Pharmacodynamic effects of dopamine stratified by race.

The purpose of this investigation was to evaluate the effects of dopamine on heart rate (HR), systolic blood pressure (SBP), aldosterone, plasma renin activity (PRA), bradykinin, prolactin, corticotropin (ACTH), urinary output (UO), and urinary sodium (UNa) stratified by race. Sixteen healthy age- and weight-matched Caucasian and African American male subjects participated in this single-blind, three-phase study. The three phases included the following treatments and assessments: (i) 90-minute infusion of D(5)W 100 mL/h and control piggyback (control period); (ii) 90-minute infusion D(5)W 100 mL/h and 3 microg/kg/min dopamine (dopamine phase); (iii) assessments repeated 24 hours after dopamine administration (washout period). Plasma was analyzed for dopamine concentrations. Dopamine significantly increased HR and SBP across the study population. In addition, UO and UNa increased, prolactin was reversibly depressed, bradykinin and ACTH were unchanged, and aldosterone significantly rebounded on washout. With regard to race differences, SBP significantly increased in African Americans compared with Caucasians, and UNa significantly increased in Caucasians compared with African Americans. In summary, 3 microg/kg/min dopamine produced significant renal, hormonal, and hemodynamic changes in healthy men. Selected effects varied by race.

Reevaluation of continuous oxygen therapy after initial prescription in patients with chronic obstructive pulmonary disease.

BACKGROUND: Long-term oxygen therapy improves survival and quality of life in hypoxemic patients with chronic obstructive pulmonary disease (COPD). The need for long-term oxygen therapy should be determined when patients are medically stable. The Third Oxygen Consensus Conference recommended reevaluating patients 1-3 months after continuous oxygen therapy (COT) is initiated, if initiated when the patient is medically unstable. METHODS: A cross-sectional study was performed to examine how often orders for COT are reevaluated pursuant to the guidelines promulgated by the Third Oxygen Therapy Consensus Conference, and to assess the impact that following these guidelines would have on the cost of COT. RESULTS: Of 226 patients prescribed home oxygen therapy, 92 had COPD as a primary diagnosis and 57 were prescribed COT. Only 19 (35%) of 55 patients who returned to the clinics were appropriately reevaluated. The rate of appropriate reevaluation was significantly higher among pulmonary physicians than among primary care physicians (65% vs 17%; odds ratio: 9.0; 95% confidence interval: 2.5-32). Of 19 patients who were appropriately reevaluated, 11 (58%) were discontinued from COT. The patients who were discontinued from COT had a significantly higher percent of predicted forced expiratory volume in the first second than those who were not (34 +/- 8.6% vs 25 +/- 8.8%; p = 0.04). CONCLUSIONS: In our study, most patients were clinically unstable when COT was prescribed, and a significant number of patients remained on COT without reevaluation. Up to 60% of those patients could potentially be discontinued from COT if appropriately reevaluated. Referring a patient initiated on COT to a pulmonary specialist for the proper use of oxygen is strongly recommended. Reevaluating such patients in a timely fashion and discontinuing unnecessary oxygen concentrators could possibly save $106-153 million per year in the United States.

Knowledge of tuberculosis in high-risk populations: survey of inner city minorities.

SETTING: Educational programs targeted toward individuals at risk for tuberculosis are needed. As an initial step in developing future programs, the present study was designed to determine the baseline knowledge about tuberculosis in at-risk individuals. METHODS: Face-to-face surveys were conducted with 505 minority subjects in the Kansas City Metropolitan area; health care providers were excluded. Thirty-six queries directed toward self-perceived and actual tuberculosis knowledge were asked. Data were tabulated and per cent correct response was determined. RESULTS: Completed surveys were available from 505 subjects: 342 females and 163 males. Most (97%) of the subjects were African Americans, with 57% between the ages of 21-40. Over two-thirds were high school graduates, and 77% reported an estimated total household annual income of <$20000. Self-perceived knowledge about tuberculosis was rated as 'little' or 'nothing' by 60% of respondents. The overall correct response score was 61%, with 55% correct response to queries related to etiology, 53% for identification of high-risk populations, 57% for possible routes of transmission, 89% for symptoms, and 49% for treatment. Males, those with annual incomes >$20000, and individuals 51-70 years old had the highest scores. CONCLUSIONS: In this high-risk inner-city population surveyed, knowledge deficits in the etiology, transmission, and treatment of tuberculosis were identified.

Continuously nebulized albuterol in severe exacerbations of asthma in adults: a case-controlled study.

A retrospective, case-controlled analysis comparing patients admitted to a medical intensive care unit with severe exacerbations of asthma who received continuously nebulized albuterol (CNA) versus intermittent albuterol (INA) treatments is reported. Forty matched pairs of patients with asthma are compared. CNA was administered for a mean of 11 +/- 10 hr. The incidence of cardiac dysrhythmias was similar between groups. Symptomatic hypokalemia did not occur. CNA patients had higher heart rates during treatment, which may reflect severity of illness. The incidence of intubation was similar. We conclude that CNA and INA demonstrated similar profiles with regard to safety, morbidity, and mortality.

Determination of CYP2C19 phenotype in black Americans with omeprazole: correlation with genotype.

BACKGROUND: Our objective was to study omeprazole as a single-dose oral probe in the determination of CYP2C19 phenotype in black subjects and to determine the correlation between phenotype and genotype. METHODS: This single-dose, open-label outpatient study was conducted at a community-based, university-affiliated teaching hospital outpatient clinic. Study subjects were 100 healthy, unrelated black adults (age range, 18 to 50 years) who were receiving no medications. Baseline omeprazole and 2-hour postingestion omeprazole and 5'-hydroxyomeprazole concentrations were measured for phenotype determination. Identification of CYP2C19m1 genotypes were performed with use of the polymerase chain reaction. RESULTS: Results were obtained for 28 men and 72 women. Ninety-eight subjects were found to be phenotypically extensive metabolizers and two to be poor metabolizers (one man; one smoker). Genotype determination revealed that the two poor metabolizers of omeprazole were homozygous for a single base pair mutation (m1/m1) in exon 5 of CYP2C19. Twenty-eight of the extensive metabolizers were heterozygous (m1/wt) and the remaining 70 were homozygous (wt/wt). No side effects were reported. CONCLUSIONS: The 2% prevalence rate of poor CYP2C19 metabolizers in this healthy black population residing in the Midwestern United States is similar to that reported in white subjects and in the Shona population of Zimbabwe but much less than in Asian subjects. Omeprazole is a safe and specific probe of the CYP2C19 enzyme system that correlates well with genotype.

Soluble versus cell-bound CD4, CD8 from bronchoalveolar lavage: correlation with pulmonary diagnoses in human immunodeficiency virus-infected individuals.

Identification and assessment of cell populations in bronchoalveolar lavage (BAL) specimens may he used to follow the course of a disease state or response to specific therapy. Beyond cellular assessment, there are indications that the presence and quantity of soluble surface antigens released from activated cells may lead to improved understanding and facilitated diagnosis of a number of disease states. This study evaluated soluble markers (sCD4 and sCD8) in BAL and serum from HIV-infected individuals undergoing diagnostic bronchoscopy, and compared these values to flow cytometry-quantified BAL and peripheral blood cell CD4 and CD8. Patient pulmonary diagnosis (based on cytology and microbiology) was compared with patient blood and BAL-soluble and cell-bound CD4 and CD8 to determine the relationship of these markers to disease states in this population. Serum sCD8 in patients with fungal infections was significantly elevated above sCD8 in patients with Pneumocystis carinii or pulmonary bacterial infections, p = 0.0001. BAL sCD4/sCD8 ratio was also significantly different in patients with bacterial vs. fungal pulmonary infections, p = 0.01. These findings suggest that soluble markers, particularly elevated sCD8, may be an important indication of pulmonary disease progression in these HIV+ patients with fungal infections.

Dextromethorphan polymorphic hepatic oxidation (CYP2D6) in healthy black American adult subjects.

The objective of this study was to assign metabolizer phenotype to 107 healthy adult black Americans using dextromethorphan as the substrate probe. Eligible subjects were unrelated, healthy, nonsmoking, aged 18-50 years, and taking no medications. Fifteen milliliters of dextromethorphan syrup (85 mumol, 30 mg) was administered orally at bedtime, and 8-h overnight urine was collected. Dextromethorphan and dextrorphan urinary areas and molar ratios were determined using high-performance liquid chromatography with fluorescence detection. A molar metabolic ratio of < 0.3 was used to segregate poor metabolizers (PM) from extensive metabolizers (EM). Data were obtained in 99 subjects: 68 women, 31 men. (Five were lost to follow-up, three did not take the probe drug.) Six (6.1%) were PM (five women, one man), and 93 were EM. The prevalence of PM was 6.1% (95% confidence interval, 2.3-12.7%) in our sample. This compares to 5 to 10% reported in white unrelated subjects and 1.9% in 106 black children (64 healthy and 42 with cancer), and 0-8.6% in black African populations. The clinical implications of these findings warrant further investigation.