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C Cox

Publications and source records attributed to C Cox.

At least 415 records · Page 23Linked to original sources
PubMed1987

Analysis of longitudinal "time series" data in toxicology.

Studies focusing on chronic toxicity or on the time course of toxicant effect often involve repeated measurements or longitudinal observations of endpoints of interest. Experimental design considerations frequently necessitate between-group comparisons of the resulting trends. Typically, procedures such as the repeated-measures analysis of variance have been used for statistical analysis, even though the required assumptions may not be satisfied in some circumstances. This paper describes an alternative analytical approach which summarizes curvilinear trends by fitting cubic orthogonal polynomials to individual profiles of effect. The resulting regression coefficients serve as quantitative descriptors which can be subjected to group significance testing. Randomization tests based on medians are proposed to provide a comparison of treatment and control groups. Examples from the behavioral toxicology literature are considered, and the results are compared to more traditional approaches, such as repeated-measures analysis of variance.

Analysis of Variance↗
PubMed1987

Blinding, unblinding, and the placebo effect: an analysis of patients' guesses of treatment assignment in a double-blind clinical trial.

We administered a questionnaire to assess maintenance of patients' blindness at the end of a double-blind clinical trial of Osmotic Release Oral System phenylpropanolamine (PPA) vs. placebo in mild obesity. Seventy-four percent of placebo participants and 43% of PPA participants guessed their treatment correctly. Appetite control was the most frequently reported basis for guessing PPA, even by placebo participants. Lack of adverse drug reactions was the most frequently reported basis for guessing placebo, even by PPA participants. Participants receiving either PPA or placebo and guessing PPA lost more weight, had less diet difficulty, and had more adverse drug reactions than had participants receiving either PPA or placebo and guessing placebo. Although blindness was probably maintained in the PPA group, the placebo group seems to have been, at least at the study's end, unblinded. These results suggest that in double-blind studies, differences in outcome or incidence of adverse drug reactions may act as unblinding factors.

Body Weight↗
PubMed1987

The predictive value of catecholamines in assessing outcome in traumatic brain injury.

Because of the central role of the sympathetic nervous system in mediating the stress response, plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) levels were measured in 61 traumatically brain-injured patients to determine whether catecholamine (CA) levels obtained within 48 hours after injury provide reliable prognostic markers of outcome. Patient outcome was determined at 1 week using the Glasgow Coma Scale (GCS) and at the time of discharge using the Glasgow Outcome Scale (GOS). Levels of NE, E, and DA correlated highly with the admission GCS score (NE: r = 0.58, p less than 0.0001; E: r = 0.46, p less than 0.0025; DA: r = 0.27, p less than 0.04). Moreover, in the 21 patients with GCS scores of 3 or 4 on admission, NE levels predicted outcome at 1 week. All six patients with NE levels less than 900 pg/ml (normal level less than 447 pg/ml) improved to GCS scores of greater than 11, while 12 of 15 with NE values greater than 900 pg/ml remained with GCS scores of 3 to 6 or died. Levels of E and DA were not as useful. Catecholamine levels also increased significantly as the GOS score worsened. Levels of NE and E were significantly higher in patients who died or remained persistently vegetative than in those with better outcomes. In the 54 patients who survived beyond 1 week, significant correlations were present between the length of hospitalization and NE (r = 0.71, p less than 0.0001) and E (r = 0.61, p less than 0.0001) levels. Concentrations of NE (r = 0.61, p less than 0.0004) and E (r = 0.48, p less than 0.01) were also highly correlated with the duration of ventilatory assistance. Analysis of the interactions of CA levels and GCS scores, duration of ventilatory assistance, and length of hospitalization revealed that the CA's either enhanced the reliability of the GCS score or were independent predictors of outcome. Thus, these findings indicate that alterations in circulating CA levels reflect the severity of the neurological insult and provide support for the use of CA measurements as a physiological marker of patient outcome in both the acute and chronic phases of traumatic brain injury.

Adolescent↗
PubMed1987

Attitudes and hiring patterns of residency graduates by Alberta pharmacy directors.

Pharmacy directors of 126 Alberta Hospitals were sent a survey requesting information on their attitudes and hiring practices of residency graduates. Sixty completed surveys were returned for a response rate of 48 percent. Seventy percent of the directors indicated that completion of a residency program was a favourable prerequisite prior to hiring. However, pharmacists with previous hospital experience were ranked with a higher preference for hiring than pharmacists with only a residency certificate. The main reason for directors hiring residency graduates was their comprehensive hospital pharmacy background. The initial starting salary for residents was equivalent to a starting salary for a pharmacist with one to two years of previous hospital experience. A residency certificate was not seen as a requisite for the director's position by the majority of the directors.

Alberta↗
PubMed1987

Mobilization and redistribution of lead over the course of calcium disodium ethylenediamine tetraacetate chelation therapy.

After its successful application to the treatment of acute Pb poisoning, Ca disodium EDTA came into routine clinical use for diagnosis and treatment of subacute and chronic Pb poisoning. Despite widespread use, few definitive conclusions have emerged about the sources of Pb mobilized by Ca disodium EDTA. Furthermore, the possibility that mobilized Pb may be redistributed has been suggested. The current studies indicate that the standard therapeutic protocol for Ca disodium EDTA has little impact on critical organs such as brain and liver and moreover, that diagnostic Ca disodium EDTA chelation may even increase the concentration of Pb in these tissues. After a 3 to 4 month exposure to Pb acetate in drinking water, different groups of rats received daily i.p. injections of saline (control), 75 or 150 mg/kg of Ca disodium EDTA for either 1, 2, 3, 4 or 5 days and were then sacrificed 24 hr after the final injection. Tissue analyses indicated that Pb was mobilized from bone and kidney and redistributed initially to both brain and liver. Levels in both brain and liver declined with subsequent Ca disodium EDTA injections, but no net loss from either tissue occurred over the 5-day treatment period despite a decline in blood Pb levels and a marked enhancement of urinary Pb excretion. These findings stress the need for further investigation of Ca disodium EDTAs effects and for parallel evaluation of alternate chelating agents, and suggest that a re-evaluation of both the diagnostic and therapeutic roles of Ca disodium EDTA may be advisable.

Animals↗
PubMed1987

Threshold dose-response models in toxicology.

After a brief discussion of the threshold concept in toxicology, we consider models for the estimation of thresholds in the case where the observed response is binary or quantal. A generalization of the four-parameter Tukey-lambda family of distributions is proposed as a useful class of models for threshold estimation. Properties of these models are discussed and the process of model fitting and evaluation is illustrated using a number of data sets. The discussion includes consideration of background or spontaneous response, and comparison with other models. One of these is the linear-plateau or hockey-stick model, which has been used in a number of toxicological studies.

Animals↗
PubMed1986

A statistical analysis of prescreening alarms in a population of normal and abnormal gynecologic specimens.

A multidimensional slit-scan flow system has been developed to serve as an automated prescreening instrument for gynecological cytology. Specimens are classified abnormal based on the number of cells having elevated nuclear fluorescence (alarms). An alarm region in a bivariate histogram of nuclear fluorescence versus nuclear-to-cell-diameter ratio is defined. Alarm region probability arrays are calculated to estimate the probability that an alarm falling in a particular bin of the alarm region is either from a normal or an abnormal specimen. From these arrays, a weighted alarm index is generated. In addition, summary indices are derived that measure how the distribution of alarms in each specimen compares with the average distributions for the normal and abnormal specimen populations. These indices together with current features are evaluated with respect to their utility in specimen classification using a nonparametric classification technique known as recursive partitioning. Resulting classification trees are presented that suggest information in the distribution of alarms in the bivariate histogram. In addition, they validate the features and rules currently used for specimen classification. Recursive partitioning appears to be useful for multivariate classification and is seen as a promising technique for other applications.

Cytodiagnosis↗
PubMed1986

Graphical analysis of multivariate pain data in analgesic trials.

In order to compare analgesic treatments effectively one must measure pain over time. In a single-dose clinical analgesic trial one typically obtains repeated pain measurements from each patient during a relatively short period (4-6 hours). Such measurements constitute multivariate data, which are usually reduced by simple addition to a single derived pain measure for analysis of between-treatment differences. In this article we consider graphical procedures for the display of multivariate, clinical analgesic data. The first of these are the traditional time-effect curves, with added "standard error bars." We also examine a multivariate display, the biplot, which is based on principal component analysis. This technique provides a representation of the raw pain scores at each time of measurement by a vector originating from the origin of a two-dimensional graph. The multivariate pain scores of individual patients are summarized by points on the graph. Differences in pain scores over time (or between treatment groups) may be examined by relating points (or ellipses representing treatment groups) to different vectors. Using actual data from a postsurgical analgesic trial, we compare the two approaches and show that the multivariate approach is a useful addition to the standard technique for display of such data.

Analgesics↗
PubMed1986

Reproduction and growth following prenatal methylmercuric chloride exposure in mice.

Reproductive effects of the environmental pollutant methylmercuric chloride administered as a single dose per os during pregnancy were studied both in treated mice (G0 generation) and in their prenatally exposed offspring (G1). Treatment at 9.5 days postfertilization caused no observed effects at doses as high as 12-18 mg Hg+/kg. In contrast, treatment at 12.5 and 15.5 days produced toxicity; results were similar and were combined for analysis. Among G0 mice, the percentage capable of delivering one or more viable pups showed an estimated threshold level response at 8.0 mg/kg. The percentage of G1 pups that were viable at 1 day post partum was significantly dose-related, with an approximate threshold exposure level of 4.3 mg/kg. Among the surviving G1 offspring, body weight in adulthood (8 months) showed a statistically significant reduction that was also dose-related. Fertility testing of G1 offspring revealed no treatment effects on mating behavior judged by time interval between pairing and parturition. However, there was a trend (statistically nonsignificant) toward a dose effect on sizes of females' litters. Sterility (inability to produce offspring) did not occur either among G1 males at 4 months of age (N = 30; dose 8-12 mg/kg) or among females up to the advanced reproductive age of 14 months (N = 29; dose 5.3-12 mg/kg). We conclude that mice exposed prenatally to methylmercuric chloride revealed no greater susceptibility to sterility than to perinatal mortality.

Animals↗
PubMed1986

Velopharyngeal insufficiency after adenoidectomy: an 8-year review.

The characteristics of 137 patients referred to the Speech Clinic at The Hospital for Sick Children, Toronto, Canada during the past 8 years for the investigation of persistent hypernasality after adenoidectomy are reported. Over 30% of the patients had preoperative factors that are thought to increase the risk, such as submucous cleft palate, fluid regurgitation through the nose, a family history of velopharyngeal insufficiency or clefting, or hypernasality. Fifty percent of the patients required pharyngoplasty to correct hypernasality, 37% required speech therapy alone, and 13% improved with no treatment.

Adenoidectomy↗
PubMed1986

Towards a behavioral typology of Alzheimer's patients.

Neuropsychological test performance and estimates of regional rates of cortical glucose metabolism obtained via positron emission tomography are presented for patients with Alzheimer's disease (AD). Analyses of these data indicated the presence of distinct subgroups characterized by qualitatively different profiles of cognitive impairment and corresponding patterns of cerebral hypometabolism. No subgroup differences were noted with regard to age at onset or reported duration of symptoms. These findings indicate that, in a given individual, AD may initially invade a relatively circumscribed cortical region. Thus, although AD may constitute a single disease process, it does not result in a unitary neuropsychological syndrome.

Adult↗
PubMed1986

GABA-agonist therapy for Alzheimer's disease.

Evidence suggesting a reduction of cerebral gamma-aminobutyric acid (GABA) neurons in Alzheimer's disease has been reported. To evaluate the possible contribution of GABA system dysfunction to the intellectual decline associated with this disorder, a controlled therapeutic trial of a potent and specific GABA agonist, THIP [4,5,6,7-tetrahydroisoxazolo(5,4,-c)pyridin-3-ol], was undertaken. Six Alzheimer patients with mild to moderately severe dementia and low spinal-fluid GABA levels received THIP at maximum individually tolerated dosage. No significant change in cognitive function could be discerned, despite attainment of dose levels that produced centrally mediated adverse effects similar to those of other GABA agonists. The results support the views that pharmacologic attempts to stimulate central GABA-mediated synaptic function may not confer therapeutic benefit to patients with Alzheimer's disease and that a GABA system deficit may not serve as a critical determinant of the dementia that characterizes this disorder.

Alzheimer Disease↗
PubMed1986

Physician utilization by three groups of ethnic elderly.

Determinants of physician utilization were examined among three groups of ethnic elderly, Vietnamese, Portuguese, and Hispanic, living in Santa Clara, California. Andersen and Newman's behavioral model provided a framework for the analysis. Univariate analysis described and compared the three groups in terms of predisposing, enabling, and need factors as well as factors related to ethnicity such as language and language of the physician. Least squares regression compared the predictors of utilization for the samples. The results showed that need is the common determinant of physician care but that the definition of need varies with ethnicity. The samples had similar rates of chronic illnesses and made equal physician visits, but the needs and factors predicting utilization differed. Contrasts were found between groups in the role of marital status on utilization. For the Portuguese, being married was a significant predictor; while for the Hispanics, being unmarried was significant. The most important predictor for the Vietnamese was satisfaction with their medical care, a factor that was not significant for the other samples. This may indicate that the physician's role transcends that of being just a health care provider for this population. The results suggest that ethnicity is not necessarily a barrier to care but that providers must be sensitive to the cultural diversities of patients and the effects they can have on utilization.

Aged↗
PubMed1986

Long-term follow-up of detrusor instability following the colposuspension operation.

Pre- and post-operative clinical and urodynamic data have been reviewed in 24 women with detrusor instability following colposuspension. Follow-up ranged from 3 to 5 years. Ten women remained asymptomatic throughout; of the remainder, four (28.6%) were improved by drug therapy. With one exception, patients who were symptomatic at the outset remained so at late follow-up.

Adult↗
PubMed1985

Early biochemical effects of an organic mercury fungicide on infants: "dose makes the poison".

Phenylmercury absorbed through the skin from contaminated diapers affected urinary excretion in infants in Buenos Aires. The effects were reversible and quantitatively related to the concentration of urinary mercury. Excretion of gamma-glutamyl transpeptidase, an enzyme in the brush borders of renal tubular cells, increased in a dose-dependent manner when mercury excretion exceeded a "threshold" value. Urine volume also increased but at a higher threshold with respect to mercury. The results support the threshold concept of the systemic toxicity of metals. gamma-Glutamyl transpeptidase is a useful and sensitive marker for preclinical effects of toxic metals.

Adult↗
PubMed1985

Growth rate and mitotic index analysis of Vicia faba L. roots exposed to 60-Hz electric fields.

Growth, mitotic index, and growth rate recovery were determined for Vicia faba L. roots exposed to 60-Hz electric fields of 200, 290, and 360 V/m in an aqueous inorganic nutrient medium (conductivity 0.07-0.09 S/m). Root growth rate decreased in proportion to the increasing strength; the electric field threshold for a growth rate effect was about 230 V/m. The induced transmembrane potential at the threshold exposure was about 4-7 mV. The mitotic index was not affected by an electric field exposure sufficient to reduce root growth rate to about 35% of control. Root growth rate recovery from 31-96% of control occurred in 4 days after cessation of the 360 V/m exposure. The results support the postulate that the site of action of the applied electric fields is the cell membrane.

Electromagnetic Fields↗