Identification of "pathologs" (disease-related genes) from the RIKEN mouse cDNA dataset using human curation plus FACTS, a new biological information extraction system

Background: A major goal in the post-genomic era is to identify and characterise disease susceptibility genes and to apply this knowledge to disease prevention and treatment. Rodents and humans have remarkably similar genomes and share closely related biochemical, physiological and pathological pathways. In this work we utilised the latest information on the mouse transcriptome as revealed by the RIKEN FANTOM2 project to identify novel human disease-related candidate genes. We define a new term patholog to mean a homolog of a human disease-related gene encoding a product ( transcript, anti-sense or protein) potentially relevant to disease. Rather than just focus on Mendelian inheritance, we applied the analysis to all potential pathologs regardless of their inheritance pattern. Results: Bioinformatic analysis and human curation of 60,770 RIKEN full-length mouse cDNA clones produced 2,578 sequences that showed similarity ( 70 - 85% identity) to known human-disease genes. Using a newly developed biological information extraction and annotation tool ( FACTS) in parallel with human expert analysis of 17,051 MEDLINE scientific abstracts we identified 182 novel potential pathologs. Of these, 36 were identified by computational tools only, 49 by human expert analysis only and 97 by both methods. These pathologs were related to neoplastic ( 53%), hereditary ( 24%), immunological ( 5%), cardio-vascular (4%), or other (14%), disorders. Conclusions: Large scale genome projects continue to produce a vast amount of data with potential application to the study of human disease. For this potential to be realised we need intelligent strategies for data categorisation and the ability to link sequence data with relevant literature. This paper demonstrates the power of combining human expert annotation with FACTS, a newly developed bioinformatics tool, to identify novel pathologs from within large-scale mouse transcript datasets.

A comparison of lipid variables as predictors of cardiovascular disease in the Asia Pacific Region

PURPOSE: Many guidelines advocate measurement of total or low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglycerides (TG) to determine treatment recommendations for preventing coronary heart disease (CHD) and cardiovascular disease (CVD). This analysis is a comparison of lipid variables as predictors of cardiovascular disease. METHODS: Hazard ratios for coronary and cardiovascular deaths by fourths of total cholesterol (TC), LDL, HDL, TG, non-HDL, TC/HDL, and TG/HDL values, and for a one standard deviation change in these variables, were derived in an individual participant data meta-analysis of 32 cohort studies conducted in the Asia-Pacific region. The predictive value of each lipid variable was assessed using the likelihood ratio statistic. RESULTS: Adjusting for confounders and regression dilution, each lipid variable had a positive (negative for HDL) log-linear association with fatal CHD and CVD. Individuals in the highest fourth of each lipid variable had approximately twice the risk of CHD compared with those with lowest levels. TG and HDL were each better predictors of CHD and CVD risk compared with TC alone, with test statistics similar to TC/HDL and TG/HDL ratios. Calculated LDL was a relatively poor predictor. CONCLUSIONS: While LDL reduction remains the main target of intervention for lipid-lowering, these data support the potential use of TG or lipid ratios for CHD risk prediction. (c) 2005 Elsevier Inc. All rights reserved.

BUPROPION/NALTREXONE FIXED-DOSE COMBINATION FOR THE TREATMENT OF OBESITY

The combination of bupropion and naltrexone is one of the most promising new possibilities for the treatment of obesity in an era of increasing prevalence of this disease and decreasing options for its pharmacological management. Although approved by FDA panel members, it was temporally rejected by the FDA afterwards, who demanded more cardiovascular safety data for its commercialization. This monograph will focus on the physiology involved in its mechanisms of action and results of clinical trials.

Prevalence of Alcohol-Related Problems in an Elderly Population and Their Association With Cognitive Impairment and Dementia

Background: Studies investigating the association between alcohol use and cognitive disorders in the elderly population have produced divergent results. Moreover, the role of alcohol in cognitive dysfunction is not clear. The aims of this study were to estimate the prevalence of alcohol-related problems in an elderly population from Brazil and to investigate their association with cognitive and functional impairment (CFI) and dementia. Methods: A community-based cross-sectional study was performed. A sample of 1,145 elderly people was examined in 2 phases. Several instruments were utilized in the first phase: the CAGE questionnaire was used to identify potential cases of alcohol-related problems, and a screening test for dementia was used to estimate CFI. The CAMDEX interview (Cambridge Examination) and DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) criteria were used for the clinical diagnosis of dementia in the second phase. Results: ""Heavy alcohol use"" (CAGE >= 2) was found in 92 subjects (prevalence: 8.2%). It was associated with gender (males, p < 0.001), low education (only in females, p = 0.002), and low socioeconomic level (p = 0.001, in females; p = 0.002, in males). The Mini Mental State Examination exhibited a nonlinear relationship with alcohol-related problems in females; ""mild-moderate alcohol use"" (CAGE < 2) presented the highest score. A significant association between alcohol-related problems and cognitive dysfunction was found only in females. ""Heavy alcohol use"" was associated with higher CFI and dementia rates compared to ""mild-moderate alcohol use"" (p = 0.003 and p < 0.001, respectively). ""Mild-moderate alcohol use"" had a tendency of association with lower CFI and dementia rates when compared to ""no alcohol use"" (p = 0.063 and 0.050, respectively). Conclusion: Our findings suggest that alcohol use does not have a linear relationship with cognitive decline.

Prevalence of Epilepsy in Children From a Brazilian Area of High Deprivation

This study assessed the prevalence rate of epilepsy and its causes in children and adolescents in one area of high deprivation in Sao Paulo, Sao Paulo, in Southeast Brazil. Between July 2005 and June 2006, 4947 families from a population of 22,013 inhabitants (including 10,405 children and adolescents between the ages of 0 and 16 years) living in the shantytown of Paraisopolis, were interviewed. In the first phase, a validated questionnaire was administered, to identify the occurrence of seizures. In the second phase, clinical history, neurologic examination, electroencephalography, and structural neuroimaging were performed. The diagnosis of epilepsy, including etiology, seizure types, and epileptic syndrome classification, was according to criteria of the International League Against Epilepsy. The screening phase identified 353 presumptive cases. In the second phase, 101 of these cases (33.8%) received the diagnosis of epilepsy. Crude prevalence of epilepsy was 9.7/1000 and prevalence of active epilepsy was 8.7/1000. Partial seizures were the most frequent seizure type (62/101). Symptomatic focal epilepsy was the most common form, and hypoxic-ischemic encephalopathy the most common etiology, reflecting the socioeconomic conditions of this specific population. Adequate public policies regarding perinatal assistance could help reduce the prevalence of epilepsy. (C) 2010 by Elsevier Inc. All rights reserved.

Prevalence of Acne Vulgaris in Patients with Down Syndrome

Background/Objective: Acne vulgaris exhibits a worldwide prevalence of up to 95% among adolescents. On the other hand, Down syndrome is an autosomal chromosomal disorder with associated dermatoses and a tendency to obesity. There are no data on its association with acne. Our aim was to detect the prevalence of acne, its forms and associated factors in Down syndrome. Method: A cross-sectional study including 89 subjects aged 10-28 years from Associacao de Pais e Amigos dos Excepcionais-Sao Paulo to verify acne, metabolic and hormonal disorders by interview, clinical and laboratory examinations. Results: We evaluated 49 (55%) males and 40 (45%) females. A weak agreement between self-estimation for acne and examination result was detected. The overall prevalence of acne was 70.8%: 83.7% in males and 55% in females. The prevalence of acne in the age groups 10-17 and 18-28 was 62 and 78.7%, respectively. Facial comedonal acne was mostly detected. The prevalence of obesity was 40%, that of metabolic disorders 7% and that of hyperandrogenism (in females) 15%. Except for gender, no other factor evaluated correlated with acne. Conclusion: A low prevalence of acne in Down syndrome, a predominance in males aged 18-28 and a facial comedonal form were detected. An association with obesity, metabolic disorders or hyperandrogenemia was not assessed. Copyright (C) 2010 S. Karger AG, Basel

The prevalence of headache among elderly in a low-income area of Sao Paulo, Brazil

There are scarce data about headache prevalence and its characteristics among elderly people. The aim was to carry out a cross-sectional study to determine the 1-year prevalence of tension-type and migraine headaches in people > 65 years old in the city of Sao Paulo, Brazil. All 1615 people living in the study catchment area who agreed to participate in the study answered a questionnaire based in the International Headache Society criteria. Prevalence (mean and 95% confidence interval) of any type of headache in the last year was 45.6% (43.2, 48.0). Prevalence of tension-type headache in the last year was 33.1% (30.8, 35.4): 28.1% (24.6, 31.6) for men and 36.4% (33.4, 39.4) for women; for migraine headaches, prevalence in the last year was 10.6% (9.1, 12.1): 5.1% (3.4, 6.8) for men and 14.1% (11.9, 16.3) for women. One-year prevalence rates of headaches, and especially of migraine headaches, are very high among the elderly in Brazil.

Impact of number of vessels disease on outcome of patients with stable coronary artery disease: 5-year follow-up of the medical, angioplasty, and bypass surgery study (MASS)

Objective: To evaluate whether the number of vessels disease has an impact on clinical outcomes as well as on therapeutic results accordingly to medical, percutaneous, or surgery treatment in chronic coronary artery disease. Methods: We evaluated 825 individuals enrolled in MASS study, a randomized study to compare treatment options for single or multivessel coronary artery disease with preserved left ventricular function, prospectively followed during 5 years. The incidence of overall mortality and the composite end-point of death, myocardial infarction, and refractory angina were compared in three groups: single vessel disease (SVD n = 214), two-vessel disease (2VD n = 253) and three-vessel disease (3VD n = 358). The relationship between baseline variables and the composite end-point was assessed using a Cox proportional hazards survival model. Results: Most baseline characteristics were similar among groups, except age (younger in SVD and older in 3VD, p < 0.001), lower incidence of hypertension in SVD (p < 0.0001), and lower levels of total and LDL-cholesterol in 3VD (p = 0.004 and p = 0.005, respectively). There were no statistical differences in composite end-point in 5 years among groups independent of the kind of treatment; however, there was a higher mortality rate in 3VD (p < 0.001). When we stratified our analysis for each treatment option, bypass surgery was associated with a tower number of composite end-point in all groups (SVD p < 0.001, 2VD p = 0.002, 3VD p < 0.001). In multivariate analysis, we found higher mortality risk in 3VD comparing to SVD (p = 0.005, HR 3.14, 95%Cl 1.4-7.0). Conclusion: Three-vessel disease was associated with worse prognosis compared to single-or two-vessel disease in patients with stable coronary disease and preserved ventricular function at 5-year follow-up. In addition, event-free survival rates were higher after bypass surgery, independent of the number of vessels diseased in these subsets of patients. (c) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Heart Transplantation in 107 Cases of Chagas` Disease

Introduction. Chagas` disease is endemic in South America. Objective. This research reviewed the experience with cardiac transplantation in Chagas` disease, emphasizing reactivation, immunosuppression, and mortality. Methods. Over 25 years from March 1985 to March 2010, 107/409 (26.2%) patients with Chagas` disease underwent heart transplantation, patients including 74 (71.1%) men and 72 (67.2%), in functional class IV with 33 (30.8%) on vasopressors and 17 (10.7%) on mechanical circulatory support. Results. The diagnosis of disease reactivation was performed by identifying the parasite in the myocardium (n = 23; 71.8%) in the subcutaneous tissue (n = 8; 25.0%), in blood (n = 11; 34.3%), or in central nervous tissue (n = 1; 3.1%). Hospital mortality was 17.7% (n = 19) due to infection (n = 6; 31.5%), graft dysfunction (n = 6; 31.5%), rejection (n 4; 21.1%), or sudden death (n = 2; 10.5%). Late mortality was 27 (25.2%) cases, which were distributed as: rejection (n = 6; 22.2%), infection (n = 6; 22.2%), (n = lymphoma 4; 14.8%), sarcoma (n = 2; 7.4%), for constrictive pericarditis (n = 2; 7.4%) reactivation of Chagas` disease in the central nervous system (n = 1; 7.1%). Conclusions. Transplantation in Chagas` disease has peculiar problems that differ from other etiologies due to the possibility of disease reactivation and the increased possibility of emergence of cancers. However, transplantation is the only treatment able to modify the natural progression of the disease in its terminal phase. Early diagnosis and rapid introduction of benzonidazole reverses the histological patterns. Immunosuppression, especially steroids, predisposes to the development of cancer and disease reactivation.

Physicians` attitudes and adherence to use of risk scores for primary prevention of cardiovascular disease: cross-sectional survey in three world regions

Objective: To evaluate physicians` attitudes and adherence to the use of risk scores in the primary prevention of cardiovascular disease (CVD). Design and methods: A cross-sectional survey of 2056 physicians involved in the primary prevention of CVD. Participants included cardiologists (47%), general practitioners (42%), and endocrinologists (11%) from several geographical regions: Brazil (n=968), USA (n=381), Greece (n=275), Chile (n=157), Venezuela (n=128), Portugal (n=42), The Netherlands (n=41), and Central America (Costa Rica, Panama, El Salvador and Guatemala; n=64). Results: The main outcome measure was the percentage of responses on a multiple-choice questionnaire describing a hypothetical asymptomatic patient at intermediate risk for CVD according to the Framingham Risk Score. Only 48% of respondents reported regular use of CVD risk scores to tailor preventive treatment in the case scenario. Of non-users, nearly three-quarters indicated that `It takes up too much of my time` (52%) or `I don`t believe they add value to the clinical evaluation` (21%). Only 56% of respondents indicated that they would prescribe lipid-lowering therapy for the hypothetical intermediate-risk patient. A significantly greater proportion of regular users than non-users of CVD risk scores identified the need for lipid-lowering therapy in the hypothetical patient (59 vs. 41%; p<0.0001).

Prevalence of fibromyalgia and chronic widespread pain in community-dwelling elderly subjects living in Sao Paulo, Brazil

Objectives: To estimate the prevalence of fibromyalgia (FM) and chronic widespread pain (CWP) in community-dwelling elderly individuals living in Sao Paulo, to assess the spectrum of problems related to these diseases using the Fibromyalgia Impact Questionnaire (FIQ) and to correlate the FIQ with the number of tender points and with pain threshold. Methods: Our sample consisted of 361 individuals (64% women, 36% men, mean age of 73.3 +/- 5.7 years). Individuals were classified into four groups: FM (according to American College of Rheumatology criteria), CWP, regional pain (RP) and no pain (NP). Pain characteristics and dolorimetry for 18 tender points and the FIQ were assessed. Results: The prevalence of FM was 5.5% [95% confidence interval (CI) = 5.4-5.7], and the prevalence of CWP was 14.1% (95% Cl: 10.5-17.7%). The frequency of RP was 52.6% and the prevalence of NP was 27.7%. FIQ scores were higher in people with FM (44.5), followed by CWP (31.4), RP (18.1) and NP (5.5) (p < 0.001). There was a positive correlation between the domains of the FIQ and the number of tender Points (p < 0.05), and a negative correlation between FIQ score and pain threshold (p < 0.05). Conclusion: In our elderly subjects, the prevalence of FM was slightly higher compared to previously reported studies, and CWP was around 14%. The spectrum of problems related to chronic pain was more severe in FM followed by CWP, strongly suggesting that these conditions should be diagnosed and adequately treated in older individuals. (C) 2010 Elsevier Ireland Ltd. All rights reserved.