Project description:Comprehensive expression profiling of disseminated neuroblastoma with favorable and unfavorable outcome using SAGE. Results provide insight into the molecular pathogenesis of spontaneous regression and progression of metastatic neuroblastoma and may be used for improving risk estimation of patients with disseminated neuroblastoma. Keywords: gene expression SAGE-based, neuroblastoma, primary tumor, disseminated disease
Project description:Comprehensive expression profiling of disseminated neuroblastoma with favorable and unfavorable outcome using SAGE. Results provide insight into the molecular pathogenesis of spontaneous regression and progression of metastatic neuroblastoma and may be used for improving risk estimation of patients with disseminated neuroblastoma. Keywords: gene expression SAGE-based, neuroblastoma, primary tumor, disseminated disease Samples analyzed: 9 (stage 4S neuroblastoma: n=5, stage 4 neuroblastoma: n=3, neuroblastoma cell line: n=1)
Project description:We describe a case of life-threatening disseminated coccidioidomycosis in a previously healthy child. Like most patients with disseminated coccidioidomycosis, this child had no genomic evidence of any known, rare immune disease. However, comprehensive immunologic testing showed exaggerated production of interleukin-4 and reduced production of interferon-?. Supplementation of antifungal agents with interferon-? treatment slowed disease progression, and the addition of interleukin-4 and interleukin-13 blockade with dupilumab resulted in rapid resolution of the patient's clinical symptoms. This report shows that blocking of type 2 immune responses can treat infection. This immunomodulatory approach could be used to enhance immune clearance of refractory fungal, mycobacterial, and viral infections. (Supported by the Jeffrey Modell Foundation and the National Institutes of Health.).
Project description:Of 150,000 new coccidioidomycosis infections that occur annually in the United States, ≈1% disseminate; one third of those cases are fatal. Immunocompromised hosts have higher rates of dissemination. We identified 8 patients with disseminated coccidioidomycosis who had defects in the interleukin-12/interferon-γ and STAT3 axes, indicating that these are critical host defense pathways.
Project description:We describe a patient with a disseminated coccidioidomycosis. Biomarkers in serum during itraconazole therapy showed a rapid clearing of Coccidioides DNA as detected by PCR. Coccidioides antibody detection by lateral flow assay became negative after one year and decreased from 1:64 to 1:8 in the complement fixation test after two years. The (1 ? 3)-ß-D-glucan levels normalised after two years without increase after cessation of antifungal therapy. Biomarkers in serum may guide treatment decisions in disseminated coccidioidomycosis.
Project description:BackgroundThe majority of dogs with coccidioidomycosis recover with administration of fluconazole or itraconazole, although some cases are refractory or the dogs do not tolerate administration of these medications.ObjectivesThe objective was to describe the treatment outcomes and therapeutic monitoring of 8 dogs with refractory coccidioidomycosis treated with posaconazole.AnimalsEight dogs with refractory coccidioidomycosis.MethodsRetrospective case series. Medical records from Veterinary Specialty Center of Tucson were searched to identify dogs with refractory coccidioidomycosis that were treated with posaconazole. Clinical information and the results of monitoring trough serum posaconazole concentrations were retrieved.ResultsEight dogs with refractory coccidioidomycosis were treated with 2.5 to 10 mg/kg per day of posaconazole. Six of 8 dogs recovered or developed clinical remission while administered posaconazole. Thirteen serum concentrations from 8 dogs tested were >1 μg/mL (range, 1.52 to >6 μg/mL) and the drug was well-tolerated by 7 dogs. One dog required dosage reductions and treatment was ultimately discontinued because of hepatotoxicosis.Conclusions and clinical importancePosaconazole should be considered as a treatment option for dogs with refractory coccidioidomycosis. Monitoring of indicators of liver function or injury along with therapeutic drug monitoring is recommended to tailor dosage in the event of hepatic toxicosis.