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.

Using a severity of illness scoring system to assess intensive care unit admissions for diabetic ketoacidosis.

OBJECTIVE: To determine the appropriateness of intensive care unit (ICU) admissions for patients with the diagnosis of diabetic ketoacidosis (DKA) at our institution. DESIGN: Retrospective chart review. SETTING: Tertiary care inner-city hospital. SUBJECTS: All subjects admitted to the medical intensive care unit (MICU) from September 1996 to June 1997 with a diagnosis of DKA were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A grading system for the severity of DKA (grades 0-IV) from a previously published work was modified. Admissions to the MICU that were deemed appropriate a priori included patients with grade III or IV DKA, patients with grade II DKA who were older than 65 yrs of age, or patients with special situations normally warranting intensive care. MAIN RESULTS: Sixty-seven cases of DKA were reviewed. Two thirds of the patients had type I diabetes mellitus, and approximately 50% were men. No deaths occurred. Forty-four patients (66%) met the a priori ICU admission criteria. The average hospital stay for all patients was 4.2 (+/-3.6) days. The mean ICU stay was significantly longer in those with DKA grade III or IV, although the total hospital stay did not differ by severity of illness score. CONCLUSIONS: One third of the patients admitted to our MICU to receive treatment for DKA did not warrant ICU treatment based on the admission criteria. These individuals had an approximate MICU length of stay of 1 day. A prospective study of the severity of illness score will be undertaken to evaluate the safety, validity, and potential resource savings of applying these DKA ICU admission criteria within our institution.

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.

Pharmacokinetics and relative bioavailability of selegiline in healthy volunteers.

Selegiline is beneficial to Parkinsonian patients as an adjunct to levodopa therapy. A sensitive flourimetric assay based on inhibition of rat brain monoamine oxidase-B (MAO-B) in vitro has been developed to study the pharmacokinetics of selegiline. This method quantitates selegiline as low as 0.25 ng ml-1. The pharmacokinetics and relative bioavailability of selegiline were investigated in healthy volunteers following oral administration of 10 mg tablet or solution. A half-life of approximately 70 min was observed following the administration of either dosage form. Although the two dosage forms exhibited a lag time, the absorption was rapid and peak plasma concentrations were observed between 30 and 45 min for the solution and 30 and 90 min for the tablets. Statistically no significant difference was found between Cmax, Tmax, AUC0-infinity and MRT between the two dosage forms. Negligible renal clearance was found in both groups, but apparent oral plasma clearance was comparatively high and indicates rapid elimination of selegiline from the body.

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.

Family leave policies, job share, and child care at U.S. schools and colleges of pharmacy.

A 10-question survey was mailed to the deans of 74 schools and colleges of pharmacy to characterize family leave policies, child care, and job share opportunities. Data were tabulated as percentage response received, and analyzed by geographic region and by public compared with private institutions. Sixty-four surveys were completed (response rate 86%). Forty-eight (75%) schools reported having a formal written family leave policy: 47 offered maternity leave, 31 parental leave, 27 caregiver leave, 24 paternal leave, and 24 adoptive or foster parent leave. The duration and compensation for family leave varied among schools. A statistical difference was found between the Northeast (100%) and South (55%) in having such a policy. On-site child care was available at 26 (41%) schools, including both infant and child care in 12 and additional sick child care in 2. Three (5%) schools reported faculty job share positions.

Drug- and chemical-induced aseptic meningitis: a review of the literature.

OBJECTIVE: The primary objective of this article is to provide readers with case reports of drug- or chemical-induced aseptic meningitis (DCAM) described in the medical literature. Background information regarding the classification of DCAM, incidence, proposed mechanisms, associated risk factors, clinical management, and sequelae is presented. DATA SOURCES: A MEDLINE search was used to identify pertinent background literature and case reports of DCAM. DATA EXTRACTION: All case reports of DCAM involve anecdotal information. A critical analysis of a causal relationship to the implicated drug or chemical and the appearance of meningeal involvement is presented. Animal data are included when pertinent. DATA SYNTHESIS: DCAM is a rare adverse event associated with numerous agents. Patients present with a variety of clinical signs and symptoms and laboratory findings of cerebral spinal fluid, when obtained, vary greatly. Most patients fully recover without sequelae. CONCLUSIONS: Numerous drugs and chemicals have been implicated in the medical literature as producing DCAM. Two proposed mechanisms of DCAM have been theorized: a delayed hypersensitivity-type reaction and direct meningeal irritation. The nonsteroidal antiinflammatory drugs, certain antibiotics, radiographic agents, and muromonab-CD3 have been most frequently implicated. There appears to be an association between the occurrence of the hypersensitivity-type reactions and underlying collagen vascular or rheumatologic disease.

Anistreplase: a novel thrombolytic agent for acute myocardial infarction.

Anistreplase, a modified congener of streptokinase, is a recently approved thrombolytic agent used in the treatment of acute myocardial infarction (AMI). Clinical studies have demonstrated anistreplase to be equally efficacious as intracoronary streptokinase when given within four hours of the onset of chest pain. Thirty units, given as a single bolus intravenous injection, result in reperfusion rates of approximately 60-70 percent. The adverse-effect profile of anistreplase compares favorably with that of streptokinase, with hemorrhagic complications being the most serious. Anistreplase has two distinct advantages over both streptokinase and alteplase: (1) it can be administered as a single bolus intravenous injection and (2) it has a longer half-life which may result in decreased reocclusion rates. Anistreplase therapy is associated with reductions in both short- and long-term mortality and has been shown to preserve left ventricular function. A large, long-term, comparative clinical trial (Third International Study of Infarct Survival or ISIS-III) investigating morbidity and mortality rates with streptokinase, alteplase, and anistreplase is ongoing, as is a direct comparative study against alteplase alone (TEAM-3, Multicenter Thrombolytic Trials of Eminase in Acute Myocardial Infarction).