RESUMO
Pipelines have been widely used for the transportation of chemical products, mainly those related to the petroleum industry. Damage in such pipelines can produce leakage with unpredictable consequences to the environment. There are different structural health monitoring (SHM) systems such as Lamb wave, comparative vacuum, acoustic emission, etc. for monitoring such structures. However, those based on piezoelectric sensors and electromechanical impedance technique (EMI) measurements are simple and efficient, and have been applied in a wide range of structures, including pipes. A disadvantage of such technique is that temperature changes can lead to false diagnoses. To overcome this disadvantage, temperature variation compensation techniques are normally incorporated. Therefore, this work has developed a complete study applied to damage detection in pipelines, including an innovative technique for compensating the temperature effect in EMI-based SHM and the modeling of piezoceramics bonded to pipeline structures using finite elements. Experimental results were used to validate the model. Moreover, the compensation method was tested in two steel pipes-healthy and damaged-compensating the temperature effect ranging from -40 °C to +80 °C, with analysis on the frequency range from 5 kHz to 120 kHz. The simulated and experimental results showed that the studies effectively contribute to the SHM area, mainly to EMI-based techniques.
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OBJECTIVE: We conducted a 12-week double-blind study of stabilization pharmacotherapy in patients with remitted psychotic depression (PD). METHODS: Seventy-one persons aged 18 years or older who had achieved remission of PD when randomized to either olanzapine plus sertraline or olanzapine plus placebo were continued on the double-blind treatment associated with remission. Symptoms of depression and psychosis, and weight, were measured once every 4 weeks. Cholesterol, triglycerides, and glucose were measured at stabilization phase baseline and Week 12/termination. RESULTS: The effect of treatment did not significantly change with time for depression, weight, or metabolic measures in the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7) experienced a relapse of major depression, psychosis, or both. Treatment groups did not differ in the frequency of relapse. In the entire study group, the adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83, 2.48) and the adjusted estimate for change in total cholesterol was a decrease of 14.8 mg/dL (95% CI: 3.5, 26.1) during the 12-week stabilization phase; the remaining metabolic measures did not significantly change. CONCLUSION: Continuation of acute treatment was associated with stability of remission.
Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Olanzapina/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Sertralina/uso terapêutico , Adulto , Idoso , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Glicemia/análise , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Transtorno Depressivo Maior/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina/administração & dosagem , Placebos/administração & dosagem , Indução de Remissão/métodos , Sertralina/administração & dosagem , Triglicerídeos/sangueRESUMO
Microtubule dynamics play a crucial role in neuronal development and function, and several neurodevelopmental disorders have been linked to mutations in genes encoding tubulins and functionally related proteins. Most recently, variants in the tubulin cofactor D (TBCD) gene, which encodes one of the five co-chaperones required for assembly and disassembly of α/ß-tubulin heterodimer, were reported to underlie a recessive neurodevelopmental/neurodegenerative disorder. We report on five patients from three unrelated families, who presented with microcephaly, intellectual disability, intractable seizures, optic nerve pallor/atrophy, and cortical atrophy with delayed myelination and thinned corpus callosum on brain imaging. Exome sequencing allowed the identification of biallelic variants in TBCD segregating with the disease in the three families. TBCD protein level was significantly reduced in cultured fibroblasts from one patient, supporting defective TBCD function as the event underlying the disorder. Such reduced expression was associated with accelerated microtubule re-polymerization. Morpholino-mediated TBCD knockdown in zebrafish recapitulated several key pathological features of the human disease, and TBCD overexpression in the same model confirmed previous studies documenting an obligate dependency on proper TBCD levels during development. Our findings confirm the link between inactivating TBCD variants and this newly described chaperone-associated tubulinopathy, and provide insights into the phenotype of this disorder.
Assuntos
Deficiências do Desenvolvimento/genética , Microcefalia/genética , Proteínas Associadas aos Microtúbulos/química , Proteínas Associadas aos Microtúbulos/genética , Convulsões/genética , Animais , Pré-Escolar , Embrião não Mamífero , Epilepsia/genética , Feminino , Humanos , Lactente , Deficiência Intelectual/genética , Imageamento por Ressonância Magnética , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/genética , Microtúbulos/patologia , Convulsões/diagnóstico por imagem , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
OBJECTIVE: Unipolar psychotic depression (PD) is a severe and debilitating syndrome, which requires intensive monitoring. The objective of this study was to provide an overview of the rating scales used to assess illness severity in PD. METHOD: Selective review of publications reporting results on non-self-rated, symptom-based rating scales utilized to measure symptom severity in PD. The clinical and psychometric validity of the identified rating scales was reviewed. RESULTS: A total of 14 rating scales meeting the predefined criteria were included in the review. These scales grouped into the following categories: (i) rating scales predominantly covering depressive symptoms, (ii) rating scales predominantly covering psychotic symptoms, (iii) rating scales covering delusions, and (iv) rating scales covering PD. For the vast majority of the scales, the clinical and psychometric validity had not been tested empirically. The only exception from this general tendency was the 11-item Psychotic Depression Assessment Scale (PDAS), which was developed specifically to assess the severity of PD. CONCLUSION: In PD, the PDAS represents the only empirically derived rating scale for the measurement of overall severity of illness. The PDAS should be considered in future studies of PD and in clinical practice.
Assuntos
Transtornos Bipolares e Relacionados/diagnóstico , Transtorno Depressivo/diagnóstico , Escalas de Graduação Psiquiátrica , Psicometria/instrumentação , Transtornos Psicóticos/diagnóstico , Índice de Gravidade de Doença , HumanosRESUMO
OBJECTIVE: Psychotic depression (PD) is a highly debilitating condition, which needs intensive monitoring. However, there is no established rating scale for evaluating the severity of PD. The aim of this analysis was to assess the psychometric properties of established depression rating scales and a number of new composite rating scales, covering both depressive and psychotic symptoms, in relation to PD. METHOD: The psychometric properties of the rating scales were evaluated based on data from the Study of Pharmacotherapy of Psychotic Depression. RESULTS: A rating scale consisting of the 6-item Hamilton melancholia subscale (HAM-D6 ) plus five items from the Brief Psychiatric Rating Scale (BPRS), named the HAMD-BPRS11 , displayed clinical validity (Spearman's correlation coefficient between HAMD-BPRS11 and Clinical Global Impression - Severity (CGI-S) scores = 0.79-0.84), responsiveness (Spearman's correlation coefficient between change in HAMD-BPRS11 and Clinical Global Impression - Improvement (CGI-I) scores = -0.74--0.78) and unidimensionality (Loevinger's coefficient of homogeneity = 0.41) in the evaluation of PD. The HAM-D6 fulfilled the same criteria, whereas the full 17-item Hamilton Depression Scale failed to meet criteria for unidimensionality. CONCLUSION: Our results suggest that the HAMD-BPRS11 is a more valid measure than pure depression scales for evaluating the severity of PD.
Assuntos
Transtornos Psicóticos Afetivos/diagnóstico , Escalas de Graduação Psiquiátrica/normas , Adulto , Transtornos Psicóticos Afetivos/fisiopatologia , Escalas de Graduação Psiquiátrica Breve , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Psicometria/instrumentação , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
Mucolipidosis type IV (MLIV) is an autosomal recessive, neurodegenerative, lysosomal storage disorder characterized by psychomotor retardation and ophthalmological abnormalities including corneal opacities, retinal degeneration and strabismus. Most patients reach a maximal developmental level of 12?15 months. The disease was classified as a mucolipidosis following observations by electron microscopy indicating the lysosomal storage of lipids together with water-soluble, granulated substances. Over 80% of the MLIV patients diagnosed are Ashkenazi Jews, including severely affected and mildly affected patients. The gene causing MLIV was previously mapped to human chromosome 19p13.2-13.3 in a region of approximately 1 cM (ref. 7). Haplotype analysis in the MLIV gene region of over 70 MLIV Ashkenazi chromosomes indicated the existence of two founder chromosomes among 95% of the Ashkenazi MLIV families: a major haplotype in 72% and a minor haplotype in 23% of the MLIV chromosomes (ref. 7, and G.B., unpublished data). The remaining 5% are distinct haplotypes found only in single patients. The basic metabolic defect causing the lysosomal storage in MLIV has not yet been identified. Thus, positional cloning was an alternative to identify the MLIV gene. We report here the identification of a new gene in this human chromosomal region in which MLIV-specific mutations were identified.
Assuntos
Proteínas de Membrana/genética , Mucolipidoses/genética , Mutação , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Mapeamento Cromossômico , Cromossomos Humanos Par 19 , Clonagem Molecular , Ilhas de CpG , Análise Mutacional de DNA , Éxons , Etiquetas de Sequências Expressas , Feminino , Deleção de Genes , Genes Recessivos , Marcadores Genéticos , Haplótipos , Humanos , Masculino , Modelos Genéticos , Dados de Sequência Molecular , Linhagem , Polimorfismo Genético , Splicing de RNA , RNA Mensageiro/metabolismo , Mapeamento por Restrição , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Canais de Cátion TRPM , Canais de Potencial de Receptor TransitórioRESUMO
Bardet-Biedl syndrome (BBS, MIM 209900) is a heterogeneous autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. The disorder is also associated with diabetes mellitus, hypertension, and congenital heart disease. Six distinct BBS loci map to 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6). Although BBS is rare in the general population (<1/100,000), there is considerable interest in identifying the genes causing BBS because components of the phenotype, such as obesity and diabetes, are common. We and others have demonstrated that BBS6 is caused by mutations in the gene MKKS (refs. 12,13), mutation of which also causes McKusick-Kaufman syndrome (hydrometrocolpos, post-axial polydactyly, and congenital heart defects). MKKS has sequence homology to the alpha subunit of a prokaryotic chaperonin in the thermosome Thermoplasma acidophilum. We recently identified a novel gene that causes BBS2. The BBS2 protein has no significant similarity to other chaperonins or known proteins. Here we report the positional cloning and identification of mutations in BBS patients in a novel gene designated BBS4.
Assuntos
Síndrome de Bardet-Biedl/genética , Obesidade/genética , Proteínas/genética , Clonagem Molecular , Consanguinidade , Etiquetas de Sequências Expressas , Humanos , Proteínas Associadas aos Microtúbulos , Dados de Sequência Molecular , MutaçãoRESUMO
OBJECTIVE: Unipolar psychotic depression (PD) is a highly debilitating condition, which needs intense monitoring and treatment. Among patients with recurrent PD, delusions tend to be very similar or identical over several separate episodes during the course of illness, but case-reports illustrating this clinical phenomenon in detail are lacking from the literature. METHODS: Case report describing the 45-year-old Ms. J, who has experienced multiple episodes of PD. The report is based on a review of her medical file. RESULTS: The delusional theme of Ms. J's initial episode of PD reappeared at several subsequent episodes. During the majority of admissions, Ms. J was treated with electroconvulsive therapy, which resulted in significant improvement in the depressive, psychotic and catatonic features. CONCLUSION: Ms. J's case illustrates that PD can be a stable phenotype over many episodes and that it is important to recognize psychotic symptoms in order to prescribe the best possible treatment.
RESUMO
Mucolipidosis II (ML II alpha/beta), or I-cell disease, is a rare genetic disease in which activity of the uridine diphosphate (UDP)-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) is absent. GlcNAc-phosphotransferase is a multimeric enzyme encoded by two genes, GNPTAB and GNPTG. A spectrum of mutations in GNPTAB has been recently reported to cause ML II alpha/beta. Most of these mutations were found to be private or rare. However, the mutation c.3503_3504delTC has been detected among Israeli and Palestinian Arab-Muslim, Turkish, Canadian, Italian, Portuguese, Irish traveller and US patients. We analysed 44 patients who were either homozygous or compound heterozygous for this deletion (22 Italians, 8 Arab-Muslims, 1 Turk, 3 Argentineans, 3 Brazilians, 2 Irish travellers and 5 Portuguese) and 16 carriers (15 Canadians and 1 Italian) for three intragenic polymorphisms: c.-41_-39delGGC, c.18G>A and c.1932A>G as well as two microsatellite markers flanking the GNPTAB gene (D12S1607 and D12S1727). We identified a common haplotype in all chromosomes bearing the c.3503_3504delTC mutation. In summary, we showed that patients carrying the c.3503_3504delTC deletion presented with a common haplotype, which implies a common origin of this mutation. Additionally, the level of diversity observed at the most distant locus indicates that the mutation is relatively ancient (around 2063 years old), and the geographical distribution further suggests that it probably arose in a peri-Mediterranean region.
Assuntos
Árabes/genética , Mucolipidoses/genética , Transferases (Outros Grupos de Fosfato Substituídos) , Árabes/história , Canadá , Análise Mutacional de DNA , Demografia/história , Europa (Continente) , Feminino , Frequência do Gene , Haplótipos , Heterozigoto , História Antiga , Homozigoto , Humanos , América Latina , Masculino , Região do Mediterrâneo , Mucolipidoses/fisiopatologia , Filogenia , Polimorfismo Genético , Deleção de Sequência , Transferases (Outros Grupos de Fosfato Substituídos)/deficiência , Transferases (Outros Grupos de Fosfato Substituídos)/genética , TurquiaRESUMO
BACKGROUND: Roberts syndrome (RBS) and SC phocomelia are caused by mutations in ESCO2, which codes for an acetyltransferase involved in the regulation of sister chromatid cohesion. Of 26 mutations described to date, only one missense mutation has been reported and all others are predicted to be truncating mutations. Genotype-phenotype analysis has been hampered by limited numbers of patients with clinical information available. OBJECTIVE: To provide unpublished clinical data for 31 patients with proven ESCO2 mutations and combine this series with previously reported clinical and mutation data on 18 cases. Methods Genotype-phenotype correlations and functional effects of two novel ESCO2 mutations were analysed. In situ hybridisation on human embryos at Carnegie stages 14, 17 and 21 was performed to study ESCO2 expression during development. RESULTS AND CONCLUSIONS: Using the cohort of 49 patients, the clinical criteria for RBS were delineated to include: growth retardation; symmetric mesomelic shortening of the limbs in which the upper limbs are more commonly and severely affected than the lower limbs; characteristic facies with microcephaly. The severity of malformations of the facies correlates with the severity of limb reduction. The occurrence of corneal opacities may be associated with specific mutations. Two new mutations, both in the ESCO2 acetyltransferase domain, are described and their acetylation effects in vitro demonstrated. In situ hybridisation on human embryos showed ESCO2 expression in the brain, face, limb, kidney and gonads, which corresponds to the structures affected in RBS.
Assuntos
Anormalidades Múltiplas/genética , Acetiltransferases/genética , Proteínas Cromossômicas não Histona/genética , Anormalidades Craniofaciais/genética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Códon/genética , Feminino , Expressão Gênica , Variação Genética , Humanos , Lactente , Masculino , Mutação de Sentido Incorreto , Fenótipo , Estrutura Terciária de Proteína/genética , Deleção de Sequência , SíndromeRESUMO
Neonatal epileptic encephalopathies with suppression bursts (SBs) are very severe and relatively rare diseases characterized by neonatal onset of seizures, interictal electroencephalogram (EEG) with SB pattern and very poor neurological outcome or death. Their etiology remains elusive but they are occasionally caused by metabolic diseases or malformations. Studying an Arab Muslim Israeli consanguineous family, with four affected children presenting a severe neonatal epileptic encephalopathy, we have previously identified a mutation in the SLC25A22 gene encoding a mitochondrial glutamate transporter. In this report, we describe a novel SLC25A22 mutation in an unrelated patient born from first cousin Algerian parents and presenting severe epileptic encephalopathy characterized by an EEG with SB, hypotonia, microcephaly and abnormal electroretinogram. We showed that this patient carried a homozygous p.G236W SLC25A22 mutation which alters a highly conserved amino acid and completely abolishes the glutamate carrier's activity in vitro. Comparison of the clinical features of patients from both families suggests that SLC25A22 mutations are responsible for a novel clinically recognizable epileptic encephalopathy with SB.
Assuntos
Sistema X-AG de Transporte de Aminoácidos/genética , Epilepsia/genética , Doenças do Recém-Nascido/genética , Proteínas de Membrana Transportadoras/genética , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Mutação/genética , Sequência de Bases , Análise Mutacional de DNA , Família , Feminino , Humanos , Recém-Nascido , Masculino , Proteínas de Transporte da Membrana Mitocondrial , Dados de Sequência Molecular , LinhagemRESUMO
The molecular mechanisms underlying the organization of ion channels and signaling molecules at the synaptic junction are largely unknown. Recently, members of the PSD-95/SAP90 family of synaptic MAGUK (membrane-associated guanylate kinase) proteins have been shown to interact, via their NH2-terminal PDZ domains, with certain ion channels (NMDA receptors and K+ channels), thereby promoting the clustering of these proteins. Although the function of the NH2-terminal PDZ domains is relatively well characterized, the function of the Src homology 3 (SH3) domain and the guanylate kinase-like (GK) domain in the COOH-terminal half of PSD-95 has remained obscure. We now report the isolation of a novel synaptic protein, termed GKAP for guanylate kinase-associated protein, that binds directly to the GK domain of the four known members of the mammalian PSD-95 family. GKAP shows a unique domain structure and appears to be a major constituent of the postsynaptic density. GKAP colocalizes and coimmunoprecipitates with PSD-95 in vivo, and coclusters with PSD-95 and K+ channels/NMDA receptors in heterologous cells. Given their apparent lack of guanylate kinase enzymatic activity, the fact that the GK domain can act as a site for protein-protein interaction has implications for the function of diverse GK-containing proteins (such as p55, ZO-1, and LIN-2/CASK).
Assuntos
Proteínas de Transporte/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Células COS , Proteínas de Transporte/metabolismo , Proteína 4 Homóloga a Disks-Large , Guanilato Quinases , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Canais Iônicos , Proteínas de Membrana , Dados de Sequência Molecular , Núcleosídeo-Fosfato Quinase/metabolismo , Proteínas/genética , Ratos , Proteínas Associadas SAP90-PSD95 , Sinapses/metabolismoRESUMO
The human WW Domain Containing Oxidoreductase (WWOX) gene was originally described as a tumor suppressor gene. However, recent reports have demonstrated its cardinal role in the pathogenesis of central nervous systems disorders such as epileptic encephalopathy, intellectual disability, and spinocerebellar ataxia. We report on six patients from three unrelated families of full or partial Yemenite Jewish ancestry exhibiting early infantile epileptic encephalopathy and profound developmental delay. Importantly, four patients demonstrated facial dysmorphism. Exome sequencing revealed that four of the patients were homozygous for a novel WWOX c.517-2A > G splice-site variant and two were compound heterozygous for this variant and a novel c.689A > C, p.Gln230Pro missense variant. Complementary DNA sequencing demonstrated that the WWOX c.517-2A > G splice-site variant causes skipping of exon six. A carrier rate of 1:177 was found among Yemenite Jews. We provide the first detailed description of patients harboring a splice-site variant in the WWOX gene and propose that the clinical synopsis of WWOX related epileptic encephalopathy should be broadened to include facial dysmorphism. The increased frequency of the c.517-2A > G splice-site variant among Yemenite Jews coupled with the severity of the phenotype makes it a candidate for inclusion in expanded preconception screening programs.
Assuntos
Face/anormalidades , Deficiência Intelectual/genética , Espasmos Infantis/genética , Proteínas Supressoras de Tumor/genética , Oxidorredutase com Domínios WW/genética , Feminino , Estudos de Associação Genética , Humanos , Judeus/genética , Masculino , Mutação , Linhagem , IêmenRESUMO
Chapsyn-110, a novel membrane-associated putative guanylate kinase (MAGUK) that binds directly to N-methyl-D-aspartate (NMDA) receptor and Shaker K+ channel subunits, is 70%-80% identical to, and shares an identical domain organization with, PSD-95/SAP90 and SAP97. In rat brain, chapsyn-110 protein shows a somatodendritic expression pattern that overlaps partly with PSD-95 but that contrasts with the axonal distribution of SAP97. Chapsyn-110 associates tightly with the postsynaptic density in brain, and mediates the clustering of both NMDA receptors and K+ channels in heterologous cells. Indeed, chapsyn-110 and PSD-95 can heteromultimerize with each other and are recruited into the same NMDA receptor and K+ channel clusters. Thus, chapsyn-110 and PSD-95 may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signalling proteins.
Assuntos
Proteínas do Tecido Nervoso/fisiologia , Núcleosídeo-Fosfato Quinase/fisiologia , Agregação de Receptores , Receptores de N-Metil-D-Aspartato/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Sequência de Aminoácidos , Animais , Encéfalo/metabolismo , Proteína 1 Homóloga a Discs-Large , Proteína 4 Homóloga a Disks-Large , Guanilato Quinases , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/química , Núcleosídeo-Fosfato Quinase/química , Núcleosídeo-Fosfato Quinase/genética , Canais de Potássio/fisiologia , Coelhos , Ratos , Frações Subcelulares/metabolismo , Distribuição Tecidual , Proteínas Supressoras de TumorRESUMO
Fabry disease is an inherited, progressive, life-threatening disease; therefore, lifelong therapy is needed. By replacing the deficient enzyme, disease progression may be delayed or halted, thereby avoiding serious complications. Hospital-based agalsidase therapy is generally perceived as inconvenient and home-based infusion therapy is greatly appreciated by patients, their families and healthcare professionals. Patients can get familiar with infusion therapy in a hospital setting and, if specific requirements are fulfilled, routine nurse-assisted infusion, or self-care, at the patient's home can be organized. A stable patient who tolerates the infusion and a suitable home environment are prerequisites for home therapy. The authors' clinical experiences underscore the safety and practicality of home therapy. In addition to a major positive impact on the patient's quality of life, home infusion therapy may reduce the constraints of hospital resources. This article reviews the collective experiences with agalsidase beta home infusion therapy and outlines how safe, patient-centred homecare can be organized. Home infusion therapy with Fabrazyme should not be withheld from patients considered eligible according to the proposed criteria. Similar approaches to other enzyme therapies are also possible.
Assuntos
Doença de Fabry/tratamento farmacológico , Doença de Fabry/enfermagem , Terapia por Infusões no Domicílio/métodos , Terapia por Infusões no Domicílio/enfermagem , Isoenzimas/uso terapêutico , alfa-Galactosidase/uso terapêutico , Enfermagem em Saúde Comunitária/organização & administração , Progressão da Doença , Monitoramento de Medicamentos , Doença de Fabry/genética , Serviços de Assistência Domiciliar/organização & administração , Terapia por Infusões no Domicílio/psicologia , Humanos , Isoenzimas/efeitos adversos , Israel , Países Baixos , Papel do Profissional de Enfermagem , Avaliação em Enfermagem , Cooperação do Paciente/psicologia , Assistência Centrada no Paciente , Guias de Prática Clínica como Assunto , Qualidade de Vida , Gestão da Segurança , Reino Unido , Estados Unidos , alfa-Galactosidase/efeitos adversosRESUMO
Mucolipidosis IIIC, or variant pseudo-Hurler polydystrophy, is an autosomal recessive disease of lysosomal hydrolase trafficking. Unlike the related diseases, mucolipidosis II and IIIA, the enzyme affected in mucolipidosis IIIC (N-Acetylglucosamine-1-phosphotransferase [GlcNAc-phosphotransferase]) retains full transferase activity on synthetic substrates but lacks activity on lysosomal hydrolases. Bovine GlcNAc-phosphotransferase has recently been isolated as a multisubunit enzyme with the subunit structure alpha(2)beta(2)gamma(2). We cloned the cDNA for the human gamma-subunit and localized its gene to chromosome 16p. We also showed, in a large multiplex Druze family that exhibits this disorder, that MLIIIC also maps to this chromosomal region. Sequence analysis of the gamma-subunit cDNA in patients from 3 families identified a frameshift mutation, in codon 167 of the gamma subunit, that segregated with the disease, indicating MLIIIC results from mutations in the phosphotransferase gamma-subunit gene. This is to our knowledge the first description of the molecular basis for a human mucolipidosis and suggests that the gamma subunit functions in lysosomal hydrolase recognition.
Assuntos
Lisossomos/metabolismo , Mucolipidoses/genética , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Sequência de Aminoácidos , Sequência de Bases , Cromossomos Humanos Par 16 , Clonagem Molecular , Feminino , Fibroblastos , Mutação da Fase de Leitura , Ligação Genética , Humanos , Escore Lod , Lisossomos/enzimologia , Masculino , Dados de Sequência Molecular , Mucolipidoses/etiologia , Linhagem , RNA Mensageiro/metabolismo , Análise de Sequência , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismoRESUMO
Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic medications in patients within their first episode of psychosis. This study examined the effectiveness of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year treatment period. Two hundred and sixty-three patients were randomized to olanzapine or haloperidol in a doubleblind, multisite, international 2-year study. Clinical symptoms and side effects were assessed at baseline and longitudinally following randomization for the duration of the study. Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity (the primary outcome measure) over the course of the study. However, the treatment groups differed on two secondary efficacy measures. Patients were less likely to discontinue treatment with olanzapine than with haloperidol: mean time (in days) in the study was significantly greater for those treated with olanzapine compared to haloperidol (322.09 vs. 230.38, p<0.0085). Moreover, remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol (57.25% vs. 43.94%, p<0.036). While extrapyramidal side effects were greater in those treated with haloperidol, weight gain, cholesterol level and liver function values were greater in patients treated with olanzapine. The data from this study suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients, which must be weighed against those adverse effects that are more likely with olanzapine.
Assuntos
Antipsicóticos/uso terapêutico , Haloperidol/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Método Duplo-Cego , Feminino , Seguimentos , Haloperidol/efeitos adversos , Humanos , Cooperação Internacional , Masculino , Testes Neuropsicológicos , Olanzapina , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Resultado do TratamentoRESUMO
A patient is described who underwent atrial septal defect repair at age 12 and presented 16 years later with angina. Coronary angiography revealed a right coronary artery to pulmonary artery fistula that had developed at the site of the previous thoracotomy. This is the first report of an acquired fistula of this type developing secondary to trauma associated with open heart surgery. Diagnosis, shunt quantification and treatment are discussed.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Vasos Coronários , Fístula/etiologia , Artéria Pulmonar , Adulto , Feminino , Fístula/diagnóstico , Fístula/fisiopatologia , Fístula/cirurgia , HumanosRESUMO
To investigate the specificity of the dexamethasone suppression test (DST) for the diagnosis of major depression in patients with diabetes mellitus, we administered 1 mg of dexamethasone to 30 nondepressed diabetics and to 58 normal controls at 11 PM. Diabetic subjects received hemoglobin A1 (Hb A1) determinations, the Hamilton Rating Scale for Depression (HRSD), and five to eight blood glucose determinations during the 48 hours surrounding the DST. Results demonstrated a significantly higher rate of nonsuppression (plasma cortisol level, greater than or equal to 5 micrograms/dL) at 4 PM the following day among diabetics (43%) than among controls (7%) but no difference between these groups in the rate of nonsuppression at 8 AM. Plasma cortisol level at 4 PM correlated with Hb A1 level but not with duration of illness, HRSD score, mean blood glucose level, or maximum blood glucose excursion. These results suggest that the results of the DST used as a diagnostic test for major depression must be interpreted with caution in patients with diabetes.