Prolonged retention after aggregation into secretory granules of human R183H-growth hormone (GH), a mutant that causes autosomal dominant GH deficiency type II

Human R183H-GH causes autosomal dominant GH deficiency type II. Because we show here that the mutant hormone is fully bioactive, we have sought to locate an impairment in its progress through the secretory pathway as assessed by pulse chase experiments. Newly synthesized wild-type and R183H-GH were stable when expressed transiently in AtT20 cells, and both formed equivalent amounts of Lubrol-insoluble aggregates within 40 min after synthesis. There was no evidence for intermolecular disulfide bond formation in aggregates of wild-type hormone or the R183H mutant. Both wildtype and R183H-GH were packaged into secretory granules, assessed by the ability of 1 mm BaCl2 to stimulate release and by immunocytochemistry. The mutant differed from wildtype hormone in its retention in the cells after packaging into secretory granules; 50% more R183H-GH than wild-type aggregates were retained in AtT20 cells 120 min after synthesis, and stimulated release of R183H-GH or a mixture of R183H-GH and wild-type that had been retained in the cell was reduced. The longer retention of R183H-GH aggregates indicates that a single point mutation in a protein contained in secretory granules affects the rate of secretory granule release.

Influence of ageing, heat shock treatment and in vivo total antioxidant status on gene-expression profile and protein synthesis in human peripheral lymphocytes

Ageing results in a progressive, intrinsic and generalised imbalance of the control of regulatory systems. A key manifestation of this complex biological process includes the attenuation of the universal stress response. Here we provide the first global assessment of the ageing process as it affects the heat shock response, utilising human peripheral lymphocytes and cDNA microarray analysis. The genomic approach employed in our preliminary study was supplemented with a proteomic approach. In addition, the current study correlates the in vivo total antioxidant status with the age-related differential gene expression as well as the translational kinetics of heat shock proteins (hsps). Most of the genes encoding stress response proteins on the 4224 element microarray used in this study were significantly elevated after heat shock treatment of lymphocytes obtained from both young and old individuals albeit to a greater extent in the young. Cell signaling and signal transduction genes as well as some oxidoreductases showed varied response. Results from translational kinetics of induction of major hsps, from 0 to 24 It recovery period were broadly consistent with the differential expression of HSC 70 and HSP 40 genes. Total antioxidant levels in plasma from old individuals were found to be significantly lower by comparison with young, in agreement with the widely acknowledged role of oxidant homeostasis in the ageing process. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Quadriceps activation in closed and in open kinetic chain exercise

Purpose: For treatment of various knee disorders, muscles are trained in open or closed kinetic chain tasks. Coordination between the heads of the quadriceps muscle is important for stability and optimal joint loading for both the tibiofemoral and the patellofemoral joint. The aim of this study was to examine whether the quadriceps femoris muscles are activated differently in open versus closed kinetic chain tasks. Methods: Ten healthy men and women (mean age 28.5 +/- 0.7) extended the knees isometrically in open and closed kinetic chain tasks in a reaction time paradigm using moderate force. Surface electromyography (EMG) recordings were made from four different parts of the quadriceps muscle. The onset and amplitude of EMG and force data were measured. Results: In closed chain knee extension, the onset of EMG activity of the four different muscle portions of the quadriceps was more simultaneous than in the open chain. In open chain, rectus femoris (RF) had the earliest EMG onset while vastus medialis obliquus was activated last (7 +/- 13 ms after RF EMG onset) and with smaller amplitude (40 +/- 30% of maximal voluntary contraction (MVC)) than in closed chain (46 +/- 43% MVC). Conclusions: Exercise in closed kinetic chain promotes more balanced initial quadriceps activation than does exercise in open kinetic chain. This may be of importance in designing training programs aimed toward control of the patellofemoral joint.

Quality of Life and Colorectal Cancer: a Review

Objectives: To describe what is known of quality of life for colorectal cancer patients, to review what has been done in the Australian setting and to identify emerging directions for future research to address current gaps in knowledge. Method: A literature search (using Medline, PsychInfo, CINAHL and Sociological Abstracts) was conducted and 41 articles identified for review. Results: Three key areas relating to quality of life in colorectal cancer patients emerged from the literature review: the definition and measurement of quality of life; predictors of quality of life; and the relationship of quality of life to survival. Results of existing studies are inconsistent in relation to quality of life over time and its relationship to survival. Small sample sizes and methodological limitations make interpretation difficult. Conclusions: There is a need for large-scale, longitudinal, population-based studies describing the quality of life experienced by colorectal cancer patients and its determinants. Measurement and simultaneous adjustment for potential confounding factors would productively advance knowledge in this area, as would an analysis of the economic cost of morbidity to the community and an assessment of the cost effectiveness of proposed interventions. Implications: As the Australian population ages, the prevalence of colorectal cancer within the community will increase. This burden of disease presents as a priority area for public health research. An improved understanding of quality of life and its predictors will inform the development and design of supportive interventions for those affected by the disease.

Effect of functional gain on satisfaction with medical rehabilitation after stroke

Objective: To examine the association between gain in motor and cognitive functional status with patient satisfaction 3-6 mo after rehabilitation discharge. Design: Patient satisfaction and changes in functional status were examined in 18,375 patients with stroke who received inpatient medical rehabilitation. Information was obtained from 144 hospitals and rehabilitation facilities contributing records to the Uniform Data System for Medical Rehabilitation and the National Follow-up Services. Results: Data analysis revealed significant (P < 0.05) differences in satisfaction responses based on whether information was collected from patient self-report or from a family member proxy, and the two subsets were analyzed separately. Logistic regression revealed the following significant predictors of satisfaction for data collected from stroke patients: cognitive and motor gain, rehospitalization, who the patient was living with at follow-up, age, and follow-up therapy. In the patient-reported data subset, compared with patients who showed improved cognitive or motor functional status, those with no change, respectively, had a 31% and 33% reduced risk of dissatisfaction. In addition, rehospitalized patients had a higher risk of dissatisfaction. For the proxy reported data subset, significant influences on satisfaction were health maintenance, rehospitalization, stroke type, ethnicity, cognitive FIM(TM) gain, length of stay, and follow-up therapy. Conclusions: Ratings of satisfaction with rehabilitation services were affected by change in functional status and whether the information was collected from patient rating or proxy response.

Effect of fatigue on torque output and electromyographic measures of trunk muscles during isometric axial rotation

Objectives: To examine the changes in torque output resulting from fatigue, as well as changes in electromyographic measures of trunk muscles during isometric axial rotation and to compare these changes between directions of axial rotation. Design: Subjects performed fatiguing right and left isometric axial rotation of the trunk at 80% of maximum voluntary contraction while standing upright. Setting: A rehabilitation center. Participants: Twenty-three men with no history of back pain. Interventions: Not applicable. Main Outcome Measures: Surface electromyographic Signals were recorded from 6 trunk muscles bilaterally. The primary torque in the transverse plane and the coupling torques in sagittal and coronal planes were also measured. Results: During the fatiguing axial rotation contraction, coupling torques of both sagittal and coronal planes were slightly decreased and no difference was found between directions of axial rotation. Decreasing median frequency and an increase in electromyographic amplitude were also found in trunk muscles with different degrees of changes in individual muscles. There were significant differences (P

O modelo de precificação de ativos de capital: teoria e evidências

Distante quatro décadas de seu aparecimento, o modelo de precificação de ativos de capital proposto pelo Nobel William Sharpe e por John Lintner, conhecido como CAPM, é ainda o modelo mais amplamente utilizado na estimativa do custo de capital de empresas e na avaliação de carteiras. O fato se deve às poderosas previsões permitidas pelo modelo sobre a medida do risco e a relação entre risco e retorno. O objetivo deste artigo é mostrar que o CAPM apresenta algumas falhas empíricas associadas a simplifi cações teóricas e difi culdades de implementação de testes que sejam válidos para o modelo. A conclusão do artigo é que as limitações do CAPM representam desafi os a serem explicados por modelos alternativos.

Formação de estratégia nas micro e pequenas empresas: um estudo no centro-oeste mineiro

Muito se tem dito e escrito sobre as peculiaridades da administração estratégica nas micro e pequenas empresas (MPE). Pouco, entretanto, tem sido feito em termos de trabalho empírico, de cunho quantitativo, quando comparado com o volume de pesquisa que trata de grandes empresas. Nesse sentido, o presente artigo buscou explorar o processo de formação de estratégias nessas empresas, descrevendo seus principais aspectos e, principalmente, verificando se há características desse processo que podem ser associadas a níveis de desempenho acima (e/ou abaixo) da média. Para tanto, utilizou-se a análise de regressão linear múltipla para entender as relações existentes entre as variáveis do processo de formação da estratégia consideradas no estudo e o desempenho; e, ainda, a análise discriminante para determinar os indicadores que diferenciam os grupos de empresas com desempenho acima e abaixo da média. Os resultados apontaram uma tendência à utilização de processos de formação de estratégia deliberados e formais. Por outro lado, reconhecemos também, uma tendência de inovação e mudança. O desempenho acima da média das micro e pequenas empresas, ao que parece, é resultado de uma receita balanceada desses dois ingredientes.

Mortalidade em idosos por diabetes mellitus como causa básica e associada

OBJETIVO:Analisar a mortalidade por diabetes mellitus em idosos e a subenumeração do diabetes como causa do óbito de acordo com estatísticas baseadas unicamente em causa básica de óbito. MÉTODOS:Foram revisadas todas as 2.974 declarações de óbito ocorridas em 1994 de idosos residentes em um núcleo habitacional localizado na cidade do Rio de Janeiro, RJ. Destas, foram estudados 291 óbitos, tendo o diabetes mellitus como causa básica (150) e associada (141). A proporção de óbitos em que a diabetes aparece como causa básica em relação ao total de óbitos por diabetes foi calculada de forma global e segundo sexo e faixa etária. RESULTADOS:Dos 291 óbitos estudados, 138 (47,4%) ocorreram em homens, e 153, em mulheres (52,6%). As taxas de mortalidade apresentaram crescimento contínuo com o avançar da idade, sendo superiores no sexo masculino, embora a diferença entre sexos tenha sido menor para a análise baseada unicamente na causa básica. Observou-se proporção elevada de óbitos domiciliares (22%). A proporção de óbitos por diabetes como causa básica foi de 51,5%, sendo maior nas mulheres do que nos homens. CONCLUSÕES:A análise das estatísticas de mortalidade baseadas unicamente na causa básica do óbito pode levar a perfis distorcidos, em função da subenumeração não ocorrer aleatoriamente. Estudos adicionais em coortes de idosos brasileiros diabéticos são necessários para permitir uma avaliação mais acurada da mortalidade nesse grupo.

Aplicação de medidas de ajuste de risco para a mortalidade após fratura proximal de fêmur

OBJETIVO: Analisar os fatores associados à mortalidade em pacientes para tratamento da fratura proximal do fêmur e as diferentes formas de ajuste de risco. MÉTODOS: Estudo de coorte não-concorrente com 390 pacientes com 50 anos ou mais. Os pacientes foram identificados no Sistema de Informações Hospitalares do Sistema Único de Saúde, internados para correção cirúrgica da fratura proximal do fêmur em um hospital universitário do município do Rio de Janeiro, entre 1995 e 2000. Foram levantados dados complementares nos prontuários desses pacientes e elaborados modelos de regressão logística para a chance de óbito em 90 dias após a data da admissão, segundo perfil dos pacientes e do tratamento. Foram calculados índices de classificação da gravidade do paciente. RESULTADOS: A taxa de mortalidade foi de 7,4% e os fatores que tiveram efeito sobre o óbito foram: idade (OR=1,06; IC 95%: 1,02;1,11), quantidade de comorbidades (OR=1,44; IC 95%: 1,12;1,69), índice de comorbidade de Charlson acima de 2 (OR=6,67; IC 95%: 2,98;22,16) e intervalo de tempo para a realização da cirurgia (OR=1,04; IC 95%:1,02;1,07). CONCLUSÕES: A quantidade de comorbidades e o índice de comorbidade de Charlson auxiliaram na predição da mortalidade.

Public health and the knowledge industry

Knowledge plays an important role in health care. The production and diffusion of health-related knowledge are increasingly under the control of private commercial interests, which are characterized by conflicts of interests that result in abuses of power. Considerable research has been done on the medical-industrial complex and its role in the production of power imbalances and the consequent abuses, but little attention has been dedicated to the role played by the publishing industry, which can be subject to the same problems. The widely diffused idea that "frequent and major changes" occur in medicine, albeit unsupported by clearcut evidence, is an effective marketing tool for both the pharmaceutical and publishing industries, who feed and thrive on physicians' insecurities. The production and distribution of knowledge should be addressed as a strategic component of public health.