Hemolytic uremic syndrome associated with clopidogrel: a case report.

Clopidogrel and ticlopidine are antiplatelet agents used in the treatment of patients with cerebrovascular and peripheral vascular disease and to reduce the risk for thrombosis in patients undergoing coronary artery stenting. Ticlopidine has been reported to have major hematologic adverse effects, including neutropenia and thrombotic thrombocytopenic purpura or hemolytic uremic syndrome (HUS). Clopidogrel, an analogue of ticlopidine, was developed because it did not show bone marrow toxic effects in either tissue culture or animal models. In human studies, to date, clopidogrel has been associated with a low incidence of severe neutropenia and no reported cases of thrombotic thrombocytopenic purpura or HUS. For these reasons, clopidogrel has been increasingly used in place of ticlopidine after coronary artery stenting. We report a case of clopidogrel-associated HUS. This observation implicates clopidogrel as a possible causative agent in HUS.

Asthma symptoms and airway hyperresponsiveness are lower during treatment with nedocromil sodium than during treatment with regular inhaled albuterol.

In a double-blind, double-dummy, multicenter study, 212 patients with asthma whose symptoms were not controlled by as-needed use of inhaled bronchodilators were randomized to receive either 4 mg of nedocromil sodium or 180 micrograms of albuterol four times daily for 12 weeks. Asthma symptom scores (daytime asthma, nighttime asthma, morning chest tightness, and cough) and peak expiratory flow rate were recorded daily on diary cards. Bronchial hyperresponsiveness was assessed by changes in diurnal variation in peak expiratory flow rate and by methacholine inhalation challenge. Statistically significant differences were found between groups favoring nedocromil sodium for relief of day and nighttime asthma and morning chest tightness. Patients treated with nedocromil sodium also had significantly lower diurnal variation in peak expiratory flow rate compared with patients treated with albuterol. Compared with patients treated with albuterol, patients treated with nedocromil sodium showed a greater improvement in cough and a decreased sensitivity to methacholine challenge. Patients in both groups reduced their as-needed albuterol use. Regular treatment with nedocromil sodium therefore led to greater asthma symptom control and reduced bronchial responsiveness compared with regular treatment with albuterol. The study also showed that more frequent use of a beta 2-agonist (for symptom relief or not) did not improve asthma control. Both drugs were well tolerated.

Conversion from twice- to once-daily extended-release theophylline treatment in patients with reversible airway obstruction.

This multicenter, randomized, investigator-blinded, parallel group study compared the effects of converting patients from a q12h extended-release theophylline preparation (Theo-Dur) to a q24h extended-release product (Uni-Dur). Patients (n = 133) first received open-label Theo-Dur treatment with dosage titrated to achieve peak serum theophylline concentrations of 10-20 micrograms/ml. Patients then were randomized to continue Theo-Dur (n = 64) or to convert to Uni-Dur (n = 60) with peak serum theophylline concentrations maintained in the desired range. Pulmonary function tests were performed during the open-label and blinded periods; patients maintained diaries and performed peak flow measurements before each dose of study treatment. Adverse events were recorded throughout the study. Respiratory status during blinded treatment was rated as the same or improved compared with open-label treatment by > 87% of evaluable patients and physicians, regardless of treatment group. There were no significant differences in mean peak serum theophylline concentrations at baseline, at the final evaluation, or at any point during the study. Few dosage adjustments were necessary (5/52, Uni-Dur; 9/57, Theo-Dur). There were no significant changes in pulmonary function test results or patient diary entries between the open-label and blinded periods. Headache and nausea were the most commonly reported adverse events. In conclusion, converting patients from twice- to once-daily theophylline treatment resulted in no significant changes in any measures of pulmonary function, and there were no significant differences between the groups during the blinded treatment period.

Effects of topical nasal treatment on asthma symptoms.

During the ragweed season of 1984 we studied 120 patients with hay fever; 58 had a history of asthma during the ragweed season the year before. They were divided into four treatment groups to receive nasal sprays of placebo, cromolyn sodium, flunisolide, or beclomethasone. In controlling hay fever symptoms all medications were superior to placebo; the glucocorticoids were more effective than was cromolyn sodium. Chest symptoms in the 58 patients with a history of asthma were also relieved by the topical nasal treatment. Various explanations for the beneficial effect of topical nasal treatment in asthma symptoms are conceivable. We consider the most likely to be improvement of nasal airway function. With restoration of the filtering action of the nose, less allergen would penetrate to the intrathoracic airways because of reduction in mouth breathing.

Mast cell pharyngitis as a cause of supraglottic edema.

A 30-year-old nonatopic woman had experienced a 9-year history of persistent symptoms of supraglottic edema. She had previously undergone epiglottectomy and excision of redundant left arytenoid tissue to improve her breathing and dysphagia. Uvular tissue was removed surgically at our clinic for histopathological examination of the excised tissues. This revealed diffuse infiltration by mast cells, many of which appeared degranulated. Uvular tissue from control patients undergoing uvulopalatopharyngoplasty for obstructive sleep apnea contained significantly fewer mast cells per high power field. To our knowledge such a degree of mast cell infiltration into supraglottic tissues has not been reported previously or associated with clinical symptoms.

Efficacy of beclomethasone nasal solution, flunisolide, and cromolyn in relieving symptoms of ragweed allergy.

Although three effective topical treatments for allergic rhinitis are available, little information to assist the clinician in choosing among them has been reported. Therefore, we conducted a randomized clinical trial to compare beclomethasone nasal solution, flunisolide, and cromolyn with placebo in 120 patients with hay fever during the ragweed season of 1984. We found that all three agents were superior to placebo (P less than 0.001) and that the glucocorticoids were more effective than cromolyn (P less than 0.001). Surprisingly, we also found that these intranasal treatments considerably reduced the symptoms of seasonal asthma. Further study of this therapeutic advantage is needed.

Episodic angioedema associated with eosinophilia.

We studied four patients with recurrent attacks of angioedema, urticaria, and fever. During attacks, body weights increased up to 18 per cent, and leukocyte counts reached 108,000 per microliter (88 per cent eosinophils). The disease did not appear to threaten the function of vital organs. The two children received prednisone intermittently; the adults did not require treatment or were given alternate-day prednisone. Glucocorticoid therapy caused defervescence and diuresis and decreased total leukocyte and eosinophil counts. No patient had evidence of cardiac involvement (follow-up, 2 to 17 years). One patient remained in spontaneous remission for 20 years before symptoms recurred. Histologic studies showed that eosinophils localized and degranulated in the dermis, and they appeared to induce edema. Although this syndrome might be classified as a variant of the hypereosinophilic syndrome, we believe it is a separate entity because of its distinctive characteristics and its benign course.

Episodic angioedema associated with eosinophilia.

Four patients with recurrent attacks of angioedema, urticaria, and fever were seen. During attacks, body weights increased up to 18% and leukocyte counts reached 108,000/microliters (88% eosinophils). Glucocorticoid therapy caused defervescence, diuresis, and decreased total leukocyte and eosinophil counts. The two children received prednisone intermittently; the adults did not require treatment or their conditions were controlled by alternate-day prednisone administration. No patient had evidence of cardiac involvement (follow-up, 2-17 years). The disease does not threaten the function of vital organs. One patient remained in spontaneous remission for 20 years before symptoms recurred. Although it might be classified as a variant of the hypereosinophilic syndrome, we believe that this syndrome is a separate entity because of its distinctive characteristics and its benign course.