Search PubMed⌕ Search

Biomedical subjects

L Regan

Publications and source records attributed to L Regan.

At least 19 recordsLinked to original sources
PubMed2006

Placental pathology of recurrent spontaneous abortion: the role of histopathological examination of products of conception in routine clinical practice: a mini review.

BACKGROUND: Histopathological examination of products of conception from miscarriages is part of routine clinical practice. The extent of additional clinically relevant information provided by this investigation in the setting of recurrent spontaneous abortion remains uncertain. METHODS: Review of the literature was performed to identify studies reporting on findings of histological examination of routinely obtained products of conception in the setting of recurrent spontaneous abortion. The initial search identified 312 potential references, but 300 were excluded on further examination due to lack of data on specific histopathological findings in routine products of conception specimens from patients with recurrent spontaneous abortion. The 12 included studies indicated that such examination may identify hydatidiform moles, villous dysmorphic features suggesting fetal aneuploidy, chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition and impaired trophoblast invasion. However, in most cases, morphological assessment cannot reliably determine the cause of the miscarriage or distinguish recurrent from sporadic miscarriage. Studies reporting on the use of additional immunohistochemical methods do not currently provide additional clinically useful diagnostic or prognostic information. CONCLUSION: Routine histological examination of products of conception in the setting of recurrent spontaneous abortion can provide important clinical information in a minority of cases.

Abortion, Habitual↗
PubMed2006

Magnetic resonance guided focused ultrasound surgery of uterine fibroids--the tissue effects of GnRH agonist pre-treatment.

OBJECTIVE: The purpose of this study was to determine the ablative effect of magnetic resonance guided focused ultrasound (MRgFUS) on fibroid tissue following the administration of gonadotrophin releasing hormone (GnRH) agonist. STUDY DESIGN: Fifty women with clinically symptomatic uterine fibroids were treated. Those with uterine diameter of 10 cm or greater were given 3 months pre-treatment with GnRH agonists. Data regarding number of ultrasound sonications, Joules of energy delivered and volume of thermal destruction was recorded. RESULTS: Twenty-seven subjects were given GnRH agonist therapy before MRgFUS and 23 women underwent MRgFUS without pre-treatment. All patients in both study groups completed MR guided FUS as an outpatient procedure with no device related adverse events reported. In the group of women who received GnRH agonists, the volume of ablation was significantly larger than that in the control group (0.06 cm3 versus 0.03 cm3, P<0.05), per Joule of energy applied. CONCLUSION: The use of GnRH agonists potentiates the thermal effects of MRgFUS in women undergoing treatment of uterine fibroids.

Adult↗
PubMed2006

Genetic thrombophilic mutations among couples with recurrent miscarriage.

BACKGROUND: Some cases of recurrent first trimester miscarriage (RM)-the loss of three or more consecutive pregnancies at <12 weeks' gestation-have a thrombotic aetiology. METHODS: We determined (i) the prevalence of three thrombophilic mutations [factor V Leiden (FVL), prothrombin G20210A (PTG) and methylenetetrahydrofolate reductase (MTHFR) C677T] amongst 357 Caucasian couples with RM and 68 parous Caucasian couples with no history of miscarriage and (ii) the prospective outcome of untreated pregnancies amongst couples with RM in which either partner carried a thrombophilic mutation. RESULTS: The allele frequencies of FVL (2%), PTG (2%) and MTHFR C677T (31%) were similar between cases and controls. The prevalence of multiple thrombophilic mutations (greater than one mutation) was also similar between cases and controls. Amongst couples in whom either partner carried greater than one thrombophilic allele, the relative risk of miscarriage in a future untreated pregnancy was 1.9 (95% confidence interval, 1.3-2.8) compared with those couples who carried no thrombophilic mutation. CONCLUSION: The prevalence of thrombophilic mutations is similar in couples with RM and parous controls. In couples with RM, multiple genetic thrombophilic mutations in either partner significantly increases the risk of miscarriage in a subsequent pregnancy.

Abortion, Habitual↗
PubMed2006

Glucose production in the human placenta.

Glucose transfer from mother to fetus by placental facilitated diffusion is the dominant mechanism by which the fetus acquires glucose. In small for gestational age pregnancies, fetal glucose concentrations tend to be lower than normal and this persists following delivery. GLUT1 is the major glucose transporter in human placenta but there is no evidence of GLUT1 deficiency as a cause of the lower fetal glucose concentration in small for gestational age pregnancy. The physiological and pathological roles of the other glucose transporters (and there are 14 currently described) are unknown. In recent years, the possibility has been raised that the placenta is itself capable of supplying glucose for fetal needs. This hypothesis derived from glucose isotope studies in normal pregnancy, where dilution of glucose isotope was demonstrated in blood samples taken from the fetal circulation during intravenous infusion of glucose isotope in the mother. Although other gluconeogenic enzymes were known to be present, the placenta was previously considered incapable of glucose secretion because it lacked functional glucose-6-phosphatase. Recent studies, however, have suggested that specific glucose-6-phosphatase may be present in placenta but it may be the product of a different gene from conventional hepatic glucose-6-phosphatase. The presence of the specific transporters necessary for glucose-6-phosphatase activity is currently being investigated. The role of placental glucose secretion in normal and growth-restricted pregnancies is an area of current study.

Amino Acid Sequence↗
PubMed2006

Gonadotrophin-releasing hormone and magnetic-resonance-guided ultrasound surgery for uterine leiomyomata.

OBJECTIVE: Magnetic-resonance-guided focused ultrasound is a novel, noninvasive technique of thermoablation for uterine leiomyomata. The hypothesis of this study was that pretreatment of leiomyomata with gonadotrophin-releasing hormone (GnRH) agonists would allow effective treatment of larger uterine leiomyomata, increasing the number of women who could benefit from this technique. METHODS: We report a prospective study of women with leiomyomata in excess of 10 cm in diameter who received GnRH agonist before magnetic-resonance-guided focused ultrasound treatment. Eligible participants were recruited from the gynecology outpatient clinics. Entry criteria were a minimal leiomyoma symptom severity score and confirmation of uterine dimensions based on screening magnetic resonance imaging. These women received a 3-month course of GnRH agonists followed by magnetic-resonance-guided focused ultrasound treatment. The primary outcome measurement was reported change in symptom severity score as judged by the Uterine Fibroid Symptom and Quality of Life questionnaire. Comparison was made at enrollment, treatment, and at 3, 6, and 12 months posttreatment. A secondary outcome was the measured change in target leiomyoma volume. RESULTS: Forty-nine women were enrolled in the study. There was a 45% reduction in median symptom severity score at 6 months and 48% at 12 months posttreatment, with 83% of women achieving at least a 10-point reduction in symptom scoring at 6 months and 89% at 12 months (P < .001). There was an average reduction in target leiomyoma volume of 21% overall at 6 months (P < .001) and 37% at 12 months (P < .001). No serious infective complications or emergency operative interventions were recorded. CONCLUSION: The use of GnRH agonist therapy before magnetic-resonance-guided focused ultrasound improves the thermoablative treatment effect. LEVEL OF EVIDENCE: II-3.

Adult↗
PubMed2006

Thrombophilia in pregnancy: a systematic review.

Growing evidence suggests that thrombophilia is associated with venous thromboembolism (VTE) and adverse pregnancy outcomes. However, methodological limitations have made it difficult to obtain a clear overview of the overall risks. We conducted a systematic review to determine the risk of VTE and adverse pregnancy outcomes associated with thrombophilia in pregnancy. The effectiveness of prophylactic interventions during pregnancy was also evaluated. Major electronic databases were searched, relevant data abstracted and study quality assessed by two independent reviewers. Odds ratios (ORs) stratified by thrombophilia type were calculated for each outcome. A total of 79 studies were included in our review. The risks for individual thrombophilic defects were determined for VTE (ORs, 0.74-34.40); early pregnancy loss (ORs, 1.40-6.25); late pregnancy loss (ORs, 1.31-20.09); pre-eclampsia (ORs, 1.37-3.49); placental abruption (ORs, 1.42-7.71) and intrauterine growth restriction (ORs, 1.24-2.92). Low-dose aspirin plus heparin was the most effective in preventing pregnancy loss in thrombophilic women (OR, 1.62). Our findings confirm that women with thrombophilia are at risk of developing VTE and complications in pregnancy. However, despite the increase in relative risk, the absolute risk of VTE and adverse outcomes remains low. There is also a lack of controlled trials of antithrombotic intervention to prevent pregnancy complications. Thus, at present, universal screening for thrombophilia in pregnancy cannot be justified clinically.

Female↗
PubMed2006

Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study.

OBJECTIVES: To assess the risk of clinical complications associated with thrombophilia in three high-risk patient groups: women using oral oestrogen preparations, women during pregnancy and patients undergoing major orthopaedic surgery. To assess the effectiveness of prophylactic treatments in preventing venous thromboembolism (VTE) and adverse pregnancy outcomes in women with thrombophilia during pregnancy and VTE in patients with thrombophilia, undergoing major orthopaedic surgery. To evaluate the relative cost-effectiveness of universal and selective VTE history-based screening for thrombophilia compared with no screening in the three high-risk patient groups. DATA SOURCES: Electronic databases including MEDLINE, EMBASE, and four other major databases were searched up to June 2003. REVIEW METHODS: In order to assess the risk of clinical complications associated with thrombophilia, a systematic review of the literature on VTE and thrombophilia in women using oral oestrogen preparations and patients undergoing major orthopaedic surgery; and studies of VTE and adverse obstetric complications in women with thrombophilia during pregnancy was carried out. Meta-analysis was used to calculate pooled odds ratios (ORs) associated with individual clinical outcomes, stratified by thrombophilia type and were calculated for each patient group. To assess the effectiveness of prophylaxis, a systematic review was carried out on the use of prophylaxis in the prevention of VTE and pregnancy loss in pregnant women with thrombophilic defects and the use of thromboprophylaxis in the prevention of VTE in patients with thrombophilia undergoing major elective orthopaedic surgery. Relevant data were summarised according to the patient groups and stratified according to the types of prophylaxis. A narrative summary was provided; where appropriate, meta-analysis was conducted. An incremental cost-effectiveness analysis was then carried out, from the perspective of the NHS in the UK. A decision analytical model was developed to simulate the clinical consequences of four thrombophilia screening scenarios. Results from the meta-analyses, information from the literature and results of two Delphi studies of clinical management of VTE and adverse pregnancy complications were incorporated into the model. Only direct health service costs were measured and unit costs for all healthcare resources used were obtained from routinely collected data and the literature. Cost-effectiveness was expressed as incremental cost-effectiveness ratios (ICERs); an estimate of the cost per adverse clinical complication prevented, comparing screening with no screening, were calculated for each patient group. RESULTS: In the review of risk of clinical complications, 81 studies were included, nine for oral oestrogen preparations, 72 for pregnancy and eight for orthopaedic surgery. For oral contraceptive use, significant associations of the risk of VTE were found in women with factor V Leiden (FVL); deficiencies of antithrombin, protein C, or protein S, elevated levels of factor VIIIc; and FVL and prothrombin G20210A. For hormone replacement therapy (HRT), a significant association was found in women with FVL. The highest risk in pregnancy was found for FVL and VTE, in particular, homozygous carriers of this mutation are 34 times more likely to develop VTE in pregnancy than non-carriers. Significant risks for individual thrombophilic defects were also established for early, recurrent and late pregnancy loss; preeclampsia; placental abruption; and intrauterine growth restriction. Significant associations were found between FVL and high factor VIIIc and postoperative VTE following elective hip or knee replacement surgery. Prothrombin G20210A was significantly associated with postoperative pulmonary embolism. However, antithrombin deficiency, MTHFR and hyperhomocysteinaemia were not associated with increased risk of postoperative VTE. In the review of the effectiveness of prophylaxis, based on available data from eight studies, low-dose aspirin and heparin was found to be the most effective in preventing pregnancy loss in thrombophilic women during pregnancy, while aspirin alone was the most effective in preventing minor bleeding. All the studies on thrombophilia and major elective orthopaedic surgery included in the review of risk complications were also used in the review of the effectiveness of thromboprophylaxis. However, there were insufficient data to determine the relative effectiveness of different thromboprophylaxis in preventing VTE in this patient group. For the cost-effectiveness analysis, of all the patient groups evaluated, universal screening of women prior to prescribing HRT was the most cost-effective (ICER pound6824). In contrast, universal screening of women prior to prescribing combined oral contraceptives was the least cost-effective strategy (ICER pound202,402). Selective thrombophilia screening based on previous personal and/or family history of VTE was more cost-effective than universal screening in all the patient groups evaluated. CONCLUSIONS: Thrombophilia is associated with increased risks of VTE in women taking oral oestrogen preparations and patients undergoing major elective orthopaedic surgery, and of VTE and adverse pregnancy outcomes in women with thrombophilia during pregnancy. There is considerable difference in the magnitude of the risks among different patient groups with different thrombophilic defects. In women who are on combined oral contraceptives, the OR of VTE among those who are carriers of the FVL mutation was 15.62 (95% confidence interval 8.66 to 28.15). However, in view of the prevalence of thrombophilia and the low prevalence of VTE in non-users of combined oral contraceptives, the absolute risk remains low. Significant risks for VTE and adverse pregnancy outcomes have been established with individual thrombophilic defects. Thrombophilic defects including FVL, high plasma factor VIIIc levels and prothrombin G20210A are associated with the occurrence of postoperative VTE in elective hip or knee replacement therapy. These associations are observed in patients who were given preoperative thromboprophylaxis and are, therefore, of clinical significance. Universal thrombophilia screening in women prior to prescribing oral oestrogen preparations, in women during pregnancy and in patients undergoing major orthopaedic surgery is not supported by current evidence. The findings from this study show that selective screening based on prior VTE history is more cost-effective than universal screening. Large prospective studies should be undertaken to refine the risks and establish the associations of thrombophilias with VTE among hormone users and in patients undergoing orthopaedic surgery. The relative value of a thrombophilia screening programme to other healthcare programmes needs to be established.

Cost-Benefit Analysis↗
PubMed2005

Aberrations of early trophoblast differentiation predispose to pregnancy failure: lessons from the anti-phospholipid syndrome.

OBJECTIVES: The epithelium of the human placenta comprises an inner cytotrophoblast (CT) which proliferates and fuses with the outer differentiated syncytiotrophoblast (ST). Turnover has been studied focussing on second and third trimester placentas but with a paucity of data describing the normal first trimester trophoblast. The aim of this study was to compare the nuclear CT:ST ratio in normal and pathological pregnancy and thus establish the relationship between cytotrophoblast and syncytiotrophoblast nuclear number during early gestation. METHODS: Archival first trimester material from placentas from healthy pregnancy and recurrent miscarriage (anti-phospholipid syndrome) was stained with H&E, cytokeratin-7 and Mib-1. The area of trophoblast as a fraction of total villous area was calculated and the number of sectioned cytotrophoblast and syncytiotrophoblast nuclei as well as the number of proliferating cytotrophoblast was evaluated. RESULTS: Normal features of trophoblast development during the first trimester (rise in trophoblast area, increase in number of syncytiotrophoblast nuclei, increase in number of proliferating cytotrophoblast, decrease in the nuclear CT:ST ratio) are absent/reversed in tissues from recurrent miscarriage (decreasing trophoblast area, constant number of syncytiotrophoblast nuclei, decreasing number of proliferating trophoblast, constant nuclear CT:ST ratio). CONCLUSIONS: Proliferation of cytotrophoblast in early gestation provides a pool of trophoblast stem cells critical for ongoing placental development. Premature cytotrophoblast differentiation in favour of syncytial fusion results in deficiencies of cytotrophoblast and rarification of villous trophoblast. Abnormal trophoblast differentiation in early gestation may be due to a premature onset of maternal perfusion of the placenta and may be a likely antecedent for conditions associated with failure of placentation such as recurrent miscarriage.

Abortion, Habitual↗
PubMed2005

Term preeclampsia is associated with minimal histopathological placental features regardless of clinical severity.

Preeclampsia (PET) is a serious complication of pregnancy, which is associated with uteroplacental disease and reduced uteroplacental perfusion. One of the histological features in placentas from pregnancies complicated by PET is infarction, representing focal severe uteroplacental ischaemia. This study examines the relationship between gestation at induced delivery and the prevalence of placental infarction using a placental pathology database to identify induced or operative deliveries on the basis of severe PET. The clinical and pathological findings were reviewed. Thirty-seven cases were identified, (4.9% of all placentas submitted). In 16 (43%), non-peripheral significant infarcts were identified histologically, including 13/20 (65%) requiring delivery before 34 weeks' compared to 3/17 (17%) requiring delivery > or = 34 weeks (z=2.9, P<0.01). Histological infarction is common in placentas from pregnancies complicated by severe PET but the prevalence is significantly greater in cases requiring delivery at earlier gestations, even when similar clinical indications for delivery are applied.

England↗
PubMed2004

A randomized controlled trial comparing medical and expectant management of first trimester miscarriage.

BACKGROUND: We aimed to determine whether outpatient treatment of miscarriage with vaginal misoprostol is more effective than expectant management in reducing the need for surgical evacuation of retained products of conception (ERPC). METHODS: Of 131 eligible women with first trimester miscarriage, 104 agreed to randomization to either 600 microg misoprostol or placebo intravaginally. They were assessed the following day and administered a second dose of their allocated treatment if miscarriage was not complete. Those not successful after two doses were seen on day 7, and, if miscarriage was not complete, an ERPC was performed. RESULTS: The success rate of medical management was 88.5% (46/52) compared with 44.2% (23/52) for expectant management. There was no significant difference in success rate (100 versus 85.7%) in women treated with an incomplete miscarriage. Women with early pregnancy failure had a success rate of 87% with misoprostol compared with 29% with expectant management [odds ratio (OR) 15.96; 95% confidence interval (CI) 5.26, 48.37]. The complete miscarriage rate was achieved quicker in the medical group than the expectant group by day 1 (32.7 versus 5.8%) and by day 2 (73.1 versus 13.5%) of treatment. There were no differences in side-effects, bleeding duration, analgesia use, pain score and satisfaction with treatment. Women in the expectant group made more outpatient visits (5.06 versus 4.44%; OR = -0.62, 95% CI -1.04, -0.19). More women in the medical group (90.4 versus 73.1%; OR 1.26, 95% CI 1.05, 1.50) would elect the same treatment in the future. CONCLUSIONS: Medical management using 600 microg misoprostol vaginally is more effective than expectant management of early pregnancy failure. Misoprostol did not increase the side-effect profile and patient acceptability was superior to expectant management.

Abortifacient Agents, Nonsteroidal↗
PubMed2003

Reproducibility of three-dimensional ultrasound diagnosis of congenital uterine anomalies.

OBJECTIVE: To examine the reproducibility of the diagnosis of congenital uterine anomalies and the repeatability of measurements of uterine cavity dimensions using three-dimensional (3D) ultrasound. METHODS: The reproducibility of diagnosis of congenital uterine anomalies was examined by re-slicing stored 3D ultrasound volumes. Each data set was evaluated by two independent observers. Assessment of uterine morphology was performed in a standardized plane, with the interstitial portions of the Fallopian tubes used as reference points. Additionally, in 35 cases of congenital uterine anomalies the width of the uterine cavity (W), fundal distortion (F) and the length of unaffected uterine cavity (C) were measured. Intraobserver and interobserver variabilities were evaluated by each observer performing all three measurements twice. RESULTS: Eighty-three 3D ultrasound volumes were examined. Both operators classified 27 uteri as normal, 33 as arcuate, 19 as subseptate and three as unicornuate. A single case of uterine anomaly was described as arcuate uterus by one operator and subseptate by another (kappa 0.97). The intraobserver variability for each of the three measurements (W, F and C) was satisfactory with limits of agreement ranging from +/-1.43 to +/-2.51 mm. The examination of the interobserver variability showed no significant differences between the two observers (F = 0.484, P > 0.05). CONCLUSION: 3D ultrasound is a reproducible method for the diagnosis of congenital uterine anomalies and for the measurement of uterine cavity dimensions.

Female↗
PubMed2003

Placental pathology, antiphospholipid antibodies, and pregnancy outcome in recurrent miscarriage patients.

OBJECTIVE: To examine whether there are characteristic histological features in placentas from ongoing pregnancies of patients with a history of recurrent miscarriage, with and without primary antiphospholipid antibody syndrome, in relation to clinical pregnancy outcome. METHODS: Patients attending a recurrent miscarriage clinic were investigated and treated according to an established protocol. One hundred twenty-one consecutive patients achieving a potentially viable pregnancy (at least 24 completed weeks' gestation), including 60 primary antiphospholipid antibody syndrome-positive cases and 61 primary antiphospholipid antibody syndrome-negative cases were included. After delivery, placental pathologic examination was carried out by a pathologist unaware of the clinical details. Histological sections were examined by two pathologists independently. Pregnancy outcome and placental findings were reviewed in relation to the maternal antiphospholipid antibody status. RESULTS: Pregnancy outcome was similar in primary antiphospholipid antibody syndrome-positive and primary antiphospholipid antibody syndrome-negative groups regarding gestation at delivery and antepartum obstetric complications. Several histological placental abnormalities were identified in both groups, but most pregnancies were clinically uncomplicated, with no significant placental abnormalities. In cases with pregnancy complications, the placental pathology was primarily that of uteroplacental vasculopathy, such as placental infarction and preeclampsia, but there were no specific placental lesions or patterns of abnormalities characteristic of primary antiphospholipid antibody syndrome-positive patients. A small subgroup of primary antiphospholipid antibody syndrome-positive patients may be at increased risk of development of maternal floor infarction or massive perivillus fibrin deposition. CONCLUSION: There are no specific histopathologic placental abnormalities characteristic of treated patients with antiphospholipid antibody syndrome and poor reproductive history, but complications of uteroplacental disease are more common.

Abortion, Habitual↗
PubMed2003

Effect of tumour necrosis factor-alpha and interleukin 1beta on endothelium-dependent relaxation in rat mesenteric resistance arteries in vitro.

1. Pre-eclampsia is associated with elevated proinflammatory cytokine levels and endothelial dysfunction. This study examined the effect of two cytokines, tumour necrosis factor-alpha (TNF) and interleukin-1beta (IL-1) on endothelium-dependent relaxation in response to acetylcholine (ACH), bradykinin (BK) and histamine (HIS) in rat mesenteric small arteries in vitro. 2. Rat mesenteric arteries were mounted in an isometric myograph. Tone was induced with phenylephrine (PE) or a depolarizing solution containing 80 mM KCl (K(80)). Relaxation was measured in response to ACH, BK, HIS and sodium nitroprusside (SNP), an endothelium-independent relaxant. Inhibition of NO synthase by a combination of N(omega)-monomethyl-L-arginine (L-NMMA) and N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly inhibited relaxation in response to ACH and BK. Addition of an inhibitor of cyclooxygenase, indomethacin, had no additional effect when added to L-NMMA and L-NAME. Inhibition of endothelium-derived hyperpolarizing factor (EDHF) by K(80) partially reduced responses to ACH and BK. Inhibition of HIS-induced relaxation was more marked with K(80). L-NMMA and L-NAME largely abolished the remaining relaxation to ACH, BK and HIS in arteries contracted with K(80). 3. Preincubation with TNF for 30 min caused an inhibition of relaxation in response to ACH and BK in arteries contracted with PE. Responses to HIS and SNP were not affected by TNF under these conditions. TNF also inhibited ACH-induced relaxation in arteries contracted with K(80). IL-1 had no effect on responses to ACH and the combination of TNF and IL-1 was not more effective than TNF alone. 4. The inhibitory effect of TNF on ACH-induced relaxation was abolished by coincubation with superoxide dismutase (SOD) and was not seen if NO synthase was inhibited by L-NMMA and L-NAME. 5. TNF inhibits the NO-dependent component of endothelium-dependent relaxation in response to ACH and BK, but does not inhibit the EDHF-dependent component. This effect may be attributable to the ability of TNF to increase levels of superoxide anions (O(2)(-)) and the ability of O(2)(-) to inactivate NO. This mechanism could contribute to the endothelial dysfunction seen in situations where TNF is elevated, such as pre-eclampsia.

Acetylcholine↗
PubMed2003

A comparative study of the morphology of congenital uterine anomalies in women with and without a history of recurrent first trimester miscarriage.

BACKGROUND: The true impact of congenital uterine anomalies on reproductive outcomes is unknown. The aim of this study was to examine differences in the morphology of uterine anomalies found in women with and without a history of recurrent miscarriage. METHODS: A total of 509 women with a history of unexplained recurrent miscarriage and 1976 low risk women were examined for the presence of congenital uterine anomalies by three-dimensional ultrasound. The anomalies were classified according to the American Fertility Society classification. In addition, the size of fundal distortion (F) and the length of the remaining uterine cavity (C) were measured to calculate a distortion ratio (F/F+C). The findings were compared with the measurements obtained in low risk women with an incidental finding of uterine anomaly. RESULTS: In all, 121 anomalies were detected in the recurrent miscarriage group and 105 in low risk women. There was no significant difference in relative frequency of various anomalies or depth of fundal distortion between the two groups. However, with both arcuate and subseptate uteri, the length of remaining uterine cavity was significantly shorter (P < 0.01) and the distortion ratio was significantly higher (P < 0.01) in the recurrent miscarriage group. CONCLUSION: The distortion of uterine anatomy is more severe in congenital anomalies, which are found in women with a history of recurrent first trimester miscarriage.

Abortion, Habitual↗
PubMed2003

Thromboelastography, whole-blood haemostasis and recurrent miscarriage.

BACKGROUND: Some cases of recurrent miscarriage have a thrombotic basis. Thromboelastography is a rapid, reproducible test of whole-blood haemostasis. METHODS: Thromboelastography was performed in 494 consecutive, non-pregnant women (median age 35 years; range 21-48) with a history of miscarriages at <12 weeks gestation (median 4; range 3-12) and 55 parous women (median age 33 years; range 20-41) with no history of pregnancy loss. The prospective outcome of untreated pregnancies amongst 108 women with recurrent miscarriage was studied. RESULTS: The maximum clot amplitude (MA) (median 66.0 mm; range 48.0-76.0) was significantly higher and the rate of clot lysis (LY30) (median 2.5%; range 0.5-7.8) significantly lower amongst women with recurrent miscarriage compared with controls (MA 61.5 mm; range 50.0-67.0; P = 0.01; LY30 4.9%; range 2.9-9.7; P = 0.01). The pre-pregnancy MA was significantly higher amongst women who subsequently miscarried (median 66.0 mm; range 54.0-73.0) compared with those whose had a live birth (median 61.7 mm; 48.0-71.5; P < 0.01). A pre-pregnancy MA >or=64 mm has a sensitivity of 68% and specificity of 82% to predict miscarriage. CONCLUSIONS: Thromboelastography identifies a subgroup of women with recurrent miscarriage to be in a prothrombotic state outside of pregnancy. Women in such a state are at increased risk of miscarriage in future untreated pregnancies.

Abortion, Habitual↗
PubMed2002

Pre-eclampsia, antiretroviral therapy, and immune reconstitution.

Antiretrovirals are standard treatment for HIV-1-positive women during pregnancy in the UK, but little is known about maternal or fetal safety. In our cohort study of 214 pregnant women with HIV-1 infection, those who received no antiretroviral therapy had a rate of pre-eclampsia significantly lower (none of 61) than those on triple antiretroviral therapy (8 of 76; odds ratio 15.3, 95% CI 0.9-270, p=0.0087). However, the rate of pre-eclampsia in HIV-1-positive women on treatment did not differ from that in uninfected controls (12 of 214; p=0.2). The association of HIV-1-related immune deficiency with a low rate of pre-eclampsia, and the restoration of this rate in women treated with triple antiretroviral therapy to the expected rate indicates a pivotal role of the immune system in the pathogenesis of pre-eclampsia. The clinical presentation of pre-eclampsia and toxic effects of antiretroviral therapy could overlap and complicate diagnosis and management in these patients.

Adult↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗