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E Robert

Publications and source records attributed to E Robert.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Occupational exposure to organic solvents and pregnancy. Review of current epidemiologic knowledge].

The findings and methodological issues of recent epidemiological studies (1989-1999) on adverse developmental effects of maternal occupational exposure to organic solvents are reviewed. Several studies suggest the possibility of a moderate increase in the risk of spontaneous abortion and congenital malformations, especially facial clefts, associated with maternal exposure to solvents. A common methodological weakness of these studies is the inaccuracy of data on exposures. Positive findings encourage further epidemiological studies of high-quality design and use of protective measures to minimize exposure to these agents from the preconceptional period to the end of pregnancy.

Abnormalities, Drug-Induced↗
PubMed1999

Exposure to yellow fever vaccine in early pregnancy.

We report on a data collection concerning exposure to yellow fever vaccine (YFV) during early pregnancy, ascertained through the European Network of Teratology Information Services (TISs) and the Pharmacovigilance Department of Pasteur Merieux Connaught (PMC). Six TISs had had no inquiry about YFV. Five submitted prospectively collected cases. Seventy-four cases were analyzed, 58 with a completed follow-up. Pregnancies ended in 46 births, five voluntary abortions and seven spontaneous abortions. Three newborns had minor anomalies and two had major defects (ureteral stenosis and triphalangeal hallux). Although the sample is too small to rule out a moderate increased risk of adverse reproductive effect of YFV, it gives no argument for such an effect and should lead to reassure pregnant women who might be inadvertently vaccinated.

Congenital Abnormalities↗
PubMed1999

High vitamin A intake in early pregnancy and major malformations: a multicenter prospective controlled study.

The European Network of the Teratology Information Services (ENTIS) collected and evaluated data on 423 pregnancies exposed during the first 9 weeks of gestation to a "high" dose of vitamin A (10,000 IU per day or more). Data were collected prospectively; 394 women (93.1%) were followed by telephone interview up to the first few weeks after the expected date of delivery, using standardized procedures. The presence of major structural malformations, excluding chromosomal and genetic diseases, was evaluated in 311 infants exposed to a median daily dose of vitamin A of 50,000 IU per day (range, 10,000-300,000 IU per day; interquartile range, 25,000-60,000 IU per day). Three infants with a major malformation were reported: pulmonary stenosis, stenotic anus with fistula, and bilateral inguinal hernia. No congenital malformations were reported among 120 infants exposed to more than 50,000 IU per day of vitamin A. When the birth prevalence rate of major malformations in the study group was compared with two internal control groups of infants exposed to: 1) "high" vitamin A exposure later in pregnancy, and 2) nonteratogenic agent exposures, the rate ratio was, respectively, 0.28 (CI 95% interval, 0.06, 1.23) and 0.50 (CI 95% interval, 0.14, 1.76). The studied sample did not provide evidence for an increased risk of major malformations, associated with "high" vitamin A intake during the organogenetic period, higher than 2.76 above the control reference risk of 1.91% (power 80%, alpha 0.10).

Abnormalities, Drug-Induced↗
PubMed1999

Intrauterine effects of electromagnetic fields--(low frequency, mid-frequency RF, and microwave): review of epidemiologic studies.

Electromagnetic radiations are named according to frequency or to wavelength (which is inversely proportional to frequency) and create electromagnetic fields (EMFs). Frequencies widely vary according to sources: high-voltage power lines, electrically heated beds, MRI, VDTs, microwave ovens, satellite, and radio/TV transmissions or cellular phone transmitters/receivers. Public concern has increased about the potential health effects of EMFs. There are arguments in favour of EMFs being biologically active, but no mechanism has been identified that explains the link between EMFs and bioeffects. Human data reviewed concern the potential reproductive effects (mainly spontaneous abortions, low birthweight and congenital malformations) of exposure to sources of EMFs: maternal residence, electrically heated beds, occupational exposure (mainly video display terminals), and medical exposures. The available epidemiologic studies all have limitations that prevent to draw clearcut conclusions on the effects of EMFs on human reproduction. EMFs are ubiquitous and unavoidable exposures. The matter of possible effects cannot be considered closed, but until our understanding of the biologic important parameters of EMFs exposures is stronger,design of new studies will be difficult and small epidemiologic studies are unlikely to provide definitive answers and should not be given high priority. No conclusion can be drawn for radiofrequencies and microwaves because of lack of data. There is no convincing evidence today that EMFs of the sort pregnant women or potential fathers meet in occupational or daily life exposures does any harm to the human reproductive process.

Electromagnetic Fields↗
PubMed1999

CHARGE Association in newborns: a registry-based study.

The CHARGE Association is a nonrandom occurrence of congenital malformations that has been described in clinical series. Reported patients have been selected on the basis of certain prior criteria. In this article, we try to identify a congenital malformation pattern corresponding to the CHARGE Association, using statistical methods and analyzing 5,260 infants with multiple malformations collected from four large registries of congenital malformations. Care was taken to identify a number of confounding characteristics that can influence the ascertainment and registration of specific congenital malformations. We have identified a cluster of malformations that generally agreed with the current clinical definition of the CHARGE Association and have added some further malformations (e.g., facial clefts). We demonstrate that others (e.g. , esophageal atresia) are probably not part of the pattern. Heart defects (H in the acronym) seems to be less helpful in identifying infants with the association. We suggest a method to select infants who probably represent the CHARGE Association for analyses of possible risk factors.

Abnormalities, Multiple↗
PubMed1999

Efficacy of routine fetal ultrasound screening for congenital heart disease in Isère County, France.

Recent literature has revealed different percentages of prenatal detection of congenital heart disease. Therefore we chose to analyse the sensitivity of this screening in Isère county and to scrutinize to which extent factors like severity of the anomaly, extracardiac anomalies and maternal age influence the sensitivity. This retrospective study covers the period from 1989 to 1995. All the pregnancies with congenital heart disease in Isère county in France were reviewed and analysed, which was possible thanks to our registry of congenital anomalies. In this period, 316 cases were registered in the central database. We obtained an overall sensitivity of 34.8 per cent. By splitting the different malformations into two groups we got a detection rate of 53.7 per cent for major malformations and 26.7 per cent for other abnormalities. This difference is significant. Nevertheless, the sensitivity remains quite low. This result stresses the need for better education of investigators in primary care units, particularly because the prenatal diagnosis of congenital heart disease has a major impact on the outcome of pregnancy, which can be seen in the increased number of abortions in this group.

Adult↗
PubMed1999

Time-course of cardiac troponin I release from isolated perfused rat hearts during hypoxia/reoxygenation and ischemia/reperfusion.

The study was designed to determine the time-course of cardiac troponin I (cTn-I) release in isolated and Langendorff-perfused rat hearts during hypoxia and reoxygenation (H/Reox), and after various durations of total ischemia and subsequent reperfusion (I/R). For this purpose, in H/Reox, cTn-I was measured with the conventional Access immunoassay (ng/ml) and a new immunoassay which operates at pg/ml, and compared with creatine kinase (CK), lactate dehydrogenase (LD) and cardiac troponin T (cTn-T). In I/R, cTn-I was compared with CK and LD. The anti-Tn-I mAbs used in cTn-I assays cross-react with cTn-I of the rat. A clear difference between time-courses and concentration levels of cTn-I in I/R and H/Reox models was found. In I/R, maximum release of cTn-I, CK and LD similarly occurred within minutes following reperfusion; however cTn-I did not return to baseline values. cTn-I levels were not linked to the duration of ischemia. In I/R, we were only able to detect small cTn-I concentrations. In H/Reox experiments, cTn-I, CK and LD increased time-dependently. We found higher cTn-I maximal peak levels detected with the Access immunoassay than with the new assay (median, 0.346 ng/ml per min/g dry wt vs 132 pg/ml per min/g dry wt). cTn-T maximal concentrations were lower than maximal cTn-I levels (median, 0.117 ng/ml per min/g dry wt). Time-courses of cTn-I release were roughly similar with both assays in the H/Reox model (r = 0.90). These data indicate that the cTn-I time-course is related to experimental model (I/R or H/Reox), but also likely depends on the sensitivity of cTn-I assays in such experimental conditions.

Animals↗
PubMed1999

A modified method for the epidemiological analysis of registry data on infants with multiple malformations.

BACKGROUND: Infants with multiple malformations are important in birth defect epidemiology and malformation monitoring because human teratogens have often caused complex malformations. Various methods for the analysis of multimalformed infants have been tried. METHOD: By using data from four large registries of congenital malformations, 5256 infants were identified with two or more among 73 selected malformations. Pairwise associations between malformations were detected by multiple logistic regression analyses, and putative confounders (programme, maternal age, autopsy, etc.) were controlled for. For each significant pairwise association, further analyses were performed in order to find associations with a possible third malformation. RESULTS: The importance of controlling for several confounders was demonstrated. Several well-known associations were found, which supports the technique used. The interpretation of three-way associations was discussed. Results from the present study were compared with those obtained using some other methods. CONCLUSIONS: Different confounders can cause biased associations. The method presented in the paper takes this into consideration and is therefore more likely than previously used techniques to give unbiased information on the clustering of different malformations among multimalformed infants.

Abnormalities, Multiple↗
PubMed1999

Effects of halothane and enflurane on ventricular conduction, refractoriness, and wavelength: a concentration-response study in isolated hearts.

BACKGROUND: Effects of halothane and enflurane on ventricular conduction, anisotropy, duration and dispersion of refractory periods, and wavelengths were studied, and putative antiarrhythmic or arrhythmogenic properties on ventricles were discussed. METHODS: High-resolution epicardial mapping system was used to study the effects of 1, 3, and 5 vol% halothane and enflurane in 30 isolated rabbit hearts. Ten hearts were kept intact to study the effects on spontaneous sinus cycle length (RR interval), perfusion pressure, and the occurrence of spontaneous dysrhythmias. In 20 other hearts, a thin epicardial layer was obtained (frozen hearts) to study ventricular conduction velocity, ventricular effective refractory period (VERP in four sites) and wavelengths. RESULTS: Halothane induced a concentration-dependent lengthening of RR interval, whereas enflurane did not. Both agents slowed longitudinal and transverse ventricular conduction velocity with no anisotropic change. Ventricular effective refractory period was prolonged at 1 vol% and was shortened at higher concentrations, with no significant increase in dispersion. Ventricular longitudinal and transverse wavelengths decreased in a concentration-dependent manner. Although changes in wavelengths could express proarrhythmic effects of volatile anesthetics, no arrhythmia occurred in spontaneously beating hearts or in frozen hearts. CONCLUSIONS: The ventricular electrophysiologic effects of halothane and enflurane were slight, suggesting that both agents are unable per se to induce functional conduction block and therefore reentrant ventricular arrhythmias.

Anesthetics, Inhalation↗
PubMed1999

Release kinetics of cardiac troponin I and cardiac troponin T in effluents from isolated perfused rabbit hearts after graded experimental myocardial contusion.

BACKGROUND: Few experimental studies report effects of direct contusion on cardiac enzyme release. Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. This investigation was designed to determine and compare the acute effects of quantified magnitudes of blunt cardiac trauma upon release of cTnI and cTnT in comparison with creatine kinase (CK) and lactate dehydrogenase (LD). METHODS: In 24 rabbit hearts prepared on a standard Langendorff apparatus, myocardial contusion (MC) was produced by a single blow with a ball falling from a predefined height, delivered directly to the surface of the heart. Hearts were divided into control (n = 6) and various quantified impacts: 75 mJoules (mJ) (n = 6), 100 mJ (n = 6), 200 mJ (n = 6). Coronary effluent samples for cTnI, cTnT, CK, and LD were collected at baseline, immediately after MC and 5, 15, 30, 45, and 60 minutes after MC. At the end of experiment, histologic condition was evaluated. RESULTS: The anti-cTnI and cTnT MAbs used in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rabbit. The time-courses of cTnI, cTnT, CK, and LD were monophasic in form. After MC, all parameters rose significantly compared with baseline and with control group. The maximal release occurred immediately after MC. The area under the cTnI curve and the maximal cTnI concentration were linked to the contusion energy when increased at 200 mJ. Maximal concentrations and areas under cTnT, CK, LD time activity curve were not linked to the contusion energy level and showed no between-energy group differences. The correlation found between maximal cTnI and maximal cTnT concentrations was 0.70 (p = 0.0001). Histologic examination showed cellular disruption and after the more severe impact, the extent of pathologic changes was more extensive. CONCLUSION: After graded experimental MC, maximal cTnI concentration and area under cTnI curve increase with the power of impact kinetic energy. Levels of cTnI allow a much higher accuracy in detecting the extent of myocardial injury postMC in comparison with cTnT, CK, and LD in this experimental study. These results should be consistent with the more extensive cTnI release with more severe impact in patients with blunt chest trauma. Furthermore, because specificity and time-course of release, both cTnI and cTnT should have a role in the diagnosis and evaluation of such patients.

Animals↗
PubMed1999

Time trends in neural tube defects prevalence in relation to preventive strategies: an international study.

OBJECTIVE: To examine time trends in neural tube defects (NTD) prevalence from 1987 to 1996 in relation to the primary prevention policies for folic acid supplementation strategies in different countries. DESIGN: Retrospective time trends analysis of NTD prevalence. SETTING: 11 birth defect registries of congenital malformations participating in the International Clearinghouse for Birth Defects Monitoring System, in the period from 1 July 1987 to 30 June 1996. SUBJECTS: 8207 live births, stillbirths and terminated pregnancies affected by anencephaly or spina bifida registered by the 11 participating centres 1987-1996. OUTCOME MEASURES: Prevalence rate ratios based on the annual rates, using the Poisson regression model. RESULTS: During the study period a significant fall in prevalence rates for all NTD is present in Atlanta (USA), England and Wales, Hungary and Japan, and a significant rise in Norway and South America. After adjusting for the secular trends observed in the earlier years of the study, no significant trend can be attributed to preventive strategies. Data on NTD prevalence are supplemented with information on folate awareness among some of the populations studied. CONCLUSION: There is no evidence that, up to the middle of 1996, any change in time trend was attributable to the introduction of national folate supplementation policies. The possible effectiveness of folate supplementation policies for the reduction of NTD clearly needs to be tried and studied for several more years. Considering that in the Western world about 50% of pregnancies are unplanned, a policy that rests on action taken before conception can only have limited success. Strategies based on food enrichment, such as was introduced in the USA from the beginning of 1998, may prove to be more successful.

Female↗
PubMed1999

Dispersion-based reentry: mechanism of initiation of ventricular tachycardia in isolated rabbit hearts.

The aim of the study was to determine whether facilitation of reentry by potassium-channel openers is related to dispersion of refractoriness and/or modification of anisotropic properties of ventricular myocardium. The dispersion of ventricular effective refractory period (VERP), longitudinal and transverse ventricular conduction velocities (thetaL and thetaT, respectively), and wavelength [lambda = VERP x theta(L or T)] were studied in Langendorff-perfused left ventricular epicardium in 20 rabbits during infusion of incremental doses of levcromakalim or nicorandil. Dispersion of refractoriness was assessed using standard deviation of VERP mean (SD-VERP), dispersion index (DI; SD-VERP/mean VERP), and maximum dispersion (Dmax = VERPmax - VERPmin). Ventricular conduction velocities and anisotropic ratio were not modified, whatever the dose used. VERP and lambda were significantly shortened at high concentrations of levcromakalim and nicorandil. At these doses, SD-VERP, DI, and Dmax were increased significantly. Analysis of ventricular tachycardia induction, performed using a high-resolution ventricular mapping system, confirmed that heterogeneity and shortening of VERP were factors inducing functional conduction block. Our data suggest that, in rabbit left ventricular epicardium, functional conduction block facilitating the occurrence of reentry could be initiated by shortening and, especially, by dispersion of refractoriness during infusion of potassium-channel openers.

Animals↗
PubMed1998

Risk of congenital anomalies near hazardous-waste landfill sites in Europe: the EUROHAZCON study.

BACKGROUND: Waste-disposal sites are a potential hazard to health. This study is a multicentre case-control study of the risk of congenital anomalies associated with residence near hazardous-waste landfill sites in Europe. METHODS: We used data from seven regional registers of congenital anomalies in five countries. We studied 1089 livebirths, stillbirths, and terminations of pregnancy with non-chromosomal congenital anomalies and 2366 control births without malformation, whose mothers resided within 7 km of a landfill site; 21 sites were included. A zone within 3 km radius of each site was defined as the "proximate zone" of most likely exposure to teratogens. FINDINGS: Residence within 3 km of a landfill site was associated with a significantly raised risk of congenital anomaly (295 cases/511 controls living 0-3 km from sites, 794/1855 living 3-7 km from sites; combined odds ratio 1.33 [95% CI 1.11-1.59], adjusted for maternal age and socioeconomic status). There was a fairly consistent decrease in risk with distance away from the sites. A significantly raised odds ratio for residence within 3 km of a landfill site was found for neural-tube defects (odds ratio 1.86 [1.24-2.79]), malformations of the cardiac septa (1.49 [1.09-2.04]), and anomalies of great arteries and veins (1.81 [1.02-3.20]). Odds ratios of borderline significance were found for tracheo-oesophageal anomalies (2.25 [0.96-5.26]), hypospadias (1.96 [0.98-3.92]), and gastroschisis (3.19 [0.95-10.77]). There was little evidence of differences in risk between landfill sites but power to detect such differences was low. INTERPRETATION: This study shows a raised risk of congenital anomaly in babies whose mothers live close to landfill sites that handle hazardous chemical wastes, although there is a need for further investigation of whether the association of raised risk of congenital anomaly and residence near landfill sites is a causal one. Apparent differences between malformation subgroups should be interpreted cautiously.

Case-Control Studies↗
PubMed1998

Associated malformations in infants and fetuses with upper or lower neural tube defects.

The paper describes associated malformations in infants born with neural tube defects (N = 3,809) from three large malformation registers and in fetuses aborted because of a diagnosed neural tube defect (N = 748) from two of the registers. In infants, upper spina bifida and encephalocele are more often associated with non-neural malformations than anencephaly or lower spina bifida. Aborted fetuses with spina bifida or encephalocele have associated malformations registered more often than infants with those neural tube defects, but the opposite is true for anencephaly. The degree of detail of the investigation of an aborted specimen or a perinatally dead infant will contribute to such differences but they can also depend on the fact that prenatal detection may be facilitated by the simultaneous presence of other malformations like body wall defects. Also, fetuses with many malformations may be more prone to abort spontaneously late in pregnancy. Variable prenatal diagnosis may, therefore, explain population differences in the pattern of associated malformations. The type of associated malformation differs with the level of the neural tube defect: this could be due to different causal mechanisms or be a question of cranio-caudal level and/or timing. For limb reduction defects, however, we did not find any association between upper limb and upper neural tube defects or lower limb and lower neural tube defects. These findings together with other epidemiological data support the idea that upper and lower neural tube defects may have different significance in epidemiological studies and should be treated separately.

Abnormalities, Multiple↗
PubMed1998

[First consultation with specialists for a child presenting with forelimb unilateral agenesis. Group for the Study and Research of Limb Agenesis (GERAM)].

After the birth of a child with a forelimb unilateral agenesis, the first consultation is of cardinal importance for the family. It should take place as soon as possible. The major point to be emphasized is that the child, although different, must not be considered as handicapped. If the aesthetic prejudice is evident, the functional incapacity is limited to some specific situations. In practice, the child with or without a prosthesis will have the same autonomy as children of the same age. A first prosthesis is usually proposed at 6 or 7 months of age. The child will wear the prosthesis more or less easily depending mainly upon the family attitude. It is recommended that the family have access to a medical team including a psychologist and an occupational therapist.

Arm↗
PubMed1998

Aggressive administration of recombinant oncotoxin AR209 (anti-ErbB-2) in athymic nude mice implanted with orthotopic human non-small cell lung tumours.

Lung cancer remains a significant public health problem in the U.S.A. and will result in an estimated 160,400 deaths in 1997. This appalling number is due in large part to the lack of adequate treatment for tumours that are refractory to surgery with curable intent, or of an adequate salvage therapy for those patients who recur after surgical resection. Because non-small cell lung cancer is refractory to traditional chemotherapy, non-traditional therapies have been developed to treat patients with this disease. Recombinant oncotoxins have been designed to target cells that express certain proteins as part of their cellular membrane. One such oncotoxin, AR209 (formerly OLX-209 [e23(Fv)PE38KDEL]), has the specificity of an anti-ErbB-2 antibody contained within a single-chain antibody domain (e23v) coupled to a portion of the Pseudomonas exotoxin A (PE38KDEL). Previous studies demonstrate that this drug is capable of significantly reducing the size of orthotopic lung tumour xenografts. However, most of the treated mice developed tumours once therapy was removed. In this study, mice were treated aggressively using one of four drug treatment schedules. Mice were treated with either intravenous or subcutaneous injections of AR209 over a 2 week period. The data indicate that AR209 significantly reduced the size of tumours and upon microscopic analysis at necropsy, some mice were cured. However, despite the treatment schedule used, many mice contained residual tumour. Residual tumours expressed the ErbB-2 protein, indicating that more aggressive treatment with AR209 may have resulted in higher rates of cure.

Animals↗
PubMed1998

[Prenatal ultrasonographic diagnosis in the epileptic mother on valproic acid. Retrospective study of 161 cases in the central eastern France register of congenital malformations].

OBJECTIVE OF STUDY: To assess the reality and efficacy of antenatal ultrasound diagnosis in epileptic women on valproic acid. STUDY DESIGN: From the France/Central-Est registry of malformations we selected both fetuses and infants presenting with malformations born to epileptic women treated with valproic acid alone or in combination regimens. We studied the evolution in the number of cases diagnosed in utero according to the period, the nature of treatment and the type of malformation. RESULTS: Among the 161 women undergoing valproic acid treatment, 60% were valproic acid alone. This rate was about 100% during the years 1994-1996. About 30% of fetuses/newborns presented with at least one of the malformations usually associated with epilepsy, namely oral clefts and heart diseases. The improvement in the rate of ultrasound diagnosis was the most pronounced for these pathologies. Other major anomalies were specific of valproic acid, accounting for 30% approximately of the malformations observed: 35 spina bifida, 18 hypospadias and 6 limb reductions. CONCLUSION: Any ultrasound examination carried the monitoring of pregnant women should assess morphology and should in the future make it possible to diagnose most of the major malformations of fetus from epileptic women treated with valproic acid.

Abnormalities, Drug-Induced↗