bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidative stress in the fetal lamb brain following intermittent umbilical cord occlusion: a path analysis
Authors: Rogers Michael Scott , Murray Henry George , Wang Chi Chiu , Pennell Craig E , Turner Anita , Yan Ping , Pang Calvin C. P. , Chang Allan M. Z.
Published: December 2003

Objective
To evaluate the relative contribution of cord occlusion length intervals between occlusions and experimental duration on oxidative stress in the fetal lamb brain.

Design
Acute, partially exteriorised fetal lambs with intermittent total cord occlusion.

Setting
The Vivarium of Westmead Hospital, University of Sydney, Australia and The Chinese University of Hong Kong.

Main
outcome measures Arterio‐venous differences in the concentration of organic hydroperoxides, measured in paired samples of carotid arterial and jugular venous blood, as an index of oxidative stress in the brain.

Methods
Thirty‐two fetal lambs were exposed to graded hypoxia, induced by intermittent total umbilical cord compression of 30 seconds, 60 seconds and 90 seconds duration, occurring every minute for a total of 27 occlusions over 81 minutes. Three sham experiments were also performed. In addition to organic hydroperoxides, carotid arterial blood samples were also assayed in 15 animals (two sham) for oxygen saturation, pH, hypoxanthine, xanthine and urate concentrations. A causal model for oxidative stress was defined: occlusions leading to hypoxia with a rise in hypoxanthine; reperfusion during intervals between occlusions leading to the accelerated production of xanthine and uric acid and the generation of oxygen free radicals, which in turn, are responsible for the rise in lipid peroxidation. Path analysis was performed to assess the strength of the relationships between these variables and the cord occlusion length, the interval between occlusions and the duration of the experiment.

Results
Sham experiments showed no change in organic hydroperoxide production. Following 30‐second umbilical cord occlusions a sixfold drop in mean organic hydroperoxides was observed between carotid arterial and jugular venous levels. In contrast, following occlusions of 60 seconds duration (or longer) a median 20‐fold increase in organic hydroperoxide production was observed. Path analysis revealed a strong indirect pathway from occlusion length → hypoxanthine → urate and weak positive pathways from oxygen saturation→ urate and from interval between occlusions → urate. After accounting for these pathways reflecting oxidative stress, a strong direct path remained from time from first occlusion → organic hydroperoxide production.

Conclusions
Peroxidation of lipids in the brain occurs under conditions of severe hypoxia and reperfusion associated with intermittent umbilical cord occlusions of 60 seconds or longer. The path analysis supported the causal model as originally defined, with the exception that the indirect pathway via pH was found to be trivial.
Factor V Leiden and G20210A prothrombin mutations are risk factors for very early recurrent miscarriage
Authors: Reznikoff‐Etiévant M.F. , Cayol V. , Carbonne B. , Robert A. , Coulet F. , Milliez J.
Published: December 2003

Objective
To determine whether there is an association between early recurrent miscarriage (before 10 weeks of pregnancy) and Factor V Leiden and G20210A prothrombin mutations.

Design
A prospective study.

Setting
Department of Gynaecology and Obstetrics, Saint Antoine Hospital, Paris, France.

Population
Two groups of women: those with early unexplained recurrent miscarriage before 10 weeks of pregnancy (n=260) and control healthy women without a previous history of thromboembolism (n=240).

Methods
Screening for defects in the protein C anticoagulant pathway was performed using the anticoagulant response to agkistrodon confortrix venom (ACV test). Protein C and Factor V Leiden mutation testing was performed for each low ACV level. Each sample was tested for the G20210A prothrombin mutation.

Results
Factor V Leiden and G20210A mutations were found to be associated with early recurrent spontaneous miscarriage before 10 weeks of pregnancy, the odds ratios being 2.4 (95% CI 1–5) and 2.7 (95% CI 1–7), respectively. Similar results were found whether or not women had had a previous live birth.

Conclusions
Early recurrent miscarriage before 10 weeks of pregnancy is significantly associated with Factor V or G20210A prothrombin mutations. These results indicate a possible role for anticoagulant prevention in these early miscarriages.
Assessment of third degree tears using three‐dimensional anal endosonography with combined anal manometry: a novel technique
Authors: Williams A.B. , Spencer J.A. , Bartram C.I.
Published: December 2003

Three‐dimensional anal endosonography has enabled sagittal and coronal reconstructions of the anal canal to be matched with longitudinal pressure data, to present a combined picture of structure and function. This novel technique has been applied to a group of women with a clinical diagnosis of a third degree tear. Endosonography showed that only 68% of women had ultrasound evidence of sphincter damage. Anal canal anatomy and pressure profile did not differ significantly between those with and those without sphincter damage, but the anterior external anal sphincter and the puborectalis tended to be shorter and the pressures were lower in those with sphincter disruption.
Placental massive perivillous fibrin deposition associated with antiphospholipid antibody syndrome
Authors: Sebire N.J. , Backos M. , Goldin R.D. , Regan L.
Published: December 2003

We present three pregnancies in which massive perivillous fibrous deposition (MPVFD) and maternal floor infarction (MFI) occurred in patients with primary antiphospholipid antibody syndrome (PAPS) attending a recurrent miscarriage clinic, and who were treated with low dose aspirin and heparin. We hypothesise that PAPS may be a predisposing factor to the development of this condition. The increased prevalence of late pregnancy complications in PAPS patients with a history of early miscarriage suggests that aspirin and heparin therapy does not eradicate the underlying pathological process but merely reduces the severity. Therefore, untreated early pregnancy losses may be converted into treated pregnancies with late antenatal complications. Some patients with PAPS may therefore be prone to suffer either the previously reported complications of the uteroplacental vasculature, such as pre‐eclampsia, and/or specific complications related to the environment of the intervillus space, such as MPVFD/MFI.
Objective assessment of bladder neck elevation and urethral compression at colposuspension
Authors: Bombieri L. , Freeman R.M. , Perkins E.P. , Williams M.P. , Shaw S.R.
Published: December 2003

Objectives
1. To assess whether magnetic resonance imaging and intra‐operative measurements are useful in assessing bladder neck elevation and urethral compression at colposuspension; 2. to see if intra‐operative measurements could be a substitute for magnetic resonance scan measurements.

Design
Prospective, observational study.

Setting
Urogynaecology Unit, NHS Trust hospital.

Population
Seventy‐seven women undergoing colposuspension.

Methods
Bladder neck elevation was assessed using magnetic resonance imaging and measuring the amount of suture bow‐stringing intra‐operatively. Urethral compression was assessed using magnetic resonance imaging and by two intra‐operative measurements: the distance between the medial sutures (with a ruler) and the distance between the urethra and the pubic bone (using paired Hegar dilators).

Results
The assessment of bladder neck elevation and compression against the pubic bone using magnetic resonance imaging was reliable (95% limits of agreement: −7.1mm to +7.1mm and −1.7mm to +3.8mm, correlation coefficient 0.92 and 0.87, respectively). The intra‐operative assessment of urethral compression with a ruler was also reproducible at both paravaginal and pectineal sites (95% limits of agreement −2.6mm to +2mm and −2.1mm to +2.4mm, respectively; correlation coefficient 0.99 for both distances). Other intra‐operative measurements of bladder neck elevation (suture bow‐stringing) and urethral compression (Hegars) did not correlate with equivalent magnetic resonance scan measurements (kappa =−0.046, P= 0.31; kappa = 0.052, P= 0.41, respectively).

Conclusions
Measurements have been found that can reliably assess bladder neck elevation and urethral compression at colposuspension. These measurements should be suitable for investigating morbidity following colposuspension.
Why do women have voiding dysfunction and de novo detrusor instability after colposuspension?
Authors: Bombieri L. , Freeman R.M. , Perkins E.P. , Williams M.P. , Shaw S.R.
Published: December 2003

Objective
To investigate the causes of voiding dysfunction and new detrusor instability after colposuspension.

Design
Prospective, observational study.

Setting
Urogynaecology unit, district general hospital.

Population
Seventy‐seven women undergoing colposuspension for genuine stress incontinence.

Methods
The following factors were investigated: 1. bladder neck elevation by magnetic resonance imaging before and after surgery; 2. urethral compression by measuring bladder neck approximation to the pubis with magnetic resonance imaging after surgery (anterior compression) and the distance between the medial stitches during surgery (lateral compression); 3. clinical and urodynamic factors.

Main outcome measures
1. Post‐operative voiding function (i.e. first day of voiding and day of catheter removal); 2. objective evidence of detrusor instability three months post‐operatively.

Results
Pre‐operative peak flow rate (P= 0.004), straining during voiding (P= 0.005), increasing age (P< 0.001), operative elevation (P< 0.001) and anterior urethral compression (P= 0.001) were associated with the number of days of post‐operative catheterisation. Increasing age (P= 0.02), previous bladder neck surgery (P= 0.04), operative elevation (P= 0.049) and anterior urethral compression (P< 0.001) were associated with detrusor instability at three months.

Conclusion
Surgical factors (bladder neck elevation and compression) are associated with voiding dysfunction and detrusor instability after colposuspension. These findings have implications for prevention.
A randomised controlled trial of the closure or non‐closure of peritoneum at caesarean section: effect on post‐operative pain
Authors: Rafique Z. , Shibli K.U. , Russell I.F. , Lindow S.W.
Published: December 2003

Objective
To compare the analgesic requirement in the post‐operative period after closure or non‐closure of the peritoneum at the caesarean delivery with a standardised anaesthetic and surgical technique.

Design
A randomised double‐blind controlled trial was performed on 100 women who underwent elective caesarean delivery.

Main outcome measures
Analgesic requirement assessed by morphine usage via patient controlled analgesia pump over the first 24‐hour period after surgery, oral analgesia used during the first four days, post‐operative pain assessed by a visual analogue scale and a verbal rating scale, and patient satisfaction assessed by verbal rating scale were the main outcome measures.

Results
Pain scores at 24 hours were similar in both groups (43.5 in closure and 40.5 in non‐closure) but during the first 24 hours the non‐closure group had used significantly less morphine than the closure group (0.64mg/kg of body weight vs 0.82mg/kg, P= 0.04). The patients in non‐closure group had significantly higher satisfaction scores after 24 hours than the closure group.

Conclusion
Non‐closure of both visceral and parietal peritoneum at the caesarean section produces a significant reduction in the post‐operative use of patient controlled analgesia pump morphine and significantly higher patient satisfaction at 24 hours post‐operatively.
Low dose 25 mg oestradiol implants and 1 mg norethisterone as continuous combined hormone therapy: a prospective study
Authors: Panay N. , Zamblera D. , Sands R. , Jones J. , Alaghband‐Zadeh J. , Studd J.W.W.
Published: December 2003

The anxiety regarding no‐bleed regimens is that breakthrough bleeding and endometrial hyperplasia may occur. We aimed to demonstrate that 25 mg oestradiol implants can be adequately opposed by a low dose of progestogen protecting against osteoporosis. Twenty‐two patients were recruited to the study. The mean age was 62 years and body mass index of 26.5. Median oestradiol rose from 77 pmol/L at baseline to 275 pmol/L at one year. Median endometrial thickness remained unchanged at 4 mm and only two women withdrew with bleeding problems. There was one case of proliferative endometrium at one year—all others samples were either atrophic or secretory. Lumbar bone density (L2–L4) rose significantly from 0.939 to 0.992 g/cm2 (+5.6%, P= 0.005) and the total femoral density rose from 0.872 to 0.890 g/cm2 (+2.1%). Bone formation markers increased significantly (serum type 1 procollagen C terminal peptide, P1CP = 112–114, P= 0.0376) and bone resorption fell (serum type 1 collagen C terminal telopeptide, 1CTP = 3.0–2.9, P= 0.2863). E25 implants and low dose progestogen appear to avoid endometrial hyperplasia and bleeding problems while increasing bone density.
Is there an increased maternal–infant prevalence of Factor V Leiden in association with severe pre‐eclampsia?
Authors: Currie Lea , Peek Michael , McNiven Michelle , Prosser Ian , Mansour Julia , Ridgway Jennifer
Published: December 2003

Objective
To compare the prevalence of the Factor V Leiden mutation in children and maternal–infant pairs in pregnancies affected by severe pre‐eclampsia with unmatched normal controls.

Design
Prospective cohort study.

Setting
Department of Women's and Children's Health, The Canberra Hospital, Garran, ACT, Australia.

Sample
Forty‐eight maternal–infant pairs where the index pregnancy was affected by severe pre‐eclampsia; 46 unmatched maternal–infant pairs where the index pregnancy was defined as normal.

Methods
DNA analysis of cheek swab samples obtained from maternal–infant pairs for the Factor V Leiden mutation.

Main outcome measure
The prevalence of the Factor V Leiden mutation in mothers, infants and maternal–infant pairs in association with severe pre‐eclampsia compared with unmatched controls.

Results
No difference was detected in the prevalence of Factor V Leiden mutation between the women and children of both groups, nor the maternal–infant pairs from each group.

Conclusions
No evidence was found of an increased prevalence of the Factor V Leiden mutation in either the mothers or children in association with severe pre‐eclampsia. This result argues against a Factor V Leiden fetal or maternal contribution to the development of severe pre‐eclampsia.
Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis
Authors: Donders Gilbert G.G. , Vereecken Annie , Bosmans Eugene , Dekeersmaecker Alfons , Salembier Geert , Spitz Bernard
Published: December 2003

Objective
To define an entity of abnormal vaginal flora: aerobic vaginitis

Design
Observational study.

Setting
University Hospital Gasthuisberg, Leuven, Belgium

Sample
631 women attending for routine prenatal care or attending vaginitis clinic.

Methods
Samples were taken for fresh wet mount microscopy of vaginal fluid, vaginal cultures and measurement of lactate, succinate and cytokine levels in vaginal fluid. Smears deficient in lactobacilli and positive for clue cells were considered to indicate a diagnosis of bacterial vaginosis. Aerobic vaginitis was diagnosed if smears were deficient in lactobacilli, positive for cocci or coarse bacilli, positive for parabasal epithelial cells, and/or positive for vaginal leucocytes (plus their granular aspect)

Results
Genital complaints include red inflammation, yellow discharge, vaginal dyspareunia. Group B streptococci, escherichia coli, staphylococcus aureus and trichomonas vaginalis are frequently cultured. Vaginal lactate concentration is severely depressed in women with aerobic vaginitis, as in bacterial vaginosis, but vaginal succinate is not produced. Also in contrast to bacterial vaginosis, aerobic vaginitis produces a host immune response that leads to high production of interleukin‐6, interleukin‐1‐β and leukaemia inhibitory factor in the vaginal fluid

Conclusion
Aerobic vaginitis is associated with aerobic micro‐organisms, mainly group B streptococci and E. coli. Its characteristics are different from those of bacterial vaginosis and elicit an important host response. The most severe form of aerobic vaginitis equals desquamative inflammatory vaginitis. In theory, aerobic vaginitis may be a better candidate than bacterial vaginosis as the cause of pregnancy complications, such as ascending chorioamnionitis, preterm rupture of the membranes and preterm delivery
Women's perceptions and experiences of routine enquiry for domestic violence in a maternity service
Authors: Bacchus Loraine , Mezey Gill , Bewley Susan
Published: December 2003

Objective
A qualitative study examining women's perceptions and experiences of routine enquiry for domestic violence in a maternity service.

Design
Purposive sampling was used to select a sub‐sample from a larger group of women who participated in a domestic violence in pregnancy screening study undertaken at Guy's and St Thomas' Hospitals in London.

Setting
Interviews were conducted in women's homes and general practitioner's surgeries.

Sample
Ten women who experienced domestic violence in the last 12 months (including pregnancy), six women who experienced domestic violence in the last 12 months, but not in pregnancy, and 16 women with no history of domestic violence.

Methods
Semi‐structured interviews conducted during the postpartum period (up to 14 months).

Main outcome measures
Women's views on the acceptability and relevance of routine enquiry for domestic violence.

Results
Routine enquiry for domestic violence in maternity settings is acceptable to women if conducted in a safe, confidential environment by a trained health professional who is empathic and non‐judgemental. The effectiveness of routine enquiry to elicit a history of domestic violence is influenced by factors such as lack of time, confidential consulting time, continuity of care, training and availability of resources.

Conclusions
Further research is needed to determine whether the use of on‐site specialist domestic violence workers will increase midwives' ability to routinely enquire about domestic violence.
Uterine artery embolisation for the treatment of symptomatic fibroids in 114 women: reduction in size of the fibroids and women's views of the success of the treatment
Authors: Watson G.M.T. , Walker W.J.
Published: December 2003

Objective
To assess the reduction in size of fibroids following uterine artery embolisation and to analyse women's views of the success of treatment.

Design
An uncontrolled case series of 114 consecutive women who underwent uterine artery embolisation for the treatment of fibroids over two years.

Setting
The Diagnostic and Interventional Radiology Department at The Royal Surrey County Hospital, Guildford, UK.

Methods
Bilateral uterine artery embolisation was performed for the treatment of symptomatic fibroids. Magnetic resonance imaging was carried out before and six months following embolisation. Women completed outcome questionnaires following their treatment.

Main outcome measures
The sites, imaging signal characteristics and percentage reduction in the volume of three dominant fibroids were determined from the magnetic resonance scans. Outcome was measured by questionnaire. Women were asked whether their symptoms resolved completely, improved, remained unchanged or deteriorated.

Results
One hundred and sixty‐five fibroids of 114 women (mean age 42) were analysed. Forty‐five percent of women had complex fibroid masses and 50% had fibroids ≥8.5cm in diameter. The median reduction in the fibroid volume was 58%. The median reduction of the volume of complex fibroid masses, submucous fibroids, fibroids ≥8.5cm and fibroids with high and low signal on T2 weighted sequences were 58%, 63%, 50%, 62% and 51%, respectively. Ninety‐one percent of the women's symptoms had resolved or improved following embolisation.

Discussion
The majority of women were satisfied with their outcome. We have shown that uterine artery embolisation is a successful treatment for symptomatic fibroids of all types, sizes and signal characteristics.
Histologic chorioamnionitis and umbilical serum levels of pro‐inflammatory cytokines and cytokine inhibitors
Authors: Døllner Henrik , Vatten Lars , Halgunset Jostein , Rahimipoor Shahnaz , Austgulen Rigmor
Published: December 2003

Objective
To study 1. whether leucocyte infiltration in placenta tissues is associated with elevated umbilical serum levels of inflammatory mediators, and 2. whether leucocyte infiltration in the presence of neonatal disease is associated with additional increase in mediator levels.

Setting
University hospital.

Population
Two groups of women with either normal delivery (n= 82) or delivery complicated by prolonged rupture of the membranes, clinical signs of intrauterine infection or preterm labour (n= 139).

Methods
Umbilical cord blood and placenta tissues were collected after delivery. Placentas were classified as non‐inflamed (i.e. without leucocyte infiltration, n= 74), or as mild (n= 84), or severe chorioamnionitis (n= 63). Mediator levels were compared between groups.

Results
Severe chorioamnionitis was associated with elevated levels of tumour necrosis factor (TNF)α, interleukin (IL)‐1β, IL‐6, IL‐8, soluble TNF receptor p55 and p75, IL‐1 receptor antagonist (IL‐1RA), and C‐reactive protein compared with non‐inflamed placentas (all P < 0.05). No differences were found between mild chorioamnionitis and placentas without infiltration. In all, 49 babies suffered from various perinatal diseases, such as clinical sepsis, respiratory distress and asphyxia, and 172 were healthy. Severe chorioamnionitis with subsequent neonatal disease (n= 23) had higher levels of all mediators, except IL‐1β and C‐reactive protein, than severe chorioamnionitis without neonatal disease (n= 40, all P < 0.01), but severe chorioamnionitis was also accompanied by a more intense and widely distributed leucocyte infiltration when neonatal disease developed.

Conclusion
High grade leucocyte infiltration in placenta tissues is associated with elevated levels of TNFα, IL‐1β, IL‐6, IL‐8, p55, p75, IL‐1RA and C‐reactive protein in umbilical serum. The presence of neonatal disease is associated with advanced chorioamnionitis, and highly elevated levels of both pro‐ and anti‐inflammatory mediators in umbilical serum.
Rescue of trophoblast apoptosis by parathyroid hormone‐related protein
Authors: Crocker Ian , Kaur Malveen , Hosking David J. , Baker Philip N.
Published: December 2003

The effects of the 1–34 N‐terminal parathyroid hormone‐related protein fragment (0–10μM) and the 67–86 parathyroid hormone‐related protein fragment (0–10μM) on trophoblast apoptosis, induced by TNFα and IFNγ or by the protein kinase inhibitor staurosporine, were investigated. TNFα/IFNγ and staurosporine significantly increased the rate of apoptosis by fivefold and by eightfold, respectively. Parathyroid hormone‐related protein (1–34) evoked a dose‐dependent rescue of both TNFα/IFNγ‐induced and staurosporine‐induced apoptosis, whereas parathyroid hormone‐related protein (67–86) had no significant effect on staurosporine‐induced apoptosis, and only significantly diminished TNFα/IFNγ‐induced apoptosis at 10μM. Parathyroid hormone‐related protein was thus found to be a cytotrophoblast apoptosis survival factor.
Does endothelial cell activation occur with intrauterine growth restriction?
Authors: Johnson M.R. , Anim‐Nyame N. , Johnson P. , Sooranna S.R. , Steer P.J.
Published: December 2003

It is possible that in fetal growth restriction without pre‐eclampsia endothelial cell activation does not occur. This might be either because there is no release of ‘factor X’ or because of maternal resistance to its effects. To test this hypothesis, we took blood samples from 26 women with pre‐eclampsia (without fetal growth restriction), 13 women with fetal growth restriction (without pre‐eclampsia) and 24 normal pregnant controls, and measured the circulating levels of three markers of endothelial cell activation (soluble VCAM, ICAM and E‐selectin) and three cytokines [tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and ‐8 (IL‐8)]. The levels of the markers of endothelial cell activation were raised in both pre‐eclampsia and fetal growth restriction pregnancies compared with controls; however, the levels of TNF‐α, IL‐6 and IL‐8 were significantly raised in pregnancies complicated by pre‐eclampsia, but not in fetal growth restriction, compared with controls. These data show that endothelial cell activation is common to both pre‐eclampsia and fetal growth restriction, but that the circulating levels of cytokines are elevated only in pre‐eclampsia. Thus, it seems likely that endothelial cell activation is a consequence of a failure of trophoblast invasion and that a further step is required, possibly involving cytokine release, for the expression of the full clinical picture of pre‐eclampsia.
Low dose acetylsalicylic acid in prevention of pregnancy‐induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches
Authors: Vainio Merja , Kujansuu Erkki , Iso‐Mustajärvi Marja , Mäenpää Juhani
Published: December 2003

Objective
To evaluate the efficacy of low‐dose acetylsalicylic acid in the prevention of pregnancy‐induced hypertension and intrauterine growth retardation in high‐risk pregnancies as determined by transvaginal Doppler ultrasound study of the uterine arteries at 12 to 14 weeks of gestation.

Design
Randomised, double blind and placebo‐controlled trial.

Setting
The Department of Obstetrics and Gynaecology, Tampere University Hospital, Finland.

Population
One hundred and twenty pregnant women considered to be at high risk of pre‐eclampsia or intrauterine growth retardation were screened by transvaginal Doppler ultrasound at 12 to 14 weeks of gestation.

Methods
Ninety pregnant women with bilateral notches in the uterine arteries were randomised to receive acetylsalicyclic acid 0.5mg/kg/day (n= 45) or placebo (n= 45) from 12 to 14 weeks of gestation.

Main outcome measures
Hypertensive disorders of pregnancy and intrauterine growth retardation.

Results
Forty‐three women on acetylsalicyclic acid and 43 on placebo were successfully followed up. The use of acetylsalicyclic acid was associated with a statistically significant reduction in the incidence of pregnancy‐induced hypertension (11.6%vs 37.2%, RR = 0.31, 95% CI 0.13–0.78) and pre‐eclampsia (4.7%vs 23.3%, RR = 0.2, 95% CI 0.05–0.86). The incidence of hypertension before 37 weeks of pregnancy was also significantly reduced (2.3%vs 20.9%, RR = 0.22, 95% CI 0.05–0.97). The reduction in the incidence of intrauterine growth retardation (2.3%vs 7%) was not statistically significant. Acetylsalicyclic acid was not associated with excess risk of maternal or fetal bleeding.

Conclusion
In women rated in Doppler velocimetry waveform analysis to be at high risk of pre‐eclampsia, low‐dose acetylsalicyclic acid reduces the incidence of pregnancy‐induced hypertension and especially proteinuric pre‐eclampsia.
The effect of oestradiol on vaginal collagen metabolism in postmenopausal women with genuine stress incontinence
Authors: Jackson Simon , James Mark , Abrams Paul
Published: December 2003

Objective
To determine whether oestrogen replacement will produce an improvement in the quantity, or quality, of pelvic collagen in postmenopausal women.

Design
A prospective double‐blind placebo controlled trial of oestrogen therapy.

Setting
Southmead Hospital, Bristol, UK.

Population
Fifty‐five postmenopausal women with a urodynamic diagnosis of genuine urinary stress incontinence.

Methods
Randomisation to a six‐month, double‐blind, placebo‐controlled, trial of oestradiol valerate 2mg once daily. A 10mg–30mg periurethral biopsy was taken from the vaginal epithelium before and after treatment. Tissue was analysed for total collagen content, intermolecular cross‐links, advanced glycation end‐products, collagen type ratios and matrix metalloproteinase (MMP) activity.

Results
Forty‐nine women completed the trial of whom 26 received oestrogen and 23 received placebo. When compared with placebo, oestrogen treatment resulted in significant decreases in total collagen (P= 0.0054), the mature cross‐link HHL (P= 0.0009) and the advanced glycation end‐product NFC‐1 (P= 0.0009). There was a significant rise in the immature cross‐link HLKNL (P= 0.0191). Oestrogen produced a significant increase in MMP‐2 expression (Pro MMP‐2, P= 0.0017).

Conclusions
Six months treatment with oestrogen has profound effects upon pelvic collagen metabolism, stimulating collagen degradation via increased proteinase activity. While aged collagen is being lost, new collagen is synthesised as witnessed by the increase in the immature cross‐links and the decrease in both mature cross‐links and advanced glycation end‐products. Collagen loss contradicts previous reports; perhaps aged collagen degradation is merely an early response to oestrogen stimulation. We have evidence of new collagen synthesis, and it may be that a longer treatment interval would show total collagen content increasing. Further studies within this field are warranted.
Meconium and fetal hypoxia: some experimental observations and clinical relevance
Authors: Westgate Jenny A. , Bennet Laura , Gunn Alistair J.
Published: December 2003

In an experimental study, chemically sympathectomised near term fetal sheep and a control group were subjected to repeated episodes of acute hypoxia. Despite severe hypotension and metabolic acidosis, no animal in the control group had meconium‐stained amniotic fluid, whereas every animal in the sympathectomised group had heavily meconium‐stained amniotic fluid at the end of the experiments. These data and the available literature do not support a direct association between acute hypoxia and meconium‐stained amniotic fluid but suggest that a reduction in sympathetic neural tone must be a component of meconium passage. Clinical and experimental data on the occurrence of meconium‐stained amniotic fluid are reviewed.
Grandmultiparae in a modern setting
Authors: Bugg G.J. , Atwal G.S. , Maresh M.
Published: December 2003

Objective
To compare the incidence of antenatal and intrapartum complications and neonatal outcomes among women who had previously delivered five or more times (grandmultiparous) with that of age‐matched control women who had previously delivered two or three times (multiparous).

Design
A matched cohort study.

Setting
An inner city university maternity hospital in the United Kingdom.

Sample
Three hundred and ninety‐seven grandmultiparous women were compared with three hundred and ninety‐seven age‐matched multiparous women.

Methods
Data on the subjects were obtained from a computerised maternity information system (SMMIS). Characteristics and complications occurring in the two groups were compared. Data validation was performed with a 10% randomised sample of the casenotes in both groups. Nineteen relevant data fields were abstracted and compared with the matched SMMIS record.

Results
The overall incidence of intrapartum complications for grandmultiparous women was 16% compared with 18% in the control multiparous women (odds ratio 0.9, 95% CI 0.6–1.3). Grand multiparity was associated with a significantly higher body mass index at booking (P <0.01) and the last antenatal clinic (P < 0.05), an increased incidence of antenatal anaemia (22%vs 16%, odds ratio 1.8, 95% CI 1.2–2.8) and a decreased incidence of elective caesarean section (6%vs 11%, odds ratio 0.5, 95% CI 0.3–0.9). Agreement was greater than 95% in all the data fields reviewed except three. In the 14 categorical variables reviewed the Cohen's kappa results were in excess of 0.6.

Conclusion
This study suggests that in a developed country with satisfactory health care conditions, grandmultiparity should not be considered dangerous, and risk assessment should be based on past and present history and not simply on the basis of parity.
Medical management of early fetal demise using sublingual misoprostol
Authors: Wagaarachchi Prabhath T. , Ashok Premila W. , Smith Norman C. , Templeton Allan
Published: December 2003

The aim of this study was to determine the efficacy of mifepristone in combination with sublingual misoprostol for the medical management of early fetal demise. Fifty‐six consecutive women were studied prospectively. The mean (SD) gestation at diagnosis was 9.6 weeks (1.84). Four women had complete miscarriage with mifepristone alone. The overall success rate was 83.9% and the median induction–miscarriage interval was 8.19 hours (range 0.83 to 37.50 hours). Of those women who had a successful outcome, 91.5% were satisfied with the regimen. Sublingual misoprostol in combination with mifepristone is an effective and safe alternative to vaginal or oral misoprostol in the management of early fetal demise.
Violent deaths: the hidden face of maternal mortality
Authors: Granja Ana Carla , Zacarias Eugenio , Bergström Staffan
Published: December 2003

Objective
To review pregnancy‐related deaths due to injuries, to identify the characteristics of these women and to compare the magnitude of injury‐related maternal deaths to that of other causes of maternal death

Design
A retrospective study was performed during a five‐year period (1991–1995), covering deaths from injuries, including suicide, homicide and accidents in Maputo, Mozambique

Setting
Department of Forensic Medicine at the Maputo Central Hospital, Mozambique

Population
The pregnant or recently pregnant (post‐abortion and postpartum) population of Maputo city, the national capital of Mozambique. Twenty‐seven cases of pregnancy‐related deaths caused by injuries were identified

Main outcome measures
Proportion of deaths due to homicide, suicide, and accidents in pregnant women or within 42 days after termination of pregnancy

Results
Ten cases were due to alleged homicide, nine to alleged suicide and six to alleged accident. Fifty‐nine percent (16/27) of women suffering an injury‐related maternal death were younger than 25 years of age. Eighty‐five percent of pregnancies were less than 28 weeks of gestational age. The magnitude of the problem of violence‐related maternal deaths compares with the magnitude of pregnancy‐induced hypertension as the fourth cause of maternal death at Maputo Central Hospital

Conclusion
The contribution of violence‐related deaths to maternal mortality is significant and must not be neglected.
Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: a systematic quantitative review
Authors: Clark T. Justin , Mann Christopher H. , Shah Neil , Khan Khalid S. , Song Fujian , Gupta Janesh K.
Published: December 2003

Objective
To determine the accuracy of outpatient endometrial biopsy in diagnosing endometrial cancer in women with abnormal uterine bleeding.

Design
A systematic quantitative review of published research.

Methods
Studies were selected if accuracy of outpatient endometrial biopsy was estimated compared with a reference standard. Diagnostic accuracy was determined by pooled likelihood ratios for positive and negative test results. There were 1013 subjects in 13 diagnostic evaluations reported in 11 primary studies.

Results
A positive test result on outpatient biopsy diagnosed endometrial cancer with a pooled likelihood ratio of 66.48 (95% CI 30.04–147.13) while a negative test result had a pooled likelihood ratio of 0.14 (95% CI 0.08–0.27). The post test probability of endometrial cancer was 81.7% (95% CI 59.7%–92.9%) for a positive test and 0.9% (95% CI 0.4%–2.4%) for a negative test.

Conclusion
Outpatient endometrial biopsy has a high overall accuracy in diagnosing endometrial cancer when an adequate specimen is obtained. A positive test result is more accurate for ruling in disease than a negative test result is for ruling it out. Therefore, in cases of abnormal uterine bleeding where symptoms persist despite negative biopsy, further evaluation will be warranted.
Levels of C‐reactive protein in pregnant women who subsequently develop pre‐eclampsia
Authors: Savvidou Makrina D. , Lees Christoph C. , Parra Mauro , Hingorani Aroon D. , Nicolaides Kypros H.
Published: December 2003

Objective
To investigate whether a maternal inflammatory response precedes the development of pre‐eclampsia.

Design
Cross‐sectional study.

Setting
Antenatal clinic in an inner city teaching hospital.

Population
Two groups of women were examined at 23–25 weeks of gestation. The first group (45 women) had normal uterine artery Doppler waveforms and subsequently had a normal pregnancy outcome. The second group (45 women) had Doppler evidence of impaired placental perfusion and 21 (47%) of them had normal outcome, 14 (31%) developed intrauterine growth restriction and 10 (22%) developed pre‐eclampsia, with or without intrauterine growth restriction.

Methods
C‐reactive protein, an acute‐phase reactant, was measured in maternal serum using a highly sensitive method with a detection limit of 0.05mg/L.

Main Outcome Measures
Development of pre‐eclampsia, as defined by the International Society for the Study of Hypertension in Pregnancy. Intrauterine growth restriction was defined as birthweight <5th centile for gestation and sex of the neonate.

Results
The serum C‐reactive protein concentration in women who subsequently developed pre‐eclampsia (median 1.56, range 0.55–3.12mg/L) or delivered a baby with birthweight <5th centile (median 0.74, range 0.64–1.58mg/L) was not significantly different from that in women with uncomplicated pregnancies (median 1.28, range 0.75–2.08mg/L; P= 0.95 and P= 0.62, respectively).

Conclusion
These findings suggest that the onset of clinical signs of pre‐eclampsia may not be preceded by a maternal inflammatory response, as assessed by measurement of C‐reactive protein.
The role of arginine vasopressin in human labour: functional studies, fetal production and localisation of V1a receptor mRNA
Authors: Thornton S. , Baldwin P.J. , Harris P.A. , Harding F. , Davison J.M. , Baylis P.H. , Timmons P.M. , Wathes D.C.
Published: December 2003

Objective
To investigate labour‐associated changes in: 1. the myometrial contractile response to arginine vasopressin compared with oxytocin in vitro 2. fetal production of arginine vasopressin and 3. myometrial vasopressin V1a receptor mRNA.

Design
The contractile response to vasopressin (compared with oxytocin) was investigated in paired myometrial strips in vitro. Blood was taken from the umbilical artery and vein at delivery and arginine vasopressin measured by radio‐immunoassay. V1a receptor mRNA was determined by in situ hybridisation.

Results
Myometrium was more sensitive to arginine vasopressin than oxytocin (P <0.05 for frequency, amplitude and activity integral in paired strips) after, but not before labour. There was a marked umbilical arteriovenous difference in arginine vasopressin concentration at delivery suggesting fetal production which was not influenced by labour. Myometrial vasopressin V1a receptor mRNA was not increased after the onset of labour.

Conclusions
The human uterus is extremely sensitive to arginine vasopressin in vitro. Arginine vasopressin is produced by the fetus but fetal formation is not increased during labour.
A deficient maternal calcium intake during pregnancy increases blood pressure of the offspring in adult rats
Authors: Bergel Eduardo , Belizán José M.
Published: December 2003

Objective
To assess in an animal model the effect of maternal dietary calcium intake during pregnancy on the blood pressure of offspring.

Design
Randomised controlled trial.

Sample
Ninety‐eight 20‐week‐old female Wistar–Kyoto rats, giving birth to a total of 119 pups that were included in the follow up study.

Methods
Rats were randomised to a calcium deficient diet, a diet with the recommended calcium levels, or a diet with calcium content much higher than the recommended levels. After one month on the experimental diet they were bred. After birth, systolic blood pressure in the offspring was measured monthly till 52 weeks of age.

Main outcome measures
Blood pressure of the offspring.

Results
The difference in blood pressure of the offspring between the normal and low maternal calcium group increased 0.49 mmHg per month (95% CI 0.18 to 0.84), 0.38 (0.07 to 0.68) between the low and high calcium group, and 0.12 (−0.20 to 0.43) between the normal and high calcium group. At the end of the follow up (52 weeks of age) blood pressure of the offspring in the deficient calcium group was 12.1 mmHg (95% CI 8.8 to 15.4, P < 0.0001) higher than in the normal calcium group and 7.5 mmHg (95% CI 4.4 to 10.5, P < 0.001) higher than the high calcium group. Blood pressure of the offspring in the high calcium group was 4.3 mmHg (95% CI 1.0 to 7.5, P= 0.0l) higher than in the normal calcium group. In a multiple regression model maternal calcium intake during pregnancy was the strongest predictor of blood pressure of the offspring during adulthood.

Conclusions
This experiment supports previous studies in humans suggesting a link between calcium intake during pregnancy and blood pressure in the offspring, and provides an animal model to explore the mechanisms involved in such association.
The impact of subcutaneous oestradiol implants on biochemical markers of bone turnover and bone mineral density in postmenopausal women
Authors: Pereda C.A. , Hannon R.A. , Naylor K.E. , Eastell R.
Published: December 2003

Objective
To evaluate the anabolic effect of oestrogen on bone by comparing the response of markers of bone formation (and resorption) and bone mineral density (BMD) to subcutaneous oestradiol implants.

Design
One year double‐blind placebo controlled randomised study.

Setting
Clinical research unit within a teaching hospital.

Population
Twenty‐one hysterectomised postmenopausal women were randomised to 25 mg oestradiol implants at baseline and at six months or to have a sham procedure at baseline and six months.

Methods
BMD and quantitative ultrasound (QUS) were assessed at baseline and one year. Bone alkaline phosphatase (bone ALP), procollagen type I N‐terminal propeptide (PINP), osteocalcin (OC), free deoxypyridinoline (iFDPD), N‐telopeptide of type I collagen (NTX), serum oestradiol and intact parathyroid hormone (PTH) were measured at baseline, 4, 8, 12 and 24 weeks.

Main outcome measures
Percentage change markers of bone turnover and PTH and change in oestradiol levels over first six months and percentage of changes in DXA and QUS over one year.

Results
PINP, bone ALP and OC increased by 28%, 7% and 9%, respectively (P < 0.01) during the first four weeks of treatment and then decreased significantly. Lumbar spine (LS) and total hip (TH) BMD increased by 5.4% and 6.0% (P < 0.001), respectively, and femoral neck (FN) BMD by 3.7% (P < 0.05) during the first year of treatment compared with control subjects. The peak serum oestradiol level was achieved four weeks after implant insertion. Mean PTH levels increased significantly in subjects receiving subcutaneous oestradiol.

Conclusion
Subcutaneous oestrogen exerted an apparent anabolic effect on bone, which was initially reflected by an increase in bone formation markers and later by a large increase in BMD.
S‐relaxin as a predictor of preterm delivery in women with symptoms of preterm labour
Authors: Vogel Ida , Glavind‐Kristensen Marianne , Thorsen Poul , Armbruster Franz P. , Uldbjerg Niels
Published: December 2003

Objective
To evaluate whether serum relaxin (S‐relaxin) can predict spontaneous delivery before 34 weeks of gestation in high risk pregnancies.

Design
A prospective cohort study.

Setting
Calculated sample size was reached over a two‐year period, during which 9507 women gave birth. Of these, 157 healthy women were eligible for the study as they were admitted with symptoms of delivery before 34 weeks of gestation. Ninety‐three women were included. Overall participation rate was 59%.

Population
Healthy women with singleton pregnancies with symptoms of delivery before 34 weeks of gestation.

Methods
S‐relaxin was measured using a standard sandwich ELISA.

Main outcome measures
End points were preterm delivery before 34 weeks of gestation and delivery within three days from initiation of symptoms. The best possible prediction of preterm delivery was established using logistic regression for risk factors individually associated with preterm delivery before 34 weeks of gestation. S‐relaxin was dichotomised to obtain best possible fit and then entered into the model. The same analyses were done for delivery within three days.

Results
Median S‐relaxin levels varied significantly in the women with preterm prelabour rupture of membranes (PPROM) (316 pg/mL), contractions (222 pg/mL) or ripe cervices (203 pg/mL) (P < 0.05). S‐relaxin above the 80th centile (≥300 pg/mL) was associated with an increased risk of preterm delivery [crude OR = 4.8; (95% CI: 1.9–12)]. Likelihood ratio of a positive test is 2.6 (1.5–4.9) and S‐relaxin resulted in a post‐test probability of preterm delivery of 0.72, compared with a pre‐test probability of 0.49. S‐relaxin contributed to the identification of delivery within three days [adj. OR = 11 (95% CI: 1.8–64)].

Conclusion
S‐relaxin may be a useful predictor in women with symptoms of delivery before 34 weeks of gestation.
Does sweeping of membranes beyond 40 weeks reduce the need for formal induction of labour?
Authors: Wong S.F. , Hui S.K. , Choi H. , Ho L.C.
Published: December 2003

Objective
To assess the efficacy of sweeping of membranes beyond 40 weeks of gestation in reducing the incidence of induction of labour, when induction was planned at 42 weeks.

Design
Prospective randomised controlled trial.

Setting
A regional obstetric unit in Hong Kong.

Population and methods
A total of 120 women with certain gestational age, determined by early pregnancy ultrasound scan, were recruited from 1st July, 1998 to 31st December, 1999. Sixty women were randomly allocated to sweeping of membranes and the other 60 women acted as control. The satisfaction for women allocated to sweeping of membranes was assessed by a questionnaire after the procedure. The two groups were assessed on intention‐to‐treat basis.

Main outcome measures
The incidence of formal induction of labour was compared between the two groups. Possible complications of sweeping of membranes such as rupture of membranes, intrapartum infection, postpartum infection, and neonatal infection were also assessed. Maternal and perinatal outcomes were also assessed.

Results
The recruitment to delivery interval was significantly shorter among women who had sweeping of membranes (3.2 versus 4.2 days, P < 0.05). The incidence of induction of labour was comparable (35.5%versus 38%, RR 0.91, 95% CI 0.57–1.46). The incidences of caesarean section and assisted vaginal delivery were comparable. The incidences of premature rupture of membranes, intrapartum, and postpartum infection were comparable. The perinatal outcomes were also comparable between the two groups. Up to 70% of women found that this procedure was associated with significant discomfort. One third of these women complained of significant pain.

Conclusions
Sweeping of membranes beyond 40 weeks does not reduce the need for formal induction of labour at 42 weeks. Although it is safe, the majority of women felt uncomfortable during the procedure.