Howard Schanker

Pneumocystis carinii Pneumonia and Mucosal Candidiasis in Previously Healthy Homosexual Men

Four previously healthy homosexual men contracted Pneumocystis carinii pneumonia, extensive mucosal candidiasis, and multiple viral infections. In three of the patients these infections followed prolonged fevers of unknown origin. In all four cytomegalovirus was recovered from secretions. Kaposis sarcoma developed in one patient eight months after he presented with esophageal candidiasis. All patients were anergic and lymphopenic; they had no lymphocyte proliferative responses to soluble antigens, and their responses to phytohemagglutinin were markedly reduced. Monoclonal-antibody analysis of peripheral-blood T-cell subpopulations revealed virtual elimination of the Leu-3 / helper/inducer subset, an increased percentage of the Leu-2 + suppressor/cytoxic subset, and an increased percentage of cells bearing the thymocyte-associated antigen T10. The inversion of the T/ helper to suppressor/cytotoxic ratio suggested that cytomegalovirus infection was an important factor in the pathogenesis of the immunodeficient state. A high level of exposure of male homosexuals to cytomegalovirus-infected secretions may account for the occurrence of this immune deficiency.

Ocular Disorders Associated with a new Severe Acquired Cellular Immunodeficiency Syndrome

Among the prominent features of a newly described acquired cellular immunodeficiency syndrome that affects previously healthy male homosexuals are multiple opportunistic infections and Kaposis sarcoma. Immunosuppression induced by cytomegalovirus infection may play a major role in the pathogenesis of this disorder. We have performed ophthalmic examinations on seven such patients and found ocular abnormalities in all cases. Six patients were examined during the course of their illness and one patient at autopsy only. Each patient had several cotton-wool spots in the affected eye. Other ocular findings included cytomegalovirus retinitis, severe retinal periphlebitis, and conjunctival Kaposis sarcoma (one case each).

Comparison of the bronchodilatory effects of cetirizine, albuterol, and both together versus placebo in patients with mild-to-moderate asthma

BACKGROUND Many potential users of the H1 antihistamine cetirizine are asthmatic and may be using inhaled albuterol. This study was conducted to assess the possible bronchodilatory effect of cetirizine in patients with mild-to-moderate asthma and to determine whether cetirizine interacts with albuterol. METHODS In a randomized, double-blind, placebo-controlled, crossover study, the effects on pulmonary function of 5, 10, and 20 mg oral doses of cetirizine with and without inhaled albuterol (180 micrograms) were determined in 12 patients at 11 time points over 8 hours. The primary measure of efficacy was forced expiratory volume in 1 second (FEV1). RESULTS Cetirizine with or without albuterol significantly increased FEV1, peak expiratory flow rate, and forced expiratory flow rate between 25% and 75% of vital capacity relative to baseline and placebo but did not have a significant effect on forced vital capacity. The effect of 20 mg of cetirizine on FEV1 was generally greater than that of 10 or 5 mg, but the difference was statistically significant only at the 30-minute time point (p < 0.05). All three cetirizine doses produced significantly greater increases than placebo in FEV1 and forced expiratory flow rate between 25% and 75% of vital capacity for 8 hours and in peak expiratory flow rate for 7 hours (p < 0.02). Albuterol alone had a significant effect on the four pulmonary function variables from 1 to 5 hours after baseline (p < 0.05), which is consistent with albuterols recommended dosing frequency of every 4 to 6 hours. Albuterol alone increased FEV1 significantly more than 5 mg of cetirizine alone but not 10 mg or 20 mg of cetirizine alone at 60, 90, and 120 minutes after baseline, but all three doses of cetirizine increased FEV1 significantly more than albuterol 7 and 8 hours after baseline (p < 0.05), indicating that the bronchodilatory action of cetirizine lasts longer than that of albuterol. Cetirizine neither potentiated nor inhibited the bronchodilatory action of albuterol, but the two drugs appeared to have an additive bronchodilatory effect. None of the cetirizine treatments caused a worsening of pulmonary function, and all were well tolerated. CONCLUSIONS Cetirizine has a significant bronchodilatory effect in patients with mild-to-moderate asthma and can be used to treat concomitant conditions (e.g., allergic rhinitis) without concern that it will interfere with the bronchodilatory effect of albuterol or cause worsening of asthma by itself.

Pneumocystis Carinii Pneumonia and Mucosal Candidiasis in Previously Healthy Homosexual Men. Evidence of a New Acquired Cellular Immunodeficiency

Four previously healthy homosexual men contracted Pneumocystis carinii pneumonia, extensive mucosal candidiasis, and multiple viral infections. In three of the patients these infections followed prolonged fevers of unknown origin. In all four cytomegalovirus was recovered from secretions. Kaposis sarcoma developed in one patient eight months after he presented with esophageal candidiasis. All patients were anergic and lymphopenic; they had no lymphocyte proliferative responses to soluble antigens, and their responses to phytohemagglutinin were markedly reduced. Monoclonal-antibody analysis of peripheral-blood T-cell subpopulations revealed virtual elimination of the Leu-3 / helper/inducer subset, an increased percentage of the Leu-2 + suppressor/cytoxic subset, and an increased percentage of cells bearing the thymocyte-associated antigen T10. The inversion of the T/ helper to suppressor/cytotoxic ratio suggested that cytomegalovirus infection was an important factor in the pathogenesis of the immunodeficient state. A high level of exposure of male homosexuals to cytomegalovirus-infected secretions may account for the occurrence of this immune deficiency.

Onset and duration of action of levocabastine nasal spray in atopic patients under nasal challenge conditions

BACKGROUND Although prior studies have documented the rapid onset of action of topical intranasal levocabastine (LEV), little is known about its duration of action under nasal challenge conditions. OBJECTIVES We sought to assess the onset and duration of action of escalating doses of LEV nasal spray by using a nasal allergen challenge (NAC) model. METHODS Eighteen asymptomatic subjects with histories of seasonal allergic rhinitis were enrolled into a randomized, single-blind, placebo-controlled, dose-ranging crossover study. Each patient was randomly assigned to receive single doses of placebo and intranasal LEV 0.1, 0.2, and 0.4 mg during 2 parts of the study. In part 1 (onset of action), NAC consisted of a single dose of allergen administered 5 minutes after study drug treatment. In part 2 (duration of action), NAC consisted of increasing doses of allergen administered 0.5, 6, 12, and 24 hours on separate days after study drug treatment. Nasal symptom scores (NSSs) and nasal peak expiratory flow rates were measured after NAC in both phases of the study. Blood samples for plasma LEV concentrations were drawn after each NAC. RESULTS In part 1, NSSs were significantly lower after the administration of LEV 0.1, 0.2, and 0.4 mg compared with placebo (P <.05). In part 2, NSSs were significantly lower after LEV doses of 0.2 and 0.4 mg compared with placebo at 0.5, 6, 12, and 24 hours after treatment (P <.05). The mean provocative dose of allergen required to elicit a positive nasal reaction was increased after LEV doses of 0.2 and 0.4 mg at 0.5, 6, and 12 hours after treatment. Nasal peak expiratory flow rates demonstrated no significant differences between LEV and placebo for any doses at any time points. Mean plasma LEV concentrations were low (range, 0 to 3. 7 ng/mL) after all doses and did not correlate with drug efficacy. CONCLUSIONS Single intranasal LEV doses of 0.1, 0.2, and 0.4 mg significantly reduced the severity of the immediate nasal response to allergen when administered 5 minutes before NAC. This protective effect against NAC continued to be present 24 hours after administration of LEV doses of 0.2 and 0.4 mg. Efficacy in blocking the reaction to NAC did not correlate with plasma LEV levels, suggesting that the inhibitory effect was due largely to topical rather than systemic effects.