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Biomedical subjects

R D Gibbons

Publications and source records attributed to R D Gibbons.

At least 55 records · Page 3Linked to original sources
PubMed1988

Reducing the number of rabbits in the Draize eye irritancy test: a statistical analysis of 155 studies conducted over 6 years.

The Draize eye irritancy test in rabbits has been the focus of recent efforts to reduce the use of live animals in toxicity testing. A suitable alternative is not yet available; therefore, we studied the adequacy of reducing the number of rabbits used per test. Data generated from 6-rabbit eye irritation tests of 155 various materials were used to determine the ability of irritation scores from all possible combinations of 5-, 4-, 3-, or 2-rabbit subsets to predict the Draize score derived from six rabbits. There are 930, 2325, 3100, and 2325 possible combinations of 155 studies for the 5-, 4-, 3-, and 2-rabbit subsets, respectively. We classify materials using a four-level adjectival rating system based on (among other factors) the Draize score. Comparisons indicated that 5-, 4-, 3-, and 2-rabbit scores were in 98, 96, 94, and 91% agreement, respectively, with the classification assigned on the basis of the 6-rabbit score. The correlation coefficients for randomly selected subsets of 5-, 4-, 3-, and 2-rabbit scores versus the Draize score for six rabbits were 0.998, 0.996, 0.992, and 0.984, respectively. This study confirms the findings of an earlier report by De Sousa et al. (1984), and indicates that a high level of accuracy can be obtained with reduced numbers of rabbits per test.

Animals↗
PubMed1988

A computerized classification technique for screening for the presence of breath biomarkers in lung cancer.

A simple computer-based screening technique has been developed for classifying human expired air components into 16 chemical classes, based on empirical formulas. The sort procedure was developed to simplify the screening of the composition of expired air samples by sorting all components into chemical classes and classifying components at the greater than 75% and greater than 90% occurrence levels. Both occurrence-rate components are then evaluated as diagnostic markers in a discriminant function model for their ability to detect lung cancer. Of the 386 components detected in the gas chromatography/mass spectrometry (GC/MS) data files, 45 components were present at the greater than 75% occurrence level and 28 components at the greater than 90% occurrence level. Thus, this preliminary sort routine, performed by using a simple macro program installed into a standard personal-computer spread-sheet, greatly reduces the amount of data required for statistical treatment. Such a sort routine can also be applied as easily to other complex GC/MS data files for the purpose of data reduction.

Biomarkers, Tumor↗
PubMed1987

A double-blind, placebo-controlled trial of lithium carbonate therapy for alcoholism.

The efficacy of lithium carbonate as a treatment for alcoholism was examined in a double-blind, placebo-controlled study of 104 men and women meeting DSM-III criteria for alcohol dependence. Subjects entered the study during inpatient treatment and were subsequently followed up for 12 months. Survival analysis disclosed essentially three categories of treatment response: one for noncompliant subjects (0% to 7% abstinent), one for compliant subjects not attaining therapeutic serum lithium levels (31% to 44% abstinent), and one for compliant subjects with therapeutic serum levels (67% abstinent). Two findings led us to believe that therapeutic serum levels of lithium were associated with better outcome over and above a behavioral compliance effect. First, in a dose-response analysis, serum lithium levels and abstinence rates were not linearly associated. Second, all subjects who started lithium carbonate therapy as inpatients were significantly less likely to relapse to drinking during the first month than were placebo-compliant subjects. There was no evidence that depressed alcoholics showed a better treatment response than nondepressed alcoholics or that lithium had any significant impact on the mood or social adjustment of alcoholics. Although the sample size and the difficulties of ascertaining placebo compliance caution against drawing firm conclusions, the data add further support to the hypothesis that lithium has an effect on drinking behavior not related to the treatment of affective symptoms.

Adult↗
PubMed1987

Methodology in psychiatric research. Report on the 1986 MacArthur Foundation Network I Methodology Institute.

This report discusses many of the issues raised during a two-day institute that focused on methodological problems encountered in psychiatric research. The topics range from the problems with psychiatric diagnosis and measurement to sampling issues and biases to specific statistical concerns. Attention is given to the need for improved communication and collaboration between psychiatric researchers and biostatisticians.

Biometry↗
PubMed1987

Regression toward the mean: more on the price of beer and the salaries of priests.

Investigators must take great care in studying the temporal association between biological and clinical data. By selecting patients on the basis of deviant levels of a biological parameter, it often is impossible to separate the effect of regression toward the mean from a temporal association of clinical interest. Experimental strategies that focus exclusively on subjects with extreme values are particularly prone to misinterpreting the effects of regression toward the mean as a temporal change in the variable of interest. We cite specific examples of two previous studies of the relationship between the dexamethasone suppression test (DST) and clinical response in depression. Contrary to the conclusions of the investigators, normalization of the DST had no relation to clinical response in the first 5 weeks of treatment. The decrease of post-dexamethasone cortisol levels occurred regardless of clinical response, most likely due to the effect of regression toward the mean.

Antidepressive Agents↗
PubMed1987

Symptoms and diagnosis of depression in alcoholics.

We examined depressive symptoms, using the Beck Depression Inventory (BDI), in a group of 50 alcoholic patients, diagnosed according to DSM III criteria during active drinking, withdrawal (4 days after their last drink), and abstinence (24 days after their last drink). DSM III diagnoses of major depression were made in 16 (32%) of the patients. The diagnoses were made using the NIMH Diagnostic Interview Schedule (DIS) between the 10th and 24th day after the patients' last drink. Depressive symptoms decreased markedly as the patients progressed from active drinking to abstinence. Alcoholic patients having a diagnosis of major depression had higher BDI scores than those not having a diagnosis of major depression. Analysis of BDI items using a two-parameter logistic item response model confirmed that the BDI measured depressive symptoms in these alcoholics. We conclude that the BDI is valid for screening for depression in alcoholic patients.

Adult↗
PubMed1987

Model for quantifying the drug involvement of medical students.

We have applied a two-parameter normal item-response model to analyze data on "drugs ever used" by freshman medical students, then used the result to predict their subsequent drug use patterns over the first 18 months of medical school. Our results provide strong evidence for the existence of a single latent dimension of "drug involvement," and they demonstrate that a student's initial position on this dimension predicts subsequent drug use well. The model applies to male and female students equally well, suggesting the dimension is not sex specific. Students' drug use is cumulative in the sense that an individual tends to add new drugs to all previous drugs, rather than "graduating" from a previous to a new drug, as he/she becomes more "drug involved." Greater "drug involvement" is also associated with more frequent use of most drug categories.

Adult↗
PubMed1986

Field articulation testing: a predictor of technical skills in surgical residents.

The relationship between a specialized form of spatial ability known as "field articulation" and technical surgical skill was investigated. This form of spatial ability is operationally defined as the ability to differentiate a simple figure from a complex configurational surround. The relationship between Hidden Figures test scores and average ratings of technical surgical skill made by 17 academic surgical faculty members in two independent institutions was highly significant. Therefore, the use of this test to screen candidates for surgical residency, as well as to assess technical skill potential in junior residents, would appear to be based on valid statistical results.

Clinical Competence↗
PubMed1986

Path analysis of psychopharmacological data: catecholamine breakdown in man.

This article applies path analysis to the problem of characterizing metabolic alterations in catecholamine systems when only static or single measures of precursor and products are available. In this article, simulated data from kinetic models of norepinephrine metabolism were examined using path analysis. The method of path analysis, which is based on correlations between compartments and not actual flow, correctly identified operative and nonoperative metabolic pathways in simulated models. In addition, actual data from normal subjects as to the 24-hour urinary values for norepinephrine, normetanephrine, vanillylmandelic acid, and 3-methoxy-4-hydroxyphenylglycol were analyzed using path analysis. It was found that metabolic routes that are known to be incomplete did not fit these data, whereas the known metabolic pathways for norepinephrine were correctly identified using path analysis. These results suggest that path analysis may provide a useful tool in identifying normal and abnormal catecholamine metabolic pathways in experimental situations where only single values of precursor and products are available.

Humans↗
PubMed1986

Quantification of scalp hair--a computer-aided methodology.

A method for obtaining a quantitative assessment of hair density is described. First, a photographic image of the scalp is digitized onto a high-resolution computer graphics screen. Second, the frequency of each of 256 gray levels (one for each of 500 vertical X 500 horizontal = 250,000 locations on the screen) is obtained and the frequency histogram of gray levels is displayed. Third, a statistical procedure, gaussian mixture analysis, is used to resolve the frequency distribution into two normally distributed component distributions. The first component distribution describes the range of gray levels that are typically associated with hair. The second component distribution describes shades of gray that are typically associated with scalp. The statistical model provides a precise measure of the proportion of the head that exhibits gray levels in each of the two component distributions (hair or scalp). The proportion of the first component distribution is a scale-independent measure of hair density. The difference in this quantity before and after treatment provides an accurate quantitative determination of the change in hair density and hence of the efficacy of treatment.

Alopecia Areata↗
PubMed1986

Consistent evidence for a biological subtype of depression characterized by low CSF monoamine levels.

Analysis of previously published CSF monoamine data has revealed statistical evidence for a biological subtype of depression, characterized by abnormally low CSF-5HIAA and CSF HVA. Using maximum likelihood gaussian mixture analysis we were able to resolve the empirical frequency distributions of both CSF HVA and CSF 5-HIAA into two component normal mixtures. Simultaneous analysis of both CSF 5-HIAA and CSF HVA revealed a two component bivariate normal mixture distribution in which 35% of the depressed patient sample were classified in the low subgroup. No evidence for mixture distributions was found in controls. Analysis of CSF MHPG revealed a single component normal distribution with virtually identical mean and variance in both patients and controls. These results are shown to be virtually identical to parallel analyses conducted on CSF monoamine data collected as part of the NIMH collaborative study on the psychobiology of depression study.

Depressive Disorder↗
PubMed1986

Computer-aided quantification of scalp hair.

In this article we present a statistical model that, when applied in conjunction with existing image analysis technology, allows for a precise quantification of two-component visual fields. Application of this methodology to the problem of quantification of hair density in patients with hair loss disorders yields excellent results. Under photographically controlled conditions this method should yield completely consistent and valid results. The complete absence of subjective bias in the application of this method makes it an extremely attractive alternative to existing procedures. Limitations to the use of this methodology are detailed, and an alternative approach is suggested.

Algorithms↗
PubMed1985

Pharmacologic evidence for specificity of pursuit dysfunction to schizophrenia. Lithium carbonate associated with abnormal pursuit.

Conflicting findings regarding the prevalence of abnormal smooth-pursuit eye movements in patients with major affective disorders call into question the specificity of impaired smooth-pursuit eye movements to schizophrenia. We report that pursuit is impaired in 88% of lithium carbonate-treated affective disorder patients whose pursuit was normal prior to receiving this drug. Over half of lithium carbonate-treated affective disorder patients in remission also showed impairment of smooth-pursuit eye movements. In conjunction with recent prevalence data on family members of psychiatric patients, the findings support the specificity of abnormal pursuit as a biological trait associated with schizophrenia, but not with the major affective disorders. The mechanisms by which lithium carbonate impairs pursuit are discussed.

Adult↗
PubMed1985

Application of modern psychometric theory in psychiatric research.

This paper describes the general statistical theory of item-response modeling as developed in the fields of statistics and education. Generalization of these procedures for application in the analysis of psychiatric rating scales is the focus of this paper. Questions of unidimensionality vs multidimensionality and choice of distributional transform (logistic vs normal) are both discussed and statistically examined using data on the Beck Depression Inventory (BDI). Application of these models to the BDI revealed two subscales that maximally differentiate high and low levels of depression in psychiatric and medically ill patients respectively. There was considerable but not complete overlap between the two subscales. These statistical models are found to have desirable properties when used to analyze psychiatric rating scales and provide a refinement over existing techniques of classical test theory and factor analysis.

Adult↗
PubMed1985

An empirical test of a Kraepelinian vs. a Bleulerian view of negative symptoms.

Confirmatory factor analysis was used to test a Kraepelinian vs. a Bleulerian interpretation of negative symptoms. The former focuses on absolute loss of functioning, while the latter emphasizes the qualitative loss of organization. Contrary to expectation, neither theory was confirmed, but rather three independent factors emerged: apathy, psychomotor retardation, and loss of goal. The implications of these findings for subtyping schemes and the conceptualization of negative symptoms are discussed.

Adolescent↗
PubMed1985

Unbiased criteria for severity of depression in alcoholic inpatients.

The internal consistency of the Beck Depression Inventory (BDI) is assessed in 106 inpatient alcoholics by using a latent trait model. The analysis confirms that the BDI measures a single underlying dimension of depressive severity among alcoholics. Seven symptoms discriminate well for severity of depression. These seven--work inhibition, guilt, self-disgust, irritability, indecision, dissatisfaction, and loss of social interest--may represent criteria for depressive severity that are not confounded by chronic drinking, physical withdrawal, unique personality organization, or life circumstances of alcoholics. Three of the symptoms--dissatisfaction, loss of social interest, indecision--may represent core criteria for depressive severity by virtue of their previously demonstrated ability to discriminate well for severity of depression among both psychiatric and medical inpatients.

Adult↗