184 research outputs found

    Assessment of DNA damages in lymphocytes of agricultural workers exposed to pesticides by comet assay in a cross-sectional study

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    Purpose: To assess the predictive power of the comet assay in the context of occupational exposure to pesticides. Materials and methods: The recruited subjects completed a structured questionnaire and gave a blood sample. Exposure to pesticides was measured by means of an algorithm based on Dosemeci’s work (Agricultural Health Study). Approximately 50 images were analyzed for each sample via fluores- cence microscopy. The extent of DNA damage was estimated by tail moment (TM) and is the product of tail DNA (%) and tail Length. Results: Crude significant risks (odds ratios, ORs) for values higher than the 75th percentile of TM were observed among the exposed subjects (score>1). The frequency of some confounding factors (sex, age and smoking) was significantly higher among the exposed workers. A significant dose–effect relationship was observed between TM and exposure score. Significant high-risk estimates (ORs), adjusted by the studied confounding factors, among exposure to pesticides and TM, % tail DNA and tail length were confirmed using unconditional logistic regression models. Conclusions: The adjusted associations (ORs) between the comet parameters and exposure to pesti- cides were significant. The sensitivity of the comet test was low (41%), the specificity (89%) and the predictive positive value (0.77) were found acceptable

    Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.

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    BACKGROUND: The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. METHODS: We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). RESULTS: An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, -20 percent; 95 percent confidence interval, -26 to -14 percent; P=0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, -17 percent; 95 percent confidence interval, -24 to -10 percent; P<0.001), bacteremias (difference in risk, -16 percent; 95 percent confidence interval, -22 to -9 percent; P<0.001), and single-agent gram-negative bacteremias (difference in risk, -7 percent; 95 percent confidence interval, -10 to -2 percent; P<0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma. CONCLUSIONS: Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia. The long-term effect of this intervention on microbial resistance in the community is not known

    Outcomes of Surgical Management of Familial Intrahepatic Cholestasis 1 and Bile Salt Export Protein Deficiencies

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    Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP-common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP-other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP-common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP-other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP-other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations.Peer reviewe

    Hemodynamic predictors of aortic dilatation in bicuspid aortic valve by velocity-encoded cardiovascular magnetic resonance

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    <p>Abstract</p> <p>Background</p> <p>Congenital Bicuspid Aortic Valve (BAV) is a significant risk factor for serious complications including valve dysfunction, aortic dilatation, dissection, and sudden death. Clinical tools for identification and monitoring of BAV patients at high risk for development of aortic dilatation, an early complication, are not available.</p> <p>Methods</p> <p>This paper reports an investigation in 18 pediatric BAV patients and 10 normal controls of links between abnormal blood flow patterns in the ascending aorta and aortic dilatation using velocity-encoded cardiovascular magnetic resonance. Blood flow patterns were quantitatively expressed in the angle between systolic left ventricular outflow and the aortic root channel axis, and also correlated with known biochemical markers of vessel wall disease.</p> <p>Results</p> <p>The data confirm larger ascending aortas in BAV patients than in controls, and show more angled LV outflow in BAV (17.54 ± 0.87 degrees) than controls (10.01 ± 1.29) (p = 0.01). Significant correlation of systolic LV outflow jet angles with dilatation was found at different levels of the aorta in BAV patients STJ: r = 0.386 (N = 18, p = 0.048), AAO: r = 0.536 (N = 18, p = 0.022), and stronger correlation was found with patients and controls combined into one population: SOV: r = 0.405 (N = 28, p = 0.033), STJ: r = 0.562 (N = 28, p = 0.002), and AAO r = 0.645 (N = 28, p < 0.001). Dilatation and the flow jet angle were also found to correlate with plasma levels of matrix metallo-proteinase 2.</p> <p>Conclusions</p> <p>The results of this study provide new insights into the pathophysiological processes underlying aortic dilatation in BAV patients. These results show a possible path towards the development of clinical risk stratification protocols in order to reduce morbidity and mortality for this common congenital heart defect.</p

    Nomenclature, Diagnosis and Management of Drug-induced Autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report.

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    Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article summarizes the major topics discussed at a joint International Conference held between Drug-Induced Liver Injury consortium and the International Autoimmune Hepatitis Group. DI-ALH is a liver injury with laboratory and/or histological features that may be indistinguishable from those of autoimmune hepatitis (AIH). Previous studies have revealed that patients with DI-ALH and those with idiopathic AIH have very similar clinical, biochemical, immunological and histological features. Differentiating DI-ALH from AIH is important as patients with DI-ALH rarely require long-term immunosuppression and often resolve spontaneously after stopping the culprit drug whereas patients with AIH mostly need long-term immunosuppression. Therefore, revision of the diagnosis on long-term follow up may be necessary in some cases. More than 40 different drugs including nitrofurantoin, methyldopa, hydralazine, minocycline, infliximab, herbal and dietary supplements such as Khat and Tinospora cordifolia have been implicated in DI-ALH. Understanding of DI-ALH is limited by the lack of specific markers of the disease that could allow a precise diagnosis and similarly, there is no single feature which is diagnostic of AIH. A management algorithm is proposed. There is an urgent need to prospectively evaluate patients with DI-ALH systematically to enable definitive characterization of this condition
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