RESUMEN
BACKGROUND: In Fabry disease, progressive glycolipid accumulation leads to damage in kidney and other organs. This study was designed to determine the prevalence rate of Fabry disease in Japanese dialysis patients. METHODS: All dialysis patients agreeing to Japan Fabry disease screening study (J-FAST) with informed consent were selected except for Fabry disease. The screening was performed by a method of measuring plasma and/or leukocytes lysosomal α-galactosidase A protein level and α-galactosidase A activity. If positive, genetic analysis was carried out upon patient's agreement. RESULTS: J-FAST dealt with 8547 patients (male 5408, female 3139). At the tertiary examination, 26 out of 8547 patients were found to be positive. Six out of 26 patients could not accept genetic analysis because of death. Remaining 20 patients agreed with genetic analysis; then 2 patients (male 2, female 0) had a variation of the α-Gal gene and 11 patients showed E66Q variations. Therefore, the frequency of Fabry disease in J-FAST was 0.04 % (2/5408) in males and 0 % (0/3139) in females, and then 0.02 % (2/8547) in all patients. The presumptive clinical diagnoses of end-stage kidney disease (ESKD) were 10 chronic glomerulonephritis, 7 diabetic nephropathy, 3 unknown etiology, 3 nephrosclerosis, 1 gouty nephropathy, 1 autosomal dominant polycystic kidney disease and 1 renal tuberculosis among 26 tertiary positive patients. Two male Fabry patients were initially diagnosed as nephrosclerosis and chronic glomerulonephritis. CONCLUSIONS: The prevalence rate of Fabry disease in J-FAST was 0.02 %. Moreover, Fabry disease could not be ruled out as the clinical diagnosis of ESKD.
Asunto(s)
Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/epidemiología , Fallo Renal Crónico/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Humanos , Japón/epidemiología , Fallo Renal Crónico/epidemiología , Tamizaje Masivo , Persona de Mediana Edad , Adulto JovenRESUMEN
The hypothesis of this research was that elderly people with many remaining teeth and good occlusion (8020 achievers) would be able to maintain proper head and body posture, despite aging. The purpose of this study, as a first stage, was to clarify the aging phenomenon of cervical curvature in 8020 achievers in comparison with that in young adults. Subjects consisted of twenty-eight 8020 achievers, with a mean age of 82.96+/-3.3 years and 26.5+/-4.0 teeth. For comparison, forty adults in their 20's with a mean age of 22.9+/-0.7 years and 28.2+/-0.6 teeth were also enrolled. The cervical vertebra was assessed based on the distance from the CV line (tangential line of the 2nd and 6th cervical vertebra) to each cervical vertebra and the angles formed by the cervical and reference lines in the cranial bone. Every distance from the CV line to each cervical vertebra in the 8020 group was bigger than that in the 20's group (p<0.01-0.001). The distance from the CV line to CV-3 and CV-5 in 8020 women was larger than that in 8020 men (p<0.05). Every distance from the CV line to each cervical vertebra in 8020 women was larger than that in 20's women (p<0.01-0.001). There was no significant difference between 8020 men and 20's men. The difference between the women's group was more marked than that between age groups for men. The cervical curvature in 8020 achievers showed a greater tendency toward cervical lordosis than that in young adults. In the 8020 achievers, the curvature in women was greater than that in men. The curvature in 8020 women seemed was marked, showing strong cervical lordosis, despite the presence of many remaining teeth and good occlusion. It remains to be determined by comparing 8020 achievers with ordinary elderly whether the condition of the teeth influences spinal curvature with aging.
Asunto(s)
Envejecimiento/fisiología , Vértebras Cervicales , Lordosis , Salud Bucal , Adulto , Anciano , Estudios de Casos y Controles , Cefalometría , Femenino , Indicadores de Salud , Humanos , Japón , Lordosis/diagnóstico , Masculino , Postura , Factores SexualesRESUMEN
The International HapMap Consortium has developed the HapMap, a resource that describes the common patterns of human genetic variation (haplotypes). Processes of community/public consultation and individual informed consent were implemented in each locality where samples were collected to understand and attempt to address both individual and group concerns. Perceptions about the research varied, but we detected no critical opposition to the research. Incorporating community input and responding to concerns raised was challenging. However, the experience suggests that approaching genetic variation research in a spirit of openness can help investigators better appreciate the views of the communities whose samples they seek to study and help communities become more engaged in the science.
Asunto(s)
Mapeo Cromosómico , Proyecto Genoma Humano , Consentimiento Informado , Cooperación Internacional , Adulto , Niño , Femenino , Variación Genética , Genética de Población , Humanos , Masculino , PadresRESUMEN
The purpose of this study was to investigate oral flora in independent persons aged over 80 years with more than 20 remaining teeth. The subjects were 22 participants of the 8020 campaign (6 males and 16 females) with a mean age of 81.3+/-1.6 years and an average of 24.7 teeth (Independent 8020 group). This group was compared with a group of 38 elderly people residing in nursing homes (10 males and 28 females) who had a mean age of 81.3+/-8.5 years and an average of 4.2 teeth (Nursing group with fewer teeth). Saliva samples were collected from the vestibular areas of the maxilla and mandible using cotton swabs. Cell numbers of microorganisms were expressed as colony forming units/ml (CFUs/ml) and compared between the two groups. The average number of Staphylococcus species was 65.2+/-74.4 CFUs/ml in the Independent 8020 group and 400.3+/-352.1 CFUs/ml in the group with fewer teeth (p<0.01); that of Candida albicans was 18.0+/-37.7 CFUs/ml in the Independent 8020 group and 152.9+/-211.9 CFUs/ml in the Nursing group with fewer teeth (p<0.05). Both species showed statistically significant differences between the two groups. This suggests that the Independent 8020 achiever group had better oral hygiene and that the presence of many teeth may be associated with an increased awareness of dental health.
Asunto(s)
Arcada Parcialmente Edéntula/microbiología , Saliva/microbiología , Actividades Cotidianas , Anciano de 80 o más Años , Candida albicans/aislamiento & purificación , Recuento de Colonia Microbiana , Femenino , Humanos , Masculino , Casas de Salud , Higiene Bucal , Staphylococcus/aislamiento & purificaciónRESUMEN
Various disorders cause hyperammonemia during childhood. Among them are those caused by inherited defects in urea synthesis and related metabolic pathways. These disorders can be grouped into two types: disorders of the enzymes that comprise the urea cycle, and disorders of the transporters or metabolites of the amino acids related to the urea cycle. Principal clinical features of these disorders are caused by elevated levels of blood ammonium. Additional disease-specific symptoms are related to the particular metabolic defect. These specific clinical manifestations are often due to an excess or lack of specific amino acids. Treatment of urea cycle disorders and related metabolic diseases consists of nutritional restriction of proteins, administration of specific amino acids, and use of alternative pathways for discarding excess nitrogen. Although combinations of these treatments are extensively employed, the prognosis of severe cases remains unsatisfactory. Liver transplantation is one alternative for which a better prognosis is reported.
Asunto(s)
Enfermedades Metabólicas/fisiopatología , Errores Innatos del Metabolismo/fisiopatología , Urea/metabolismo , Niño , Humanos , Enfermedades Metabólicas/terapia , Errores Innatos del Metabolismo/genética , Errores Innatos del Metabolismo/terapia , Pronóstico , Compuestos de Amonio Cuaternario/envenenamientoRESUMEN
A critical review from standpoints of ethical, legal and social implications (ELSI) is required to properly develop and distribute genetic services, including genetic testing. In addition to assure analytical validity, clinical validity and clinical utility of the testing, public opinion and perceptions of the community regarding implementation of the testing are important for obtaining informed consent prior to testing. Otherwise, the testing could be done on only limited numbers of community members. Development of effective inversion in clinical practices and regulation to provide confidentiality of all genetic information should bolster the attitude of the community. Education of the public and mass media is the most important factor if progress is to be made in the clinical application of human genome research, and to avoid "genohype".
Asunto(s)
Servicios Genéticos , Pruebas Genéticas , Diagnóstico Prenatal , Recolección de Datos , Asesoramiento Genético , Privacidad Genética , Servicios Genéticos/ética , Servicios Genéticos/normas , Genética Médica/educación , Humanos , Consentimiento Informado , Japón , Opinión PúblicaRESUMEN
Since 1979, at least 13,000 affected babies have been identified with one of the tested diseases. The outcome for patients is generally favorable if adequate treatment is given. Recently, ethical issues have arisen concerning whether or not written informed consent should be required, under what conditions the residual blood spot may be used for research purposes other than that originally designed, and whether or not the test is cost-effective. Mandatory screening seems acceptable under certain conditions, but parental education and opportunity for refusal should be part of the system. Refusal should be documented only after an attempt has been made to persuade parents to consent. Informed consent is necessary if there is uncertainty about the test's benefit to the child. Parents should be informed of the potential research value of the samples and assured that research results will not be linked to any particular/individual newborn. If identified or coded blood spots are used for research, IRB review and approval by IRB must occur. The net health care benefit from screening for six disorders in Japan was 0.25 billion yen ($2.2 million) per 100,000 screened newborns compared to $3.2 million for PKU and CH in the US for 100,000 screened newborns.
Asunto(s)
Ética Clínica , Consentimiento Informado , Tamizaje Neonatal/ética , Tamizaje Neonatal/organización & administración , Recolección de Muestras de Sangre , Humanos , Recién Nacido , Japón , Programas Obligatorios , Tamizaje Neonatal/economía , Padres/psicología , Negativa a Participar , Programas VoluntariosRESUMEN
BACKGROUND: Most cases of dyslipidemia found in adults are non-familial. However, in children, especially young children, dyslipidemias other than familial hypercholesterolemia (FH) have not yet been characterized. METHODS: From April 1990 to March 1999, 56 181 children were screened, and 1380 showed abnormal levels of apolipoprotein B (more than 2.5 standard deviations above the mean). Among these, 1198 were re-examined and further characterized by measuring lipids and apolipoproteins, and by their familial histories. RESULTS: Seventy-seven percent of the children (928 of 1198) recalled were diagnosed as being dyslipidemic. Ninety-one children were FH, 423 were type IIa, 128 were type IIb, 98 were type IV, and 188 were hypoalphalipoproteinemia. The presumed incidence of FH was 0.19%, IIa 0.87%, IIb 0.26%, IV 0.20%, and hypoalphalipoproteinemia 0.39%, taking into account the percentage of subjects who refused recall. At regular follow-ups, in many children with type IIb, the phenotypic expression changes from type IIb to IIa or IV. Thus, lipid and apolipoprotein levels were determined in 77 family members in 34 families of children with type IIb. Forty-five family members were dyslipidemic (type IIa 18, type IIb 11, type IV 16). As a result, 27 children (79%) with type IIb met the criteria for familial combined hyperlipidemia. CONCLUSIONS: Children with dyslipidemia had more family or genetic background than adults. Unexpectedly, children with type IIb were mostly familial combined hyperlipidemia. Thus, setting appropriate eating patterns during childhood might be important for normalizing risk factors for atherosclerotic coronary heart disease, especially in children with FH or type IIb.
Asunto(s)
Hiperlipidemias/epidemiología , Análisis de Varianza , Apolipoproteínas B/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad Coronaria/prevención & control , Estudios de Seguimiento , Humanos , Hiperlipidemia Familiar Combinada/sangre , Hiperlipidemia Familiar Combinada/epidemiología , Hiperlipidemias/sangre , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/epidemiología , Hiperlipoproteinemia Tipo IV/sangre , Hiperlipoproteinemia Tipo IV/epidemiología , Lactante , Japón/epidemiología , Tamizaje Masivo , Estudios Retrospectivos , Enfermedad de Tangier/sangre , Enfermedad de Tangier/epidemiología , Triglicéridos/sangreAsunto(s)
Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa , Diagnóstico Diferencial , Femenino , Genes Dominantes , Humanos , Hiperamonemia/diagnóstico , Hiperamonemia/etiología , Masculino , Mutación , Ornitina Carbamoiltransferasa/genética , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/genética , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/terapia , Pronóstico , Cromosoma XRESUMEN
Hereditary tyrosinemia type 1 (HT1) (McKusick 276700), a severe autosomal recessive disorder of tyrosine metabolism, is caused by mutations in the fumarylacetoacetate hydrolase gene Fah (EC 3.7.1.2), which encodes the last enzyme in the tyrosine catabolic pathway. HT1 is characterized by severe progressive liver disease and renal tubular dysfunction. Homozygous disruption of the gene encoding Fah in mice causes neonatal lethality (e.g., lethal Albino deletion c14CoS mice), an event that limits use of this animal as a model for HT1. A new mouse model was developed with two genetic defects, Fah and 4-hydroxyphenylpyruvate dioxygenase (Hpd). The Fah-/- Hpd-/- mice grew normally without evidence of liver and renal disease, and the phenotype is similar to that in Fah+/+ Hpd-/- mice. The renal tubular cells of Fah-/- Hpd-/- mice, particularly proximal tubular cells, underwent rapid apoptosis when homogentisate, the intermediate metabolite between HPD and FAH, was administered to the Fah-/- Hpd-/- mice. Simultaneously, renal tubular function was impaired and Fanconi syndrome occurred. Apoptotic death of renal tubular cells, but not renal dysfunction, was prevented by pretreatment of the animals with YVAD, a specific inhibitor of caspases. In the homogentisate-treated Fah-/- Hpd-/- mice, massive amounts of succinylacetone were excreted into the urine, regardless of treatment with inhibitors. It is suggested that apoptotic death of renal tubular cells, as induced by administration of homogentisate to Fah-/- Hpd-/- mice, was caused by an intrinsic process, and that renal apoptosis and tubular dysfunctions in tubular cells occurred through different pathways. These observations shed light on the pathogenesis of renal tubular injury in subjects with FAH deficiency. These Fah-/- Hpd-/- mice can serve as a model in experiments related to renal tubular damage.