Angiogenesis, vascular endothelial growth factor and the endometrium.
(1/195)
Angiogenesis is an essential component of endometrial renewal. The formation of new vessels depends on interactions between various hormones and growth factors, and this review focuses on the expression of angiogenic growth factors in the human endometrium. Peptide and non-peptide angiogenic factors interact during endometrial renewal, including epidermal growth factor (EGF), transforming growth factors (e.g. TGF-beta), platelet-derived endothelial growth factor/thymidine phosphorylase (PD-ECGF/TP), tumour necrosis growth factors and vascular endothelial growth factor (VEGF). Their role in the proliferation and migration of endothelial cells from pre-existing vessels is described, concentrating on VGEF and its receptors (VEG-R1 and -R2), and the fibroblast growth factor (FGF) family. The actions of the products of the VEGF gene are outlined, and the hormonal and non-hormonal control of their localization in the human endometrium and biological actions on vasculature and coagulation are described. Finally, the role of VEGF in menorrhagia is assessed. (+info)
SF 36 health survey questionnaire: I. Reliability in two patient based studies.
(2/195)
OBJECTIVE: To assess the reliability of the SF 36 health survey questionnaire in two patient populations. DESIGN: Postal questionnaire followed up, if necessary, by two reminders at two week intervals. Retest questionnaires were administered postally at two weeks in the first study and at one week in the second study. SETTING: Outpatient clinics and four training general practices in Grampian region in the north east of Scotland (study 1); a gastroenterology outpatient clinic in Aberdeen Royal Hospitals Trust (study 2). PATIENTS: 1787 patients presenting with one of four conditions: low back pain, menorrhagia, suspected peptic ulcer, and varicose veins and identified between March and June 1991 (study 1) and 573 patients attending a gastroenterology clinic in April 1993. MAIN MEASURES: Assessment of internal consistency reliability with Cronbach's alpha coefficient and of test-retest reliability with the Pearson correlation coefficient and confidence interval analysis. RESULTS: In study 1, 1317 of 1746 (75.4%) correctly identified patients entered the study and in study 2, 549 of 573 (95.8%). Both methods of assessing reliability produced similar results for most of the SF 36 scales. The most conservative estimates of reliability gave 95% confidence intervals for an individual patient's score difference ranging from -19 to 19 for the scales measuring physical functioning and general health perceptions, to -65.7 to 65.7 for the scale measuring role limitations attributable to emotional problems. In a controlled clinical trial with sample sizes of 65 patients in each group, statistically significant differences of 20 points can be detected on all eight SF 36 scales. CONCLUSIONS: All eight scales of the SF 36 questionnaire show high reliability when used to monitor health in groups of patients, and at least four scales possess adequate reliability for use in managing individual patients. Further studies are required to test the feasibility of implementing the SF 36 and other outcome measures in routine clinical practice within the health service. (+info)
SF 36 health survey questionnaire: II. Responsiveness to changes in health status in four common clinical conditions.
(3/195)
OBJECTIVE: To assess the responsiveness of the SF 36 health survey questionnaire to changes in health status over time for four common clinical conditions. DESIGN: Postal questionnaires at baseline and after one year's follow up, with two reminders at two week intervals if necessary. SETTING: Clinics and four training general practices in Grampian region in the north east of Scotland. PATIENTS: More than 1,700 patients aged 16 to 86 years with one of four conditions: low back pain, menorrhagia, suspected peptic ulcer, and varicose veins; and a random sample of 900 members of the local general population for comparison. MAIN MEASURES: A transition question measuring change in health and the eight scales of the SF 36 health survey questionnaire; standardised response means (mean change in score for a scale divided by the standard deviation of the change in scores) used to quantify the instrument's responsiveness to changes in perceived health status, and comparison of patient scores at baseline and follow up with those of the general population. RESULTS: The response rate exceeded 75% in a patient population. Changes across the SF 36 questionnaire were associated with self reported changes in health, as measured by the transition question. The questionnaire showed significant improvements in health status for all four clinical conditions, whether in referred or non-referred patients. For patients with suspected peptic ulcer and varicose veins the SF 36 profiles at one year approximate to the general population. CONCLUSIONS: These results provide the first evidence of the responsiveness of the SF 36 questionnaire to changes in perceived health status in a patient population in the United Kingdom. (+info)
Making sense of ambiguity: evaluation in internal reliability and face validity of the SF 36 questionnaire in women presenting with menorrhagia.
(4/195)
OBJECTIVE: To determine the face validity and internal reliability of the short form 36 (SF 36) health survey questionnaire in women presenting with menorrhagia. DESIGN: Postal survey of women recruited by their general practitioners followed by interviews of a selected subsample. PATIENTS: 348 women who had consulted their general practitioner with excessive menstrual bleeding and completed questionnaires after treatment. 49 women selected from this group were interviewed in depth about their health status, and requested to complete the SF 36 questionnaire. MAIN MEASURES: Subjective accounts of functioning and wellbeing as measured by the eight scales of the SF 36 questionnaire. RESULTS: Data from the postal survey indicated that the inverted question markgeneral health perceptions inverted question mark and inverted question markmental health inverted question mark scales of the SF 36 questionnaire had lower internal reliability coefficients than documented elsewhere. In the follow up interviews several questions on the SF 36 questionnaire were commented on as inappropriate or difficult to answer for patients with heavy menstrual bleeding. CONCLUSIONS: Some questions on the SF 36 questionnaire were difficult to answer for this group of patients. Such problems can adversely effect the validity of the measure. It is suggested that comments of patients upon measures such as the SF 36 questionnaire could both determine the appropriateness of such measures for given studies and influence questionnaire design. (+info)
Relaxin stimulates expression of vascular endothelial growth factor in normal human endometrial cells in vitro and is associated with menometrorrhagia in women.
(5/195)
Although the role of the reproductive hormone, relaxin, in rodents is well documented, its potential contribution to human reproduction is less well defined. In this study, we examine the effects of relaxin on human endometrial cells in vitro and describe the clinical effects of relaxin on menstrual flow in women. In cultured endometrial cells, relaxin specifically induces the expression of an angiogenic agent, vascular endothelial growth factor (VEGF). cAMP is implicated as a second messenger involved in VEGF stimulation. VEGF expression is temporally regulated in the endometrium, and our results suggest that relaxin, which is secreted by the corpus luteum and is present in the endometrium during the menstrual cycle and pregnancy, may be involved in regulating endometrial VEGF expression. Relaxin was recently tested in a clinical trial for efficacy in the treatment of progressive systemic sclerosis, and was administered at levels up to 10 times higher than that measured during pregnancy. The most frequent relaxin-related adverse event reported during the course of the study was the onset of menometrorrhagia, defined in this study as heavier-than-usual or irregular menstrual bleeding. The intensification of menstrual flow observed in these patients is consistent with the hypothesis that relaxin mediates neovascularization of the endometrial lining. (+info)
Randomised controlled trial of educational package on management of menorrhagia in primary care: the Anglia menorrhagia education study.
(6/195)
OBJECTIVE: To determine whether an educational package could influence the management of menorrhagia, increase the appropriateness of choice of non-hormonal treatment, and reduce referral rates from primary to secondary care. DESIGN: Randomised controlled trial. SETTING: General practices in East Anglia. SUBJECTS: 100 practices (348 doctors) in primary care were recruited and randomised to intervention (54) and control (46). INTERVENTIONS: An educational package based on principles of "academic detailing" with independent academics was given in small practice based interactive groups with a visual presentation, a printed evidence based summary, a graphic management flow chart, and a follow up meeting at 6 months. OUTCOME MEASURES: All practices recorded consultation details, treatments offered, and outcomes for women with regular heavy menstrual loss (menorrhagia) over 1 year. RESULTS: 1001 consultation data sheets for menorrhagia were returned. There were significantly fewer referrals (20% v 29%; odds ratio 0. 64; 95% confidence interval 0.41 to 0.99) and a significantly higher use of tranexamic acid (odds ratio 2.38; 1.61 to 3.49) in the intervention group but no overall difference in norethisterone treatment compared with controls. There were more referrals when tranexamic acid was given with norethisterone than when it was given alone. Those practices reporting fewer than 10 cases showed the highest increase in prescribing of tranexamic acid. CONCLUSIONS: The educational package positively influenced referral for menorrhagia and treatment with appropriate non-hormonal drugs. (+info)
Menorrhagia and uterine artery blood flow.
(7/195)
Menorrhagia is a significant problem in women of reproductive age. In half of the cases no specific aetiology is known. Vascular factors play a role but remain poorly understood. We chose to study whether any association exists between the flow impedance of uterine arteries and the amount of menstrual blood loss. The study population consisted of 60 spontaneously menstruating 35- to 49-year-old women without endometrial hyperplasia, polyps, or submucous fibroids. The pulsatility index (PI) from uterine arteries, arcuate arteries, and radial arteries was measured by transvaginal colour Doppler. Menstrual blood loss was measured by the alkaline haematin method. A significant inverse correlation was found between uterine artery PI and the amount of menstrual blood loss, suggesting that women with lower uterine flow impedance bleed more. A regression model confirmed that this association was specific and not explained by uterine size, fibroids or any other of the 11 potential confounders included in the model. The correlation between uterine artery PI and amount of menstrual blood loss suggests that vascular factors may be involved in the pathogenesis of menorrhagia. (+info)
Nitric oxide synthase expression and steroid regulation in the uterus of women with menorrhagia.
(8/195)
Menorrhagia (excessive menstrual bleeding) is a common clinical problem of unknown aetiology. The free-radical and vasodilator nitric oxide (NO) relaxes the myometrial smooth muscle and is a strong candidate for the cause of excessive blood loss in menorrhagic patients. The aim of this study was to measure NO production in women with and without menorrhagia to detect nitric oxide synthase (NOS) isoforms in uterine cells and to investigate any steroid effects on myometrial NOS expression. We showed for the first time that menorrhagic endometrium produces significantly higher amounts of NOx (the sum of NO(2-) and NO(3-)) than control endometrium (P < 0.01). Inducible NOS (iNOS) protein was detected by immunoblotting in endometrial and myometrial tissue extracts. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) experiments revealed an induction of myometrial smooth muscle endothelial NOS (eNOS) expression by progesterone and 17beta-oestradiol, while myometrial iNOS expression was unaffected by steroid hormones. These results are consistent with the hypothesis that NO plays a role in excessive menstrual bleeding and provide the first evidence on steroid regulation of eNOS in the human non-pregnant uterus. (+info)