Experience with needle biopsy for coccidioidal lung nodules.

Three hundred forty-eight patients with solitary pulmonary nodules underwent needle biopsy of the lung in an endemic area for coccidioidomycosis. The purposes of the study were to establish the value of smears and cultures from needle biopsy specimens in the diagnosis of solitary coccidioidal granuloma and to determine how the final diagnosis was established for patients without a clear-cut diagnosis after initial biopsy. Spherules of Coccidioides immitis were initially identified in 49 of the 96 patients with coccidioidomas. Only three of 35 cultures from biopsy-proved coccidioidal lesions were positive (8.6% yield); nevertheless, cultures were cost-effective in nondiagnostic cases. Thoracotomy should be delayed until the results of cultures are known if findings of skin tests, serologic studies, and roentgenography make a benign diagnosis plausible.

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.

Sleep apnea syndrome. Practical diagnostic method.

We report a method of evaluating sleep apnea by equipment available and easily assembled in the majority of community hospitals. Two cases fully studied by this method are presented.

Perils of childhood. Immunization against measles, mumps, and rubella.

Some children with a positive history and skin test for egg allergy require a unique desensitization protocol for the measles, mumps and rubella (MMR) vaccine. The pathophysiology of food allergies, skin testing and the MMR desensitization protocol are described. Strategies appropriate to the children's developmental stage are suggested to enhance the nurse's supportive role throughout the desensitization process.

A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler.

BACKGROUND: Formoterol is a beta2-adrenergic agent which, when inhaled, produces rapid and long-lasting bronchodilatation. OBJECTIVE: The aim of this study was to compare the efficacy, safety, and tolerability of formoterol powder for inhalation delivered via the Aerolizer device with placebo and with albuterol delivered via metered-dose inhaler in patients with mild to moderate persistent asthma. METHODS: In a multicenter, double-blind, parallel-group study, 541 patients were randomized at 26 trial sites to receive either formoterol, 12 microg twice daily; formoterol, 24 microg twice daily; albuterol, 180 microg four times daily; or a placebo for 12 weeks. The effects of each treatment on lung function, asthma symptoms, and frequency of rescue albuterol use were evaluated. Adverse effects and clinical laboratory parameters were also evaluated. RESULTS: The bronchodilatory effects of formoterol were rapid in onset and persisted for 12 hours. Both formoterol doses were more effective than placebo and albuterol for objective measures of lung function. Morning and evening peak expiratory flow rates were more improved with formoterol, and formoterol provided significantly greater improvements in asthma symptom scores compared with both albuterol and placebo. Overall, patients taking formoterol used significantly less rescue medication than did those taking albuterol or placebo. Nocturnal awakenings occurred less often with formoterol than with placebo or albuterol. The therapeutic effects of formoterol were maintained over the entire 12 weeks of treatment. Adverse events were similar for all treatment groups, and clinical laboratory data were unremarkable. CONCLUSIONS: Rapid-onset, long-acting formoterol, administered via the Aerolizer inhaler, is an effective and safe treatment for patients with mild to moderate persistent asthma.

High-dose ketoconazole for treatment of fungal infections of the central nervous system.

Mortality and complication rates remain unacceptably high with conventional intravenous and intrathecal therapy for patients with coccidioidal meningitis and intracerebral fungal lesions. We studied the ventricular and lumbar cerebrospinal fluid penetration of ketoconazole and the responses to therapy in two patients receiving ketoconazole orally, 800 mg daily, and amphotericin B intraventricularly for meningeal and extrameningeal coccidioidomycosis. Five patients received only 1200 mg of ketoconazole: one had uncomplicated coccidioidal meningitis, three had obstructive hydrocephalus due to coccidioidal meningitis, and one had a histoplasmal brain abscess. Ketoconazole concentrations in ventricular and lumbar fluid ranged from 0.05 to 1.65 micrograms/mL 4 and 8 hours after the dose. The mean penetration of ketoconazole (+/- SD) was 1.9% +/- 0.8% for ventricular fluid and 5.4% +/- 2.6% for lumbar fluid. Ketoconazole concentrations in cerebrospinal fluid varied directly with those in serum and with cerebrospinal fluid protein content. The encouraging clinical responses, convenience, safety, and the consistent penetration of ketoconazole into obstructed and nonobstructed cerebrospinal fluid support the use of these regimens as alternatives to conventional therapy.

Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis.

The pharmacokinetics of fluconazole, a new oral azole, were evaluated in cerebrospinal fluid and sera of eight patients with coccidioidal meningitis. At a dose of 50 mg/day, peak concentrations of 2.5 to 3.5 and 2.0 to 2.3 micrograms/ml occurred at 2 to 6 and 4 to 8 h in serum and cerebrospinal fluid, respectively. At 100 mg/day, peak concentrations of 4.5 to 8.0 and 3.4 to 6.2 micrograms/ml occurred at 2 to 4 and 4 to 12 h, respectively. The mean ratios of the concentration in cerebrospinal fluid to that in serum were 73.8% at 50 mg/day and 88.7% at 100 mg/day. Results suggested that there was a prolonged half-life in both cerebrospinal fluid and serum and that it was slightly longer in the former. Minimal toxicity was noted in 34 patient months of therapy (12 months on 50 mg daily; 22 months on 100 mg daily). After a mean of 4.5 months of therapy, five patients responded to therapy and three were unevaluable. The penetration of fluconazole into cerebrospinal fluid was substantial, toxicity was minimal, and early clinical experience was encouraging. Fluconazole holds promise as the sole or adjunctive therapy for fungal meningitis.