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Biomedical subjects

P Fedio

Publications and source records attributed to P Fedio.

At least 37 records · Page 2Linked to original sources
PubMed1987

Alzheimer's disease: low cerebral somatostatin levels correlate with impaired cognitive function and cortical metabolism.

Somatostatin-like immunoreactivity in Alzheimer CSF was significantly lower than in that from age-matched controls. The degree of reduction correlated with indices of intellectual impairment and decline in cortical glucose utilization as determined by PET. There was a close association between reduction in CSF somatostatin and glucose hypometabolism in the parietal lobe. In postmortem cortical tissue from Alzheimer patients, somatostatin levels were lower in posterior parietal but not in anterior frontal cortex. Loss of somatostatin-containing neurons, especially in the parietal association cortex, may be a critical determinant for Alzheimer dementia.

Alzheimer Disease↗
PubMed1986

Muscarinic agonist therapy of Alzheimer's disease. A clinical trial of RS-86.

Cholinergic projections to the cerebral cortex from certain basal forebrain nuclei degenerate in Alzheimer's disease. Nevertheless, attempts to alleviate this disorder through the administration of drugs that increase the availability of acetylcholine to postsynaptic receptor sites have generally yielded disappointing results. In an attempt to evaluate the therapeutic efficacy of cholinomimetics that act independently of the presynaptic cholinergic terminals, a double-blind, placebo-controlled trial of the muscarinic agonist RS-86 (2-ethyl-8 methyl-2,8 diazospiro [4.5]-decane-1,3-dione hydrobromide) was undertaken. Eight patients with Alzheimer's disease with mild to moderately advanced dementia received RS-86 orally at maximum individually tolerated dose levels for eight days. Although some verbal and visuospatial tests showed slight alterations, no consistent overall change in cognitive performance could be discerned. These results lend further support to the view that short-term administration of cholinomimetic monotherapies may fail in the symptomatic treatment of Alzheimer's dementia.

Aged↗
PubMed1986

Reye's syndrome. Salicylate metabolism, viral antibody levels, and other factors in surviving patients and unaffected family members.

To investigate possible etiologic factors for Reye's syndrome (RS), five survivors and their unaffected family members were studied. This study showed low salicylate levels among the patients with RS compared with siblings and parents when challenged with three doses of aspirin. Thus, the patients with RS, three to ten years after having had RS, exhibited normal or increased ability to metabolize aspirin. We found significantly higher antibody levels to influenza A and varicella among the patients with RS, further supporting the importance of these viral infections in the etiology of the syndrome.

Adolescent↗
PubMed1986

Cerebral mapping of apraxia in Alzheimer's disease by positron emission tomography.

The ability to mimic skilled movements or to pantomime them in response to spoken command was compared with psychometric performance and with regional glucose utilization as estimated by [18F]fluorodeoxyglucose positron emission tomography in 17 right-handed patients with Alzheimer's disease and 6 age-matched normal subjects. Apraxia scores, both on tests to command and to imitation, were significantly lower in the Alzheimer patients. Imitation scores correlated best with performance on tests of visual--spatial ability and with cortical metabolism in the right parietal lobe; command scores related most closely with the results of tests reflecting verbal proficiency and with cortical metabolism in the left inferior hemisphere, especially frontally. Apraxia to command and imitation may thus reflect neuronal dysfunction in distinct cerebral regions in patients with Alzheimer's disease.

Aged↗
PubMed1986

Towards a behavioral typology of Alzheimer's patients.

Neuropsychological test performance and estimates of regional rates of cortical glucose metabolism obtained via positron emission tomography are presented for patients with Alzheimer's disease (AD). Analyses of these data indicated the presence of distinct subgroups characterized by qualitatively different profiles of cognitive impairment and corresponding patterns of cerebral hypometabolism. No subgroup differences were noted with regard to age at onset or reported duration of symptoms. These findings indicate that, in a given individual, AD may initially invade a relatively circumscribed cortical region. Thus, although AD may constitute a single disease process, it does not result in a unitary neuropsychological syndrome.

Adult↗
PubMed1986

GABA-agonist therapy for Alzheimer's disease.

Evidence suggesting a reduction of cerebral gamma-aminobutyric acid (GABA) neurons in Alzheimer's disease has been reported. To evaluate the possible contribution of GABA system dysfunction to the intellectual decline associated with this disorder, a controlled therapeutic trial of a potent and specific GABA agonist, THIP [4,5,6,7-tetrahydroisoxazolo(5,4,-c)pyridin-3-ol], was undertaken. Six Alzheimer patients with mild to moderately severe dementia and low spinal-fluid GABA levels received THIP at maximum individually tolerated dosage. No significant change in cognitive function could be discerned, despite attainment of dose levels that produced centrally mediated adverse effects similar to those of other GABA agonists. The results support the views that pharmacologic attempts to stimulate central GABA-mediated synaptic function may not confer therapeutic benefit to patients with Alzheimer's disease and that a GABA system deficit may not serve as a critical determinant of the dementia that characterizes this disorder.

Alzheimer Disease↗
PubMed1986

Huntington's disease: effect of cysteamine, a somatostatin-depleting agent.

Somatostatin levels in the basal ganglia are elevated in Huntington's disease. A controlled therapeutic trial of the somatostatin-depleting agent, cysteamine, was therefore conducted in five patients, including one with the rigid-akinetic form. Maximum tolerated dosage for 2 weeks produced no consistent change in extrapyramidal or dementia scores. Somatostatin concentrations were not significantly altered in plasma or CSF. Growth hormone levels, on the other hand, more than doubled, suggesting a functionally significant decrease in central somatostatin levels.

Adult↗
PubMed1985

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↗
PubMed1985

Long-term neuropsychologic sequelae of childhood leukemia: correlation with CT brain scan abnormalities.

Previous studies have failed to establish a direct relationship between behavioral disorders and organic pathology in long-term survivors of childhood acute lymphoblastic leukemia. We evaluated 23 long-term survivors who received central nervous system preventive therapy with cranial irradiation and intrathecal chemotherapy, using neuropsychologic tests and computed tomographic brain scans. The patients were in continuous first remission for 7 to 11 years, and none were receiving chemotherapy. On the basis of their CT scan findings, they were divided into three groups: 10 with normal CT findings, five with intracerebral calcifications, and eight with cortical atrophy. Neuropsychologic test results allowed prediction of CT scan findings with an 87% accuracy (P less than 0.001), indicating a strong correlation between the presence and type of CT scan abnormality and neuropsychologic functioning. Tests that measured verbal memory, attention, and functions correlated with frontal lobe integrity were most powerful in discriminating between groups.

Adolescent↗
PubMed1984

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↗
PubMed1984

Wechsler Adult Intelligence Scale performance. Cortical localization by fluorodeoxyglucose F 18-positron emission tomography.

We compared local cerebral glucose metabolism, as determined by positron emission tomography following administration of fluorodeoxyglucose F 18, with Wechsler Adult Intelligence Scale (WAIS) scores in 22 right-handed persons. Five study subjects were normal volunteers and the remainder had Alzheimer's disease. Subtest scores within the verbal IQ group or the performance IQ group were generally highly interrelated; there was usually no correlation between the verbal and performance subtests. The cortical distribution of regions in which glucose metabolism was most closely associated with verbal subtest scores generally centered in the left parasylvian area. In contrast, scores on the performance subtests mainly localized to the right posterior parietal region. Most WAIS subtests thus appeared to evaluate primarily either verbal or visuospatial cognitive functions and either left parasylvian or right posteroparietal cortical activity.

Aged↗
PubMed1984

Resumption of behavior following intracarotid sodium amobarbital injection.

Recovery rates of selected behaviors following intracarotid sodium amobarbital injection were examined in 17 patients with unilateral focal temporal lobe epilepsy. Left hemisphere injections resulted in more prolonged disruption of naming (p less than 0.00001), reading (p less than 0.0001), matching-to-sample behaviors (p less than 0.05), and short-term recognition memory for pictures (p less than 0.0001) and words (p less than 0.0003) than did right hemisphere injections. In addition, recovery of behaviors was prolonged if the injection was administered to the hemisphere contralateral to that with the primary seizure focus (p less than 0.005). A trend toward a similar pattern was seen in the postinjection electroencephalogram with the maximum slowing found in the injected hemisphere prolonged if the epileptic focus was in the contralateral hemisphere (p = 0.06). These findings suggest a negative effect of an epileptic lesion on the contralateral hemisphere.

Amobarbital↗
PubMed1984

Regional cortical dysfunction in Alzheimer's disease as determined by positron emission tomography.

Local cerebral glucose metabolism and psychometric function were compared in 17 patients with Alzheimer's disease and 5 healthy age-matched controls. Performance on tests of global intellectual function averaged 30 to 45% lower in the Alzheimer's group. Mean cortical glucose metabolism, as determined by positron emission tomography following fluorine-18-labeled fluorodeoxyglucose administration, was reduced by 30% in the Alzheimer's group. There was a significant positive correlation between the degree of overall dementia and the amount of metabolic reduction. The distribution of cortical hypometabolism was not uniform: the posterior parietal lobes and contiguous portions of the posterior temporal and anterior occipital lobes were most severely involved. The frontal cortex was relatively spared. These findings are compatible with the major clinical deficits found in patients with Alzheimer's disease and may help focus future biochemical probes into the pathophysiology of this disease.

Alzheimer Disease↗