RESUMO
Multiple genetic variants may contribute to the risk of developing Alzheimer's disease. We have analyzed polymorphisms in 9 genes to determine whether particular combinations would contribute to this risk. The genes were APOE, LDLr, CST3, CTSD, TNF, BACE1, MAPT, STH, eNOS, and TFCP2. Three risk groups for the disease were identified. Risk group I was younger, was heterozygous for the CST3 (GA), CTSD2936 (AG), TNF -308 (AG) genetic variants. Risk group II was older, was homozygous for the -427 APOE promoter polymorphism (TT), and heterozygous for the MAPT deletion and for the STH variant (QR). Group III had both the youngest and oldest subjects, were heterozygous for the -863 (AC) and -1031 (CT) TNF promoter polymorphisms. All three groups carried the APOE 4 allele and were heterozygous for both BACE1 polymorphisms. The control groups were carriers of the APOE 3 allele and were homozygous for the BACE1 genetic variants.
Assuntos
Doença de Alzheimer/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Secretases da Proteína Precursora do Amiloide/genética , Apolipoproteína E3/genética , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Ácido Aspártico Endopeptidases/genética , Catepsina D/genética , Análise por Conglomerados , Cistatina C/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Receptores de LDL/genética , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: Alzheimer's disease is complex, with variants in multiple genes contributing to interactions increasing risk for the disease. Brain-derived neurotrophic factor (BDNF) promotes neuronal survival and modulates hippocampal-dependent memory. METHODS: We examined 11 SNPs that spanned the gene on chromosome 11p14 in 220 Alzheimer's patients and 128 control spouses. RESULTS: Not all of the SNPs were informative, due to minor allele frequencies of <2%. Neither C270T nor two SNPs that reside proximal to exon V had significant association with the disease. However, we did find that the heterozygous form of the rs6265 SNP (Val66Met), as well as the diplotype of three SNPs (rs6265, rs11030104, rs2049045; H1-GTC/H2-ACG) all were highly significant in APOE 4 non-carriers (OR = 2.734; p = 0.0096). CONCLUSION: The combination of the diplotypes for three SNPs exhibited significant p values for Alzheimer's APOE 4 non-carriers. The two SNPs (rs11030104 and rs2049045) are found between exons VI and VII, while the Val66Met polymorphism is located in the coding exon VIII; the total distance for the three SNPs is 14308 bp. Whether the SNPs are involved with alternative splicing of the VII/VIII transcript is of considerable interest.
Assuntos
Doença de Alzheimer/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Cromossomos Humanos Par 11 , Variação Genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/patologia , Córtex Cerebral/patologia , Mapeamento Cromossômico , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Valores de Referência , Medição de RiscoRESUMO
BACKGROUND: Multiple genes have been provisionally associated with Alzheimer's disease, including the coding polymorphisms in exons 8 and 13 in the low density lipoprotein receptor gene (LDLR), situated on chromosome 19p13.2. METHODS: The sample groups consisted of 180 AD patients and 141 control spouses. We carried out genotyping of LDLR8 and LDLR13. RESULTS: The LDLR8 GG genotype was common, found in 84% of the unaffected control subjects and 91% of the AD patients in our study. There was a ninefold elevation in risk associated with GG:CC versus A- and T- among APOE4+ subjects when compared with APOE4- subjects (odds ratio 9.3; 95% confidence interval 1.8 to 48.2). With the additional information on LDLR polymorphism, we defined an overall 12 fold elevation in risk for APOE4 in combination with LDLR GG:CC (11.9; 2.8 to 50.0; Fisher's exact test, p = 0.0002; standard power 0.999), compared with other subjects lacking all three of these polymorphisms. CONCLUSION: These results imply a functional interaction between ApoE and LDL receptor proteins that determines risk for Alzheimer's disease.
Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Polimorfismo Genético , Receptores de LDL/genética , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína E4 , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/genéticaRESUMO
Cystatin C, a protease inhibitor with widespread distribution, is upregulated in response to injury. Levels are elevated in the brains of patients with Alzheimer disease (AD). We compared frequencies for the CST 3 exon 1 polymorphism in patients with AD and controls. A proportional odds model indicated that the CST 3 A and APOE4 combination carried a high risk: a 14-fold elevation for men and 16-fold for women. These risks apply to risk at ages older than 64 years and to a shift in onset to ages younger than 65 years.
Assuntos
Doença de Alzheimer/genética , Cistatinas/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/epidemiologia , Apolipoproteína E4 , Apolipoproteínas E/genética , Cromossomos Humanos Par 20/genética , Cistatina C , Éxons/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo Genético , Fatores de RiscoRESUMO
Malignant lipoid cell tumors of the ovary are rare lesions that are frequently associated with endocrinologic abnormalities. A case of a woman with this lesion who developed Cushing's syndrome with progression of tumor is presented. Neither aggressive medical therapy with ketoconazole nor multiagent chemotherapy was beneficial in controlling tumor growth or physical and biochemical manifestations of Cushing's syndrome.
Assuntos
Síndrome de Cushing/etiologia , Neoplasias Ovarianas/complicações , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Síndrome de Cushing/complicações , Síndrome de Cushing/tratamento farmacológico , Feminino , Humanos , Hipopotassemia/tratamento farmacológico , Hipopotassemia/etiologia , Cetoconazol/uso terapêutico , Metotrexato/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Vimblastina/administração & dosagemAssuntos
Atenção à Saúde/tendências , Política de Saúde/tendências , Demografia , Emprego , Hospitais , Enfermagem , Estados UnidosRESUMO
Major issues facing general hospitals today include the spiraling cost of health care and attempts by both the hospital industry and government to stem it. Although psychiatric care has not contributed substantially to the inflation in health care costs, the author predicts that psychiatric services would not escape public regulation of hospital costs. He urges psychiatrists to pay closer attention to the influential role of health systems agencies in determining health care needs.
Assuntos
Controle de Custos , Custos e Análise de Custo , Economia Hospitalar , Educação Médica , Fiscalização e Controle de Instalações , Órgãos dos Sistemas de Saúde , Hospitais de Ensino/economia , Serviços de Saúde Mental/economia , Estados UnidosRESUMO
Preventive medicine and primary health care, rather than advanced medical technology, appear to be the focus of health care delivery in China. In fact, the author says, one could imagine a decision being made not to install a CT scanner so that more physician extenders could be trained to improve nutritional standards, help eliminate infectious diseases, and provide health education information to people who would not otherwise be exposed to these services.
Assuntos
Atenção à Saúde , Programas Nacionais de Saúde , China , Hospitais , Medicina Tradicional Chinesa , Assistentes Médicos , Medicina Preventiva , Atenção Primária à SaúdeRESUMO
A new challenge for hospital trustees is that of managing infinite demands with finite resources. Meeting the challenge will require educated decisions arrived at through a participatory process; a rethinking of the institution's goals; a structured evaluation procedure for deciding among alternatives; and a strong data base.
