RESUMO
OBJECTIVES: The recommended treatment for Eating Disorders (EDs) is multidisciplinary and multimodal. Nonetheless, the complex linkage of the different disciplines involved is not necessarily simple. We analyzed the experience of healthcare professionals faced with psychiatric and psychological symptoms in adolescents with EDs in two "multidisciplinary" inpatient units embedded predominantly in different paradigms - one pediatric and one psychiatric. METHODS: Qualitative analysis of 20 healthcare staff members' interviews from different professional backgrounds working in inpatient units for EDs in Montreal (Canada) and Paris (France). RESULTS: The "Complex patients" theme discusses the need for a global approach to the multiplicity of symptoms presented by these patients. "Management and its limits" describes the daily management of psychiatric symptoms in both units. "Psychiatry and Adolescent medicine: from opposition to collaboration" describes the different levels at which these disciplines work together and how this cooperation may be evolving. CONCLUSIONS: The complex entanglement intrinsic in EDs of the patients' somatic, psychosocial, psychiatric, and adolescent problems requires collaboration between disciplines, but the modalities of this collaboration are multiple and evolve non-linearly in specialized treatment units. A multilevel approach must be offered, with the degree of collaboration (multidisciplinary, interdisciplinary and transdisciplinary) appropriate to the complexity of each adolescent's issues.
Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Psiquiatria , Humanos , Adolescente , Criança , Pacientes Internados , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Unidades Hospitalares , Atitude do Pessoal de SaúdeRESUMO
BACKGROUND: The growing number of spastic ataxia of Charlevoix-Saguenay (SACS) gene mutations reported worldwide has broadened the clinical phenotype of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The identification of Quebec ARSACS cases without two known SACS mutation led to the development of a multi-modal genomic strategy to uncover mutations in this large gene and explore phenotype variability. METHODS: Search for SACS mutations by combining various methods on 20 cases with a classical French-Canadian ARSACS phenotype without two mutations and a group of 104 sporadic or recessive spastic ataxia cases of unknown cause. Western blot on lymphoblast protein from cases with different genotypes was probed to establish if they still expressed sacsin. RESULTS: A total of 12 mutations, including 7 novels, were uncovered in Quebec ARSACS cases. The screening of 104 spastic ataxia cases of unknown cause for 98 SACS mutations did not uncover carriers of two mutations. Compounds heterozygotes for one missense SACS mutation were found to minimally express sacsin. CONCLUSIONS: The large number of SACS mutations present even in Quebec suggests that the size of the gene alone may explain the great genotypic diversity. This study does not support an expanding ARSACS phenotype in the French-Canadian population. Most mutations lead to loss of function, though phenotypic variability in other populations may reflect partial loss of function with preservation of some sacsin expression. Our results also highlight the challenge of SACS mutation screening and the necessity to develop new generation sequencing methods to ensure low cost complete gene sequencing.
Assuntos
Predisposição Genética para Doença/genética , Proteínas de Choque Térmico/genética , Espasticidade Muscular/genética , Mutação/genética , Ataxias Espinocerebelares/congênito , Estudos de Coortes , Análise Mutacional de DNA , Eletromiografia , Feminino , Heterozigoto , Humanos , Masculino , Espasticidade Muscular/etnologia , Fenótipo , Quebeque , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Ataxias Espinocerebelares/etnologia , Ataxias Espinocerebelares/genéticaRESUMO
The intention of this article is to compare the containment performance of a Type II microbiological safety cabinet (MSC) confronted with the simultaneous generation of a saline nanoparticle aerosol and a tracer gas (SF(6)). The back dissemination coefficient, defined as the ratio of the pollutant concentration measured outside the enclosure to the pollutant flow rate emitted inside the enclosure, is calculated in order to quantify the level of protection of each airborne contaminant tested for three enclosure operating configurations: an initial configuration (without perturbations), a configuration exposing a dummy in front of the enclosure (simulation of an operator), and a configuration employing the movement of a plate in front of the enclosure (simulation of human movement). Based on the results of this study, we observed that nanoparticulate and gaseous behaviours are strongly correlated, thus showing the predominance of air-driven transport over particle-specific behaviour. The average level of protection afforded by the MSC was found systematically slightly higher for the nanoaerosol than for the gas in the studied configurations (emission properties of the source, operating conditions, and measurement protocols). This improved protection efficiency, however, cannot be considered as a warrant of protection for operators since operating condition and ventilation parameters are still more influential on the containment than the pollutant nature (i.e. nanoaerosol or gas).
Assuntos
Contenção de Riscos Biológicos/normas , Gases/análise , Nanopartículas/análise , Saúde Ocupacional/normas , Aerossóis , Movimentos do Ar , Humanos , Manequins , Exposição Ocupacional/análise , Exposição Ocupacional/prevenção & controle , Equipamentos de Proteção/normas , Projetos de Pesquisa , VentilaçãoRESUMO
It has been reported that thrombin generation test (TGT) may be a useful tool to monitor recombinant factor VIIa (rFVIIa). However, TGT does not reflect the stability of fibrin clot and its resistance to fibrinolysis which are crucial. Using whole-blood thromboelastography (TEG) and tissue plasminogen activator (tPA), we developed an in-vitro model to assess fibrin clot stability. Fibrin fibres were thicker in haemophiliacs compared with controls (P < 0.0001). After addition of rFVIIa 90 µg kg(-1), the diameter of fibrin fibres was dramatically decreased (P = 0.006). TEG-tPA assay showed a dose-dependent improvement of clot stability in the presence of rFVIIa. These data demonstrate a significant correlation between fibrin clot structure and its stability (P = 0.001). We also showed a correlation between thrombin generating capacity and clot resistance to fibrinolysis. Despite this overall correlation, a relatively large spreading around a general trend was observed, suggesting that the two assays bring complementary information on the haemostatic effect of rFVIIa.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Fator VIIa/uso terapêutico , Fibrina/efeitos dos fármacos , Hemofilia A/tratamento farmacológico , Hemostáticos/uso terapêutico , Trombina/biossíntese , Análise de Variância , Hemofilia A/metabolismo , Hemostasia/efeitos dos fármacos , Humanos , Microscopia Eletrônica de Varredura , Modelos Biológicos , Proteínas Recombinantes/uso terapêutico , Tromboelastografia/métodos , Ativador de Plasminogênio Tecidual/análiseRESUMO
We prospectively assessed contrast-enhanced sonography for evaluating the degree of liver fibrosis as diagnosed via biopsy in 99 patients. The transit time of microbubbles between the portal and hepatic veins was calculated from the difference between the arrival time of the microbubbles in each vein. Liver biopsy was obtained for each patient within 6 months of the contrast-enhanced sonography. Histological fibrosis was categorized into two classes: (1) no or moderate fibrosis (F0, F1, and F2 according to the METAVIR staging) or (2) severe fibrosis (F3 and F4). At a cutoff of 13 s for the transit time, the diagnosis of severe fibrosis was made with a specificity of 78.57%, a sensitivity of 78.95%, a positive predictive value of 78.33%, a negative predictive value of 83.33%, and a performance accuracy of 78.79%. Therefore, contrast-enhanced ultrasound can help with differentiation between moderate and severe fibrosis.
Assuntos
Algoritmos , Biópsia , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Cirrose Hepática/diagnóstico , Fosfolipídeos , Hexafluoreto de Enxofre , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , França , Humanos , Cirrose Hepática/classificação , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
Coarse grain modelling of macromolecules is a new approach, potentially well adapted to answer numerous issues, ranging from physics to biology. We propose here an original DNA coarse grain model specifically dedicated to protein-DNA docking, a crucial, but still largely unresolved, question in molecular biology. Using a representative set of protein-DNA complexes, we first show that our model is able to predict the interaction surface between the macromolecular partners taken in their bound form. In a second part, the impact of the DNA sequence and electrostatics, together with the DNA and protein conformations on docking is investigated. Our results strongly suggest that the overall DNA structure mainly contributes in discriminating the interaction site on cognate proteins. Direct electrostatic interactions between phosphate groups and amino acid side chains strengthen the binding. Overall, this work demonstrates that coarse grain modeling can reveal itself a precious auxiliary for a general and complete description and understanding of protein-DNA association mechanisms.
Assuntos
DNA/química , Modelos Químicos , Proteínas/química , Simulação por Computador , DNA/metabolismo , Modelos Moleculares , Conformação de Ácido Nucleico , Estrutura Secundária de Proteína , Proteínas/metabolismo , TermodinâmicaRESUMO
OBJECTIVES: Number-processing may be altered following brain injury and might affect the everyday life of patients. We developed the first ecological tool to assess number-processing disorders in brain-injured patients, the Ecological Assessment Battery for Numbers (EABN; in French, the BENQ). The aim of the present study was to standardize and validate this new tool. MATERIAL AND METHODS: Standardization included 126 healthy controls equally distributed by age, sex and sociocultural level. First, 17 patients were evaluated by the EABN; then scores for a subgroup of 10 were compared with those from a French analytical calculation test, the Évaluation Clinique des Aptitudes Numériques (ECAN). The concordance between the EABN and the ECAN was analyzed to determine construct validity. Discrimination indexes were calculated to assess the sensitivity of the subtests. RESULTS: Standardization highlighted a major effect of sociocultural level. In total, 9 of 17 patients had a pathological EABN score, with difficulties in telling time, making appointments and reading numerical data. The results of both the EABN and ECAN tests were concordant (Kendall's w=0.97). Finally, the discriminatory power was good, particularly for going to the movies, cheque-writing and following a recipe: scores were>0.4. CONCLUSION: The EABN is a new tool to assess number-processing disorders in adults. This tool has been standardized and has good psychometric properties for patients with brain injury.
Assuntos
Lesões Encefálicas Traumáticas/complicações , Discalculia/diagnóstico , Discalculia/etiologia , Testes Neuropsicológicos/normas , Acidente Vascular Cerebral/complicações , Atividades Cotidianas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Classe Social , Inquéritos e Questionários , Adulto JovemRESUMO
The prevalence of myotonic dystrophy (MyD) in the Saguenay-Lac-Saint-Jean (SLSJ) region (Quebec, Canada) is 30 to 60 times the world's prevalence. We identified 746 patients (673 still alive) distributed in 88 families. Using a population-based register of the SLSJ area and several marriage repositories from northeastern Quebec, we could trace back all patients to a couple who settled in "Nouvelle-France" in 1657. The MyD gene was then passed on over 10 to 14 generations. This genealogical reconstruction is a strong argument in favor of the genetic homogeneity of MyD in the SLSJ region.
Assuntos
Distrofia Miotônica/genética , Feminino , Humanos , Masculino , Distrofia Miotônica/epidemiologia , Linhagem , Prevalência , Quebeque/epidemiologia , Inquéritos e QuestionáriosRESUMO
We evaluated the muscular disability of 295 patients affected by the adult form of myotonic dystrophy (DM) and living in the Saguenay-Lac-Saint-Jean region (Quebec, Canada). The patients are known to have a common ancestral couple, and a homogeneous DM mutation is presumed. Using a five-point muscular disability rating scale (MDRS), we confirmed, in each age group, the wide expressivity of the muscular involvement usually observed in DM. Based on the duration of the disease and the MDRS, we also found a great variation in the rate of disease progression. There were no significant relationships between the rate of disease progression and the sex of the patient, the sex of the affected parent, or the age at onset of the disease. Furthermore, there was an absence of association between the age at onset and the sex of the patient or the sex of the affected parent. The variable severity of the muscular involvement, and the absence of relationship between age at onset and rate of disease progression, suggest a multiallelic influence at the DM locus or at other loci.
Assuntos
Músculos/fisiopatologia , Distrofia Miotônica/fisiopatologia , Adolescente , Adulto , Idoso , Envelhecimento/fisiologia , Criança , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Distrofia Miotônica/genética , Caracteres Sexuais , Fatores de TempoRESUMO
OBJECTIVE: To determine the age and causes of death as well as the predictors of survival in patients with myotonic dystrophy (DM). METHODS: In a longitudinal study, a cohort of 367 patients with definite DM was followed for 10 years. RESULTS: During the 10-year period, 75 of the 367 DM patients (20%) died. The mean age at death (53.2 years, range 24 to 81) was similar for men and women. Among these 75 patients, 32 (43%) died of a respiratory problem, 15 (20%) of cardiovascular disease, 8 (11%) of a neoplasia, and 8 (11%) died suddenly. The ratio of observed to expected deaths was significantly increased to 56.6 (95% confidence interval [CI] 38.7 to 78.0) for respiratory diseases, 4.9 (95% CI 2.7 to 7.7) for cardiovascular diseases, and 2.5 (95% CI 1.1 to 4.6) for neoplasms. The mean age at death was 44.7 years for the childhood phenotype of DM, 47.8 years for the early-adult, 55.4 years for the adult, and 63.5 years for the mild phenotype (F = 4.8, p = 0.005). The age-adjusted risk of dying was 3.9 (95% CI 1.3 to 11.0) times greater for a patient with a distal weakness and 5.6 (95% CI 2.2 to 14.4) times greater for a patient with proximal weakness as compared with a person without limb weakness. CONCLUSIONS: Life expectancy is greatly reduced in DM patients, particularly in those with early onset of the disease and proximal muscular involvement. The high mortality reflects an increase in death rates from respiratory diseases, cardiovascular diseases, neoplasms, and sudden deaths presumably from cardiac arrhythmias.
Assuntos
Distrofia Miotônica/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Coleta de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/genética , Fenótipo , Fatores de Risco , Análise de SobrevidaRESUMO
The nucleoproteic filaments of RecA polymerized on single stranded DNA are able to integrate double stranded DNA in a coaxial arrangement (with DNA stretched by a factor 1.5), to recognize homologous sequences in the duplex and to perform strand exchange between the single stranded and double stranded molecules. While experimental results favor the hypothesis of an invasion of the minor groove of the duplex by the single strand, parallel minor groove triple helices have never been isolated or even modeled, the minor groove offering little space for a third strand to interact. Based on an internal coordinate modeling study, we show here that such a structure is perfectly conceivable when the two interacting oligomers are stretched by a factor 1.5, in order to open the minor groove of the duplex. The model helix presents characteristics that coincide with known experimental data on unwinding, base pair inclination and inter-proton distances. Moreover, we show that extension and unwinding stabilize the triple helix. New patterns of triplet interaction via the minor groove are presented.
Assuntos
Modelos Estatísticos , Conformação Molecular , Recombinases Rec A/química , Recombinases Rec A/metabolismo , Simulação por Computador , Cinética , Modelos MolecularesRESUMO
A detailed molecular mechanical study has been made on the complexes of netropsin with the double stranded oligonucleotide (dA)12.(dT)12 and with the triple helix (dA)12.(dT)12.(dT)12. The complexes were built using computer graphics and energy refined using JUMNA program. In agreement with circular dichroism experiments we have shown that 3 netropsins can bind the minor grooves of the triple helix and of the double helix. The groove geometry in the duplex and in the triplex is very similar. However a detailed analysis of the energetic terms shows, in agreement with thermal denaturation studies, that the affinity of netropsin toward the double helices is larger than towards triple helices.
Assuntos
DNA/química , DNA/metabolismo , Netropsina/química , Netropsina/metabolismo , Modelos Químicos , Modelos Moleculares , Conformação de Ácido Nucleico , Ácidos Nucleicos Heteroduplexes , Oligonucleotídeos/química , Oligonucleotídeos/metabolismo , Conformação Proteica , SoftwareRESUMO
A trans-diamminedichloroplatinum(II) (trans-DDP) intrastrand adduct within the sequence d(TCTG*TG*TC).d(GACACAGA) (where G* represents a platinated guanine) is modeled on the basis of qualitative experimental data concerning global unwinding and curvature as well as information on base pairing. Modeling is performed using the internal coordinate JUMNA program, specific to nucleic acids, and modified to include the possibility of covalently bound ligands. Calibration of the energy functions representing the Pt-N7 bond with guanine is described. The platinum atom and the platinum-nitrogen bonds are parameterized for use in the Hückel Del Re method to calculate monopoles at each atom. These monopoles are consistent with the Flex force field included in Jumna. By developing an appropriate minimization protocol we are able to generate stable, distorted three-dimensional structures compatible with the experimental data and including an unusually high global unwinding. No a priori geometric assumptions are made in generating these structures.
Assuntos
Cisplatino/farmacologia , Reagentes de Ligações Cruzadas/farmacologia , Adutos de DNA , DNA/efeitos dos fármacos , Conformação de Ácido Nucleico/efeitos dos fármacos , Algoritmos , Simulação por Computador , DNA/química , Modelos Moleculares , Oligodesoxirribonucleotídeos/químicaRESUMO
In the present study, we searched for possible effects of DNA strandedness (single and double), on two types of damages, frank strand breaks (FSB, observed at neutral pH) and alkali labile sites (ALS, leading to breaks at alkaline pH) induced by irradiation with gamma-rays (60Co) or fast neutrons (p34,Be). Sequencing gel electrophoresis allowed us to follow the occurrence of these damages at each nucleotide site in single (ss-ss), double (ds-ds), and half single-half double (ss-ds and ds-ss) stranded oligonucleotides. Globally, in DNA with random sequences of bases, no differences in FSB and ALS yield between the single and the double-stranded conformations were observed. One observes, however, an increased alkaline lability at some guanine sites belonging to single-stranded region of ss-ds or ds-ss. Nevertheless, strandedness influences the radiosensitivity of some particular sequences, i.e. the 5'-AATT sequences. This region is less radiosensitive than the rest of DNA in the double helical, but not in the single-stranded conformation. The results are discussed in terms of DNA conformation.
Assuntos
Dano ao DNA , DNA de Cadeia Simples/efeitos da radiação , DNA/efeitos da radiação , Sequência de Bases , Eletroforese , Radical Hidroxila , Modelos Moleculares , Dados de Sequência MolecularRESUMO
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS; MIM SACS 270550) is frequent in northeastern Québec. Two causal mutations have been identified in the 11.7-kb single exon sacsin gene by sequence-based analyses. Mutation g.6594delT (DeltaT) was reported in 96% of the patients whereas a g.5254C --> T nonsense mutation has been observed only in 2 families. Here we report a reliable and inexpensive method to detect more than 95% of the ARSACS disease alleles from northeastern Québec using allele-specific oligonucleotide (ASO) hybridization. This procedure is being incorporated into the diagnosis of ARSACS, as well as being used for carrier detection in at-risk families from northeastern Québec.
Assuntos
Análise Mutacional de DNA , Proteínas de Choque Térmico/genética , Degenerações Espinocerebelares/genética , Alelos , DNA/sangue , Humanos , Sondas de Oligonucleotídeos , Reação em Cadeia da Polimerase , Quebeque , Degenerações Espinocerebelares/diagnósticoRESUMO
In 1971, Andermann and Andermann described an autosomal recessive syndrome found within the Charlevoix and the Saguenay populations (Quebec, Canada) characterized by agenesis of the corpus callosum (ACC) associated with motor and sensory neuropathy, mental retardation and dysmorphic features. A study of CT in 64 patients demonstrated a total ACC in 37 cases (57.8%), partial ACC in 6 cases (9.4%) and the presence of the corpus callosum in 21 cases (32.8%). The latter was confirmed by MRI in 3 cases. CT of patients without ACC revealed a high frequency of developmental or degenerative midline anomalies, particularly interhemispheric fissure enlargement and posterior fossa atrophy. The clinical presentation and the natural course of the neuropathy, the intellectual impairment and the behavioural manifestations are identical amongst individuals with or without ACC. Individuals with or without ACC are found within the same family and often within the same sibship. These observations support the hypothesis of a single genetic syndrome in which the constant manifestation is the motor and sensory neuropathy.
Assuntos
Agenesia do Corpo Caloso , Neuropatia Hereditária Motora e Sensorial/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adolescente , Adulto , Criança , Pré-Escolar , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Feminino , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Humanos , Masculino , Linhagem , RadiografiaRESUMO
BACKGROUND: Using a population-based register of the Saguenay-Lac-Saint-Jean region (Quebec, Canada), the genealogical reconstruction of 533 individuals with intracranial aneurysm (IA) showed a familial aggregation (the presence of aneurysm in two or more first- to third-degree relatives) for 159 (29.8%) of them; this proportion is much higher than reported elsewhere. OBJECTIVE: As part of an ongoing project to assess a genetic predisposition to intracranial aneurysms in the Saguenay-Lac-Saint-Jean population, the objective of the present study was to determine whether age-specific rates of reputed cerebral aneurysms were higher than in other populations. DESIGN: A retrospective study of cases of proven ruptured IAs which were hospitalized during the 1973 to 1992 period was conducted. Age-adjusted rates were computed and compared to those reported in the Helsinki population. RESULTS: We identified 412 cases of ruptured aneurysms. The age-adjusted incidence rate was 7.2/100,000/year (6.2 for men, 8.1 for women), which is similar to the incidence rates reported in other studies. Although the mean age at time of rupture was younger (46.6 years +/- 13.8) than usually reported, no increase in age-specific incidence rates was detected. CONCLUSIONS: The results of this epidemiological study neither support nor reject the hypothesis of a genetic predisposition to intracranial aneurysms in the Saguenay-Lac-Saint-Jean population.
Assuntos
Aneurisma Roto/epidemiologia , Aneurisma Intracraniano/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Canadá , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores SexuaisRESUMO
BACKGROUND: The Saguenay-Lac-Saint-Jean (SLSJ) region is a geographically isolated area (population 285,955) located in the Northeastern part of the Province of Quebec, Canada. Using a population-based register, the genealogical reconstruction of 502 individuals with ruptured intracranial aneurysm (RIA) showed a familial aggregation (the presence of aneurysm in two or more first- to third-degree relatives) for 144 (28.7%) of them; this proportion is much higher than reported elsewhere. OBJECTIVE: In order to assess the genetic predisposition to RIA in the SLSJ population, the objective of the present study is to compare familial and non-familial cases and to provide an estimate of the recurrence risk ratio for siblings. RESULTS: The age at the time of rupture, the number of intracranial aneurysms for each patient and the location of RIAs were not statistically different in the familial versus the non-familial group. Of the 3449 siblings, 20 (0.58%) had suffered a RIA. The recurrence risk ratio calculated for siblings (defined as the risk of disease among siblings divided by the estimated population prevalence) is 1.6 (CI 95% 1.0-2.4). In other respects, we observed very large kinships in the SLSJ population, with an average number of siblings of 7.2 (SD +/- 3.4), ranging from 0 to 17 individuals. With such large families and on the basis of chance alone, we expected 31.3% of the patients to have at least one first- to third-degree relative with RIA. CONCLUSION: These data show that siblings of patients with RIA in the SLSJ population have a greater risk of RIA than the general population. Nevertheless, the largest part of the familial occurrence observed in the SLSJ region can be explained by accidental aggregation, due to large kinships. We propose that, in this population, an underlying genetic predisposition must be suspected only when three or more cases of RIA are identified among first- to third-degree relatives.
Assuntos
Malformações Arteriovenosas Intracranianas/genética , Malformações Arteriovenosas Intracranianas/fisiopatologia , Adulto , Idoso , Aneurisma Roto/epidemiologia , Aneurisma Roto/genética , Aneurisma Roto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Quebeque/epidemiologia , Recidiva , Fatores de RiscoRESUMO
The genes for myotonic dystrophy (MD) and for apolipoprotein E (ApoE) belong to a chromosome 19 synthenic group of markers. A familial linkage analysis between MD and ApoE was performed using the J Ott LIPED program (IBM PC/XT, April 1984) to estimate the genetic distance between these 2 genes. Of a total of 136 individuals in 11 MD families, 81 were confirmed to be affected by the disease and 41 were asymptomatic. ApoE phenotypes were determined in 115 of these 122 individuals. No recombinant was observed out of 74 meioses which were informatives for both MD and the ApoE isoproteins. A global maximal lod score Z of 19.00 was obtained at the recombination fraction theta = 0. The upper theta value at the confidence interval corresponding to the peak lod score (Z max) - 1 was 0.03. This suggests that the loci for MD and ApoE are at a distance of 0 to 0.03 Morgan. Since ApoE and apolipoprotein C2 (ApoC2) have been shown by others to be about 40 kb apart, our data are therefore consistent with the distance estimate of 0.02 Morgan reported between MD and ApoC2. The D19S19 (LDR152) polymorphic DNA sequence is also tightly linked to MD on chromosome 19. The segregation of ApoE isoproteins and of ApoC2 and D19S19 DNA polymorphism was utilized for evaluating the probability for individuals at risk of inheriting the disease gene in MD families. Data are presented on 3 families to emphasize the usefulness of genetic markers to estimate the MD gene carrier status of asymptomatic individuals and also for those presenting a partial syndrome. The limitations of such approach are also discussed.
Assuntos
Apolipoproteínas E/genética , Ligação Genética , Heterozigoto , Distrofia Miotônica/genética , Feminino , Marcadores Genéticos , Humanos , Masculino , Linhagem , FenótipoRESUMO
Falls from heights represent an uncommon means of suicide. Regional variations are attributable to the presence of particular sites which attract suicidal individuals. The Jacques Cartier Bridge in Montreal is one such site, though less well known than North American sites such as the Golden Gate Bridge or Niagara Falls. According to Coroner's records, 54 suicides were associated with the bridge for the period 1988 to 1993. All but one of the suicides were the result of jumps from the bridge. The median age of victims was 30 years, and 46 of the victims were male. Bridge-specific verbalization of suicidal intent and prior history of medically diagnosed psychiatric disorders are frequently noted. Based on a review of the effectiveness of preventive measures, we propose limiting access to jumping by means of a fence along the bridge railing.