Progression of kidney disease in type 2 diabetes – beyond blood pressure control: an observational study

BACKGROUND: The risk factors for progression of chronic kidney disease (CKD) in type 2 diabetes mellitus (DM) have not been fully elucidated. Although uncontrolled blood pressure (BP) is known to be deleterious, other factors may become more important once BP is treated. METHODS: All patients seen in the outpatient clinics of our hospital between January 1993 and September 2002 with type 2 DM and clinical evidence of CKD were evaluated. Progression of kidney disease was evaluated by rate of decline of glomerular filtration rate (GFR) as estimated from the simplified MDRD formula. Variables associated with progression in univariate analyses were examined by multivariate analysis to determine the factors independently associated with kidney disease progression. RESULTS: 343 patients (mean age 69 years; all male; 77% Caucasian) were studied. Mean BP, glycated hemoglobin, and serum cholesterol during the study period were 138/72 mmHg, 8.1%, and 4.8 mmol/L, respectively. Mean decline of GFR was 4.5 ml min-1 1.73 m(2)-1 yr-1 (range -14 to +32). Low initial serum albumin (p < 0.001), black race (p < 0.001), and degree of proteinuria (p = 0.002), but not blood pressure, glycated hemoglobin, or serum cholesterol, were independently associated with progression. CONCLUSION: In a cohort of diabetic patients with CKD in whom mean BP was < 140/80 mmHg, the potentially remediable factors hypoalbuminemia and proteinuria but not blood pressure were independently associated with progression of kidney disease. Further understanding of the relationship between these factors and kidney disease progression may lead to beneficial therapies in such patients

Mitochondrionopathy Phenotype in Doxorubicin-Treated Wistar Rats Depends on Treatment Protocol and Is Cardiac-Specific

Although doxorubicin (DOX) is a very effective antineoplastic agent, its clinical use is limited by a dose-dependent, persistent and cumulative cardiotoxicity, whose mechanism remains to be elucidated. Previous works in animal models have failed to use a multi-organ approach to demonstrate that DOX-associated toxicity is selective to the cardiac tissue. In this context, the present work aims to investigate in vivo DOX cardiac, hepatic and renal toxicity in the same animal model, with special relevance on alterations of mitochondrial bioenergetics. To this end, male Wistar rats were sub-chronically (7 wks, 2 mg/Kg) or acutely (20 mg/Kg) treated with DOX and sacrificed one week or 24 hours after the last injection, respectively. Alterations of mitochondrial bioenergetics showed treatment-dependent differences between tissues. No alterations were observed for cardiac mitochondria in the acute model but decreased ADP-stimulated respiration was detected in the sub-chronic treatment. In the acute treatment model, ADP-stimulated respiration was increased in liver and decreased in kidney mitochondria. Aconitase activity, a marker of oxidative stress, was decreased in renal mitochondria in the acute and in heart in the sub-chronic model. Interestingly, alterations of cardiac mitochondrial bioenergetics co-existed with an absence of echocardiograph, histopathological or ultra-structural alterations. Besides, no plasma markers of cardiac injury were found in any of the time points studied. The results confirm that alterations of mitochondrial function, which are more evident in the heart, are an early marker of DOX-induced toxicity, existing even in the absence of cardiac functional alterations

Diminished myelin-specific T cell activation associated with increase in CTLA4 and Fas molecules in multiple sclerosis patients treated with IFN-beta

Multiple sclerosis (MS) is a chronic inflammatory disease of the white matter of the central nervous system (CNS) characterized by focal areas of demyelination. Interferon-beta (IFN-beta) provides an effective treatment that lessens the frequency and severity of exacerbations in relapsing-remitting multiple sclerosis (RRMS), but the mechanisms by which IFN-beta is efficient remain uncertain. The data presented here demonstrate that IFN-beta impairs the proliferative response to myelin basic protein (MBP) and myelin, as well as increasing the expression of the CTLA4 intracellular molecule. Moreover, this treatment increases the expression of surface Fas molecules and of the soluble form of these molecules. Our hypothesis is that the increase in Fas and CTLA4 molecules in MS patients may lead to lymphocyte apoptosis, which suggests possible mechanisms underlying the therapeutic response to IFN-beta.271086587

The presence of serum anti-Ascaris lumbricoides IgE antibodies and of Trichuris trichiura infection are risk factors for wheezing and/or atopy in preschool-aged Brazilian children

<p>Abstract</p> <p>Background</p> <p>The elucidation of factors that trigger the development of transient wheezing in early childhood may be an important step toward understanding the pathogenesis of asthma and other allergic diseases later in life. Transient wheezing has been mainly attributed to viral infections, although sensitisation to aeroallergens and food allergens may occur at an early age. In developing countries, intestinal helminthic infections have also been associated with allergy or atopy-related disorders.</p> <p>Objective</p> <p>The aim of this study was to explore the association of <it>Trichuris trichiura </it>and <it>Ascaris lumbricoides </it>infections with wheezing and atopy in early childhood.</p> <p>Study design</p> <p>A cross-sectional study using a Portuguese-language ISAAC phase I questionnaire, adapted for preschool-aged children, nested in a cohort study of childhood diarrhoea, was conducted on 682 children. Two faecal samples per child were examined for the presence of intestinal helminthic infection. IgE antibodies against three allergenic preparations <it>(Dermatophagoides pteronyssinus, Blomia tropicalis </it>and common child food), as well as against <it>A. lumbricoides </it>antigens, were measured in a sub-sample of these children, whose parents allowed the procedure. Atopy was defined by the presence of levels of serum IgE antibodies ≥0.35 kU/L against at least one of the three tested allergenic preparations.</p> <p>Results</p> <p>Active <it>T. trichiura </it>infection but not <it>A. lumbricoides </it>infection was positively associated with wheezing in the total studied children population [adjusted OR = 2.60; CI = 1.54;4.38] and in the atopic children sub-population [adjusted OR = 3.07; CI = 1.00;9.43]. The association with atopy was also positive and statistically significant only in the brute analysis [OR = 2.13; CI = 1.03;4.40]. Anti-<it>A. lumbricoides </it>IgE antibodies, but not current <it>A. lumbricoides </it>infection, were positively associated with wheezing in atopic children [adjusted OR = 2.01; CI = 1.00;4.50] and in non-atopic children [adjusted OR = 3.07; CI = 1.13;8.35] and it was also associated with atopy [adjusted OR = 7.29; CI = 3.90; 13.4]. On the other hands, reports of wheezing were not significantly associated with atopy.</p> <p>Conclusions</p> <p>These data corroborate previous studies showing that wheezing is predominantly associated with infection in early childhood and shows that anti-<it>A. lumbricoides </it>IgE antibodies, but not active <it>Ascaris </it>infections, are associated with wheezing and atopy. Additionally, the data demonstrate that <it>T. trichiura </it>infection may play a role in the pathogenesis of atopic wheezing in early childhood.</p

Ectopic opening of the common bile duct and duodenal stenosis: an overlooked association

<p>Abstract</p> <p>Background</p> <p>Ectopic opening of the common bile duct into the duodenal bulb (EO-CBD-DB) is a rare disease that may be complicated by duodenal ulcer, deformity, stenosis and biliary stones. The aim of this study is to report clinical presentations, endoscopic diagnosis and treatment of this entity as well as to investigate its association with duodenal stenosis.</p> <p>Methods</p> <p>Gastroduodenoscopic findings and radiological imaging were evaluated for ectopic papilla and duodenal stenosis. Diagnostic methods, endoscopic procedures and long-term outcomes of the endoscopic treatment were presented.</p> <p>Results</p> <p>EO-CBD-DB was found in 74 (77.1%) of the 96 patients with duodenal deformity/stenosis (79 male, 17 female, mean age: 58.5, range: 30-87 years). The papilla with normal appearance was retracted to the bulb in 11 while it was at its usual location in the remaining 11. The history of biliodigestive surgery was more common in patients with EO-CBD-DB who were frequently presented with the common bile duct stone-related symptoms than the other patients. Thirteen (17.6%) of the patients with EO-CBD-DB were referred to surgery. Endoscopic treatment was completed in 60 (81.1%) patients after an average of 1.7 (range: 1-6) procedures. These patients were on follow-up for 24.8 (range: 2-46) months. Endoscopic intervention was required in 12 (20%) of them because of recurrent biliary problems. Treatment of the patient who had stricture due to biliary injury during laparoscopic cholecystectomy is still continued.</p> <p>Conclusions</p> <p>The presence of EO-CBD-DB should be considered particularly in middle-aged male patients who have duodenal deformity/stenosis. Endoscopic treatment is feasible in these patients. The long-term outcomes of endoscopic therapy need to be compared with surgical treatment.</p

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Reliability of two behavioral tools to assess pain in preterm neonates

CONTEXT: One of the main difficulties in adequately treating the pain of neonatal patients is the scarcity of validated pain evaluation methods for this population. OBJECTIVE: To analyze the reliability of two behavioral pain scales in neonates. TYPE OF STUDY: Cross-sectional. SETTING: University hospital neonatal intensive care unit. PARTICIPANTS: 22 preterm neonates were studied, with gestational age of 34 ± 2 weeks, birth weight of 1804 ± 584 g, 68% female, 30 ± 12 hours of life, and 30% intubated. PROCEDURES: Two neonatologists (A and B) observed the patients at the bedside and on video films for 10 minutes. The Neonatal Facial Coding System and the Clinical Scoring System were scored at 1, 5, and 10 minutes. The final score was the median of the three values for each observer and scale. A and B were blinded to each other. Video assessments were made three months after bedside evaluations. MAIN MEASUREMENTS: End scores were compared between the observers using the intraclass correlation coefficient and bias analysis (paired t test and signal test). RESULTS: For the Neonatal Facial Coding System, at the bedside and on video, A and B showed a significant correlation of scores (intraclass correlation score: 0.62), without bias between them (t test and signal test: p > 0.05). For the Clinical Scoring System bedside assessment, A and B showed correlation of scores (intraclass correlation score: 0.55), but bias was also detected between them: A scored on average two points higher than B (paired t test and signal test: p 0,05). Para a Escala de Conforto Clínico à beira do leito, os escores obtidos por A e B mostraram uma correlação significante (0,55), foi detectado: o escore obtido por A foi, em média, dois pontos superior ao de B (teste t e do sinal: p < 0,05). Para a mesma escala aplicada em vídeo, os escores obtidos por A e B não mostraram correlação (0,25) e detectou-se viés (teste t e do sinal: p < 0,05). CONCLUSÃO: Os resultados reforçam a confiabilidade do Sistema de Codificação da Atividade Facial Neonatal aplicado à beira do leito para a avaliação da dor no recém-nascido pré-termo.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Neonatal DivisionUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of EpidemiologyUNIFESP, EPM, Neonatal DivisionUNIFESP, EPM, Department of EpidemiologySciEL