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Biomedical subjects

A Philippe

Publications and source records attributed to A Philippe.

At least 19 recordsLinked to original sources
PubMed2006

Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders.

BACKGROUND: Autism spectrum disorders (ASD) refer to a broader group of neurobiological conditions, pervasive developmental disorders. They are characterised by a symptomatic triad associated with qualitative changes in social interactions, defect in communication abilities, and repetitive and stereotyped interests and activities. ASD is prevalent in 1 to 3 per 1000 people. Despite several arguments for a strong genetic contribution, the molecular basis of a most cases remains unexplained. About 5% of patients with autism have a chromosome abnormality visible with cytogenetic methods. The most frequent are 15q11-q13 duplication, 2q37 and 22q13.3 deletions. Many other chromosomal imbalances have been described. However, most of them remain undetectable using routine karyotype analysis, thus impeding diagnosis and genetic counselling. METHODS AND RESULTS: 29 patients presenting with syndromic ASD were investigated using a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Eight clinically relevant rearrangements were identified in 8 (27.5%) patients: six deletions and two duplications. Altered segments ranged in size from 1.4 to 16 Mb (2-19 clones). No recurrent abnormality was identified. CONCLUSION: These results clearly show that array comparative genomic hybridisation should be considered to be an essential aspect of the genetic analysis of patients with syndromic ASD. Moreover, besides their importance for diagnosis and genetic counselling, they may allow the delineation of new contiguous gene syndromes associated with ASD. Finally, the detailed molecular analysis of the rearranged regions may pave the way for the identification of new ASD genes.

Adolescent↗
PubMed2005

Molecular cytogenetic analysis of five 2q37 deletions: refining the brachydactyly candidate region.

Deletions of the 2q37 region are associated with a recognizable pattern of MCA/MR so-called the AHO-like syndrome. Brachydactyly is a variable but characteristic feature of this clinical entity. Here we report on five cases of cytogenetically visible de novo deletions of this 2q37 chromosome region. Using FISH, we characterized at the molecular level the breakpoints of these deletions using a set of 15 BACs, PACs and YACs. In four patients, terminal deletions of variable size ranged between 6.2 and 10 Mb. The fifth patient had an interstitial deletion with an AHO-like phenotype including brachydactyly. These findings when compared to previous observations allowed us to narrow down the brachydactyly critical region between BACs RP11-585E12 and RP11-351E10. It contains HDAC4 and STK25 candidate genes loci.

Adult↗
PubMed2005

Data on diabetes from the French cohort study in schizophrenia.

To establish the impact of antipsychotic medication on the incidence of diabetes, we have analysed data from the prospective French Cohort study of mortality in schizophrenia. This generated a large database of 3470 patients with schizophrenia initially enrolled in 1993 for which data collection on comorbidity has been collected systematically every three years since. The primary objective of the study was to evaluate the mortality rate in the study cohort. From this database, the prevalence and incidence of diabetes can be studied. In 1993, nine patients in 10 were prescribed conventional antipsychotics and the remainder amisulpride and clozapine. Since the introduction of risperidone and olanzapine, atypical antipsychotics are now used in one-third of patients. Multiple antipsychotic medications are used in many patients, with the exception of those receiving clozapine. At inclusion, 2.2% of patients in the study cohort had a diagnosis of diabetes. Morbidity rates were higher in females than in males (3.4% and 1.6%, respectively) and it was only in females that the standard morbidity ratio with respect to the general population was significantly elevated (2.2; 95% confidence intervals: 1.6 and 2.9). The prevalence of diabetes in the study cohort rose over the course of the study. Multivariate regression analysis was performed in order to identify potential determinants of diabetes. For pre-existing diabetes, four factors were identified: age at first hospitalisation, age, obesity and duration of schizophrenia. The same factors with the exception of length of illness were identified for the incident cases. There was no evidence for an interaction between the class and type of antipsychotic medication and risk of treatment emergent diabetes. However, the use of multiple antipsychotic treatments makes the individualisation of specific risks associated with any other antipsychotic drug impossible.

Adolescent↗
PubMed2004

Neurodevelopmental pattern of succinic semialdehyde dehydrogenase deficiency (gamma-hydroxybutyric aciduria).

Succinic semialdehyde dehydrogenase (SSADH deficiency) (MIM 271980) is a defect in gamma-aminobutyric acid catabolism, resulting in the accumulation of gamma-hydroxybutyric acid (GHB) and causing neurological and cognitive disorders of varying severity. The non-specific nature and the difficulties in detection of urinary GHB explain why this disorder is largely underdiagnosed. Of 350 patients identified worldwide, to date only six adults with SSADH deficiency have been reported in the literature. Here we describe two additional cases in brothers up to ages 26 and 28 years. This retrospective report sheds light on the clinical features of SSADH deficiency in relation to the physiopathological involvement of GHB, and tries to identify the specific neurodevelopmental pattern of this learning disability.* Features of this are: early impaired psychomotor development with hypotonia and disturbances in motor coordination; impaired development of language, mainly due to poor auditory perception; and seizures and psychotic features in late adolescence or adulthood. Moreover, narcolepsy-like symptoms could be a consistent feature of the disease.

Adolescent↗
PubMed2003

[Suicide in the elderly at home and in retirement homes in France].

BACKGROUND: Suicide in the elderly attracts less attention that in the young. However it is more frequent among the former. The retirement home receives the populations most isolated from their families and those most vulnerable from a psychological and physical point of view. The aim of this research is to provide information concerning suicide in the elderly in France, to specify the means employed and to compare suicide rates at home and in retirement homes METHODS: The statistics utilized are those of population size (censuses) and medical causes of death. With these latter causes a relation cannot be made between place of residence and place where the death by suicide is registered. They therefore underestimate suicide rates which are only considered at the home or retirement home. Consequently different estimations have been made. RESULTS: Suicide rates are higher in the retirement home than at home for both sexes. However, for men, the suicide rates in retirement homes are similar to those recorded for isolated men living at home. On the contrary, for women, the retirement home seems to constitute a specific risk in itself with suicide rates quite distinct from the other situations studied. In the retirement homes, conversely to men, it is the youngest women, (65 to 74 years) who have the highest rates. Hanging is the most prevalent mean of suicide both at home and in the retirement homes. Jumping from a high place is the second mean utilized in the retirement homes where fire arms and consumption of substances are less represented CONCLUSIONS: There are few studies in France concerning suicide in the elderly. Due to the demographic evolution, the number of suicides among the aged may well increase considerably in the years to come.

Age Factors↗
PubMed2002

Y chromosome haplogroups in autistic subjects.

The male to female ratio in autism is 4:1 in the global autistic population, but increases to 23:1 in autistic subjects without physical or brain abnormalities.(1) Despite this well-recognised gender difference, male predisposition to autistic disorder remains unexplained and the role of sex chromosomes is still debated. Numerical and structural abnormalities of the sex chromosomes are among the most frequently reported chromosomal disorders associated with autism. However, genome scans have failed to detect linkage on the X chromosome(2,3,4) and this approach cannot study the non-recombining region of the Y chromosome. In this study, we searched for a specific Y chromosome effect in autistic subjects. Using informative Y-polymorphic markers, the Y chromosome haplotypes of 111 autistic subjects from France, Sweden and Norway were defined and compared with relevant control populations. No significant difference in Y-haplotype distribution between the affected and control groups was observed. Although this study cannot exclude the presence of a Y susceptibility gene, our results are not suggestive of a Y chromosome effect in autism.

Autistic Disorder↗
PubMed2002

Linkage and association of the glutamate receptor 6 gene with autism.

A genome scan was previously performed and pointed to chromosome 6q21 as a candidate region for autism. This region contains the glutamate receptor 6 (GluR6 or GRIK2) gene, a functional candidate for the syndrome. Glutamate is the principal excitatory neurotransmitter in the brain and is directly involved in cognitive functions such as memory and learning. We used two different approaches, the affected sib-pair (ASP) method and the transmission disequilibrium test (TDT), to investigate the linkage and association between GluR6 and autism. The ASP method, conducted with additional markers on the 51 original families and in eight new sibling pairs, showed a significant excess of allele sharing, generating an elevated multipoint maximum LOD score (ASPEX MLS = 3.28). TDT analysis, performed in the ASP families and in an independent data set of 107 parent-offspring trios, indicated a significant maternal transmission disequilibrium (TDTall P = 0.0004). Furthermore, TDT analysis (with only one affected proband per family) showed significant association between GluR6 and autism (TDT association P = 0.008). In contrast to maternal transmission, paternal transmission of GluR6 alleles was as expected in the absence of linkage, suggesting a maternal effect such as imprinting. Mutation screening was performed in 33 affected individuals, revealing several nucleotide polymorphisms (SNPs), including one amino acid change (M867I) in a highly conserved domain of the intracytoplasmic C-terminal region of the protein. This change is found in 8% of the autistic subjects and in 4% of the control population and seems to be more maternally transmitted than expected to autistic males (P = 0.007). Taken together, these data suggest that GluR6 is in linkage disequilibrium with autism.

Amino Acid Sequence↗
PubMed2002

Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder.

Previous studies have provided conflicting evidence regarding the association of the serotonin transporter (5-HTT) gene with autism. Two polymorphisms have been identified in the human 5-HTT gene, a VNTR in intron 2 and a functional deletion/insertion in the promoter region (5-HTTLPR) with short and long variants. Positive associations of the 5-HTTLPR polymorphism with autism have been reported by two family-based studies, but one found preferential transmission of the short allele and the other of the long allele. Two subsequent studies failed to find evidence of transmission disequilibrium at the 5-HTTLPR locus. These conflicting results could be due to heterogeneity of clinical samples with regard to serotonin (5-HT) blood levels, which have been found to be elevated in some autistic subjects. Thus, we examined the association of the 5-HTTLPR and VNTR polymorphisms of the 5-HTT gene with autism, and we investigated the relationship between 5-HTT variants and whole-blood 5-HT. The transmission/disequilibrium test (TDT) revealed no linkage disequilibrium at either loci in a sample of 96 families comprising 43 trios and 53 sib pairs. Furthermore, no significant relationship between 5-HT blood levels and 5-HTT gene polymorphisms was found. Our results suggest that the 5-HTT gene is unlikely to play a major role as a susceptibility factor in autism.

Adolescent↗
PubMed2000

Assessing the impact of a consensus conference on long-term therapy for schizophrenia.

OBJECTIVE: Our aim was to assess the impact of six recommendations regarding drug prescription on the clinical practices of French psychiatrists. The recommendations were part of the conclusions of a consensus conference entitled "Long-term therapy of schizophrenia" (Paris, January 1994). METHODS: The impact of the conference was assessed on the basis of awareness of the existence of the conference, knowledge of its conclusions, and actual changes in clinical practice. We performed: a) a survey of a representative sample of 396 psychiatrists 2 years after the conference; and b) an analysis of changes in drug prescriptions in a cohort of 2,407 patients with schizophrenia under treatment at the time of the conference. RESULTS: Overall, 78% of interviewed psychiatrists were aware of the existence of the conference and 70% of its conclusions. Declared prescription practices conformed with conference conclusions about 60% (10%-95%) of the time. No difference in practices was noted between psychiatrists who were aware of the recommendations and those who were not. Single neuroleptic prescriptions increased in the cohort study in line with the main conference recommendation. The increase was small, but significant from 51.1% to 56.4%, and mainly concerned patients recently put on treatment. Contrary to recommendations, prescriptions of anticholinergics plus neuroleptics inexplicably rose from 48.2% to 54.3%. CONCLUSION: Small changes in prescription habits occurred in the wake of the consensus conference, but we cannot really ascribe them to a direct impact of the conference. Despite the great pains we took in disseminating the conclusions of the conference as widely as possible, it is clear that a more forceful action plan (e.g., including continuous medical education) is required.

Adolescent↗
PubMed1999

Whole blood serotonin and plasma beta-endorphin in autistic probands and their first-degree relatives.

BACKGROUND: Whole blood serotonin (5-HT) and C-terminally directed beta-endorphin protein immunoreactivity (C-ter-beta-EP-ir) are known to be elevated in autistic subjects and might be possible markers of genetic liability to autism. This study thus investigates the familial aggregation of 5-HT and of C-ter-beta-EP-ir levels in first degree relatives of autistic probands. METHODS: In a sample of 62 autistic subjects and 122 of their first-degree relatives, compared to age and sex-matched controls, we measured 5-HT by radioenzymology and C-ter-beta-EP-ir by radioimmunoassay. RESULTS: We confirm the previously reported familiality of hyperserotoninemia in autism as mothers (51%), fathers (45%) and siblings (87%) have elevated levels of 5-HT, and we reveal presence of elevated levels of C-ter-beta-EP-ir in mothers (53%) of autistic subjects. CONCLUSIONS: Familial aggregation of quantitative variables, such as concentration of neurotransmitters, within unaffected relative could serve as an intermediate phenotype and might thus help the search of genetic susceptibility factors in autism.

Adolescent↗
PubMed1999

Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study.

Family and twin studies have suggested a genetic component in autism. We performed a genome-wide screen with 264 microsatellites markers in 51 multiplex families, using non-parametric linkage methods. Families were recruited by a collaborative group including clinicians from Sweden, France, Norway, the USA, Italy, Austria and Belgium. Using two-point and multipoint affected sib-pair analyses, 11 regions gave nominal P -values of 0.05 or lower. Four of these regions overlapped with regions on chromosomes 2q, 7q, 16p and 19p identified by the first genome-wide scan of autism performed by the International Molecular Genetic Study of Autism Consortium. Another of our potential susceptibility regions overlapped with the 15q11-q13 region identified in previous candidate gene studies. Our study revealed six additional regions on chromosomes 4q, 5p, 6q, 10q, 18q and Xp. We found that the most significant multipoint linkage was close to marker D6S283 (maximum lod score = 2.23, P = 0.0013).

Adolescent↗
PubMed1998

Relation between attempted suicide and suicide rates among young people in Europe.

STUDY OBJECTIVE: To determine if there are associations between rates of suicide and attempted suicide in 15-24 year olds in different countries in Europe. DESIGN: Attempted suicide rates were based on data collected in centres in Europe between 1989 and 1992 as part of the WHO/EURO Multicentre Study of Parasuicide. Comparison was made with both national suicide rates and local suicide rates for the areas in which the attempted suicide monitoring centres are based. SETTING: 15 centres in 13 European countries. PATIENTS: Young people aged 15-24 years who had taken overdoses or deliberately injured themselves and been identified in health care facilities. MAIN RESULTS: There were positive correlations (Spearman rank order) between rates of attempted suicide and suicide rates in both sexes. The correlations only reached statistical significance for male subjects: regional suicide rates, r = 0.65, p < 0.02; national suicide rates, r = 0.55, p < 0.02. CONCLUSIONS: Rates of attempted suicide and suicide in the young covary. The recent increase in attempted suicide rates in young male subjects in several European countries could herald a further increase in suicide rates.

Adolescent↗
PubMed1995

Adenylosuccinate lyase (ADSL) and infantile autism: absence of previously reported point mutation.

Autism is a heterogeneous neuropsychiatric syndrome of unknown etiology. There is evidence that a deficiency in the enzyme adenylosuccinate lyase (ADSL), essential for de novo purine biosynthesis, could be involved in the pathogenesis of certain cases. A point mutation in the ADSL gene, resulting in a predicted serine-to-proline substitution and conferring structural instability to the mutant enzyme, has been reported previously in 3 affected siblings. In order to determine the prevalence of the mutation, we PCR-amplified the exon spanning the site of this mutation from the genomic DNA of patients fulfilling DSM-III-R criteria for autistic disorder. None of the 119 patients tested were found to have this mutation. Furthermore, on preliminary screening using singlestrand conformation polymorphism (SSCP), no novel mutations were detected in the coding sequence of four ADSL exons, spanning approximately 50% of the cDNA. In light of these findings, it appears that mutations in the ADSL gene represent a distinctly uncommon cause of autism.

Adenylosuccinate Lyase↗
PubMed1994

Difference between plasma N- and C-terminally directed beta-endorphin immunoreactivity in infantile autism.

OBJECTIVE: The authors investigated whether there is excessive opioid activity in infantile autism by measuring plasma beta-endorphin in patients with autism compared with patients who had Rett's syndrome and normal comparison subjects. METHODS: Radioimmunoassays for beta-endorphin using C-terminally and N-terminally directed antisera were applied to plasma samples from 67 children who met both DSM-III-R and ICD-10 diagnostic criteria for infantile autism, 22 girls with Rett's syndrome, and 67 normal children matched in age and sex with the children with autism. RESULTS: Median N-terminally directed beta-endorphin immunoreactivity appeared to be slightly lower in subjects with autism (7 pg/ml) and clearly higher in the girls with Rett's syndrome (40 pg/ml) than in the comparison subjects (9 pg/ml). Median C-terminally directed beta-endorphin immunoreactivity was higher in the girls with Rett's syndrome (35 pg/ml) and much higher in patients with autism (70 pg/ml) than in comparison subjects (8 pg/ml). CONCLUSIONS: These findings demonstrate the existence of a wide discrepancy between C- and N-terminally directed beta-endorphin immunoreactivity among children with autism. Despite the fact that the nature of the antigen recognized in the plasma of autistic children by the C-terminally directed anti-beta-endorphin serum remains to be characterized, the difference between C- and N-terminally directed beta-endorphin immunoreactivity might suggest an abnormal processing of the pro-opiomelanocortin gene in infantile autism.

Adolescent↗
PubMed1993

Intranasal treatment of perennial allergic rhinitis. Comparison of azelastine nasal spray and budesonide nasal aerosol.

The efficacy and tolerability of azelastine (CAS 58581-89-8) nasal spray (0.14 mg/nostril b.i.d.) and budesonide (CAS 51333-22-3) nasal aerosol (0.05 mg/nostril b.i.d.) were compared in a 6-week, multicentre, parallel group study of 193 patients suffering from perennial allergic rhinitis. Total rhinitis symptoms complex (TSC) scores derived from 10 rhinitis symptoms improved during treatment by a mean of 11.4 +/- 6.8 with azelastine and 10.8 +/- 6.4 with budesonide. Response rates, defined as a decrease in TSC of at least 50% at the end of therapy, was 79% with azelastine and 73% with budesonide. There were no significant differences between the treatment groups with respect to either target variable. Objective measurements of nasal flow rate showed a return to normal values during the 6-week therapy. Signs of rhinitis identified by rhinoscopic examination improved in parallel to symptoms. Both medications were well tolerated. The incidence of adverse events of possibly causal relationship to therapy was low. The most frequent event in azelastine treated patients was the experience of an "unpleasant" taste or smell. Occasional epistaxis occurred in both treatment groups but more frequently with budesonide. Results indicate that with the dose used azelastine nasal spray is an effective treatment for perennial allergic rhinitis comparable to that of budesonide nasal aerosol.

Administration, Intranasal↗
PubMed1992

[Mortality due to suicide, accidents and undetermined causes in hospitalized mental patients 1968-1982].

An analysis of the national statistics on mortality in psychiatric hospitals, covering 14 years from 1968 to 1982, provided rates of deaths by suicides, accidents and ill-defined symptoms (chapters 16 and 17 in the ICD). Death rates among psychiatric inpatients are compared to rates in the general population. For suicide, there is an increase of about 45% in patients under 75, which is higher than for the general population. The evolution for accidents is close to that found in the general population. The death rate by ill-defined symptoms is decreasing. The increase in the rates of deaths by suicide found both in France and in several other countries suggests that the major changes (sectorization policy and use of psychotropic drugs), in the care lead to increased risk of suicide for certain patients due to shortened hospital stays and subsequent intermittent institutional care. Specific modes of death can also be described: senility without mention of psychosis, airway obstruction by false passages, notably in subjects under 55, accidental falls, hangings and drownings are particularly important in the observed over-mortality.

Accidents↗