The French Cochlear Implant Registry (EPIIC): Cochlear implantation complications.

OBJECTIVES: The aim of this study was to evaluate peri- and post-operative complications related to cochlear implantations. We searched for risk factors predicting these complications and analyzed the complications in the youngest and most elderly. STUDY DESIGN: Retrospective analysis of cochlear implant patients. MATERIALS AND METHODS: All patients who underwent cochlear implantation in France between January 2012 and December 2016 were anonymized and registered in the EPIIC database. This population included 3483 adults and 2245 children. Their demographic and surgical data and their incidence of peri- or post-operative complications, including their severity, whether major or minor, were all indicated. RESULTS: The global complication rate was 6.84%. The risk of complication was higher in initial implantation versus reimplantation (P<0.0001). The risk was also higher for bilateral implantation versus unilateral (P<0.0001). Complications were more frequent for patients with cochlear malformation (P=0.002). There was no difference in complication rates across age groups; babies under 1 year old, and the elderly over 80 and even over 90, did not have more complications than the rest of the population. Patients treated in the daily care unit had no more complications than those who were hospitalized for one night or more (P=0.64). CONCLUSION: Cochlear implantation is a safe technique with a low incidence of complications. The absence of increased risk in patients at the extremes of the age spectrum justifies offering this solution to all, without age limitation.

Gastric Dilation due to a Neuroleptic Agent in an Elderly Patient: A Case Report.

Neuroleptics may cause side effects, some of which are little known. We describe here a case of gastric dilation related to treatment with a neuroleptic in an elderly man. To our knowledge, such a case has never been reported in the literature. A 76-year-old man, living in a nursing home, was hospitalized for general weakness and abdominal pain. He had dementia with behavioral disorders treated with cyamemazine, a sedative and anxiolytic neuroleptic. Given a clinical suspicion of intestinal occlusion, an abdominopelvic computerized tomography scan was performed before the patient was admitted to our hospital. This computerized tomography scan did not show intestinal occlusion and there was no mention of gastric dilation in the computerized tomography scan report. Thus, acute gastroenteritis was suspected. The usual medications were stopped and symptomatic treatment for gastroenteritis was started. Quickly, his clinical state and biological parameters returned to normal and his usual treatment, including cyamemazine, was started again. The next day, the digestive symptoms, except for obstipation, reappeared. The abdominal X-ray showed gastric dilation without intestinal occlusion. The neuroleptic was stopped again and symptoms vanished the next day. This report underlines all of the necessary precautions and surveillance around drug prescription, especially in elderly persons.

Genome screen for asthma and related phenotypes in the French EGEA study.

A genome-wide search was conducted in 107 nuclear families with at least two siblings with asthma, as part of the French EGEA study. A two-stage analysis strategy was applied to the 107 families divided into two independent subsets of 46 and 61 families, where all regions detected in the first set of families were tested for replication in the second set. In addition, all regions reported by published genome scans in different populations were examined in the total sample. A total of 254 markers were typed in the first set of families and 70% of them in the second set. Linkage was investigated by model-free methods for asthma and four asthma-related phenotypes: bronchial responsiveness (BR), skin test response, total immunoglobulin E (IgE) levels, and eosinophil count. The two-stage analysis led to the detection of three regions: 11p13 for IgE, 12q24 for eosinophils, and 17q12-21 for asthma and skin tests. Among the regions reported by published genome screens, seven were found in the 107 French EGEA families: three being already detected by the two-stage analysis, 11p13 (p = 0.005), 12q24 (p = 0.0008), and 17q12-21 (p = 0.001), and four additional ones, 1p31 (p = 0.005) for asthma, 11q13 (p = 0.006) for IgE, 13q31 (p = 0.001) for eosinophils, and 19q13 (p = 0.02) for BR.

Are animal models of diabetes relevant to the study of the genetics of non-insulin-dependent diabetes in humans?

Although it is well-recognized that non-insulin-dependent diabetes-mellitus (NIDDM) shown a strong genetic component the search for candidate genes has been very difficult since NIDDM is a complex, heterogeneous, multifactorial syndrome resulting from both genetic susceptibility and environmental risk factors. Therefore, the use of inbred animal models is an essential component of genetic investigations in this field. As these lines are genetically homogeneous, it is possible to direct mating for optimal genetic crosses and control environmental factors. Strains with spontaneous NIDDM may be constituted from animals with one or several genetic mutation(s) transmitted generation to generation or selected from non-diabetic outbred animals by repeated breeding. The ob/ob and db/db mice, which are rodent models of NIDDM and obesity, belong to the first category. Recent studies using the positional cloning approach allowed the mapping of ob gene and identification of its product, leptin, which is a protein secreted by white adipose tissue and involved in the control of food intake. The db gene encodes the leptin receptor. The search for genetic linkage was undertaken in polygenic models, especially the Goto-Kakisaki (GK) rat which was obtained by selective breeding of individuals with glucose intolerance from a non-diabetic Wistar rat colony. Though precise definition of sub-phenotypes of glucose tolerance and insulin secretion, the mapping of microsatellite markers and QTL analysis, it has proved possible to identify many independent loci containing genes regulating glucose homeostasis and insulin secretion. In another polygenic model, the OLETF rat, a locus present on chromosome X was identified. Many complementary approaches in different strains may lead to the identification of candidate genes for NIDDM and help direct the search for candidate genes in humans who show synteny relationships with rodents.

Analysis of quantitative trait loci for blood pressure on rat chromosomes 2 and 13. Age-related differences in effect.

Previous studies have suggested the presence of quantitative trait loci (QTLs) influencing blood pressure on rat chromosomes 2 and 13. In this study, we mapped the QTLs in F2 rats derived from a cross of the spontaneously hypertensive rat and the Wistar-Kyoto rat and analyzed the effect of the QTLs on blood pressures measured longitudinally between 12 and 25 weeks of age. We analyzed 16 polymorphic markers spanning 147.3 cM on chromosome 2 and 13 markers spanning 91.6 cM on chromosome 13. Both chromosomes contained QTLs with highly significant effects on blood pressure (peak logarithm of the odds [LOD] scores, 5.64 and 5.75, respectively). On chromosome 2, the peak was localized to a position at anonymous marker D2Wox7, 2.9 cM away from the gene for the sodium-potassium ATPase alpha 1-subunit. On chromosome 13, the major peak coincided with the marker D13Mit2, 21.7 cM away from the renin gene, but there was a suggestion of multiple peaks. The effect of the QTL on chromosome 2 was seen throughout from 12 to 25 weeks of age, whereas interestingly, the effect for the QTL on chromosome 13 was maximal at 20 weeks of age but disappeared at 25 weeks of age, presumably because of the effect of either epistatic factors or environmental influences. The findings provide important information on QTLs influencing blood pressure on rat chromosomes 2 and 13 that will be useful in localizing and identifying the causative genes and emphasize the importance of age being taken into account when the effects of individual QTLs on a trait that shows significant age-related changes are being analyzed.

Chromosomal mapping of genetic loci associated with non-insulin dependent diabetes in the GK rat.

Goto-Kakizaki (GK) rats are a well characterized model for non-insulin dependent diabetes mellitus (NIDDM). We have used a combination of physiological and genetic studies to identify quantitative trait loci (QTLs) responsible for the control of glucose homeostasis and insulin secretion in a F2 cohort bred from spontaneously diabetic GK rats. The genetic dissection of NIDDM allowed us to map up to six independently segregating loci predisposing to hyperglycaemia, glucose intolerance or altered insulin secretion, and a seventh locus implicated in body weight. QTLs implicated in glucose tolerance and adiposity map to the same region of rat chromosome 1, and may indicate the influence of a single locus. Our study demonstrates that distinct combinations of genetic loci are responsible for different physiological characteristics associated with the diabetic phenotype in the GK rat, and it constitutes an important step for directing the search for the genetic factors involved in human NIDDM.

Higher maternal than paternal inheritance of diabetes in GK rats.

Results from crosses between Goto-Kakizaki (GK) rats, which exhibit spontaneous non-insulin-dependent diabetes mellitus (NIDDM), and outbred nondiabetic Wistar rats have demonstrated an effect of maternal inheritance on diabetes in offspring of the first generation (F1). At 6 weeks of age, F1 offspring of sex-directed crosses exhibited plasma glucose values intermediate between GK and Wistar parents. Hyperglycemia in F1 rats born of female GK rats (F1GK) was more marked than in those born of female Wistar (F1W) rats. At 3 months of age, F1 rats showed a marked impairment of both glucose tolerance and insulin secretion, which was intermediate between GK and Wistar rats. Glucose intolerance was more pronounced in F1GK rats than in F1W. By contrast, insulin secretion in F1W rats was more deteriorated than in F1GK rats. No deletion in mitochondrial DNA was observed in the GK rats, which decreased the possibility of a mitochondrial inheritance effect as an explanation of our findings. These data support a polygenic model in diabetes inheritance of NIDDM and suggest that, in addition to genetic factors, a perturbed maternal metabolism can contribute to its inheritance.