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Biomedical subjects

M Gaffney

Publications and source records attributed to M Gaffney.

11 recordsLinked to original sources
PubMed1992

Striatal subregions are differentially vulnerable to the neurotoxic effects of methamphetamine.

Methamphetamine (m-AMPH) or saline was repeatedly administered to rats. One week later, the caudate-putamen of the m-AMPH-treated rats revealed a decrease in both [3H]mazindol-labeled dopamine uptake sites and tissue dopamine content. Moreover, the resulting pattern of decline in these measures was regionally heterogeneous. The ventral caudate-putamen displayed the greatest decrease in both [3H]mazindol binding and dopamine content while the neighboring nucleus accumbens and the dorsal caudate-putamen remained relatively intact. These results indicate a regional difference in the susceptibility of striatal dopaminergic terminals to the neurotoxic effects of methamphetamine.

Animals↗
PubMed1992

Variance components in comparative bioavailability studies.

Variance components in comparative bioavailability studies are examined. Assay measurement error is shown to be negligible relative to other variance components, and hence, repeat assay does not appreciably increase study precision and is unnecessary. More important is the finding that repeat administration of each formulation to each subject may substantially decrease the variance of the formulation difference and may allow the use of fewer subjects in a study. The benefit of repeat administration depends on the relative sizes of the within-subject variance component and the subject-formulation interaction component. In addition, repeat administration allows separate estimation of the within-subject component and the subject-formulation component. The former component is important for assessing bioequivalence, and the latter component, for assessing interchangeability of formulations.

Analysis of Variance↗
PubMed1992

Response of negative symptoms of schizophrenia to neuroleptic treatment.

BACKGROUND: In view of the inconclusive reports in the literature about the response to neuroleptics of chronic schizophrenics with negative symptoms, the authors further evaluated this issue. METHOD: A sample of 30 ambulatory chronic schizophrenics meeting DSM-III-R criteria who had to a marked degree at least two negative symptoms of the five on the Scale for the Assessment of Negative Symptoms (SANS) received various therapeutic dosages of thiothixene for 3 months. The average dose was 26.75 mg/day. Subjects were periodically evaluated with the Brief Psychiatric Rating Scale, Negative Symptoms Rating Scale (a modified version of the SANS), and the Randt Memory Test. The time effect on treatment was calculated by repeated measures of analysis of variance. The relationship between the positive and negative symptoms was tested by an analysis of covariance. RESULTS: Both negative and positive symptoms improved with treatment. The negative symptoms tended to respond to treatment predominantly independently of the positive ones. At the end of the study, 63% (N = 19) of patients had improved moderately, 16% (N = 5) had improved slightly, and 20% (N = 6) had not improved. CONCLUSION: The data require further support from a long-term follow-up study that may show the extent to which these gains are maintained over time.

Adult↗
PubMed1990

Computed tomography scans and negative symptoms in schizophrenia: chronic schizophrenics with negative symptoms and nonenlarged lateral ventricles.

Computed tomography scans of 31 chronic schizophrenics with negative symptoms and 31 age-matched normal volunteers were assessed for ventricular size, cortical atrophies, third ventricle diameter, and cerebellar atrophies. No significant differences were found in the size of the lateral ventricles or third ventricles between the chronic schizophrenics and the controls. The frontal horns in patients did show a tendency toward increased size compared with controls. Sulci width showed significant differences between patients and controls. The clinical variables, except for the memory test, did not correlate with any brain morphology. A meta-analysis was performed on 17 studies that used the planimetric method in order to evaluate the relationships between the size of the lateral ventricles in patients and their respective controls. We found significant differences between the group of studies using normal controls and the group using medical controls.

Adult↗
PubMed1990

Results of a double-blind placebo controlled trial of a new serotonin uptake inhibitor, sertraline, in the treatment of obsessive-compulsive disorder.

Eighty-seven patients with a DSM-III diagnosis of obsessive-compulsive disorder (OCD) without depression were entered into a double-blind, placebo-controlled study of the efficacy of sertraline, a new serotonin uptake inhibitor. After a 1-week washout period, patients were randomly assigned to receive either placebo or sertraline. After a 2-week titration period in which the once-daily sertraline dose was increased from 50 mg/day to a maximum of 200 mg/day, dosage was maintained until the end of the eighth week, then patients were titrated off medication over the next 2 weeks. Efficacy was measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), NIMH General Obsessive-Compulsive Scale, Maudsley Obsessive Compulsive (MOC) Inventory, and Clinical Global Impressions (CGI) Severity and Improvement scales. Results on the MOC Inventory showed trends in favor of active drug that were not statistically significant compared with placebo. Results of the Y-BOCS total score, the NIMH score, and the global severity and improvement scores demonstrated a statistically significant superiority of sertraline compared with placebo.

1-Naphthylamine↗
PubMed1988

Examination of the role of cigarette smoke in lung carcinogenesis using multistage models.

The widely used multistage model of Armitage and Doll is fit to the British physician lung cancer data of Doll and Hill under the assumption that cigarette smoke induces the initial and penultimate changes. It is shown that the best fit of this model in continuing smokers gives predictions not in accordance with incidence in ex-smokers and dose-response. A better global fit can be obtained by increasing the number of stages, but this de-emphasizes initiation and is inconsistent with the rise of incidence in nonsmokers. Thus, one should look to other models. A two-stage model with clonal growth in which smoking initiates normal target cells and promotes the clonal growth of just the smoke-initiated cells is proposed. This model is shown to agree with the Doll and Hill data and thus it has empirical plausibility that should encourage biological studies of clonal growth in carcinogenesis.

Adult↗
PubMed1987

Clinical pharmacokinetics of nifedipine gastrointestinal therapeutic system. A controlled-release formulation of nifedipine.

The pharmacokinetics of nifedipine following intravenous administration can be represented by an open two-compartment model with a terminal elimination half-life of about two hours. Nifedipine is extensively biotransformed to inactive metabolites, and the total body clearance (450 to 700 ml/minute) is primarily due to hepatic metabolism. Nifedipine undergoes significant tissue distribution in that the steady-state volume of distribution (0.62 to 0.77 liter/kg) is more than twice the volume of distribution of the central compartment (0.25 to 0.29 liter/kg). Although nifedipine is almost completely absorbed from the gastrointestinal tract, oral bioavailability ranges from 45 to 68 percent because of first-pass metabolism. Nifedipine given three times daily shows no accumulation in plasma and no changes in pharmacokinetic behavior during a one-week study period. Pharmacokinetic studies on the gastrointestinal therapeutic system (GITS) show that the bioavailability of the GITS dosage form (relative to the capsule) is about 65 percent after a single dose, but increases to about 86 percent at steady-state because of residual absorption more than 24 hours after dosing. Linear pharmacokinetics are seen following administration of single oral doses of nifedipine GITS as indicated by dose-proportional increases in the area under the plasma drug concentration-time curve over the range of 30 to 180 mg. Administration of the GITS dosage form in the presence of food slightly increases the rate of drug absorption, but does not influence the extent of drug bioavailability. Dose-dumping has not been observed, even with dosing after a meal containing a high level of fat. The GITS tablets provide zero-order delivery of nifedipine, and drug absorption persists beyond the dosing interval of 24 hours. Thus, the GITS dosage form will permit once-a-day dosing and maintain the desired, constant plasma drug concentration with minimal fluctuation.

Biological Availability↗
PubMed1987

The diversity of the secondary Salmonella typhimurium-specific B cell repertoire.

This report describes the first analysis of the expressed B cell repertoire specific for a bacterium. In this study, responses to an acetone-killed and dried preparation of Salmonella typhimurium strain TML (AKD-TML) are described. The results show that AKD-TML can stimulate splenic B cells from primed CBA/Ca mice over a wide dose range. The average frequency of secondary TML-specific B cells is 16.4 per 10(5) splenic B cells. This frequency is similar to that observed for another complex, natural antigen, the hemagglutinin of influenza virus. The majority of all secondary TML-specific B cells (greater than 70%) secrete immunoglobulin M, but most of these clones also secrete other isotypes of which immunoglobulins G2 and A are the most prevalent. Analysis of the specificity of secondary TML-specific B cells showed that the vast majority of these B cells were specific for the lipopolysaccharide (LPS) molecule. Moreover, fine specificity analysis demonstrated that approximately two-thirds of these anti-LPS-specific B cell clones are directed against the core polysaccharides or lipid A regions of the LPS molecule, while only about one-third are directed toward the O antigen region. Since anti-S. typhimurium serum antibodies are directed primarily against the O antigens, these studies suggest that the serum levels of antibodies to a given epitope on a bacterial antigen may not be a true reflection of the expressed B cell repertoire when analyzed at the single B cell level. These studies also suggest that the role of antibodies to lipid A molecules in the development of protective immunity to S. typhimurium be reevaluated.

Animals↗
PubMed1986

Public health implications of carcinogenic exposure under the multistage model.

Mathematical implications of the multistage model of carcinogenesis are developed in order to answer important quantitative questions about environmentally induced cancer from the perspective of public health and intervention. Excess cancer incidence due to constant and interval exposure is examined theoretically for a stationary population under the multistage model of Armitage and Doll (Br J Cancer 1954;8:1-12). The time patterns for excess population incidence are simulated for the two types of exposure and the particular cellular change affected by the carcinogen. It is shown that the cumulative excess population incidence does not depend on which cellular change is induced by exposure and increases linearly with exposure duration. However, agents which affect earlier stages induce cancers which appear later in the population and, as a result, their detection by epidemiologic methods may be expected to occur later. Thus, such agents are more dangerous since control measures may be delayed, allowing greater cumulative incidence.

Carcinogens↗