Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016199 (flank pain)
 2,189 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted a phase I-II study of the safety, tolerance, and plasma pharmacokinetics of liposomal amphotericin B (L-AMB; AmBisome) in order to determine its maximally tolerated dosage (MTD) in patients with infections due to Aspergillus spp. and other filamentous fungi. Dosage cohorts consisted of 7.5, 10.0, 12.5, and 15.0 mg/kg of body weight/day; a total of 44 patients were enrolled, of which 21 had a proven or probable infection (13 aspergillosis, 5 zygomycosis, 3 fusariosis). The MTD of L-AMB was at least 15 mg/kg/day. Infusion-related reactions of fever occurred in 8 (19%) and chills and/or rigors occurred in 5 (12%) of 43 patients. Three patients developed a syndrome of substernal chest tightness, dyspnea, and flank pain, which was relieved by diphenhydramine. Serum creatinine increased two times above baseline in 32% of the patients, but this was not dose related. Hepatotoxicity developed in one patient. Steady-state plasma pharmacokinetics were achieved by day 7. The maximum concentration of drug in plasma (C(max)) of L-AMB in the dosage cohorts of 7.5, 10.0, 12.5, and 15.0 mg/kg/day changed to 76, 120, 116, and 105 microg/ml, respectively, and the mean area under the concentration-time curve at 24 h (AUC(24)) changed to 692, 1,062, 860, and 554 microg x h/ml, respectively, while mean CL changed to 23, 18, 16, and 25 ml/h/kg, respectively. These data indicate that L-AMB follows dose-related changes in disposition processing (e.g., clearance) at dosages of >or=7.5 mg/kg/day. Because several extremely ill patients had early death, success was determined for both the modified intent-to-treat and evaluable (7 days of therapy) populations. Response rates (defined as complete response and partial response) were similar for proven and probable infections. Response and stabilization, respectively, were achieved in 36 and 16% of the patients in the modified intent-to-treat population (n = 43) and in 52 and 13% of the patients in the 7-day evaluable population (n = 31). These findings indicate that L-AMB at dosages as high as 15 mg/kg/day follows nonlinear saturation-like kinetics, is well tolerated, and can provide effective therapy for aspergillosis and other filamentous fungal infections.
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PMID:Safety, tolerance, and pharmacokinetics of high-dose liposomal amphotericin B (AmBisome) in patients infected with Aspergillus species and other filamentous fungi: maximum tolerated dose study. 1170 29

Renal aspergillosis is an extremely uncommon complication in HIV-infected patients. In general, prognosis is poor and the need for nephrectomy is emphasized. We report the case of a 37-year-old patient with AIDS since April 2003 (CD4 count 10 cells/mm(3), a high viral load, Candida esophagitis, bilateral pneumonia, HIV encephalopathy). Treatment with zidovudine, lamivudine, nevirapine, and lopinavir/ritonavir was started. Adherence to this medication proved to be a problem, but after 18 weeks of HAART the CD4 count was 110 cells/mm(3) and viral load was undetectable. One year later, he presented with hematuria and flank pain. Computed tomography (CT) scan revealed multiple lesions in both kidneys. Cultures of the abscess aspirates yielded Aspergillus fumigatus. Our review of 18 reported cases shows that prognosis of renal aspergillosis is poor if nephrectomy is not performed. However, in the present case a conservative approach was chosen to avoid life-long dialysis. The patient was treated successfully with a combination of voriconazole, percutaneous drainage, and highly active antiretroviral therapy (HAART). Renal function was completely preserved. Reported cases from the literature of renal aspergillosis in HIV-infected patients are summarized in this paper.
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PMID:Bilateral renal aspergillosis in a patient with AIDS: a case report and review of reported cases. 1809 36

In immunosuppressed individuals, such as hematopoietic stem cell transplant recipients, adenoviruses (ADVs) are a well-known cause of morbidity and mortality, with limited treatment options. However, only a few cases were reported in patients with acquired immunodeficiency syndrome (AIDS), and little is known about the relevance of such an infection in these patients with many other concomitant opportunistic infections. We report the case of a 34-year-old man with AIDS presenting with gross hematuria, right flank pain, and acute decrease in kidney function superimposed on chronic kidney disease. His CD4 count was 0/muL despite highly active antiretroviral therapy. A computed tomographic scan showed enlargement of the right renal pelvis. Cystoscopy showed no clots or macroscopic lesions. Urine analysis showed no bacteria or abnormal epithelial cells. ADV was found in viral culture and by using real-time polymerase chain reaction in the patient's urine and later in blood. The renal biopsy specimen showed ADV-related tubulointerstitial nephritis with intranuclear inclusions in tubular cells stained by anti-ADV antibodies, in addition to chronic tubular and vascular changes. The ADV serotype belonged to subgroup B. Cidofovir therapy was contraindicated for this patient; therefore, he was administered intravenous ribavirin. The efficiency of this treatment could not be assessed because he rapidly developed neutropenia and disseminated aspergillosis and died. This case illustrates another cause of acute kidney disease in very immunosuppressed patients with AIDS, probably underdiagnosed.
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PMID:A case report of adenovirus-related acute interstitial nephritis in a patient with AIDS. 1815 41