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Biomedical subjects

C Cox

Publications and source records attributed to C Cox.

At least 433 records · Page 24Linked to original sources

Performance and exposure indices of rats exposed to low concentrations of lead.

To further characterize the lower end of the function relating lead exposure and biological exposure indices to behavior, male weanling rats were exposed chronically to drinking solutions containing 25 ppm sodium acetate (controls) or 25 ppm lead acetate. Behavioral training began when the animals reached 50 days of age, and performance on a fixed-interval 1-min schedule of food reinforcement was then assessed over 90 experimental sessions (136 days). This exposure produced overall response rate increases over the first 40 sessions that were similar to those observed previously with higher concentrations of lead. Response rates of the two groups tended to merge subsequently. The increased overall response rates in the treated group derived primarily from an increased frequency of shorter interresponse times (IRTs) and increased running rates (calculated without the postreinforcement interval). Blood lead (PbB) and zinc protoporphyrin (ZPP) values were determined following sessions 30, 60, and 90. PbB values of the lead-exposed group averaged 15 to 20 micrograms/dl throughout the study; ZPP did not differ. The mean brain lead value of the treated group was 0.07 micrograms Pb/g. Blood-brain ratios (1.38 to 4.06) were substantially greater than those previously observed at higher exposures. These data extend to even lower exposures, and lower blood lead concentrations, the effective concentration for behavioral effects, and further emphasize the importance of the sensitivity of the endpoint in assessing behavioral toxicity.

Animals↗

On the nature of the verbal memory deficit in Alzheimer's disease.

Verbal memory was investigated in patients with Alzheimer's disease (AD) with previously documented deficits in word production and comprehension. Procedures were employed to evaluate word recall and recognition within the context of both "multistore" and "levels of processing" models of memory. In addition, memory abilities were evaluated with respect to performance on measures of verbal fluency and language comprehension. As expected, the AD patients performed significantly worse than normal individuals on all tasks. However, in each experiment their pattern of recall across conditions was found to be qualitatively similar to that produced by normal subjects. It was argued that the memory impairment associated with Alzheimer's disease may be largely due to an inability to encode a sufficient number of stimulus features or attributes. Furthermore, this encoding deficit includes, but is not limited to, semantic attributes. Similarities between the performance of the AD patients and reported findings with Korsakoff patients and normal subjects with "weak" memory were discussed.

Aged↗

Toxicokinetics of toluene in the rat.

Toxicokinetic experiments with toluene that rely on data pooled from several animals have typically provided estimates of rate constants based on single exponential functions; in the present study a within-subject design was used to describe the time course of toluene in the blood to see if additional exponential terms could be resolved. Each rat was exposed for 2 h to either 1 000, 1 780, or 3 000 ppm of toluene. Blood samples were drawn at different times from indwelling jugular cannulae, and blood toluene concentrations were determined by vapor phase equilibrium chromatography. There was substantial variability between the peak blood values of the animals at each exposure concentration. Nonlinear regression was used to determine regression parameters for data drawn from individual animals. A bi-exponential function was found to minimize significantly the residual sum of squares observed during elimination. However, only a single exponential function could be resolved reliably during uptake. The mean half-time during uptake was approximately 34 min; the two half-times for elimination averaged approximately 6 and 90 min. Because of between-subject variability, a more accurate description of the time course of toluene uptake and elimination can be provided by kinetic studies that use a within-subject design.

Animals↗

Double-blind, randomized trial of a calf lung surfactant extract administered at birth to very premature infants for prevention of respiratory distress syndrome.

Organic solvent extraction of surfactant obtained by lavage of calf lungs yields a highly surface-active material. A double blind, randomized clinical trial to determine the effect of this material on respiratory distress syndrome in premature infants was initiated in the Neonatal Intensive Care Unit at the University of Rochester in December 1983. Infants 25 to 29 weeks gestational age were eligible for entry into the trial. At the time of this interim analysis 32 patients had been randomly selected and entered into the trial, 16 surfactant-treated patients and 16 in a control group who received only saline. At birth, intrapulmonary instillation of the calf lung surfactant extract dispersed in saline or saline alone occurred in the delivery room immediately after intubation and prior to ventilation; infants were then ventilated and treated as usual. At 6, 12, 24, 48, and 72 hours after birth, the severity of respiratory distress was categorized as either minimal, intermediate, or severe based on oxygen and mean airway pressure requirements. Differences observed at six hours after birth were of marginal significance, but at 12 and 24 hours the surfactant-treated group had significantly (P less than .01) less severe respiratory distress compared with the control group. Differences between treated and control infants were not statistically significant at 48 and 72 hours after birth. In four surfactant-treated infants the severity of respiratory distress worsened between 24 and 48 hours after birth, suggesting that one dose of surfactant at birth may not be sufficient for some infants.

Clinical Trials as Topic↗

Differential perceptual-spatial impairment in Huntington's and Alzheimer's dementias.

Because the severity of memory disorders exhibited by neuropsychiatric patients overshadows other cognitive deficiencies, we explored the visuoperceptual and constructive abilities of patients with Alzheimer's (AD) or Huntington's (HD) disease. The tasks assessed directional sense with reference to egocentric space, as well as visuodiscriminative and constructive skills of patients and matched controls. A double dissociation was found: the performance of patients with AD was found to be significantly impaired on tasks involving extrapersonal perception and construction but not on the test of egocentric space. In contrast, visuoconstructive performance by patients with HD was not significantly impaired, while salient deficits were apparent when manipulation of personal space was required. These differential patterns of defects may have been aligned with neuropathologic changes in different cortical and subcortical structures, respectively, in patients with AD and HD.

Adult↗

Computerized tomography and neuropsychological test measures in adolescents with obsessive-compulsive disorder.

The authors administered CAT scans and neuropsychological tests to 16 adolescents with obsessive-compulsive disorder (mean age +/- SD = 13.7 +/- 1.6 years) and 16 matched controls. The patients had a mean ventricular-brain ratio (VBR) significantly higher than the controls' and showed spatial-perceptual deficits similar to those found in patients with frontal lobe lesions. Memory, reaction time, and decision time did not differ significantly from controls'. Neurodevelopmental examination of seven patients yielded a high frequency of age-inappropriate synkinesias and left hemibody signs. These results suggest CNS dysfunctioning in children with obsessive-compulsive disorder, with possible right cerebral involvement. However, the patients' neuropsychological test deficits and VBRs were not correlated.

Adolescent↗

Rheumatoid arthritis: is serum vitamin B12 high in active disease?

Seven clinical and laboratory indices of disease activity were compared with serum vitamin B12 levels in 32 patients with rheumatoid arthritis treated with penicillamine (16 patients) or sulphasalazine (16 patients) for up to 24 weeks. Prior to treatment each patient had active disease but a normal or low serum vitamin B12 concentration. During treatment, significant improvements occurred in all clinical and laboratory measurements but vitamin B12 levels were unchanged. We have been unable to confirm a reported positive association between rheumatoid disease activity and serum B12 concentration.

Adult↗

Anticonvulsant and antipunishment effects of toluene.

Toluene can have striking acute behavioral effects and is subject to abuse by inhalation. To determine if its actions resemble those of drugs used in the treatment of anxiety ("anxiolytics"), two sets of experiments were undertaken. Inasmuch as prevention of pentylenetetrazol-induced convulsions is an identifying property of this class of agents, we first demonstrated that pretreatment with injections of toluene delayed the onset of convulsive signs and prevented the tonic extension phase of the convulsant activity in a dose-related manner. Injections of another alkyl benzene, m-xylene, were of comparable potency to toluene. Inhalation of toluene delayed the time to death after pentylenetetrazol injection in a manner related to the duration and concentration of exposure; at lower convulsant doses, inhalation of moderate concentrations (EC50, 1311 ppm) prevented death. Treatment with a benzodiazepine receptor antagonist (Ro 15-1788) failed to reduce the anticonvulsant activity of inhaled toluene. Anxiolytics also attenuate the reduction in response rate produced by punishment with electric shock. Toluene increased rates of responding suppressed by punishment when responding was maintained under a multiple fixed-interval fixed-interval punishment schedule of reinforcement. Distinct antipunishment effects were observed after 2 hr of exposure to 1780 and 3000 ppm of toluene; the rate-increasing effects of toluene were related to concentration and to time after the termination of exposure. Thus, toluene and m-xylene resemble in several respects clinically useful drugs such as the benzodiazepines.

Animals↗

Behavioral detection of 60-Hz electric fields by rats.

Rats partially deprived of food were trained individually to press a lever in the presence of a vertical, 60-Hz electric field and not to press in its absence. Correct detections that occurred during brief, 3- or 4-s trials occasionally produced a food pellet. The probability of detecting the field was found to increase as field strength increased. The threshold of detection, ie, the field strength required for detections at a probability of 0.5 after correction for errors, was generally between 4 and 10 kV/m. The range of field strengths between almost zero and almost 100% correctness of detection was approximately 8 kV/m. A logistic function provided a good description of the increase in the detection probability with increasing field strength. These performances occurred reliably in 19 rats, some of which were studied for 2 years. Control procedures showed that the behavior required that the rat be in the electric field; the behavior was not controlled by any of several potentially confounding variables.

Animals↗

On the mechanism of 60-Hz electric field induced effects in Pisum sativum L. roots: vertical field exposures.

Roots of Pisum sativum L. were chronically exposed to 60-Hz vertical electric fields ranging from 150 to 450V/m in an aqueous medium whose conductivity was approximately 0.07 S/m. Control and exposed roots were grown concomitantly in the same tank whose medium was continuously circulated and maintained at 19 degrees C. The experiments were conducted blind. Root growth rates were determined daily and the mitotic index was determined for various intervals over a 24-h period, ranging from 12 h before to 12 h after electrode energization. Root growth rates were affected in a dose dependent relationship by exposures greater than 250 V/m. Mitotic indices were not affected by 150 V/m but were affected at 350 V/m; the former exposure did not alter root growth rates, the latter did. The growth rates of vertically exposed roots were compared to those of horizontally exposed roots; the former are more sensitive at a given field strength. The observations are consistent with the postulate that the electric field acts upon the cell through a perturbation of the transmembrane potential.

Analysis of Variance↗

Delayed behavioral toxicity of lead with increasing exposure concentration.

Twenty-one-day-old male Long-Evans hooded rats were exposed chronically to drinking solutions containing 500 ppm sodium acetate (controls) or 50, 100, or 500 ppm lead acetate. Performance on a fixed interval 1-min schedule of food reinforcement was assessed over 155 sessions. Blood lead values were monitored serially and brain lead determinations made at the end of testing (335 days of lead exposure). The lowest concentration of lead in the drinking water was associated with increases in the rate of fixed-interval responding over the first 30 sessions. At the two higher concentrations, response rate values similar to controls over the first 40 sessions were followed by rate increases. The latency to maximum rate depended on concentration; the highest concentration was associated with the longest latency. Response rates of rats exposed to 50 ppm lead gradually returned to control levels after 120 sessions, while increased rates were sustained in rats at 100 and 500 ppm lead, even 100 days after lead exposure was terminated. Marked individual differences in susceptibility to lead-induced rate increases were observed in all treatment lead values also reflected exposure concentrations. Blood-brain ratios averaged 0.743 to 0.913, which agree with other data for the rat and human. These results confirm the vulnerability to lead of rats beyond the neonatal period, and extend the range of conditions under which such effects occur.

Animals↗

Absence of an effect of diagnostic ultrasound on sister-chromatid exchange induction in human lymphocytes in vitro.

The frequency of sister-chromatid exchanges in human lymphocytes cultured in vitro was not changed after a 30-min exposure to a 2 MHz focused, diagnostic ultrasound beam with a pulse repetition rate of 1000 Hz, 1 musec burst duration, 100 W/cm2 temporal peak, spatial peak intensity. These results are consistent with those obtained with a number of other cell types and are contrary to some previously reported effects for human lymphocytes.

Bromodeoxyuridine↗

Evaluation of current clinical trial methodology in analgesimetry based on experts' opinions and analysis of several analgesic studies.

There is general agreement that the controlled clinical trial is the best method for analgesic evaluation. Current practice in clinical analgesimetry, however, varies considerably with regard to design, measurement of pain, and statistical analysis. We attempted to assess the degree of this diversity by a questionnaire survey of a sample of investigators who are currently conducting clinical pain studies. To examine how various statistical methods perform in practice, we reanalyzed data from four of our published analgesic studies using a number of standard methods.

Analgesia↗