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Biomedical subjects

C Randolph

Publications and source records attributed to C Randolph.

At least 37 records · Page 2Linked to original sources
PubMed1996

Lipoprotein profiles and glucose tolerance in lean and obese chimpanzees.

We compared serum lipid profiles and glucose tolerance of obese and lean chimpanzees maintained on a 10.9% fat diet. Seven of 14 obese and 6 of 17 lean chimpanzees were hypercholesterolemic (low density lipoprotein cholesterol > 160 mg/dl), three obese and three lean animals had total cholesterol/high density lipoprotein cholesterol ratios of 5.9-10.7, and two obese and one lean chimpanzee had abnormal glucose tolerance. Useful numbers of captive chimpanzees thus exhibit metabolic abnormalities without recourse to high fat diets and could serve as surrogates in studies of human metabolic diseases.

Analysis of Variance↗
PubMed1995

Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: a positron emission tomography study.

To determine the neural circuitry engaged by performance of the Wisconsin Card Sorting Test (WCST), a neuropsychological test traditionally considered to be sensitive to prefrontal lesions, regional cerebral blood flow was measured with oxygen-15 water and positron emission tomography (PET) while young normal subjects performed the test as well as while they performed a specially designed sensorimotor control task. To consider which of the various cognitive operations and other experiential phenomena involved in the WCST PET scan are critical for the pattern of physiological activation and to focus on the working memory component of the test, repeat WCST scans were also performed on nine of the subjects after instruction on the test and practice to criteria. We confirmed that performance of the WCST engages the frontal cortex and also produces activation of a complex network of regions consistently including the inferior parietal lobule but also involving the visual association and inferior temporal cortices as well as portions of the cerebellum. The WCST activation in the dorsolateral prefrontal cortex (DLPFC) remained significant even after training and practice on the test, suggesting that working memory may be largely responsible for the physiological response in DLPFC during the WCST and, conversely, that the DLPFC plays a major role in modulating working memory.

Adolescent↗
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

Memory and intelligence in lateralized temporal lobe epilepsy and schizophrenia.

Recent neuroimaging studies of patients with schizophrenia have suggested structural and functional abnormalities of mesial temporal lobe structures. We compared the intelligence and memory test performance of 70 patients with schizophrenia and 72 patients with focal, lateralized temporal lobe epilepsy (30 left, 42 right temporal lobe) in order to examine the adequacy of a temporal lobe model of schizophrenic cognitive deficits. The groups did not differ in age, education, or Full Scale IQ. The right temporal lobe group had better overall memory performance than either the left temporal or schizophrenic patients. Unlike the schizophrenic patients, the memory impairment of the left temporal group was most evident with verbal materials and was amplified by delayed testing. Both epilepsy groups had better visual memory than the schizophrenic group. The clear differences in performance pattern between groups suggests that lateralized temporal lobe dysfunction does not by itself provide an adequate model of schizophrenic cognitive impairment.

Adult↗
PubMed1995

Implicit memory in Alzheimer's disease.

While patients with Huntington's disease (HD) and Korsakoff's syndrome (KS) demonstrate "preserved" performance on implicit word-stem completion tasks, patients with Alzheimer's disease (AD) are typically found to be impaired. It has been hypothesized that AD patients do poorly as a result of degenerative changes in posterior cortical association areas thought to mediate performance on this type of implicit memory task, and that the relative sparing of these areas in KS and HD results in their "preserved" performance. The present study was undertaken to examine the implicit memory performance of AD patients on this task after equating their explicit performance to that of normal controls by manipulating the number of encoding exposures. When this was accomplished, the implicit memory performance of AD patients was equivalent to that of controls. The results are discussed within the context of a critical review of the evidence for the existence of separable neural systems in mediating implicit and explicit memory.

Aged↗
PubMed1995

Patterns of relaxin and steroids in the reproductive cycle of the common marmoset (Callithrix jacchus): effects of prostaglandin F2 alpha on relaxin and progesterone secretion during pregnancy.

We measured the concentrations of relaxin (Rlx), progesterone, and estradiol-17 beta in serum samples obtained twice or three times weekly from marmosets during the estrous cycle and pregnancy. The cyclic patterns and concentrations of progesterone and estradiol-17 beta were similar to those reported by previous investigators. Rlx was not detected in individual serum samples ( < 0.62-1.25 ng/ml) obtained from nonpregnant marmosets. However, pooling of luteal serum from all animals permitted assay of much larger volumes of serum (0.4 ml vs. 0.1 ml), and a concentration of about 1 ng/ml was detected. Rlx was first detected in serum in the second or third week of the 21-wk marmoset pregnancy, rose to a peak during Weeks 10-14, and then declined slowly as the time of parturition approached. The pattern of Rlx was unlike that observed during pregnancy in Old World monkeys, chimpanzees, or women, and resembled, instead, that seen in rodents, carnivores, and equids. Progesterone and estradiol-17 beta likewise increased throughout pregnancy, and their patterns were similar to those previously described for marmosets by other investigators. The concentrations of the steroids and Rlx in serum of pregnant marmosets was 10-fold or more higher than those found in Old World monkeys, baboons, chimpanzees, or women. Spontaneous abortions in two of the marmosets were accompanied by precipitous falls in serum levels of progesterone, estradiol-17 beta, and Rlx. Following s.c. injection of the luteolytic agent prostaglandin F2 alpha (PGF2 alpha) into two marmosets at midpregnancy, serum progesterone and Rlx fell to low levels. These animals received a progestin, 17 alpha-ethyl-19-nortesterone, to preclude abortion. Serum progesterone rose again, but serum Rlx remained low for the duration of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Veterinary↗
PubMed1995

Wechsler adult intelligence scale-revised in the evaluation of anterior temporal lobectomy candidates.

We wished to (a) determine the ability of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) to discriminate between patients with epilepsy of left or right temporal lobe (LTLE, RTLE) origin and (b) examine the ability of Kaufman's (1990) WAIS-R short forms to estimate actual Full-Scale IQ (FSIQ). We administered the WAIS-R to 215 nonretarded, left hemisphere dominant patients with invasively verified epilepsy of unilateral TL origin without lesions demonstrated by magnetic resonance imaging (MRI) (excluding mesial temporal sclerosis, MTS). LTLE (n = 106) and RTLE (n = 109) groups were compared on the WAIS-R subtests and summary IQ scores. Verbal-Performance IQ (VIQ-PIQ) discrepancies of various magnitudes, and Verbal Comprehension (VC) and Perceptual Organization (PO) scores derived by factor analysis. The LTLE group scored significantly lower on the Vocabulary subtest, and none of the other indexes reliably distinguished LTLE from RTLE patients. The Kaufman 2, 3, and 4 subtest short forms were significant predictors of FSIQ, with the 4 subtest short form having the highest correlation and lowest error of estimate.

Adult↗
PubMed1994

Schizophrenia and temporal lobe epilepsy. A neuropsychological analysis.

BACKGROUND: Recent neuroimaging studies have reported structural abnormalities of mesial temporal lobe structures in schizophrenia. This study compared the neuropsychological performance of patients with schizophrenia with patients with either left or right temporal lobe epilepsy to determine if lateralized, developmental temporal lobe dysfunction provides a model of the cognitive impairments observed in schizophrenia. METHODS: A total 66 patients with schizophrenia and 101 patients with medically intractable focal temporal lobe epilepsy (48 left temporal, 53 right temporal) received a comprehensive neuropsychological battery. RESULTS: The three groups did not differ on age, years of education, or Full-Scale IQ. However, clear differences were noted in performance profiles. Patients with schizophrenia scored significantly higher than either epilepsy group on a measure of word reading thought to reflect premorbid competence. Patients with schizophrenia demonstrated greater attentional impairment and motor slowing than either epilepsy group. The patients with schizophrenia had superior semantic knowledge and verbal memory compared with the left temporal lobe group. On the Wisconsin Card Sorting Test the patients with schizophrenia obtained significantly fewer categories than either temporal lobe group, but were not significantly more perseverative. CONCLUSIONS: Data suggest lateralized temporal lobe dysfunction does not provide an adequate model of the cognitive impairments seen in schizophrenia. The disorders seem to follow different developmental paths: In early-onset epilepsy, the acquisition of cognitive skills and academic knowledge is compromised, while in schizophrenia cognitive functions are lost. Extratemporal pathologic features, most likely of the frontal lobe, are implicated in the cognitive dysfunction of schizophrenia.

Adult↗
PubMed1994

D-cycloserine treatment of Alzheimer disease.

Degeneration of cortical glutamatergic projections may contribute to the cognitive decline in Alzheimer disease (AD). To evaluate whether 1glutamate system stimulation might confer symptomatic benefit, we administered D-cycloserine, a putative partial indirect agonist at certain N-methyl-D-aspartate (NMDA) glutamate receptors, to 12 patients with probable AD. The patients (seven men, five women) had a mean age of 65 +/- 8.4 years; Mini Mental State Examination scores ranged from 15 to 25. A dose escalation phase, in which cycloserine was given in daily oral doses from 25 to 500 mg (total of six dose levels, 1 week per dose), was followed by a "best dose" crossover comparison with placebo under double-blind conditions. The crossover phase consisted of 2 weeks of cycloserine and 2 weeks of placebo, separated by a 1-week washout period. We observed no significant or consistent effect on neuropsychological outcome measures. The results suggest that short-term potentiation of NMDA-mediated glutamatergic transmission may not prove useful in the symptomatic treatment of Alzheimer dementia.

Aged↗
PubMed1994

Electroencephalographic abnormalities in monozygotic twins with Tourette's syndrome.

The association of attentional, neuropsychological, and behavioural abnormalities with Tourette's syndrome (TS) suggests that the abnormal function of the disorder extends beyond the motor circuits of the basal ganglia. To explore this possibility we studied, with conventional 18-channel electroencephalography, monozygotic twins ranging from 8 to 26 years of age, where at least one member of the twin pair suffered from TS. In nine out of the 11 twin pairs that differed in clinical severity of the tic disorder, the twin with the more severe course of illness had a significantly more abnormal electroencephalogram (EEG) by qualitative visual analysis. Most of the differences were due to excessive frontocentral theta activity, suggesting dysfunction outside the basal ganglia. There was also a significant relationship between a lower global neuropsychological testing score and a worse overall EEG. In eight of nine twin sets with different global neuropsychological testing scores, the twin with the lower score had a worse EEG. A similar relationship was found between birth weight and overall EEG quality. In the nine sets that differed in birth weight, the twin with a lower birth weight had a worse EEG in seven of the sets. The EEG findings are unlikely to be unlikely to be a medication effect because the same result was seen in the six twin pairs who had been medication-free for at least six months before entry into the study. The origin of this slowing may relate to the interaction between environmental insults to the central nervous system and the genetic component of TS, an interaction producing damage to the cortex, thalamus, or both.

Adolescent↗
PubMed1994

Coadministration of fluvoxamine increases serum concentrations of haloperidol.

Four patients with chronic schizophrenia were treated with a combination of fluvoxamine, haloperidol, and benztropine. The combination significantly impaired performance on tests of delayed recall memory and attentional function. Haloperidol concentrations in serum were monitored in three patients and were robustly elevated by fluvoxamine.

Adult↗
PubMed1993

Tourette's syndrome in monozygotic twins. Relationship of tic severity to neuropsychological function.

OBJECTIVE: To determine whether there is a relationship between tic severity and neuropsychological function in Tourette's syndrome (TS). DESIGN: The study employed a case-control series involving monozygotic twin pairs, divided into more severe and less severe groups based on tic severity and tested with a neuropsychological battery of tests. SETTING: Twin pairs were recruited nationwide and evaluated in the National Institute of Mental Health Neuropsychiatric Research Hospital. PATIENTS: Twelve twin pairs (mean age, 10.5 years; range, 8 to 16 years) in which at least one member met criteria for a diagnosis of TS. RESULTS: Global neuropsychological performance was significantly worse in the twins with more severe tic symptoms, with significant differences emerging on individual tests of attention, visuospatial perception, and motor function. In each twin pair, the twin with more severe tics had poorer global neuropsychological function. CONCLUSIONS: The results suggest that the nongenetic factors that influence tic severity in TS exert a similar effect on neuropsychological function, and that these two clinical manifestations of TS may share a common pathophysiologic state.

Adolescent↗
PubMed1993

The functional neuroanatomy of Tourette's syndrome: an FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls.

Regional metabolic rates for glucose estimated using [18F]fluorodeoxyglucose positron-emission tomography were compared in 16 drug-free patients with Tourette's syndrome (TS) and 16 age- and sex-matched normal volunteers. Tourette's syndrome patients were characterized by decreased normalized metabolic rates in paralimbic and ventral prefrontal cortices, particularly in orbitofrontal, inferior insular, and parahippocampal regions. Similar decreases were observed in subcortical regions, including the ventral striatum (nucleus accumbens/ventromedial caudate) and in the midbrain. These changes were more robust and occurred with greater frequency in the left hemisphere. They were associated with concomitant bilateral increases in metabolic activity the supplementary motor, lateral premotor, and Rolandic cortices. Effects of prior exposure to neuroactive drugs did not account for these findings. These results suggest that an altered relationship between limbic-related regions of the cortex and striatum and cortical regions involved in the initiation of movement may play a role in the pathogenesis of this illness.

Adult↗
PubMed1993

Assessment of intellectual function in dementing disorders: validity of WAIS-R short forms for patients with Alzheimer's, Huntington's, and Parkinson's disease.

While commonly administered in the neuropsychological assessment of dementia, the Wechsler Adult Intelligence Scale-Revised (WAIS-R) is excessively long (70-90 min) and difficult for many patients. The present study examined WAIS-R data from patients with clinically distinct dementing disorders, including those with Alzheimer's, Huntington's, and Parkinson's disease (N = 148). The profiles of performance of these three patient groups across subtests were remarkably similar, suggesting that the use of a short form would not result in the loss of clinically significant information. The validity of several published short forms was reviewed. Although all of these systematically over- or underestimated Full Scale IQ for these patients, after a scaling table revision the Kaufman (1990) form appears to provide an accurate estimate of IQ. The use of this short form is therefore recommended to minimize frustration and fatigue on the part of the patient, and to allow the inclusion of other tests critical to the evaluation of dementia within a single assessment session.

Aged↗
PubMed1993

Implicit memory in patients with schizophrenia and normal controls: effects of task demands on susceptibility to priming.

Two experiments employing a stem-completion priming paradigm are reported. The first of these compared patients with schizophrenia (SC) to normal controls and demonstrated impaired implicit memory in the SC patients under task conditions identical to those used previously with other patient groups. The second experiment was designed to examine the effects of implicit task demands and stimulus selection upon susceptibility to priming, with a second group of SC patients and normal controls. Results indicated that the ability to carry out the task demands of the implicit condition (i.e., generate completions for word-stems) was inversely related to susceptibility to priming in both the SC patients and controls. In addition, the baseline probability of specific completions was found to be correlated with the ease of priming those completions, suggesting a possible mechanism for producing statistical dissociations between implicit and explicit retrieval conditions with this paradigm. These findings suggest that certain implicit tasks may be susceptible to nonmemory psychological influences that have not been adequately investigated to date; these may be responsible for "normalizing" the performance of amnesic patients as well as producing statistical dissociations from explicit memory tasks.

Adult↗