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Drug Hypersensitivity (drug + hypersensitivity)
Selected AbstractsDrug hypersensitivity , allergy passionALLERGY, Issue 8 2006P. Demoly No abstract is available for this article. [source] RESEARCH ARTICLE: RPD3 and ROM2 are required for multidrug resistance in Saccharomyces cerevisiaeFEMS YEAST RESEARCH, Issue 3 2008Silvia Borecka-Melkusova Abstract The PDR5 gene encodes the major multidrug resistance efflux pump in Saccharomyces cerevisiae. In drug-resistant cells, the hyperactive Pdr1p or Pdr3p transcriptional activators are responsible for the PDR5 upregulation. In this work, it is shown that the RPD3 gene encoding the histone deacetylase that functions as a transcriptional corepressor at many promoters and the ROM2 gene coding for the GDP/GTP exchange protein for Rho1p and Rho2p participating in signal transduction pathways are required for PDR5 transcription under cycloheximide-induced and noninduced conditions. Transposon insertion mutations in ROM2, RPD3 and some other genes encoding specific subunits of the large Rpd3L protein complex resulted in enhanced susceptibility of mutant cells to antifungals. In the rpd3, and rom2, mutants, the level of PDR5 mRNA and the rate of rhodamine 6G efflux were reduced. Unlike rpd3,, in rom2, mutant cells the drug hypersensitivity and the defect in PDR5 expression were suppressed by PDR1 or PDR3 overexpressed from heterologous promoters and by the hyperactive pdr3-9 mutant allele. The results indicate that Rpd3p histone deacetylase participating in chromatin remodeling and Rom2p participating in the cell integrity pathway are involved in the control of PDR5 expression and modulation of multidrug resistance in yeast. [source] A case of acute hepatitis E associated with multidrug hypersensitivity and cytomegalovirus reactivationHEPATOLOGY RESEARCH, Issue 2 2007Yasuhiro Takikawa A 65-year-old Japanese man was hospitalized because of acute hepatitis and severe cholestasis due to hepatitis E virus (HEV) infection combined with a drug reaction to a cold preparation. He died of disseminated intravascular coagulation and severe intestinal bleeding due to systemic cytomegalovirus reactivation following the development of severe eruptions with marked eosinophilia due to drug hypersensitivity to taurine and ursodeoxycholate preparations. The close interaction between viral infection or reactivation and drug hypersensitivity was considered as a pathophysiology in this case, which emphasizes the need for further study of the immunological mechanism of the interaction. [source] A case of fatal anaphylaxis in a dog associated with a dexamethasone suppression testJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 3 2005DACVECC, DACVIM, Michael Schaer DVM Abstract Objective: To describe a case of fatal anaphylaxis in a dog associated with a ,routine' dexamethasone suppression test. Case summary: An 8-year-old, spayed female dog, was treated with parenteral dexamethasone for a diagnosis of immune-mediated thrombocytopenia. The dog had responded to treatment, but 9 months later was evaluated for endogenous hyperadrenocorticism, prior to surgery for a ruptured anterior cruciate ligament. A normal ACTH stimulation test was followed by a high-dose dexamethasone suppression test. Immediately following the intravenous injection of dexamethasone, the dog developed severe anaphylactic shock and died. The postmortem examination findings supported the diagnosis of anaphylaxis. New information provided: The anaphylaxis in this dog was fulminating and by-passed the usual early signs of drug hypersensitivity. This is the first case in the veterinary literature reporting on dexamethasone as the cause of this dog's catastrophic event. [source] In vitro detection and characterization of drug hypersensitivity using flow cytometryALLERGY, Issue 1 2010M. Martin Abstract Background:, The lymphocyte transformation test (LTT) is the only in vitro test for detecting drug sensitization at the cellular level irrespective of the reaction's phenotype. However, the LTT includes working with radioactive substances and is considered impracticable for routine laboratory investigation. Objective:, The aim of this study was to assess drug-specific cytokine production by means of flow cytometry as an alternative nonradioactive approach which may be more appropriate for routine testing and may provide in addition more information about the pathophysiology of the reaction than proliferation-based assays, like the LTT. Method:, Peripheral blood mononuclear cells of 19 patients were incubated with culprit drugs (n = 28) or irrelevant antigens (n = 10). Ten healthy persons served as controls for all different drugs (n = 15). Intracellular interleukin (IL)-5, interferon (IFN)-, and IL-10 production was investigated using flow cytometry. Accuracy of the flow cytometry test system was confirmed using different statistical tests, i.e. receiver operating characteristic curve and Mann,Whitney rank test. In addition, drug-specific secretion of IL-5, IL-2 and IFN-, were analysed using enzyme-linked immunosorbent assay (ELISA). Results:, Drug-specific cytokine production could be demonstrated in 75% of the patients using flow cytometry and in 79% using ELISA respectively. Combining ELISA and flow cytometry increased the sensitivity to 100%. Analysis of involved T-cell subsets [e.g. CD4+ or CD8+; T helper (TH) 1 or TH 2] allowed characterization of the in vitro lymphocyte reactivity pattern. Conclusions:, Analysis of drug-specific cytokine production by means of flow cytometry proved a useful and reliable approach for the in vitro detection and characterization of drug hypersensitivities. [source] Drug-specific in vitro release of IL-2, IL-5, IL-13 and IFN-, in patients with delayed-type drug hypersensitivityALLERGY, Issue 9 2009P. Lochmatter Background:, The most prevalent drug hypersensitivity reactions are T-cell mediated. The only established in vitro test for detecting T-cell sensitization to drugs is the lymphocyte transformation test, which is of limited practicability. To find an alternative in vitro method to detect drug-sensitized T cells, we screened the in vitro secretion of 17 cytokines/chemokines by peripheral blood mononuclear cells (PBMC) of patients with well-documented drug allergies, in order to identify the most promising cytokines/chemokines for detection of T-cell sensitization to drugs. Methods:, Peripheral blood mononuclear cell of 10 patients, five allergic to ,-lactams and five to sulfanilamides, and of five healthy controls were incubated for 3 days with the drug antigen. Cytokine concentrations were measured in the supernatants using commercially available 17-plex bead-based immunoassay kits. Results:, Among the 17 cytokines/chemokines analysed, interleukin-2 (IL-2), IL-5, IL-13 and interferon-, (IFN-,) secretion in response to the drugs were significantly increased in patients when compared with healthy controls. No difference in cytokine secretion patterns between sulfonamide- and ,-lactam-reactive PBMC could be observed. The secretion of other cytokines/chemokines showed a high variability among patients. Conclusion:, The measurement of IL-2, IL-5, IL-13 or IFN-, or a combination thereof might be a useful in vitro tool for detection of T-cell sensitization to drugs. Secretion of these cytokines seems independent of the type of drug antigen and the phenotype of the drug reaction. A study including a higher number of patients and controls will be needed to determine the exact sensitivity and specificity of this test. [source] Diagnosis of nonimmediate reactions to ,-lactam antibioticsALLERGY, Issue 11 2004A. Romano Nonimmediate manifestations (i.e. occurring more than 1 h after drug administration), particularly maculopapular and urticarial eruptions, are common during , -lactam treatment. The mechanisms involved in most nonimmediate reactions seem to be heterogeneous and are not yet completely understood. However, clinical and immunohistological studies, as well as analysis of drug-specific T-cell clones obtained from the circulating blood and the skin, suggest that a type-IV (cell-mediated) pathogenic mechanism may be involved in some nonimmediate reactions such as maculopapular or bullous rashes and acute generalized exanthematous pustulosis. In the diagnostic work-up, the patient's history is fundamental; patch testing is useful, together with delayed-reading intradermal testing. The latter appears to be somewhat more sensitive than patch testing, but also less specific. In case of negative allergologic tests, consideration should be given to provocation tests, and the careful administration of the suspect agents. With regard to in vitro tests, the lymphocyte transformation test may contribute to the identification of the responsible drug. Under the aegis of the European Academy of Allergology and Clinical Immunology (EAACI) interest group on drug hypersensitivity and the European Network for Drug Allergy (ENDA), in this review we describe the general guidelines for evaluating subjects with nonimmediate reactions to , -lactams. [source] Cytotoxic mechanisms in different forms of T-cell-mediated drug allergiesALLERGY, Issue 6 2004P. C. Kuechler Background:, Cytotoxic mechanisms are involved in different forms of drug induced exanthems. Methods:, Here we compare the killing pathways of CD4+, CD8+ and CD4/CD8+ T-cell lines (TCL) and clones derived from patients suffering from maculopapular, bullous and pustular drug eruptions. In vitro, perforin and Fas-mediated killing was analysed in cytotoxicity assays against autologous Epstein,Barr virus (EBV)-transformed B-cell lines, Fas-transfected mouse lymphoblasts and natural killer (NK)-target cells. In addition, affected skin lesions and the TCL and clones were stained for perforin and FasL-expression. Results:, We detected perforin and some FasL-mediated killing in all three types of exanthems. Some of the drug-specific T-cell clones analysed exerted mainly perforin-, other more FasL-mediated killing showing no strict relationship between their perforin- and Fas-mediated cytotoxic capacity. Using a cell culture method focusing on the generation of cytotoxic T cells, we detected drug-specific CD8+, TCR,,+ T cells, which failed to proliferate to drug presentation by antigen presenting cells but killed in a drug dependent way. Interestingly, these cells had substantial natural killer-like T cell(s) like features as they were CD56+ and CD94+ and had the ability to kill the NK-sensitive cell line K562. Conclusion:, Our data underline the important role of cytotoxic mechanisms in different forms of drug induced exanthems and suggest that even some T cells with NK-like characteristics may be involved in drug hypersensitivity. [source] Antituberculosis drugs and hepatotoxicityRESPIROLOGY, Issue 6 2006Wing Wai YEW Abstract: Isoniazid, pyrazinamide and rifampicin have hepatotoxic potential, and can lead to such reactions during antituberculosis chemotherapy. Most of the hepatotoxic reactions are dose-related; some are, however, caused by drug hypersensitivity. The immunogenetics of antituberculosis drug-induced hepatotoxicity, especially inclusive of acetylaor phenotype polymorphism, have been increasingly unravelled. Other principal clinical risk factors for hepatotoxicity are old age, malnutrition, alcoholism, HIV infection, as well as chronic hepatitis B and C infections. Drug-induced hepatic dysfunction usually occurs within the initial few weeks of the intensive phase of antituberculosis chemotherapy. Vigilant clinical (including patient education on symptoms of hepatitis) and biochemical monitoring are mandatory to improve the outcomes of patients with drug-induced hepatotoxicity during antituberculosis chemotherapy. Some fluoroquinolones like ofloxacin/levofloxacin may have a role in constituting non-hepatotoxic drug regimens for management of tuberculosis (TB) in the presence of hepatic dysfunction. Isoniazid administration is currently the standard therapy for latent TB infection. Rifamycins like rifampicin or rifapentine, alone or in combination with isoniazid, may also be considered as alternatives, pending accumulation of further clinical data. During treatment of latent TB infection, regular follow up is essential to ensure adherence to therapy and facilitate clinical monitoring for hepatic dysfunction. Monitoring of liver chemistry is also required for those patients at risk of drug-induced hepatotoxicity. [source] 1222: Pharmacological overview of the ophthalmic anaesthesiaACTA OPHTHALMOLOGICA, Issue 2010E FISCHER Purpose Review of the chemical properties, differences between the effectiveness of the ophthalmological used local anaesthetics. Historical overview from 1860, year of the isolation of cocaine, to date. Methods Didactic and substantive summary of the literature. Results Specification of the basicity, lipophilicity, physicochemical properties, and the advantages, and disadvantages of adding adrenalin in different concentrations. Local anaesthetics also have adverse effects. All stimulate central nervous system, therefore it is very important to have a proper anamnesis, especially information about drug hypersensitivity from the patient. Conclusion Interventions must be carried out in the view of drug interactions, with personalized choice of drugs and dose. [source] Drug allergy claims in children: from self-reporting to confirmed diagnosisCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2008E. Rebelo Gomes Summary Background Poorly documented self-reported drug allergy (DAll) is a frequent problem in daily clinical practice and has a considerable impact on prescription choices. The diagnostic work-up of drug hypersensitivity (DHs) allows a better classification of the reactions and provides patients with more reliable information and recommendations for future treatments. Objective To assess the prevalence of self-reported adverse drug reactions (ADRs) and DAll in a paediatric population and to investigate children reporting suspected DAll in order to achieve a firm diagnosis. Design The first phase was based on a cross-sectional survey assessing the life occurrence of ADRs and self-reported DAll carried out at the outpatient clinic of a paediatric hospital. The second phase was based on the diagnostic work-up in children with parent-reported DAll, including detailed anamnesis and in vitro and in vivo investigations (skin and provocation tests). Participants One thousand four hundred and twenty-six parents responded to the initial survey. Sixty of the 67 patients with reported DAll were evaluated at the allergy clinic. Results The prevalences of self-reported ADRs and DAll were 10.2% and 6.0%, respectively. Most of the suspected allergic reactions were non-immediate cutaneous events attributable to ,-lactam antibiotics and occurred in very young children. Thirty-nine of the 60 patients consulting for evaluation had a plausible clinical history and were recommended further investigation. DHs was diagnosed in three children only, based on positive responses in skin (n=1) and oral provocation (n=2) tests. Conclusion ADRs are frequently reported in children, and many children are classified as having a DAll. After complete evaluation, only a few of these reactions can be attributed to DHs and DAll. Most of the patients (94% in this study) could actually tolerate the initially suspected drug. [source] | ||||||||||