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Biomedical subjects

B W Steele

Publications and source records attributed to B W Steele.

At least 19 recordsLinked to original sources

Intrauterine growth of full-term infants: impact of prenatal cocaine exposure.

OBJECTIVE: The objectives of this study were to estimate the effect of prenatal cocaine exposure on fetal growth and gestational age after controlling for exposure to alcohol, tobacco, and marijuana and other covariates; to evaluate whether prenatal cocaine exposure has a disproportionate adverse effect on head circumference compared with overall somatic growth; and to assess whether the effect of prenatal cocaine exposure on fetal growth is mediated by cocaine's suspected effect on gestational age. METHODS: The study population includes 476 neonates participating in the Miami Prenatal Cocaine Study, a longitudinal follow-up of in utero cocaine exposure. The sample, restricted to full-term neonates born to African-American inner-city mothers, included 253 infants exposed prenatally to cocaine (with or without alcohol, tobacco, or marijuana exposure) and 223 non-cocaine-exposed infants, of whom 147 were drug-free and 76 were exposed to varying combinations of alcohol, tobacco, or marijuana. RESULTS: Evidence based on structural equations and multiple regression models supports a hypothesis of cocaine-associated fetal growth deficits (0.63 standard deviation) and an independent mild effect on gestational age (0.33 standard deviation). There was no evidence of a disproportionate adverse effect on birth head circumference once the impact on overall growth was estimated. There was evidence that some but not all of the cocaine effect on fetal growth was direct and some was indirect, acting via an intermediate influence of cocaine on gestational age. CONCLUSIONS: Cocaine-associated growth deficits, symmetrical and partially mediated by gestational age, were observed in this sample of inner-city African-American full-term infants prospectively enrolled at birth. Long-term implications will be the subject of future reports from this longitudinal investigation.

Adult↗

Sources of variability: a College of American Pathologists Therapeutic Drug Monitoring study.

OBJECTIVE: To determine the magnitudes and sources of analytic variation in testing for therapeutic drugs. Specifically, among laboratories using the same analytic method, to compare the within-laboratory variation (including both short- and long-term variation) with the between-laboratory variation. DESIGN: Four identical challenges were prepared from a lyophilized pool of spiked sera and were sent in pairs 4 months apart to laboratories participating in a nationwide proficiency-testing program. For each of 25 drugs, the variability in reported results from laboratories using the same method was investigated using nested analysis of variance. SETTING: The first 2 mailings of the College of American Pathologists Therapeutic Drug Monitoring Survey, 1996, sets Z and ZM. MAIN OUTCOME MEASURES: For each drug, total variance was partitioned into within- and between-laboratory components for common methods. The within-laboratory component was further partitioned into short- and long-term components. PARTICIPANTS: The approximately 5000 laboratories enrolled in the survey. RESULTS: For the 25 drugs, the average percentages of the total variance due to short-term, within-laboratory variance; long-term, within-laboratory variance; between-laboratory variance; and total laboratory variance were 25.0% (range, 8.8--50.6%), 57.8% (35.3--73.7%), 17.3% (5.0--35.4%), and 82.7% (64.6--95.0%), respectively. CONCLUSION: For all drugs tested, the within-laboratory component of variance was greater than the between-laboratory component of variance. Within laboratories, the magnitude of the long-term component was generally greater than the magnitude of the short-term component. This information will be helpful in determining the clinical utility of various drug assays and in evaluating the appropriateness of regulations involving therapeutic drug testing.

Analysis of Variance↗

An evaluation of analytic goals for assays of drugs: a College of American Pathologists Therapeutic Drug Monitoring Survey Study.

OBJECTIVE: To determine if the levels of imprecision of the commonly used analytic methods for drug measurements are suitable for long-term therapeutic drug monitoring. DESIGN: In 1996, 4 identical lyophilized samples (2 in the first mailing and 2 in the second mailing 4 months later) were sent to laboratories participating in a nationwide proficiency testing program. Similarly, in 1999, replicates from a liquid pool of spiked sera were mailed 3 times, 4 months apart, to participating laboratories. For each of 11 drugs regulated under the Clinical Laboratory Improvement Amendments of 1988 and 1 metabolite, the total variance for each method was partitioned into within- and between-laboratory components. The total within-laboratory and the total survey coefficients of variation (CVs) for each method were then compared with the "acceptable" precision criteria of Glick, Burnett, and Fraser for each drug. SETTING: The first 2 mailings of the College of American Pathologists Therapeutic Drug Monitoring surveys for 1996, sets Z and ZM, and the 3 mailings of 1999, sets ZM, Z, and Z2. MAIN OUTCOME MEASURES: For each drug studied, the CV of each method was compared with the various imprecision criteria, and if greater than any of the criteria, the method was then tabulated as not meeting that specific criterion.Participants.-The approximately 5000 participants of the survey. RESULTS: The number of methods deemed as not having acceptable total long-term within-laboratory precision by the various criteria ranged from 35% to 88% in 1996 and from 22% to 77% in 1999. CONCLUSION: The number of failures possibly indicates that many of the reagent assays being utilized are not precise enough for long-term therapeutic drug monitoring of chronically administered drugs or that the published criteria used to evaluate the data in this study are too stringent.

Data Collection↗

Benzodiazepines in Miami-Dade County, Florida driving under the influence (DUI) cases (1995-1998) with emphasis on Rohypnol: GC-MS confirmation, patterns of use, psychomotor impairment, and results of Florida legislation.

Benzodiazepines are central nervous system depressant drugs often detected in biological samples from driving under the influence (DUI) offenders. They are associated with marked psychomotor impairment and represent up to 20% of all Miami-Dade County, Florida DUI urine samples analyzed in our laboratory annually. Flunitrazepam emerged in the mid-1990s as an illegal drug in the U.S. that was predominantly abused recreationally and associated with sexual assaults. Immunoassays for benzodiazepines do not discriminate between different benzodiazepines, and certain metabolites, such as 7-aminoflunitrazepam, react poorly with immunoassay reagents. A simple and sensitive method for the detection and quantitation of major benzodiazepines and metabolites by gas chromatography with mass selective detection is presented. This method was used to confirm benzodiazepines in general and flunitrazepam in particular. Data collected over a three-and-a-half-year period are summarized. Whereas flunitrazepam was present in up to 10% of DUI cases in 1995 and 1996 and had fast become the most frequently encountered benzodiazepine in Miami-Dade County DUI-related urine samples, a dramatic drop in case numbers followed the legal reclassification of the drug as a Schedule I substance in Florida in February 1997. Flunitrazepam was often used alone or in combination with cannabis and cocaine. A recent rise in clonazepam cases coincides with the decrease in flunitrazepam confirmation and may indicate a new trend in the abuse of benzodiazepines in South Florida.

Benzodiazepines↗

Peripheral human T lymphocyte maintenance of immune functional capacity and phenotypic characteristics following in vivo cocaine exposure.

The effects of cocaine exposure upon the host's immune response is equivocal since a variety of studies have generated conflicting conclusions, often as the result of differences between in vitro and/or animal models and the actual conditions experienced in humans who are acutely abusing this drug. To further address this issue, we have studied a group of patients who were positive for cocaine or cocaine metabolites and we evaluated a variety of functional parameters of T-lymphocytes and other peripheral lymphoid cell populations, as well as immunophenotypic characteristics of these cells. When compared to normal controls and patients who were negative for cocaine, we found that the cocaine-positive patients had T-cell functional assays which were essentially normal, with the exception of a slight depression in PHA stimulation. Likewise, the immunophenotype of the peripheral blood lymphocytic populations showed normal percentages and numbers of their T cell subsets (CD4, CD8), NK cells, and B cells. Multicolor flow cytometry analysis revealed no difference in T cell subpopulations positive for the "memory" marker, CD62L. No correlation could be established between levels of cocaine or cocaine metabolites and any phenotypic, demographic, or functional parameter. In summary, these results demonstrate that individuals acutely exposed to cocaine do not show markedly altered T cell function or fluctuations in phenotypically identified cell populations. These studies imply that acute cocaine exposure does not predispose individuals to grossly apparent immunosuppression. However, the possibility that subtle, transient, or more specific changes in the immune system may be incurred by use of cocaine, particularly with chronic exposure, remains to be determined.

Adult↗

The effects of modifying proficiency testing materials on thyroid function test results. A College of American Pathologists Ligand Assay Survey Study.

OBJECTIVE: To gain insight on the matrix effects, and possible clinical implications, resulting from diluting and concentrating proficiency testing survey material used for the measurement of thyroid function tests. DESIGN: To the standard set of five proficiency survey samples, three supplementary "Wildcard" samples were added. These additional samples were manufactured by overfilling and underfilling vials prior to lyophilization so as to vary the thyroxine-binding protein concentrations. Survey participants measured thyroxine, free thyroxine, and the triiodothyronine uptake and related tests on the Wildcard samples. In addition, free thyroxine indices were calculated. SETTING: The first mailing of the 1995 College of American Pathologists (CAP) Ligand Assay--Series 1 Survey. MAIN OUTCOME MEASURES: Results obtained from the regular set of survey samples and the Wildcard set were compared to values expected by the laws of conservation of matter and mass action. PARTICIPANTS: The approximately 2000 participants of the first mailing of the 1995 CAP Ligand Assay--Series 1 Survey. RESULTS: Numerous assays systems did not give the predicted results, including all of the single-step radioimmunoassays for free thyroxine and over three quarters of free thyroxine index determinations. CONCLUSIONS: Varying the dilution of proficiency survey material produced results that were not predicted by the laws of conservation of matter and of mass action. Although these observations may have been the result of matrix effects, one cannot rule out the possibility that certain thyroid assays may not work in clinical situations having abnormal thyroxine-binding protein concentrations.

Data Collection↗

Rapid cocaine screening of urine in a newborn nursery.

A rapid cocaine screening test, the Abuscreen OnTrak assay, was compared with the EMIT (enzyme-multiplied immunoassay technique) screening test to determine relative accuracy in 450 newborn infants sequentially tested for urinary cocaine during a 6-week period at a large urban hospital. The Abuscreen Ontrak screen had a sensitivity of 96% and a specificity of 100%.

Cocaine↗

m-Hydroxybenzoylecgonine: an important contributor to the immunoreactivity in assays for benzoylecgonine in meconium.

Meconium has been reported to be a more suitable specimen than maternal or neonatal urine for detecting fetal exposure to cocaine. In a study comparing various immunoassays with gas chromatography/mass spectrometry (GC/MS), several unexplained discrepancies among the assays were noted. Using methanol extracts of meconium samples, an immunoreactive spot that was more polar than benzoylecgonine was detected by thin-layer chromatography (TLC). An extract of this spot analyzed by GC/MS yielded a fragmentation pattern indicative of an aryl hydroxylated benzoylecgonine. Standards of m-hydroxybenzoylecgonine, o-hydroxybenzoylecgonine, and p-hydroxybenzoylecgonine were synthesized; it was determined that m-hydroxybenzoylecgonine had the same retention time and ion ratios as the TLC immunoreactive spot. Furthermore, m-hydroxybenzoylecgonine proved to be immunoreactive. Ten meconium samples immunoreactive for benzoylecgonine were analyzed by GC/MS. Results before and after hydrolysis with beta-glucuronidase (type IX) showed free m-hydroxybenzoylecgonine comprising 59 to 94% of the total m-hydroxybenzoylecgonine and showed total m-hydroxybenzoylecgonine values ranging from 0.2 to 6.3 times as high as benzoylecgonine. Therefore, m-hydroxybenzoylecgonine appears to be a quantitatively important cocaine metabolite in meconium, which is responsible for a significant portion of the discrepancy between benzoylecgonine concentrations in meconium extracts as measured by immunoassay and GC/MS.

Artifacts↗

Failure of Centers for Disease Control criteria to identify hepatitis B infection in a large municipal obstetrical population.

The Centers for Disease Control (CDC) has recommended screening pregnant women from high-risk populations for hepatitis B surface antigen (HBsAg). To assess the adequacy of the risk criteria, all women presenting for delivery to a large municipal hospital were screened. Sera from 5356 women were tested, and questionnaires designed to identify women at high risk were completed by 78% of these patients. Sixty-four women were found to be HBsAg seropositive (1.2%). If the CDC criteria had been applied for screening, 30 of the seropositive mothers (47%) would not have been identified. Women from some Latin American and Caribbean countries not recommended for screening were found to have a relatively high prevalence of hepatitis B infection. Reluctance to give a history of venereal disease or illicit drug use may be another factor in the failure of the CDC screening strategy. To achieve effective immunoprophylaxis of newborns, all pregnant women should be screened for HBsAg carriage.

Carrier State↗

Automated fibronectin assay using light-scattering optics on a centrifugal analyzer.

We describe an automated, kinetic nephelometric method for fibronectin on the Multistat III F/LS Centrifugal Analyzer (Instrumentation Laboratory Inc., Lexington, MA 02173). Antiserum is diluted with polyethylene glycol. Calibrators and samples are prediluted with potassium phosphate buffer (10 mmol/L, pH 7.0) containing 8.5 g of NaCl per litre. Intensity (I) is read at 5 and 180 s and the resulting delta I plotted against concentration. A non-linear least squares curve fitting and interpolation of results is carried out automatically. Three controls, with values of between 190-370 gave coefficients of variation between 4 and 7 percent, and the sensitivity of the method is to 25 mg/L.

Adult↗

Plasma fibronectin in medical ICU patients.

Plasma fibronectin levels in 66 medical ICU (MICU) patients were measured daily. Mean values of initial levels were significantly higher in survivors (266 +/- 14 mg/L) than nonsurvivors (179 +/- 13 mg/L; p less than .0003). There was extensive overlap between survivors and nonsurvivors. The clinical categories of sepsis, disseminated intravascular coagulation (DIC), adult respiratory distress syndrome (ARDS), and hepatic failure with GI bleeding were associated with low fibronectin levels. Within all diagnostic categories the mean initial fibronectin level of the survivors was higher than that of nonsurvivors. This difference was significant only in the septic group (p less than .02). Patients with minimum fibronectin levels less than 195 mg/L had a 65% mortality rate; patients with minimum levels greater than or equal to 195 mg/L had a 17% mortality rate. Fibronectin, via its role in reticuloendothelial system (RES) function, may have a pathophysiologic role in a variety of medical illnesses.

Adolescent↗

Erythrocyte Na+, K+-ATPase and serum digoxin concentrations.

Digoxin therapy has been made more rational by the measurement of serum digoxin concentrations. However, difficulties remain because of the overlap between "therapeutic" and "toxic" serum concentrations and the lack of an obvious therapeutic endpoint in many patients. An assay which measures the degree of interaction between digoxin and its putative receptor, the membrane Na+, K+-ATPase, might be capable of resolving some of these difficulties. Therefore, as a first approach in this direction we evaluated the relationship between serum digoxin concentration and the degree of inhibition of RBC ghost Na+, K+-ATPase activity in patients receiving digoxin therapy. Utilizing an improved micro-assay technique, Na+, K+-ATPase activity was determined in aliquots of RBC ghosts before and after removal of bound digoxin. In 27 patients a significant relationship was present between serum digoxin concentration and the degree of RBC ghost Na+, K+-ATPase inhibition. However, at any serum digoxin concentration, there was a variation in the magnitude of enzyme inhibition from patient to patient. This study confirms the feasibility of determining the degree of in vivo RBC Na+, K+-ATPase inhibition in man and demonstrates, for the first time, a highly significant but somewhat variable relationship between serum digoxin concentrations and the magnitude of RBC digoxin receptor inactivation. This quantitative, functional, individualized assay of digoxin effects may prove to be of clinical value in the future.

Digoxin↗

Serum creatine kinase MB isoenzyme activity in long-term hemodialysis patients.

Serum creatine kinase MB isoenzyme (CK-MB) activity was determined in 46 male long-term hemodialysis patients without evidence of myocardial infarction. Thirteen (28.3%) showed mild elevations. The abnormality persisted in seven of eight patients on repeated measurement at three- to eight-month intervals. There was a significant correlation between serum CK-MB and CK-MN activity, and the activity of both enzymes rose after intramuscular injection. The reason for the abnormality is not known. It is possible that skeletal muscle is the source of elevated enzyme activity. Caution should be exercised in the interpretation of serum CK-MB activity in the diagnosis of acute myocardial infarction in this patient population.

Adult↗

Serum lipoprotein levels during chlorthalidone therapy. A Veterans Administration-National Heart, Lung, and Blood Institute cooperative study on antihypertensive therapy: mild hypertension.

In a joint Veterans Administration-National Heart, Lung, and Blood Institute study of mild hypertension, 1,012 men and women, 21 to 50 years of age and with diastolic pressure from 85 to 105 mm Hg, were randomized into two double-blind treatment groups. Subjects in the active group received chlorthalidone or chlorthalidone plus reserpine, while the other subjects received matching placebo tablets. After one year of treatment, the chlorthalidone group had increases of 10.0 +/- 1.8 (SE) mg/dL in total cholesterol level, 9.8 +/- 5.2 mg/dL in triglyceride level, and 12.6 +/- 3.4 mg/dL in low-density lipoprotein-cholesterol level above the changes in the placebo group. There was no difference in high-density lipoprotein changes between the two groups (0.1 +/- 0.8 mg/dL). The possible net effect on risk of increasing lipid values while lowering pressure in the long-term treatment of mild hypertension with thiazides or related diuretics must be further evaluated.

Adult↗

An enzymatic approach to lipoprotein quantification.

Lipoprotein cholesterol levels were determined without ultracentrifugation by using modified enzymatic methods for cholesterol, high-density-lipoprotein (HDL) cholesterol, and triglyceride and the formula, low-density-lipoprotein (LDL) cholesterol = total cholesterol-HDL cholesterol-triglycerides/5. The methods for cholesterol and triglyceride determinations were standardized for accuracy and precision by the Center for Disease Control's Lipid Standardization Laboratory, which monitored this laboratory for 16 months. The lipoprotein cholesterol values obtained correlated well with lipoprotein cholesterol values determined at the Minnesota Lipid Research Clinic Laboratory using ultracentrifugation. LDL cholesterol determined at the Minneapolis Veterans Administration Hospital Laboratories (Y axis) produced a curve with an intercept of 9.38 mg/dl, a slope of .977, standard error of the estimate (Sy.x) of 8.8 mg/dl, and a correlation coefficient (r) of .983 (n = 32). HDL cholesterol was Y = 0.998 X + .89 mg/dl, Sy.x = 1.6 mg/dl (r = .984, n = 53), and very-low-density-lipoprotein (VLDL) cholesterol was Y = 1.010 X -1.32 mg/dl, Sy.x = 1.3 mg/dl (r = .996, n = 54).

Cholesterol↗