Phosphorylated zidovudine concentrations in mononuclear cells in pediatric patients with human immunodeficiency virus infections.

PURPOSE: The efficacy of zidovudine (ZDV) in patients with HIV-1 infection may decrease over time due to its decreased activation. The objectives of this study were to determine ZDV concentrations in plasma, active phosphorylated zidovudine (pZDV) concentrations in mononuclear cells, and assess the markers of immune function and drug toxicity during extended therapy. METHODS: Pediatric patients (aged 3 months to 18 years) with HIV-1-infection were enrolled in the study. For each patient, one blood sample was collected at each of eight routine visits to measure plasma ZDV and ZDV concentrations by a radioimmunoassay. Data including demographic information, immunological markers (CD2+, CD3+, CD4+, CD5+/19+, CD8+, CD16+, CD19+, CD38+/8+ lymphocytes), hematologic function (absolute neutrophil count, white blood cell with differential, hemoglobin, and red blood cell count), concurrent medications, and dosage regimens were obtained. RESULTS: The data from 13 patients were as follows: age: 2-18 years; range of ZDV dose: 76-238 mg/m2, total ZDV daily dosage: 264-720 mg/m2; duration of ZDV therapy prior to study: 1 to 37 months; time in study: 180-394 days; plasma ZDV concentration range: 5-1021 ng/ml; and pZDV concentration range: 0-5.382 pmol/10(6) cells. Both plasma ZDV and intracellular pZDV concentrations had a marked inter- and intrapatient variability. The pZDV concentrations decreased significantly over time in one pediatric patient (p < 0.05), tended to decrease but not significantly in three patients, and no decrease was detected in nine patients due to high variability. In our population, neither immunological nor drug toxicity markers changed over time. CONCLUSIONS: Marked inter- and intrapatient variability in pZDV concentrations was observed. The ability to phosphorylate ZDV, however, did not appear to change significantly in 12 of 13 pediatric patients with HIV-1 infection during the study period of 6-13 months.

Fenoterol: clinical trial of a new long acting bronchodilator.

The bronchodilator and side effects of fenoterol and isoproterenol were evaluated in 19 asthmatic adults in a double-blind study. The study demonstrated that fenoterol has an onset of action which is just as rapid as isoproterenol and a duration of action that is markedly superior. Side effects were minimal.

Pulmonary function in former alcoholics.

Pulmonary function was evaluated in 44 former alcoholics (abstinence, 0.5 to 32 years) without cardiac or specific pulmonary disease. All were members of Alcoholics Anonymous. Fourteen subjects (32 percent) were non-smokers, ex-smokers, and cigar or pipe smokers, yet 28 subjects (64 percent) had abnormal expiratory flow rates, and 17 (39 percent) had an elevated value for the ratio of the residual volume to the total lung capacity. Single-breath diffusing capacity was abnormal in seven subjects (16 percent). Of interest was the high incidence (77 percent) of obstructive phenomena among the women. This high incidence of abnormalities among both the men and women could not be attributed to previous pulmonary infection or smoking. Comparison of these patients with chronic alcoholics suggests that the obstructive component in these patients is, in part, a result of their past alcoholic intake and that it is not reversed by abstinence. On the other hand, the impairment in diffusion, which was so common in alcoholics, appears to be reversible with sobriety.

The First Second Timed vital capacity and the course of obstructive lung diseases.

Previous work has shown that with increasing airway obstruction in chronic obstructive pulmonary disease, the decrement in the maximum midexpiratory flow (MMEF) is exponential. Therefore, with severe obstructive disease the decrease in the MMEF as the disease progresses is difficult to discern. This work points out that the fall in first second timed vital capacity (FEV1/FVC x 100) is linear through the course of the disease and, therefore, the decrement, in absolute terms, continues unaltered regardless of how severe the obstruction becomes. It is suggested that the FEV1/FVC x 100 might be more useful in monitoring the course of severe disease than the MMEF. However, it is stressed that both measurements are useful for large groups, but may not be useful in individual cases.

Detection of acute effects of cigarette smoking on airway dynamics: A critical and comparative study of pulmonary function tests.

In an effort to determine which measure of airway dynamics was the most sensitive to airway obstruction, comparisons were made between a variety of tests. Twenty cigarette smokers were studied both before and immediately after smoking a cigarette. The maximum midexpiratory flow (FEV25-75) and the FEV1/FVC per cent were abnormal in the largest number of cases. Closing volume was abnormal in only one case. Significant worsening in function after smoking a cigarette occurred in airway resistance and specific conductance. A lesser degree of impairment in airway dynamics was evident from FEV25-75 and first-second expired volume. The closing volume showed no change.

Pulmonary function tests and the diagnosis of bronchial asthma.

The uncertainties which combine to make the physiological profile of bronchial asthma difficult to define are discussed in this article. Although the clinician may take comfort when the physiologist has substantiated his diagnosis, he should not defer to the physiologist when pulmonary function testing fails to support his assessment of the patient.

The uses of simple spirometry.

The use of spirometry to determine pulmonary function has been complicated by the proliferation of measurements possible from the expiratory effort. Non-pulmonary physiologists face the problem of making a choice between a multiplicity of spirometric tests. Some guidelines for ventilatory testing are offered. The various uses of spirometry are indicated and those tests which best subserve these uses are suggested.