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Introduction: CTCF-related disorder (CRD) is a neurodevelopmental disorder (NDD) caused by monoallelic pathogenic variants in CTCF. The first CTCF variants in CRD cases were documented in 2013. To date, 76 CTCF variants have been further described in the literature. In recent years, due to the increased application of next-generation sequencing (NGS), growing numbers of CTCF variants are being identified, and multiple genotype-phenotype databases cataloging such variants are emerging. Methods: In this study, we aimed to expand the genotypic spectrum of CRD, by cataloging NDD phenotypes associated with reported CTCF variants. Here, we systematically reviewed all known CTCF variants reported in case studies and large-scale exome sequencing cohorts. We also conducted a meta-analysis using public variant data from genotype-phenotype databases to identify additional CTCF variants, which we then curated and annotated. Results: From this combined approach, we report an additional 86 CTCF variants associated with NDD phenotypes that have not yet been described in the literature. Furthermore, we describe and explain inconsistencies in the quality of reported variants, which impairs the reuse of data for research of NDDs and other pathologies. Discussion: From this integrated analysis, we provide a comprehensive and annotated catalog of all currently known CTCF mutations associated with NDD phenotypes, to aid diagnostic applications, as well as translational and basic research.
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The signs, symptoms, and bone marrow findings of the recently described virus-associated hemophagocytic syndrome was seen in a patient we treated. The manifestations of this syndrome may not be specific to viral infections and may possibly occur in other infectious processes. Autopsy findings in the present case showed it to be associated with disseminated miliary tuberculosis. Concomitant viral infection was excluded. To our knowledge, only one similar patient has previously been described.
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Eritrócitos/patologia , Histiócitos/patologia , Fagocitose , Tuberculose Miliar/patologia , Viroses/patologia , Idoso , Medula Óssea/patologia , Humanos , Masculino , SíndromeRESUMO
Cholestatic jaundice developed in four patients after the administration of prajmalium bitartrate. The clinical, histologic, ultrastructural, and immunologic findings were determined. In all patients, the clinical and morphologic features indicated idiosyncrasy. Two antibodies distributed in a granular pattern along the bile canaliculi were detected by immunofluorescence in all patients. In one patient, autoimmune markers were found in the serum, and in two instances, the migration-inhibition factor assay against the offending drug was found to be positive. The data support the concept that immunologic processes may participate in the production of the cholestatic syndrome.
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Ajmalina/análogos & derivados , Colestase/induzido quimicamente , Prajmalina/efeitos adversos , Idoso , Anticorpos/análise , Reações Antígeno-Anticorpo , Colestase/imunologia , Colestase/patologia , Proteínas do Sistema Complemento/análise , Feminino , Humanos , Imunoglobulinas/análise , Fígado/imunologia , Fígado/patologia , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Prajmalina/imunologiaRESUMO
The selection of the most appropriate therapy for hypertension remains a controversial issue. Little information is available regarding the prescribing patterns of antihypertensives in the primary care setting in Israel. The use of antihypertensives in 200 patients of the Maccabi Health Fund was, therefore, examined from April to June 1994. Sixty-four per cent of patients received monotherapy and 36% combination therapy. The most commonly prescribed medication for monotherapy were angiotensin-converting enzyme (ACE) inhibitors (33.6%), followed by beta-blockers (28.1%) and calcium channel antagonists (26.6%). Diuretics were prescribed to 7.0% of the patients. Analysis of overall drug utilization showed that diuretics were used in 21.5% of patients, beta-blockers in 39.5%, calcium channel blockers in 46% and ACE inhibitors in 40% of patients. Despite the growing evidence of the benefits of diuretics and beta-blockers, our results show a low utilization of these agents in comparison to other countries. It may be speculated that the lack of national guidelines, the absence of utilization reviews by third party providers as well as differences in patient population and climate conditions may all contribute to the current prescribing habits of physicians in the Israeli community.
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Anti-Hipertensivos/uso terapêutico , Medicina Comunitária , Hipertensão/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doença das Coronárias/complicações , Complicações do Diabetes , Diuréticos/uso terapêutico , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-IdadeRESUMO
A woman developed congestive heart failure after a normal delivery. The underlying disease was diagnosed as calcific constrictive pericarditis, and the patient underwent pericardiectomy.
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Calcinose/fisiopatologia , Pericardite Constritiva/fisiopatologia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Adulto , Feminino , Humanos , GravidezRESUMO
OBJECTIVE: To test the hypothesis that subjects who clear chylomicron remnants slowly from plasma may be at higher risk of coronary artery disease than indicated by their fasting plasma lipid concentrations. DESIGN: Case control study over three years. SETTING: An 800 bed general municipal hospital. SUBJECTS: 85 normolipidaemic patients with coronary artery disease selected prospectively and matched with 85 normolipidaemic subjects with normal coronary arteries on angiography. INTERVENTIONS: All subjects were given a vitamin A fat loading test which specifically labels intestinal lipoproteins with retinyl palmitate. MAIN OUTCOME MEASURE: Postprandial lipoprotein metabolism. RESULTS: The area below the chylomicron remnant retinyl palmitate curve was significantly increased in the coronary artery disease group as compared with the controls (mean 23.4 (SD 15.0) v 15.3 (8.9) mumol/l.h; 95% confidence interval of difference 4.37 to 11.82). CONCLUSION: Normolipidaemic patients with coronary artery disease had significantly higher concentrations of chylomicron remnants in plasma than normolipidaemic subjects with normal coronary vessels. This may explain the mechanism underlying the susceptibility to atherosclerosis of coronary artery disease patients with normal fasting lipid values. As diet and drugs can ameliorate the accumulation of postprandial lipoproteins in plasma, the concentration of chylomicron remnants should be measured in patients at high risk of coronary artery disease.
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Quilomícrons/metabolismo , Doença das Coronárias/etiologia , Lipídeos/sangue , Adulto , Idoso , Estudos de Casos e Controles , Quilomícrons/sangue , Doença das Coronárias/metabolismo , Gorduras na Dieta , Feminino , Humanos , Lipoproteínas/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Triglicerídeos/metabolismo , Vitamina AAssuntos
Aspirina/administração & dosagem , Fibrinolíticos/administração & dosagem , Hemostasia Cirúrgica , Cuidados Pré-Operatórios/métodos , Tromboembolia/prevenção & controle , Anticoagulantes/administração & dosagem , Biópsia por Agulha , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Medição de Risco , Procedimentos Cirúrgicos OperatóriosAssuntos
Uremia/etiologia , Idoso , Desidratação/complicações , Humanos , Masculino , Inanição/complicaçõesAssuntos
Anemia Hipocrômica/etiologia , Complexo Ferro-Dextran/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Anemia Hipocrômica/tratamento farmacológico , Criança , Feminino , Humanos , Infusões Parenterais , Complexo Ferro-Dextran/efeitos adversos , Masculino , Pessoa de Meia-IdadeRESUMO
Current evidence for the role of immune mechanisms in drug-induced liver disease is briefly surveyed. Cell-mediated immune reactions are frequently reported in the disease process, while humoral sensitization is poorly documented. The use and limitations of new diagnostic techniques in identifying drug hypersensitivity are discussed.
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Doença Hepática Induzida por Substâncias e Drogas/imunologia , Hipersensibilidade/complicações , Complexo Antígeno-Anticorpo , Autoanticorpos/análise , Doença Hepática Induzida por Substâncias e Drogas/patologia , Haptenos , Humanos , Hipersensibilidade/diagnóstico , Imunidade CelularRESUMO
A patient with rheumatoid arthritis developed nephrotic syndrome with reversible renal failure following gold therapy. Histological examination of renal biopsy disclosed the typical picture of membranous nephropathy. After prolonged treatment with steroids and cyclophosphamide, complete recovery was achieved. The likely mechanism involved and the clinical implications are discussed.
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Injúria Renal Aguda/induzido quimicamente , Ouro/efeitos adversos , Síndrome Nefrótica/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Idoso , Artrite Reumatoide/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Ciclofosfamida/uso terapêutico , Feminino , Ouro/uso terapêutico , Humanos , Síndrome Nefrótica/tratamento farmacológico , Prednisona/uso terapêuticoRESUMO
An elderly patient presenting with severe tetany secondary to hypocalcaemia causing bilateral fractures of the femoral necks, was proved to have coeliac disease. Severe muscle pains, an organic mental syndrome and personality changes are rare complications of coeliac disease and are reversible with treatment.