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E Robert

Publications and source records attributed to E Robert.

At least 55 records · Page 3Linked to original sources
PubMed1997

The epidemiology of diaphragmatic hernia.

We studied the epidemiology of diaphragmatic hernia based on 1439 cases collected from a French, a Swedish, and a California birth defect registry. This is the largest epidemiological material available up to now. Isolated diaphragmatic hernia existed in 875 infants, diaphragmatic hernia with associated malformations in 486, and with chromosome anomalies in 78. Among unilateral forms, right-sided hernias were found in about 20%, equally often in isolated and associated forms. There is a male excess of the same magnitude in isolated and associated forms but among the latter varying between programs. There was a change in the sex distribution of associated cases in California before 1988 and after which is not fully explained. The twinning rate is increased and is similar in isolated and associated forms. There is no marked effect of maternal age or parity on the risk of diaphragmatic hernia. Except for well-known conditions, no specific combination of associated malformations was found. Marked differences in recorded rates were found between the programs but not between races within the California program. The differences appear to a large extent to be due to different ascertainment, also apparent in different survival rates. Marked variations in rate with time is seen in the two programs with an extended observation time, again at least partly explainable by varying ascertainment.

California↗
PubMed1997

Effects of ketamine on ventricular conduction, refractoriness, and wavelength: potential antiarrhythmic effects: a high-resolution epicardial mapping in rabbit hearts.

BACKGROUND: The aims of the study were to verify the effects of ketamine on ventricular conduction velocity and on the ventricular effective refractory period, to determine its effects on anisotropy and on homogeneity of refractoriness, and to use wavelength to determine whether ketamine has antiarrhythmic or arrhythmogenic properties. METHODS: A high-resolution epicardial mapping system was used to study the effects of 50, 100, 150, and 200 microM racemic ketamine in 15 isolated, Langendorff-perfused rabbit hearts. Five hearts were kept intact to study the effects of ketamine on spontaneous sinus cycle length (RR) interval and its putative arrhythmogenic effects. In 10 other hearts, a thin epicardial layer was obtained by an endocardial cryoprocedure (frozen hearts) to study ventricular conduction velocity, ventricular effective refractory periods (five sites), and ventricular wavelength. RESULTS: Ketamine induced a concentration-dependent lengthening of the RR interval. Ketamine slowed longitudinal and transverse ventricular conduction velocity with no anisotropic change, and it prolonged the ventricular effective refractory period with no significant increase in dispersion. Ventricular longitudinal and transverse wavelengths tend to increase, but this was not statistically significant. Finally, no arrhythmia could be induced regardless of the ketamine concentration. CONCLUSION: Ketamine slowed ventricular conduction and prolonged refractoriness without changing anisotropy or increasing dispersion of refractoriness. Although these effects should result in significant antiarrhythmic effects of ketamine, this should not be construed to suggest a protective effect in ischemic or other abnormal myocardium.

Anesthetics, Dissociative↗
PubMed1997

Comparison of proarrhythmogenic effects of two potassium channel openers, levcromakalim (BRL 38227) and nicorandil (RP 46417): a high-resolution mapping study on rabbit heart.

This study was designed (a) to test and (b) to compare proarrhythmic effects of levcromakalim and nicorandil; and (c) determine the mechanism of arrhythmia initiation by using high-resolution ventricular epicardial mapping on 44 Langendorff-perfused rabbit hearts. Eighteen hearts were kept intact and received incremental doses (1-500 microM) of levcromakalim, nicorandil, and isosorbide dinitrate. In 26 hearts, a thin layer of epicardium was obtained after endocardial cryotechnique (frozen hearts). In intact hearts, isosorbide dinitrate did not produce any arrhythmia. In contrast, levcromakalim induced spontaneous ventricular fibrillation (VF) in all hearts at 50 microM, whereas only one VF occurred at 500 microM nicorandil. These three drugs produced a dose-dependent bradycardia in intact hearts. In frozen hearts, arrhythmias were induced by 5 microM levcromakalim and 50 microM nicorandil. Isosorbide dinitrate had no proarrhythmogenic effect. Epicardial mapping showed that most of induced ventricular tachycardias were based on reentry around an arc of functional conduction block. Ventricular conduction velocities did not change, but levcromakalim and nicorandil shortened ventricular effective refractory period. We conclude that (a) levcromakalim and nicorandil, used in toxic concentrations, have direct proarrhythmic effects; (b) nicorandil proarrhythmogenic effects are 10 times less marked than those of levcromakalim (arrhythmia is solely the result of the potassium channel opener property of nicorandil); and (c) most of ventricular tachycardias induced are based on reentry.

Animals↗
PubMed1997

Receptor-targeted recombinant adenovirus conglomerates: a novel molecular conjugate vector with improved expression characteristics.

To develop improved strategies for gene transfer to hematopoietic cells, we have explored targeted gene transfer using molecular conjugate vectors (MCVs). MCVs are constructed by condensing plasmid DNA containing the gene of interest with polylysine (PL), PL linked to a replication-incompetent adenovirus (endosomolytic agent), and PL linked to streptavidin for targeting with biotinylated ligands. In this report, we compare gene transfer to K562 cells by using the previously described transferrin-targeted MCV (Trans-MCV) to a novel transferrin-targeted MCV. In the novel MCV, the transferred gene (luciferase) is in the genome of recombinant replication-incompetent adenovirus (recMCV), which also acts as the endosomolytic agent. The level of luciferase gene expression was fivefold higher in K562 cells transfected with Trans-recMCV than in cells transfected with Trans-MCV. Furthermore, targeted transfection with recMCV resulted in prolonged luciferase expression that declined 14 to 20 days after transfection, in comparison with Trans-MCV, where luciferase expression declined by 4 to 8 days. Moreover, targeted transfection of K562 cells with the Trans-recMCV resulted in persistent luciferase gene expression for 6 months. Analysis of luciferase gene expression in K562 single-cell clones that were subcloned 5 weeks after transfection with Trans-recMCV showed that 35 to 50% of the single-cell clones had intermediate to high levels of luciferase gene expression that was stable for 6 months, with the remaining clones showing low or no luciferase gene expression. Stable gene expression was associated with integration of adenovirus sequences into genomic DNA.

Adenoviridae↗
PubMed1997

Epidemiology of choanal atresia with special reference to the CHARGE association.

OBJECTIVE: To present epidemiologic data on the relatively rare malformation choanal atresia, based on a large collection of material and with special stress on the significance of the so-called CHARGE (coloboma, heart defect, choanal atresia, retarded growth and development, genital anomaly, and ear defect with deafness) association. METHODS: Data from three large registries of congenital malformations were used. Based on more than 5 million births, 444 infants with choanal atresia were identified. RESULTS: The average rate of choanal atresia is 0.82 per 10,000 and varies among programs. There is no statistically significant difference between races in rates, even though white infants have a higher rate than those of other races. The higher rate found in the California program is mainly attributable to unilateral, isolated cases. Unilateral atresia occurs equally often on the right and left. Among all cases of choanal atresia, the sex distribution is normal, a slightly increased risk at twinning exists, and no effect of maternal age or parity is seen. Chromosome anomalies are found in 6% of infants with choanal atresia, and 21 infants (5%) have monogenic syndromes or conditions. An analysis of associated malformations (present in 47% of the infants without chromosome anomalies) indicated that although a weak nonrandom association can be demonstrated between the malformations entering the so-called CHARGE complex, only a small proportion of infants with choanal atresia and other components of that condition probably represent this entity. The term CHARGE association seems to be overused in clinical practice. CONCLUSION: To be meaningful, the term CHARGE should be restricted to infants with multiple malformations and choanal atresia and/or coloboma combined with other cardinal malformations (heart, ear, and genital) and with a total of at least three cardinal malformations. Growth retardation should not be used in the definition.

Abnormalities, Multiple↗
PubMed1996

Major congenital malformations in Down syndrome.

We studied major malformations in 5,581 infants with Down syndrome (DS) from three registers of congenital malformations. THe prevalence at birth of 23 different malformations was compared with the program-specific rates for each malformation in non-DS infants. An about 300 times risk increase was seen for annular pancreas, cataracts and duodenal atresia and an about 100 times risk increase for megacolon and small choanal atresia. Esophageal, anal and small bowel atresia, preaxial polydactyly, and omphalocele all showed risk increases between 10 and 30 times. Statistically significantly elevated risk ratios around 3-5 were seen for cleft palate, cleft lip/palate, and limb deficiencies. No increased risk was seen for neural tube defects, hydrocephaly, microtia, renal agenesis or severe dysgenesis, hypospadias or polydactyly other than preaxial. Oral clefts were more often present in DS in the Swedish material than in the other two materials. Cardiac defects were registered in 26% of all cases (varying between programs) but 28% of the cardiac defects were unspecified. DS infants born to women younger than 25 years had a significantly increased risk for megacolon and there was a trend increasing risk for esophageal or anal atresia with maternal age. A decreased risk for cardiac defect in DS infants born to teenage mothers was found, quite pronounced for endocardial cushion defects and ventricular septum defects. There were no statistically significant differences in the sex distribution of specific malformations in infants with DS and in non-DS infants.

Adult↗
PubMed1996

Teratogen update: electromagnetic fields.

Public concern is increasing about the potential health effects of extremely low frequency (ELF) electromagnetic fields (EMFs) naturally present or generated by electrical appliances and those of very low frequency (VLF) fields, like those generated by video display terminals (VDTs). There are arguments in favour of EMFs being biologically active but no mechanism has been identified that explains the link between EMFs and bioeffects. More than 50 studies on exposures of animals to EMFs have been performed within the last few years. Although there were a few statistically significant effects in the studies reviewed, no replicable results were found among laboratories. The extent of effects observed, if any, was always low, and deserves further investigation before relevance to humans can be considered. Human data reviewed concern the potential reproductive effects (mainly) spontaneous abortions, low birthweight, and congenital malformations) of exposure to various sources of EMFs: maternal residence, heated waterbeds, electric blankets, and ceiling heating coils, occupational exposure (mainly video display terminals), and magnetic resonance imaging. The totality of the evidence that is thus far available provides no convincing evidence to indicate that low frequency EMFs of the sort that might be met in occupational or daily life exposures does any harm to the human reproductive process. It is suggested that those counseling pregnant women follow the guidelines established by WHO in agreement with the International Non-ionizing Radiation Committee. This group does not consider that the results of published studies provide a basis for restricting human exposure to electromagnetic fields and radiation.

Animals↗
PubMed1996

Pregnancy outcome after prenatal quinolone exposure. Evaluation of a case registry of the European Network of Teratology Information Services (ENTIS).

OBJECTIVE: To study potential teratogenic effects of quinolone exposure during pregnancy. STUDY DESIGN: Prospective follow-up study. Subjects are pregnant women who contacted a teratology information center for risk information on quinolone treatment. A total of 549 pregnancies was collected by the European Network of Teratology Information Services between 1986 and 1994. In addition 116 prospectively documented pregnancies and 25 retrospective case reports on malformed children from other databases were analyzed. RESULTS: The malformation rate among the live-born babies in the prospective ENTIS cohort was approximately 4.8%. No specific patterns of congenital abnormalities were found. The results do not suggest an elevated risk for spontaneous abortion, prematurity, intrauterine growth retardation and postnatal disorders. CONCLUSION: The present study does not reveal any clear adverse reactions (fetal and neonatal toxicity, including birth defects) due to the in utero exposure to quinolones. Hence, termination of pregnancy because of such exposure is not indicated. However, considering the limitations of this study and the fact that diseases urgently requiring quinolone treatment are rare, it appears advisable to prefer penicillin, cephalosporins and erythromycin as antibiotics of choice.

4-Quinolones↗
PubMed1996

The descriptive epidemiology of anophthalmia and microphthalmia.

BACKGROUND: Anophthalmia and microphthalmia are serious eye malformations which recently have been associated with exposure to Benomyl. Data on these malformations are scarce in the literature and reported prevalences at birth vary strongly. METHODS: Data from three large registers of congenital malformations were analysed and comprised 849 malformed infants based on close to 5.7 million births. RESULTS: This is the largest available epidemiological study on anophthalmia and microphthalmia. The prevalence at birth was 1.50 per 10,000, varying between 0.92 and 2.29 between registers but no varying significantly between races in the California register. The variation in rates was mainly due to different inclusion of chromosomally abnormal infants (mainly trisomy 13) and of infants with microphthalmia occurring with major non-eye malformations. On the other hand, rates of anophthalmia and isolated microphthalmia were similar. Other major non-eye malformations were found in 73% of infants without a known chromosome anomaly. The malformation was bilateral in 53-60% of infants except when microphthalmia existed without any other malformations when only 27% were bilateral. Sex distribution was normal, there was a slight excess of twins, and an increased risk at high maternal age. CONCLUSIONS: In analytical studies searching for the cause of these malformations, it may be useful to restrict the analysis to infants with anophthalmia or isolated microphthalmia as the recording of such cases seems to be more reliable than of microphthalmia occurring with other malformations. The conclusions presented in the literature on the possible effect of Benomyl are partly based on data with apparent very incomplete ascertainment.

Abnormalities, Multiple↗
PubMed1996

Case-control study on maternal residential proximity to high voltage power lines and congenital anomalies in France.

The literature indicates that exposure to electro-magnetic fields (EMF) may result in an increased incidence of cancer and spontaneous abortion. The aim of the present study was to determine whether living closer to high voltage power lines (HVPL) increased the risk of congenital anomalies. We studied residential exposure in any municipality in the Central-East Region of France where there was at least one residence within 500 metres of a HVPL. This was a matched case-control design. The cases consisted of all children with congenital anomalies, identified to the population-based registry in Central-East France between 1988-91. We chose two random controls, matched for birth year and municipality, for each case. For every case and control, we measured the distance from the HVPL to the maternal residence at the time of birth of the child as a surrogate for EMF exposure. Using 100 metres from an HVPL as the cut-point between exposure and non-exposure to electro-magnetic fields produced by HVPL, yielded an odds ratio of 0.95 (95% (confidence interval) CI: 0.45-2.03). Using 50 metres as the cut-point, yielded an OR of 1.25 (95% CI: 0.49-3.22). Among the 11 cases within 100 metres, there were 2 children with chromosomal anomalies, but otherwise there was no pattern in the occurrence of specific anomalies. These data indicate a lack of association between distance to HVPL and the total number of congenital anomalies. This study does not have enough statistical power to determine whether the prevalence of a specific congenital anomaly is significantly increased as a result of living near a HVPL.

Case-Control Studies↗
PubMed1996

The epidemiology of anotia and microtia.

We studied a large data set from three registries of congenital malformations (central-east France, Sweden, and California), a total of 954 cases, known chromosome anomalies excluded. The prevalence at birth varied significantly between programmes, probably to a large extent because of different ascertainment and inclusion criteria, from 0.76 per 10,000 births in the French programme to 2.35 in the Swedish. Within the California programme, there is a racial variability in prevalence with lower values among whites (and probably blacks) than in Hispanics and Asians. Also the proportion of anotia and microtia varies between races with the lowest proportion of anotia in whites. Anotia and microtia are equally often associated with other malformations and show other similar epidemiological characteristics. In unilateral cases, the right side is more frequently malformed than the left side, especially when the ear malformation is isolated. There is a male excess, most pronounced in isolated forms. Among associated malformations, facial clefts and cardiac defects are the most common ones (each about 30% of infants with associated malformations), followed by anophthalmia or microphthalmia (14%), limb reduction defects or severe renal malformations (11%), and holoprosencephaly (7%). There is a maternal parity effect seen, an increased risk at parity 4+ (standardised for maternal age), more pronounced for anotia than microtia.

Abnormalities, Multiple↗
PubMed1996

Electrophysiologic and proarrhythmogenic effects of therapeutic and toxic doses of imipramine: a study with high resolution ventricular epicardial mapping in rabbit hearts.

Electrophysiologic and proarrhythmogenic effects of imipramine were studied by use of 21 Langendorff-perfused rabbit hearts and high-resolution mapping to analyze epicardial activation of the left ventricle. In 16 hearts, a thin layer of epicardium was obtained by an endocardial cryotechnique (frozen hearts). Five hearts were kept intact (nonfrozen imipramine-treated group). Preparation stability was verified in six frozen hearts. In 10 frozen and in 5 nonfrozen hearts, 0.01, 0.1, 1.0, 2.0 and 5.0 micrograms/ml imipramine were administered. In nonfrozen imipramine-treated hearts, imipramine induced bradycardia at 5.0 micrograms/ml (291.8 +/- 40.5 vs. 495.2 +/- 54.4 msec, P = .02), one A-V block at 5.0 micrograms/ml and two monomorphic ventricular tachycardias (MVT) at 2.0 and 5.0 micrograms/ml. In 4/10 frozen hearts, three MVT were induced at 1.0 microgram/ml imipramine and one MVT at 2.0 micrograms/ml imipramine. All MVT were based on reentry around a line of functional conduction blocks. Imipramine (2.0 micrograms/ml) slowed longitudinal and transversal ventricular conduction velocities at a pacing cycle length of 1000 msec from 71.7 +/- 6.1 to 63.0 +/- 7.7 cm/sec (P = .008) and from 32.9 +/- 2.6 to 27.7 +/- 2.8 cm/sec (P = .009), respectively, and prolonged ventricular effective refractory period from 141.9 +/- 9.3 to 279.1 +/- 112.6 msec (P = .03). Imipramine induced dose- and use-dependent slowing of ventricular conduction velocity facilitating functional conduction blocks and reentrant MVT.

Animals↗
PubMed1996

[Epidemiological study of intestinal atresias: central-eastern France Registry 1976-1992].

OBJECTIVE: Our purpose was to describe the epidemiology of small intestinal atresia. STUDY DESIGN: We used data collected by the Central-East France Congenital Malformations Registry from 1976 through 1992 to evaluate the prevalence of different types of intestinal atresia in liveborn and stillborn infants and to study some demographic and clinical features such as sex ratio, multiple births, gestational age, birth weight, maternal age, maternal disease, associated malformations. RESULTS: Through surveillance of more than 1.5 million births, we identified 344 liveborn and 14 stillborn infants with intestinal atresia (1A). The prevalence of 1A was 2.25 per 10,000 livebirths. Fifty percent of the liveborn infants had duodenal atresia, 36% had jejunoileal atresia, 7% had colic atresia, 3% had intestinal duplication and 5% had multiple atresia. The twinning rate was 4.4% which is significantly higher than in the non malformed population. Gestational age was less than 37 weeks in 35.4% of the cases. Birth weight was less than 2,500 g in 52% of the cases. For those two variables we observed significant differences among the different types of malformations. Study of 1A rates by maternal age showed an increased risk below the age of 20 (p < 10(-5)). We didn't find significant differences compared to the population for ovulation induction and maternal diabetes. Study of associated malformations demonstrated significant differences in rates and types of associated malformations in the different groups of 1A which suggests heterogenous embryological mechanisms. CONCLUSION: These findings confirm the literature data for most of the epidemiological characteristics. Only the association of an increased risk in the teenage mothers group was not previously described. This finding has to be confirmed by others studies.

Abortion, Therapeutic↗
PubMed1996

[Example of teratogen detection using a birth defects registry: depakine and spina bifida].

Most of the human teratogens were discovered as a result of case reports and not primarily through epidemiological studies. We report the detection of a teratogenic effect based both clinical experience and epidemiological analysis. The possibility that anticonvulsant drugs might be teratogenic has been discussed in the literature for several decades. In 1982, we suggested a specific association between valproic acid and spina bifida. The observation was coming both from personal interviews with families of liveborn infants operated upon for spina bifida and from registry data: among 200,000 infants born in the Rhône-Alpes region between August 1979 and August 1982, 11 had spina bifida and were born to epileptic women, 9 of them treated with valproate. Further data confirmed these findings and led to an estimation of about 1-2% for the risk to have an infant with spina bifida after use of valproic acid. The detection of valproic acid teratogenicity raised from an unusual set of circumstances in the Rhône-Alpes region: the existence of a birth defects registry, a special interest for spina bifida, a questionnaire with a routine question on epilepsy, a high prescription rate of valproic acid (28% of women in childbearing age) and the registry status of member of the International Clearinghouse for Birth Defects Monitoring Systems. From a public health point of view, this finding has led doctors to consider treatment with valproic acid as a new indication for prenatal diagnosis. 20 new cases were prenatally detected in 10 years in the Central East region of France.

Anticonvulsants↗