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Biomedical subjects

S W Chapman

Publications and source records attributed to S W Chapman.

At least 19 recordsLinked to original sources
PubMed1995

Alopecia associated with fluconazole therapy.

OBJECTIVE: To describe the association between fluconazole and reversible alopecia. DESIGN: A retrospective survey of 1) patients enrolled in NIAID Mycoses Study Group (MSG) protocols involving the long-term use of fluconazole for treatment of endemic mycoses and 2) patients treated with fluconazole outside of a protocol setting but by the MSG investigators who were MSG members. SETTING: 26 MSG sites in the United States. PATIENTS: 33 patients with various deep and superficial mycoses who developed alopecia while receiving fluconazole. RESULTS: 11 of 26 investigators reported a total of 33 patients with substantial alopecia related to fluconazole therapy. Underlying mycoses included blastomycosis, sporotrichosis, histoplasmosis, cryptococcosis, coccidioidomycosis, and mucosal candidiasis. In separate MSG studies, 17 of 136 (12.5%) and 8 of 40 (20%) patients had substantial reversible alopecia associated with fluconazole therapy. Eight patients who were not in the protocol had similar adverse effects. Twenty-nine of 33 patients (88%) received at least 400 mg of fluconazole daily for a mean of 7.1 months. Alopecia developed a median of 3 months after initiation of fluconazole therapy and involved the scalp in all patients. Other sites were involved in about one third of patients. Three patients required wigs because of extensive hair loss. Alopecia resolved within 6 months of discontinuation of fluconazole therapy or reduction of the daily dose by at least 50%. CONCLUSIONS: Alopecia appears to be a common adverse event associated with higher-dose (400 mg/d) fluconazole given for 2 months or longer. This effect may be severe but is reversed by discontinuing fluconazole therapy or substantially reducing the daily dose.

Adult↗
PubMed1995

Fluconazole in the treatment of chronic pulmonary and nonmeningeal disseminated coccidioidomycosis. NIAID Mycoses Study Group.

PURPOSE: To determine the efficacy and safety of fluconazole as treatment for coccidioidomycosis. PATIENTS AND METHODS: This was a multicenter, open-label, single-arm study. Of 78 patients enrolled, 22 had soft-tissue, 42 had chronic pulmonary, and 14 had skeletal coccidioidomycosis. Forty-nine had at least one concomitant disease, 7 of whom had HIV infection. Patients were given oral fluconazole 200 mg/d. Nonresponders were increased to 400 mg/d. Treatment courses were long: a mean of 323 +/- 230 days at 200 mg and 433 +/- 178 days at 400 mg. Predefined assessment of disease-related abnormalities was performed at the time of enrollment and repeated at least every 4 months. A satisfactory response was defined as any reduction of baseline abnormality by month 4 and at least 51% reduction by month 8. RESULTS: Among 75 evaluable patients, a satisfactory response was observed in 12 (86%) of the 14 patients with skeletal, 22 (55%) of the 40 patients with chronic pulmonary, and 16 (76%) of the 21 patients with soft-tissue disease. Five patients (7%) required modification of treatment due to toxicity. Forty-one patients who responded were followed off drug. Fifteen (37%) of them experienced reactivation of infection. CONCLUSION: Fluconazole 200 or 400 mg/d is well tolerated and a moderately effective treatment for chronic pulmonary or nonmeningeal disseminated coccidioidomycosis. The relapse rate following therapy is high. Treatment trials with higher doses appear warranted. The relative efficacy of fluconazole versus other azoles or amphotericin B remains unknown.

Adult↗
PubMed1995

Treatment of blastomycosis with fluconazole: a pilot study. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

There are few clinical data concerning the use of fluconazole, a triazole antifungal agent with in vitro activity against Blastomyces dermatitidis, in the treatment of human blastomycosis. We conducted a multicenter, randomized, open-label pilot trial comparing two daily doses of fluconazole (200 mg and 400 mg) in the treatment of non-life-threatening, non-CNS blastomycosis. Twenty-four patients were enrolled in the study, and 23 patients were evaluable for efficacy analysis. Overall, treatment of 15 (65%) of 23 patients was successful, including eight (62%) of 13 who received 200 mg daily and seven (70%) of 10 who received 400 mg daily. The mean duration of therapy for successfully treated patients was 6.7 months. Of the six patients whose prior antifungal therapy had failed, all six eventually responded to fluconazole treatment. We conclude that fluconazole (200 mg to 400 mg daily) given for at least 6 months is moderately effective treatment for blastomycosis.

Adolescent↗
PubMed1995

Fluconazole penetration into the human prostate.

Fluconazole concentrations in the serum and prostate of human volunteers undergoing transurethral resection for benign prostatic hypertrophy were measured. There was a high correlation (r = 0.783) between serum (mean = 6.6 micrograms/ml) and tissue (mean = 1.9 micrograms/g) fluconazole concentrations, and these data were used to construct a model for local tissue concentrations.

Cryptococcosis↗
PubMed1994

Cutaneous manifestations of fungal infection.

Fungal infection of the skin and subcutaneous tissue may result from either direct contact or inoculation injury (primary infection) or from hematogenous spread from a primary focus of disease (secondary infection). The parainfectious lesions of erythema nodosum and erythema multiforme are manifestations of the host's immune response to the invading fungus, particularly Histoplasma capsulatum and Coccidiodes immitis. In some patients, skin lesions may be the only sign of a systemic fungal infection, and prompt recognition of these lesions may facilitate early diagnosis and treatment. This article first addresses the pathogenesis, host defenses, and diagnosis of fungal skin infections. The specific cutaneous manifestations of the superficial, cutaneous, subcutaneous, and systemic mycoses are then reviewed.

Antifungal Agents↗
PubMed1992

Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group.

OBJECTIVE: To assess the efficacy and toxicity of orally administered itraconazole in the treatment of nonmeningeal, nonlife-threatening forms of blastomycosis and histoplasmosis. DESIGN: Prospective, nonrandomized, open trial. SETTING: Multicenter trial at 14 university referral centers. PATIENTS: Eighty-five patients with culture or histopathologic evidence of blastomycosis (48 patients) or histoplasmosis (37 patients). Patients receiving other systemic antifungal therapy were excluded. INTERVENTIONS: Itraconazole was administered orally at doses of 200 to 400 mg/d. Patients in whom treatment was considered a success were treated for a median duration of 6.2 months (blastomycosis) and 9.0 months (histoplasmosis). Disease activity was assessed at baseline; drug efficacy and toxicity were evaluated at monthly intervals during therapy, and efficacy was evaluated at regular follow-up visits after completion of therapy. The median duration of posttreatment evaluation for successfully treated patients was 11.9 months (blastomycosis) and 12.1 months (histoplasmosis). MEASUREMENTS AND MAIN RESULTS: Among the 48 patients with blastomycosis, success was documented in 43 (90%). The success rate for patients treated for more than 2 months was 95% (38 of 40). Among the 37 patients with histoplasmosis, success was documented in 30 (81%). The success rate for patients treated for more than 2 months was 86% (30 of 35). All patients with histoplasmosis in whom treatment failed had chronic cavitary pulmonary disease. Toxicity was minor; only 25 (29%) patients experienced any side effects, and itraconazole toxicity necessitated stopping therapy in only 1 patient. CONCLUSIONS: Itraconazole is a highly effective therapy for nonmeningeal, nonlife-threatening blastomycosis and histoplasmosis. The drug is associated with minimal toxicity.

Adult↗
PubMed1992

Pharmacologic modulation of interleukin-1 expression by amphotericin B-stimulated human mononuclear cells.

Fever and chills occur frequently with amphotericin B (AB) administration, but the mechanism that causes these reactions has not been definitively established. A variety of proinflammatory cytokines, including interleukin-1 (IL-1) and tumor necrosis factor, have been shown to be important mediators of fever. In order to clarify the cellular and biochemical responses associated with AB-induced fever, the experiments described sought to (i) establish whether human mononuclear cells exposed to AB in vitro expressed IL-1 beta, (ii) evaluate whether clinically used premedications for fever prophylaxis in AB-treated patients were effective in down-regulating IL-1 beta expression in vitro, (iii) evaluate whether methylxanthine agents with immunomodulatory actions effected in vitro IL-1 beta expression, and (iv) define the dose and time dependency of the modulating effects. Peripheral blood mononuclear cells were isolated by density centrifugation and resuspended to 10(6) cells per ml in culture wells of Linbro plates. When cocultured for 2 h with human mononuclear cells, both Escherichia coli lipopolysaccharide and AB stimulated IL-1 beta expression in a dose-related fashion. AB-induced IL-1 beta expression was suppressed by hydrocortisone (HC), pentoxifylline, and an investigational theobromine, A81-3138, in a linear, dose-related manner. In contrast, indomethacin, meperidine, and diphenhydramine had no effect on IL-1 beta expression. Our in vitro data indicate that serum HC concentrations of greater than 1 to 2 micrograms/ml may be sufficient to modulate IL-1 beta expression. Pentoxifylline and A81-3138 may also be effective in modulating IL-1 beta expression by mononuclear cells at concentrations achievable in serum. These new agents may prove to be effective alternatives to HC or may be added with HC to suppress febrile reactions secondary to AB administration. Clinical studies with pentoxifylline as a premedication for AB seem warranted.

Amphotericin B↗
PubMed1992

Itraconazole in antifungal therapy.

OBJECTIVE: This overview compares and contrasts the pharmacotherapy of itraconazole with that of other antifungal agents. DATA SOURCES: Primary literature on itraconazole was identified through a medical literature search from 1976 through 1991. This search included journal articles, abstracts, conference proceedings, and reports of animal and human research published in the English language. STUDY SELECTION: All primary literature was reviewed regardless of the study design or outcome. Literature evaluations of efficacy were ranked using a literature rating scale (Dalen JE, Hirsh J. Arch Intern Med 1986;146:462-72), which was slightly modified to include case reports and observations. DATA EXTRACTION: All data were collected and represented with a primary focus on itraconazole's mechanism of action, pharmacokinetics, clinical efficacy in systemic mycotic infections, drug interactions, and adverse reactions. All articles were referenced in the final data presentation unless grouped data had been accurately reviewed and published. DATA SYNTHESIS: Despite the paucity of controlled comparative trials with itraconazole in patients with deep mycoses, results on efficacy are encouraging. It is still unclear what role itraconazole will have in the prophylaxis of fungal infections in immunocompromised hosts. The favorable pharmacokinetic profile permits once- or twice-daily administration and itraconazole appears to be safe and well tolerated. CONCLUSIONS: Itraconazole should prove to be a useful replacement for ketoconazole on hospital formularies. This recommendation is based on itraconazole's greater apparent safety and efficacy. Reevaluation of this agent will be necessary upon the release of newer imidazoles and triazoles.

Antifungal Agents↗
PubMed1991

Peritoneal blastomycosis.

Blastomycosis is a systemic fungal infection caused by Blastomyces dermatitidis. Involvement of the peritoneum is unusual, with only two previously reported cases that occurred in association with disseminated disease. A single case of histopathologically proven blastomycosis involving the peritoneum is presented, as well as a short overview of previously published cases on gastrointestinal and peritoneal blastomycosis. The case is unique in that chronic peritonitis was the only manifestation of disease. The diagnosis was made by laparoscopy.

Adult↗
PubMed1990

Increasing ICU staff handwashing: effects of education and group feedback.

This study provides an evaluation of the effectiveness of methods to increase handwashing (HW) by nurses working in an intensive care unit. After baseline observations, two interventions were implemented in sequence: three series of classes conducted by the infection control nurse (ICN); and feedback to staff about handwashing errors on the previous day. Staff were aware that handwashing was being observed throughout the study. The educational intervention produced an immediate increase in HW that was followed by a decline to baseline rates over four weeks. Feedback produced an improvement to 97% compliance that was sustained until completion of the study. Improvement in HW compliance following specified critical procedures was also observed following interventions.

Communication↗
PubMed1990

Amphotericin B blunts erythropoietin response to anemia.

Amphotericin B causes a normochromic, normocytic anemia thought to be mediated by direct marrow toxicity or suppression of erythropoietin production. Serial hemoglobin, hematocrit, amphotericin B, and erythropoietin levels were determined before, during, and after completion of amphotericin B therapy for three patients without significant renal disease or active hematologic malignancy. Patients with systemic fungal diseases treated with itraconazole served as controls. Serum erythropoietin levels were determined by radioimmunoassay and amphotericin B by high-performance liquid chromatography. Despite anemia in all amphotericin B-treated patients, erythropoietin levels declined or remained relatively constant during therapy while erythropoietin levels in controls were appropriate for the degree of anemia. Within 2 weeks of completion of amphotericin B treatment, two patients had increasing erythropoietin levels in response to anemia. Amphotericin B appears to suppress but not abolish the erythropoietin response to anemia; this effect disappears quickly after discontinuation of the drug.

Amphotericin B↗
PubMed1990

Imidazoles and triazoles in antifungal therapy.

Fungal infections range from superficial mycoses involving skin or mucous membranes to severe opportunistic infections that may be fatal. The selection of chemotherapeutic agents useful for the treatment of fungal infections includes many topical or systemic imidazoles and triazoles. This overview compares and contrasts the pharmacology and therapeutic use of these agents. This review will focus primarily on these agents' mechanism of action, pharmacokinetics, clinical studies, and adverse reactions.

Animals↗
PubMed1990

Nocardiosis in transplant recipients.

Nocardia is an increasingly important opportunistic pathogen in immunosuppressed patients, especially solid organ transplant recipients. Infection is most often caused by Nocardia asteroides and presents as lung disease in 80% to 90% of infected transplant patients. Radiographic findings are nonspecific and include nodular infiltrates, cavitation, and pleural effusion. Dissemination to other organs, especially to the central nervous system (CNS) and skin, occurs in up to 40% of transplant recipients. A presumptive diagnosis is most rapidly made by the direct visualization in tissue, lower respiratory secretions, or wound drainage of filamentous, gram-positive, beaded rods that are partially acid fast. Specimens for culture should be held for at least 3 weeks when the diagnosis is suspected. The prognosis of nocardial infection is related to the site of disease, rapidity of diagnosis, and extended treatment with a sulfonamide. Mortality is highest in patients with CNS involvement. Prophylactic trimethoprim-sulfamethoxazole should be considered in transplant centers with excess rates of nocardial infection. Hopefully, future refinement of immunosuppressive regimens will be accompanied by a reduction in frequency of Nocardia infections in transplant recipients.

Brain Abscess↗
PubMed1989

Paraneoplastic eosinophilia. Report of a case with in vitro studies of hemopoiesis.

Eosinophilia is an unusual paraneoplastic manifestation. The authors describe for the first time the association of eosinophilia and metastatic medullary carcinoma of the thyroid. The eosinophil count normalized during remission after chemotherapy but increased at time of relapse. The patient's serum enhanced eosinophilic differentiation of human multipotential hemopoietic precursors but was inhibitory to in vitro growth of murine myelopoietic precursors. The number of multipotential colonies which could be cultured in vitro was lower in the patient's peripheral blood than in normal controls. The authors conclude that a tumor-related circulating factor caused eosinophilia by inducing eosinophilic differentiation and inhibiting myeloid differentiation. Such a mechanism of paraneoplastic eosinophilia has not been previously described.

Cells, Cultured↗