Apolipoprotein E (ApoE) polymorphism influences lipid metabolism, but its association with arterial hypertension is controversial. The objective of this study was to examine the association between ApoE polymorphism and prevalent hypertension in a large unselected population of older adults. Participants from the baseline of the Bambuí Health Aging Study whose ApoE genes had been genotyped were selected for this study (N = 1406, aged 60-95 years). These subjects represented 80.7% of the total elderly residents in Bambuí city, MG, Brazil. Hypertension was defined as a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg, or the use of anti-hypertensive medication. The exposure variable was the ApoE genotype as follows: ε3 carriers, ε3ε3; ε2 carriers, ε2ε2 or ε2ε3, and ε4 carriers, ε3ε4 or ε4ε4. Potential confounding variables were age, gender, traditional cardiovascular risk factors, uric acid, and creatinine levels. The prevalence of hypertension was 61.3%. Compared with the ε3 homozygotes, neither the ε2 nor the ε4 carrier status was associated with hypertension (adjusted prevalence ratios = 0.94, 95%CI = 0.83-1.07 and 0.98, 0.89-1.07, respectively). On the other hand, the ε2 allele carriers had lower LDL cholesterol levels (P < 0.001) and the ε4 carriers had higher LDL cholesterol levels (P = 0.036). This study provides epidemiologic evidence that the ApoE genotype is not associated with prevalent hypertension in old age.
Apolipoprotein E (ApoE) is one of the most extensively studied genes in the context of aging, but there are few population-based studies on ApoE polymorphism in the elderly in developing countries. The objective of the present study was to assess ApoE allele and genotype distribution in a large elderly community-based sample and its association with age, sex and skin color. Participants included 1408 subjects (80.8% of all residents aged ≥60 years) residing in Bambuí city, MG, Brazil. The DNA samples were subjected to the polymerase chain reaction amplification, followed by the restriction fragment length polymorphism technique, with digestion by HhaI. Analysis was carried out taking into consideration the six ApoE genotypes (ε3/ ε3, ε3/ε4, ε2/ε3, ε4/ε4, ε2/ε4, and ε2/ε2), the three ApoE alleles, and the number of ApoE4 alleles for each individual. The ε3 allele predominated (80.0%), followed by ε4 (13.5%) and ε2 (6.5%). All six possible genotypes were observed, the ε3/ε3 genotype being the most frequent (63.4%). This distribution was similar to that described in other western populations. Sex was not associated with number of ApoE4 alleles. Black skin color was significantly and independently associated with the presence of two ApoE4 alleles (age-sex adjusted OR = 7.38; 95%CI = 1. 93-28.25), showing that the African-Brazilian elderly have a high prevalence of the ε4 allele, as observed in blacks from Africa. No association between number of ApoE4 alleles and age was found, suggesting the absence of association of ApoE genotype with mortality in this population.
Long expansions of transcribed trinucleotide microsatellites have been etiologically associated with some neurological diseases. The investigation of such novel polymorphisms has thus become a subject of great interest. We searched the expressed sequence tag databank for reiterated trinucleotides and selected EST00493 (D2S196E) with 14 tandem ACA triplets as a potentially polymorphic locus. Size variation was readily detected, with four common alleles containing 12-15 repeats. In addition, we observed distinct heteroduplexes in amplifications from individuals with identical ACA genotypes. Sequencing of their polymerase chain reaction (PCR) products revealed a G-->A transition immediately preceding the trinucleotide repeats, hence defining 8 distinct haplotypes and 36 possible genotypes. Indeed, mutation detection enhancement gel electrophoresis of mixed PCR products from cloned haplotypes revealed 24 distinct heteroduplex patterns for the six possible trinucleotide heterozygotes. The observation of heteroduplex patterns in non-denaturing polyacrylamide gel electrophoresis (instead of the more commonly used denaturing gels) can thus be utilized to increase the informativeness of microsatellite polymorphisms by unraveling otherwise cryptic sequence variation. The D2S196E polymorphism has proved useful for demonstrating microsatellite instability and loss of heterozygosity in colorectal tumors.
Two different pathogenetic mechanisms are proposed for colorectal cancers. One, the so-called "classic pathway", is the most common and depends on multiple additive mutational events (germline and/or somatic) in tumor suppressor genes and oncogenes, frequently involving chromosomal deletions in key genomic regions. Methodologically this pathway is recognizable by the phenomenon of loss of heterozygosity. On the other hand, the "mutator pathway" depends on early mutational loss of the mismatch repair system (germline and/or somatic) leading to accelerated accumulation of gene mutations in critical target genes and progression to malignancy. Methodologically this second pathway is recognizable by the phenomenon of microsatellite instability. The distinction between these pathways seems to be more than academic since there is evidence that the tumors emerging from the mutator pathway have a better prognosis. We report here a very simple methodology based on a set of tri-, tetra-and pentanucleotide repeat microsatellites allowing the simultaneous study of microsatellite instability and loss of heterozygosity which could allocate 70% of the colorectal tumors to the classic or the mutator pathway. The ease of execution of the methodology makes it suitable for routine clinical typing.
Apolipoprotein E (ApoE) is one of the most extensively studied genes in the context of aging, but there are few population-based studies on ApoE polymorphism in the elderly in developing countries. The objective of the present study was to assess ApoE allele and genotype distribution in a large elderly community-based sample and its association with age, sex and skin color. Participants included 1408 subjects (80.8% of all residents aged ≥60 years) residing in Bambuí city, MG, Brazil. The DNA samples were subjected to the polymerase chain reaction amplification, followed by the restriction fragment length polymorphism technique, with digestion by HhaI. Analysis was carried out taking into consideration the six ApoE genotypes (ε3/ ε3, ε3/ε4, ε2/ε3, ε4/ε4, ε2/ε4, and ε2/ε2), the three ApoE alleles, and the number of ApoE4 alleles for each individual. The ε3 allele predominated (80.0%), followed by ε4 (13.5%) and ε2 (6.5%). All six possible genotypes were observed, the ε3/ε3 genotype being the most frequent (63.4%). This distribution was similar to that described in other western populations. Sex was not associated with number of ApoE4 alleles. Black skin color was significantly and independently associated with the presence of two ApoE4 alleles (age-sex adjusted OR = 7.38; 95%CI = 1. 93-28.25), showing that the African-Brazilian elderly have a high prevalence of the ε4 allele, as observed in blacks from Africa. No association between number of ApoE4 alleles and age was found, suggesting the absence of association of ApoE genotype with mortality in this population.
Introdução: púrpura de Henoch-Schönlein (PHS) é uma vasculite sistêmica que acomete vasos de pequeno calibre com depósitos de imunocomplexos contendo IgA. Esta vasculite já foi extensamente estudada em crianças, mas sua história natural em adultos é menos conhecida. Objetivos: descrever uma série de pacientes adultos com PHS. Pacientes e Métodos: membros do Grupo Mineiro de Estudo das Vasculites foram convidados a reportar pacientes com PHS apresentando-se na idade adulta. Foi realizada revisão padronizada de prontuários. Resultados: 11 pacientes, dois homens e nove mulheres, com idade + desvio padrão (DP) de 39,4 +/-20,1 anos foram estudados. Nove pacientes apresentaram púrpura; sete apresentaram artrite; quatro apresentaram envolvimento gastrintestinal e dez (91%) pacientes apresentaram glomerulonefrite (GN). Oito pacientes foram submetidos à biópsia renal. Seis deles apresentaram GN endocapilar proliferativa e dois apresentaram apenas proeminência mesangial mínima. Em outros três pacientes, o diagnóstico de PHS foi confirmado através de biópsia de pele. Todos os pacientes receberam corticóide, em cinco associado a outros agentes imunossupressores. Após seguimento (média + DP) 39,0 + 64,6 meses, quatro pacientes (36%) apresentaram comprometimento da função renal, mas apenas um (9%) desenvolveu insuficiência renal terminal e foi submetido a transplante renal com sucesso. Após o seguimento, sete (64%) estão em remissão completa e quatro em remissão parcial. Conclusão: em adultos, PHS representa uma entidade clínica distinta, com maior freqüência de envolvimento renal e vasculite sistêmica mais grave. Entretanto, o prognóstico nesta série foi tão bom quanto em crianças, talvez pela terapia imunossupressiva mais vigorosa. Nine patients presented purpura, seven presented arthritis, four patients had gastrointestinal involvement and ten patients (91%) presented glomerulonephritis (GN). Eight patients were subjected to renal biopsies. Six of them presented endocapillary proliferative GN and only two of them had minimal mesangial proliferation. In the other three patients, HSP was confirmed by skin biopsies. All patients received steroids, in five of them steroids were combined with other immunosuppressive agents. After a follow-up of 39.0 +/-64.6 months, four patients (36%) presented impairment of renal function, but only one (9%) developed end stage renal disease and was successfully appeared to renal transplantation. At the end of follow-up, seven patients (64%) are in complete remission and four in partial remission. Conclusion: in adulthood, HSP represents a distinct clinical syndrome with a higher frequency of renal involvement and more severe systemic vasculitis. Nevertheless, the final outcome in this series was as good as reported in children, maybe due to aggressive immunosuppressive therapy. Palavras
ing home-acquired pneumonia (NHAP) and do not normally require empirical coverage. 3 Regarding guidelines, the suggestion for treating nonambulatory residents of long-term care facilities (LTCFs) is mentioned only briefly in the recent consensus guidelines for community-acquired pneumonia. 2 That statement directs the reader to the consensus guidelines for treatment of healthcare-associated pneumonia (HCAP). 1 Careful examination of those guidelines reveals a strong bias toward hospitalized patients and the acknowledgment that the evidence-based studies of the relationship between risk factors and bacteriology were primarily of patients with ventilator-associated pneumonia, which were then extrapolated to patients with HCAP.
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