Safety and efficacy of fenproporex for obesity treatment: a systematic review

ABSTRACT OBJECTIVE To evaluate clinical evidence on the safety and efficacy of fenproporex for treating obesity. METHODS MEDLINE, LILACS and Cochrane Controlled Trials Register were searched as well as references cited by articles and relevant documents. Two authors independently assessed the studies for inclusion and regarding risk of bias, collected data, and accuracy. Eligible studies were all those placebo-controlled that provided data on the efficacy and safety of Fenproporex to treat obesity. RESULTS Only four controlled studies met the inclusion criteria. One randomized, placebo-controlled trial on Fenproporex was found on electronic databases. Three placebo-controlled studies (in non-indexed journals) were identified by hand-searching. Patients with cardiovascular and other comorbidities were excluded in all studies. Trials lasted from 40 to 364 days and doses ranged from 20 to 33.6 mg/d. All controlled studies found that weight loss among Fenproporex-treated patients was greater than that produced by the placebo, but drug effect was modest. Fenproporex produced additional weight reductions of 4.7 kg (one year), 3.8 kg (six months) and 1.55 kg (two months) in average, in relation to diet and exercise only (three trials). Insomnia, irritability, and anxiety were the most frequently reported side effects in the four studies. CONCLUSIONS There is a paucity of randomized, placebo-controlled trials on Fenproporex and those identified here present major methodological flaws. These studies suggest that Fenproporex is modestly effective in promoting weight loss. Nonetheless, they failed to provide evidence that it reduces obesity-associated morbidity and mortality. Data from these studies are insufficient to determine the risk-benefit profile of Fenproporex. Abuse potential and amphetamine-like adverse effects are causes for concern.

ERICA: prevalences of hypertension and obesity in Brazilian adolescents

ABSTRACT OBJECTIVE To estimate the prevalence of arterial hypertension and obesity and the population attributable fraction of hypertension that is due to obesity in Brazilian adolescents. METHODS Data from participants in the Brazilian Study of Cardiovascular Risks in Adolescents (ERICA), which was the first national school-based, cross-section study performed in Brazil were evaluated. The sample was divided into 32 geographical strata and clusters from 32 schools and classes, with regional and national representation. Obesity was classified using the body mass index according to age and sex. Arterial hypertension was defined when the average systolic or diastolic blood pressure was greater than or equal to the 95th percentile of the reference curve. Prevalences and 95% confidence intervals (95%CI) of arterial hypertension and obesity, both on a national basis and in the macro-regions of Brazil, were estimated by sex and age group, as were the fractions of hypertension attributable to obesity in the population. RESULTS We evaluated 73,399 students, 55.4% female, with an average age of 14.7 years (SD = 1.6). The prevalence of hypertension was 9.6% (95%CI 9.0-10.3); with the lowest being in the North, 8.4% (95%CI 7.7-9.2) and Northeast regions, 8.4% (95%CI 7.6-9.2), and the highest being in the South, 12.5% (95%CI 11.0-14.2). The prevalence of obesity was 8.4% (95%CI 7.9-8.9), which was lower in the North region and higher in the South region. The prevalences of arterial hypertension and obesity were higher in males. Obese adolescents presented a higher prevalence of hypertension, 28.4% (95%CI 25.5-31.2), than overweight adolescents, 15.4% (95%CI 17.0-13.8), or eutrophic adolescents, 6.3% (95%CI 5.6-7.0). The fraction of hypertension attributable to obesity was 17.8%. CONCLUSIONS ERICA was the first nationally representative Brazilian study providing prevalence estimates of hypertension in adolescents. Regional and sex differences were observed. The study indicates that the control of obesity would lower the prevalence of hypertension among Brazilian adolescents by 1/5.

Interstitial pneumonitis in canine visceral leishmaniasis

Forty-one naturally infected dogs with visceral leishmaniasis from an urban area of Corumbá (Mato Grosso do Sul-BRAZIL) were studied and three types of lung involvement due to visceral leishmaniasis were characterized; a cellular, a cellular-fibrotic and a fibrotic type. These types seem to represent a sequential evolutive proce'as. Visceral leishmaniasis frequently causes an interstitial pneu monitis in naturally infected dogs (80.5%) as well as in man and experimentally infected hamsters.

Histopathological patterns of the liver involvement in visceral leishmaniasis

The hepatic changes observed in liver specimen from either biopsy or necropsy of 47 patients with visceral leishmaniasis permited us to define three different histopathological patterns of involvement: typical, nodular, and fibrogenic. These patterns seem to be representative of different evolutive stages of the hepatic involvement in the disease either towards a more benign evolution or to more chronic stage with fibrosis and "cirrhosis". These histopathological evolutive stages are related to the prognosis of the disease.

Visceral larva migrans: a seroepidemiological survey in five municipalities of São Paulo State, Brazil

An enzyme-linked immunosorbent assay (ELISA), employing antigens from Toxocara canis larvae and the absortion of suspected sera with Ascaris lumbricoides extracts was used in a seroepidemiological study performed in five municipalities of São Paulo State, Brazil (São Paulo, Campinas, Santos, Marília and Presidente Prudente) in order to determine the frequency of antibodies to Toxocara. In 2,025 blood samples collected, 806 proceeded from male subjects and 1,219 from females; 483 samples were collected from subjects under 15 years of age and the remaining 1,542 from subjects aged 15 years or over. Among the 2,025 sera investigated, 3.60% had antibodies to Toxocara at significant levels. A moderate predominance of infection with Toxocara among male subjects (3.72%) was observed, although the difference was not statistically significant when this rate was compared with that for female (3.28%). Related to age, a higher frequency of positive results was detected among subjects under 15 years (6.41%) against the older group (2.53%). A trend of more elevated rates of infection was observed in municipalities with high demographic densities (São Paulo, Campinas and Santos). Nevertheless, such findings only appeared to be statistically significant in subjects younger than 15 years.

Cisticercose músculo-cutânea e visceral - doença rara?

O presente trabalho teve como objetivos estimar a freqüência das formas músculo-cutánea e visceral da cisticercose em exames anátomo-patológicos e necrópsias realizados em Brasilia, Distrito Federal (estudo retrospectivo) e diagnosticar a cisticercose músculo-cutânea em pacientes residentes na mesma região geográfica (estudo prospectivo). Em 64.911 protocolos de exames anátomo-patológicos, o diagnóstico de cisticercose foi observado em 30 (0,05%), sendo que em 27 (90,0%) os cistos estavam nos tecidos músculo-cutâneo-mucoso, em 1 (3,3%) em gânglio e em 2 (6,7%) no sistema nervoso central. Entre aqueles com cistos nos tecidos músculo-cutâneo-mucoso 2 (7,4%) tinham cisticercos em língua. Em 1520 protocolos de necrópsia, encontraram-se 25 (1,6%) com diagnóstico de cisticercose, sendo: 24(96,0%) com neurocisticercose, seja isolada ou associada a outras formas da doença; e 2 (8,0%) com cisticercos em coração, 2 (8,0%) em músculo esquelético e 1 (4,0%) em fígado, seja isolados ou associados a outras localizações do parasito. Foram também examinados 1122 indivíduos, realizando-se em todos eles as reações sorológicas de imunofluorescência indireta e ELISA para cisticercose e a investigação radiológica de partes moles e crânio. Encontraram-se 59 (5,3%) com ambas reações sorológicas reagentes (10 entre eles com o diagnóstico de cisticercose confirmado por biópsias); e 32 (2,8%) com calcificações nas radiografias de partes moles e/ou crânio, mas apresentando ambas reações sorológicas não-reagentes. Entre os pacientes com os testes imunológicos reagentes, a neurocisticercose foi diagnosticada em 39 (66,1%), a cisticercose muscular em 25 (42,4%); a cutânea em 12 (20,3%); e a visceral em 2 (3,4%), sendo em 1 (1,7%) ovariana e em 1 (1,7%) miocárdica, pleural e renal. Os resultados permitem concluir que a forma músculo-cutânea é observada freqüentemente entre pacientes com cisticercose residentes em Brasília. A forma visceral também foi encontrada, com os cisticercos localizados em diferentes órgãos, sendo que os pacientes afetados não apresentavam as manifestações clínicas.

Pre-meal tomato (Lycopersicon esculentum) intake can have anti-obesity effects in young women?

The effect of pre-meal tomato intake in the anthropometric indices and blood levels of triglycerides, cholesterol, glucose, and uric acid of a young women population (n=35, 19.6 ± 1.3 years) was evaluated. During 4 weeks, daily, participants ingested a raw ripe tomato (~90 g) before lunch. Their anthropometric and biochemical parameters were measured repeatedly during the follow-up time. At the end of the 4 weeks, significant reductions were observed on body weight (-1.09 ± 0.12 kg on average), % fat (-1.54 ± 0.52%), fasting blood glucose (-5.29 ± 0.80 mg/dl), triglycerides (-8.31 ± 1.34 mg/dl), cholesterol (-10.17 ± 1.21 mg/ dl), and uric acid (-0.16 ± 0.04 mg/dl) of the participants. The tomato pre-meal ingestion seemed to interfere positively in body weight, fat percentage, and blood levels of glucose, triglycerides, cholesterol, and uric acid of the young adult women that participated in this study.

Avaliação de três esquemas terapêuticos com o antimoniato de N-metil-glucamina no tratamento da leishmaniose visceral no estado do Pará, Brasil

Avaliaram-se, de forma retrospectiva, três esquemas terapêuticos à base do antimoniato de N-metil-glucamina (Glucantime) usados no tratamento de 43 casos autóctones de leishmaniose visceral (Estado do Pará), observados em crianças de 1 a 12 anos de idade, no período de 1985 a 1990. Dos 43 casos, 28 (grupo A) foram tratados com 40 mg/SbV/kg administrados IV a intervalos de 48 hs, em séries de 15 doses (esquema I); 8 (grupo B) receberam 40mg/SbV/kg administrados IV diariamente, durante 15 dias (esquema II), e 7 (grupo C) receberam 20 mg/SbV/kg administrados IV diariamente, durante 15 dias (esquema III). Considerando que o controle de cura da doença foi essencialmente clínico, admitiu-se que o esquema III representaria a melhor opção terapêutica, em razão de: a) ter promovido taxa de cura equivalente aos esquemas que usaram o dobro dessa dose, b) a relação custo-benefício desse esquema torna-o menos dispendioso, c) pode ser usado durante período mais prolongado, com menor risco de produzir efeitos de toxicidade, e d) não existem, a nível local (Pará), relatos de casos de resistência da doença associados ao uso desse esquema.

Clinical and laboratorial features of visceral toxocariasis in infancy

Forty children with a diagnosis of Visceral Toxocariasis were evaluated prospectively from February 1982 to June 1989. Diagnosis was established by clinical, laboratorial and serological (ELISA - ES Toxocara canis antigen) evaluations. A great clinical polymorphism was found in our patients, ranging from unspecific or absent manifestations to an exhuberant symptomatology. The laboratorial findings were: leukocytosis,eosinophilia and elevation of serum gammaglobulin and isohemagglutinin levels. No significant relationship between clinical findings and laboratorial parameters was found. Serology (ELISA) was a method of great diagnostic support but did not show a correlation with clinical and laboratorial findings in this study. There was a significant relationship between pulmonary manifestations and the presence of signs and/or symptoms, when the patients were sent to us. Our findings, especially the high incidence of pulmonary manifestations, suggest that Visceral Toxocariasis has to be included in the differential diagnostic of children with pulmonary manifestations, characteristic epidemiological data and associated eosinophilia.

Visceral leishmaniasis and Acquired Immunodeficiency Sydrome (AIDS): case report

This is a case report that describe an association of AIDS, visceral leishmaniasis and probable disseminated tuberculosis. Due to the spread of AIDS in developing areas worldwide this association would be more frequently, seen on subjects from endemic areas where this protozoonosis is prevalent. More than one opportunistic infection related with the endemic diseases of the developing regions can be associated with those immunocompromised patients.

Plasma levels of tumor necrosis factor-alpha in patients with visceral leishmaniasis (Kala-Azar). Association with activity of the disease and clinical remisson following antimonial therapy

Evaluation of TNF-alpha in patients with Kala-azar has drawn increasing interest due to its regulatory role on the immune system, in addition to its cachetizing activity. The objective of this study was to examine the association between plasma levels of TNF-alpha, measured by immunore-activity (ELISA) and bioactivity (cytotoxicity assay with L-929 cells), and clinical manifestations of visceral leishmaniasis. Plasma samples from 19 patients with Kala-azar were obtained before, during and at the end of antimonial therapy. TNF-alpha determinations was done by using the cytotoxicity assay (all patients) and the enzyme-linked immunoassay (ELISA - 14 patients). A discrepancy between results obtained by ELISA and cytotoxicity assay was observed. Levels of circulating TNF-alpha, assessed by ELISA, were higher in patients than in healthy controls, and declined significantly with improvement in clinical and laboratory parameters. Plasma levels before treatment were 124.7 ± 93.3 pg/ml (mean ± SD) and were higher than at the end of therapy 13.9 ± 25.1 pg/ml (mean ± SD) (p = 0.001). In contrast, plasma levels of TNF-alpha evaluated by cytotoxicity assay did not follow a predicted course during follow-up. Lysis, in this case, might be not totally attributed to TNF-alpha. The discrepancy might be attributed to the presence of factor(s) known to influence the release and activity of TNF-alpha.

A Leishmaniose visceral em Portugal Continental : 1999-2009

RESUMO - As alterações climáticas alteraram a incidência e distribuição mundial de zoonoses, ao modificarem o perfil epidemiológico dos seus vectores. A leishmaniose visceral é reemergente na bacia mediterrânica, sendo o seu impacto real subestimado. Em Portugal, é endémica em três regiões, de declaração obrigatória desde 1948 e o reservatório é o canídeo. O aumento da incidência da doença no cão e a escassez de informação epidemiológica tornou pertinente investigar a realidade nacional. A partir das bases de dados das notificações e dos grupos de diagnósticos homogéneos hospitalares, foram identificados todos os casos e, consultados todos os processos clínicos dos doentes com episódios de internamento nos hospitais do continente entre 1999-2009. Ocorreram 730 internamentos para 375 indivíduos na maioria: homens, eurocaucasianos, com em média, 27 anos e, residência em Lisboa e Vale do Tejo. A sintomatologia e comorbilidades dos doentes vão de encontro ao descrito internacionalmente. A doença foi subnotificada, com uma demora média de 19 dias. A letalidade foi de 5%. A taxa de incidência média do continente foi de 0,294/100000 habitantes, sem padrão de sazonalidade. O corredor endémico de Bortman construído apresentou picos com amplitudes de 2-3 anos. O mapeamento dos doentes evidenciou casos em regiões não endémicas acompanhando a distribuição da leishmaniose canina. Seria pertinente que futuras investigações construíssem uma modelação matemática que confirmasse a tendência do corredor endémico (pico em 2011?) para accionar um sistema de alerta nos Serviços de Saúde. Seria também útil a avaliação das condições geoclimáticas das localidades com casos para evidenciar possíveis similitudes no território. -------ABSTRACT - Climate changed the incidence and worldwide distribution of zoonosis while the epidemiological profile of their vectors was changing. Visceral leishmaniasis is reemerging in the Mediterranean basin and its real impact underestimated. In Portugal, it’s endemic in three regions; the notification occurs since 1948 and dog is the reservoir. The increased incidence of the canines’ disease and the scarcity of epidemiological information relevant investigate the national reality. From Notifications and Homogeneous’ Diagnostics Groups system databases, all cases were identified and also analyze all clinical processes of inpatients’ hospitals in 1999- 2009 in Portugal. 730 admissions occurred for 375 patients. In most they were men, Caucasians, with an average of 27 years and residency in Lisboa e Vale do Tejo. The symptoms and comorbilidades patient go against described internationally. The disease was under notified, with an average delay of 19 days. Lethality was 5%. The incidence rate was 0,294/100000 inhabitants, without seasonality. The endemic’s Bortman corridor presents peak amplitudes of 2-3 years. Mapping patient’s residency shows that cases’ distribution is similar to endemic canine leishmaniasis. It would be appropriate a research to build a mathematical modeling up to confirm the trend of corridor endemic (peak in 2011?), to trigger an alert system for health services. It would also be useful to evaluate the geo-climatics conditions of localities with cases to highlight possible similarities in the territory.