Time trends and predictors of mortality from ill-defined causes in old age: 9 year folllow-up of the Bambuí cohort study (Brazil)

The study objective was to examine differentials in time trends and predictors of deaths assigned to symptoms, signs and ill-defined conditions in comparison with other ill-defined conditions (ill-defined cardiovascular diseases, cancer and injury) in a population-based cohort study. Of 1,606 baseline participants aged 60 years and over, 524 died during 9-year follow-up and were included in this study. Deaths coded to "symptoms" declined by 77% in the period from 1997-1999 to 2003-2005. Deaths coded to other ill-defined conditions remained unchanged. The calendar period 2003-2005 (RR = 0.25; 95%CI: 0.09-0.70) and in-hospital deaths (RR = 0.16; 95%CI: 0.08-0.34) were independently associated with "symptoms", but not with other ill-defined conditions. Baseline socio-demographic characteristics and chronic diseases were not predictors of these outcomes. International and national agencies have focused on the reduction of deaths assigned to "symptoms" to improve the registration of vital statistics, while other ill-defined conditions have received little attention. Our data provide evidence supporting the need to redress this situation.

Mortes evitáveis em menores de um ano, Brasil, 1997 a 2006: contribuições para a avaliação de desempenho do Sistema Único de Saúde

Os óbitos de menores de um ano foram classificados em causas evitáveis, mal definidas e não evitáveis empregando a Lista Brasileira de Mortes Evitáveis, entre 1997-2006. Foram calculados tendências dos coeficientes de mortalidade infantil por causas de morte e se usou regressão não linear para avaliação de tendência. As causas evitáveis e as causas mal definidas apresentaram significativa redução (p < 0,001). As causas reduzíveis de mortalidade apresentaram redução de 37%. A mortalidade por causas reduzíveis por adequada atenção ao parto declinou em 27,7%; adequada atenção ao recém-nascido, 42,5%; e por adequada atenção à gestação cresceu 28,3%. Concluiu-se que os serviços de saúde contribuíram para a redução da mortalidade infantil. O declínio das causas mal definidas de morte indica ampliação do acesso aos serviços de saúde. O aumento do acesso e atenção ao parto e aos cuidados com recém-nascido contribuíram para a redução de óbitos infantis. O aumento da mortalidade por adequada atenção à gestação revela a necessidade de aprimoramento da atenção pré-natal.

Avaliação das declarações de nascido vivo como fonte de informação sobre defeitos congênitos

OBJETIVO: Estimar a prevalência de defeitos congênitos (DC) em uma coorte de nascidos vivos (NV) vinculando-se os bancos de dados do Sistema de Informação de Mortalidade (SIM) e do Sistema de Informação sobre Nascidos Vivos (SINASC). MÉTODOS: Estudo descritivo para avaliar as declarações de nascido vivo como fonte de informação sobre DC. A população de estudo é uma coorte de NV hospitalares do 1º semestre de 2006 de mães residentes e ocorridos no Município de São Paulo no período de 01/01/2006 a 30/06/2006, obtida por meio da vinculação dos bancos de dados das declarações de nascido vivo e óbitos neonatais provenientes da coorte. RESULTADOS: Os DC mais prevalentes segundo o SINASC foram: malformações congênitas (MC) e deformidades do aparelho osteomuscular (44,7%), MC do sistema nervoso (10,0%) e anomalias cromossômicas (8,6%). Após a vinculação, houve uma recuperação de 80,0% de indivíduos portadores de DC do aparelho circulatório, 73,3% de DC do aparelho respiratório e 62,5% de DC do aparelho digestivo. O SINASC fez 55,2% das notificações de DC e o SIM notificou 44,8%, mostrando-se importante para a recuperação de informações de DC. Segundo o SINASC, a taxa de prevalência de DC na coorte foi de 75,4%00 NV; com os dados vinculados com o SIM, essa taxa passou para 86,2%00 NV. CONCLUSÕES: A complementação de dados obtida pela vinculação SIM/SINASC fornece um perfil mais real da prevalência de DC do que aquele registrado pelo SINASC, que identifica os DC mais visíveis, enquanto o SIM identifica os mais letais, mostrando a importância do uso conjunto das duas fontes de dados.

Influência do local de nascimento e do transporte sobre a morbimortalidade de recém-nascidos prematuros

OBJETIVO: Verificar a influência do local de nascimento e do transporte sobre a morbimortalidade de recém-nascidos prematuros na Região Sul do Brasil. MÉTODOS: Estudo de coorte com recém-nascidos prematuros transferidos para a unidade de tratamento intensivo de referência (grupo transporte = 61), tendo sido acompanhados até a alta. Os dados sobre o atendimento no hospital de origem e transporte foram obtidos no momento da internação. Esse grupo foi comparado com neonatos da maternidade de referência, pareados por idade gestacional (grupo controle = 123), tendo como desfecho primário o óbito e desfechos secundários as alterações da glicemia, temperatura e saturação de oxigênio no momento da internação e a incidência de enterocolite necrosante, displasia broncopulmonar e sepses. Na associação entre as variáveis e o desfecho, foi utilizado o risco relativo. Foi adotado um nível de significância de α = 5% e β = 90%. RESULTADOS: A distância média percorrida foi de 91 km. A idade gestacional média foi de 34 semanas. Entre os recém-nascidos transferidos, 23% (n = 14) não tiveram atendimento pediátrico na sala de parto. No transporte, 33% dos recém-nascidos foram acompanhados por pediatra, e os equipamentos utilizados foram: incubadora (57%), bomba de infusão (13%), oxímetro (49%) e aparelho para aferição da glicemia (21%). O grupo transporte apresentou maior incidência de hiperglicemia, risco relativo (RR) = 3,2 (2,3-4,4), hipoglicemia, RR = 2,4 (1,4-4,0), hipertermia, RR = 2,5 (1,6-3,9), e hipoxemia, RR = 2,2 (1,6-3,0). Foram observados 18% de óbitos no grupo dos transferidos e 8,9% no grupo controle, RR = 2,0 (1,0-2,6). CONCLUSÕES: A pesquisa expõe deficiências no atendimento e transporte dos recém-nascidos, sendo necessária uma melhor organização do atendimento perinatal e do transporte na região nordeste do Rio Grande do Sul.

Childhood and adolescent obesity and adult mortality: a systematic review of cohort studies

This systematic review addressed cohort studies on obesity in childhood and adolescence and adult mortality, published from January 1990 to March 2007. We searched the PubMed database with the following uniterms: obesity, mortality, child, adolescent; obesity and mortality; overweight and mortality. References were also analyzed. The age limit was 2 to 18 years. Quality of the articles was assessed, and eight were identified and reviewed. All used weight and stature for determination of obesity, and seven used body mass index (BMI). The quality score varied from 9 to 17. Evidence of association between obesity in childhood and adolescence and adult mortality should be viewed with caution. Use of BMI and potential confounders were discussed. Further research is needed to analyze the relationship between childhood and adolescent obesity and adult mortality.

Matched case-control study evaluating the frequency of the main agents associated with neonatal diarrhea in piglets

A case-control study was carried out in litters of 1 to 7-day-old piglets to identify the main infectious agents involved with neonatal diarrhea in pigs. Fecal samples (n=276) from piglets were collected on pig farms in the State of Rio Grande do Sul, Brazil, from May to September 2007. Litters with diarrhea were considered cases (n=129) and normal litters (n=147) controls. The samples were examined by latex agglutination test, PAGE, conventional isolating techniques, ELISA, PCR, and microscopic methods in order to detect rotavirus, bacterial pathogens (Escherichia coli, Clostridium perfringens type A and C, and Clostridium difficile), and parasites (Coccidian and Cryptosporidium spp.). Outbreaks of diarrhea were not observed during sampling. At least one agent was detected in fecal samples on 25 out of 28 farms (89.3%) and in 16 farms (57.1%) more than one agent was found. The main agents diagnosed were Coccidia (42.86%) and rotavirus (39.29%). The main agents identified in litters with diarrhea were Clostridium difficile (10.6%), Clostridium perfringens type A (8.8%) and rotavirus (7.5%); in control litters, Clostridium difficile (16.6%) and Coccidian (8.5%). Beta hemolytic Escherichia coli and Clostridium perfringens type C were not detected. When compared with controls, no agent was significantly associated with diarrhea in case litters. These findings stress the need for caution in the interpretation of laboratorial diagnosis of mild diarrhea in neonatal pigs, as the sole detection of an agent does not necessarily indicate that it is the cause of the problem.

Uso de hidrolizado proteico en los pacientes de una unida de terapia intensiva neonatal

Introducción. La leche humana es el primer alimento escogido para alimentar a los recién nacidos (RN), especialmente a los prematuros (RNPT y a los de peso muy bajo (RNMBP). Cuando esta leche no está disponible, deben ser recetadas fórmulas especializadas, que promuevan un crecimiento y desarrollo adecuados. El uso de los hidrolizados proteicos (HP) en la UTI neonatal ha sido promovido, debido al riesgo potencial que los RNPT/MBP presentan, por la inmadurez gastrointestinal, problemas de absorción e intolerancia alimentaria. Sin embargo, tales formulaciones no fueran elaboradas para atender las necessidades específicas de estos niños, y pueden, cuando son utilizadas, ocasionar un déficit nutricional. Objetivo. Comparar la progresión de la nutrición enteral (NE) (a través de la oferta de volumen, calorías y proteínas), la evolución ponderal, y las complicaciones clínicas entre recién nacidos de peso muy bajo (RNPMB) alimentados con fórmula para prematuros (FP) e hidrolizado proteico (HP) en la UTI neonatal. Casuística y métodos. Fueran estudiados dos grupos de RNPMB: grupo 1:13RNPMB con edad gestacional media de nacimiento de 30 semanas, peso medio de nacimiento de 1 167 gramos, que recibieron FP. Grupo 2:8 RN con edad gestacional media de nacimiento de 29 semanas, peso medio de nacimiento de 1 141 gramos, alimentados con HP. Las ofertas de volumen, la de calorías y la de proteínas fueran diariamente calculadas para todos los niños en ambos grupos. La nutrición parenteral (NP) que complementaría a la terapia nutricional en las primeras semanas, también fue calculada. Los RNMBP fueron pesados diariamente, por la mañana, en balanza digital (escala de 10 g) debidamente calibrada. El peso medio diario fue calculado hasta el dia 15 de vida. Fueron construidas curvas de crescimento, a través del polinomio de segundo grado para ambos grupos. Para el análisis estadístico se utilizó el test de medias. Resultados. ) La oferta media de volumen, calorías y proteínas fue mayos en la primera semana en el grupo 2, pero de una forma no significativa (p=0.38; 0.34 y 0.05, respectivamente). En las semanas subsequentes, no hubo diferencias significativas en la progresión de NE entre los grupos. No fueron observadas complicaciones clínicas, sólo ocurrieron dos casos de distensión abdominal en el grupo 1, pero no fueron caracterizados como enterocolitis necrosante (ECN). No hubo diferencias estadísticas relacionadas con el aumento de peso entre los dos grupos durante el periodo de estudio; sin embargo, el grupo 1 presentó una tendencia de mejor evolución. conclusión. La prograsión de la NE fue semejante con la utilización de los dos tipos de fórmulas, no feron encontradas diferencias en el aumento de peso de los grupos, y no hubo complicaciones clínicas en ninguno de ellos. No hubo ventajas en el uso del HP en la UTI neonatal; por tanto, no está indicado para RNPMB, sin disfunción intestinal, debido a que su composición nutricional no prevé las necesidades de este grupo de niños

TCF7L2 Polymorphism rs7903146 Is Associated with Coronary Artery Disease Severity and Mortality

Background: TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. Methods and Results: two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR = 2.32 95% CI 1.27-4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). Conclusions: rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets.

Maternal immunization with ovalbumin prevents neonatal allergy development and up-regulates inhibitory receptor Fc gamma RIIB expression on B cells

Background: Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA) on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period. Results: Maternal immunization with OVA showed increased levels of Fc gamma RIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-gamma-secreting T cells and IL-4 and IL-12-secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specifc IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced Fc gamma RIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers. Conclusion: Maternal immunization upregulates the inhibitory Fc gamma RIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.

Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods. METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's files and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specific positive predictive value, negative predictive value, and accuracy. RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%), and PCR, 6/77 (8%). Only one patient had positive immunohistochemical findings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity, 88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%. CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low. (C) 2009 The WJG Press and Baishicleng. All rights reserved.

Analysis of the histologic features in the differential diagnosis of intrahepatic neonatal cholestasis

AIM: To compare the histologic features of the liver in intrahepatic neonatal cholestasis (IHNC) with infectious, genetic-endocrine-metabolic, and idiopathic etiologies. METHODS: Liver biopsies from 86 infants with IHNC were evaluated. The inclusion criteria consisted of jaundice beginning at 3 mo of age and a hepatic biopsy during the 1st year of life. The following histologic features were evaluated: cholestasis, eosinophilia, giant cells, erythropoiesis, siderosis, portal fibrosis, and the presence of a septum. RESULTS: Based on the diagnosis, patients were classified into three groups: group 1 (infectious; n = 18), group 2 (genetic-endocrine-metabolic; n = 18), and group 3 (idiopathic; n = 50). There were no significant differences with respect to the following variables: cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and presence of a septum. A significant difference was observed with respect to erythropoiesis, which was more severe in group 1 (Fisher's exact test, P = 0.016). CONCLUSION: A significant difference was observed in IHNC of infectious etiology, in which erythropoiesis was more severe than that in genetic-endocrine-metabolic and idiopathic etiologies, whereas there were no significant differences among cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and the presence of a septum. (C) 2009 The WIG Press and Baishideng. All rights reserved.

Trends in socioeconomic inequalities in cancer mortality in Barcelona: 1992-2003

Background: The objective of this study was to assess trends in cancer mortality by educational level in Barcelona from 1992 to 2003. Methods: The study population comprised Barcelona inhabitants aged 20 years or older. Data on cancer deaths were supplied by the system of information on mortality. Educational level was obtained from the municipal census. Age-standardized rates by educational level were calculated. We also fitted Poisson regression models to estimate the relative index of inequality (RII) and the Slope Index of Inequalities (SII). All were calculated for each sex and period (1992-1994, 1995-1997, 1998-2000, and 2001-2003). Results: Cancer mortality was higher in men and women with lower educational level throughout the study period. Less-schooled men had higher mortality by stomach, mouth and pharynx, oesophagus, larynx and lung cancer. In women, there were educational inequalities for cervix uteri, liver and colon cancer. Inequalities of overall and specific types of cancer mortality remained stable in Barcelona; although a slight reduction was observed for some cancers. Conclusion: This study has identified those cancer types presenting the greatest inequalities between men and women in recent years and shown that in Barcelona there is a stable trend in inequalities in the burden of cancer.

Inequalities in mortality of men by oral and pharyngeal cancer in Barcelona, Spain and Sao Paulo, Brazil, 1995-2003

Background: Large inequalities of mortality by most cancers in general, by mouth and pharynx cancer in particular, have been associated to behaviour and geopolitical factors. The assessment of socioeconomic covariates of cancer mortality may be relevant to a full comprehension of distal determinants of the disease, and to appraise opportune interventions. The objective of this study was to compare socioeconomic inequalities in male mortality by oral and pharyngeal cancer in two major cities of Europe and South America. Methods: The official system of information on mortality provided data on deaths in each city; general censuses informed population data. Age-adjusted death rates by oral and pharyngeal cancer for men were independently assessed for neighbourhoods of Barcelona, Spain, and Sao Paulo, Brazil, from 1995 to 2003. Uniform methodological criteria instructed the comparative assessment of magnitude, trends and spatial distribution of mortality. General linear models assessed ecologic correlations between death rates and socioeconomic indices (unemployment, schooling levels and the human development index) at the inner-city area level. Results obtained for each city were subsequently compared. Results: Mortality of men by oral and pharyngeal cancer ranked higher in Barcelona (9.45 yearly deaths per 100,000 male inhabitants) than in Spain and Europe as a whole; rates were on decrease. Sao Paulo presented a poorer profile, with higher magnitude (11.86) and stationary trend. The appraisal of ecologic correlations indicated an unequal and inequitably distributed burden of disease in both cities, with poorer areas tending to present higher mortality. Barcelona had a larger gradient of mortality than Sao Paulo, indicating a higher inequality of cancer deaths across its neighbourhoods. Conclusion: The quantitative monitoring of inequalities in health may contribute to the formulation of redistributive policies aimed at the concurrent promotion of wellbeing and social justice. The assessment of groups experiencing a higher burden of disease can instruct health services to provide additional resources for expanding preventive actions and facilities aimed at early diagnosis, standardized treatments and rehabilitation.

Trends in dermatomyositis- and polymyositis-related mortality in the state of Sao Paulo, Brazil, 1985-2007: multiple cause-of-death analysis

Background: Dermatomyositis (DM) and polymyositis (PM) are rare systemic autoimmune rheumatic diseases with high fatality rates. There have been few population-based mortality studies of dermatomyositis and polymyositis in the world, and none have been conducted in Brazil. The objective of the present study was to employ multiple-cause of-death methodology in the analysis of trends in mortality related to dermatomyositis and polymyositis in the state of Sao Paulo, Brazil, between 1985 and 2007. Methods: We analyzed mortality data from the Sao Paulo State Data Analysis System, selecting all death certificates on which DM or PM was listed as a cause of death. The variables sex, age and underlying, associated or total mentions of causes of death were studied using mortality rates, proportions and historical trends. Statistical analysis were performed by chi-square and H Kruskal-Wallis tests, variance analysis and linear regression. A p value less than 0.05 was regarded as significant. Results: Over a 23-year period, there were 318 DM-related deaths and 316 PM-related deaths. Overall, DM/PM was designated as an underlying cause in 55.2% and as an associated cause in 44.8%; among 634 total deaths females accounted for 71.5%. During the study period, age-and gender-adjusted DM mortality rates did not change significantly, although PM as an underlying cause and total mentions of PM trended lower (p < 0.05). The mean ages at death were 47.76 +/- 20.81 years for DM and 54.24 +/- 17.94 years for PM (p = 0.0003). For DM/PM, respectively, as underlying causes, the principal associated causes of death were as follows: pneumonia (in 43.8%/33.5%); respiratory failure (in 34.4%/32.3%); interstitial pulmonary diseases and other pulmonary conditions (in 28.9%/17.6%); and septicemia (in 22.8%/15.9%). For DM/PM, respectively, as associated causes, the following were the principal underlying causes of death: respiratory disorders (in 28.3%/26.0%); circulatory disorders (in 17.4%/20.5%); neoplasms (in 16.7%/13.7%); infectious and parasitic diseases (in 11.6%/9.6%); and gastrointestinal disorders (in 8.0%/4.8%). Of the 318 DM-related deaths, 36 involved neoplasms, compared with 20 of the 316 PM-related deaths (p = 0.03). Conclusions: Our study using multiple cause of deaths found that DM/PM were identified as the underlying cause of death in only 55.2% of the deaths, indicating that both diseases were underestimated in the primary mortality statistics. We observed a predominance of deaths in women and in older individuals, as well as a trend toward stability in the mortality rates. We have confirmed that the risk of death is greater when either disease is accompanied by neoplasm, albeit to lesser degree in individuals with PM. The investigation of the underlying and associated causes of death related to DM/PM broaden the knowledge of the natural history of both diseases and could help integrate mortality data for use in the evaluation of control measures for DM/PM.

Expression of an activating mutation in the gene encoding the K(ATP) channel subunit Kir6.2 in mouse pancreatic beta cells recapitulates neonatal diabetes

Neonatal diabetes is a rare monogenic form of diabetes that usually presents within the first six months of life. It is commonly caused by gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of the plasmalemmal ATP-sensitive K(+) (K(ATP)) channel. To better understand this disease, we generated a mouse expressing a Kir6.2 mutation (V59M) that causes neonatal diabetes in humans and we used Cre-lox technology to express the mutation specifically in pancreatic beta cells. These beta-V59M mice developed severe diabetes soon after birth, and by 5 weeks of age, blood glucose levels were markedly increased and insulin was undetectable. Islets isolated from beta-V59M mice secreted substantially less insulin and showed a smaller increase in intracellular calcium in response to glucose. This was due to a reduced sensitivity of K(ATP) channels in pancreatic beta cells to inhibition by ATP or glucose. In contrast, the sulfonylurea tolbutamide, a specific blocker of K(ATP) channels, closed K(ATP) channels, elevated intracellular calcium levels, and stimulated insulin release in beta-V59M beta cells, indicating that events downstream of K(ATP) channel closure remained intact. Expression of the V59M Kir6.2 mutation in pancreatic beta cells alone is thus sufficient to recapitulate the neonatal diabetes observed in humans. beta-V59M islets also displayed a reduced percentage of beta cells, abnormal morphology, lower insulin content, and decreased expression of Kir6.2, SUR1, and insulin mRNA. All these changes are expected to contribute to the diabetes of beta-V59M mice. Their cause requires further investigation.