bluuebunny/crossref_metadata_2025 huggingface dataset:
Looking to the future
Authors: Lamont Ronald F.
Published: December 2003

Since the 7th and 13th Study Groups of the Royal College of Obstetricians and Gynaecologists met in 1977 and 1985, respectively, no meeting of this magnitude has convened to discuss the problems of spontaneous preterm labour and delivery and the associated fetomaternal mortality and morbidity. In the 17 years or so since that time, advances have been made in our understanding of the mechanisms of labour, the role of infection, the benefit of antepartum corticosteroids and the development of safer more specific tocolytics. In the future, an understanding of the genetic risk of spontaneous preterm labour and preterm birth is essential, particularly with respect to the predisposition to produce potentially damaging pro‐inflammatory cytokines. The examination of the tissue damage will require pathologists specifically trained in perinatal pathology if the aetiology is to be ascertained and future management tailored to the risks. A greater understanding of fetomaternal immunology and response to antigen exposure in pregnancy may help us to understand which fetomaternal pairs are at greatest risk of responding by delivering preterm, with greater or lesser tissue damage than others with similar risk. Specifically, the relation between spontaneous preterm labour and proteinuric pre‐eclampsia with their common immunology, inflammatory response and tissue damage leading to either spontaneous preterm labour or iatrogenic preterm birth will need to be addressed. This meeting has been very clinically and obstetrically orientated, in future we will need to involve epidemiologists, neonatologists, microbiologists, genito‐urinary medicine physicians, immunologists, geneticists, biochemists, physiologists and endocrinologists. Although spontaneous preterm labour and preterm birth are the major causes of perinatal mortality and morbidity in the developed world, the definition and management protocols for spontaneous preterm labour varies from unit to unit and country to country. A process has already begun, hopefully fuelled by this meeting and those attending, to develop an international consensus on definitions and evidence‐based practical guidelines on the management of spontaneous preterm labour. Perhaps in the longer term it may be possible to influence standards of care, outcome measures and training across international boundaries.
Women awaiting hysterectomy: a qualitative study of issues involved in decisions about oophorectomy
Authors: Bhavnani Vanita , Clarke Aileen
Published: December 2003

Objective
Women awaiting abdominal hysterectomy have a further decision to take—whether or not to undergo a prophylactic oophorectomy. Prophylactic oophorectomy (removal of healthy ovaries) is commonly undertaken as an adjunct to hysterectomy to prevent ovarian cancer in women who are already having a hysterectomy for menorrhagia, fibroids or severe menstrual pain. It causes an immediate ‘surgical menopause’—women no longer produce endogenous oestrogens and they are advised to take hormone replacement therapy (HRT). This descriptive study was undertaken as part of a larger pilot study.

Design
Qualitative interviewing study.

Setting
Hospital outpatient departments in southern England.

Sample
Women on waiting lists for hysterectomy for benign conditions.

Methods
In‐depth semi‐structured interviews were undertaken with 16 women awaiting hysterectomy to examine their views of prophylactic oophorectomy, menopause and HRT use. Interviews were transcribed. Nud*ist was used to organise the data. Analysis was undertaken by two researchers working independently who then met to agree themes.

Results
Women held treatment preferences both about the removal or retention of their ovaries and about subsequent HRT use. Many of the women did not want oophorectomy because of a dislike of a sudden menopause. Those who were planning to have an oophorectomy tended to have more severe symptoms. Some women were fearful of ovarian cancer—one woman described it as a ‘silent killer’. A further theme was apparent in the discussion of ovaries as ‘redundant’ with further discussion of healthy versus problematic ovaries. Many women felt inadequately informed about their treatment options and were unaware of important longer term outcomes of oophorectomy such as an increased risk of osteoporosis or of coronary heart disease.

Conclusion
It appears that many women emphasise the ‘natural’ when considering oophorectomy and the use of HRT. Women were uneasy both about a sudden menopause and about the risks of ovarian cancer. And although these women were all about to undergo surgery, they had experienced an apparent serious lack of information especially about long term risks and benefits on which they might base their decision.
Vaginal hysterectomy in nulliparous women without prolapse: a prospective comparative study
Authors: Agostini Aubert , Bretelle Florence , Cravello Ludovic , Maisonneuve Anne Sophie , Roger Valérie , Blanc Bernard
Published: December 2003

Objective
To compare vaginal hysterectomy success and complication rates in nulliparous and primiparous or multiparous women.

Design
A comparative prospective study.

Setting
Department of Gynaecology, La Conception Hospital, Marseille, France.

Population
Three hundred and forty‐five consecutive patients without genital prolapse requiring hysterectomy for benign conditions and without previous pelvic surgery or caesareans were treated prospectively by vaginal hysterectomy. Fifty‐two patients were nulliparous and 293 were primiparous or multiparous.

Methods
Data of patients were collected prospectively.

Main outcome measures
Operative time, length of hospital stay, oophorectomy, conversion to laparotomy, intra‐ and post‐operative complications.

Results
The mean operative time was significantly longer in nulliparous patients [95 (55.2) vs 79.9 (34.9) minutes, P < 0.01]. The overall complication rate was significantly higher [7/52 (13.46%) vs 13/293 (4.44%), P= 0.02, RR = 3.03 (1.27–7.23)] as was the haemorrhage rate in nulliparous compared with the primiparous and multiparous women [4/52 (7.69%) vs 5/293 (1.7%), P= 0.03, RR = 4.51 (1.25–16.23)]. Vaginal hysterectomy was successfully performed in 96.2% (50/52) of the nulliparous and 99.7% (292/293) of the parous patients [P= 0.06, RR = 1.04 (0.98–1.09)].

Conclusion
The success rate of vaginal hysterectomy in nulliparous women is high. However, the risk of complications seems higher than in the parous women. Laparoscopy assisted vaginal hysterectomy in nulliparous women needs further investigations.
Non‐invasive fetal electrocardiography in singleton and multiple pregnancies
Authors: Taylor Myles J.O. , Smith Mark J. , Thomas Matthew , Green Andrew R. , Cheng Floria , Oseku‐Afful Salome , Wee Ling Y. , Fisk Nicholas M. , Gardiner Helena M.
Published: December 2003

Objectives
To document the duration of fetal cardiac time intervals in uncomplicated singleton pregnancies using a novel non‐invasive fetal electrocardiography (fECG) system and to demonstrate this technique's ability to acquire recordings in twin and triplet pregnancies.

Design
Prospective cross sectional observational study.

Setting
Antenatal wards and clinics, day assessment unit and centre for fetal care at a tertiary referral hospital, London, UK.

Population or Sample
Three hundred and four singleton and multiple pregnancies, 15–41 weeks of gestation.

Methods
Using electrodes sited on the maternal abdomen, a fetal electrocardiography (fECG) system was developed and tested on 304 pregnant women from 15 to 41 weeks of gestation, of whom 241 were uncomplicated singletons, 58 had twin and 5 had triplet pregnancies. The composite abdominal signals were stored on a laptop computer and the fECG derived off‐line using a digital signal processing technique. For singletons, linear regression was used to analyse PR, QRS, QT and QTc intervals, and construct time‐specific reference ranges.

Main outcome measure
Duration of fECG time intervals as a function of gestational age. Success of signal seperation in singleton, twin and triplet pregnancies.

Results
For singletons, a total of 250 recordings was obtained from 241 individuals with a signal separation success rate of 85% (213/250). Success rates were significantly poorer between 27 and 36 weeks of gestation (2 × k χ2, P < 0.0001), with 84% (31/37) of separation failures occurring during this period. P, Q, R and S waves were seen in all cases where fetal signals were separated and were used to generate fECG time interval reference ranges. In 22% (43/199) of analysed cases, no T waves were identified, 63% (27/43) of whom were ≤24 weeks of gestation. In twins and triplets, separate fetal signals were obtained in 78% (91/116) and 93% (14/15), respectively; P, Q, R and S waves were evident in all averaged fECGs, while T waves were identified in 59% (54/91) and 57% (8/14).

Conclusions
This study provides reference ranges with gestation for fECG intervals derived non‐invasively from normal singleton pregnancies and demonstrates the feasibility of obtaining complete fECG recordings non‐invasively across a wide gestational range in pregnancies of all pluralities. The fECG time intervals described will enable the identification of pathological fECG recordings from high risk pregnancies where fECG abnormalities are suspected.
Validation of the Welch Allyn ‘Vital Signs’ blood pressure measurement device in pregnancy and pre‐eclampsia
Authors: Reinders A. , Cuckson A.C. , Jones C.R. , Poet R. , O'Sullivan G. , Shennan A.H.
Published: December 2003

Objective
To establish the accuracy the Welch Allyn ‘Vital Signs’ blood pressure monitor in pregnancy and pre‐eclampsia according to a modified British Hypertension Society protocol.

Design
Prospective observational study.

Setting
Maternity Unit/Obstetric Ward, Guy's and St Thomas' Hospital, London, UK.

Population
Forty‐three pregnant women of whom 12 had pre‐eclampsia.

Methods
Nine sequential same‐arm measurements were taken from each woman by two trained observers, alternating between a mercury sphygmomanometer and the device. The last seven readings were analysed according to the British Hypertension Society protocol. The accuracy of the device was determined using the grading scale indicated by the British Hypertension Society protocol (grade A/B = pass, grade C/D = fail).

Main outcome measures
Grading criteria of the British Hypertension Society Protocol.

Results
The Welch Allyn ‘Vital Signs’ monitor achieved a grade A for both systolic and diastolic pressures in pregnant women who did not have pre‐eclampsia. In those women with pre‐eclampsia, it achieved a grade D and B for systolic and diastolic pressures, respectively. The mean differences between the observers and the device in women without pre‐eclampsia were −2.6 (6.4) and −1.5 (7.2) mmHg for systolic and diastolic pressures [and in pre‐eclamptic women −7.8 (6.3) and −5.5 (6.5)mmHg]. It therefore fulfils criteria set by the Association for the Advancement of Medical Instrumentation (mean <5 mmHg and standard deviation <8 mmHg) in pregnancy, but not in pre‐eclampsia.

Conclusion
This is the first automated device suitable for robust clinical use that can be recommended for use in pregnancy. However, it should be borne in mind that—similar to other devices—it significantly under‐recorded readings obtained in pre‐eclamptic women.
The effects of a progesterone metabolite, 5β‐dihydroprogesterone, on oxytocin receptor binding in human myometrial membranes
Authors: Astle Shirley , Khan Raheela N. , Thornton Steven
Published: December 2003

Objective
To determine the effect of the progesterone metabolite 5β‐dihydroprogesterone on human oxytocin receptor binding in myometrial membranes and on whole‐cell calcium current in single myometrial cells.

Design
Receptor binding studies in human myometrial membranes prepared from biopsies taken before or after the onset of labour and in Chinese hamster ovary cells expressing the human oxytocin receptor. Whole cell patch‐clamp experiments were undertaken on isolated myometrial cells.

Setting
University research laboratories and University hospital.

Population
Patients undergoing caesarean section at term either prior to or following onset of labour.

Methods
Myometrial biopsies were taken from women undergoing caesarean section. The binding affinities of oxytocin, 5β‐dihydroprogesterone and atosiban were determined in myometrial membranes and Chinese hamster ovary cells expressing the human oxytocin receptor. The effect of 5β‐dihydroprogesterone on inward current was also determined in isolated myometrial cells.

Main outcome measures
Receptor binding affinity and electrophysiological inward current.

Results
5β‐Dihydroprogesterone did not reduce oxytocin receptor binding in myometrial membranes or Chinese hamster ovary cells expressing the human oxytocin receptor. Nor did it influence calcium current under whole‐cell patch conditions in single myometrial cells. In contrast, atosiban inhibited binding in myometrial membranes prepared from samples taken either prior to or following labour (Ki= 112 and 108 nM, respectively). The affinity of atosiban for the oxytocin receptor was much lower than oxytocin (Ki= 5 and 6 nM in samples taken before or after labour, respectively) in myometrial membranes and in Chinese hamster ovary cells expressing the human oxytocin receptor (Ki= 63 M and 1 nM for atosiban and oxytocin, respectively).

Conclusions
We conclude that 5β‐dihydroprogesterone is unlikely to regulate myometrial activity as a result of a direct effect on oxytocin receptor binding or inward calcium current.
Women's attitudes to HIV screening in pregnancy in an area of low prevalence
Authors: Jha Swati , Gee Harry , Coomarasamy Aravinthan
Published: December 2003

Objectives
To identify factors that influence acceptance of the human immunodeficiency virus (HIV) screening test by pregnant women.

Design
Prospective survey using questionnaires.

Setting
An antenatal clinic at a tertiary referral hospital.

Population
200 pregnant women of multiethic origin residing in a low prevalence area.

Methods
Two hundred consecutive women attending the antenatal booking clinic were interviewed. We collected data on reasons for opting in or out and factors that could influence the rate of acceptance, such as ethnicity, age, parity, level of education, first language and marital or relationship status.

Main outcome measure
Attitudes of pregnant women to HIV screening.

Results
The rate of acceptance of HIV screening was 160/200(80%). The most frequent reasons for opting in were the perceived benefits of screening (92/160, 58%) and the fact that the test is now routinely offered (87/160, 54%). The most frequent reason for refusal of screening was perceived low risk of HIV (27/40, 68%). Logistic regression analysis showed that ethnicity, age, parity and level of formal education did not play a role in influencing uptake of the test. However, women whose first language was English were more likely to opt in compared with those whose first language was not English (P= 0.016) and those who were married or in a stable relationship were more likely to opt in than those who were not (P < 0.001).

Conclusion
We have not reached the national target of 90% in our region. This appears to be due to a combination of factors, the main one being a perception of low risk. Greater knowledge of the ease of transmission of HIV may alter this perception, which may improve acceptance of the test.
Laparoscopic myomectomy for fibroids penetrating the uterine cavity: is it a safe procedure?
Authors: Seracchioli R. , Colombo F.M. , Bagnoli A. , Govoni F. , Missiroli S. , Venturoli S.
Published: December 2003

Objective
The purpose of the study was to evaluate the post‐operative course and follow up of women who had undergone laparoscopic removal of intramural fibroids penetrating the uterine cavity.

Design
Retrospective study.

Setting
Center for Reconstructive Pelvic Endosurgery, Italy.

Population
Thirty‐four women with fibroids penetrating the uterine cavity.

Methods
Laparoscopic myomectomy.

Main outcome measures
Feasibility and safety of surgical technique, length of operation, blood loss, intra‐ or post‐operative complications, length of hospital stay, resolution of symptoms and future obstetric outcome.

Results
The mean operative time was 79 (SD 30) minutes; the mean reduction in haemoglobin was 1.1 ± 0.9 g/dL. No intra‐ or post‐operative complications were observed. The average post‐operative stay in hospital was 54 (SD 22) hours. Nineteen (73%) out of 26 patients who had experienced symptoms prior to surgery reported resolution of these symptoms post‐operatively. All patients resumed work within a mean time of 20 (SD 8) days. Among 23 of the 32 patients attempting pregnancy during the follow up period, nine (39%) conceived within one year. Seven pregnancies went to term without complications.

Conclusion
The clinical results of this study suggest that laparoscopic myomectomy for intramural fibroids penetrating the uterine cavity is a safe procedure, providing well known advantages of minimal access surgery.
The 24‐hour pad test in continent women and men: normal values and cyclical alterations
Authors: Karantanis E. , O'Sullivan R. , Moore K.H.
Published: December 2003

Objective
To obtain control values for the 24‐hour pad test in a wide age range of continent women using accurate weighing scales and to compare the results obtained from pantyliners and pads in women and men.

Design
Prospective anonymous study.

Setting
A Sydney Tertiary Urogynaecology Unit.

Population
One hundred and forty continent women and 14 continent men.

Methods
A 24‐hour pad test was performed in 120 continent women of widely varying ages, in whom hormonal status and exercise habits were documented. These continent women wore a standardised pantyliner for 24 hours and a high precision beam balance (accuracy 0.1 g) was used to measure the loss on the pad. To assess any variation in pad weights with differing pads, 20 female volunteers undertook the 24‐hour test firstly with pantyliners then larger pads. To understand evaporative qualities of the two types of pads, one male wore each type of pad, instilled with 5 mL normal saline for eight hours overnight. Furthermore, to understand the contribution of vaginal secretions, a group of male volunteers performed a 24‐hour test with pantyliners followed by pads.

Main outcome measures
Pad weight, with regard to hormonal status, exercise, pad type and gender.

Results
The median age of subjects was 48 (interquartile range [IQR] 32–60), with a median pad weight gain of 0.3 g (IQR 0.2–0.6; 95th centile 1.3 g). Subgroup analysis showed no significant trends for pad loss in relation to menopause status, use of hormone replacement therapy or hormonal contraception and exercise status during the 24‐hour period. Control values for pantyliners were not significantly different from those for continence pads. In addition, normal values in 14 males showed similar results, regardless of pad type.

Conclusions
The response rate of 39% might limit the applicability of the results. However, our finding that women lose only 0.3 g of vaginal secretions in 24 hours is much lower than previously reported. This might arise from the use of a highly accurate beam balance and the recruitment of a large sample of women with widely varying ages. This result might lower the threshold for objective diagnosis of urinary incontinence and alters the pad test definition of ‘cure’.
Hormone replacement therapy and hypercoagulability. Results from the Prospective Collaborative Danish Climacteric Study
Authors: Sidelmann J.J. , Jespersen J. , Andersen L.F. , Skouby S.O.
Published: December 2003

Objective
To assess the influence of a variety of HRT regimens on the haemostatic balance using markers of fibrin turnover and inhibitors of coagulation.

Design
An open randomised study allocating women to either a control group or five different HRT treatment groups.

Setting
Gentofte Hospital, Hellerup, and Rigshospitalet, Copenhagen, Denmark.

Population
One hundred and forty‐nine postmenopausal women without previous venous thromboembolic disease.

Methods
Prothrombin fragment 1+2 (F1+2), fibrin degradation products, antithrombin, protein C, total protein S and activated protein C‐normalised ratio were measured at baseline and after 6 and 12 months of HRT in six groups of healthy postmenopausal women: (A) no HRT (reference group), (B) continuous oestradiol valerate (E2V) plus cyproterone acetate, (C) cyclic E2V plus cyproterone acetate, (D) continuous combined oestrogen (E2) plus norethindrone acetate, (E) E2 combined with local delivery of levonorgestrel and (F) E2V plus medroxyprogesterone.

Main outcome measures
HRT‐induced changes in the concentration of inhibitors of coagulation and markers of fibrin turnover during 12 months of treatment.

Results
Significant decreases of antithrombin and protein S were found in all treatment groups, of protein C in Groups C, D, E and F and of activated protein C‐normalised ratio in Groups E and F. Fibrin degradation products increased after three months of treatment, whereas F1+2 was persistently increased after three months in Group F. The cumulative response of antithrombin was significantly lower in Groups D, E and F than in the reference group. The cumulative response of protein S and activated protein C‐normalised ratio was lower, whereas that of F1+2 was significantly higher in Group F than in the reference group.

Conclusion
HRT reduces the inhibitory potential of coagulation significantly. The effect is related to the type of E2/progestin combination administered, but seems to be oestrogen‐derived as the most pronounced effect is found with only quarterly progestin intake. Such procoagulant activity of HRT may well translate into clinical manifestations in thrombosis‐prone individuals.
Randomised clinical trial to assess anal sphincter function following forceps or vacuum assisted vaginal delivery
Authors: Fitzpatrick Myra , Behan Michael , O'Connell P. Ronan , O'Herlihy Colm
Published: December 2003

Objective
To compare, in a prospective, randomised controlled trial, differences in anal sphincter function following forceps or vacuum assisted vaginal delivery in an institution practising standardised management of labour.

Design
Prospective, randomised controlled trial.

Setting
Tertiary‐referral maternity teaching hospital.

Population
One hundred and thirty women.

Methods
Primiparous women were recruited antenatally and if an instrumental delivery was indicated, were randomised to either a vacuum or low‐cavity, non‐rotational forceps assisted delivery. Follow up consisted of a symptom questionnaire, anal manometry and endoanal ultrasound at three months postpartum.

Main outcome measures
Faecal continence scores, anal manometry, endoanal ultrasound.

Results
Sixty‐one women delivered with forceps assistance (40 for failure to progress in the second stage) and 69 with vacuum assistance (33 for failure to progress); 16/69 vacuum deliveries proceeded to a forceps assisted delivery (23%). There were no statistical differences in the antecedent antenatal factors between the two groups. A third degree perineal tear followed 10 (16%) forceps and 5 (7%) vacuum deliveries. Based on intention‐to‐treat analysis, 36 (59%) women complained of altered faecal continence after forceps delivery compared with 23 (33%) following vacuum delivery three months postpartum (RR 2.88, 95% CI 1.41–5.88). Endoanal ultrasound was reported as abnormal following 34 (56%) forceps deliveries and 34 (49%) vacuum deliveries (RR 1.3, 95% CI 0.65–258). After exclusion of ‘failed vacuum’, median anal canal resting pressure was significantly lower following forceps delivery compared with vacuum delivery alone (P= 0.004). There were no significant differences in degree of ultrasound abnormality between the two groups.

Conclusions
Symptoms of altered faecal continence are significantly more common following forceps assisted vaginal delivery. Based on continence outcome, when circumstances allow, vacuum should be the instrument of first choice in assisted delivery.
A cost–utility analysis of tension‐free vaginal tape versus colposuspension for primary urodynamic stress incontinence
Authors: Manca Andrea , Sculpher Mark J. , Ward Karen , Hilton Paul
Published: December 2003

Objective
To assess the cost effectiveness of tension‐free vaginal tape compared with open Burch colposuspension as a primary treatment for urodynamic stress incontinence.

Design
Cost–utility analysis alongside a multicentre randomised comparative trial.

Setting
Gynaecology or Urology departments in 14 centres in the UK and Ireland, including University‐associated teaching hospitals and district general hospitals.

Population
Women with urodynamic stress incontinence. Exclusion criteria were: (1) detrusor overactivity; (2) major voiding problems; (3) prolapse; (4) previous surgery for incontinence or prolapse.

Methods
Resource use data were collected on all 344 patients in the trial, including length of hospital stay, time in theatre and management of complications; resource use was costed using UK unit costs at 1999–2000 prices.

Main outcome measures
Health outcomes were expressed in terms of quality‐adjusted life years (QALYs) between baseline and six months follow up, based on women's responses to the EQ‐5D health questionnaire.

Results
Tension‐free vaginal tape resulted in a mean cost saving of £243 (95% CI £341 to £201) compared with colposuspension. Differential mean QALYs per patient (tension‐free vaginal tape − colposuspension) was 0.01 (95% CI −0.01 to 0.03). The probability of tension‐free vaginal tape being, on average, less costly than colposuspension, was 100%, and the probability of tension‐free vaginal tape being more cost effective than colposuspension was 94.6% if the decision‐maker was willing to pay £30,000 per additional QALY.

Conclusion
The results from this trial suggest that, over a post‐operative period of six months, tension‐free vaginal tape is a cost effective alternative to colposuspension. The results will need to be reassessed on the basis of longer follow up.
A viable alternative to surgical vacuum aspiration: repeated doses of intravaginal misoprostol over 9 hours for medical termination of pregnancies up to eight weeks
Authors: Singh Kuldip , Fong Y.F. , Dong F.
Published: December 2003

Objective
To study the efficacy of repeated doses of vaginal misoprostol over 9 hours in a day care setting for terminating pregnancies up to eight weeks of gestation.

Design
An open, single arm prospective study conducted between January 2000 and December 2001.

Setting
Fertility Control Clinic, National University Hospital, Singapore.

Population
One hundred and fifty pregnant women with an unwanted pregnancy up to eight weeks of gestation requesting medical abortion.

Methods
The women were given an initial dose of 800 μg of vaginal misoprostol. A further dose of 400 μg was repeated every 3 hours for a maximum of three doses.

Main outcome measures
The complete abortion rate defined as successful cases that did not require vacuum aspiration.

Results
The complete abortion rate was 84.7% and 96.0% at 15 days and 43 days after initial administration of vaginal misoprostol. The mean interval between first dose of misoprostol and the onset of expulsion of products of conception (SD) was 8.1 hours (6.3). The mean and the median percentage changes in the serum β‐hCG levels at day 15 as compared with pre‐abortion levels were statistically significant (P < 0.001) and were a good predictor of the likely outcome of the medical abortion. The mean duration of bleeding (SD) was 11.7 days (4.7) and the mean duration between the onset of procedure and the return of normal menstruation (SD) was 35.5 days (5.7). There was no significant change in haemoglobin concentration. Lower abdominal pain, fever (>38.0°C) and diarrhoea were the most common side effects.

Conclusions
This regimen of repeated doses of vaginal misoprostol every 3 hours over a period of 9 hours, in keeping with the plasma level and pharmacokinetic of misoprostol administered vaginally, is an effective method of medical abortion that approaches the efficacy of surgical vacuum aspiration. The regimen would offer a suitable option for women requesting termination of pregnancy up to eight weeks of gestation in countries where mifespristone is and will never be made available.
Case–control study of teratogenic potential of thiethylperazine, an anti‐emetic drug
Authors: Czeizel A.E. , Vargha P.
Published: December 2003

Objective
Thiethylperazine is a commonly used anti‐emetic drug during pregnancy in Hungary. One experimental study in mice and rats found an increased occurrence of cleft palate after the use of thiethylperazine during pregnancy but the human data of thiethylperazine have not been reported. Thus, the aim of the study was to investigate the possible human teratogenic effect of thiethylperazine.

Design
Case–control approach.

Setting
The teratogenic potential of thiethylperazine was evaluated in the population‐based large data set of the Hungarian Case–Control Surveillance of Congenital Abnormalities between 1980 and 1996.

Sample
Of 38,151 newborn infants without any congenital abnormalities (control group), 746 (2.0%) had mothers who were treated with thiethylperazine, while of 22,843 cases with congenital abnormalities, 411 (1.8%) had mothers who were treated with thiethylperazine during pregnancy.

Methods
Case–control pair analysis.

Main outcome measure
Different congenital abnormalities.

Results
The pairs of cases with congenital abnormalities and their matched controls without congenital abnormalities were compared and this approach showed a somewhat higher rate of cleft lip ± palate (OR: 2.0 with 95% CI: 1.0–4.0) in infants born to mothers with thiethylperazine treatment during the first trimester of pregnancy.

Conclusion
Our data do not indicate clear teratogenic effect of thiethylperazine, however, a weak association was found between thiethylperazine use and cleft lip ± palate.
The Haven: a pilot referral centre in London for cases of serious sexual assault
Authors: Kerr Evelyn , Cottee Charlotte , Chowdhury Rima , Jawad Ruhi , Welch Jan
Published: December 2003

Objective
Several schemes have been reported to improve treatment of rape and to encourage reporting. The development of a comprehensive forensic and follow up service for complainants of sexual assault is described, and activities of the first year are reviewed.

Design
Retrospective review of case records of complainants examined in The Haven.

Setting
Department of Sexual Health in a London teaching hospital.

Sample
All case records, 676 complainants, from the first year of cases seen in The Haven.

Methods
Description of setting up a service in partnership between the National Health Service and the Metropolitan Police, called The Haven. Analysis of a standardised proforma used for case records.

Results
Mean age of complainants is 26 years (range 11–66); 6% were male. Assailant was categorised as a stranger in 52% of cases; attack involved physical violence in 50% of cases; 24% of victims had genital injuries; 39% had other physical injuries. Immediate care given at time of forensic examination included 30% of women receiving emergency contraception and 5% of clients receiving post‐exposure prophylaxis against HIV. Fifty‐five percent of clients returned for a sexual health screen and/or counselling. Thirty‐one percent received screening for sexually transmitted infections and 12% were diagnosed with one or more infections.

Conclusions
Requirements following sexual assault include forensic examination, first aid, postcoital contraception, prevention and management of sexually transmitted infections and psychosocial support. Provision of these services within a sexual health setting is feasible.
Myometrial microvascular endothelial cells express oxytocin receptor
Authors: Weston G.C. , Cann L. , Rogers P.A.W.
Published: December 2003

Objective
1. To establish whether microvascular endothelial cells from the human myometrium (MMECs) express oxytocin receptor, and to compare its expression levels relative to HUVECs. 2. To verify an up‐regulation of oxytocin receptor expression in MMECs as a result of vascular endothelial growth factor (VEGF), which had been found in a previous study.

Design
Laboratory scientific study.

Setting
University department.

Population or Sample
Myometrial biopsies from 12 hysterectomy specimens.

Methods
MMECs and HUVECs were established in vitro. Immunohistochemistry of in vitro cultures was performed to investigate protein expression of the oxytocin receptor. Semi‐quantitative RT‐PCR and Northern blots were performed to examine the presence and relative abundance of oxytocin receptor mRNA in MMECs and HUVECs, and in both cell types with and without VEGF. Total RNA from oxytocin acetate (100 nmol/L) and vehicle stimulated endothelial cell cultures was used to examine gene expression differences on a 10.5K cDNA microarray.

Main outcome measures
Oxytocin receptor mRNA and protein; gene expression anlysis.

Results
Oxytocin receptor mRNA and protein was present in MMECs. The level of expression was the same as for the HUVECs, but much less than the pregnant myometrium. No effect on gene expression could be demonstrated by gene expression microarray following 10 hours of oxytocin stimulation. Twenty‐four hours of VEGF stimulation did not significantly alter oxytocin receptor mRNA expression in MMECs or HUVECs.

Conclusion
The myometrial microvasculature expresses oxytocin receptor. This finding means that oxytocin may exert some of its effects on the myometrial microvasculature. No evidence could be found for a transcriptional effect of oxytocin stimulation in this study, but further work on the role of the myometrial vessel oxytocin receptor is needed.
Preterm birth in a French population: the importance of births by medical decision
Authors: Papiernik E. , Zeitlin J. , Rivera L. , Bucourt M. , Topuz B.
Published: December 2003

This analysis describes the prevalence of preterm birth by medical decision among 50,307 live births from the district of Seine‐Saint‐Denis in France, using a classification that distinguishes between medically decided preterm births associated with premature rupture of membranes and those for other reasons. Thirty‐seven percent of singleton and 28% of twin preterm births result from labour induction or a caesarean section in the absence of labour. One‐quarter of singleton indicated preterm births are associated with premature rupture of membranes. Between 28 and 31 weeks of gestation, 40% of all singleton preterm births result from a medical decision not associated with premature rupture of membranes. The high levels of indicated preterm birth must be taken into account in evaluations of preterm birth rates and trends in developed countries.
Antenatal screening for human platelet antigen‐1a: results of a prospective study at a large maternity hospital in Ireland
Authors: Davoren Anne , McParland Peter , Crowley John , Barnes Anthony , Kelly Gabrielle , Murphy William G.
Published: December 2003

ObjectiveFetomaternal mismatch for human platelet antigen (HPA)‐1a accounts for approximately 85% of cases of neonatal alloimmune thrombocytopenia. The purpose of the study was to determine the prevalence of the HPA‐1a negative platelet phenotype in a cohort of pregnant women in Ireland, the rate of alloimmunisation to HPA‐1a in HPA‐1 mismatched pregnancies and the associated incidence of neonatal alloimmune thrombocytopenia.

DesignA prospective case–control study.

SettingThe antenatal clinics of a large maternity teaching hospital.

Population or samplePregnant women, regardless of parity, presenting at the antenatal clinics.

MethodsAn enzyme‐linked immunosorbent assay (ELISA) designed for simultaneous HPA‐1a typing and antibody detection was used. Further analysis for HPA‐1a alloantibodies was performed using commercial ELISA's (GTI PakPlus and Pak1) and the monoclonal antibody immobilisation of platelet antigens assay. Confirmation of serological typing was by the polymerase chain reaction technique using sequence‐specific primers (PCR‐SSP).

Main outcome measuresThe presence of the HPA‐1a negative phenotype and its association with the development of maternal anti‐HPA‐1a and infant thrombocytopenia.

ResultsEighty‐four of 4090 consecutive women enrolled in the study tested positive for HPA‐1a in the screening ELISA. Confirmatory genotyping was performed on 67 women (representing 80% of the cohort), and 54 women (representing 3272 non‐selected pregnancies), were homozygous for the HPA‐1b allele (1.7%). Three of 34 (9%) women who delivered HPA‐1a positive babies had detectable anti‐HPA‐1a and all three babies had neonatal alloimmune thrombocytopenia, for an overall incidence of 1:1100 non‐selected pregnancies.

ConclusionsThe observed prevalence of 1.7% for the HPA‐1a negative platelet phenotype is as expected from studies in other countries. While we have demonstrated the practicability of antenatal HPA‐1a screening, further research is warranted to investigate maternal parameters predictive of severe fetal thrombocytopenia in HPA‐1a alloimmunised pregnancies.
The influence of smoking on the pregnancy‐associated plasma protein A, free β human chorionic gonadotrophin and nuchal translucency
Authors: Niemimaa Marko , Heinonen Seppo , Seppälä Maija , Ryynänen Markku
Published: December 2003

Objective
To analyse the effects of smoking on first trimester parameters used in prenatal screening for Down's Syndrome.

Design
A chart study.

Setting
Primary care centres and maternity clinics of the participating universities' and central hospitals.

Population
Three thousand and one hundred fifteen women screened by nuchal translucency measurement and 4436 women screened by maternal serum samples. Only normal singleton pregnancies were included.

Methods
The mean multiples of median of pregnancy associated plasma protein A (PAPP‐A), free beta human chorionic gonadotrophin (β‐hCG) and nuchal translucency were compared by independent samples t test after logarithmic transformation of the data between smokers and non‐smokers.

Main outcome measures
PAPP‐A and free β‐hCG concentrations and nuchal translucency measurements.

Results
PAPP‐A was significantly reduced and nuchal translucency increased if the mother smoked. The smokers were more frequently considered as being at high risk for Down's Syndrome.

Conclusions
Correcting PAPP‐A median for smokers down by 20% might improve the accuracy of the risk evaluations given to individual women. If the association between increased nuchal translucency and smoking can be confirmed, it poses interesting questions as to the reasons for increased nuchal translucency among normal pregnancies.
Pathways to evidence‐based reproductive healthcare in developing countries
Authors: Geyoushi Bohaira E. , Matthews Zoë , Stones R. William
Published: December 2003

Objective
Developing country clinicians are aware of the discourse of evidence‐based medicine but heavily constrained in their ability to access and apply new knowledge. This study aimed to obtain primary descriptive data about access to and application of reproductive health‐related medical knowledge in developing countries.

Design
Qualitative study using semi‐structured interviews.

Setting
India and Yemen.

Sample
Forty‐one doctors working in obstetrics, gynaecology, general practice and family planning services.

Methods
Interviews were tape recorded and transcribed verbatim. A theory‐driven approach was conducted to carry out thematic analysis.

Main outcome measures

Results
Doctors felt the need to update their knowledge but this was not always achieved due to time and financial constraints. Alternative knowledge sources were described including the Internet, scientific meetings, medical family networks and speciality medical societies but access to these was limited by the expense of equipment, unfamiliarity with the technology and restricted advertisement of scientific meetings and conferences. Institutional hierarchy and conflict of generations were identified as barriers to change. Demoralisation was a common obstacle. On the positive side, involvement in medical education was a powerful driver for seeking new knowledge and applying research evidence to clinical practice.

Conclusions
Priorities are to identify needs specific to different countries and medical settings in the developing world, access for all to full text journals and educational activities that fully engage practitioners in the early stages of their careers. Clinical teachers are the nodal group with the strongest incentive to obtain and use new knowledge.
Chronic open angle glaucoma: patient awareness of the nature of the disease, topical medication, compliance and the prevalence of systemic symptoms
Authors: Deokule Sunil , Sadiq Saghir , Shah Sunil
Published: December 2003

Purpose:  To study the awareness of the nature of the disease, compliance with treatment, and prevalence of systemic symptoms in a group of patients with chronic open angle glaucoma (COAG).

Method:  A structured questionnaire was designed and given to 260 consecutive COAG patients attending a general ophthalmology clinic. Questions related to the increased risk of COAG amongst family members, screening of family members, nature of field defects, variation in IOP, topical treatment and availability of a free eye test for a COAG patient in the UK were asked. Compliance and systemic symptoms were also assessed.

Results:  Forty‐one per cent (107 of 260) of patients in the study group were aware of the increased risk of COAG in family members and 45.5% (118 of 260) of patient's family members had undergone screening for COAG. Seventy‐three per cent (191 of 260) of the patients were aware of their own and their family members’ entitlement to a free eye test. Seventy‐seven per cent of patients claimed full compliance. Thirty per cent of patients were noted to have systemic symptoms.

Conclusions:  The awareness of the nature of COAG in this population was low and incidence of perceived drug related systemic symptoms very high. Both of these may contribute to poor compliance.
Effect of light filters on reading speed in normal and low vision due to age‐related macular degeneration
Authors: Eperjesi Frank , Fowler Colin W. , Evans Bruce J. W.
Published: December 2003

Purpose:  To investigate the effects of light filters on reading speed in normal and low vision due to age‐related macular degeneration (AMD).

Methods:  Reading speed was determined for 12 subjects with normal vision and 12 subjects with non‐exudative AMD using stationary lowercase nonsensical print in Times Roman font and four light filters; a yellow Corning Photochromic Filter (CPF) 450, a grey neural density (ND) filter, an individual filter obtained using the Intuitive Colorimeter® and a clear filter.

Results:  There was no statistically significant light filter effect on reading speed for the normal subjects. The AMD group demonstrated a statistically significant 5% average improvement in reading speed with the CPF450 compared with the other filters although some AMD subjects had improvements of 10–15%.

Conclusions:  Light filters obtained using the Intuitive Colorimeter® performed poorly when compared with the CPF450, ND and clear filters for both the study groups. For the AMD group, average reading speed was statistically greater with the CPF450 than the other filters, however it is questionable whether the improvement (5%) would be clinically significant. As some of the subjects with AMD had greater improvements with the CPF450 we advocate clinical assessment of light filters using existing protocols on an individual basis.
Continuity of Bethe solutions with respect to chain length N and winding numbers {λl}
Authors: Caspers W. J. , Wal A. , Łabuz M. , Kuźma M. , Lulek T.
Published: December 2003

Bethe solutions for r reversed spins are characterized by a set of winding numbers {λ1⩽λ2⩽⋯⩽λr}. Such classification is, however, not unique since the same sequences can describe different solutions and different sequences yield essentially equivalent states. These ambiguities should find their resolution in a complete configuration. We demonstrate here that in general a solution with a fixed sequence of winding numbers evolves in a quasicontinuous way as the function of N, the number of spins. This property could be disturbed in some cases at special transition point Ntr. We explain analytically the origin of this discontinuity. Consideration was addressed for three and four spin deviations.
Continuous symmetries of Lagrangians and exact solutions of discrete equations
Authors: Dorodnitsyn Vladimir , Kozlov Roman , Winternitz Pavel
Published: December 2003

One of the difficulties encountered when studying physical theories in discrete space–time is that of describing the underlying continuous symmetries (like Lorentz, or Galilei invariance). One of the ways of addressing this difficulty is to consider point transformations acting simultaneously on difference equations and lattices. In a previous article we have classified ordinary difference schemes invariant under Lie groups of point transformations. The present article is devoted to an invariant Lagrangian formalism for scalar single-variable difference schemes. The formalism is used to obtain first integrals and explicit exact solutions of the schemes. Equations invariant under two- and three-dimensional groups of Lagrangian symmetries are considered
The dynamics of conformational isomerization in flexible biomolecules. II. Simulating isomerizations in a supersonic free jet with master equation dynamics
Authors: Evans David A. , Wales David J. , Dian Brian C. , Zwier Timothy S.
Published: December 2003

Infrared-induced conformational isomerization of N-acetyl-tryptophan methyl amide is studied theoretically using a microcanonical Rice–Ramsperger–Kassel–Marcus description of the rates on potential energy surfaces calculated using the AMBER and OPLS-AA force fields. The results are compared with the experimental data from Dian et al. in the preceding paper [J. Chem. Phys. 120, 133 (2004)]. An exhaustive search of the potential energy surfaces locates all minima and transition states on these surfaces. A simple model is proposed for the vibrational cooling, and an appropriate cooling rate is chosen as the standard conditions for the master equation simulations by comparison with experiment. The two potential energy surfaces differ in the relative energies of minima and the heights of key transition states, leading to differences in the dominant pathways and rates of conformational isomerization. The predicted quantum yields depend sensitively on the cooling rate, varying from the slow cooling limit in which equilibrium populations are achieved to the fast quenching limit in which conformational isomerization is shut off. The excitation energy is varied from 5 to 20 kcal mol−1. At the lowest energies, isomerization is completely quenched, while at the highest energies, equilibrium conditions are achieved. In between these extremes, the quantum yields are sensitive to the excitation energy, and can be used to locate the rate-limiting barriers to isomerization.
Nonadiabatic holonomy operators in classical and quantum completely integrable systems
Authors: Giachetta G. , Mangiarotti L. , Sardanashvily G.
Published: December 2003

Given a completely integrable system, we associate to any connection on a fiber bundle in invariant tori over a parameter manifold the classical and quantum holonomy operator (generalized Berry’s phase factor), without any adiabatic approximation.