Biomedical subjects

C Cox

Publications and source records attributed to C Cox.

At least 235 records · Page 13Linked to original sources

PubMed1995

A test of the hypothesis that a 60-Hz magnetic field affects ornithine decarboxylase activity in mouse L929 cells in vitro.

Four replicate experiments were performed to test the hypothesis that a 4-hr exposure of L929 cells in vitro to a 60 Hz, 10 microT magnetic field results in a large increase in ornithine decarboxylase (ODC) enzyme activity (1-2). A positive control yielded a highly statistically significant increase in ODC activity. However, magnetic field exposure had no statistically significant effect on extractable ODC activity of L929 cells relative to that of sham-exposed cells.

Analysis of Variance↗

PubMed1995

Location-scale cumulative odds models for ordinal data: a generalized non-linear model approach.

Proportional odds regression models for multinomial probabilities based on ordered categories have been generalized in two somewhat different directions. Models having scale as well as location parameters for adjustment of boundaries (on an unobservable, underlying continuum) between categories have been employed in the context of ROC analysis. Partial proportional odds models, having different regression adjustments for different multinomial categories, have also been proposed. This paper considers a synthesis and further generalization of these two families. With use of a number of examples, I discuss and illustrate properties of this extended family of models. Emphasis is on the computation of maximum likelihood estimates of parameters, asymptotic standard deviations, and goodness-of-fit statistics with use of non-linear regression programs in standard statistical software such as SAS.

Humans↗

PubMed1995

Reduced expression of preproenkephalin in striatal neurons from Huntington's disease patients.

Differential loss of neurons and terminals occurs in Huntington's disease. Neurons expressing preproenkephalin (PPE) appear to be more vulnerable than neurons expressing preprotachykinin and terminals in the lateral pallidum (containing enkephalin) are more affected than terminals in the medial pallidum (containing substance P). We used in situ hybridization histochemistry and emulsion autoradiography to quantify the number of PPE expressing neurons and the neuronal levels of PPE mRNA in striatum of individuals who died with Huntington's disease and normal controls. We found a grade-related decline in the number of PPE-labeled neurons per field in the striatum of individuals with Huntington's disease compared with controls. Three measures of the neuronal level of PPE mRNA, the mean number of silver grains per PPE neuron, the median number of grains per PPE neuron, and the percentage of PPE neurons with more than 30 grains, were all significantly reduced (41 to 80% of control) in Huntington's disease striatum. The magnitude of the reduction in levels of PPE mRNA per neuron was related to the grade of lesions. These data support the notion that decreased levels of PPE mRNA may account, in part, for the greater loss of enkephalin staining in lateral pallidal terminals compared with substance P staining in medial pallidal terminals. Decreased levels of PPE mRNA may result in clinical symptoms prior to the loss of neurons. The reduction in expression of PPE mRNA suggests that surviving striatal neurons may be affected by the expression of the Huntington's disease gene prior to their imminent cell death.

Adult↗

PubMed1995

Sulfuric acid aerosol followed by ozone exposure in healthy and asthmatic subjects.

These studies evaluated symptom and pulmonary function responses of humans sequentially exposed to sulfuric acid aerosol and ozone. Thirty healthy subjects and 30 allergic asthmatic subjects underwent 3-hr exposures in an environmental chamber to 100 micrograms/m3 sulfuric acid and sodium chloride (control) aerosols (in random order), followed 24 hr later by 3-hr exposures to ozone (0.08, 0.12, or 0.18 ppm). Each subject was studied four times, receiving each aerosol preexposure followed by two of the three ozone concentrations. For the healthy group, no convincing symptomatic or physiologic effects of exposure to either the aerosol or ozone on lung function were found. For the asthmatic group, preexposure to sulfuric acid altered the pattern of response to ozone in comparison with sodium chloride preexposure and appeared to enhance the small mean decrements in FVC that occurred in response to 0.18 ppm ozone (means +/- SE: -3.6 +/- 1.5% with sodium chloride preexposure, -6.8 +/- 1.7% with sulfuric acid preexposure). Individual responses among asthmatic subjects were quite variable, some demonstrating reductions in FEV1 of more than 35% following ozone exposure. Analysis of variance of changes in FVC revealed evidence for interactions between aerosol and ozone exposure both immediately after (P = 0.005) and 4 hr after (P = 0.030) exposure. Similar effects were seen for FEV1. When normal and asthmatic subjects were combined, four-way analysis of variance revealed an interaction between ozone and aerosol for the entire group (P = 0.0022) and a difference between normal and asthmatic subjects (P = 0.0048). There was no significant effect of exposures on symptoms for either normal or asthmatic subjects. Asthmatic subjects differ from healthy volunteers in their functional responses following sequential exposures to aerosols and ozone and appear to represent a susceptible population.

Adult↗

PubMed1995

The intensity of the pupillary light reflex does not correlate with the number of retinal photoreceptor cells.

The purpose of this study was to determine if the pupillary light reflex (PLR) can serve as an indicator of the number of photoreceptor cells present in the rat retina to a sufficient degree of precision to be useful for testing the functional effects of retinal transplantation. The PLR was measured as percentage constriction of normal Fischer 344 rats (n = 14) and compared to the PLR of light-damaged (1300 luxes/30 days exposure) Fischer rats (n = 13). Additionally, the PLR of RCS-rdy+ (congenic) rats (n = 8) was compared to the PLR or RCS dystrophic rats (n = 7). Three eyes from each group were randomly chosen for morphometry. The number of photoreceptor nuclear profiles per 60 microns of retinal length was counted at six predetermined loci and averaged. The mean PLR of Light-Damaged F344 group (64%) was significantly different from the mean PLR of the Normal F344 group (75%) (P = 0.003). However, the mean PLR of the RCS Dystrophic group (72%) did not differ from the mean PLR of the RCS Congenic group (71%) (P = 0.82). Morphometry revealed that the mean number of photoreceptor nuclear profiles within each group of animals was vastly different: Normal F344 = 138, Light Damaged F344 = 19, Congenic RCS = 93, and Dystrophic RCS = 1. No correlation was found between intensity of PLR and number of photoreceptors present (r = 0.11, P = 0.78).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1995

A repeated measures approach to the detection of the acute behavioral effects of toluene at low concentrations.

Acute behavioral effects of solvents are frequently the critical parameter considered for the recommendation of exposure limit values. Studies of toluene's acute effects on animal behavior during exposure have not been particularly sensitive; increasing the number of observations at low concentrations and the number of animals studied is a reasonable approach to increasing the ability to detect small acute effects. The effects of toluene (178-3000 ppm) were determined in 12 rats trained to nose poke on a probabilistic schedule of food delivery in a small exposure chamber that was highly ventilated with air or a toluene test atmosphere. Animals served as their own controls and were exposed to toluene twice a week for 2 hr during behavioral evaluation. At least six determinations of the effects of toluene were made at concentrations of 178, 300, and 560 ppm, and at least three determinations at 1000, 1780, and 3000 ppm. Biphasic concentration-effect, time-effect, and concentration-response functions were observed. Rates of nose poking increased in 4 of 12 animals at 178 ppm and in 9 of 12 animals at 300 ppm; all animals were affected at 560 ppm. The concentration at which a 10% rate increase occurred was determined by regression analysis to be 156 ppm with the lower 95% confidence limit or "benchmark" concentration being 116 ppm. Weighted regression analysis produced slightly higher estimates of these parameters, 182 and 157 ppm, respectively, while conventional logistic regression revealed that 10% of animals would be affected at a concentration of 114 ppm with a lower confidence limit of 63 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Simple radioimmunological assay of anti-alpha-galactosyl antibody (anti-Gal): application to autoimmune thyroid diseases and thyroid-associated ophthalmopathy.

Two radioimmunological techniques for the measurement of anti-alpha-galactosyl (anti-Gal) antibodies were developed and we demonstrated that this antibody is present in the serum of most untreated patients with Graves' disease, thyroid-associated ophthalmopathy (TAO) and autoimmune thyroiditis. Thyrotropin-binding inhibiting immunoglobulins (TBII) and Thyroid Stimulating Antibodies (TSAb) are frequently found in serum of patients with Graves' disease but not with autoimmune thyroiditis. Although TBII and anti-Gal were found sometimes simultaneously in the same serum samples, we demonstrated that anti-Gal could be present in the absence of TBII and reciprocally.

Animals↗

PubMed1995

Ultrasound accelerates transport of recombinant tissue plasminogen activator into clots.

Fibrinolysis is accelerated in vitro in an ultrasound field, and externally applied high frequency ultrasound also accelerates thrombolysis in animal models. Although the mechanism of this effect is not known, ultrasound does not cause mechanical disruption of clots but rather accelerates enzymatic fibrinolysis. To determine if accelerated fibrinolysis could be related to increased transport of enzyme into clot, we have examined the effect of insonification on the distribution of plasminogen activator between clot and surrounding fluid in vitro. Plasma clots were overlayed with plasma containing 125I-radiolabeled, active-site-blocked recombinant tissue plasminogen activator (rt-PA) and incubated in the presence of 1-MHz ultrasound at 4 W/cm2 or in the absence of ultrasound. The rate of uptake of rt-PA was significantly faster in the presence of ultrasound, reaching 15.5 +/- 1.4% at 4 h compared to 8.2 +/- 1.0% in the absence of ultrasound (p < 0.0001). Similarly, ultrasound increased transport of enzyme from the clot into the surrounding fluid. To determine the effect of ultrasound on the spatial distribution of enzyme, plasma clots were overlayed with plasma containing radiolabeled rt-PA and incubated in the presence or absence of ultrasound. The clots were then snap-frozen, and the radioactivity in serial cryotome sections was determined. Exposure to ultrasound altered the rt-PA distribution, resulting in significantly deeper penetration of rt-PA into the clots. We conclude that exposure to ultrasound increases uptake of rt-PA into clots and also results in deeper penetration. These effects of ultrasound on enzyme transport may contribute to the accelerated fibrinolysis observed in an ultrasound field.

Biological Transport↗

PubMed1995

The functional neuroanatomy of Tourette's syndrome: an FDG-PET Study. II: Relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness.

We analyzed F-18 fluoro-deoxyglucose PET scans carried out in 18 drug-free patients with Tourette's syndrome (TS) in order to evaluate relationships between cerebral metabolism and complex cognitive and behavioural features commonly associated with this disorder. These features (obsessions and compulsions, impulsivity, coprolalia, self-injurious behavior, echophenomena, depression, and measures of attentional and visuospatial dysfunction) were associated with significant increases in metabolic activity in the orbitofrontal cortices. Similar increases, although less robust, were observed in the putamen and, in the case of attentional and visuospatial measures, in the inferior portions of the insula. On the other hand, behavioral and cognitive features were not associated with metabolic rates in other subcortical (midbrain, ventral striatum), paralimbic (parahippocampal gyrus), or sensorimotor regions (supplementary motor area, lateral premotor or Rolandic cortices), in which metabolism had, in some cases more robustly, distinguished these TS patients from controls (Braun et al., 1993). These results suggest that a subset of regions in which metabolic activity appears to be associated with the diagnosis of TS per se, may be explicitly associated with the emergence of complex behavioral and cognitive features of the illness. This is most conspicuous in the orbitofrontal cortices, and it is consistent with the observation that these features resemble the elements of a behavioral syndrome typically seen in patients with lesions of the orbitofrontal cortex.

Adult↗

PubMed1995

Age of onset and medical illness in older depressed inpatients.

Age of onset of depressive episodes may serve as a useful marker of pathogenetic heterogeneity in late-life depression. Medical illness may play an important role in the pathogenesis of depression in the elderly, but its relationship to age of onset has not been carefully examined. We prospectively studied 110 older inpatients with DSM-III-R major depression. Using multiple regression techniques, we found that medical illness was not independently associated with age of onset. Independent predictors of older age of onset were age, male sex, absence of substance abuse history, and absence of melancholia. Our discussion reconsiders the usefulness of age of onset as a primary research variable for elucidating heterogeneity in late-life depression.

Activities of Daily Living↗

PubMed1995

Executive function in children with Tourette syndrome and/or attention deficit hyperactivity disorder.

Tourette Syndrome (TS) in children is associated with various neurobehavioral disorders including attention deficit hyperactivity disorder (ADHD). Children with TS and ADHD show some difficulties with neuropsychological tasks, but we do not know if children with TS alone have neuropsychological deficits. To assess specific cognitive differences among children with TS and/or ADHD, we administered a battery of neuropsychological tests, including 10 tasks related to executive function (EF), to 10 children with TS-only, 48 with ADHD-only, and 32 with TS + ADHD. Children in all groups could not efficiently produce output on a timed continuous performance task [Test of Variables of Attention (TOVA) mean reaction time and reaction time variability]. Children with TS-only appeared to have fewer EF impairments and significantly higher perceptual organization scores than children with TS + ADHD or ADHD-only. These findings suggest that deficiencies in choice reaction time and consistency of timed responses are common to all three groups, but children with TS-only have relatively less EF impairment than children with TS + ADHD or ADHD-only.

Adolescent↗

PubMed1995

Substantia nigra lesions in Alzheimer disease and normal aging.

Clinical and pathological overlap between Alzheimer disease (AD) and Parkinson's disease (PD) has been well described; however, the mechanisms of overlap between these two disorders remain unknown. We retrospectively examined clinical and neuropathological features from 66 individuals participating in the Rochester Alzheimer Disease Center to determine the association of AD with substantia nigra (SN) pathology. SN pathology, identified by a loss of pigmented neurons and the presence of gliosis, pigment-laden macrophages, and Lewy bodies, was blindly scored in 48 AD cases and 18 normal elderly controls. We found moderate or severe pathology in the SN in 2 control brains (11%) and 29 AD brains (60%). The numbers of neocortical and hippocampal neurofibrillary tangles (NFTs) and senile plaques (SPs) were not associated with nigral pathology. There was also no significant association of SN pathology with NFTs or SPs in the striatum, the site to which these neurons project. There was no significant association of increasing SN pathology with aging among AD patients, nor with increasing severity and duration of AD. The signs and symptoms of an extrapyramidal movement disorder were, however, associated with increasing SN pathology. We confirm that pathological lesions in the SN are a common feature of AD and an uncommon feature in normal aging. AD is a significant risk factor for SN lesions and PD, but the pathologic severity of AD, as measured by NFTs and SPs, was not associated with SN lesions.

Aged↗

PubMed1995

Autonomic modulation of heart rate variability during endotoxin shock in rabbits.

OBJECTIVE: Gram-negative septic shock is associated with severe hypotension and autonomic cardiovascular dysfunction. We hypothesized that in an anesthetized rabbit model of endotoxin shock, autonomic modulation of cardiac activity, as measured by power spectral analysis of heart rate (HR) variability, would be decreased compared with the anesthetized control rabbits. DESIGN: Experimental, comparative study. SETTING: Laboratory of a university hospital. SUBJECTS: Fourteen adult male New Zealand white rabbits (2.7 to 3.1 kg body weight) were studied under anesthesia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied the absolute and temporal changes in HR power spectra and plasma catecholamine concentrations in eight experimental and six control New Zealand white rabbits during Escherichia coli endotoxin-induced shock. HR, respirations, arterial blood pressure (BP), HR power spectra, and plasma catecholamine concentrations were measured at 5- to 10-min intervals for 60 mins in control rabbits or until the mean arterial pressure (MAP) decreased by > or = 20 mm Hg in experimental rabbits. There were no differences in basal HR, respiratory rate, BP, HR power spectra, or catecholamine concentrations between groups. After endotoxin administration, MAP decreased (82 +/- 7 vs. 62 +/- 5 mm Hg; p < .05) as did log low-frequency HR power (-2.14 +/- 2.46 vs. -2.20 +/- 2.48 beats/min2; p < .05). Low-frequency HR power and MAP remained unchanged in control animals. Log high-frequency HR power decreased in control and experimental rabbits (-1.02 +/- 1.34 vs. -1.69 +/- 2.12 [control], p < .05; -1.53 +/- 2.19 vs. -2.19 +/- 2.85 beats/min2 [experimental], p < .05). While there was an inverse relationship between low- and high-frequency HR power and MAP, the direction of change was opposite in six of six rabbits in the control group and in six of eight rabbits in the experimental group. Plasma catecholamine concentrations did not change during the experiment in either group. CONCLUSIONS: Sympathetic modulation of cardiac activity decreased, while the sympathomedullary response remained unchanged during endotoxin shock. We speculate that a concomitant decrease in low-frequency HR power as MAP decreases may prove to be an early marker for impending shock.

Animals↗

PubMed1995

Hypocellular myelodysplastic syndromes (MDS): new proposals.

To determine whether hypocellular MDS differs from normo/hypercellular MDS, we attempted to identify hypocellular MDS cases either by correcting the bone marrow (BM) cellularity by age (28 patients) or by using a single arbitrary value of BM cellularity (25 patients) and compared these two groups of hypocellular cases to the normo/hypercellular MDS cases (72 patients). 18 patients were common to both hypocellular groups. Patients with hypocellular MDS in both of these selected groups have similar features with regard to age and sex distribution, peripheral blood and bone marrow parameters, FAB subtypes, karyotypes, leukaemic transformation, and survival. However, the median age of patients in < 30% BM cellularity group was higher than those patients in the age-corrected group (69 years v 62 years). The selection of < 30% cellularity excluded 10 cases in the age group < 70 years but included another seven patients in the age group of > 70 years. However, correction of BM cellularity by age revealed that those included patients (selected for < 30% cellularity) who had normocellular BM by their age. Therefore we recommend the age-correcting grouping to ensure comparable series for comparison, for response to treatment, and survival. Finally, BM cellularity does not appear to be an important factor on prognosis in MDS, because patients with hypocellular MDS in both selected groups have similar prognosis to those with normo/hypercellular MDS patients.

Adult↗

PubMed1995

Attitudes of older people toward suicide and assisted suicide: an analysis of Gallup Poll findings.

OBJECTIVES: To describe the older population's attitudes toward suicide and assisted suicide, and to determine whether lenient attitudes are associated with known demographic and psychosocial risk factors for completed suicide. DESIGN: Telephone survey conducted by the Gallup Organization in November 1992. PARTICIPANTS: A sample of 802 adults in the United States (541 women and 261 men) aged 60 years and older. MEASUREMENTS: The dependent variables, attitudes toward suicide, were assessed with five attitude statements. Participants rated their agreement with each statement on 4-point Likert-type scales, subsequently dichotomized for use in univariate analyses and logistic regressions. The independent variables included income and demographic and psychosocial risk factors for suicide: age, gender, race, marital status, religiousness, self-rated health, and satisfaction with family relationships. RESULTS: The majority of respondents did not express lenient attitudes. In comparison with survey findings of physicians and the general population, a relatively smaller percentage (41%) of these older respondents believe that physician-assisted suicide should be legalized. Agreement with one or more of the attitudes presented was associated with age, gender, race, marital status, and religiousness in univariate analyses (P < .05), and race, religiousness (P < .001), gender, self-rated health, and satisfaction with family relations (P < .08) in logistic regressions. CONCLUSIONS: The hypothesized relations between risk factors for suicide and lenient attitudes toward suicide were supported. Although none of the risk factors was associated with all five attitudes, in combination the results suggested that a common set of variables predict both lenient attitudes toward suicide and suicidal behavior. Future research is necessary to determine the role of depression and other factors that may mediate the observed relationships and to determine whether the presence of specific, strongly held attitudes sanctioning suicide in an older person signals the need to assess suicide risk.

Aged↗

PubMed1995

Lack of carbamazepine toxicity in frail nursing home patients: a controlled study.

OBJECTIVE: To assess the effects of carbamazepine and placebo on measures of toxicity in frail nursing home patients. DESIGN: A nonrandomized, double-blind, placebo-controlled crossover study. SETTING: Two nursing homes in Rochester, New York. PARTICIPANTS: Twenty-five subjects (mean age 84.5 years) with dementia. INTERVENTION: Carbamazepine and placebo during two 5-week periods separated by a 2-week washout. The modal dose for each patient was 300 mg/day. MEASUREMENTS: Adverse experiences, comorbid events, and physical signs and symptoms were assessed continuously, and laboratory data were examined at the beginning and end of each treatment period. RESULTS: One subject died with a pneumonia (and elevated white blood cell count), and one subject developed probable carbamazepine-induced tics. There was a minimal drop in hematocrit and a slight elevation of liver enzymes, none of which was clinically significant. There was otherwise no excess of adversity or comorbid events on carbamazepine versus placebo, and there was no change in electrolytes or other laboratory measures. CONCLUSION: The findings indicate that carbamazepine in this dose range was well tolerated for the 5-week treatment period in this frail sample. These data supplement the literature regarding carbamazepine toxicity, which is devoid of controlled studies in older subjects.

Aged↗

PubMed1995

Attitudes toward self-determined death: a survey of primary care physicians.

OBJECTIVE: To survey physicians to determine whether sociodemographic and practice-related variables are predictive of their attitudes toward suicide. DESIGN: Mailed questionnnaire survey. SETTING: Monroe County, New York. PARTICIPANTS: A 50 percent random sample of practicing primary care physicians. Of 186 potential respondents, 114 (61.3%) physicians returned questionnaires. MEASUREMENT: In addition to age and gender, independent variables included medical specialty, practice composition defined in terms of patient age, and textbook knowledge of depression and suicide. The dependent variable, attitude toward suicide, was measured using four standard opinion survey questions and six items based on a case vignette. Dependent variables were rated on a Likert-type scale and subsequently dichotomized for use in logistic regression analysis. RESULTS: Approximately 61 percent of the respondents believe that suicide can be rational under certain circumstances, 51 percent believe that physicians should not assist suicides under any circumstances, and 31 percent support legalization of assisted suicide under certain circumstances. Regression analyses revealed that gender was a significant predictor for three of the ten attitude items. Medical specialty, clinical and epidemiological knowledge of depression and suicide, and physician age significantly predicted one attitude item. CONCLUSIONS: These results suggest that physicians' attitudes toward suicide are multidetermined. Although gender, age, medical specialty, and knowledge of depression and suicide predict certain attitudes, the logistic regression analyses were not highly successful in predicting respondents' attitudes. Given the power of physicians to command public attention and to influence public and legal opinion, it is vital that future research continue to explore the determinants of physicians' attitudes toward self-determined death.

Adult↗

PubMed1995

Older age and the underreporting of depressive symptoms.

OBJECTIVE: To determine whether older age is associated with a decrease in self-reported depressive symptoms, independent of examiner-rated symptoms, in inpatients with major depression. DESIGN: Survey study. SETTING: Inpatient psychiatric units at a university medical center. PATIENTS: Eligible subjects were those over 20 years of age with a primary diagnosis of DSM-III-R major depression. Participation was sought from all subjects over 60 years of age and from every second or every third younger subject, depending on rater availability. Of 137 eligible subjects, 97 completed all study measures. MEASUREMENTS: The Beck Depression Inventory (BDI), as a measure of self-reported depressive symptoms, was the dependent variable. The Hamilton Rating Scale for Depression (Ham-D) was used to assess examiner-rated symptoms. MAIN RESULTS: Older age (P = .03) was associated negatively and examiner-rated depressive symptoms (P = .0001) were associated positively with BDI score. Other variables, including gender, education, age of depression onset, and medical illness burden, were not independently associated with BDI. Examination of depressive symptom subtotals (psychologic/affective vs. somatic/neurovegetative) revealed that only the self-reported psychologic/affective subtotal was significantly associated with age (P = .0018). CONCLUSIONS: Some older patients with clinically significant depression underreport their symptoms. When asking older patients about depressive symptoms, clinicians should view negative responses only within larger clinical contexts and should obtain information from other sources as needed. Similar concerns must temper interpretation of research that relies on subject self-report to study depression in late life.

Age Factors↗