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

Isolated renal infections with fungal organisms of the class Zygomycetes are rare, but these infections are most frequently seen in patients who are immunocompromised. We report the case of a 45-year-old African American man who presented with symptoms of right-sided pyelonephritis, including fever, dysuria, and flank pain. The patient's history was significant only for sickle cell trait, and no evidence of immunosuppression was identified. Renal ultrasound imaging revealed a hypoechoic lesion in the superior pole of the right kidney, and the radiologic differential diagnoses included neoplasm, abscess, and infarct. Urine cultures were negative, but urinalysis showed white blood cells, which were too numerous to count. A computed tomography scan of the abdomen and pelvis performed 2 weeks after the initial presentation showed a slight increase in the renal mass, despite antimicrobial therapy, and a right nephrectomy was subsequently performed. On gross sectioning, an 8.5-cm well-circumscribed lesion was identified in the upper pole of the kidney. Microscopic sections showed extensive necrosis of the renal parenchyma, and, in areas of both infarcted and viable renal tissue, large, broad, aseptate fungal hyphae with irregular branching. Angioinvasion with associated thrombosis was seen in the renal tissue. The morphologic features of the organism were most compatible with that of a zygomycete. No evidence of disseminated fungal disease was identified on imaging studies. This case represents a successful outcome of a rarely reported isolated renal zygomycosis in a patient with no known underlying risk factors for the infection and illustrates the wide range of clinical presentations with which zygomycotic infections may present.
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PMID:Primary renal zygomycotic infarction mimicking renal neoplasia in an immunocompetent patient. 1970 Oct 78

Background: Zygomycoses are uncommon, frequently fatal diseases caused by fungi of the class Zygomycetes. The majority of human cases are caused by Mucorales (genus-rhizopus, mucor, and absidia) fungi. Renal involvement is uncommon and urine microscopy, pottasium hydroxide mount, and fungal cultures are frequently negative. Case Presentation: A twenty-one-year-old young unmarried lady presented to our emergency department with bilateral flank pain, fever, nausea, and decreased urine output of one-month duration. She was found to have azotemia with sepsis with bilateral hydronephrosis with a left renal pelvic obstructing stone. Even after nephrostomy drainage and broad spectrum antibiotics, her condition worsened. She developed disseminated fungal infection, and timely systemic antifungal followed by bilateral nephroscopic clearance saved the patient. Conclusion: Although renal fungal infections are uncommon, a high index of suspicion and early antifungal and surgical intervention can give favorable outcomes.
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PMID:Percutaneous Management of Systemic Fungal Infection Presenting As Bilateral Renal Fungal Ball. 2770 55