Sammy C. Campbell

Ketoconazole treatment of nonprimary coccidioidomycosis: Evaluation of 60 patients during three years of study☆

Sixty patients with coccidioidomycosis were treated with ketoconazole rather than with another antifungal agent, and their responses were evaluated in relation to the predominant site of involvement. For the three main groups, improvement occurred in 12 of 19 patients with chronic pulmonary infections, in 20 of 23 with soft tissue lesions and in six of 11 with skeletal involvement. Infections in soft tissues improved most rapidly (average of 34 days) and often with 200 mg per day, whereas pulmonary and skeletal infections improved more slowly (63 and 165 days, respectively), usually requiring 400 mg per day. Of 12 patients with response in whom therapy has been discontinued, seven have had relapses. Recurrence was apparent usually within the first month and after six months or less of treatment. Patients in remission had received ketoconazole for six to 17 months. Untoward drug effects included abdominal complaints (23 percent) and gynecomastia (8 percent). Therapy was discontinued in only three patients for side effects. Our findings support the use of ketoconazole in the treatment of certain forms of chronic coccidioidal infections.

The usefulness of fiberoptic bronchoscopy in evaluating new pulmonary lesions in the compromised host

Thirty-four fiberoptic bronchoscopies employing various bronchoscopic technics were carried out in 33 immune-compromised patients for the evaluation of new pulmonary lesions. Transbronchial biopsy was performed only with fluoroscopic guidance and was omitted in patients with a bleeding tendency. Bronchial brushing and bronchial washing were successfully carried out despite the presence of contraindications to biopsy. Brushing and washing were diagnostically useful in 66 and 74 per cent of the cases, respectively, compared to 71 per cent for forceps biopsy. The combined over-all yield was 88 per cent, with no serious complications encountered. The most common etiology of new infiltrates was opportunistic infection. Among bacterial infections, gram-negative organisms were the most common, and among fungal etiologies, Coccidioides immitis was the predominant pathogen in this series from Tucson, Arizona. Although the roentgenographic pattern was not helpful in predicting the etiology of the new infiltrates, diffuse lesions were more frequently evaluated correctly by fiberoptic bronchoscopy than localized lesions. The low incidence of complications and the high over-all yield indicate that fiberoptic bronchoscopy, employing bronchial brushing and washing as supplements to transbronchial biopsy (and as a replacement to biopsy in patients with a bleeding diathesis), can be very useful in evaluating new pulmonary lesions in the immune-compromised patient. When used together, these technics significantly increase the diagnostic yield and eliminate the risks associated with performing more invasive diagnostic procedures in the compromised host.

Long-term safety of nebulized formoterol: results of a twelve-month open-label clinical trial.

Formoterol fumarate is a long-acting β2-agonist that is an effective bronchodilator for the maintenance management of patients with chronic obstructive pulmonary disease. The safety profile of the newly developed nebulized formoterol was evaluated over a twelve-month period in an open-label, active-control study. After completing a twelve-week double-blind double-dummy period, 569 subjects with chronic obstructive pulmonary disease entered an open-label extension study and received twice-daily 20 µg formoterol fumarate inhalation solution for nebulization (FFIS) or 12 µg formoterol fumarate dry powder inhalation (FA) for 52 weeks. Most of the FFIS-treated subjects (86%) completed at least six months of open-label treatment with over 90% compliance, comparable to the FA group (88%). Results of safety monitoring for adverse events, laboratory values, and cardiac changes were similar between treatment groups. Three hundred forty (73%) of FFIS-treated subjects and 83 (78%) of FA-treated subjects experienced an adverse event over the course of the study, the majority of which were mild to moderate and considered unrelated to treatment. COPD exacerbation occurred in 15.8% of FFIS-treated and 17.9% of FA-treated subjects. Deaths, serious adverse events, and discontinuations for adverse events occurred in 1.3, 16.2, and 5.4% of the nebulized group versus 1.9, 17.9, and 7.5% of the inhaled group, respectively. There were no clinically important changes from baseline in laboratory tests, including serum potassium and glucose, or vital signs and no treatment-related increases in cardiac arrhythmias, heart rate, or QTc prolongation. We conclude that nebulized formoterol fumarate twice daily is well tolerated over long-term treatment in moderate-to-severe COPD subjects and has a similar safety profile to the DPI formulation.

Central ventilatory depression by oral propranolol

Propranolol, 20 mg, was given orally four times daily for 5 days and placebo four times daily for 5 days in a randomized, double‐blind fashion to nine healthy subjects. At the beginning of the study and on the last day of each medication pulse rate, blood pressure, airways resistance, maximum expiratory flow versus volume (using air and using 80% helium and 20% oxygen), spirometry before and after inhaled isoproterenol, and ventilatory and occlusion pressure responses to rebreathing carbon dioxide were measured. Results were compared by the Wilcoxon signed‐rank test. Propranolol was associated with decreases in pulse rate (P = 0.002), systolic blood pressure (P = 0.024), and diastolic blood pressure (P = 0.027). There were no differences in airway resistance or the change of expiratory flow with helium‐oxygen. Propranolol did not alter the preisoproterenol spirometry values but did reduce the response to isoproterenol. There were decreases in ventilatory responses (P = 0.004) and occlusion pressure responses (P = 0.006) at an end‐tidal carbon dioxide of 60 mm Hg. Propranolols beta‐adrenergic blockade supresses central ventilatory response to carbon dioxide.

Ventilatory Effects of Ketorolac and Morphine in Chronic Obstructive Pulmonary Disease

SummaryKetorolac (ketorolac-tromethamine) is a non-narcotic drug with an analgesic efficacy comparable with that of narcotic agents in postoperative pain. This single-dose single-blind randomised multicentre crossover study evaluated the ventilatory effects of intramuscular ketorolac 30mg and intramuscular morphine 10mg in 34 patients with mild to moderate stable chronic obstructive pulmonary disease. Patients had a screening visit (no drug) for baseline spirometry and 2 follow-up visits, 1 week apart, at which they received either morphine or ketorolac. Assessments of ventilatory response to hypercapnia were made before drug administration and hourly for 4 hours after administration at each of the 2 follow-up visits. At each hourly assessment there were statistically significant decreases in mean minute ventilation and mean inspiratory flow after morphine but not after ketorolac. Significantly more patients reported adverse effects after morphine than after ketorolac. The absence of ventilatory depression and improved tolerability indicates an advantage of ketorolac over morphine in the treatment of postoperative pain.

Protective effects of inhaled aminophylline on methacholine-induced airway responses in greyhound dogs

Abstract Aminopylline can be delivered as a heated aerosol via an air-powered small-volume nebulizer. We tested the hypothesis that inhaled aminophylline could attenuate the effects of inhaled methacholine on the airways. Five greyhound dogs were anesthetized, intubated, and ventilated. An esophageal balloon and flow transducer were placed in the ventilator circuit and connected to a BICORE CP-100 respiratory monitor. We measured mean lung resistance, lung dynamic compliance, and work of breathing. Each dog was pretreated for 30 minutes with three different formulations given randomly on separate days: aerosolized saline and intravenous saline, aerosolized aminophylline and intravenous saline, and aerosolized saline and intravenous aminophylline. The dogs were then exposed to a series of five inhalations of methacholine of increasing concentrations given at 15-minute intervals. The results demonstrated a significant reduction in the work of breathing and lung resistance and significantly increased compliance after treatment with aerosolized aminophylline but not with intravenous aminophylline. These findings support our hypothesis that aerosolized aminophylline has a protective effect against methacholine-induced bronchospasm. The results further suggest the possible use of aerosolized aminophylline for the treatment of obstructive lung disease.