RESUMO
Antibodies are an essential component of the adaptative immune response and hold long-term memory of the immunological experiences throughout life. Antibody defects represent approximately half of the well-known primary immunodeficiencies requiring immunoglobulin replacement therapy. In this article, the authors review the current indications and therapeutic protocols in the Latin American environment. Immunoglobulin replacement therapy has been a safe procedure that induces dramatic positive changes in the clinical outcome of patients who carry antibody defects
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Assuntos
Humanos , Síndromes de Imunodeficiência/tratamento farmacológico , Imunoglobulinas/uso terapêutico , Síndromes de Imunodeficiência/diagnóstico , América Latina , Injeções Subcutâneas , Padrões de Prática MédicaRESUMO
Antibodies are an essential component of the adaptative immune response and hold long-term memory of the immunological experiences throughout life. Antibody defects represent approximately half of the well-known primary immunodeficiencies requiring immunoglobulin replacement therapy. In this article, the authors review the current indications and therapeutic protocols in the Latin American environment. Immunoglobulin replacement therapy has been a safe procedure that induces dramatic positive changes in the clinical outcome of patients who carry antibody defects.
Assuntos
Imunização Passiva/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/terapia , Guias como Assunto , Humanos , Síndromes de Imunodeficiência/imunologia , América LatinaRESUMO
Primary immunodeficiency diseases (PIDD) are associated with significant morbidity and mortality and result in a significant public health burden. This is in part due to the lack of appropriate diagnosis and treatment of these patients. It is critical that governments become aware of this problem and provide necessary resources to reduce this impact on health care systems. Leading physicians in their respective countries must be supported by their own governments in order to implement tools and provide education and thus improve the diagnosis and treatment of PIDD. The Latin American Society of Primary Immunodeficiencies (LASID) has initiated a large number of activities aimed at achieving these goals, including the establishment of a PIDD registry, development of educational programmes and guidelines, and the introduction of a PIDD fellowship programme. These initiatives are positively impacting the identification and appropriate treatment of patients with PIDD in Latin America. Nevertheless, much remains to be done to ensure that every person with PIDD receives proper therapy(AU)
Assuntos
Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , América Latina , Infecções/epidemiologia , Fatores de Risco , Recidiva , Imunoglobulinas/análise , Predisposição Genética para DoençaRESUMO
Primary immunodeficiency diseases (PIDD) are associated with significant morbidity and mortality and result in a significant public health burden. This is in part due to the lack of appropriate diagnosis and treatment of these patients. It is critical that governments become aware of this problem and provide necessary resources to reduce this impact on health care systems. Leading physicians in their respective countries must be supported by their own governments in order to implement tools and provide education and thus improve the diagnosis and treatment of PIDD. The Latin American Society of Primary Immunodeficiencies (LASID) has initiated a large number of activities aimed at achieving these goals, including the establishment of a PIDD registry, development of educational programmes and guidelines, and the introduction of a PIDD fellowship programme. These initiatives are positively impacting the identification and appropriate treatment of patients with PIDD in Latin America. Nevertheless, much remains to be done to ensure that every person with PIDD receives proper therapy.
Assuntos
Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Congressos como Assunto , Humanos , América Latina , Sociedades MédicasRESUMO
Early diagnosis and appropriate therapy are essential for the best prognosis and quality of life in patients with primary immunodeficiency diseases (PIDDs). Experts from several Latin American countries have been meeting on a regular basis as part of an on going effort to improve the diagnosis and treatment of PIDD in this region. Three programmes are in development that will expand education and training and improve access to testing facilities through out Latin America. These programmes are: an educational out reach programme (The L-Project); an immunology fellowship programme; and the establishment of a laboratory network to expand access to testing facilities. This report provides the status of these programmes based on the most recent discussions and describes the next steps toward full implementation of these programmes (AU)
Assuntos
Humanos , Masculino , Feminino , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/genética , Consenso , Projetos , Educação/tendências , América Latina , Isotipos de Imunoglobulinas/sangue , Imunidade Celular , Prontuários Médicos , Proteínas do Sistema ComplementoRESUMO
Early diagnosis and appropriate therapy are essential for the best prognosis and quality of life in patients with primary immunodeficiency diseases (PIDDs). Experts from several Latin American countries have been meeting on a regular basis as part of an ongoing effort to improve the diagnosis and treatment of PIDD in this region. Three programmes are in development that will expand education and training and improve access to testing facilities throughout Latin America. These programmes are: an educational outreach programme (The L-Project); an immunology fellowship programme; and the establishment of a laboratory network to expand access to testing facilities. This report provides the status of these programmes based on the most recent discussions and describes the next steps toward full implementation of these programmes.
Assuntos
Comitês Consultivos , Hispânico ou Latino , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia , Sistema de Registros , Alergia e Imunologia/educação , Bolsas de Estudo , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/epidemiologia , Testes Imunológicos/normas , América Latina , Educação de Pacientes como Assunto , Guias de Prática Clínica como Assunto , Estados UnidosRESUMO
INTRODUCTION: Bacterial viruses play crucial roles in the pathogenesis of many systemic diseases. They are known to inhabit the oral cavity, both as free virions and as prophages in lysogenic bacterial strains; however, there has been no report of bacteriophages in endodontic infections. In this study, we sought to detect, isolate, and describe temperate bacteriophages harbored by Enterococcus faecalis strains isolated from endodontic infections. METHODS: Ten E. faecalis strains were isolated from root canals of teeth undergoing retreatment following unsuccessful endodontic therapy. Mitomycin C was used to induce any prophages present in the bacterial isolates. The induced phages were purified and examined using electron microscopy. The DNA extracted from one of the phage isolates was subjected to restriction endonuclease digestion and agarose electrophoresis analysis. RESULTS: Lysogeny was demonstrated in 4 of the 10 E. faecalis strains. Three of the lysogenic strains yielded phages exhibiting a Siphoviridae morphology, with long, non-contractile tails 130 nm in length, and spherical/icosahedral heads 41 nm in diameter. The virus induced from the fourth lysogenic E. faecalis strain had a contractile tail characteristic of Myoviridae. Restriction endonuclease analysis of NsiI and NdeI DNA fragments from one of the Siphoviridae phage isolates (phage phiEf11) indicated a genome size of approximately 41 kbp. CONCLUSION: This is the first report of lysogenic bacteria and their inducible viruses in infected root canals.
Assuntos
Cavidade Pulpar/virologia , Enterococcus faecalis/virologia , Periodontite Periapical/virologia , Siphoviridae/isolamento & purificação , Dente não Vital/virologia , Bacteriófagos/fisiologia , DNA Viral/análise , Falha de Restauração Dentária , Enterococcus faecalis/efeitos dos fármacos , Humanos , Lisogenia/efeitos dos fármacos , Mitomicina/farmacologia , Myoviridae/isolamento & purificação , Retratamento , Virologia/métodos , Ativação ViralRESUMO
We set out to identify molecular mechanisms underlying the onset of necrotic Ca(2+) overload, triggered in two epithelial cell lines by oxidative stress or metabolic depletion. As reported earlier, the overload was inhibited by extracellular Ca(2+) chelation and the cation channel blocker gadolinium. However, the surface permeability to Ca(2+) was reduced by 60%, thus discarding a role for Ca(2+) channel/carrier activation. Instead, we registered a collapse of the plasma membrane Ca(2+) ATPase (PMCA). Remarkably, inhibition of the Na(+)/K(+) ATPase rescued the PMCA and reverted the Ca(2+) rise. Thermodynamic considerations suggest that the Ca(2+) overload develops when the Na(+)/K(+) ATPase, by virtue of the Na(+) overload, clamps the ATP phosphorylation potential below the minimum required by the PMCA. In addition to providing the mechanism for the onset of Ca(2+) overload, the crosstalk between cation pumps offers a novel explanation for the role of Na(+) in cell death.
Assuntos
Trifosfato de Adenosina/metabolismo , Cálcio/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Sódio/metabolismo , Animais , ATPases Transportadoras de Cálcio/metabolismo , Linhagem Celular , Membrana Celular/metabolismo , Cães , Células HeLa , Humanos , Modelos Biológicos , Necrose , Estresse Oxidativo , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Human malignant infantile osteopetrosis (arOP; MIM 259700) is a genetically heterogeneous autosomal recessive disorder of bone metabolism, which, if untreated, has a fatal outcome. Our group, as well as others, have recently identified mutations in the ATP6i (TCIRG1) gene, encoding the a3 subunit of the vacuolar proton pump, which mediates the acidification of the bone/osteoclast interface, are responsible for a subset of this condition. By sequencing the ATP6i gene in arOP patients from 44 unrelated families with a worldwide distribution we have now established that ATP6i mutations are responsible for approximately 50% of patients affected by this disease. The vast majority of these mutations (40 out of 42 alleles, including seven deletions, two insertions, 10 nonsense substitutions and 21 mutations in splice sites) are predicted to cause severe abnormalities in the protein product and are likely to represent null alleles. In addition, we have also analysed nine unrelated arOP patients from Costa Rica, where this disease is apparently much more frequent than elsewhere. All nine Costa Rican patients bore either or both of two missense mutations (G405R and R444L) in amino acid residues which are evolutionarily conserved from yeast to humans. The identification of ATP6i gene mutations in two families allowed us for the first time to perform prenatal diagnosis: both fetuses were predicted not to be affected and two healthy babies were born. This study contributes to the determination of genetic heterogeneity of arOP and allows further delineation of the other genetic defects causing this severe condition.
Assuntos
Mutação , Osteopetrose/genética , ATPases Vacuolares Próton-Translocadoras/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Canais de Cloreto/genética , Cromossomos Humanos Par 11 , Análise Mutacional de DNA , Éxons , Feminino , Genes Recessivos , Haplótipos , Humanos , Lactente , Recém-Nascido , Íntrons , Masculino , Dados de Sequência Molecular , Osteopetrose/enzimologia , Reação em Cadeia da Polimerase , Homologia de Sequência de Aminoácidos , Vacúolos/enzimologia , Vacúolos/genéticaRESUMO
The effect of osmotic stress on sugar transport was investigated in Clone 9 epithelial cells, which express the glucose uniporter GLUT1, and in 3T3-L1 adipocytes, which express both GLUT1 and GLUT4. An acute hyperosmotic shock increased the uptake of sugars in both cell types. In Clone 9 cells, this was followed by a regulatory volume increase (RVI) response. Stimulation of transport was rapid and reversible, with half-lives (t 1/2) for stimulation of 2-deoxy-D-glucose uptake of 5.6 +/- 0.9 (n=6) and 22.7 +/- 1.5 (n=4) min for Clone 9 cells and adipocytes respectively. The effect was dose dependent, reaching a maximum at 1.1 osM of 2.9 +/- 0.1-fold (n=3) for Clone 9 cells and 8.2 +/- 0.8-fold (n=3) for adipocytes. In the latter, this stimulation correlated with translocation of the glucose transporter isoform GLUT4 to the cell surface and was not significantly different from that elicited by 160 nM insulin (7.6 +/- 1.2-fold, n=3). The effect of osmotic shock was not, however, influenced by inhibitors of either phosphoinositide 3-kinase (PI 3-kinase) (wortmannin, 250 nM) or of p38 mitogen-activated protein kinase (p38 MAP kinase) (SB203580, 20 microM), which reportedly prevent GLUT4 translocation and/or activation by insulin respectively. These inhibitors also had no effect on the stimulation of transport by osmotic shock in Clone 9 cells. However, in contrast to adipocytes, the effect of osmotic shock on glucose transport in Clone 9 cells reflected primarily a change in the intrinsic activity of cell surface transporters and there was only a minor change in their subcellular distribution as assessed by cell immunostaining or no change as assessed by surface biotinylation. These results indicate that the response of cells to osmotic shock can involve changes both in transporter activity and location. The signal transduction pathways involved include neither PI 3-kinase nor the classical, osmotically-activated component, p38 MAP kinase.
Assuntos
Adipócitos/metabolismo , Células Epiteliais/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteínas Musculares , Pressão Osmótica , Células 3T3 , Adipócitos/citologia , Animais , Antimetabólitos/farmacocinética , Transporte Biológico/fisiologia , Membrana Celular/metabolismo , Desoxiglucose/farmacocinética , Células Epiteliais/citologia , Glucose/metabolismo , Transportador de Glucose Tipo 1 , Transportador de Glucose Tipo 4 , Mamíferos , Camundongos , Ratos , Solução Salina Hipertônica/farmacocinética , Sorbitol/farmacocinética , Sacarose/farmacocinéticaRESUMO
We evaluated children (15-months old and older) with recurrent upper respiratory tract infections and normal levels of immunoglobulins in serum for specific polysaccharide immunodeficiency using an enzyme-linked immunosorbent assay method. Results showed that of 12 patients vaccinated with Act-HIB vaccine, one did not develop specific antibodies to Haemophilus influenzae type b, demonstrating that such immunodeficiency is present in Costa Rican children.
Assuntos
Anticorpos Antibacterianos/biossíntese , Infecções por Haemophilus/imunologia , Polissacarídeos Bacterianos/imunologia , Infecções Respiratórias/imunologia , Pré-Escolar , Costa Rica , Ensaio de Imunoadsorção Enzimática , Feminino , Vacinas Anti-Haemophilus/imunologia , Haemophilus influenzae tipo b/imunologia , Humanos , Lactente , Masculino , Recidiva , Infecções Respiratórias/microbiologiaRESUMO
The aim of this work was to investigate the role of cytosolic free calcium ([Ca(2+)]c) in the stimulation of GLUT1 by metabolic stress and insulin. Chelation of [Ca(2+)]c with bapta, introduced in rat liver epithelial Clone 9 cells in the acetoxymethyl (AM) form, decreased their basal rate of 2-deoxyglucose uptake in a dose-dependent fashion. Maximal inhibition at 75 microM bapta was by 38 +/- 8% (n = 8). The effect was partially reversed by ionomycin. Basal sugar uptake was also decreased by lowering extracellular [Ca(2+)] in ionomycin-permeabilized cells. Increasing [Ca(2+)]c over its resting level of 168 +/- 32 (n = 27) had no affect on sugar uptake. Chelation of [Ca(2+)]c did not change the abundance of surface GLUT1 and had no significant effect on the affinity of GLUT1 for sugars. In addition, calcium chelation abolished the activation of GLUT1 by azide, arsenate, 2,4-dinitrophenol and insulin. However, [Ca(2+)]c did not increase in the presence of azide. We conclude that [Ca(2+)]c, near or below its resting level, modulates GLUT1 activity over a considerable range and plays a permissive role in the activation of the carrier by metabolic stress and insulin.
Assuntos
Cálcio/metabolismo , Citosol/metabolismo , Insulina/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , 2,4-Dinitrofenol/farmacologia , Animais , Arseniatos/farmacologia , Azidas/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Cultivadas , Quelantes/farmacologia , Citosol/efeitos dos fármacos , Desoxiglucose/farmacocinética , Relação Dose-Resposta a Droga , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Transportador de Glucose Tipo 1 , Insulina/farmacologia , Ionomicina/farmacologia , Ionóforos/farmacologia , RatosRESUMO
In the genetic disorder ataxia telangiectasia (AT), humoral (B) and cellular (T) immunological abnormalities are frequently observed. As a consequence, AT patients are predisposed to life-threatening sinopulmonary infections. The pathogenic mechanisms remain unknown, but a role for ATM in signal transduction from membrane receptors has been proposed. We have explored the effects of a defective ATMgene on isolated human T-lineage cells from 13 AT patients with proven T cell dysfunction by transforming their CD4(+) and CD8(+) T lymphocytes with Herpesvirus saimiri, and analyzing their signaling behavior as compared to normal controls. Several functional parameters were assayed in response to both membrane (anti-CD3 and IL-2) and transmembrane (phorbol myristate acetate plus the calcium ionophore ionomycin) stimuli: (i) calcium mobilization, (ii) induction of activation molecules (CD25, CD40 ligand, CD69 and CD71), (iii) cytokine synthesis (IL-2 and tumor necrosis factor-alpha) and (iv) proliferation. All these early and late activation events were found to be normal in the transformed ATM-/-T cells, indicating that ATM is not necessary for their induction. As expected, ATM-/- transformed T cells showed an increased radiosensitivity by both radioresistant DNA synthesis and cell survival assays. In contrast to an earlier report testing transformed B lymphocytes, our results indicate that transformed mature peripheral T lymphocytes from AT patients do not have intrinsic immune function defects. Rather, the described T-lineage signaling impairments observed in patients may be secondary in vivo to extrinsic ATM-dependent suppressive factors and/or to a developmental defect. These transformed T cells may help to understand the distinct biological role of ATM in different cell types and to develop rational therapies for the immunological dysfunction of AT patients.
Assuntos
Ataxia Telangiectasia/imunologia , Linfócitos T CD4-Positivos/fisiologia , Linfócitos T CD8-Positivos/fisiologia , Transformação Celular Viral , Herpesvirus Saimiriíneo 2/fisiologia , Ativação Linfocitária , Proteínas Serina-Treonina Quinases/fisiologia , Transdução de Sinais , Adolescente , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular , Criança , Proteínas de Ligação a DNA , Humanos , Tolerância a Radiação , Proteínas Supressoras de TumorRESUMO
Osteopetrosis is a heterogeneous group of diseases characterized by lack of osteoclast function. Osteopetrosis is found spontaneously in most mammalian species and many transgenic animals have been created, but so far no animal model has been found that genetically corresponds to human malignant autosomal recessive osteopetrosis. The only curative treatment for malignant osteopetrosis is bone marrow transplantation. A review of the literature and preliminary data from IBMTR shows that infants transplanted with marrow from an HLA-identical sibling or unrelated volunteer donor have an actuarian five-year survival with a functioning graft of 50-70%, while those transplanted with a T-cell-depleted mismatched marrow have a very poor survival of only about 10%.
Assuntos
Transplante de Medula Óssea , Osteopetrose/etiologia , Osteopetrose/terapia , Animais , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Sobrevivência de Enxerto , Humanos , Camundongos , Osteoclastos/metabolismo , Prognóstico , Ratos , Índice de Gravidade de Doença , Transplante Autólogo , Resultado do TratamentoRESUMO
We describe a 15-month-old eutrophic immunocompetent male who presented with fever, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. Leishmania amastigotes were identified in spleen and bone marrow specimens. In addition, tissue culture, animal inoculation, and isoenzyme analysis identified the parasite as Leishmania donovani infantum or Leishmania donovani chagasi. The infant was successfully treated with an antimonial drug. These findings represent the first case of visceral leishmaniasis reported in Costa Rica.
Assuntos
Antígenos de Protozoários/análise , Leishmania donovani/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Animais , Antiprotozoários/uso terapêutico , Costa Rica , Humanos , Lactente , Leishmaniose Visceral/tratamento farmacológico , Masculino , Resultado do TratamentoRESUMO
OBJECTIVE: To find the incidence and prevalence of juvenile chronic arthritis (JCA) in the urban area of San José, Costa Rica. METHODS: During the year preceding our 2 year prospective, population based study, we conducted an educational program on JCA. The physicians caring for children < 16 years of age from all centers in the study area followed the program. They were asked to refer all cases of possible JCA according to EULAR criteria. The children were all evaluated at the National Children's Hospital. RESULTS: Of 189 children referred, 48 fulfilled EULAR criteria for JCA. The 2 year incidence rate for JCA was 13.7 per 100,000 children < 16 years old. This corresponds to an annual incidence per 100,000 children of 6.8 (95% CI 4.1-9.6). The incidence rate for pauciarticular onset JCA was 3.9 per 100,000. At the prevalence date, 122 cases of JCA were recorded, corresponding to a prevalence of 34.9 per 100,000 children < 16 years. When patients in remission were excluded, the prevalence was 31.4 per 100,000 (95% CI 25.5-37.2). The pauciarticular onset form was the most common, 71% of all prevalence cases. The highest incidence and prevalence were noted for pauciarticular girls with late onset JCA. No incidence peak was found in preschool age. The girl-to-boy ratio was 1.5/1. Antinuclear antibodies (ANA) were positive in only 7 cases (6.3%). IgM rheumatoid factor was found in 13 children (10.6%). Chronic iritis was observed in 4 cases, all of them ANA negative and older than 7 years of age at onset of arthritis. CONCLUSION: The incidence and prevalence observed were lower than those reported in other population based studies, but within the confidence intervals of their data. The incidence rate for pauciarticular JCA was significantly lower than that reported in other comparable studies. ANA positive pauciarticular preschool girls and associated uveitis were rarely encountered.
Assuntos
Artrite Juvenil/epidemiologia , Adolescente , Idade de Início , Anticorpos Antinucleares/imunologia , Artrite Juvenil/complicações , Artrite Juvenil/imunologia , Criança , Pré-Escolar , Costa Rica/epidemiologia , Países em Desenvolvimento , Feminino , Humanos , Incidência , Lactente , Estudos Longitudinais , Masculino , Projetos Piloto , Prevalência , Estudos Prospectivos , Encaminhamento e Consulta , Distribuição por Sexo , População Urbana , Uveíte/etiologiaRESUMO
Ataxia telangiectasia (A-T) is an autosomal recessive disorder with a broad range of clinical manifestations and a frequency of 1:40,000-100,000 live births. Epidemiological studies have suggested that A-T heterozygotes are at an elevated risk of breast cancer. ATM mutations occur worldwide over the entire ATM gene, making it difficult to identify heterozygotes in large populations. However, some founder-effect mutations are specific for certain populations. Here, we present four mutations in Costa Rican A-T patients that accounted for 86-93% of 41 patients studied in two batches. We have developed assays for rapid detection of these four mutations which can be used diagnostically. They will also enable the Costa Rican population to be used as a model for analyzing the role of ATM heterozygosity in cancer development and other disorders.
Assuntos
Ataxia Telangiectasia/genética , Efeito Fundador , Triagem de Portadores Genéticos , Testes Genéticos/métodos , Haplótipos , Ataxia Telangiectasia/diagnóstico , Códon de Terminação , Costa Rica , Éxons/genética , Genes Recessivos , Humanos , Mutação Puntual , Mapeamento por Restrição , Deleção de SequênciaRESUMO
To facilitate the evaluation of ATM heterozygotes for susceptibility to other diseases, such as breast cancer, we have attempted to define the most common mutations and their frequencies in ataxia-telangiectasia (A-T) homozygotes from 10 ethnic populations. Both genomic mutations and their effects on cDNA were characterized. Protein-truncation testing of the entire ATM cDNA detected 92 (66%) truncating mutations in 140 mutant alleles screened. The haplotyping of patients with identical mutations indicates that almost all of these represent common ancestry and that very few spontaneously recurring ATM mutations exist. Assays requiring minimal amounts of genomic DNA were designed to allow rapid screening for common ethnic mutations. These rapid assays detected mutations in 76% of Costa Rican patients (3), 50% of Norwegian patients (1), 25% of Polish patients (4), and 14% of Italian patients (1), as well as in patients of Amish/Mennonite and Irish English backgrounds. Additional mutations were observed in Japanese, Utah Mormon, and African American patients. These assays should facilitate screening for A-T heterozygotes in the populations studied.
Assuntos
Ataxia Telangiectasia/etnologia , Ataxia Telangiectasia/genética , Mutação , Proteínas Serina-Treonina Quinases , Proteínas/genética , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular , Análise Mutacional de DNA , DNA Complementar/análise , Proteínas de Ligação a DNA , Etnicidade/genética , Feminino , Haplótipos , Heterozigoto , Humanos , Masculino , RNA/análise , Grupos Raciais/genética , Proteínas Supressoras de TumorRESUMO
OBJECTIVE: To validate a Spanish language version of the Childhood Health Assessment Questionnaire (CHAQ) for use in Costa Rica and to evaluate the feasibility, reliability, and cross cultural equivalency of this version. METHODS: The original questionnaire, translated without modification into Spanish, was administered to 12 children, all above 10 years of age, with the diagnosis of juvenile chronic arthritis (JCA) and to their parents. There were several problems in comprehension, and self-administration with this version was not possible. For this reason a teacher and a psychologist were consulted to create a modified Costa Rican version. We administered this 2nd version to 46 children with JCA and 62 of their parents. RESULTS: The modified Costa Rican HAQ (CR-CHAQ) was self-administered by 93.5% of the patients and 84% of the parents. The median time to complete the questionnaire was 12 min for the children, 10 min for the parents. The main difficulty in comprehension was the pain score for both groups. Test-retest (Spearman R = 0.73) and interobserver (Spearman R = 0.70) reliability were good. Validity of the instrument was confirmed by the high correlation between the disability and discomfort scores and conventional clinical variables. There was satisfactory correlation between the disability score and conventional clinical variables. Discriminant validity was confirmed by the capacity of the CR-CHAQ to evaluate patients as being in different categories of disease activity. CONCLUSION: After modifications, the CR-CHAQ achieved cross cultural equivalency.
Assuntos
Artrite Juvenil/diagnóstico , Nível de Saúde , Idioma , Inquéritos e Questionários , Adolescente , Criança , Costa Rica , Avaliação da Deficiência , Estudos de Viabilidade , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Dor , Reprodutibilidade dos TestesRESUMO
In an effort to localize a gene for ataxia-telangiectasia (A-T), we have genotyped 27 affected Costa Rican families, with 13 markers, in the chromosome 11q22-23 region. Significant linkage disequilibrium was detected for 9/13 markers between D11S1816 and D11S1391. Recombination events observed in these pedigrees places A-T between D11S1819 and D11S1960. One ancestral haplotype is common to 24/54 affected chromosomes and roughly two-thirds of the families. Inferred (ancestral) recombination events involving this common haplotype in earlier generations suggest that A-T is distal to D11S384 and proximal to D11S1960. Several other common haplotypes were identified, consistent with multiple mutations in a single gene. When considered together with all other evidence, this study further sublocalizes the major A-T locus to approximately 200 kb, between markers S384 and S535.