing intrauterine device has been compared to a surgical procedure (transcervical resection of the endometrium (TCRE)) in two trials. (ABSTRACT TRUNCATED)
Female↗
Modulation of N-type calcium channels translocation in RINm5F insulinoma cells.
An intracellular pool of N-type voltage-operated calcium channels has recently been described in both IMR32 human neuroblastoma and PC12 rat pheochromocytoma cells. These channels were found to be accumulated in subcellular fractions where the chromogranin B-containing secretory granules were also enriched. Upon exocytosis N-type calcium channels were reversibly inserted in the plasma membrane. We have now extended this study to RINm5F rat insulinoma cells, and characterized the parallelism between the 'regulated' secretion of serotonin and the recruitment of surface calcium channels. Exocytosis was stimulated by different means, such as depolarization with high KCl, high Ba(2+)alone or protein kinase C activation; on the other hand exocytosis was inhibited with the non-selective calcium channel antagonist Cd(2+)or with noradrenaline. Stimulated release was always accompanied, with parallel kinetics, by calcium channel recruitment, while inhibition of secretion blocked calcium channel recruitment too. During repetitive depolarizations we revealed a potentiation of [Ca(2+)]()i transients in single Fura-2 loaded RINm5F cells, that was accompanied by an increase in surface VOCCs, suggesting a physiological role for the newly recruited channels. 2000 Academic Press@p$hr
Animals↗
Granulocyte-macrophage colony-stimulating factor augments phagocytosis of Mycobacterium avium complex by human immunodeficiency virus type 1-infected monocytes/macrophages in vitro and in vivo.
The role of human immunodeficiency virus type 1 (HIV-1) infection on the ability of human monocytes/macrophages to phagocytose Mycobacterium avium complex (MAC) in vivo and in vitro and the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on this function were investigated. By use of a flow cytometric assay to quantify phagocytosis, HIV-1 infection was found to impair the ability of monocyte-derived macrophages to phagocytose MAC in vitro, whereas GM-CSF significantly improved this defect. Phagocytosis was not altered by exposure to a mutant form of GM-CSF (E21R) binding only to the alpha chain of the GM-CSF receptor, suggesting that signaling by GM-CSF that leads to augmentation of phagocytosis is via the beta chain of the receptor. In a patient with AIDS and disseminated multidrug-resistant MAC infection, GM-CSF treatment improved phagocytosis of MAC by peripheral blood monocytes and reduced bacteremia. These results imply that GM-CSF therapy may be useful in restoring antimycobacterial function by human monocytes/macrophages.
Adult↗
Decision to delivery intervals for assisted vaginal vertex delivery.
OBJECTIVE: To describe the time interval between decision for assisted vaginal delivery and the birth of the baby in different clinical circumstances. DESIGN: A prospective analysis of 225 consecutive women with a singleton fetal cephalic presentation in the second stage of labour requiring an operative vaginal delivery for various reasons. SETTING: A maternity unit in a district general hospital delivering more than 6,000 women annually. MAIN OUTCOME MEASURES: The decision to delivery interval and the immediate and short term maternal and neonatal outcomes according to indication for operative vaginal delivery. RESULTS: The mean (SD) decision to delivery interval was 34.4 minutes (28.3) with a range of 5 to 101 minutes. For those delivered because of suspected fetal distress, the interval of 26.5 minutes (14.0) was significantly shorter than for those performed without fetal distress 39.5 minutes (19.0) (P < 0.0001); for cases with fetal distress, forceps were significantly quicker at 23.3 minutes (14.3) than the ventouse 29.2 minutes (13.2) (P = 0.04). The longer the interval in cases of fetal distress the less favourable the condition of the neonate at birth, although this trend did not reach statistical significance and was not seen for deliveries expedited for other reasons. Perineal repair was required following 96% forceps deliveries compared with 87% ventouse (P = 0.015). Perineal trauma was not influenced by the interval between decision and delivery. CONCLUSIONS: If speed of delivery is important, use of forceps results in a quicker birth than use of the ventouse, without any compromise to the condition of the baby at delivery, and with similar rates of perineal trauma.
Adult↗
Should tissue from pregnancy termination and uterine evacuation routinely be examined histologically?
OBJECTIVE: To assess the value of routine histological examination of tissue samples collected at termination of pregnancy in the first trimester and emergency surgical uterine evacuation. SETTING: The gynaecological department of a teaching hospital. DESIGN: Prospective study of women attending the gynaecological department in a 12-month period. PARTICIPANTS: All women undergoing a therapeutic first trimester medical or surgical abortion or an emergency surgical evacuation of a failed pregnancy, suspected incomplete spontaneous miscarriage or incomplete induced abortion. MAIN OUTCOME: Association of pre-operative clinical diagnosis and the post-operative histological result. RESULTS: Of 1,576 women studied, the histological report confirmed that products of conception were obtained in 1,465 (93%); in two women (0.13%) molar changes were reported confirming the preoperative diagnosis by ultrasound. Products of conception were not confirmed in the tissue specimens in 0.5% medical terminations, 5% surgical terminations, 10% evacuations following a previous evacuation, 12% evacuations for a failed pregnancy, and 19% evacuations for an incomplete miscarriage. In 87 women (6%), decidua was reported; two of these women had undergone an evacuation for an ultrasound diagnosis of spontaneous miscarriage, but in both a tubal ectopic pregnancy was subsequently diagnosed. CONCLUSION: There did not appear to be any obvious benefit from routine histological examination of tissue removed at termination of pregnancy or emergency uterine evacuation. The histological result was sometimes not consistent with the pre-operative diagnosis and may result in unnecessary further investigation and treatment unless due consideration is given to the clinical presentation.
Abortion, Induced↗
3beta-hydroxysteroid dehydrogenase autoantibodies are rare in premature ovarian failure.
Premature ovarian failure (POF) is a disorder of heterogeneous etiology, and autoimmunity has been suspected as one cause of POF. The steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3betaHSD), has been characterized as a potential autoantigen in POF as well as in insulin-dependent diabetes mellitus (type 1 diabetes). Here we studied the presence of steroid cell antibodies (SCA), autoantibodies to 3betaHSD and to two other known autoantigens in ovarian failure, steroidogenic enzymes 17alpha-hydroxylase (P450c17), and side-chain cleavage enzyme (P450scc) in POF patients and patient groups with autoimmune polyendocrinopathy syndromes type 1 and 2 (APS1 and -2), isolated Addison's disease, type 1 diabetes, and healthy controls. The SCA were found in 2 of 48 POF, 11 of 15 APS1, and 1 of 9 APS2, and autoantibodies to in vitro translated 3betaHSD protein were detected in 1 POF serum associated with Addison's disease and 3 APS1 sera. All 3betaHSD precipitating sera were also positive for SCA. However, no SCA or 3betaHSD autoantibodies were found in 38 Addison's disease, 28 type 1 diabetes, and 71 healthy control sera. In analysis of autoantibodies to P450c17 and P450scc, antibodies to these enzymes were not found in POF sera, but were found in 10 and 12 APS1 patient sera, respectively, and 1 APS2 patient serum contained anti-P450c17 antibodies. Our results show that autoantibodies to 3betaHSD in POF patients are rare and are also found in patients with APS1.
3-Hydroxysteroid Dehydrogenases↗
Analysis of loss of heterozygosity and KRAS2 mutations in ovarian neoplasms: clinicopathological correlations.
The molecular events that give rise to ovarian epithelial neoplasms are not well understood. In particular, it is not known whether adenocarcinomas arise from benign or low malignant potential (LMP) precursors. We have examined a large series of benign (25) and LMP (31) ovarian tumors for loss of heterozygosity (LOH) at multiple loci on 17 chromosomes. LOH was observed in benign tumors on chromosomes 6 (14%) and 9 (5%) and on the X chromosome (33%) only. LOH on these chromosomes was also detected in a small number of LMP neoplasms, suggesting that these may derive sometimes from benign precursors. In addition, we examined LOH in 93 adenocarcinomas. Analysis of associations between LOH events showed that LOH on chromosomes 5 and 17 (P = 0.0002) and on chromosomes 17 and 18 (P = 0.00007) were associated significantly with each other, which suggests that these may represent cooperative, progressive events. No novel significant associations were identified between LOH events and stage, grade, or histology, which would indicate the existence of genetic heterogeneity in ovarian neoplasms. KRAS2 mutations were detected more often in LMP neoplasms than in malignant tumors (P = 0.004) and were detected more often in Stage I/II malignant tumors than in Stage III/IV malignant tumors (P = 0.033), suggesting that LMP tumors with KRAS2 mutations are unlikely to progress to frank malignancy. Univariate (but not multivariate) survival analysis showed that LOH of chromosomes 11 (P = 0.039) and 17 (P = 0.04) was associated with a significantly worse prognosis. Replication of these novel findings is necessary, and the identification, isolation, and characterization of the critical genes affected by LOH will determine their importance in the pathogenesis of ovarian malignancies.
Chromosome Deletion↗
Serum endometrial IgG antibodies and soluble CD23 concentrations in patients with endometriosis.
OBJECTIVE: Serum endometrial antibodies have been found inconsistently in patients with endometriosis. Soluble CD23 is elevated in diseases associated with B cell activation. We evaluated serum levels of soluble CD23 and endometrial IgG antibodies in patients with endometriosis to determine whether there is B cell activation in this condition. DESIGN: Fifty-seven patients with pelvic pain diagnosed as endometriosis and 40 patients without pelvic pain or endometriosis who had laparoscopic sterilisation were sequentially recruited into the study. Blood was collected and the sera assayed by ELISA for endometrial IgG antibodies and soluble CD23. RESULTS: There was a significant difference between endometriosis and control group in both the serum IgG endometrial antibodies (p < 0.05) and soluble CD23 (p < 0.05). There was significant but weak correlation between endometrial antibodies and soluble CD23 (r = 0.3, p = 0.039), particularly in mild but not severe endometriosis. CONCLUSIONS: These data suggest the existence of B cell activation in patients with endometriosis with a significant correlation between endometrial antibodies and soluble CD23. Mild endometriosis appears to be immunologically more active than the severe form. The value of soluble CD23 in the management of endometriosis needs further evaluation.
Adult↗
Inhibin as a marker for ovarian cancer.
Inhibin is a polypeptide hormone produced by the granulosa cells of the ovary, and is present in body fluids as dimers of various sizes each comprising an alpha- and beta-subunit. Free forms of the alpha-subunit also circulate, and the presently available radioimmunoassay (Monash assay) cannot distinguish these from biologically active dimeric inhibin. Recently we described a new two-site enzyme immunoassay able for the first time to measure the levels of dimeric inhibin throughout the human menstrual cycle. The sensitivity limit of this assay is 2 pg ml-1 in human serum with cross-reactivity against activin of 0.05%. The normal range of inhibin in post-menopausal women is < 5 pg ml-1, in pre-menopausal women 2-80 pg ml-1 (2-10 pg ml-1 in the follicular phase, 40-80 pg ml-1 in the luteal phase). This assay was used to determine inhibin levels in sera from 15 (five pre-menopausal and ten post-menopausal) patients with granulosa cell tumours of the ovary. It was raised in a pre-menopausal patient preoperatively (261 pg ml-1), in six post-menopausal patients (32, 43, 54, 66, 24 and 58 pg ml-1) and one pre-menopausal patient with recurrent tumour, (237 pg ml-1), all confirmed clinically. Inhibin was normal in six patients in remission. Oestradiol levels were normal in all patients. Serial levels of inhibin predicted recurrence before overt clinical relapse in two patients. In 29 patients with malignant epithelial ovarian tumours inhibin levels were modestly elevated in nine and normal in the rest. Three patients with endometrioid histology, two with undifferentiated tumours, three with mucinous adenocarcinoma and one with clear cell carcinoma had elevated inhibin levels. Functional inhibin is secreted by all granulosa cell tumours of the ovary studied and can be used as a tumour marker to determine response to therapy and predict recurrence and is superior to oestradiol. A more detailed analysis of the levels of inhibin, and its subunits in epithelial ovarian cancer is needed to identify the molecular forms of the immunoreactive material before optimised assays can be applied to this more common tumour.
Adult↗
Fluorescence in situ hybridization analysis using cosmid probes to define chromosome 6q abnormalities in ovarian carcinoma cell lines.
Deletion of 6q is a frequent finding in ovarian carcinoma, which would suggest that this region contains one or more putative tumor suppressor genes. Chromosome 6q abnormalities in six ovarian carcinoma cell lines were analyzed by G-banding and fluorescence in situ hybridization (FISH). Using a variety of probes, including a chromosome 6 paint, a probe specific for the chromosome 6 centromere, and cosmids that map to q24 (cCI6-115), q25 (cCI6-4), q26 (cCI6-91, cCI6-119), and q27 (cCI6-13, cCI6-24, and cCI6-111), abnormalities of 6q were found in three cell lines. In cell line OAW42 (hypotetraploid), the sequences complementary to cCI6-119, cCI6-91, and cCI6-13 probes were lost in two homologues of chromosome 6, which indicates the deletion of genetic material from bands q26-27. The same bands were translocated in cell line PEO1 (hypertriploid). The probes from this region were absent on two copies of chromosome 6, but hybridized to two or three markers. In cell line 59M (hyperdiploid) an interstitial deletion proximal to q24 was detected in one chromosome 6. We conclude that it is very likely that a gene or genes localized in bands 6q26-27, and perhaps in the region proximal to 6q24, play a critical role in the development or progression of ovarian carcinoma.
Adenocarcinoma↗
Detection of dimeric inhibin throughout the human menstrual cycle by two-site enzyme immunoassay.
OBJECTIVE: We have developed and validated a two-site immunoassay for the measurement of dimeric inhibin in plasma and subsequently measured dimeric inhibin levels in plasma through the normal female menstrual cycle. DESIGN: Recombinant inhibin added to plasma samples was quantitatively recovered in both follicular and luteal phase, and serial dilutions of samples were tested for parallelism to similar dilutions of recombinant 32 kDa inhibin. Daily samples were assayed from four women through a menstrual cycle. PATIENTS: (a) Four groups of six women who (i) were in the follicular phase of a normal menstrual cycle, (ii) were in the luteal phase of a normal menstrual cycle, (iii) were post-menopausal and (iV) who had received hMG to induce superovulation. (b) Four healthy female volunteers aged 25-33. RESULTS: Post-menopausal women had less than 2 ng/l of inhibin whereas six women treated with hMG had dimeric inhibin concentrations up to 1125 ng/l. During the early follicular phase, at the time of onset of menstruation, extremely low levels of dimeric inhibin were found (3.4 ng/l (CI 2.2-5.0)) while in the late follicular phase, there was a marked increase in dimeric inhibin concentration. The concentration of dimeric inhibin was maximal (65.6 ng/l (CI 53.1-81.1)) in the mid-luteal phase. The overall pattern of dimeric inhibin concentration during the menstrual cycle was similar to that observed with previous inhibin assays although the magnitude of change was considerably greater. CONCLUSION: The human ovary, in particular the corpus luteum, secretes significant amounts of dimeric and therefore biologically active inhibin.
Adult↗
NEUROSECRETION OF CRUSTACEAN HYPERGLYCEMIC HORMONE EVOKED BY AXONAL STIMULATION OR ELEVATION OF SALINE K+ CONCENTRATION QUANTIFIED BY A SENSITIVE IMMUNOASSAY METHOD
A sandwich-type enzyme-linked immunosorbent assay (ELISA) was utilized to quantify crustacean hyperglycemic hormone (as Carcinus maenas equivalents) released by single X-organ­sinus gland systems of the crab Cardisoma carnifex during continuous perifusion. Basal rates of secretion (20­60 pg min-1) were stable for at least 4 h. Electrical stimulation (600 stimuli in 5 min) of the axon tract increased secretion two- to threefold, but only if it resulted in neural activity that was propagated to the terminals of the sinus gland. No difference was observable when stimuli were given repetitively or as a series of trains. Perifusion with saline having ten times the normal K+ concentration augmented secretion by as much as fivefold. Augmented secretion of crustacean hyperglycemic hormone evoked by either electrical or K+ stimulation appeared abruptly but declined slowly (over tens of minutes) after stimulation was stopped. K+-evoked secretion of crustacean hyperglycemic hormone was maintained without decrement for at least 1 h. Basal secretion increased in saline from which Ca2+ had been omitted, but decreased in saline containing Mn2+. Neither electrical stimulation nor high [K+] augmented secretion in Ca2+-deficient saline or if Mn2+ was present. Introduction of Mn2+ during K+-evoked secretion immediately reduced release to unstimulated levels; secretion resumed promptly upon removal of Mn2+. Tetrodotoxin reversibly blocked both electrical and secretory responses to axonal stimulation, but it did not block basal or K+-evoked secretion. Release of crustacean hyperglycemic hormone by isolated axon terminals was augmented two- to threefold by perifusion with saline having ten times the normal K+ concentration. The responses were similar to those of the intact systems, having a rapid onset, well-maintained secretion and a long 'tail' of secretion after removal of the K+ stimulus.
Journal Article↗
The contribution of a hidden male factor to unexplained infertility.
OBJECTIVE: To assess sperm function in patients with unexplained infertility in comparison with normal fertile men. DESIGN: Prospective study. SETTING: Infertility outpatient clinic and donor insemination program, University Department of Obstetrics and Gynecology at the Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Nineteen patients with unexplained infertility and nineteen normal fertile men from a donor insemination program. MAIN OUTCOME MEASURES: Monitoring of reactive oxygen species generation; computerized assessment of the hyperactivated motility pattern of the spermatozoa under capacitating conditions, with and without the addition of follicular fluid (FF); evaluation of sperm-zona pellucida (ZP) binding. RESULTS: Reactive oxygen species generation was not significantly different between the study and control group. Follicular fluid-induced hyperactivation (HA) was significantly lower in patients with unexplained infertility than in the donors, but no difference was found comparing spontaneous HA (without FF) between the two groups. Follicular fluid-induced HA was completely absent in 39% of infertile men and only one fertile man. A low sperm-ZP binding ratio (< or = 0.3) was observed in 28% (5/18) of patients with unexplained infertility. In all, nine infertile men (47%) had 0% FF-induced HA and/or low sperm-ZP binding ratio. CONCLUSIONS: Assessing FF-induced HA and sperm-ZP binding may have clinical significance in distinguishing a subgroup of men with unexplained infertility with sperm function abnormalities in which the fertilizing capacity of the spermatozoa might be reduced. These patients cannot be identified by the conventional semen analysis. Both tests may also be useful in planning the appropriate treatment for couples with unexplained infertility.
Female↗