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Biomedical subjects

S Berent

Publications and source records attributed to S Berent.

At least 37 records · Page 2Linked to original sources
PubMed1995

The erythromycin breath test predicts the clearance of midazolam.

Midazolam, a commonly used sedative and amnestic medication, has recently been shown to be largely metabolized in the liver by a cytochrome P450, termed CYP3A4. There is at least a tenfold intersubject variability in the liver content and catalytic activity of CYP3A4, which may in part account for the known interpatient differences in the kinetics of midazolam. To test this hypothesis, we determined the intravenous midazolam kinetics of 20 medically stable, hospitalized patients, whose hepatic CYP3A4 activities were determined with use of the [14C-N-methyl]erythromycin breath test. During the kinetic study, we also performed psychometric testing designed to quantitate the level of sedation and amnesia. We found a significant positive correlation between the erythromycin breath test results and weight adjusted clearance (in milliliters per minute per kilogram) of both total midazolam (r = 0.52; p = 0.03) and unbound midazolam (r = 0.61; p < 0.01). The relatively low dose of midazolam used (0.0145 mg/kg) produced significant but transient sedation and memory impairment in some of the patients. We conclude that interpatient differences in liver CYP3A4 activity in part account for the variations in midazolam kinetics. Our observations account for reported drug interactions involving midazolam and suggest that patients with low CYP3A4 activity may be most susceptible to prolonged amnestic effects occasionally produced by this short-acting benzodiazepine.

Adult↗
PubMed1995

Neuropsychological predictors of complex obstacle avoidance in healthy older adults.

Global cognitive impairment in older adults has been associated with a greater risk of falling, and tripping has been implicated as an important factor in a large percentage of these falls. In order to evaluate the role of specific cognitive domains in tripping and falling, 23 healthy older adults completed basic and complex obstacle avoidance tasks, as well as a battery of neuropsychological tests. Using multiple regression analysis, a select pattern of neuropsychological measures was found to predict the decrement in performance evident as avoidance task complexity increased. Whereas measures of problem solving, response inhibition, general anxiety, and variability in attention were found to be significant predictors (in that order) of the relative decline in successful obstacle avoidance, measures of visuo-spatial discrimination and memory did not.

Accidental Falls↗
PubMed1994

Effects of depression on memory performance and metamemory in children.

OBJECTIVE: To investigate the effects of depression on memory performance and metamemory in children. METHOD: Performance on automatic memory tasks (frequency of occurrence), effortful memory tasks (Children's Auditory Verbal Learning Test), and a Metamemory Battery were examined in 21 unmedicated, depressed children and 21 nondepressed controls (matched for age, gender, and full-scale IQ). Subjects were divided into three groups based on depression severity (high depressed, low depressed, nondepressed). RESULTS: High depressed patients demonstrated performance deficits relative to nondepressed and low depressed children on the Children's Auditory Verbal Learning Test, Immediate Recall trial. Both groups of depressed children performed more poorly on the Metamemory Battery when compared to nondepressed children. Severity of depression differentiated overall performance. Metamemory performance of depressed subjects indicates possible difficulty with overestimation of memory abilities. No differences were found on automatic memory task performance. CONCLUSIONS: Memory impairment in depression varies as a function of severity and may be evident only when a certain level of depression is reached. Overestimation of memory ability by depressed children may be an attempt to compensate for feelings of inadequacy or inferiority. It may also lead depressives to use poor judgment in selecting appropriate solutions for problems. Targeting these cognitive distortions could be a focal point of clinical and educational interventions.

Attention↗
PubMed1993

Neuropsychological deficits are correlated with frontal hypometabolism in positron emission tomography studies of older alcoholic patients.

In an extension of previous work, we studied the behavioral correlates of medial frontal lobe glucose hypometabolism in chronically alcohol-dependent patients. Thirty-one male patients who were detoxified, medically stable, and free of other central nervous system risk factors for neuropsychological impairment were examined with (1) anatomic imaging (CT or MR), (2) functional imaging with [18F] fluorodeoxyglucose (18F-FDG) and positron emission tomography (PET), and (3) a battery of neuropsychological tests, including two measures of abstraction known to be generally sensitive to frontal lobe disease or dysfunction [the Wisconsin Card Sorting Test (WCST) and the Halstead Category Test (HCT)]. 18F-FDG PET data from 18 age- and sex-matched normal control subjects were used for comparison. All patients met criteria for severe alcohol dependence and for at least a mild degree of alcoholic-induced cognitive impairment. Although the mean IQ level of the alcoholic patients was in the average range, the concepts attained and the error scores on the WCST and HCT were significantly impaired in comparison with established norms. Local cerebral metabolic rate for glucose (LCMRglc) was significantly decreased in a sagittal strip of the medial frontal cortex in the alcoholic patients as compared with the normal controls. Comparison of data from PET scans and anatomic images indicated that the reduced LCMRglc could not be attributed to reduced amounts of tissue alone. A statistically significant relationship was found between LCMRglc in the medial frontal region of the cerebral cortex and performance on the WCST, but not the HCT. These findings suggest that chronic alcohol intake results in impaired function of cerebral tissue in the medial frontal region.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Neuropsychological prediction of treatment efficacy and one-year outcome in schizophrenia.

The present study was conducted to establish the degree of interrelationship between neuropsychological functioning in the acute phase of the schizophrenic illness, clinical measures of treatment response (positive and negative symptoms), and 1-year outcome. Nineteen SADS/RDC schizophrenic inpatients were clinically rated during a 2-week drug washout period and again following 4 weeks of neuroleptic treatment. The findings revealed that reduced attentional ability in the baseline phase significantly predicted the presence of higher residual negative symptoms following 4 weeks of treatment, while neurocognitive status was unrelated to positive symptom response. With respect to prediction of the 1-year outcome, poor functional status of this schizophrenic population was significantly associated with the presence of baseline memory dysfunction.

Adult↗
PubMed1993

In vivo cerebral metabolism and central benzodiazepine-receptor binding in temporal lobe epilepsy.

Positron emission tomography measured interictal cerebral glucose metabolism with [18F]fluorodeoxyglucose and central benzodiazepine-receptor binding with [11C]flumazenil in 10 mesial temporal lobe epilepsy (TLE) patients and in normal subjects. Eight TLE patients had mesial temporal, lateral temporal, and thalamic hypometabolism ipsilateral to EEG ictal onsets, with additional extratemporal hypometabolism in four. One had unilateral anterior mesial temporal hypometabolism only, and one had normal metabolism. Each patient had decreased benzodiazepine-receptor binding in the ipsilateral anterior mesial temporal region, without neocortical changes. Thus, interictal metabolic dysfunction is variable and usually extensive in TLE, whereas decreased central benzodiazepine-receptor density is more restricted to mesial temporal areas. Metabolic patterns in TLE may reflect diaschisis, while benzodiazepine-receptor changes may reflect localized neuronal and synaptic loss that is specific to the epileptogenic zone. [11C]Flumazenil imaging may be useful in presurgical evaluation of refractory complex partial seizures.

Adult↗
PubMed1993

Perceptual analysis of speech disorders in progressive supranuclear palsy.

We used oral motor examinations and quantitative perceptual speech analysis to study deviant speech dimensions in 44 patients with progressive supranuclear palsy (PSP). All patients had dysarthria with variable degrees of spasticity, hypokinesia, and ataxia; 28 patients had all three of these components, and 16 patients had only two components. Twenty-two patients (50%) had predominantly spastic components, 15 (34%) had predominantly hypokinetic components, six (14%) had predominantly ataxic components, and in one (2%) the spastic, hypokinetic, and ataxic components were equal. Stuttering occurred in nine patients (20%) and palilalia in five (11%). The finding of a mixed dysarthria with a combination of spastic, hypokinetic, and ataxic components might assist in diagnosis and is consistent with the widespread neuropathologic changes found in PSP.

Aged↗
PubMed1992

Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome.

Patients with chronic hypercortisolemia due to Cushing's syndrome (CS) exhibit cognitive dysfunction. Because glucocorticoid excess is associated with hippocampal damage in animals, and the hippocampus participates in learning and memory, we explored the relationships between hippocampal formation (HF) volume, memory dysfunction, and cortisol levels in 12 patients with CS. After magnetic resonance imaging, HF volume was determined using digital sum of track ball traces of dentate gyrus, hippocampus proper and subiculum, correcting for total intracranial volume. For 27% of the patients, HF volume fell outside the 95% confidence intervals for normal subject volume given in the literature. In addition, there were significant and specific correlations between HF volume and scores for verbal paired associate learning, verbal recall, and verbal recall corrected for full-scale IQ (r = 0.57 to 0.70, p < 0.05). HF volume was negatively correlated with plasma cortisol levels (r = -0.73, p < 0.05). These studies suggest an association between reduced HF volume, memory dysfunction, and elevated cortisol in patients with CS.

Adolescent↗
PubMed1992

Verbal fluency and positron emission tomographic mapping of regional cerebral glucose metabolism.

Impairment in verbal fluency (VF) has been a consistently reported clinical feature of focal cerebral deficits in frontal and temporal regions. More recent behavioral activation studies with healthy control subjects using positron emission tomography (PET), however, have noted a negative correlation between performance on verbal fluency tasks and regional cortical activity. To see if this negative relationship extends to steady-state non-activation PET measures, thirty-three healthy adults were given a VF task within a day of their 18F-2-fluoro-2-deoxy-D-glucose PET scan. VF was found to correlate positively with left temporal cortical region metabolic activity but to correlate negatively with right and left frontal activity. VF was not correlated significantly with right temporal cortical metabolic activity. Some previous studies with normals using behavioral activation paradigms and PET have reported negative correlations between metabolic activity and cognitive performance similar to that reported here. An explanation for the disparate relationships that were observed between frontal and temporal brain areas and VF might be found in the mediation of different task demands by these separate locations, i.e., task planning and/or initiation by frontal regions and verbal memory by the left temporal area.

Adult↗
PubMed1992

Childhood epilepsy and the role of psychology.

The relatively long history of psychology's involvement in the field of epilepsy is discussed. The view of epilepsy is that of a chronic disorder with onset in childhood, at a time when normal development is at risk for interference from the direct and secondary aspects of repetitive seizures, the neurological abnormalities from which they arise, and the clinical interventions that attempt to control them. The objective and scientifically based methods of psychology are viewed as particularly well suited to these topics. Past efforts by psychologists have increased understanding of the syndrome that is epilepsy, and have paved the way for opportunities to further contribute to the theoretically and practically important problems associated with epilepsy.

Adaptation, Psychological↗
PubMed1992

Longitudinal sensitivity of the Fuld cholinergic profile to Alzheimer's disease.

The diagnostic sensitivity of a profile (Fuld, 1984) thought to mark cholinergic changes in Alzheimer's Disease (AD) was examined in a sample of 53 patients meeting criteria for AD on two occasions and in 19 patients for three occasions. The low obtained sensitivities of the Fuld profile (17%-26%) across testings is consistent with previous studies that used a single time point. The findings also revealed unstable positive and negative profiles over time. There were no performance differences on intellectual or memory measures when comparing subjects identified as positive or negative by the Fuld index. The results demonstrate that the index is insensitive to the dementing process and is a poor diagnostic marker for AD.

Aged↗
PubMed1992

Progressive subcortical gliosis and progressive supranuclear palsy can have similar clinical and PET abnormalities.

In studies of cerebral glucose metabolism utilising positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose, patients with the clinical picture of progressive supranuclear palsy (PSP) have shown predominantly frontal glucose hypometabolism. This is presumed to represent deafferentation of cerebral cortical from subcortical structures. In these studies, however, the diagnosis of PSP has not been verified by pathological examination. Necropsy examinations were performed in three patients with the clinical features of PSP in whom PET had demonstrated predominantly frontal hypometabolism. In two of these patients the diagnosis of PSP was confirmed pathologically, and no morphological abnormalities were found in the cerebral cortex. The third patient had extensive cortical and subcortical neuronal loss and gliosis without neurofibrillary tangles, consistent with the diagnosis of progressive subcortical gliosis (PSG). Even in retrospect no unique clinical neurological abnormality or finding on laboratory investigation could be identified that distinguished this latter patient from those with pathologically confirmed PSP. We conclude that PSG and PSP may be indistinguishable during life, and necropsy confirmation is needed for definite diagnosis.

Blood Glucose↗
PubMed1990

Neuropsychological changes in olivopontocerebellar atrophy.

We used standardized neuropsychological measures of intellectual, cognitive, psychomotor, and emotional functioning to compare 39 patients with olivopontocerebellar atrophy and 25 normal controls of similar age. The patients reflected greater depression, anxiety, and subjective emotional discomfort than did the control subjects. While 4 of the patients had below-normal IQ scores (Wechsler Adult Intelligence Scale [WAIS-R] Full-Scale IQ [FSIQ] less than 80), their clinical histories suggested lifelong functioning at such levels. As a group, the patients were not abnormal in general intellectual functioning and related cognitive abilities (WAIS-R FSIQ, mean [+/- SD], 93.46 +/- 13.19; Wechsler Memory Scale mental quotient, 108.95 +/- 17.43). These scores were lower than those of the normal controls (WAIS-R FSIQ, 113.72 +/- 12.68; mental quotient, 127.80 +/- 12.40); however, the controls were a highly educated group with intelligence levels that were higher than those of the average population. Moreover, when education and motor dysfunction were statistically covaried, no significant differences between the patients and the normal controls were apparent on the cognitive and intellectual tasks. Further analysis of specific memory performance in a subgroup of patients and controls matched for age, sex, and education yielded findings that were comparable with the overall group analysis. We conclude that motor dysfunction and depressed mood could leave patients with olivopontocerebellar atrophy appearing to be impaired in memory, even demented, when they are not.

Adult↗
PubMed1990

Cerebellar and frontal hypometabolism in alcoholic cerebellar degeneration studied with positron emission tomography.

Local cerebral metabolic rate for glucose was studied utilizing 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 14 chronically alcohol-dependent patients and 8 normal control subjects of similar age and sex. Nine of the 14 patients (Group A) had clinical signs of alcoholic cerebellar degeneration, and the remaining 5 (Group B) did not have signs of alcoholic cerebellar degeneration. PET studies of Group A revealed significantly decreased local cerebral metabolic rates for glucose in the superior cerebellar vermis in comparison with the normal control subjects. Group B did not show decreased rates in the cerebellum. Both Groups A and B showed decreased local cerebral metabolic rates for glucose bilaterally in the medial frontal area of the cerebral cortex in comparison with the normal control subjects. The severity of the clinical neurological impairment was significantly correlated with the degree of hypometabolism in both the superior cerebellar vermis and the medial frontal region of the cerebral cortex. The degree of atrophy detected in computed tomography scans was significantly correlated with local cerebral metabolic rates in the medial frontal area of the cerebral cortex, but not in the cerebellum. The data indicate that hypometabolism in the superior cerebellar vermis closely follows clinical symptomatology in patients with alcoholic cerebellar degeneration, and does not occur in alcohol-dependent patients without clinical evidence of cerebellar dysfunction. Hypometabolism in the medial frontal region of the cerebral cortex is a prominent finding in alcohol-dependent patients with or without alcoholic cerebellar degeneration.

Adult↗
PubMed1990

Anxiety and cerebral cortical metabolism in normal persons.

The State-Trait Anxiety Inventory (STAI) was administered to 43 normal volunteers immediately before and after a positron emission tomography (PET) procedure with [18F]-2-fluoro-2-deoxy-D-glucose (18F-FDG). High trait-anxious individuals had significantly higher state (situational) anxiety associated with the PET scan procedure than did low trait-anxious persons. State anxiety decreased significantly for all respondents following the PET scan procedure. No significant relationships between global or regional cortical metabolic rates and state anxiety were observed. The direct cortical metabolic effects of heightened anxiety in the scan setting, should they exist, are likely obscured in the normal variance of the 18F-FDG method.

Adolescent↗