Clearance of Pneumocystis carinii cysts in acute P carinii pneumonia: assessment by serial sputum induction.

STUDY OBJECTIVES: To determine the feasibility of repeat sputum induction in acute Pneumocystis carinii pneumonia (PCP) and to define the rate of clearance of P carinii cysts from the respiratory tract of HIV-seropositive patients with acute PCP. DESIGN: Prospective cohort evaluation. SETTING: University medical center. PARTICIPANTS: Twenty-four HIV-seropositive subjects with acute PCP. MEASUREMENTS: Sputum induction for P carinii 2, 3, 4, and 6 weeks after initial diagnosis, and follow-up for 1 year. RESULTS: Eighty-eight percent of subjects had residual cysts at 2 weeks, 76% at 3 weeks, 29% at 4 weeks, and 24% at 6 weeks postdiagnosis. A prior AIDS-defining illness (p = 0.033) or prior PCP (p = 0.004) predicted relapse within 6 months, but persistent cysts at 3 weeks did not; 8 of 16 sputum-positive subjects and 1 of 5 sputum-negative subjects experienced a relapse within 6 months (p = 0.34). Secondary prophylaxis with trimethoprim-sulfamethoxazole was associated with a reduced risk of relapse. CONCLUSIONS: Serial sputum induction coupled with direct fluorescent antibody staining is a feasible, noninvasive method of respiratory tract surveillance for the eradication of P carinii during and after acute PCP. Three-quarters of HIV-seropositive patients with acute PCP have persistent cysts in their lungs at the end of antimicrobial treatment, despite clinical recuperation, but only one quarter have residual cysts 6 weeks postdiagnosis. A prior AIDS-defining illness and prior PCP are positively associated, and subsequent trimethoprim-sulfamethoxazole prophylaxis is negatively associated, with relapse within 6 months, while persistent organisms at 3 weeks do not appear to be a significant predictor of relapse risk.

Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis.

Severe alpha-1-antitrypsin deficiency is the only proven genetic risk factor for chronic obstructive pulmonary disease (COPD). We have assembled a cohort of 44 probands with severe, early-onset COPD, who do not have severe alpha-1-antitrypsin deficiency. A surprisingly high prevalence of females (79.6%) was found. Assessment of the risk to relatives of these early-onset COPD probands for airflow obstruction and chronic bronchitis was performed to determine whether significant familial aggregation for COPD, independent of alpha-1-antitrypsin deficiency, could be demonstrated. First- degree relatives of early-onset COPD probands had significantly lower FEV1 and FEV1/FVC values than control subjects (p < 0.01), despite similar pack-years of smoking. Reduced spirometric values in first-degree relatives of early-onset COPD probands were found only in current or ex-cigarette smokers. The mean FEV1 in current or ex-smoking first-degree relatives was 76.1 +/- 20.9% predicted compared to 89.2 +/- 14.4% predicted in current or ex-smoking control subjects (p < 0.01); in lifelong nonsmokers, the mean FEV1 was 93.4% predicted for both control subjects and first-degree relatives of early-onset COPD probands. Generalized estimating equations, adjusting for age and pack-years of smoking, demonstrated increased odds of reduced FEV1 and chronic bronchitis in current or ex-smoking first-degree relatives of early-onset COPD probands. Using a new method to estimate relative risk from relative odds, we estimate that the relative risks for FEV1 below 60%, FEV1 below 80%, and chronic bronchitis are each approximately three in current or ex-smoking first-degree relatives of early-onset COPD probands. The increased risk to relatives of early-onset COPD probands for reduced FEV1 and chronic bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for COPD that are expressed in response to cigarette smoking.

Employee assistance programs: a worldwide perspective.

Once limited to U.S. corporations, employee assistance programs (EAPs) are now spreading around the world. The authors review global EAP trends and identify similarities and differences among EAPs in North America, Europe, Central and South America, the Asia-Pacific region, and the Caribbean. Through affiliations between international professional associations and services to multinational corporations, the EAP field is quietly creating globalized behavioral health services.

Trimethoprim-sulfamethoxazole and hypouricemia.

BACKGROUND: Hypouricemia has been reported in a substantial fraction of patients with AIDS and attributed to an HIV-related renal urate transport defect. We tested the alternative hypothesis that hypouricemia was associated with the administration of high-dose trimethoprim-sulfamethoxazole (TMP-SMX). METHODS: Sociodemographic, clinical, and repeated laboratory data on 45 hospitalized patients with Pneumocystis carinii pneumonia (PCP) with and without HIV infection, were abstracted by a blinded reviewer. The primary outcome of interest was the percent change in serum uric acid concentration from baseline to hospital day 5 +/- 1. RESULTS: Subjects who received TMP-SMX were older (mean age 44.8 vs. 37.0, p = 0.02), less likely to be HIV-seropositive (61% vs. 94%, p = 0.01), and more likely to have received glucocorticoid therapy (75% vs. 35%, p = 0.01) than those who received pentamidine, dapsone-trimethoprim, clindamycin-primaquine, sulfadiazine-pyramethamine, or a combination of these agents. The administration of TMP-SMX was associated with a 37% +/- 12% reduction in serum uric acid concentration, adjusting for the effects of age, sex, race, HIV antibody status, renal function, serum sodium, and the use of diuretics and glucocorticoids (p = 0.005). CONCLUSION: Among a diverse cohort of hospitalized patients with PCP, treatment with high-dose TMP-SMX was strongly associated with a reduction in serum uric acid concentration over time.

Diurnal variation of urinary leukotriene E4 and histamine excretion rates in normal subjects and patients with mild-to-moderate asthma.

BACKGROUND: Leukotriene E4 (LTE4) and histamine excreted into the urine reflect the in vivo synthesis and release of cysteinyl leukotrienes and histamine, respectively. We examined the diurnal variation of the excretion rate of these mediators over 4 consecutive days in normal subjects (n = 5) and patients with stable mild-to-moderate asthma (n = 8). METHODS: Sixteen consecutive 6-hour urine samples were collected over 4 days. Urinary LTE4 concentrations were determined by reverse-phase high-pressure liquid chromatography, followed by ELISA. Urinary histamine concentrations were measured by ELISA. The excretion rates of these compounds were normalized relative to urinary creatinine content. RESULTS: The mean urinary LTE4 excretion rate was 83.8 +/- 38.2 pg/mg creatinine (mean +/- SD) in normal subjects; in patients with asthma, the urinary LTE4 excretion rate (110.0 +/- 59.2 pg/mg creatinine) was significantly higher than that in normal subjects (p < 0.05). The urinary histamine excretion rate was not different between normal subjects (24.0 +/- 12.5 ng/mg creatinine) and patients with asthma (31.5 +/- 25.8 ng/mg creatinine). A robust and systematic within-day variation (p < 0.01), but no day-to-day variation, was observed in histamine excretion rate. Although the magnitude of variation in LTE4 excretion within a day was significantly greater in patients with asthma than in normal subjects (p < 0.05), we could not identify any specific diurnal variation pattern in either the normal or the asthma group. No significant correlation was observed between urinary LTE4 and histamine excretion rate within any subject. CONCLUSIONS: Patients with asthma excrete LTE4 in the urine at a greater rate than normal subjects. Although no systematic variation in urinary LTE4 excretion rates over the course of a day was observed in either normal subjects or patients with stable asthma, the presence of a systematic diurnal variation of urinary histamine excretion exists in both groups.

Small cell lung cancer. Case report.

The selection of appropriate chemotherapeutic and/or radiation therapy for small cell lung cancer should be done after careful diagnosis and staging workup. A patient with small cell lung cancer is presented and explanation given for each step in diagnosis and staging.

Acetazolamide and furosemide attenuate asthma induced by hyperventilation of cold, dry air.

We investigated the assumption that the efficacy of inhaled diuretics in asthma is dependent upon inhibition of the Na+/K+/2Cl- cotransporter. We compared the protective effect of acetazolamide, a diuretic without significant effect on the loop cotransporter, with the protection provided by inhaled furosemide in a cold, dry air hyperventilation model of asthma. Seven asthmatic subjects underwent a baseline bronchial challenge and then received a nebulized dose of 80 mg of furosemide or 500 mg of acetazolamide or saline placebo in a randomized, double-blind, placebo-controlled crossover design. Repeat challenges were performed immediately and at 2 and 4 h postnebulization. Acetazolamide caused a 47.2% increase in the amount of cold, dry air required to reduce the FEV1, by 20% (expressed in terms of respiratory heat loss as PD20RHL), from 0.79 multiplied or divided by (x/divided by) 1.13 kcal/min (geometric mean x/divided by geometric SEM) at baseline to 1.17 x/divided by 1.09 kcal/min postnebulization (p < 0.025). Furosemide increased the geometric mean PD20RHL by 53.9%, from 0.86 x/divided by 1.12 kcal/min to 1.33 x/divided by 1.12 kcal/min (p < 0.001). There was no significant change after placebo inhalation (0.81 x/divided by 1.15 kcal/min versus 0.87 x/divided by 1.10 kcal/min, NS). Airway responsiveness had returned to baseline by 2 h postnebulization on all 3 days. Furosemide also caused bronchodilatation, producing a 14.1% rise in the mean FEV1 (p < 0.005 versus prenebulization), whereas neither acetazolamide nor placebo altered airway tone significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasculitis with recurrent pulmonary hemorrhage in a long-term survivor after autologous bone marrow transplantation.

We report an unusual vasculitic syndrome in a long-term survivor of autologous bone marrow transplant. Clinical and pathologic studies revealed a cutaneous and pulmonary leukocytoclastic vasculitis complicated by recurrent pulmonary hemorrhage. Serologic studies revealed an elevated anti-neutrophil cytoplasmic antibody titer. The vasculitis has been successfully controlled with prednisone, cyclophosphamide, and trimethoprim/sulfamethoxazole.

Adolescent self-esteem related to feelings toward parents and friends.

The study was conducted to see if there is a developmental process whereby the self-esteem of young adolescents is more closely related to feelings toward parents and that of older adolescents more closely related to feelings toward best friends. The subjects, 138 eighth-graders and 139 eleventh-graders, completed the Inventory of Family Feelings with regard to parents and best male and female friends and the Tennessee Self Concept Scale. Self-esteem was found to be significantly related to feelings toward parents and toward friends for adolescents of both grades. Feelings toward parents were generally more closely related to self-esteem than feelings toward friends, although the relationship between self-esteem and feelings toward parents was decreased with the older group. If a developmental shift in the relationship between self-esteem and feelings toward friends occurs, it does so slowly, showing only a slight beginning by the eleventh grade.