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Immunosuppressive Doses (immunosuppressive + dose)
Selected AbstractsImmune-mediated hemolytic anemia and severe thrombocytopenia in dogs: 12 cases (2001,2008)JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 3 2010Elizabeth S. Orcutt DVM Abstract Objective , To identify and characterize the syndrome of immune-mediated hemolytic anemia (IMHA) with concurrent severe thrombocytopenia (,15.0 × 109 platelets/L; [15.0 × 103 platelets/,L]), and to evaluate prognostic factors, clinicopathologic findings, complications, treatment, outcome, and survival of dogs with this hematologic disorder. Design , Retrospective, observational study. Setting , Veterinary teaching hospital. Animals , Twelve client-owned dogs with IMHA and severe thrombocytopenia (,15.0 × 109 platelets/L; [15.0 × 103 platelets/,L]), without evidence of overt disseminated intravascular coagulation. Interventions , The following data were recorded and analyzed from the electronic medical record: signalment, history, concurrent diseases, clinical signs at presentation, clinicopathologic data, diagnostic testing, radiographic findings, treatment modalities, length of hospitalization, complications, and clinical outcome. All dogs were treated with immunosuppressive doses of corticosteroids. Measurements and Main Results , Twelve dogs were identified with the diagnosis of IMHA and severe thrombocytopenia; of these, 9 (75%) survived, 3 (25%) were euthanized, and none died. Dogs that survived were significantly younger than nonsurvivors (P=0.03). There were no specific clinical signs or therapies associated with survival. Conclusions , Dogs in this study had a mortality rate similar to reported rates for dogs with either disease alone. Overall, younger dogs were more likely to survive. No association between different treatment modalities and overall survival was identified. [source] Treatment of Immune-Mediated Hemolytic Anemia in Dogs with CyclophosphamideJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2000Kristine Burgess A review of 60 cases of immune-mediated hemolytic anemia (IMHA) in the dog was performed in order to characterize the disease and to identify potential prognostic indicators. Dogs ranged in age from 1 to 13 years, with a mean age of 6.5 years. The 2 most commonly affected breeds were Cocker Spaniels and Labrador Retrievers. Fifty-two of the 60 dogs tested (87%) were autoagglu-tination positive and spherocytes were present in 45 (75%). Forty-one (89%) of 46 patients tested positive for the presence of immunoglobulin on the red blood cell surface (Coombs assay). The most common clinical signs at presentation were lethargy, weakness, pale mucous membranes, icterus, hemoglobinuria, and anorexia. PCV less than 25% was present in 59 (98%) dogs. At the time of presentation, 35 dogs (58%) had a nonregenerative anemia, whereas 25 patients (42%) had a regenerative response. Thrombocytopenia was seen in 41 (68%) dogs. Nine of 34 dogs (26%) had a prolonged prothrombin time, 19 of 34 (56%) had a prolonged activated partial thromboplastin clotting time, and 12 of 34 (35%) had abnormal fibrinogen concentrations. All dogs received prednisone at immunosuppressive doses (2.2,4.4 mg/kg PO as a single or divided dose every 24 hours) and cyclophosphamide as primary therapy. Forty-one dogs (63%) received cyclophosphamide at 50 mg/m2 q24h for 4 days, whereas 9 dogs (15%) received an initial high dose (200 mg/m2) followed by 3 days of a lower dose (50 mg/m2 q24h). No statistical difference in survival times was found for either protocol. Thirteen dogs were treated with azathioprine in addition to cyclophosphamide and prednisone. The median survival time of dogs that received all 3 drugs was 370 days as compared to 9 days for those dogs that were treated with cyclophosphamide and prednisone alone. Thirty-one (52%) dogs died from the disease, 13 (22%) dogs were alive, and 15 (25%) dogs were lost to follow-up. The median length of survival for all dogs was 21 days. Eight dogs that were discharged from the hospital suffered a relapse (PCV < 25%). [source] Pemphigus Herpetiformis in ChildhoodPEDIATRIC DERMATOLOGY, Issue 5 2010Isabela B. Duarte M.D. The clinical features of this form of pemphigus resembles dermatitis herpetiformis, however, histological examination and immunofluorescence yield findings diagnostic for pemphigus. A 5-year-old female patient with clinical features suggestive of dermatitis herpetiformis is reported. Histopathological exam showed skin with subcorneous blisters, epidermal spongiosis containing predominantly neutrophils, few eosinophils and rare acantholytic cells. Direct immunofluorescence showed intercellular deposits of IgG and C3. The skin lesions responded poorly to dapsone associated with systemic corticosteroid therapy. A complete remission of bullous lesions was obtained with azathioprine and immunosuppressive doses of systemic corticosteroids (prednisone). A case of PH in childhood is reported here, emphasizing the rarity and young age of onset. [source] Characterization of Herpes Simplex Virus type 1 thymidine kinase mutants engineered for improved ganciclovir or acyclovir activityPROTEIN SCIENCE, Issue 9 2002Mark S. Kokoris Abstract Herpes Simplex Virus type 1 (HSV-1) thymidine kinase (TK) is currently the most widely used suicide agent for gene therapy of cancer. Tumor cells that express HSV-1 thymidine kinase are rendered sensitive to prodrugs due to preferential phosphorylation by this enzyme. Although ganciclovir (GCV) is the prodrug of choice for use with TK, this approach is limited in part by the toxicity of this prodrug. From a random mutagenesis library, seven thymidine kinase variants containing multiple amino acid substitutions were identified on the basis of activity towards ganciclovir and acyclovir based on negative selection in Escherichia coli. Using a novel affinity chromatography column, three mutant enzymes and the wild-type TK were purified to homogeneity and their kinetic parameters for thymidine, ganciclovir, and acyclovir determined. With ganciclovir as the substrate, one mutant (mutant SR39) demonstrated a 14-fold decrease in Km compared to the wild-type enzyme. The most dramatic change is displayed by mutant SR26, with a 124-fold decrease in Km with acyclovir as the substrate. Such new "prodrug kinases" could provide benefit to ablative gene therapy by now making it feasible to use the relatively nontoxic acyclovir at nanomolar concentrations or ganciclovir at lower, less immunosuppressive doses. [source] Successful treatment of disseminated cutaneous phaeohyphomycosis in a dogAUSTRALIAN VETERINARY JOURNAL, Issue 12 2006IM Swift A 7-year-old castrated male Whippet developed deep ulcerative skin lesions whilst receiving immunosuppressive doses of prednisolone and cyclosporine for the treatment of immune-mediated haemolytic anaemia. The lesions were determined to be a phaeohyphomycosis, caused by Curvularia lunata. The dog was treated with a combination of systemic antifungals and weaning off immunosuppressants and made a complete recovery. To the authors' knowledge, this is the first case report of the successful treatment of disseminated cutaneous phaeohyphomycosis in a dog. [source] Review of select transplant subpopulations at high risk of failure from standard immunosuppressive therapyCLINICAL TRANSPLANTATION, Issue 5 2000Mark H Deierhoi Despite improvements in short-term graft and patient survival rates for solid organ transplants, certain subgroups of transplant recipients experience poorer clinical outcome compared to the general population. Groups including pediatrics, African-Americans, diabetics, cystic fibrosis patients, and pregnant women require special considerations when designing immunosuppressive regimens that optimize transplant outcomes. Problems specific to pediatric transplant recipients include altered pharmacokinetics of immunosuppressive drugs, such as cyclosporine (CsA) and tacrolimus (poor absorption, increased metabolism, rapid clearance), the need to restore growth post-transplantation, and a high incidence of drug-related adverse effects. African-Americans have decreased drug absorption and bioavailability, high immunologic responsiveness, and a high incidence of post-transplant diabetes mellitus. Diabetics and cystic fibrosis patients exhibit poor absorption of immunosuppressive agents, which may lead to underimmunosuppression and subsequent graft rejection. Pregnant women undergo physiologic changes that can alter the pharmacokinetics of immunosuppressives, thus requiring careful clinical management to minimize the risks of either under- or overimmunosuppression to mother and child. To achieve an optimal post-transplant outcome in these high-risk patients, the problems specific to each group must be addressed, and immunosuppressive therapy individualized accordingly. Drug formulation greatly impacts upon pharmacokinetics and the resultant level of immunosuppression. Thus, a formulation with improved absorption (e.g., CsA for microemulsion), higher bioavailability, and less pharmacokinetic variability may facilitate patient management and lead to more favorable outcomes, especially in groups demonstrating low and variable bioavailability. Other strategies aimed at improving transplant outcome include the use of higher immunosuppressive doses, different combinations of immunosuppressive agents, more frequent monitoring, and management of concurrent disease states. [source] | ||||||||||