bluuebunny/crossref_metadata_2025 huggingface dataset:
External cephalic version with epidural anaesthesia after failure of a first trial with beta‐mimetics
Authors: Rozenberg Patrick , Goffinet François , de Spirlet Marina , Durand‐Zaleski Isabelle , Blanié Pierre , Fisher Catherine , Lang Anne‐Christine , Nisand Israel
Published: August 2005

Objective
To assess the efficacy, tolerance, and cost of external version under epidural anaesthesia and beta‐mimetic tocolysis after the failure of an initial attempt with tocolysis alone.

Design
Prospective open study.

Participants
Sixty‐eight women with breech presentation at around 36 weeks of gestation and an attempted external cephalic version under salbutamol that failed, who consented to try a second attempt under epidural anaesthesia.

Results
The overall success rate under epidural anaesthesia was 39.7% (27/68), and complications occurred in two cases. The total cost of attempting external version was higher than the cost of expectant management.

Conclusions
The efficacy of external cephalic version under epidural reduces the rate of caesarean sections associated with breech presentation, but its relative safety remains in question. Moreover, our economic analysis discourages the hope of lowered costs suggested by earlier reports that this technique is more expensive than expectant management, except in institutions with a policy of systematic caesarean sections when version fails.
The effect of thrombophylaxis on pregnancy outcome in patients with recurrent pregnancy loss associated with factor V Leiden mutation
Authors: Younis Johnny S. , Ohel Gonen , Brenner Benjamin , Haddad Sami , Lanir Naomi , Ben‐Ami Moshe
Published: August 2005

Objective
To observe the effect of thrombophylaxis on pregnancy in women with a history of unexplained recurrent pregnancy loss also carrying the factor V Leiden mutation.

Methods
Between 1 January and 31 December 1996, activated protein C (APC) resistance and factor V Leiden mutation were prospectively measured in 56 nonpregnant women, with a history of two or more unexplained recurrent pregnancy losses. During the same study period, seven women carrying the factor V Leiden mutation conceived, and were subsequently followed throughout their pregnancy. Subcutaneous low molecular weight heparin (LMWH, enoxaparin, 40 mg/day) and oral low dose aspirin (100 mg/day) were administered throughout the pregnancies, starting at early first trimester. Ultrasound and Doppler umbilical and fetal middle cerebral arterial flow studies were performed in the second and third trimesters, and the course and outcome of the pregnancies were documented.

Results
Activated protein C resistance and factor V Leiden were found in 20 (36%) and 12 (21%) women of the study, respectively. Five of the seven pregnancies occuring progressed uneventfully to term with normal fetal growth, normal Doppler flow studies and uneventful neonatal outcome. Two of the seven women had early missed abortions.

Conclusions
Thrombophylaxis, beginning in early pregnancy, in women with unexplained recurrent pregnancy loss associated with factor V Leiden mutation, seems to be safe and allow normal fetal development and good neonatal outcome. To prove the efficacy of thrombophylaxis by LMWH and low dose aspirin in this setting prospective controlled studies seem to be justified.
Comparative trends in cause‐specific fetal and neonatal mortality in twin and singleton births in the North of England, 1982–1994
Authors: Glinianaia Svetlana V. , Pharoah Peter , Sturgiss Steve N.
Published: August 2005

Objective
To examine trends in cause‐ and birthweight‐specific fetal and neonatal mortality rates in twins and singletons.

Design
Descriptive analysis based on a regional register.

Setting
The Northern Health Region of England, 1982–1994.

Sample
Two hundred and thirty‐six fetal and 356 neonatal twin deaths; 2687 fetal and 2301 neonatal singleton deaths from a population of 10,734 twins and 505,477 singletons.

Main outcome measures
Fetal and neonatal autopsy rates, cause‐ and birthweight‐specific fetal and neonatal mortality rates in twins and singletons.

Results
The extended perinatal mortality (including stillbirths and neonatal deaths) rate (EPMR) was 55.2 per 1000 in 1982–1994 in twins compared with 9.9 per 1000 in singletons. The relative risk for twin compared with singleton deaths was 5.6 (95% CI 5.1‐6.1) being highest for immaturity (12.9, 95% CI 11.1–15.0). A significant decrease in the EPMR occurred in both twins and singletons in 1988–1994 compared with 1982–1987. The EPMR decreased mainly due to a reduction of deaths from antepartum asphyxia in twins and intrapartum asphyxia and trauma in singletons, as well as a reduction in congenital malformations in both groups. In both twins and singletons, birthweight‐specific mortality rates improved between 1982–1987 and 1988–1994.

Conclusion
The higher relative risk for twin deaths remained stable due to a similar decrease in the EPMR for both twins and singletons. The cause‐specific relative risk in twins declined for antepartum asphyxia. The mortality rate resulting from lethal congenital malformations decreased in twins and singletons mainly due to earlier detection and subsequent termination of pregnancy.
The continuing fall in incidence of hypoxic‐ischaemic encephalopathy in term infants
Authors: Smith Julie , Wells Louise , Dodd Keith
Published: August 2005

Objective
To examine trends in incidence of hypoxic‐ischaemic encephalopathy in term infants over a twenty‐one year period.

Design
A retrospective analysis of medical records of all term infants admitted to a neonatal unit with hypoxic‐ischaemic encephalopathy during the years 1992–1996 (period C) and a comparison with data from the years 1976–1980 (period A) and 1984–1988 (period B) from the same unit (previously published1).

Setting
A District Health Authority in Central England serving a population of about 450,000.

Sample
All term infants admitted with clinical features of hypoxic‐ischaemic encephalopathy.

Main outcome measures
Incidence of three grades of hypoxic‐ischaemic encephalopathy, disability and mortality.

Results
In each five year period there were similar numbers of births. Over the time‐span of this study the stillbirth rate and neonatal mortality rate has consistently fallen. The overall incidence of hypoxicischaemic encephalopathy in term infants was significantly lower (P < 0.001; OR 0.42 CI 0.29–0.59) in the present study period (C) compared with the earlier study period B (1.9 vs 4.6 per 1000 total live births). The fall in moderately and severely affected infants between the present and the first study period was significant (1.2 vs 2.6 per 1000 total live births, P < 0.001: OR 0.46 CI 0.29–0.72). The number of deaths and the incidence of cerebral palsy in survivors fell progressively over the 21 years spanned by this study.

Conclusion
This study shows that the incidence of hypoxic‐ischaemic encephalopathy and its sequelae in term infants has fallen significantly. The use of cardiotocography and caesarean section rates have risen but the relative contributions of changes in clinical practice are uncertain.
Decision to delivery intervals for assisted vaginal vertex delivery
Authors: Okunwobi‐Smith Yetunde , Cooke Inez , MacKenzie I. Z.
Published: August 2005

Objective
To describe the time interval between decision for assisted vaginal delivery and the birth of the baby in different clinical circumstances.

Design
A prospective analysis of 225 consecutive women with a singleton fetal cephalic presentation in the second stage of labour requiring an operative vaginal delivery for various reasons.

Setting
A maternity unit in a district general hospital delivering more than 6000 women annually.

Main outcome measures
The decision to delivery interval and the immediate and short term maternal and neonatal outcomes according to indication for operative vaginal delivery.

Results
The mean (SD) decision to delivery interval was 34.4 minutes (28.3) with a range of 5 to 101 minutes. For those delivered because of suspected fetal distress, the interval of 26.5 minutes (14.0) was significantly shorter than for those performed without fetal distress 39.5 minutes (19.0) (P < 0.0001); for cases with fetal distress, forceps were significantly quicker at 23.3 minutes (14.3) than the ventouse 29.2 minutes (13.2) (P= 0.04). The longer the interval in cases of fetal distress the less favourable the condition of the neonate at birth, although this trend did not reach statistical significance and was not seen for deliveries expedited for other reasons. Perineal repair was required following 96% forceps deliveries compared with 87% ventouse (P= 0.015). Perineal trauma was not influenced by the interval between decision and delivery.

Conclusions
If speed of delivery is important, use of forceps results in a quicker birth than use of the ventouse, without any compromise to the condition of the baby at delivery, and with similar rates of perineal trauma.
The outcome of pregnancy in Kell alloimmunisation
Authors: Grant S. R. , Kilby M. D. , Meer L. , Weaver J. B. , Gabra G. S. , Whittle M. J.
Published: August 2005

Objective
To assess management and outcome of pregnancies with anti‐Kell in the West Midlands in the UK over 13 years.

Design
A retrospective review of casenotes.

Setting
A regional referral clinic for red cell alloimmune disease and fetal medicine unit at a university hospital.

Population
Sixty‐five pregnancies were identified in 52 Kell‐sensitised women with Kell positive partners from the records of the Birmingham Blood Transfusion Centre.

Methods
Information from the casenotes was entered on a database and comparisons were made using the SPSS for Windows statistics package.

Main outcome measures
Mode of sensitisation, degree of fetal or neonatal anaemia, need for transfusion, gestation at delivery, birthweight and pregnancy outcome.

Results
Alloimmunisation was transfusion‐related in 29 pregnancies and pregnancy‐induced in 33. The cause could not be identified in three cases. There were 22 proven Kell positive fetuses, of which 18 were affected, in which alloimmunisation was pregnancy‐related in 12 cases and transfusion‐related in five. Antibody titres and amniotic fluid OD450 were not helpful in management. Severe or very severe disease occurred in 50% of the affected pregnancies (9/18). There was no difference in pregnancy outcome between transfusion or pregnancy induced sensitisation.

Conclusions
Anti‐Kell alloimmunisation is an uncommon cause of serious anaemia in a significant proportion of affected pregnancies. There appears to be no difference between that caused by pregnancy or transfusion. Estimation of fetal haemoglobin concentration by cordocentesis is recommended, as antibody titres and amniocentesis are not helpful.
The maternal cerebral circulation in pre‐eclampsia: investigations using Laplace transform analysis of Doppler waveforms
Authors: Brackley Karen J. , Ramsay Margaret M. , Pipkin Fiona Broughton , Rubin Peter C.
Published: August 2005

Objective
To compare the maternal cerebral circulation in pre‐eclampsia and normal pregnancy using an alternative method of Doppler waveform analysis called the Laplace transform analysis, which provides haemodynamic data additional to standard Doppler indices.

Design
A prospective cross‐sectional study.

Setting
Department of Obstetrics and Gynaecology, Nottingham University Hospital.

Sample
The study involved 17 women in the third trimester of a normal pregnancy, 11 with pregnancyinduced hypertension and 26 with pre‐eclampsia.

Methods
Doppler recordings were obtained from the internal and external carotid and middle cerebral arteries, with the measurements in hypertensive women being carried out before any treatment was given. The waveforms were then subjected to Laplace transform analysis which provides information on vessel wall stiffness and upstream and downstream flow conditions.

Main outcome measures
The determination of the Laplace transform analysis parameters, including alpha, the natural frequency of oscillation and real pole, and pulsatility index.

Results
Laplace transform analysis demonstrated a significant increase in vessel wall stiffness in all the arteries in hypertensive pregnancies, but this was more marked in pre‐eclampsia. The data were also consistent with, but do not prove, increased downstream resistance in the middle cerebral artery in women with pre‐eclampsia but not in those with pregnancy‐induced hypertension.

Conclusions
The Laplace transform analysis of Doppler waveforms yields important physiological information concerning the cerebral circulation in pre‐eclampsia, not detected using conventional Doppler indices. The results suggest that both pre‐eclampsia and pregnancy‐induced hypertension are associated with increased cerebral arterial wall stiffness and that, in addition, there may be cerebral vasoconstriction in pre‐eclampsia.
Is an atherogenic lipoprotein profile in the fetus a prerequisite for placental vascular disease?
Authors: Wang Jian , Trudinger Brian
Published: August 2005

Objective
To measure the blood apolipoprotein A‐1 and apolipoprotein B in the fetal circulation in normal pregnancy and in pregnancy with evidence of vascular disease in the fetal umbilical placental circulation defined in the antenatal period by Doppler ultrasound study.

Design
An observational study to compare fetal plasma apolipoprotein levels in normal and complicated pregnancy.

Setting
A university hospital tertiary referral obstetric unit.

Samples
Umbilical vein blood was collected at delivery from 22 normal fetuses delivered by elective caesarean section for non fetal reasons and 30 fetuses with evidence of umbilical placental vascular disease identified antenatally by Doppler ultrasound study.

Methods
Plasma apolipoprotein A‐1 and B were determined using an enzyme‐linked immunosorbent assay (ELISA) methods.

Main outcome measures
Fetal plasma levels of apolipoprotein A‐1 and B were measured.

Results
There was a significantly lower level of fetal plasma apolipoprotein A‐1 in placental insufficiency [placental insufficiency vs normal pregnancy, median 0.30 g/L (interquartile range 0.24, 0.39 g/L) vs 0.35 g/L (0.31, 0.42 g/L), P= 0.045]. In contrast, the levels of fetal plasma apolipoprotein B in placental insufficiency [0.20 g/L (0.17, 0.26 g/L)] were significantly increased compared with normal pregnancy [0.16 g/L (0.14, 0.20 g/L), P= 0.03]. The ratio of fetal plasma apolipoprotein B to A‐1 was also substantially higher in placental insufficiency [0.68 (0.55, 0.83)] than in normal pregnancy [0.45 (0.36, 0.60), P= 0.0003].

Conclusions
Our study has demonstrated that levels of fetal plasma apolipoprotein A‐1, apolipoprotein B and the ratio of apolipoprotein B to A‐1 were altered in the fetuses who are victims of umbilical placental insufficiency in the same direction as in adults associated with a high risk of atherogenesis.
Has endometrial ablation replaced hysterectomy for the treatment of dysfunctional uterine bleeding? National figures
Authors: Bridgman Stephen A. , Dunn Kate M.
Published: August 2005

Objectives
To describe trends in the use of endometrial ablation and hysterectomy for the treatment of dysfunctional uterine bleeding.

Design
Analysis of hospital admissions data.

Setting
National Health Service Hospitals in England.

Population
Women who underwent a hysterectomy or endometrial ablation for dysfunctional uterine bleeding between 1989 and 1996.

Main outcome measures
Annual operation rates and standardised operation ratios for England and for the National Health Service Regions within it, and proportion of operations for dysfunctional uterine bleeding that were endometrial ablations or hysterectomies.

Results
There was an initial rise in operation rates for endometrial ablation until 1992/3, since when the rates have fallen. Hysterectomy rates have remained relatively steady since the introduction of endometrial ablation. The total operation rates for dysfunctional uterine bleeding initially increased but have tended to fall since 1992/3. The ratio of hysterectomy to endometrial ablation for dysfunctional uterine bleeding troughed at 3:1 in 1992/3, but by 1995/6 had increased to 4:1.

Conclusions
Rather than replacing hysterectomy in the treatment of dysfunctional uterine bleeding, endometrial ablation appears to have added an alternative operative technique. This led to an increase in the total number of operations for this condition, perhaps by lowering the threshold for intervention.
Lateral distribution of nonendometriotic benign ovarian cysts
Authors: Vercellini Paolo , Pisacreta Anna , Vicentini Sarah , Stellato Giovanna , Pesole Antonella , Crosignani Pier Giorgio
Published: August 2005

To investigate the left‐ and right‐sided distribution of nonendometriotic benign ovarian cysts, data were collected on 406 women undergoing first‐line surgery for tumours with various histotypes. Considering the unilateral cysts, the observed proportion of left lesions was 65/129 (50.4%) in the serous, 38/79 (48.1%) in the mucinous, 59/134 (44.0%) in the dermoid, 11/21 (52.4%) in the parovarian, and 3/7 (42.9%) in the miscellaneous cysts group, without significant differences from the expected 50%. This contrasts with the finding of a significantly more frequent development of endometriomas on the left ovary, and suggests that the pathogenesis of endometriotic and nonendometriotic cysts is different.
Double‐blind randomised controlled trial of glyceryl trinitrate spray for external cephalic version
Authors: Yanny Heba , Johanson Richard , Baldwin K. Joanne , Lucking Linda , Fitzpatrick Ray , Jones Peter
Published: August 2005

A placebo controlled trial of glyceryl trinitrate was carried out in women whose first attempt at external cephalic version without tocolysis had been unsuccessful. No significant differences between groups were found and no side effects were noted. It is recommended that a larger, possibly multicentre study, should be undertaken.
Prothrombin 20210 G→A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy
Authors: McColl M. D. , Ellison J. , Reid F. , Tait R. C. , Walker I. D. , Greer I. A.
Published: August 2005

Over 50 unselected women with maternal venous thromboembolism were screened for the prothrombin 20210 G→A and MTHFR C677T mutations, in addition to screening for other thrombophilias. The prevalence of thrombophilia in these women was compared with its prevalence in the general population in our area. The prothrombin (OR 4.4; 95% CI 1.2‐16) and factor V Leiden (OR 4.5; 95% CI 2.1‐14.5) mutations were more common in our patients, compared with the general population, whereas women homozygous for the C677T mutation in the methylene tetrahydrofolate reductase gene (OR 0.45; 95% CI 0.13‐1.58) were not. It is recommended that women with a personal or strong family history of venous thromboembolism should be screened for the prothrombin mutation either before or early in pregnancy, in addition to screening for other thrombophilias. Screening for the MTHFR mutation does not appear to identify women at increased risk of maternal venous thrombosis.
Inter‐observer variation in histopathological diagnosis and grading of vulvar intraepithelial neoplasia: results of an European collaborative study
Authors: Preti Mario , Mezzetti Maura , Robertson Chris , Sideri Mario
Published: August 2005

Objective
To evaluate the inter‐observer variability of vulvar intraepithelial neoplasia diagnosis and grading system.

Design
Prospective study.

Sample
Histological sections of 66 vulvar biopsies.

Methods
Six consultant pathologists working at different European institutions independently reviewed 66 vulvar biopsies. The following variables were investigated: specimen adequacy, gross categorisation into benign or neoplastic changes, presence of atypical cytological pattern, presence of neoplastic architectural pattern, grade of vulvar intraepithelial neoplasia, presence of histopathologic associated findings for human papillomavirus infection.

Main outcome measures
The degree of inter‐observer variation for each histopathologic parameter was assessed by Kappa (κ) statistics. The frequency and the degree of disagreement were calculated by a symmetrical agreement matrix showing the number paired classifications.

Results
A good agreement (overall weighted κ= 0.65, unweighted κ= 0.46) was observed for grading vulvar intraepithelial neoplasia. Human papillomavirus infection associated findings and specimen adequacy were the variables with less inter‐observer agreement (overall weighted κ 0.26 and 0.22, respectively). Exact agreement between two pathologists for grade of vulvar intraepithelial neoplasia was observed in 63.6% of paired readings; the rate of paired agreement reached 73.9% considering vulvar intraepithelial neoplasia 2 and 3 as a single class. Conversely, only 5.0% of vulvar intraepithelial neoplasia 1 diagnoses were concordant in paired analysis.

Conclusions
Current terminology offers a reproducible tool in the hands of expert pathologists. While on the diagnosis of ‘high grade’ vulvar intraepithelial neoplasia (vulvar intraepithelial neoplasia 2 and 3) there is good agreement, the diagnostic category of vulvar intraepithelial neoplasia 1 is not reproducible.
Reproductive failure in women living in iodine deficient areas of West Africa
Authors: Dillon J. C. , Milliez J.
Published: August 2005

Objectives
To investigate the association between iodine status and reproductive failure in a population of West African women.

Design
Epidemiological survey on iodine deficiency disorders carried out in 1996–1997.

Setting
The iodine deficient areas of Senegal (Casamance and Senegal Oriental).

Population
Four thousand nine hundred and eighty women, aged 10 to 50, of whom 1544 adolescent and 462 pregnant women were examined for thyroid size and urinary iodine excretion. Their iodine status was associated with their fertility rate and reproductive failures.

Results
Reproductive failure (defined as repeated miscarriages and stillbirth) was associated with low iodine status, with severe iodine deficiency increasing the risk. Poor nutritional status and illiteracy had a significant effect on the outcome of pregnancy: underweight women had a fourfold higher risk, and those who were illiterate an eightfold higher risk, of failed pregnancy, compared with nutritionally healthy, literature women.

Conclusions
These findings emphasise the need to implement an effective iodine supplementation programme targeted at young and pregnant women in this area of western Africa. They also emphasise the importance of improving the nutritional status of young girls and the crucial role played by education in the prevention of reproductive failure.
Views of Finnish doctors on fetal screening
Authors: Hemminki Elina , Toiviainen Hanna , Santalahti Päivi
Published: August 2005

Objective
To investigate the views of Finnish doctors concerning fetal screening.

Design
Anonymous, questionnaire survey conducted in 1996–1997.

Population
A representative sample of gynaecologists, paediatricians and general practitioners in Finland. Both leading doctors and ordinary practitioners were included.

Results
Most doctors said that serum screening for Down's syndrome and ultrasound screening for structural abnormalities should be available for all pregnant women. In response to more direct questions, doctors acknowledged many drawbacks to Down's serum screening, notably the worry due to false positives. Only a few were against abortion, and a fifth said fetal screening is partly based on a eugenic ideology. There were some differences between the different doctor groups, but the overall impression was of similarity rather than divergence, both between the different specialist groups, and by the position of the doctor (leading vs ordinary).

Conclusions
Finnish doctors support current fetal screening, but many acknowledged resulting ethical, psychological, and social problems.
The effect of immersion on haemodynamic and fetal measures in uncomplicated pregnancies of nulliparous women
Authors: Kwee A. , Graziosi G. C. M. , van Leeuwen J. H. Schagen , van Venrooy F. V. , Bennink D. , Mol B. W. J. , Cohlen B. J. , Visser G. H. A.
Published: August 2005

Objective
To evaluate the effect of immersion in water on maternal haemodynamic measures and fetal heart rate patterns in healthy nulliparous women.

Design
A randomised cross‐over study.

Participants
Twenty pregnant women were studied between 26–29 weeks and between 34–37 weeks of gestation.

Methods
The women were either immersed in water for 35 minutes or rested on a bed for a similar period of time. Maternal blood pressure, thoracic electrical bioimpedance, urine and blood samples, and fetal heart rate patterns were obtained before and after immersion or bedrest.

Results
Compared with bedrest and pre‐immersion values, immersion resulted in a significant decrease in blood pressure, which returned to baseline values within 1.5 hour. Urine production increased for a short period after immersion, but 24 hour samples showed no difference compared with bedrest. Sodium, potassium and creatinine levels in urine remained constant. No significant changes were found for the other haemodynamic measures. There were no effects on fetal heart rate nor on its variation.

Conclusion
In healthy pregnant women immersion for 35 minutes has a clear effect on blood pressure and urine production. However, these effects are short lasting.
Wrong turn—dead end
Authors: Kent Andrew S. H. , Eed Renaldo , Beynon John L.
Published: August 2005

The phenomenon of transperitoneal migration of sperm has been described and considered in the literature but can only be proven under a unique set of circumstances. The possibility of an ectopic pregnancy in an unreversed tubal remnant after a reversal of sterilisation in the contralateral tube has been postulated1 but never reported. The aim of this report is to describe such an occurrence with a resultant ectopic pregnancy being diagnosed in a noncontiguous tubal remnant.
A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women
Authors: Carey Beverly J. , Carey Adam H. , Patel Sanjaykumar , Carter Graham , Studd John W. W.
Published: August 2005

Objective
To determine the pharmacokinetics of a progesterone cream following short and long term dermal administration.

Design
Single‐centre, randomised, multiple‐dose, open‐label study.

Setting
Reproductive Medicine Trust, London.

Population
Twenty‐four healthy postmenopausal women aged between 40 and 65 years were recruited through an advertisement in a local newspaper.

Methods
The women were randomly allocated to progesterone cream 40 mg daily or 20 mg, twice daily, for 42 days.

Main outcome measures
The concentration of progesterone in the serum was measured on days 1 and 42 before the morning dose, and at 2, 4, 6, 12 and 24 hours after the morning dose. Serum follicle stimulating hormone, oestradiol, testosterone and urinary pregnanediol‐3‐glucuronide were also measured on days 1 and 42.

Results
Three subjects dropped out before using the cream and two more dropped out after the first treatment leaving a reportable sample of 19 women. There was a rise in the mean progesterone concentration at each sampling time between days 1 and 42. There was evidence of a rise in pregnane‐diol‐3‐glucuronide over the course of the study. There was no change in follicle stimulating hormone, oestradiol or testosterone. There was no difference between the two regimens.

Conclusions
Transdermal progesterone (40 mg) per day for 42 days causes a small increase in serum progesterone concentration, although there is wide variation. Whether such levels are of clinical benefit remains to be seen.
Nifedipine or prazosin as a second agent to control early severe hypertension in pregnancy: a randomised controlled trial
Authors: Hall D. R. , Odendaal H. J. , Steyn D. W. , Smith M.
Published: August 2005

Objective
To determine whether nifedipine or prazosin is the more appropriate second‐line antihypertensive agent in pregnancy.

Design
Randomised controlled trial.

Setting
Tygerberg Hospital, a tertiary referral centre.

Population
Women with early, severe pre‐eclampsia or hypertension in pregnancy, whose blood pressure could not be adequately controlled by methyldopa 2 g/day, but were otherwise stable.

Methods
Nifedipine or prazosin were given and increased as necessary in a stepwise fashion. Once the maximum dose was reached, the other drug was added in a crossover pattern. Failure to control blood pressure, or the onset of maternal/fetal complications were indications for delivery. Patients reaching a minimum gestation of 34 weeks without complications were delivered electively.

Main outcome measures
Antenatal days gained; major maternal complications and perinatal survival.

Results
Days gained on the second antihypertensive agent did not differ significantly (P= 0.9), while more days were gained using nifedipine as the crossover ‘third agent’ (P= 0.01). In the nifedipine group better renal function was recorded, but more cases with isolated low platelet counts occurred. More cases of pulmonary oedema as well as more nonviable mid‐trimester and third trimester intrauterine deaths occurred in the prazosin group.

Conclusion
Nifedipine and prazosin as second agents allowed comparable amounts of time to be gained, although this changed when used as crossover third‐line agents. The efficacy and safety of nifedipine in this study are consistent with the results of other studies. A greater number of intrauterine deaths occurred in the prazosin group.
Detection of fetal Rhesus D and sex using fetal DNA from maternal plasma by multiplex polymerase chain reaction
Authors: Zhong Xiao Yan , Holzgreve Wolfgang , Hahn Sinuhe
Published: August 2005

Objective
To test the sensitivity, specificity and reproducibility using fetal DNA obtained from plasma of pregnant women by polymerase chain reaction for the simultaneous detection of both fetal sex and Rhesus D genotype.

Method
Blood samples were obtained from 22 Rhesus D negative pregnant women about to undergo an invasive procedure. DNA was extracted from the plasma fraction and analysed by a multiplex nested polymerase chain reaction using Y chromosome—and Rhesus D—specific primers. The results of this experimental procedure were compared with those obtained from the analysis performed on material gained by the invasive procedure.

Results
The sensitivity of the plasma polymerase chain reaction‐based method was surprisingly high, with both fetal genotypes being correctly determined in almost 100% of the cases examined. In only one instance was a false positive result for the detection of Rhesus D recorded, which on subsequent analysis was negative.

Conclusions
The ease and rapidity with which the plasma polymerase chain reaction‐based method can be performed makes it a promising method for the analysis of multiple fetal loci, such as Rhesus D and sex.
Dyslipoproteinaemia in postmenopausal women with a history of eclampsia
Authors: Hubel Carl A. , Snaedal Sunna , Ness Roberta B. , Weissfeld Lisa A. , Geirsson Reynir T. , Roberts James M. , Arngrímsson Reynir
Published: August 2005

Objective
To test the hypothesis that postmenopausal women with a history of eclampsia manifest a more high risk lipid profile than postmenopausal women with a history of normal pregnancy.

Setting
The Department of Obstetrics and Gynaecology, National University Hospital, Reykjavik, Iceland, and the Magee‐Womens Research Institute, Pittsburgh, Pennsylvania, USA.

Participants
Thirty Icelandic women with a history of eclampsia, aged between 50 and 67 years at the time of re‐examination (cases) were individually matched for current age, and for age and parity at index pregnancy, to 30 unrelated Icelandic women with a history of normal pregnancy (controls).

Methods
The participating women completed a health and family history questionnaire and underwent a physical examination. Fasting plasma low density lipoprotein diameter, serum lipids, insulin, and glucose were measured.

Results
Mean low density lipoprotein size was significantly smaller and apolipoprotein B concentration was higher in women with prior eclampsia. The percentage of cases receiving blood pressure medication (33%) was significantly greater than controls (6.7%). Thirteen cases had had hypertensive complications in at least one other pregnancy (recurrent subgroup); postmenopausally, these women displayed significantly increased diastolic blood pressures, smaller‐sized low density lipoprotein, increased apolipoprotein B, decreased high density lipoprotein2 (HDL2) cholesterol, and increased total cholesterol: HDL cholesterol ratio compared with their controls. Fourteen cases were normotensive in all other pregnancies (nonrecurrent); these showed no differences from their controls.

Conclusions
Dyslipoproteinaemia is more prevalent among postmenopausal women with prior eclampsia, especially with recurrent hypertension in pregnancy, than in postmenopausal women with prior normal pregnancies.
Raised maternal serum inhibin A concentration at 10 to 14 weeks of gestation is associated with pre‐eclampsia
Authors: Sebire N. J. , Roberts L. , Noble P. , Wallace E. , Nicolaides K. H.
Published: August 2005

Maternal serum inhibin A and free β human chorionic gonadotrophin (β‐hCG) were measured in 759 chromosomally normal, pregnant women at 10–14 weeks of gestation. There were nine who subsequently developed pre‐eclampsia and in these women the maternal serum inhibin A concentration was significantly higher than in the normotensive controls.
Analysis of B 10.D2 Recombinant Congenic Mouse Strains Shows That Audiogenic and β‐CCM‐Induced Seizures Depend on Different Genetic Mechanisms
Authors: Martin Benoit , Chapouthier Georges , Motta Roland
Published: August 2005

Summary: The rate of occurrence of audiogenic seizures and seizures induced by the benzodiazepine receptor inverse agonist methyl‐β‐carboline‐3‐carboxylate (β‐CCM) were analyzed in several recombinant congenic strains of mice bred from B10.D2 and DBA/2J. Although both types of seizures have similar behavioral patterns and might involve GABAergic mechanisms, no correlation was observed between the occurrence of the two types of seizures across the strains, suggesting that these two types of seizures depend on different genetic mechanisms.
High Signal Intensity on T2‐ Weighted MRI Correlates with Hypoperfusion in Temporal Lobe Epilepsy
Authors: Ryvlin P. , Garcia‐Larrea L. , Philippon B. , Froment J. C. , Fischer C. , Revol M. , Mauguière F.
Published: August 2005

Summary: Single‐photon emission computed tomography (SPECT) and [99mTc]HMPAO were used to assess the functional significance of nonspecific magnetic resonance imaging (MRI) abnormalities observed in patients with temporal lobe epilepsy and no focal lesion on CT scan. We studied 18 patients whose MRI was normal or showed high signal intensity on T2‐weighted images (T2WIs) at the site of the EEG focus in 11 and 7 cases, respectively. EEG was monitored during regional cerebral blood flow (rCBF) study. Lateralized hypoperfusion was present in 7 of 17 interictal(41%) and in one Postictal cases; it was located in the temporal lobe on the side of the EEG focus in all, and was significantly more frequent in patients with high signal intensity on T2WI (86%) than in patients with a normal MRI (18%). The degree of temporal perfusion asymmetry measured in each individual was higher in patients whose MRI was abnormal.
Pattern‐Sensitive Epilepsy: Genetic Aspects in Two Families
Authors: Brinciotti M. , Trasatti G. , Pelliccia A. , Matricardi M.
Published: August 2005

Summary: We report two families in which five members (three in one and two in the other) suffer from patternsensitive epilepsy. In all affected members seizures were induced by environmental visual patterned stimuli. Diagnosis was confirmed by neurophysiological studies, including EEG with pattern and intermittent light stimulation and visual evoked potentials. The role of genetic aspects and the relationship between this form of reflex seizures and photosensitive epilepsy are emphasized.
Severe Burns as a Consequence of Seizures in Patients with Epilepsy
Authors: Spitz Mark C.
Published: August 2005

Summary: We report 10 seizure‐related thermal injuries severe enough to require hospitalization in patients with epilepsy. Eight of the ten incidents were with patients who had had seizures with impaired consciousness two or more times a month. This suggests that seizure frequency is a risk factor and implies the importance of striving for optimal seizure control. Two burns each occurred from an electric iron, a hand‐held hair dryer, and stove‐top cooking. Minimizing these activities, especially in patients with frequent consciousness‐altering seizures, may be useful. Three burns occurred while showering; these resulted in the most severe injuries, with hospital stays of 29, 30, and 41 days. Simple plumbing devices may have prevented these injuries.
Acute Intermittent Porphyria and Epilepsy: Safety of Clonazepam
Authors: Suzuki Atsushi , Aso Kosaburo , Ariyoshi Chikako , Ishimaru Minori
Published: August 2005

Summary: A young woman with acute intermittent porphyria (AIP) and juvenile myoclonic epilepsy began to have generalized tonic‐clonic seizures (GTCs) at age 13. Subsequently, she had myoclonic seizures, which were often precipitated by visual stimulation, tended to occur in the morning, and sometimes evolved into GTCs. Valproate (VPA) resulted in a worsening of latent AIP, and treatment with a combination of phenytoin (PHT), carbamazepine (CBZ), and clonazepam (CZP) led to severe neuropathy of AIP and an electrolyte imbalance. These conditions were improved by water restriction, infusion of high doses of carbohydrates, and discontinuation of all antiepileptic drugs (AEDs) except for CZP. CZP appeared to be effective both in improving GTCs and myoclonic seizures and did not induce any symptoms of AIP. CZP may be porphyrogenic but can be used safely at a low dose for treatment of epilepsy in patients with AIP.
Carbamazepine‐Induced Eosinophilic Colitis
Authors: Anttila Veli‐Jukka , Valtonen Matti
Published: August 2005

Summary: Severe watery diarrhea and eosinophilic colitis induced by carbamazepine (CBZ) has not been described previously. We report the first known case of CBZ‐induced watery diarrhea and eosinophilic colitis in a 57‐year‐old man receiving CBZ for secondarily generalized tonic‐clonic seizures that developed after a cerebral infarction.
Thyroid Function with Antiepileptic Drugs
Authors: Isojärvi Jouko I. T. , Pakarinen Arto J. , Myllylä Vilho V.
Published: August 2005

Summary: Serum thyroid hormone balance was assessed in 108 patients receiving chronic antiepileptic drug (AED) therapy. Forty‐five patients were receiving carbamazepine (CBZ), 26 phenytoin (PHT), 16 CBZ‐PHT, 11 valproate (VPA), and 10 CBZ‐VPA. Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in patient groups receiving CBZ and/or PHT. Serum T4 concentrations were below the normal range in 24 (53.3%) CBZ patients, II (42.3%) PHT patients, 12 (75%) CBZ‐PHT patients, and in all 10 patients (100%) receiving CBZ‐VPA. Furthermore, serum levels of FT4 were below the normal range in 13 (28.9%) CBZ patients, 6 PHT (23.1%) patients, 5 (31.3%) CBZ‐PHT patients, and 5 (50%) CBZ‐VPA patients. Despite the decreased serum T4 and FT4 levels in these patients, serum basal and stimulated thyrotropin (TSH) concentrations were normal, except for the slightly increased basal TSH in the CBZ‐VPA group. In the VPA group, the findings were different from those in other patients: T4 serum levels were unchanged and FT4, T3, and basal TSH levels increased, but stimulated TSH levels did not differ from those of the control group. The decrease in serum thyroid hormone levels during CBZ and/or PHT medication probably is caused by an accelerated hepatic plasma clearance of these hormones due to induction of hepatic microsomal enzyme systems by these AEDs. VPA, an AED with no liver enzyme‐inducing properties, does not cause similar changes. The feedback mechanism is not activated, possibly because of a hypothalamic interference by CBZ and PHT. The effects of VPA on serum thyroid hormone and TSH levels may be mediated by effects on TSH secretion and on the protein binding of thyroid hormones.
Valproate Metabolites in Serum and Urine During Antiepileptic Therapy in Children with Infantile Spasms: Abnormal Metabolite Pattern Associated with Reversible Hepatotoxicity
Authors: Fisher E. , Siemes H. , Pund R. , Wittfoht W. , Nau H.
Published: August 2005

Summary: The purpose of this study was to identify abnormal metabolite patterns of valproate (VPA) as possible early indicators of VPA‐induced liver toxicity. In a prospective study, we determined serum and urine levels of VPA metabolites by gas chromatography‐mass spectrometry (GC‐MS) during the course of therapy in 25 children treated for infantile spasms with high VPA doses (100mg/kg body weight/day). Most patients had similar metabolite profiles: The main metabolites in serum were the β‐oxidation products (2‐en‐VPA and 3‐keto‐VPA) and the major diunsaturated metabolite 2,3′‐dien‐VPA. Glucuronide conjugates and the oxidation products represent the most abundant metabolites in urine. Other metabolites, including the potential hepatotoxin 4‐en‐VPA, were detected only in low concentrations. Two children had transiently aberrant metabolite profiles, indicating altered β‐oxidation, (levels of 2‐en‐VPA, 2,3′‐dien‐VPA, and 3‐en‐VPA were markedly increased) in connection with hepatomegaly and increased liver enzyme activities at a time when both had febrile infections and were receiving dexamethasone comedication. At no time were increased levels of 4‐en‐VPA or its derivatives detected. Establishing the VPA metabolite profile may aid in evaluation of patients who show signs and symptoms of liver dysfunction during VPA therapy. The present study shows that initial stages of hepatotoxicity reactions to VPA may be accompanied by characteristic changes in VPA metabolism; early detection of such abnormal metabolite patterns might decrease the risk of severe hepatic injury.
Associations Between Risk Factors for Valproate Hepatotoxicity and Altered Valproate Metabolism
Authors: Kondo Tsuyoshi , Kaneko Sunao , Otani Koichi , Ishida Masayuki , Hirano Takayuki , Fukushima Yutaka , Muranaka Hideki , Koide Nobuo , Yokoyama Masaru
Published: August 2005

Summary: The effects of three risk factors for valproate (VPA) hepatotoxicity (i.e., young age, polypharmacy, and high VPA serum level) on the metabolism of VPA to its monounsaturated metabolites 12‐en‐VPA (2‐en), 3‐en‐VPA (3‐en) and 4‐en‐VPA (4‐en)l were investigated in 106 patients treated with VPA (56 cases of monotherapy and 50 cases of polytherapy). In the monotherapy group, there was a significant negative correlation between age and 4‐en/VPA ratio. In the same group, the 4‐en/VPA ratio showed a significant positive correlation with serum VPA level, while 3‐enIVPA and 2‐enIVPA ratios showed significant negative correlations. In patients > 10 years, the 4‐enlVPA ratio was significantly higher, while the 2‐enIVPA ratio was significantly lower in the polytherapy group than in the monotherapy group. Our results indicate that all three risk factors clearly increase the metabolic conversion of VPA to 4‐en, the most toxic VPA metabolite, and that polytherapy and high VPA serum level result in the inhibited beta‐oxidative metabolism of VPA to 2‐en. These altered VPA metabolic profiles are strikingly similar to the abnormal VPA metabolism previously reported in cases with fatal hepatic failure. Although VPA‐induced fatal hepatotoxicity has been regarded as an idiosyncratic reaction, it is possible that these three factors enhance susceptibility to VPA hepatotoxicity by altering the metabolism of VPA.
Valproate Therapy Induces von Willebrand Disease Type I
Authors: Kreuz W. , Linde R. , Funk M. , Meyer‐Schrod R. , Föll E. , Nowak‐Göttl U. , Jacobi G. , Vigh Zs. , Scharrer I.
Published: August 2005

Summary: To investigate the increased tendency of hemorrhage in patients receiving valproate (VPA) therapy, we studied coagulation parameters in 30 randomized children of a group of 83 children receiving antiepileptic drug (AED) therapy. Besides a reduction in fibrinogen concentration and platelet count, we observed a significant decrease in factor VIII‐complex. A decrease in factor VIII:C was noted in 33%, a decrease in von Willebrand factor (vWF:Ag) was noted in 83% and a decrease in ristocetin‐cofxtor activity (vWF:Rcof) was noted in 66% of the children. We classified a von Willebrand syndrome type I in 67% of our patients receiving VPA therapy. Sixty‐three percent of patients had a history of bleeding, and 23% had a prolonged bleeding time. We compared our results with those of a control group and of a group of patients with congenital von Willebrand disease (vWD), from which patients with multimer types II and III were excluded. Because coagulation parameters in patients with congenital vWD are similar to those receiving AED therapy, we designated the increased tendency to hemorrhage as VPA‐induced vWD. The decrease in coagulation parameters were not dependent on either VPA dose or period of administration. In patients receiving VPA therapy, this result must be considered, especially during surgical intervention and after traumatic events.
Intractable Diarrhea from Carbamazepine
Authors: Iyer Vasudeva , Holmes J. William , Richardson Ronald L.
Published: August 2005

Summary: Diarrhea has been reported as an early, mild, and uncommon complication of carbamazepine (CBZ) therapy. We report three cases of intractable diarrhea induced by CBZ necessitating discontinuation of the drug.
Induction of Epileptiform Activity by Temperature Elevation in Hippocampal Slices from Young Rats: An In Vitro Model for Febrile Seizures?
Authors: Tancredi V. , D'Arcangelo G. , Zona C. , Siniscalchi A. , Avoli M.
Published: August 2005

Summary: Extracellular field potential recordings were performed in the CA1 subfield of hippocampal slices obtained from Wistar rats aged 2–38 days. When the brain tissue was maintained at 35°–36°C (values obtained in the tissue chamber well), single‐shock orthodromic stimuli elicited a response in the stratum pyramidale that consisted of a single population spike. In contrast, when the temperature in the well was increased to levels >38.2°C for periods of 5–15 min, the same type of stimuli elicited an epileptiform response characterized by a 250‐ to 600‐ms‐long, positive‐going field potential with superimposed, multiple, negative‐going population spikes. This potential resembled the epileptiform response recorded in the hippocampal slice in the presence of convulsants such as penicillin or bicuculline. Once the temperature was restored to control values (i.e., 35°–36°C) after induction of epileptiform activity, the abnormal response could be observed for 2 h. In some experiments (approximately one third of the successful trials), spontaneous epileptiform discharges appeared during and persisted after the increase in temperature. The ability of the hyperthermic period to induce epileptiform changes was age dependent: Epileptiform activity outlasting the period of temperature elevation was not observed in slices obtained from rats aged <4 days or >28 days. Our data show that epileptiform activity can be induced by a transient increase in temperature and that the age of the animals from which slices are obtained plays an important role in the appearance of this phenomenon. Both characteristics indicate that this in vitro model of epileptiform activity might represent an experimental preparation suitable for studying the cellular and pharmacologic mechanisms underlying febrile convulsions. Knowledge of these mechanisms might help in designing better strategies for therapeutic management of such seizures.