Success to reach 3cm of dilation with a Dinoprostone Vaginal Insert in primiparous women with a previous cesarean section versus nulliparous: A retrospective case-control study.

Background The best methods of labour induction have still been controversial because of an increased risk of uterine rupture, especially in exposed women of labour induction with prostaglandins. We here attempted to determine, after Dinoprostone Vaginal Insert, previous cesarean women (exposed women), compared with nulliparous women (non-exposed women), are more likely 1) to have the dilated cervix (up to 3 cm or more), and 2) to require cesarean after cervix being dilated 3 cm or more. Methods This retrospective observational study included 43 exposed women and 188 non exposed women . A propensity score was calculated to balance the background differences including age, BMI, Bishop. Main findings Exposed women were significantly less likely to reach 3 cm of cervix dilation than non exposed women (62.8 and 67.6% [study] vs. 83 and 81.3% [control] before and after propensy score analysis, respectively (p < 0.05)). However exposed women were significantly less likely to require cesarean than non exposed women (4.9 vs. 17.2% p = 0.03) after inverse probability of treatment weighting once 3 cm dilation was reached. Conclusion After Dinoprostone Vaginal Insert, women with scarred uterus were less likely to reach 3 cm of cervix dilation but once 3 cm of dilation was achieved, they were less likely to require cesarean.

Activation state of circulating eosinophils in nasal polyposis.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease with an uncertain pathophysiology. It is characterized by polyps rich in eosinophils, with an activation status already investigated at the tissue level. In a group of CRSwNP patients, we assessed the activation status of circulating eosinophils in the blood before migration into tissues. METHODS: Thirteen patients with CRSwNP and 16 healthy volunteers were enrolled. Several biologic parameters were studied: blood count of eosinophils; plasma eosinophil cationic protein; oxidative metabolism by chemiluminescence at baseline or when activated by phorbol 12-myristate 13-acetate or platelet-activating factor, with or without interleukin-5 (IL-5); percent of granulosar cells; and mean fluorescence intensity (MFI) by flow cytometry. RESULTS: The mean number of eosinophils was significantly higher in patients with CRSwNP, whose eosinophils showed increased oxidative metabolism in the basal or activated state significantly decreasing in the presence of IL-5. There was also a higher percentage of CD49d+ , CD25+ , and CCR3+ cells in patients, and a nonsignificant decrease in descending order in MFI between the control group, patients with normal eosinophil levels, patients with hypereosinophilia, and patients with aspirin-exacerbated respiratory disease. CONCLUSION: This study demonstrates a priming state of circulating eosinophils in CRSwNP patients when compared with healthy controls, as evidenced by the extent of oxidative metabolism, with increased sensitivity to IL-5 and by the observed variations of percent and MFI of CD49d, CCR3, and CD25. This priming is thus found at the peripheral level and occurs before the migration of eosinophils to polyps, reflecting the systemic and not just local nature of abnormalities in CRSwNP.

Diagnostic accuracy of copeptin sensitivity and specificity in patients with suspected non-ST-elevation myocardial infarction with troponin I below the 99th centile at presentation.

OBJECTIVE: To determine whether copeptin-us can rule out diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI) without prolonged monitoring and serial blood sampling in patients with high-sensitive cardiac troponin I (hs-cTnI) below the 99th centile at presentation to the emergency department (ED) [corrected]. DESIGN: Prospective, non-randomised, individual blinded diagnostic accuracy study. SETTING: Two EDs of a rural region of France. PARTICIPANTS: Patients with chest pain suspected of NSTEMI with onset within the last 12 h were considered for enrollment. INTERVENTIONS: Serial clinical, electrographical and biochemical investigations were performed at admission and after 2, 4, 6 and 12 h. Hs-cTnI was measured using an assay with Dimension VISTA, Siemens [corrected]. Copeptin was measured by the BRAHMS copeptin-us assay on the KRYPTOR Compact Plus system. The follow-up period was 90 days. PRIMARY AND SECONDARY OUTCOME MEASURES: Copeptin, troponin, myoglobin and creatine kinase values. Clinical and paraclinical events. The final diagnosis was adjudicated blinded to copeptin result. RESULTS: During 12 months, 102 patients were analysed. Final diagnosis was NSTEMI for 7.8% (n=8), unstable angina for 3.9% (n=4), cardiac but non-coronary artery disease for 8.8% (n=9), non-cardiac chest pain for 52% (n=53) and unknown for 27.5% (n=28). There was no statistical difference for copeptin values between patients with NSTEMI and others (respectively 5.5 pmol/L IQR (3.1-7.9) and 6.5 pmol/L IQR (3.9-12.1), p=0.49). Only one patient with NSTEMI had a copeptin value above the cut-off of 95th centile at admission. CONCLUSIONS: In this study, copeptin does not add a diagnostic value at admission to ED for patients with suspected acute coronary syndrome without ST-segment elevation and with hs-cTnI below the 99th centile [corrected]. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier: NCT01334645.

The long-term effects of occupational exposure to vinyl chloride monomer on microcirculation: a cross-sectional study 15 years after retirement.

OBJECTIVES: To assess residual long-term microcirculation abnormalities by capillaroscopy, 15 years after retiring from occupational exposure to vinyl chloride monomer (VCM). DESIGN: Cross-sectional study. SETTING: Allier, one of the major areas of polyvinyl chloride production in France. PARTICIPANTS: We screened 761 (97% men) retired workers exposed to chemical toxics. Exposure to chemicals other than VCM excluded potential participants. PRIMARY AND SECONDARY OUTCOME MEASURES: These participants underwent a medical examination including a capillaroscopy, symptoms of Raynaud and comorbidities, as well as a survey to determine exposure time, direct or indirect contact, type of occupation, smoking status and time after exposure. A double blind analysis of capillaroscopic images was carried out. A control group was matched in age, sex, type of occupation. RESULTS: 179/761 retired workers were only exposed to VCM at their work, with 21 meeting the inclusion criteria and included. Exposure time was 29.8±1.9 years and time after exposure was 15.9±2.4 years. Retired workers previously exposed to VCM had significantly higher capillaroscopic modifications than the 35 controls: enlarged capillaries (19% vs 0%, p<0.001), dystrophy (28.6% vs 0%, p=0.0012) and augmented length (33% vs 0%, p<0.001). Time exposure was linked (p<0.001) with enlarged capillaries (R(2)=0.63), dystrophy (R(2)=0.51) and capillary length (R(2)=0.36). They also had higher symptoms of Raynaud (19% vs 0%, p=0.007) without correlation with capillaroscopic modifications. CONCLUSIONS: Although VCM exposure was already known to affect microcirculation, our study demonstrates residual long-term abnormalities following an average of 15 years' retirement, with a time-related exposure response. Symptoms of Raynaud, although statistically associated with exposure, were not related to capillaroscopic modifications; its origin remains to be determined.

CSF N-glycan profiles to investigate biomarkers in brain developmental disorders: application to leukodystrophies related to eIF2B mutations.

BACKGROUND: Primary or secondary abnormalities of glycosylation have been reported in various brain diseases. Decreased asialotransferrin to sialotransferrin ratio in cerebrospinal fluid (CSF) is a diagnostic marker of leukodystrophies related to mutations of genes encoding translation initiation factor, EIF2B. We investigated the CSF glycome of eIF2B-mutated patients and age-matched normal individuals in order to further characterize the glycosylation defect for possible use as a biomarker. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a differential N-glycan analysis using MALDI-TOF/MS of permethylated N-glycans in CSF and plasma of controls and eIF2B-mutated patients. We found in control CSF that tri-antennary/bisecting and high mannose structures were highly represented in samples obtained between 1 to 5 years of age, whereas fucosylated, sialylated structures were predominant at later age. In CSF, but not in plasma, of eIF2B-mutated patient samples, we found increased relative intensity of bi-antennary structures and decreased tri-antennary/bisecting structures in N-glycan profiles. Four of these structures appeared to be biomarker candidates of glycomic profiles of eIF2B-related disorders. CONCLUSION: Our results suggest a dynamic development of normal CSF N-glycan profiles from high mannose type structures to complex sialylated structures that could be correlated with postnatal brain maturation. CSF N-glycome analysis shows relevant quantitative changes associated with eIF2B related disorders. This approach could be applied to other neurological disorders involving developmental gliogenesis/synaptogenesis abnormalities.

Serum S100B determination in the management of pediatric mild traumatic brain injury.

BACKGROUND: The place of serum S100B measurement in mild traumatic brain injury (mTBI) management is still controversial. Our prospective study aimed to evaluate its utility in the largest child cohort described to date. METHODS: Children younger than 16 years presenting at a pediatric emergency department within 3 h after TBI were enrolled prospectively for blood sampling to determine serum S100B concentrations. The following information was collected: TBI severity determined by using the Masters classification [1: minimal or Glasgow Coma Scale (GCS) 15, 2: mild or GCS 13-15, and 3: severe or GCS <13]; whether hospitalized or not; good or bad clinical evolution (CE); whether cranial computed tomography (CCT) was prescribed; and related presence (CCT+) or absence (CCT-) of lesions. RESULTS: For the 446 children enrolled, the median concentrations of S100B were 0.21, 0.31, and 0.44 µg/L in Masters groups 1, 2, and 3, respectively, with a statistically significant difference between these groups (P < 0.05). In Masters group 2, 65 CCT scans were carried out. Measurement of S100B identified patients as CCT+ with 100% (95% CI 85-100) sensitivity and 33% (95% CI 20-50) specificity. Of the 424 children scored Masters 1 or 2, 21 presented "bad CE." S100B identified bad CE patients with 100% (95% CI 84-100) sensitivity and 36% (95% CI 31-41) specificity. Of the 242 children hospitalized, 81 presented an S100B concentration within the reference interval. CONCLUSIONS: Serum S100B determination during the first 3 h of management of children with mTBI has the potential to reduce the number of CCT scans, thereby avoiding unnecessary irradiation, and to save hospitalization costs.

Reference ranges for serum S100B protein during the first three years of life.

OBJECTIVE: Clinical and diagnostic management of traumatic brain injuries is problematic in young children. To facilitate this management, we describe blood reference ranges for the well established biomarker S100B in children younger than 3 years. DESIGN AND METHODS: Serum S100B concentrations were determined by electro-chemiluminescence immunoassay in a population of 186 healthy children aged 0-3 years. RESULTS: Four age groups emerged, i.e. 0-3, 4-9, 10-24 and 25-36 months. We also found an interesting inverse correlation with head circumference. CONCLUSION: This study provides useful serum S100B values from the largest cohort of healthy children aged 0-3 years old.

[Coupling proteinemia and serum protein electrophoresis: evaluation of the capillary technique (Capillarys 2, Sebia), experience from Clermont-Ferrand]. / Évaluation du couplage protéinémie + électrophorèse des protéines sériques totales par technique capillaire (Capillarys 2, Sebia) : expérience clermontoise.

Serum protein electrophoresis (SPE) is a routine analysis that requires to quantify the total serum proteins in order to calculate the concentration in g/L of each electrophoretic protein fraction. Aim of this study was to evaluate the performances of the « Capillarys Total protein ¼ kit (Sebia®), coupled to the Capillarys 2 system (Sebia®), allowing the proteinemia quantification by capillary electrophoresis (EC) simultaneously to the electrophoretic separation. We compared the proteinemia analyzed in EC with the spectrophotometric reference technique for 904 serums. Our results validated the performances of this kit used on the Capillarys 2 system. We noticed interferences identified for 5.8% of total serums: serums with strong monoclonal immunoglobulinemia (proteinemia of 0 g/L), with inconsistent electrophoretic profile (proteinemia not calculated), and lipemic serums (discordant proteinemia). After exclusion of the lipemic serums or serums without proteinemia associated to the EC profile, a good correlation was found for these 94.2% serums analyzed in EC (r = 0.93) in comparison with the reference technique. Then, the kit developed by Sebia® to perform SPE coupled to proteinemia analysis is usable in routine analysis except for the lipemic serums and for the serum with intense monoclonal immunoglobulinemia. Advantage of such a coupling is to better organize the unit specifically implicated in proteins exploration. But this technique is longer, leading to slowing EC analyses. Taking in account these limitations and restrictions, and in view of the development of complete pre-analytical chains in hospital labs, this technique, despite its performance, was not retained by Sebia® for future commercialization.

[Allergenic environment in asthmatic children in Annaba (Algeria)]. / Environnement allergénique d'une population d'enfants asthmatiques à Annaba (Algérie).

We determined blood levels of total and specific immunoglobulins E in a cohort of 75 asthmatic children at Annaba (mean age: 9 years, sex ratio M/F: 1,64). Analysis clinical investigation and biological results allowed us to estimate the clinico-biological relations in this population. We showed that: atopy based on family criteria was very frequent (74%); the symptoms of atopy associated with asthma were frequent for atopic children (96%) whose majority (46%) had severe asthma (grade 3) that required treatment. Sensitization to trophallergens was rare in this population and always associated with sensitizations to pneumallergens (acariens: 2/3; cockroaches: 50%). Sensitizations to pneumallergens seemed promoted by climatic conditions in the area of Annaba that increased the risk of developing allergic diseases.

Effect of lingual nerve block on burning mouth syndrome (stomatodynia): a randomized crossover trial.

Burning mouth syndrome (stomatodynia) is associated with changes of a neuropathic nature the main location of which, peripheral or central, remains unknown. A randomised, double-blind crossover design was used to investigate the effects of lingual nerve block on spontaneous burning pain and a possible correlation with the effects of topical clonazepam, the patient's response to a psychological questionnaire, and the taste and heat thresholds. The spontaneous burning was measured with a visual analogue scale (VAS) just before and 15 min after injection. The decreases in VAS score after lidocaine or saline injection were not significantly different (2.7+/-3.9 and 2.0+/-2.6, respectively; n=20). However, two groups of patients could be identified: in a "peripheral group" (n=10) the VAS decrease due to lingual nerve injection was 4.3+/-3.1cm after lidocaine and 0.9+/-0.3 cm after saline (p=0.02). In a "central group" (n=7), there were an increase in pain intensity score (-0.8+/-2.6 cm) after lidocaine and a decrease (1.5+/-3.0 cm) after saline (p=0.15). An increase in the hospital anxiety and depression (HAD) score and a decreased taste sensitivity and heat pain threshold of painful oral area were seen in patients compared with age-and-sex-matched controls (p<0.05). Topical clonazepam treatment tended to be more effective (p=0.07) and HAD score lower (p<0.03) in the peripheral than in the central group. These results suggest that the neuropathic disorder associated with stomatodynia may be predominantly peripheral, central or mixed depending on the individual. Topical application of clonazepam and HAD may serve as indicators of which mechanism is dominating.

Is pregnancy the time to change alcohol consumption habits in France?

BACKGROUND: Although it is well known that France has a cultural history of alcohol use, no recent French data on alcohol consumption during pregnancy in a large sample are available. METHODS: To determine the alcohol consumption patterns among pregnant women in France, we analyzed data from a 1-year multicenter self-survey. Sociodemographic profile, obstetrical history, neonatal data, and a self-report for assessing drinking patterns during pregnancy including AUDIT were recorded from women who delivered recently. Cases of fetal alcohol syndrome (FAS) were also reported. RESULTS: A total of 837 pregnant women have described all parameters. The mean age at delivery of our sample was 29.7 years (SD = 4.8 years). A total of 52.2% of women indicated that they had consumed alcohol at least once during their pregnancy, and among abstainers 54.5% had a positive AUDIT score. Of the pregnant women who consumed alcohol, 13.7% reported at least one binge drinking episode (5 or more drinks on 1 occasion) during pregnancy. Binge drinking is significantly more frequent than regular alcohol consumption (at least 1 drink more than 1 time per week) during pregnancy. A prevalence rate of FAS of 1.8 per 1,000 live births was observed. CONCLUSIONS: There is a large population of women who still drink alcohol during pregnancy, particularly in binge drinking episodes. This underlines the need to clearly inform women of childbearing age about the dangers of alcohol during pregnancy as related to all types of consumption. Moreover, acting to prevent alcohol consumption prior to pregnancy may also greatly influence prenatal drinking.

GC-MS determined cotinine in an epidemiological study on smoking status at delivery.

The objective of this study was to measure the plasma cotinine levels in pregnant women and their newborns using a gas chromatography-mass spectrometry (GC-MS) method in an epidemiological-delivered population with a wide range of tobacco intakes. Nearly 1000 pregnant women from regional maternity wards (n=1007) were selected for the study. Each patient kept a tobacco diary and underwent a blood test to assess cotinine levels and at the same time that the newborns' cordonal plasma was taken. These values were then cross-checked. Cotinine was estimated using a selected-ion monitoring mode with a 1.5 ng/ml quantification limit. The cotinine levels in mothers and newborns were highly correlated, whatever the mother's smoking status, with a calculated cut-off for cotinine levels in active smokers of 21.5 ng/ml. Finally, the cotinine determined through this GC-MS method offered a sensitive and accurate measure of tobacco exposition of the pregnant women and their babies.

Osteoarthritis of the thumb carpometacarpal joint in women and occupational risk factors: a case-control study.

PURPOSE: Among other etiologic factors involved in first carpometacarpal (CMC) osteoarthritis (OA), occupational factors have been postulated as influencing the occurrence of this condition. Very few epidemiologic studies, however, have evaluated this topic. Determining the occupational risk factors is important in proposing preventive measures at the workplace. This case-control study was undertaken to explore whether there was a history of greater exposure to some occupational factors (eg, occupations, hand postures, tasks involving the CMC joint) in women requiring surgery for CMC OA compared with women with no CMC OA noted by history and physical examination. METHODS: The case subjects were 61 women surgically treated for primary CMC OA and the control subjects were 120 aged matched women without history or features of CMC OA. A detailed structured interview was developed to elicit information about age, smoking habits, medical history, lifestyle history, and occupational factors. Occupational factors were based on a detailed history of jobs, coded according to the International Standard Classification of Occupations. For the main occupation/job held for the longest duration and during an average working day, subjects were asked about hand posture or tasks involving requirements presumed to cause a strain or a high load to the CMC joint and about certain work conditions. RESULTS: Of the 61 case and 120 control subjects, 5 and 14, respectively, had never worked. There was no difference between the average number of jobs through the working lifetime of the group of case subjects compared with the group of control subjects. Logistic regression analysis showed that after adjustment for age, smoking status, obesity, CMC OA family history, hysterectomy history, parity, and occasional job, the following occupational factors were risk factors for CMC OA: occupations presumed to be associated with increased risk for CMC OA, occupations involving repetitive thumb use, and jobs perceived by the subject having not enough rest breaks during a day. The group of case subjects had a higher prevalence of hysterectomy history and family CMC OA history compared with the group of control subjects. CONCLUSIONS: Although previous studies have reported that work and exposure history may lack precision as risk factors, our results give further evidence to support the role of certain occupational factors in the occurrence of CMC OA in women. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Limits of usual biochemical alcohol markers in cord blood at term: a fetal/maternal population-based study.

BACKGROUND: After maternal alcohol consumption during pregnancy, many neonates affected by less apparent forms of fetal alcohol syndrome disorder (FASD) do not receive proper diagnosis or treatment. There is thus a need for laboratory markers for early detection of alcohol-exposed neonates. The aim of our study was to assess the efficiency of the usual alcohol biomarkers measured in cord blood to identify alcohol-exposed neonates immediately after birth. METHODS: A 1-year study was conducted in the labor wards of the maternity units of the Auvergne, Central France at the time of term delivery. The patients answered an anonymous self-completion survey concerning alcohol use (Alcohol Use Disorder Identification Test; AUDIT) during their pregnancy. Aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase concentrations and the percentage of carbohydrate-deficient transferrin were measured in maternal and cord blood. RESULTS: We collected 870 maternal-fetal sample pairs. Two cases (0.2%) of typical FASD were detected. We report a non-significant correlation between maternal and cord blood biomarkers. None of the cord blood biomarkers differed significantly between newborns of alcohol-exposed and unexposed mothers. CONCLUSIONS: We demonstrate that the usual alcohol biomarkers are not effective in cord blood for identifying alcohol-exposed neonates.

Occult maternal exposure to environmental tobacco smoke exposure.

BACKGROUND: Environmental tobacco smoke (ETS) is a recognised air pollutant. Its harmful effects have been found to be implicated in health disorders, including unfavourable pregnancy outcomes. The discrepancy between self-reported environmental tobacco smoke exposure and cotinine levels in pregnant non-smokers in France was examined. METHOD: Plasma cotinine was determined by a CPG-SM method on women who had answered a self-questionnaire describing their habits and environment during pregnancy. RESULTS: Of 698 pregnant women reported as non-smokers, 305 (43.7%) claimed not to be exposed to ETS, yet 196 of these (64.3%) had plasma cotinine levels above the limit of detection. CONCLUSION: Self-reported data on ETS exposure in pregnant women therefore underestimate actual exposure. However, cotinine assay can rectify this misclassification. An accurate identification of this risk factor will help to change attitudes towards ETS and avert its adverse effects on mother and fetus.

Glutathione S-transferase M1 and GST T1 genetic polymorphisms and Raynaud's phenomenon in French vinyl chloride monomer-exposed workers.

Occupational vinyl chloride monomer (VCM) exposure can induce Raynaud's phenomenon (RP). However, not all VCM workers developed RP, which suggests an underlying genetic susceptibility. Genetic polymorphisms of glutathione S-transferases (GSTs), involved in VCM metabolism, have been shown to influence certain VCM-related health effects. We have conducted a case-control study of 58 subjects with RP along with 247 subjects without RP, from a population of 305 French workers exposed or formerly exposed to VCM, to assess any association between GST M1 and GST T1 gene polymorphisms, either separately or in combination, and the presence of RP. None of the GST M1 or GST T1 genotypes were significantly associated with the presence of RP among studied VCM workers. A combination of positive genotypes for both GST M1 and GST T1 was significantly associated with RP presence, compared to the other combinations of genotypes (OR=2.1, 95% CI=1.1-3.8). OR adjusted for age, smoking status, alcohol consumption and history of treated hypertension did not reach significance (OR=2.0, 95% CI=0.9-5.2). None of the GST M1 and GST T1 genotypes seem to contribute separately to the presence of RP, suggesting that they are not, when taken alone, a major determinant of interindividual variability for VCM-induced PR. However, the combination of both positive GST M1 and GST T1 genotypes appears to contribute slightly to susceptibility to RP in VCM-exposed subjects. Nevertheless, our study-the first to examine the role of a genetic component in the occurrence of RP secondary to occupational exposure to a chemical-corroborates the previous considerations that interaction between the genetic constitution and environmental factors is of importance in determining the health-adverse effects of VCM exposure.

Antenatal detection and impact on outcome of congenital diaphragmatic hernia: a 12-year experience in Auvergne, France.

OBJECTIVE: To evaluate the detection rate of prenatal diagnosis and its impact on outcome in congenital diaphragmatic hernia (CDH). STUDY DESIGN: We retrospectively studied 51 cases of CDH registered in the Auvergne area from January 1992 to December 2003 (Birth Defect Registry of Auvergne, Institut Européen des Génomutations). Our main outcome measurements were the detection rate of prenatal diagnosis, the incidence and types of associated anomalies and outcome (termination of pregnancy, in utero fetal demise, neonatal death, survival at the time of registration). RESULTS: Twenty-nine cases of isolated CDH were identified of which 13 were detected prenatally (45%) at a mean gestational age of 26.1 weeks and 22 cases of CDH with associated anomalies with prenatal diagnosis of CDH or any associated anomaly in 16 (73%; p=0.03) at a mean gestational age of 23.9 weeks. In the prenatally detected group (29 cases), there was 1 (3%) in utero fetal death (IUFD), 17 (59%) terminations of pregnancy (TOP) and 11 (38%) live births with early neonatal death in 7 (24%) cases despite delivery in a tertiary care centre in 10/11 cases (four survivors=14%). Most of the undetected cases were isolated CDH (16/22=73%) of which 1 (5%) was a stillborn and 21 (95%) live births with 17 survivors (77%) although 15/21 (71%) were not born at the tertiary care centre (p=0.001). The overall survival rate was 41% with a large variability depending on associated anomalies and prenatal diagnosis (p<0.0001) (prenatally detected cases: 3/13 (23%) isolated CDH and 1/16 (6%) CDH with associated anomalies; undetected cases: 13/16 (81%) isolated CDH and 4/6 (67%) CDH with associated anomalies). CONCLUSION: Prenatal diagnosis of CDH leads to the delivery of affected babies in tertiary care centres but it remains a challenge in particular for isolated CDH cases and it is associated with a lower survival rate. Associated anomalies contribute to prenatal detection, are related to a higher TOP rate but do not facilitate the detection of diaphragmatic defect per se.

Histological response in patients treated by interferon plus ribavirin for hepatitis C virus-related severe fibrosis.

BACKGROUND: Studies of viral hepatitis C have suggested that fibrosis can regress, at least in patients with sustained virological response. A recent study suggested that cirrhosis was reversible in sustained and non-virological responders. AIM: To study fibrosis progression rate and cirrhosis reversion in patients treated for severe fibrosis with interferon or interferon + ribavirin. PATIENTS AND METHODS: Ninety-nine patients were treated with interferon + ribavirin and 64 with interferon. The Metavir fibrosis score and the semiquantitative fibrosis score (SFS) were used to assess fibrosis. RESULTS: In sustained responders, fibrosis progression rate decreased from 0.26 Metavir unit (interquartile range: 0.19-0.34) to -0.67 (-0.67 to 0) (P < 0.0001) and from 0.81 SFS unit (0.48-1.13) to -1.33 (-3.67 to 0) (P < 0.0001). In non-responders, fibrosis progression rate decreased from 0.25 Metavir unit (0.17-0.33) before treatment to 0 (0-0) during treatment (P = 0.002) and from 0.63 SFS unit (0.49-1.12) to 0 (-2.67-1.33) (P = 0.18). Six out of 18 (33%) sustained virological responders and four of 43 (9%) non-responders regressed from cirrhosis (F4) to severe fibrosis (F3) (P = 0.058). No patient with cirrhosis had a decrease of Metavir fibrosis score of 2 points. CONCLUSION: Interferon can slow fibrosis progression in sustained virological responders with severe fibrosis. In patients with a non-virological response and treated for 12 months the fibrosis progression rate was nil, meaning that only fibrosis stabilization could be obtained in these patients. Then, longer treatment duration (3-4 years) could be evaluated in non-virological responders.

Ectopic pregnancy is again on the increase. Recent trends in the incidence of ectopic pregnancies in France (1992-2002).

BACKGROUND: We aimed to assess the recent incidence trends of ectopic pregnancies (EP) in France (1992-2002). METHODS: A population-based register of all women aged 15-44 years with EP was set up in Auvergne (central France). We calculated rates of EP as a 'reproductive failure' or as a 'contraceptive failure', frequencies of exposure to the two main risk factors for EP (cigarette smoking and chlamydial infection) and contraceptive methods between 1992 and 2002. RESULTS: The overall EP rate decreased by 2%, from 96.4 per 100 000 women aged 15-44 in 1992 to 95.3 per 100 000 in 2002. However, the rate of 'reproductive failure' EP increased by 17%, while the rate of 'contraceptive failure' EP, mostly intrauterine device failure, decreased by 29%. CONCLUSION: Appropriate analysis reveals that the rate of EP as reproductive failure is increasing again in France. This result is of interest for many European and North America countries where chlamydial infections or smoking or both are increasing in women of reproductive age. The rates of EP as contraceptive failure and of that as reproductive failure evolve differently in the population and should not be confused in epidemiological studies.

Frequency, risk factors, and outcome of hyperlactatemia in HIV-positive persons: implications for the management of treated patients.

BACKGROUND: The nucleoside reverse transcriptase inhibitors used for the treatment of HIV-positive persons are now clearly associated with metabolic disorders. We determined the prevalence of and risk factors for hyperlactatemia in HIV-positive persons to assess the relevance of lactate venous blood concentrations during antiretroviral therapy. METHODS: We conducted a prospective cross-sectional study of venous lactate determinations with 282 consecutive HIV-positive persons who, in addition to a physical examination, had blood samples taken every 3-4 months for routine biochemical, immunologic, and viral assessment. The frequencies of hyperlactatemia and lactic acidosis were determined, and the risk factors were analyzed by a multivariate logistic regression model. The effect of modification of antiretroviral therapy in patients with moderate hyperlactatemia was also assessed. RESULTS: From 782 blood lactate determinations, we identified 65 (23%) patients with moderate hyperlactatemia and 5 (1.8%) with lactate concentrations >5 mmol/L (2 with severe lactic acidosis; 0.7%). Older age, drug regimens containing stavudine [adjusted odds ratio (OR) = 2.5] or a combination of stavudine-didanosine (adjusted OR = 3.1), and the use of buprenorphine (adjusted OR = 14.7) were independent predictors of hyperlactatemia. Among 65 patients with moderate hyperlactatemia, 39 did not have their treatments changed, and 26 had a new combination therapy that was associated with a clinical improvement and a more pronounced decrease in lactate (-1.66 vs -0.99 mmol/L; P <0.05). CONCLUSIONS: Chronic compensated and moderate hyperlactatemia was common in our population study. Measurement of lactate, under standardized conditions, may be useful in optimizing management of HIV-positive persons on antiretroviral therapy.