Mustard allergy is a not-uncommon disorder that can induce severe reactions. Significant associations with mugwort pollinosis and several plant-derived food allergies are demonstrated, suggesting a new mustard-mugwort allergy syndrome. A relationship between this syndrome and food-dependent exercise-induced anaphylaxis is also reported.
During hyposensitization therapy with aluminium-precipitated antigen solutions, a small % of patients develop persistent subcutaneous nodules at the injection site; the existence of delayed sensitivity to aluminium has been implicated in the pathogenesis of these nodules. We studied the prevalence of aluminium sensitivity (using patch, prick and intradermal tests) and common contact allergens (TRUE Test) in 20 healthy subjects, and in 40 patients treated with aluminium-containing extracts, 20 of whom had persistent subcutaneous nodules that remained for more than 2 months, the other half having no nodular reactions or nodules that remained for less than 2 months. Aluminium sensitivity was found only in those patients of the treated group who had persistent nodular reactions, 4 cases of positivity to an aluminium chloride patch test being found. All 4 cases were women, nodules remained for more than 6 months, and intracutaneous tests were negative. 3 of them also had contact sensitivity to nickel. In 2 cases, nodules were removed for histological and histochemical examination, showing non-specific inflammatory granulomas, and aluminium crystals being found in only 1 case. It is concluded that delayed sensitivity to aluminium appears to be implicated in the pathogenesis of persistent nodular reactions, but sensitivity to aluminium was not found in patients treated with aluminium-precipitated extracts without persistent nodular reactions.
In the immunocompetent setting, antiviral therapy-related anemia has recently been shown to be associated with a sustained virological response (SVR). Our goal was to assess whether this is also true for liver transplantation (LT). We included 160 LT patients with recurrent hepatitis C virus (HCV) who were treated with pegylated interferon and ribavirin (RBV) between 2002 and 2010; 76% of the patients were men, the median age of the patients was 56 years (range ¼ 33-75 years), 63% had advanced fibrosis, and 86% were infected with HCV genotype 1a or 1b. The baseline immunosuppression was tacrolimus in 56% of the patients. Mycophenolate mofetil (MMF) was used in 15%. Anemia was defined as a hemoglobin (Hb) level < 10 g/dL. Significant anemia was present when the Hb decline was >5 g/dL. Anemia and significant anemia developed in 67% and 41% of the patients, respectively. Erythropoietin was used in 60%. Factors independently associated with significant anemia included low estimated creatinine clearance [relative risk (RR) ¼ 0.951, 95% confidence interval (CI) ¼ 0.925-0.978, P ¼ 0.0001], a longer time from LT to therapy (RR ¼ 1.001, 95% CI ¼ 1.000-1.001, P ¼ 0.002), high baseline viremia (RR ¼ 3.2, 95% CI ¼ 1.3-8.1, P ¼ 0.01), cyclosporine A (CSA)-based immunosuppression (RR: 3.472, 95% CI: 1.386-8.695; P ¼ 0.008), and the use of MMF (RR: 5.346, 95% CI: 1.398-20.447; P ¼ 0.014). An SVR occurred in 43% of the patients; the factors associated with an SVR included baseline variables (younger recipient age, younger donor age, infections with non-1 HCV genotypes, body mass index, and mild fibrosis) and on-treatment factors related to adherence or viral kinetics. Anemia resulted in RBV dose reductions but was not associated with the virological response at any time. In conclusion, anemia is a very frequent complication in LT patients during antiviral therapy and is associated with increased RBV dose reduction but not with an SVR. Predictors of anemia include MMF or CSA immunosuppression, high viremia, and renal insufficiency.
A sustained virological response (SVR) is achieved by 30% of naive liver transplantation (LT) recipients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV). Almost no data are available about retreatment. The aim of this study was to assess the efficacy, tolerability, and SVR predictors of retreatment. Data were collected from 4 centers on the retreatment of prior nonresponders to standard therapy or PEG-IFN (with or without RBV) and relapsers. Seventy-nine of 301 treatment-experienced LT patients (26%), who had a median age of 59 years (range ¼ 35-77 years) and were mostly male (72%) and infected with genotype 1 (87%), were retreated with PEG-IFN and RBV at a median of 6.9 years after LT. During the first course of therapy, 35% were treated with interferon, 49% received tacrolimus, 52% received steroids, and 49.5% were relapsers. Retreatment was started at a median of 1.9 years (range ¼ 45 days to 8.2 years) after the end of the first course. The proportion of patients with cirrhosis increased from 10% to 37% (P < 0.001). In addition, in retreated patients, full initial RBV doses (P ¼ 0.03), growth factors [erythropoietin (P < 0.001) and granulocyte colony-stimulating factor (P ¼ 0.048)], and transfusions (P ¼ 0.03) were used more frequently, and the treatment duration was longer (P ¼ 0.03). An endof-treatment response was achieved in 61%, whereas SVR, which was associated with improved survival, occurred in 28 (35%). The variables predicting SVR were age (P ¼ 0.04), disease severity [fibrosis (50% with F0-F2 versus 26% with F3-4), P ¼ 0.03; bilirubin, P ¼ 0.006; platelet count, P ¼ 0.03], adherence, and viral kinetics. None of the patients without an early virological response achieved SVR. There was a trend of prior relapsers achieving higher SVR rates than prior nonresponders. In conclusion, SVR, which was achieved by approximately one-third of the retreated patients, can be predicted with the same variables used for naive LT recipients (age, disease severity, adherence, and viral kinetics) and is associated with enhanced survival. Liver Transpl 19:69-77, 2013. V C 2012 AASLD.Received July 3, 2012; accepted July 29, 2012.After liver transplantation (LT), a response to interferon (IFN)-based therapies resulting in the permanent eradication of hepatitis C virus (HCV) is associated with improved histology, reduced disease progression, a decreased risk of clinical decompensation, and improved overall graft and patient survival.
The genome revolution represents a complete change on our view of biological systems. The quantitative determination of changes in all major molecular components of the living cells, the "omics" approach, opened whole new fields for all health sciences. Genomics, transcriptomics, proteomics, metabolomics, and others, together with appropriate prediction and modeling tools, will mark the future of developmental toxicity assessment both for wildlife and humans. This is especially true for disciplines, like teratology, which rely on studies in model organisms, as studies at lower levels of organization are difficult to implement. Rodents and frogs have been the favorite models for studying human reproductive and developmental disorders for decades. Recently, the study of the development of zebrafish embryos (ZE) is becoming a major alternative tool to adult animal testing. ZE intrinsic characteristics makes this model a unique system to analyze in vivo developmental alterations that only can be studied applying in toto approaches. Moreover, under actual legislations, ZE is considered as a replacement model (and therefore, excluded from animal welfare regulations) during the first 5 days after fertilization. Here we review the most important components of the zebrafish toolbox available for analyzing early stages of embryotoxic events that could eventually lead to teratogenesis.
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