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Biomedical subjects

N R Cutler

Publications and source records attributed to N R Cutler.

At least 127 records · Page 7Linked to original sources
PubMed1985

Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography.

The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.

Adolescent↗
PubMed1985

Computed tomographic analysis of brain morphometrics in 30 healthy men, aged 21 to 81 years.

Computed transverse axial tomography (CT) was employed to examine brain morphometrics in 30 healthy men, aged 21 to 81 years. Seven consecutive CT slices 30 to 80 mm above the inferior orbitomeatal line were analyzed. CT numbers in gray and white matter regions were not correlated significantly with age (p greater than 0.05), nor were right/left ratios for derived parameters. The volume of gray matter was correlated negatively with age (p less than 0.05), and the volume of cerebrospinal fluid correlated positively with age, in the seven slices. The volumes of the lateral and third ventricles were elevated in the elderly, and volumes of the thalamus and lenticular nucleus were reduced. The results demonstrate that brain atrophy, evidenced by a loss of gray matter and by dilatation of cerebrospinal fluid spaces, occurs in the healthy elderly, and provide baseline CT-derived brain morphometric data for healthy men in relation to age.

Adult↗
PubMed1985

Clinical history, brain metabolism, and neuropsychological function in Alzheimer's disease.

Data concerning 7 patients with a diagnosis of presumptive Alzheimer's disease (mean age, 65.6 years) are presented in detail in relation to the patients' regional cerebral metabolic rates for glucose. Rates were measured by positron emission tomography with fluorine 18-labeled fluoro-2-deoxy-D-glucose under conditions of reduced visual and auditory stimulation. A relationship was found between severity of dementia and brain metabolism. In patients with mild to moderate Alzheimer's disease, memory and intellectual deficits were evident without major reductions in absolute metabolic rates, while ratios of regional to whole brain metabolism revealed reductions in regions of the parietal lobes. In the late, severe form of the disease, brain metabolic rates were consistently and significantly reduced. The findings suggest that memory and intellectual deficits are reflected in reductions of brain metabolism in some brain regions in mild to moderate forms of Alzheimer's disease and that, in the late, severe form of the disease, reductions occur consistently throughout the brain.

Aged↗
PubMed1985

Salicylate protein binding in serum from young and elderly subjects as measured by diafiltration.

The protein binding of salicylate was measured by continuous ultrafiltration (diafiltration) at 22 degrees C in serum obtained from 5 healthy young (mean age: 27 years) and 5 healthy elderly (mean age: 73 years) male volunteers. Unbound salicylate increased disproportionately with increasing total salicylate concentration, up to 7000 mumol, in all sera. The fraction bound of salicylate was significantly lower in sera from elderly but this was not due to decreased albumin or total protein concentrations. The binding of salicylate to serum proteins was characterized by two classes of binding sites. The high affinity site had an association constant of either 9490 l/mol (young) or 7560 l/mol (elderly) and the number of binding sites was either 4.7 (young) or 3.7 (elderly). The total binding capacity of the low affinity site, 112 l/mol, in sera from elderly was significantly less than the binding capacity, 631 l/mol, in sera from young. Differences in binding capacity of the low affinity site partially accounted for a two to three-fold increase in the salicylate free fraction in elderly sera. These data suggest that age-related differences in serum protein binding may influence salicylate pharmacokinetics.

Adult↗
PubMed1985

Relations between neuropsychological and cerebral metabolic asymmetries in early Alzheimer's disease.

Regional CMRglc (rCMRglc) values were determined with positron emission tomography (PET) in 10 patients with mild to moderate clinically diagnosed Alzheimer's disease (AD) and in 26 healthy controls. rCMRglc in frontal, parietal, and temporal association cortices were significantly more laterally asymmetrical in AD patients than in controls (p less than 0.05). Furthermore, lateral asymmetry of rCMRglc in AD patients but not in the control subjects correlated significantly with asymmetry of language and visuospatial functions such that lower left than right rCMRglc was associated with relatively greater impairment of language and vice versa. The results demonstrate that discrepancies between language and visuospatial deficits in patients with early AD are related to asymmetrical reductions in cerebral cortical glucose metabolism.

Aged↗
PubMed1985

Brain metabolism as measured with positron emission tomography: serial assessment in a patient with familial Alzheimer's disease.

This paper presents, for the first time, repeated assessments of cerebral metabolism and neuropsychological competence in early Alzheimer's disease. Regional cerebral metabolic rates for glucose were measured with positron emission tomography and 18F-fluoro-2-deoxy-D-glucose on three occasions at 8-month intervals, in a 57-year-old man with Alzheimer's disease of 2 1/2 years' duration and with a family history of neuropathologically confirmed Alzheimer's disease. Data were compared with mean cerebral metabolic rates from 12 healthy men. No differences in regional cerebral metabolic rates for glucose were found on the initial patient scan, whereas metabolism on the second and third scans was reduced significantly in the parietal lobes and bilaterally in some parietal lobe regions. Memory loss was demonstrable at the first scan, but then and at later scans, other aspects of cognitive performance remained within normal limits (Wechsler Adult Intelligence Scale, Boston Naming Test, Two-dimensional Block Construction). The results show that memory loss can precede a measurable reduction of cerebral metabolism in early Alzheimer's disease, but that later reductions in parietal lobe metabolism may not be accompanied by additional measurable neuropsychological deficits.

Aged↗
PubMed1985

NIH Conference. Alzheimer's disease and Down's syndrome: new insights.

Neuropathologic and neurochemical studies of older adults with Down's syndrome and those with Alzheimer's disease reveal striking similarities. Genetic studies indicate that near relatives of patients with Alzheimer's disease are at increased risk of developing Alzheimer's disease, and the risk appears to be age specific. These families with familial Alzheimer's disease have also been found to have a high incidence of Down's syndrome. Neurochemical data suggest that a cholinergic deficiency must be present for dementia to develop, and serial assessments of brain metabolic function with positron emission tomography in Alzheimer's disease have shown that the parietal lobe has reductions in metabolic function before the onset of neuropsychologic deficits in this brain region. Neuropsychologic testing indicates that patients with Down's syndrome over 35 years old have poorer cognitive skills than do younger patients. Brain metabolic function is excessively reduced in the demented adults with Down's syndrome.

Adult↗
PubMed1984

Creutzfeldt-Jakob disease: a case of 16 years' duration.

A 46-year-old man with Creutzfeldt-Jakob disease confirmed postmortem had a 16-year course of very slowly progressing incoordination and mental deterioration, suggesting Alzheimer's disease. The disease course transformed abruptly into a 7-week terminal phase of florid Creutzfeldt-Jakob disease. Dementing illnesses of unknown cause were present in the patient's paternal lineage.

Brain↗
PubMed1984

Human brain glucose utilization and cognitive function in relation to age.

Brain oxidative metabolism was examined with positron emission tomography and [18F]2-deoxy-D-glucose in 40 healthy men aged 21 to 83 years, under conditions of reduced visual and auditory stimulation. The mean cerebral metabolic rate for glucose (CMRglc) equaled 4.6 to 4.7 mg X 100 gm-1 X min-1 and did not correlate significantly with age (p greater than 0.05). Regional cerebral metabolic rates for glucose (rCMRglc) and Q ratios (rCMRglc/CMRglc), which had lower coefficients of variation than did rCMRglc, also did not correlate with age. Hyperfrontality of cerebral metabolism was absent at all ages. Age decrements were demonstrated in the error score on the Benton Revised Visual Retention Test and in the Performance Subtest scaled score of the Wechsler Adult Intelligence Scale (WAIS) but not in the Verbal Subtest scaled score of the WAIS. The cognitive test scores did not correlate with brain metabolic rates. The results indicate that brain oxidative metabolism, when measured under resting conditions with reduced sensory input, is not reduced in relation to age in healthy men. Furthermore, no significant relations between intelligence and resting cerebral metabolism are evident.

Adult↗
PubMed1984

Neuroendocrine responses to apomorphine in depressed patients and healthy control subjects.

Increasing evidence implicates altered dopamine function in major affective illness. In the present study, growth hormone responses to the dopamine agonist apomorphine were not different for 14 male depressed patients and 16 healthy male volunteers. Baseline and post-apomorphine prolactin levels were lower for the depressed patients than the control subjects, but the percent decrease following apomorphine was not different for the two groups. Neuroendocrine responses were not significantly altered during chronic treatment with the dopamine agonist piribedil. These neuroendocrine results suggest that decreased baseline prolactin levels in depressed patients do not reflect altered postsynaptic receptor sensitivity in the tuberoinfundibular dopamine system.

Adult↗
PubMed1984

Low dose bromocriptine: a study of acute effects in chronic mediated schizophrenics.

An acute low oral dose (2 mg) of bromocriptine was administered in a randomized double blind fashion to 11 chronic symptomatic mediated schizophrenic patients. There was an overall improvement for the group on the Brief Psychiatric Rating Scale (BPRS) following bromocriptine. Plasma homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, and vanilloyl-mandelic acid concentrations were unchanged after bromocriptine. Bromocriptine concentrations in the plasma showed a large inter-individual variation. There was a significant inverse correlation between plasma bromocriptine concentration and total BPRS score at 60 minutes post-bromocriptine administration. These results suggest a need for further replication in a larger study population and a need for controlled studies with chronic administration of low dose bromocriptine in chronic medicated schizophrenic patients.

Adult↗
PubMed1984

Alterations in auditory processing of speech stimuli during aging in healthy subjects.

Studies of auditory processing during aging in man have not provided a consensus on whether aging affects the ability to process speech stimuli. To evaluate the relationship between speech recognition tasks and age, we examined 36 male subjects between the ages of 21 and 83 years, who were screened for the absence of disease, particularly in the cardiovascular and neurologic systems. Measures were obtained on the following tests: pure tone thresholds, speech reception threshold, speech discrimination, low-pass filtered speech, and binaural fusion. A statistically significant correlation was found between pure tone thresholds and age for all frequencies. When the effect of peripheral hearing loss was taken into account, speech measures did not correlate with age, with the exception of low-pass filtered speech in the left ear. Our findings suggest that the aging process in healthy man is not necessarily accompanied by deficits in the processing of speech stimuli beyond those which are due to peripheral hearing loss.

Adult↗
PubMed1984

Vancomycin disposition: the importance of age.

We examined the influence of age on vancomycin kinetics in 12 normal healthy men (six young and six elderly) after an intravenous infusion of 6 mg/kg. Serial blood and urine samples were collected for up to 2 days after dosing and were assayed for unchanged drug by a specific radioimmunoassay. Serum concentrations of vancomycin after infusion declined in a multiphasic manner. Both serum and urinary excretion data were simultaneously fit by a three-compartment model with SAAM-27 computer programs. Estimates of mean t1/2 obtained from the terminal phase of the drug disposition profile showed the t1/2 to be longer in the elderly than in the young subjects (12.1 and 7.2 hr). Although there was no change in the initial distribution volume of the central compartment, total systemic and renal clearances were reduced in the elderly and did not correlate with renal function. The increase in the vancomycin volume of distribution at steady state was ascribed to enhanced tissue binding of drug in the elderly, since the mean fraction of vancomycin bound in systemic pool of the young and elderly did not differ (0.53 and 0.56). In-depth analysis of excretion data tends to support suggestions of vancomycin excretion solely by glomerular filtration. Our data strongly suggest the need for adjustment or modification of recommended vancomycin dosing schedules in the elderly.

Adult↗
PubMed1984

Peripheral catecholamine enzyme function and cognitive impairment of elderly schizophrenics and controls.

Alterations of peripheral and central catecholamine systems are found in both schizophrenic and demented subjects. Reported here are the results of bivariate and multivariate analyses of cognitive function and peripheral catecholamine enzyme activities in a group of elderly schizophrenic patients and controls. The entire sample shows an inverse relationship of platelet monoamine oxidase (MAO) activity with cognitive impairment after controlling for the effects of age, race, and gender. Schizophrenic subjects also demonstrated an inverse relationship of plasma dopamine beta hydroxylase (DBH) activity with cognitive impairment. Demented subjects were characterized in both groups as having increments in platelet MAO activity. Demented schizophrenic subjects also were characterized by increments in plasma DBH activity. Results from this sample are discussed with respect to findings from other studies and future research.

Aged↗
PubMed1984

NIH Conference. Brain imaging: aging and dementia.

The brain imaging techniques of positron emission tomography using [18F]-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings.

Adult↗
PubMed1984

Combined immunochemical and electrophoretic determinations of proteins in paired serum and cerebrospinal fluid samples.

Albumin and immunoglobulin G were simultaneously determined in paired serum and cerebrospinal fluid samples from healthy volunteers. The albumin quotient and the IgG index were calculated to establish normal values. High-resolution electrophoresis was also performed with the same samples and the electrophoretic patterns were correlated with the numerical values to improve the reliability of the test results. Representative examples from abnormal conditions are also shown, to illustrate the increased accuracy and useful applications of this combined analysis in the diagnosis of neurological conditions.

Adult↗