Leukocyte migration inhibition in amiodarone-associated pneumonitis

Amiodarone-associated pneumonitis is now a well-known clinical entity, but the mechanism for the induction of the pulmonary disease is ill defined. In four patients with this disorder, evidence was obtained for elaboration of a lymphokine, leukocyte inhibitory factor (LIF), by peripheral blood lymphocytes after incubation with amiodarone in the direct leukocyte migration inhibition test. Control lymphocytes from normal subjects, as well as from patients receiving amiodarone but without pneumonitis, failed to elaborate LIF in the presence of the drug in this test. This production of LIF suggests that pneumonitis associated with amiodarone therapy is also associated with a specific cellular immune response to the drug.     

A new diagnostic approach in lymphangiomatosis. Apropos of a case

Lymphangiomyomatosis is a rare disease affecting exclusively women usually in child-bearing age. It is characterized by proliferation of an atypical smooth muscle involving the pulmonary, mediastinal and retroperitoneal lymph system. The case reported here concerns a 53-year old woman presenting with an interstitial pulmonary lesion giving a characteristic image at CT. The patient also had recurrent chylothorax and a renal angiomyolipoma explored by CT and magnetic resonance imaging. The diagnosis of lymphangiomyomatosis was made on a cluster of arguments, without having recourse to surgical lung biopsy.     

Sampling technique and rheology of human tracheobronchial mucus

The aims of this work were: (1) to establish a technique for the sampling of human tracheobronchial mucus not contaminated by saliva or topical anesthesia, and (2) to measure its viscoelastic properties. After local anesthesia of the hypopharynx by topical application of 4% xylocaine, a double-sleeve microbiology specimen brush was introduced into a flexible bronchoscope placed in the trachea. The brush was left in direct contact with the bronchial mucosa for 20 to 30 s to allow mucus to collect on it. The mucus sample was then scraped from the brush and immediately covered with paraffin oil. Its viscoelastic properties were determined by the magnetic microrheometer technique. Excluding the time to anesthetize, the whole procedure took less than 1 min (thus minimizing the effect of cough) and resulted in sufficient mucus for rheologic analysis in approximately 90% of trials, i.e., 2.1 +/- 1.5 (SD) mg. Mucus specimens were collected from 20 fasting healthy nonsmoking subjects; 17 of them returned for a second collection several days later. Values for mucus mechanical impedance (vector sum of elasticity and viscosity) at 1 rad/s were: Control 1, 141 +/- 41 (SE); Control 2, 155 +/- 58 dyn/cm2. There was a large variation in mucus viscoelasticity, both between subjects (CV, 130%) and within the same subject (CV, 55%) on different days. In 7 subjects, mucus samples were collected 15 min after intravenous injection of 0.6 mg atropine. Viscoelasticity in these samples was 708 +/- 147 dyn/cm2, a value significantly different from Control 1 (p less than 0.05) and Control 2 (p less than 0.05) values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory manifestations of mycosis fungoides. Apropos of a case

Mycosis fungoides is today classified amongst the cutaneous T lymphomas. The course of the disease is slow, first strictly dermatological, then with polyvisceral spread most often presenting as lymphadenopathy. Pulmonary involvement, with a poor prognosis, is often recognised only at autopsy. The differential diagnosis between pulmonary involvement by the disease and isolated or associated opportunistic infectious pathology is virtually impossible during the patient's lifetime except by surgical lung biopsy. The case reported here illustrates these data and has the particular feature of the onset of pulmonary involvement during cutaneous remission of the disease, contrasting with the visceral spread found at autopsy.     

Provocation test coupled with bronchoalveolar lavage in diagnosis of drug (nilutamide)-induced hypersensitivity pneumonitis

A 79-year-old man was given a cumulative dose of 16.5 g of nilutamide for treatment of prostate cancer. He then presented with a respiratory illness having clinical, radiologic and functional characteristics of interstitial pneumonitis. No other cause of pneumonitis was found. Bronchoalveolar lavage showed a lymphocytic alveolitis with an inverted lymphocyte subset ratio. After an 11-week period of drug withdrawal, clinical, radiologic and functional improvement was observed along with a normal alveolar lymphocytosis. Nilutamide therapy was then resumed for five weeks and induced the recurrence of clinical, functional and alveolar abnormalities. Nilutamide treatment was finally stopped and two months later, clinical and functional abnormalities resolved. This observation seems to exemplify the possible diagnostic value of coupling provocation test with BAL cell data in hypersensitivity pneumonitis induced by drugs. In addition, these data support the role of a cell-mediated immunologic mechanism in the pathogenesis of nilutamide-induced pneumonitis.     

Pharmacokinetic interactions between NSAIDs (indomethacin or sulindac) and H2-receptor antagonists (cimetidine or ranitidine) in human volunteers

The reciprocal effects on pharmacokinetic parameters after a single oral dose of the nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin and sulindac and repeated oral doses of the H2-receptor antagonists cimetidine and ranitidine were determined in two groups of nine healthy subjects each (indomethacin and sulindac groups). Administration of NSAIDs increased the AUC and decreased the oral clearance and apparent volume of distribution of the H2-receptor antagonists without modifying their t1/2. Urinary data and observed modifications in ranitidine and cimetidine metabolites seem to justify a greater increase of H2-receptor antagonist bioavailability with indomethacin (p less than 0.05) than with sulindac (NS). The administration of ranitidine significantly reduced the sulindac volume of distribution without modifying its clearance, which caused an increase in the maximum concentration and a decrease in the t1/2 (p less than 0.05). The effects of cimetidine on the two NSAIDs were more intense than the effect of ranitidine: the decrease in sulindac volume of distribution (p less than 0.02) was accompanied by a significant reduction in sulindac clearance (p less than 0.05). AUC and urinary amounts of sulindac's sulfone metabolite were decreased. These results show that NSAIDs increased the bioavailability of H2-receptor antagonists, and that the latter drugs decrease the volume of distribution of NSAIDs. Furthermore, cimetidine modifies the oxidation metabolism of sulindac.     

Hormonal modulation in systemic lupus erythematosus. Preliminary clinical and hormonal results with cyproterone acetate

We prospectively studied the effects of hormonal modulation using the antigonadotropic drug, cyproterone acetate (CA), in 7 female patients who had moderately active systemic lupus erythematosus. CA was taken orally at a mean daily dose of 50 mg for 21-33 months by 6 patients (9 months by the seventh patient) without any side effects. The number of clinical lupus exacerbations during CA treatment was lower than that during the corresponding pretreatment period (15 of 170 patient-months versus 27 of 156 patient-months; P less than 0.05), despite a reduction in the daily maintenance dose of corticosteroids or antimalarial drugs. Mean plasma testosterone levels were low initially and remained unchanged (0.66 +/- 0.31 to 0.59 +/- 0.23 nmoles/liter), whereas plasma estradiol decreased markedly (from 0.6 +/- 0 38 to 0.11 +/- 0.03 nmoles/liter), resulting in a significant reduction in the estradiol:testosterone ratio (from 1.19 +/- 0.68 to 0.23 +/- 0.12) and in the plasma concentration of the sex hormone-binding protein. Thus, cyproterone acetate induced improvement in clinical lupus activity in parallel with the expected lower estradiol:testosterone balance.