Historical exposure to non-persistent environmental pollutants and risk of type 2 diabetes in a Spanish sub-cohort from the European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND: Environmental factors are believed to account for a substantial burden of type 2 diabetes mellitus (T2DM). Non-persistent environmental pollutants (npEPs) are a group of widely-used chemicals identified as endocrine/metabolic disrupting chemicals and obesogens. The aim of this study was to analyse the potential associations of serum levels of three groups of npEPs with the risk of incident T2DM. METHODS: This is a longitudinal study within a sub-sample of Granada EPIC-Spain cohort (n = 670). We quantified serum concentrations of 7 npEPs: four parabens (Methylparaben (MP) ethylparaben (EP), propylparaben (PP) and butilparaben (BP); two benzophenones: Benzophenone 1 (BP1), Benzophenone 3 (BP3); and Bisphenol A (BPA). Exposure was assessed by means of chemical analyses of serum samples collected at recruitment, and information on potential confounders was gathered by using validated questionnaires at baseline. Follow-up was performed by review of patients' clinical records. Cox Proportional Hazards Models were used for the statistical analyses. RESULTS: Median follow-up time was 23 years. There were 182 (27%) incident T2DM diagnoses in our sub-cohort. MP was the most frequently detected npEP, 88.42% samples above the limit of detection, and BP showed the lowest percentage of detection (19.21%). Those individuals within the fourth PP quartile (0.53-9.24 ng/ml) showed a statistically significant increased risk of T2DM (HR = 1.668 p = 0.012), while BP1 concentrations showed an inverse non-significant trend with the risk. CONCLUSIONS: We evidenced a potential contribution of npEP exposure on T2DM, but no clear trend was observed. However, limitations in relation to exposure estimation might influence our findings and further research is warranted to confirm our results.

Transforming Growth Factor Beta 1 and Vascular Risk in Alcoholics.

INTRODUCTION: Transforming growth factor beta-1 (TGF-ß1) is a pleiotropic cytokine. Its relationship with atherosclerosis is debatable, protective or deleterious effects have been described. Alcoholics are at increased vascular risk. Although TGF-ß1 is increased in alcoholics, its role on vascular risk factors has not been analyzed. This is the objective of this study. PATIENTS AND METHODS: 79 heavy alcoholics and 34 controls were included. Calcium deposition in the aortic arch was assessed in the plain thorax X-ray film. Ankle-brachial index was recorded in 48 patients. All the patients underwent complete laboratory evaluation, including serum levels of TGF-ß1, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, and interferon-γ (IFN-γ).We analyzed the relationships between TGF-ß1 and vascular risk factors by both univariate (parametric or non parametric tests), or multivariate analysis to discern on which variables TGF-ß1 levels depend. RESULTS: Serum TGF-ß1 levels were higher among patients (t = 2.73; P = 0.008), but no differences exist among cirrhotics (17246 ± 11,021 pg/mL) and non-cirrhotics (21,340 ± 12,442 pg/mL). TGF-ß1 showed significant correlations with total cholesterol (r = 0.28; P = 0.017) and HDL- cholesterol (r = 0.25; P = 0.042), and inverse correlations with body mass index (BMI; ρ = -0.37; P = 0.004), IL-4 (ρ = -0.31; P = 0.009), INF-γ (ρ = -0.28; P = 0.001), and IL-6 (ρ = -0.38; P = 0.001). By multivariate analysis, only BMI, IL-6 and HDL-cholesterol showed independent relationships with TGF-ß1. No relationships were observed with ankle-brachial index or calcium in the aortic arch, hypertension, diabetes, left ventricular hypertrophy or atrial fibrillation. CONCLUSION: TGF-ß1 levels are increased in alcoholics, but are unrelated to vessel wall calcification or arterial stiffness.

[Knowledge and attitude among general practitioners in Andalusia (Spain) on the identification of subjects at high risk of breast and colorectal cancer]. / Conocimientos y actitudes de los médicos de Atención Primaria de Andalucía (España) sobre la detección de personas con riesgo elevado de cáncer de mama y colorrectal.

AIMS: To assess the knowledge and attitude among general practitioners in Andalusia on the identification of subjects with elevated risk for breast cancer, colorectal cancer, and hereditary cancers, as well as to detect barriers to accessibility to the screening programs. METHODS: A descriptive, cross-sectional study was conducted based on an online survey of 24 questions. Data are shown as frequencies, and association tests were statistically used. The level of significance was set at<.05. RESULTS: Survey response rate was 32%, of which 224 were valid, and included 56% men, and a mean age±DE of 46±12 years. Established criteria for high risk breast cancer were already known by 71.4% [95% CI 65-76], being worst in those living in big cities (P<.014). Among general practitioners, 86% were allowed to order mammography in women with lumps or at moderate to high risk for breast cancer. As regards colorectal cancer, 87.9% of general practitioners knew the risk factors. Among general practitioners, 58.2% [95% CI 49-62] were allowed to order a colonoscopy if clinical suspicion was present, especially if they lived in large cities (P<.0001). CONCLUSIONS: The screening program for breast cancer is well-known by general practitioners, and the access to mammography is successful. Most of the general practitioners consider the follow-up program for persons at high risk for colorectal cancer appropriate, although half of those surveyed had some barriers to ordering colonoscopy. Knowledge on hereditary cancer is limited, and varies among areas. There is also a general lack of awareness on hereditary cancer and genetic counselling units.

Relative and combined effects of selenium, protein deficiency and ethanol on hepatocyte ballooning and liver steatosis.

Oxidative damage plays a key role in alcohol-mediated liver alterations. Selenium, a potent antioxidant, is decreased in alcoholics. This study was conducted to analyse if the supplementation with selenium may alter liver changes in a murine model fed ethanol and/or a 2 % protein-containing diet, following the Lieber-DeCarli design. Adult male Sprague Dawley rats were divided into eight groups which received the Lieber-DeCarli control diet; an isocaloric, 36 % ethanol-containing diet; an isocaloric, 2 % protein-containing diet; and an isocaloric diet containing 2 % protein and 36 % ethanol diet; and other similar four groups to which selenomethionine (1 mg/kg body weight) was added. After sacrifice (5 weeks later), liver fat amount and hepatocyte areas of pericentral and periportal cells were measured, and liver and serum selenium, activity of liver glutathione peroxidase (GPX), and liver malondialdehyde were determined. Ethanol-fed rats showed increased hepatocyte areas and fat accumulation especially when ethanol was added to a 2 % protein diet. Selenium caused a decrease in hepatocyte ballooning and liver fat amount, but an increase in GPX activity, and a marked increase in serum and liver selenium. The present study demonstrates that selenium, added to the diet of rats in the form of seleniomethionine, prevents the appearance of early signs of ethanol-mediated liver injury under the conditions of the Lieber-DeCarli experimental design.

Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women: the EPIC-InterAct Study.

AIMS/HYPOTHESIS: We examined the independent and combined associations of physical activity and obesity with incident type 2 diabetes in men and women. METHODS: The InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a randomly selected subcohort of 16,154 individuals, drawn from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Physical activity was assessed by a four-category index. Obesity was measured by BMI and waist circumference (WC). Associations between physical activity, obesity and case-ascertained incident type 2 diabetes were analysed by Cox regression after adjusting for educational level, smoking status, alcohol consumption and energy intake. In combined analyses, individuals were stratified according to physical activity level, BMI and WC. RESULTS: A one-category difference in physical activity (equivalent to approximately 460 and 365 kJ/day in men and women, respectively) was independently associated with a 13% (HR 0.87, 95% CI 0.80, 0.94) and 7% (HR 0.93, 95% CI 0.89, 0.98) relative reduction in the risk of type 2 diabetes in men and women, respectively. Lower levels of physical activity were associated with an increased risk of diabetes across all strata of BMI. Comparing inactive with active individuals, the HRs were 1.44 (95% CI 1.11, 1.87) and 1.38 (95% CI 1.17, 1.62) in abdominally lean and obese inactive men, respectively, and 1.57 (95% CI 1.19, 2.07) and 1.19 (95% CI 1.01, 1.39) in abdominally lean and obese inactive women, respectively. CONCLUSIONS/INTERPRETATION: Physical activity is associated with a reduction in the risk of developing type 2 diabetes across BMI categories in men and women, as well as in abdominally lean and obese men and women.

Changes in cytokine levels during admission and mortality in acute alcoholic hepatitis.

Cytokine levels are raised in acute alcoholic hepatitis. However, there are disparate results regarding the duration of altered plasma levels, and there are also discrepancies about the relation of changes during the first 15 days after admission with short-term (in-hospital) or long-term mortality. In 56 patients with acute alcoholic hepatitis we found that IL-8, IL-4, Interferon-γ (IFN-γ), malondialdehyde and C-reactive protein remained higher in patients than in 18 age- and sex-matched controls at admission, at the 7th day and at the 15th day after admission. Moreover, IL-4 levels (and to a lesser extent, IL-10 and IFN-γ ones) increased along the three determinations. However, comparing patients who died during the admission with those who did not, there were no statistically significant differences, but there was a nearly significant trend for MDA (Z=1.89; p=0.059), with higher levels among those who died. When changes between the first and the second determinations were compared with long-term survival, only IL-8 and IFN-γ showed a relation with mortality. IFN-γ values increased among those who survived and decreased among those who died (p=0.048). IFN-γ values at the first determination also showed a relation with long-term mortality, especially when patients with IFN-γ values in the first quartile were compared with those of the 4th one (log rank=5.64; p=0.018; Breslow=4.64; p=0.031). Besides Interferon-γ, only C-reactive protein showed differences between the first and the 4th quartile regarding mortality (Log rank=4.50; p=0.034; Breslow 4.33; p=0.038). In contrast with other studies, no relation was found between TNF-α or IL-6 and mortality.

Breast cancer incidence in Spain before, during and after the implementation of screening programmes.

BACKGROUND: A downturn in breast cancer (BC) incidence among Spanish women has been recently reported and attributed to screening saturation. This article analyses BC trends and their relationship with the introduction of the screening programme in all Spanish regions having available information. MATERIAL AND METHODS: The study covers the period 1980-2004. All Spanish population-based cancer registries with 10 years of uninterrupted registration furnished data on invasive BC. Trends in BC incidence among women aged <45 years and among those aged > or =45 years were assessed using Poisson transition models to estimate the existence of a change-point in the overall trend. Furthermore, in those regions that had registered BC incidence before implementing the screening programme, the annual percentage change in women aged > or =45 years was computed before screening, during the first round of screening and after full coverage had been achieved. RESULTS: The study included 82 699 incident cases. Whereas BC increased during the 1980s and 1990s, from 2001 onwards a decline was observed among women aged > or =45 years. This phenomenon was clearly visible in regions that had implemented BC screening before 2000 and attained high participation rates. In such areas, BC incidence rose sharply during screening implementation, with an overall increase of approximately 20%-30%. BC incidence fell once full coverage was achieved and tended to level off or even increase thereafter, as was the case in Navarre. In women aged <45 years, BC increased by 1.7% per annum across the period. CONCLUSIONS: Screening has strongly influenced recent BC trends among Spanish women aged > or =45 years. Our results support the influence of screening saturation on the recent decline of BC. Among younger women, incidence is still rising, probably reflecting the lifestyle changes observed in younger generations.

Alcoholic myopathy: vitamin D deficiency is related to muscle fibre atrophy in a murine model.

AIMS: Chronic myopathy has been described in alcoholics, characterized by atrophy of type II fibres, and vitamin D deficiency. Low serum vitamin D levels are frequent in alcoholics. The possibility exists that serum vitamin D levels are related to muscle changes in a murine experimental model. METHODS: Histological analysis of the right gastrocnemius muscle was performed in four groups of adult Sprague-Dawley rats, sacrificed after 5 weeks of treatment following the Lieber-DeCarli model. We studied the association between muscle histological changes and the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products (malondialdehyde); parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), free testosterone, 1,25 dihydroxyvitamin D3 (vitamin D) and corticosterone; and serum calcium and magnesium. RESULTS: Alcoholic animals showed type IIa and IIb fibre atrophy, especially the low-protein-fed ones, an effect dependent on protein deficiency. A significant relationship was observed between serum vitamin D levels and IIa fibre area (rho = 0.56, P = 0.002), and also, as a trend, between vitamin D and type IIb fibre area (rho = 0.39, p = 0.053); between vitamin D and muscle GPX (rho = 0.40, P = 0.025) and SOD activities (rho = 0.43, P = 0.012). Muscle GPX activity was significantly related with type I fibre area (rho = 0.49, P = 0.01) and muscle SOD, with type IIa fibre area (rho = 0.38, P = 0.045). Serum testosterone was also related with type IIa fibre area (rho = 0.61, P < 0.001). No relation was observed between serum PTH, corticosterone, or IGF-1 and fibre area PTH and antioxidant systems. Multiple regression analysis disclosed that the only parameter independently related with type IIa fibre area was serum vitamin D. CONCLUSION: Low vitamin D levels are related to muscle fibre atrophy, and altered levels of muscle antioxidant enzymes could play a role in alcoholic myopathy.

Prognostic value of nutritional status in alcoholics, assessed by double-energy X-ray absorptiometry.

OBJECTIVES: This study was performed in order to assess nutritional status of 77 alcoholic patients. METHODS: Patients underwent a total body double-energy X-ray absorptiometry (DEXA) analysis, with estimation of lean and fat mass at different parts of the body. RESULTS: Lean mass, but not fat mass, was significantly reduced among alcoholics, compared to 31 age-matched controls, especially at right arm, legs, and total body. Lean mass at both arms was significantly related to liver function parameters (albumin, prothrombin activity, bilirubin) and, inversely, with ethanol consumption. The 24 patients who died during a follow-up period of 88 months showed less lean mass at both arms, trunk, and left leg, and also less fat at the left arm, than survivors. When right and left arm lean mass were classified in quartiles, Kaplan-Meier curves showed significant differences between dead and survivors. Left arm lean mass was the parameter which was independently related to mortality when encephalopathy was not included in a stepwise Cox regression analysis, but was displaced by this last parameter when it was also introduced in the analysis. CONCLUSION: Lean mass is reduced in alcoholics, is related to liver function derangement and ethanol consumption, and is related to mortality.

Lipid peroxidation and serum cytokines in acute alcoholic hepatitis.

AIMS: Increased exposure of Kupffer cells to intestinal-borne Gram-negative bacteria enhances the metabolism and leads to cytokine production by these cells. Activation of Kupffer cells increases free radical release, which may, in turn, enhance cytokine secretion, creating a positive feedback loop, which contributes to liver inflammation. Cytokines act on T cells, inducing their proliferation and secretion of additional interleukins. Lipid peroxidation products (malondialdehyde; MDA) form adducts with proteins and acetaldehyde, triggering a T cell immune response. Controversy exists about the predominance of either Th-1 or Th-2 cellular responses. We performed the present study in order to analyse the cytokine pattern in patients with acute alcoholic hepatitis, its relation to MDA and the relation between all these parameters and liver function and prognosis. SUBJECTS AND METHODS: The study included 53 male alcoholics, 47 followed up for a median time of 32 months, during which 17 of them died. We measured serum MDA, tumour necrosis factor-alpha, interferon gamma (IFNG) and interleukins (IL) 4, 6, 8, and 10. RESULTS: MDA levels were raised in cirrhotics and non-cirrhotics with alcoholic hepatitis, maintaining a relationship with bilirubin and Maddrey index, and with mortality in the univariate analysis. Both IFNG and IL-4 were raised in our patients compared with controls, as well as IL-8, and IL-6, but IL-10 were below the detection limit in the majority of cases, especially in cirrhotics. Using a Cox regression model, Maddrey index displaced MDA in the survival analysis. CONCLUSIONS: Our data lend support to the hypothesis that activation of both Th-1 and Th-2 cell subsets take place. MDA levels are raised in alcoholics with alcoholic hepatitis and are closely related to liver function derangement and to survival, although this is displaced by Maddrey index using Cox regression model.

Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24-h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. DESIGN: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. RESULTS: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R(partial)(2) = 17.2%) for beta-cryptoxanthin, total carrots ((partial)(2) = 13.4%) and root vegetables (R(partial)(2) = 13.3%) for alpha-carotene, and tomato products (R(partial)(2) = 13.8%) for lycopene. For 24HDR, the highest R(partial)(2) was for fruits in relation to beta-cryptoxanthin (7.9%). CONCLUSIONS: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.

Paciente con dolor simétrico en tobillos y muñecas y ginecomastia / Patient with symmetric pain in ankles and wrists and gynecomasty

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Case report. Pulmonary involvement in an adult male affected by type B Niemann-Pick disease.

We report the case of a 39-year-old male patient affected by type B Niemann-Pick disease, in whom pulmonary involvement became evident 15 years after the initial diagnosis. Pulmonary involvement was discovered incidentally during the evaluation of a dry cough and exertional dyspnoea which occurred in the context of an acute febrile, self-limiting illness. In this case, the pulmonary involvement is clinically mild, with minimal alteration of the diffusing capacity for carbon monoxide (DL(CO)), despite moderate fibrosis and widespread infiltration of both alveoli and interstitium by sea blue histiocytes.

Fumador de 49 años con red venosa superficial en tórax y cuello y disfonía / Collateral circulation in thorax and dysphonia in a 49-year old smoker

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