Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics

Alcoholism is a major health problem in Western countries, yet relatively little is known about the mechanisms by which chronic alcohol abuse causes the pathologic changes associated with the disease. It is likely that chronic alcoholism affects a number of signaling cascades and transcription factors, which in turn result in distinct gene expression patterns. These patterns are difficult to detect by traditional experiments measuring a few mRNAs at a time, but are well suited to microarray analyses. We used cDNA microarrays to analyze expression of approximately 10 000 genes in the frontal and motor cortices of three groups of chronic alcoholic and matched control cases. A functional hierarchy was devised for classification of brain genes and the resulting groups were compared based on differential expression. Comparison of gene expression patterns in these brain regions revealed a selective reprogramming of gene expression in distinct functional groups. The most pronounced differences were found in myelin-related genes and genes involved in protein trafficking. Significant changes in the expression of known alcohol-responsive genes, and genes involved in calcium, cAMP, and thyroid signaling pathways were also identified. These results suggest that multiple pathways may be important for neuropathology and altered neuronal function observed in alcoholism.

Prediction of mortality in patients without angina: Use of an exercise score and exercise echocardiography

Background Exercise testing has limited efficacy for identifying coronary artery disease (CAD) in the absence of anginal. symptoms. Exercise echocardiography is more accurate than standard exercise testing, but its efficacy in this situation has not been defined. We sought to identify whether the Duke treadmill. score or exercise echocardiography (ExE) could be used to identify risk in patients without anginal symptoms. Methods We studied 1859 patients without typical or atypical angina, heart failure, or a history or ECG evidence of infarction or CAD, who were referred for ExE, of whom 1832 (age 51 15 years, 944 men) were followed for up to 10 years. The presence and extent of ischaemia and scar were interpreted by expert reviewers at the time of the original study. Results Exercise provoked significant (>0.1 mV) ST segment depression in 215 patients (12%), and wall motion abnormalities in 137 (8%). Seventy-eight patients (4%) died before revascularization, only 17 from known cardiac causes. The independent predictors of death were age (RR 1.1, p

Estimates of global mortality attributable to smoking in 2000

Background Smoking is a risk factor for several diseases and has been increasing in many developing countries. Our aim was to estimate global and regional mortality in 2000 caused by smoking, including an analysis of uncertainty. Methods Following the methods of Peto and colleagues, we used lung-cancer mortality as an indirect marker for accumulated smoking risk. Never-smoker lung-cancer mortality was estimated based on the household use of coal with poor ventilation. Relative risks were taken from the American Cancer Society Cancer Prevention Study, phase II, and the retrospective proportional mortality analysis of Liu and colleagues in China. Relative risks were corrected for confounding and extrapolation to other regions. Results We estimated that in 2000, 4.83 (uncertainty range 3.94-5.93) million premature deaths in the world were attributable to smoking; 2.41 (1.80-3.15) million in developing countries and 2.43 (2.13-2.78) million in industrialised countries. 3.84 million of these deaths were in men. The leading causes of death from smoking were cardiovascular diseases (1.69 million deaths), chronic obstructive pulmonary disease (0.97 million deaths), and lung cancer (0.85 million deaths). Interpretation Smoking was an important cause of global mortality in 2000. In view of the expected demographic and epidemiological transitions and current smoking patterns in the developing world, the health loss due to smoking will grow even larger unless effective interventions and policies that reduce smoking among men and prevent increases among women in developing countries are implemented.

Demographic profile and health conditions of the elderly in a community in an urban area of Southeastern Brazil

Some specific characteristics of the aging of the Brazilian population in different areas, states and communities all over the country, have shown significant variations. Historical series of demographic and health indicators for the population in their sixties and over in Brazil, state of S. Paulo and in the municipal district of Araraquara are listed as follows: level of education and urban population growth rate, income distribution, mortality rates and main causes of death. In 1991 the aged constituled were 7,8% of the Brazilian population and 9,7% in Araraquara community. The elderly population (of 70 years of aged and above) as a proportion of the whole, has increased and already stands for 40%. The same trend holds good for both the proportion of aged within the urban population and their level of education wich increased to 90% in 1991. The main causes of death are chronic degenerative diseases which have replaced the infectious illness: firts, the diseases of the circulatory sistem (which account for more than 40% of all deaths) and the neoplasms (which let to 15% of the deaths). On the basis of these health and demographic data relating to people of 60 years of age and over, this study suggests some procedures for the improvement of the quality of the assistance given to the target population: a) the assistance give to the aged should be improved by providing gerontological training for general physicians and nurses, both of public and private clinics; b) the already exixting educational activities for the aged, for health workers and for teachers of secundary education should be further developed; c) the number of day-hospitals should be increased for the purpose of avoiding unnecessary confinement so as maintain the low rate of institutionalization in homes for the elderly (0,7% in Araraquara). It is reported that at least 35% of the aged population in this area is entitled to private health assistance, wich brings out the importance of including such services in the local health programs for this group.

The contribution of multitemporal information from multispectral satellite images for automatic land cover classification at the national scale

Thesis submitted to the Instituto Superior de Estatística e Gestão de Informação da Universidade Nova de Lisboa in partial fulfillment of the requirements for the Degree of Doctor of Philosophy in Information Management – Geographic Information Systems

Multi-scale vegetation classification using earth observation data of the Sundarban mangrove forest, Bangladesh.

Dissertation submitted in partial fulfilment of the requirements for the Degree of Master of Science in Geospatial Technologies.

The involvement of CDH1 in cancer angiogenesis

Dissertação para obtenção do Grau de Mestre em Biotecnologia

ACUTE KIDNEY INJURY CAUSED BY Crotalus AND Bothrops SNAKE VENOM: A REVIEW OF EPIDEMIOLOGY, CLINICAL MANIFESTATIONS AND TREATMENT

SUMMARY Ophidic accidents are an important public health problem due to their incidence, morbidity and mortality. An increasing number of cases have been registered in Brazil in the last few years. Several studies point to the importance of knowing the clinical complications and adequate approach in these accidents. However, knowledge about the risk factors is not enough and there are an increasing number of deaths due to these accidents in Brazil. In this context, acute kidney injury (AKI) appears as one of the main causes of death and consequences for these victims, which are mainly young males working in rural areas. Snakes of the Bothrops and Crotalus genera are the main responsible for renal involvement in ophidic accidents in South America. The present study is a literature review of AKI caused by Bothrops and Crotalus snake venom regarding diverse characteristics, emphasizing the most appropriate therapeutic approach for these cases. Recent studies have been carried out searching for complementary therapies for the treatment of ophidic accidents, including the use of lipoic acid, simvastatin and allopurinol. Some plants, such as Apocynaceae, Lamiaceae and Rubiaceae seem to have a beneficial role in the treatment of this type of envenomation. Future studies will certainly find new therapeutic measures for ophidic accidents.

Juvenile Systemic Lupus Erythematosus in Portugal: Clinical and Immunological Patterns of Disease Expression in a Cohort of 56 Patients

Objective: To define the pattern of disease expression and to gain better understanding in patients with juvenile onset systemic lupus erythematosus (SLE) in Portugal. Methods: The features of unselected patients with systemic lupus erythematosus who had disease onset before the age of 18 years were retrospectively analysed in three Portuguese centres with Pediatric Rheumatology Clinic over a 24-year period (1987-2011). Demographic, clinical and laboratory manifestations, therapy and outcome were assessed. Results: A cohort of 56 patients with a mean age at disease onset of 12.6±4.04 years (mean±1SD) (range, 1.0-17.0 years) and a mean period of follow-up of 5.5±5.4 years. Forty six (82.1%) patients were female. The most common disease manifestations were musculoskeletal (87.5%), mucocutaneous (80.3%) and haematological abnormalities (75%). Lupus nephritis was diagnosed in 46.4% of patients and consisted of glomerular ne - phritis in all cases. Neuropsychiatric manifestations occurred in 21.4% but severe central nervous system complications were uncommon, as brain infarcts and organic brain syndrome in 4 (7.1%) patients. Antinuclear antibodies and anti-double stranded DNA were positive in most patients in (98.2% and 71.4% respectively), as well as low C3 and/or C4 were observed frequently (85.7%). Generally, most patients had a good response to therapy as demonstrated by a significant decreasing of SLEDAI score from disease presentation to the last evaluation. The SLEDAI at diagnosis, the maximum SLEDAI and the incidence of complications were significantly higher in patients with neurolupus and/or lupus nephritis. Therapy included oral steroids (87.5%), hydroxychloroquine (85.7%), azathioprine (55.4%), IV cyclophosphamide (28.6%) along with other drugs. Six (10.7%) patients were treated with rituximab. Long-term remission was achieved in 32%, disease was active in 68%, adverse reactions to therapy occurred in 53.6% and complications/severe manifestations in 23.2%. Two patients died, being active disease and severe infection the causes of death. Conclusions: This study suggests that in our patients the clinical and laboratory features observed were similar to juvenile systemic lupus erythematosus patients from other series. Clinical outcome was favourable in the present study. Complications from therapy were frequent. Objective: To define the pattern of disease expression and to gain better understanding in patients with juvenile onset systemic lupus erythematosus (SLE) in Portugal. Methods: The features of unselected patients with systemic lupus erythematosus who had disease onset before the age of 18 years were retrospectively analysed in three Portuguese centres with Pediatric Rheumatology Clinic over a 24-year period (1987-2011). Demographic,clinical and laboratory manifestations, therapy and outcome were assessed. Results: A cohort of 56 patients with a mean age at disease onset of 12.6±4.04 years (mean±1SD) (range, 1.0-17.0 years) and a mean period of follow-up of 5.5±5.4 years. Forty six (82.1%) patients were female. The most common disease manifestations were musculoskeletal (87.5%), mucocutaneous (80.3%) and haematological abnormalities (75%). Lupus nephritis was diagnosed in 46.4% of patients and consisted of glomerular ne - phritis in all cases. Neuropsychiatric manifestations occurred in 21.4% but severe central nervous system complications were uncommon, as brain infarcts and organic brain syndrome in 4 (7.1%) patients. Antinuclear antibodies and anti-double stranded DNA were positive in most patients in (98.2% and 71.4% respectively), as well as low C3 and/or C4 were observed frequently (85.7%). Generally, most patients had a good response to therapy as demonstrated by a significant decreasing of SLEDAI score from disease presentation to the last evaluation. The SLEDAI at diagnosis, the maximum SLEDAI and the incidence of complications were significantly higher in patients with neurolupus and/or lupus nephritis. Therapy included oral steroids (87.5%), hydroxychloroquine (85.7%), azathioprine (55.4%), IV cyclophosphamide (28.6%) along with other drugs. Six (10.7%) patients were treated with rituximab. Long-term remission was achieved in 32%, disease was active in 68%, adverse reactions to therapy occurred in 53.6% and complications/severe manifestations in 23.2%. Two patients died, being active disease and severe infection the causes of death. Conclusions: This study suggests that in our patients the clinical and laboratory features observed were similar to juvenile systemic lupus erythematosus patients from other series. Clinical outcome was favourable in the present study. Complications from therapy were frequent.

Molecular targeting of proteins by homocysteine: implications in familial and clinical hypercholesterolemia

Cardiovascular diseases (CVDs) are one of the leading causes of death and disability worldwide and one of its underlying causes is hypercholesterolemia. Hypercholesterolemia can have genetic (familial hypercholesterolemia, FH) and non-genetic causes (clinical hypercholesterolemia, CH), the first much more severe, with occurrence of premature atherosclerosis. While the pathophysiological role of homocysteine (Hcy) on CVD is still controversial, molecular targeting of protein by S and N-homocysteinylation offers a new paradigm to be considered in the vascular pathogenesis of hypercholesterolemia. On this regard, the present study aims to give new insights on protein targeting by Hcy in both CH and FH conditions. A total of 187 subjects were included: 65 normolipidemic and 122 hypercholesterolemic. Total (tHcy) and free (fHcy) fractions were quantified in serum samples after validation of an HPLCFD method, to assess S-homocysteinylation. Also, the lactonase (LACase) activity of paraoxonase-1 (PON1) was quantified by a colorimetric assay, as a surrogate of N-homocysteinylation. tHcy does not differ among groups. Nevertheless, fHcy declines in the hypercholesterolemic groups, with more evidence to the FH population. Consequently, there seems to be an increase of Shomocysteinylation, regardless of lipid lowering therapy (LLT). Also, despite of LLT use, LACase activity is lower in FH, thus the risk for protein N-homocysteinylation seems to be higher. Moreover, the decrease in LACase/ApoA1 and LACase/HDL ratios in FH, shows that HDL is dysfunctional in this population, despite its normal concentration values. Data supports that the pathophysiological role of Hcy on hypercholesterolemia may reside in its ability to post-translationally modify proteins. This role is particularly evident in FH condition. In the future, it will be interesting to identify which target proteins are modified and thus involved in vascular pathology progression.

Complications of tracheobronchial foreign body aspiration in children: report of 5 cases and review of the literature

Foreign body aspiration (FBA) is one of leading causes of death in children, especially among those younger than 3 years of age. The inhalation of a foreign body may cause a wide variety of symptoms, and early diagnosis is highly associated with the successful removal of the inhaled foreign material. Despite the great advances in endoscopic procedures and anesthesia, a large number of difficulties and complications still result from foreign body aspiration. We describe 5 cases of serious acute complications following aspiration of foreign bodies that became lodged in the tracheobronchial tree, including pneumomediastinum, pneumothorax, total atelectasis, foreign body dislodgment, and need for thoracotomy in children admitted into our intensive care unit in 1999 and 2000; these were all situations that could have been prevented with early recognition and prompt therapeutic intervention.

Ontological representation of tumor-node-metastasis classification and an ontology-driven classifier: a study on colorectal cancer

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Informática Médica)

Clinical and pathological assessment of 82 patients with cardiovascular diseases undergoing autopsy at the Hospital das Clínicas of the Faculdade de Medicina de Botucatu from 1988 to 1993

OBJECTIVE: To evaluated the clinical diagnostic, efficiency for basic death causes in patients dying of circulatory disease and de relative frequency of those diseases. METHODS: Analysis of medical record data of 82 patients, ages from 16 to 84 years old (68 over 40 years old), whose died of circulatory disease and had undergone necropsy in the period from 1988 to 1993 years in the University Hospital of Medicine Faculty of Botucatu-UNESP, Br. RESULTS: The functional class of patients were III or IV, in 78%, and 81.7% needed urgent hospitalization. By the clinical judgment the death were by ischemic heart disease in 32 (21 acute myocardial infarction), Chagas'disease in 12, valvopathy in 11, cardiomyopathy in 7, heart failure with no specification of cardiopathy in 11 and other causes in 9. At the necropsy the death cause was ischemic heart disease in 34 patients, valvopathy in 10, Chagas'disease in 10, cardiomyopathy in 5, and heart failure with no specification of cardiopathy in 2.The concordance taxes were in thhe same order: 94,6%, 90,0%, 83.3%, 71.4% and 28.5%. CONCLUSION: There was a great efficiency of clinical diagnosis for death cause in a general university hospital. The ischemic heart disease were the main causes of death.

Trends in the risk of mortality due to cardiovascular diseases in five Brazilian geographic regions from 1979 to 1996

OBJECTIVE - To analyze the trends in risk of death due to cardiovascular diseases in the northern, northeastern, southern, southeastern, and central western Brazilian geographic regions from 1979 to 1996. METHODS - Data on mortality due to cardiovascular, cardiac ischemic, and cerebrovascular diseases in 5 Brazilian geographic regions were obtained from the Ministry of Health. Population estimates for the time period from 1978 to 1996 in the 5 Brazilian geographic regions were calculated by interpolation with the Lagrange method, based on the census data from 1970, 1980, 1991, and the population count of 1996, for each age bracket and sex. Trends were analyzed with the multiple linear regression model. RESULTS - Cardiovascular diseases showed a declining trend in the southern, southeastern, and northern Brazilian geographic regions in all age brackets and for both sexes. In the northeastern and central western regions, an increasing trend in the risk of death due to cardiovascular diseases occurred, except for the age bracket from 30 to 39 years, which showed a slight reduction. This resulted from the trends of cardiac ischemic and cerebrovascular diseases. The analysis of the trend in the northeastern and northern regions was impaired by the great proportion of poorly defined causes of death. CONCLUSION - The risk of death due to cardiovascular, cerebrovascular, and cardiac ischemic diseases decreased in the southern and southeastern regions, which are the most developed regions in the country, and increased in the least developed regions, mainly in the central western region.

Retrospective Study of the Survival of Patients who Underwent Cardiopulmonary Resuscitation in an Intensive Care Unit

OBJECTIVE: To evaluate clinical and evolutive characteristics of patients admitted in an intensive care unit after cardiopulmonary resuscitation, identifying prognostic survival factors.METHODS: A retrospective study of 136 patients admitted between 1995 and 1999 to an intensive care unit, evaluating clinical conditions, mechanisms and causes of cardiopulmonary arrest, and their relation to hospital mortality.RESULTS: A 76% mortality rate independent of age and sex was observed. Asystole was the most frequent mechanism of death, and seen in isolation pulmonary arrest was the least frequent. Cardiac failure, need for mechanical ventilation, cirrhosis and previous stroke were clinically significant (p<0.01) death factors.CONCLUSION: Prognostic factors supplement the doctor's decision as to whether or not a patient will benefit from cardiopulmonary resuscitation.