RESUMEN
OBJECTIVE: A characteristic feature of spinocerebellar ataxia type 2 (SCA2) is saccadic slowing at early disease stages. We sought to determine whether this sign is detectable before clinical manifestation and quantifies the disease progression throughout life in linear fashion. METHODS: In a specialized ataxia clinic, 54 presymptomatic carriers of SCA2 polyglutamine expansions and 56 relatives without mutation were documented with regard to their maximal saccade velocity (MSV). RESULTS: Among the control individuals, a significant effect of aging on MSV was observed. After elimination of this age influence through a matched-pair approach, a presymptomatic decrease of MSV could be shown. The MSV reduction was stronger in carriers of large expansions. In the years before calculated disease manifestation, the MSV impairment advanced insidiously. CONCLUSION: Saccade velocity is a sensitive SCA2 endophenotype that reflects early pontine degeneration and may be a useful diagnostic parameter before the onset of ataxia. SIGNIFICANCE: Future neuroprotective therapies of polyglutamine neurodegeneration may be assessed by MSV from earliest to prefinal disease stages.
Asunto(s)
Trastornos de la Motilidad Ocular/etiología , Trastornos de la Motilidad Ocular/fisiopatología , Músculos Oculomotores/fisiopatología , Movimientos Sacádicos/fisiología , Ataxias Espinocerebelosas/complicaciones , Ataxias Espinocerebelosas/fisiopatología , Adolescente , Adulto , Anciano , Ataxinas , Cerebelo/fisiopatología , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Vías Nerviosas/fisiopatología , Trastornos de la Motilidad Ocular/diagnóstico , Músculos Oculomotores/inervación , Valor Predictivo de las Pruebas , Pronóstico , Ataxias Espinocerebelosas/diagnóstico , Adulto JovenRESUMEN
A characteristic feature of spinocerebellar ataxia type 2 (SCA2) is saccadic slowing at early disease stages. We sought to determine whether this sign is detectable before clinical manifestation and quantifies the disease progression throughout life in linear fashion. In a specialized ataxia clinic, 54 presymptomatic carriers of SCA2 polyglutamine expansions and 56 relatives without mutation were documented with regard to their maximal saccade velocit Spinocerebellar ataxia type 2 Among the control individuals, a significant effect of aging on MSV was observed. After elimination of this age influence through a matched-pair approach, a presymptomatic decrease of MSV could be shown. The MSV reduction was stronger in carriers of large expansions. In the years before calculated disease manifestation, the MSV impairment advanced insidiously.Saccade velocity is a sensitive SCA2 endophenotype that reflects early pontine degenerationPolyglutamine expansion and may be a useful diagnostic parameter before the onset of ataxia. Significance: Future neuroprotective therapies of polyglutamine neurodegeneration may be assessed by MSV from earliest to prefinal disease stages...(AU)
Asunto(s)
HumanosRESUMEN
Acid rain precipitation has become a major environmental concern. Many long-range projects in the United States and Europe are devoted to the problems associated with acid rain pollution. In Puerto Rico, there has been no formal study on acid rain. The rainfall pH values and the air-mass trajectory of the northeastern part of the island of Puerto Rico on the surface were analyzed from January 1998 to December 2000. The air-mass trajectory was classified in five different sectors, according to where it originates. The mean pH value measured during that period showed a tendency toward acidity. The 80% of the air-mass trajectory that arrived at the station occurred in Sector I, with a pH value of 4.30. The lowest pH value measured was 4.16, and it occurred in Sector V, where the air mass originates in the northwest part of the island.
Asunto(s)
Lluvia Ácida/análisis , Monitoreo del Ambiente , Ambiente , Concentración de Iones de Hidrógeno , Formulación de Políticas , Puerto Rico , Valores de ReferenciaRESUMEN
Recent reports have shown an association between cytochrome P450IID6 (CYP2D6) polymorphism and Parkinson's disease. We investigated the association between this polymorphism and the risk for developing essential tremor (ET). Leukocytic DNA from 91 unrelated ET patients and a control group of 258 unrelated healthy individuals was studied for the occurrence of eight different CYP2D6 allelic variants by using allele-specific PCR amplification Xbal and EcoRI-RFLP's analyses. The prevalence for these allelic variants in the ET and control groups were, respectively: CYP2D6*1 76.9 and 78.7%, CYP2D6*2 0.5 and 0.2%, CYP2D6*3 0 and 1%, CYP2D6*4 12.1 and 12.2%, CYP2D6*5 1.6 and 1.7%, CYP2D6*9 4.4 and 2.9%, CYP2D6*2x2 4.4 and 3.2%. The prevalence of subjects with absent CYP2D6 activity (those carrying two defect genes) was 1.1 and 3.1% in ET and control groups, respectively. Both groups studied were in Hardy-Weinberg equilibrium. These results indicate that mutations at the CYP2D6 gene do not seem to be a major factor in determining susceptibility to ET, and reinforces the view that ET and parkinsonism are distinct conditions.
Asunto(s)
Citocromo P-450 CYP2D6/genética , Enfermedad de Parkinson/genética , Polimorfismo Genético/genética , Temblor/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Análisis Mutacional de ADN , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Reacción en Cadena de la Polimerasa , Factores de Riesgo , Temblor/diagnósticoRESUMEN
The arylamine N-acetyltransferase (NAT2) polymorphism has been related to the risk of developing non-insulin-dependent diabetes mellitus (NIDDM). Several studies suggested an excess of rapid acetylators among NIDDM patients. This may be explained by an increased risk to develop NIDDM among subjects with the rapid acetylator capacity, or by changes in the acetylator status due to the disease or drug therapy. In order to elucidate this controversial topic, we have studied by a mutation-specific polymerase chain amplification (PCR) method the occurrence of seven point mutations at the coding region of the NAT2 gene in genomic DNA from 111 patients with NIDDM and 217 healthy controls. In addition, we have studied by the combined use of PCR and restriction fragment length polymorphism the occurrence of seven allelic variants of the CYP2D6 gene in the same subjects. In contrast to previous phenotyping studies, no relationship was found between NAT2 polymorphism and NIDDM or its complications such as nephropathy or neuropathy. The CYP2D6 genotype was similar between cases and controls. Our findings do not provide a genetic basis for any association of NIDDM and NAT2 polymorphism, suggesting that any excess of subjects with the rapid acetylator phenotype among patients with NIDDM should be secondary to the disease or concomitant drug therapy.