Active clinical trials for "Mycoses"

Multiple factors are associated with a large variability in voriconazole exposure following standard dose administration, such as non-linear saturable pharmacokinetics, drug-drug interactions, liver disease, patient age, and genetic polymorphism of the metabolic enzymes. Voriconazole is extensively metabolized by the human hepatic enzymes, primarily mediated by CYP2C19. The polymorphisms account for a relatively large portion of inter-individual variance observed in voriconazole plasma concentrations. However, there are limited data on the relationships between voriconazole blood levels and clinical outcomes or safety in Asian populations. The purpose of this study is to investigate the relationships of voriconazole blood levels with genetic polymorphism, safety, and clinical outcomes in immunocompromised patients with invasive pulmonary aspergillosis.

A fixed-dosing regimen of voriconazole is routinely used as prophylaxis against aspergillosis in liver transplant patients admitted to the transplant intensive care unit at UPMC. We hypothesize that use of a fixed-dosing regimen of voriconazole will lead to a large degree of variability in drug exposure among liver transplant patients due to: 1) variability in absorption and elimination caused by physiological characteristics unique to this patient population 2) its non-linear pharmacokinetics and 3) the potential for polymorphism in the genes that encode for cytochrome P-450 enzymes that metabolize voriconazole. This is a pilot clinical pharmacokinetic evaluation that will: 1) characterize the plasma concentration versus time profile of voriconazole in liver transplant patients receiving a fixed-dosing regimen to assess for extremes in systemic exposure 2) determine the oral bioavailability of voriconazole in liver transplant patients 3) assess for functionally significant allelic variation of the cytochrome P-450 enzymes that metabolize voriconazole (CYP2C9, CYP2C19 and CYP3A4/5) in both recipient blood and allograft tissue that may contribute extremes in systemic exposure among liver transplant patients. This evaluation will allow for an assessment of the adequacy of the prophylactic regimen in achieving therapeutic drug concentrations in all subjects. Additionally, the utility of genotyping as a clinical tool to identify patients at risk for extremes in voriconazole exposure will be evaluated. The characterization of the pharmacokinetics in liver transplant patients may be utilized to define an optimal therapeutic regimen that will be individualized to target specific concentrations to maximize efficacy and minimize side-effects.

Current study aims at assessing the efficacy of doxycycline as a potential treatment modality for early stages of MF.

The clinical efficacy of mechlorethamine gel (Valchlor) as a maintenance therapy after low dose total skin electron beam therapy (TSEBT) for the treatment mycosis fungoides cutaneous T-cell lymphoma will be evaluated in this study. Subjects will be treated with low dose TSEBT (12 Gy total) over a period of two weeks. After a 30 day observation period and confirmation that their disease stage has been downgraded to IA or IB, subjects will use Valchlor as a maintenance therapy over the course of one year. The efficacy of Valchlor as a maintenance drug will be followed clinically through Modified Severity Weight Assessment Tool (mSWAT) and percent body surface area measurements (%BSA). Furthermore, subjects will be followed histopathologically through skin biopsies performed at the screening visit, immediately after observation period, one month after the start of the maintenance period, and twelve months after the start of the maintenance period (4 biopsies total).

To investigate pharmacokinetics(PK) and pharmacodynamics(PD) of Caspofungin in ICU patients after received a loading dose of 70mg followed by 50mg (35mg if Child-Pugh score is 7-9), 40 patients will be recruited. Blood samplings for PK analysis will be collected on day 4 in this study. Caspofungin plasma concentrations are measured by using solid phase extraction and reverse phase high-performance liquid chromatography. Safety analyses will be taken daily during the treatment of Caspofungin. Tests for drug tolerance of fungi and efficacy assessment (clinical and mycological responses) will be taken every 3 days by clinical and mycological tests.

The purpose of this study is to determine whether F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) is useful for the therapy strategy of hepatosplenic candidiasis.

In patients with invasive fungal infection (IFI) rapid diagnosis is essential for early initiation of appropriate antifungal therapy and thereby survival. Conventional culture is still the Gold-Standard for diagnosis of IFI. Sensitivity of conventional culture, however, is low (50%) and time to results minimum 24 hours. Therefore usage of serological tests detecting fungal antigens has increased dramatically over recent years. Main advantages of this new methods are rapid results and higher sensitivity when compared to conventional culture. One of the most promising serological marker currently used is beta-D-Glucan, which is a component of the fungal cell wall. ß-D-Glucan has been detected in IFI caused by Aspergillus, Candida and Fusarium spp. The Fungitell Assay (Associates of Cape Code, Inc.) was developed and validated for detection of ß-D-Glucan in peripheral blood. Up to date information about clinical performance of the Fungitell Assays in bronchoalveolar lavage fluid (BAL) is limited. This study will therefore evaluate clinical and diagnostic performance of the Fungitell Assay in BAL from patients with solid organ transplant or hematologic malignancy. In addition Mn/A-Mn, the lateral flow device test for aspergillosis, and Galactomannan, as well as PCR will be determined and used as comparators for BDG performance.

In this study we will measure the concentration of the drug called voriconazole which is used to fight infections caused by fungus in children who usually are cancer patients and have their immune system down. Since we know the dose in adults, and we think we know the matching doses in the young patients ages 2 to less than 15 years old, we will compare the amount of drug that goes into the system with what we know works in adults. We give the drug by a needle directly into the blood, then few days later we stop that and give the drug by mouth. Meanwhile, we draw a little bit of blood at certain times to measure the drug in it.

The most frequent cutaneous T-cell lymphomas (CTCL) are mycosis fungoid and Sezary syndrome. The diagnosis of these lymphomas is difficult using current methods, especially because numerous benign dermatological conditions can mimick CTCL both clinically and under microscopic examination. Recently, the KIR receptor CD158k has been shown to be a marker for Sezary syndrome in both the blood and skin. We hypothesize that other receptors from the same family may help fro the diagnosis of these lymphomas. To address this issue, we will study the expression of all known KIR receptor in the skin of patients presenting with a skin eruption, which may correspond to either a cutaneous T-cell lymphoma or a benign dermatological disease. The final diagnosis will be established by a panel of experts, allowing constitution of 2 groups of patients : the cutaneous T-cell lymphoma group, and the benign inflammatory disease group. The expression of the different KIRs will be analyzed in both group in a blinded fashion, in order to determine whether one or a several KIRs may be differentially expressed.

Prevention of invasive fungal infection in high risk patients following liver transplant.