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Biomedical subjects

B R Reed

Publications and source records attributed to B R Reed.

10 recordsLinked to original sources

Cognitive function and regional cerebral blood flow in Parkinson's disease.

In order to investigate relationships between cognition and regional brain function, we studied 20 non-demented patients with idiopathic Parkinson's disease (PD), 21 mildly demented patients with Alzheimer's disease (AD) and 24 control subjects using cognitive testing and single photon emission computerized tomographic (SPECT) measurements of relative regional cerebral blood flow (rCBF). Neuropsychological tests were grouped into clusters reflecting frontal lobe executive abilities, perseveration, memory and visuospatial ability, with a summary score summarizing performance in all four of these spheres. SPECT imaging utilized the tracer [123I]N-isopropyl-p-iodoamphetamine with a relative measure of regional tracer uptake normalized to occipital radiotracer uptake (rCBF ratios). Patients with PD performed more poorly than controls in all cognitive domains, and were intermediate to AD patients and controls in tests of memory and overall cognitive functioning. Those PD patients who performed most poorly on neuropsychological testing showed lowest rCBF ratios in left and right temporal lobes. Using a stepwise multiple regression procedure, we examined patterns of correlations between cognitive clusters and predictor variables, including rCBF ratios, in the PD patients. We found that while patient age was a strong determinant of performance on the memory cluster and the summary score, dorsolateral frontal lobe perfusion and scores on a depression inventory accounted for a greater proportion of the variance of the frontal lobe and perseveration clusters than did age. These results imply that different neural mechanisms are responsible for the different aspects of cognitive decline seen in PD patients, with overall cognitive function closely related to age and temporal perfusion, while frontal lobe abilities are more linked to frontal perfusion and the presence of depression.

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Sunscreen Q & A.

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Humans

Diminished glucose transport in Alzheimer's disease: dynamic PET studies.

Dynamic positron emission tomography with [18F]fluorodeoxyglucose was used in six patients with Alzheimer's disease (AD) and seven healthy age-matched control subjects to estimate the kinetic parameters K1*, k2*, and k3* that describe glucose transport and phosphorylation. A high-resolution tomograph was used to acquire brain uptake data in one tomographic plane, and a radial artery catheter connected to a plastic scintillator was used to acquire arterial input data. A nonlinear iterative least-squares fitting procedure that included terms for the vascular fraction and time delay to the peripheral sampling site was used to fit a three-compartment model to the brain data. Regions studied included frontal, temporal, occipital, and the entire cortex and subcortical white matter. The values obtained for the individual rate constants and regional CMRglc (rCMRglc; calculated using regional values of the rate constants) were higher than those reported previously. A significant (p less than 0.05) decrease was found in K1* in frontal and temporal cortex in the AD patients compared with the controls, with values of 0.157 and 0.161 ml/g/min in frontal and temporal cortex, respectively, of controls and 0.127 and 0.126 ml/g/min in frontal and temporal cortex of the AD patients. rCMRglc was also significantly (p less than 0.02) lower in the AD patients than controls in all cortical brain regions. Lower values of k3* were found in all brain regions in the AD patients, although these were not statistically significant. These findings provide evidence of an in vivo abnormality of forward glucose transport in AD.(ABSTRACT TRUNCATED AT 250 WORDS)

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Low incidence of antibodies to recombinant human tissue-type plasminogen activator in treated patients.

Sera from over 1,600 patients who received recombinant human tissue plasminogen activator (rt-PA) during clinical trials were assessed for the presence of antibodies to this therapeutic agent. The rt-PA was administered by a variety of dosage regimens for several different indications. Two different forms of rt-PA were used; one was predominantly two chain form, and the other was a predominantly one chain form. A sensitive radioimmunoprecipitation assay was used to measure antibodies to rt-PA in patients' serum before and after treatment. Of 932 patients tested with this assay, 929 were negative for antibodies to t-PA. Three patients developed low titers after treatment. Additional serum samples were obtained from these three patients within 2 years after rt-PA therapy and were negative for antibodies to t-PA. With the limited number of positive samples, no correlation could be found with dose or type of rt-PA, dosing regimen or clinical diagnosis. The virtual absence of antibody formation was confirmed in an additional 754 patients using a novel competitive two-site ELISA. It can be concluded that a single infusion of rt-PA was virtually unassociated with antibody formation, suggesting that repeat treatments could be given when necessary without the risk of immunologic complications as are seen with streptokinase or its derivatives.

Animals

Alzheimer's disease. Age at onset and single-photon emission computed tomographic patterns of regional cerebral blood flow.

We performed this study to determine whether early- and late-onset Alzheimer's disease differ physiologically. Ten patients with a presenile (before 65 years old) onset of the disease and 16 with senile onset of the disease were evaluated clinically and neuropsychologically and studied with single photon emission computed tomography using the blood flow tracer [123I]N-isopropyl-p-iodoamphetamine. Although the presenile subjects had more severe neuropsychological abnormalities in all realms of cognitive function, including language, and showed greater reductions in regional blood flow than the older patients, they were also more severely demented, thus complicating interpretation of the results. Two indexes of cerebral perfusion, a ratio of regional flow compared with occipital flow and a left-right asymmetry index, demonstrated relative left frontal hypoperfusion in presenile- but not senile-onset patients and did not appear to be an artifact of the severity differences. Although no asymmetry of cognitive function was noted, the perfusion asymmetry provides biological evidence for an alteration in left-hemisphere function in patients with the early onset of Alzheimer's disease.

Age Factors

Effects of caring for a demented relative on elders' life events and appraisals.

Weekly ratings of events and appraisals were collected from 19 caregivers of dementia patients and 19 control subjects over 4 weeks. Caregivers reported more negative events overall and rated them as more undesirable than did control subjects, but significant differences were found in events of only 2 of the 11 life areas that were measured. Caregivers' negative appraisals were more frequent and more intense than those of control subjects in virtually every life area. These preliminary data fail to demonstrate a global disruption of caregiver's activities and suggest the importance of appraisals in determining the impact of caregiving.

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Focal Alzheimer's disease.

Alzheimer's disease is characterized by relative sparing of primary sensory and motor cortex and a lack of sensory or motor symptomatology. We report a case of presenile onset dementia accompanied by a slowly progressive hemiparesis. Autopsy examination showed severe pathologic involvement of somatosensory cortex with neuritic plaques and neurofibrillary tangles, in addition to degeneration of the nucleus basalis and locus ceruleus. Neurochemical and immunocytochemical studies showed a moderate cortical cholinergic deficiency with normal somatostatin-like immunoreactivity and a profuse immunostaining of somatosensory cortex with the Alz-50 antibody. These unusual features emphasize that Alzheimer's disease is extremely variable in its clinical symptomatology, pathologic distribution, and neurochemical dimensions.

Alzheimer Disease

Experimental canine anaphylaxis: cyclic nucleotides, histamine, and lung function.

We studied the effects of Ascaris suum antigen (iv) in 32 natively allergic, anesthetized dogs. After thoracotomy, bilateral cervical vagotomy, and propranolol, samples of peripheral lung frozen in situ were obtained for measurement of cyclic nucleotides and histamine. Following Ascaris, lung histamine decreased 20.4 +/- 3.7% (mean +/- SE), cAMP increased 391 +/- 122%, and cGMP increased 110 +/- 20% with increased plasma histamine and physiological changes of anaphylaxis. No significant changes occurred in 10 control dogs. Release of histamine, reflecting immunological degranulation of mast cells, correlated closely with the physiological effects of anaphylaxis. beta-Adrenergic stimulation with isoproterenol prevented these physiological effects of anaphylaxis in three dogs studied. Furthermore, the level of cAMP induced in lung tissue by beta-adrenergic stimulation in these dogs correlated with the degree of inhibition of immunologically induced histamine release. These results illustrate the suitability of this experimental preparation to study the biochemical and physiological mechanisms of anaphylaxis in vivo.

Anaphylaxis

Reduced temporal lobe blood flow in Alzheimer's disease.

We used single photon emission computed tomography with the blood flow tracer [123I]N-isopropyl-p-iodoamphetamine (IMP) to study regional cerebral blood flow (rCBF) in 50 mildly and moderately demented Alzheimer's disease (AD) patients to evaluate rCBF as a function of disease severity. Relative rCBF (normalized to occipital cortex) was significantly lower than controls in temporal cortex for both mildly and moderately demented patients. Similar numbers of patients in both groups demonstrated perfusion abnormalities in temporal neocortex. Parietal cortex was more variably involved with greater numbers of moderately than mildly demented patients showing perfusion abnormalities. Relative rCBF in dirsolateral frontal cortex was reduced only in the moderately demented patients. Disease severity, as measured by the Mini Mental Status Examination, was associated with relative rCBF only in dorsolateral frontal and parietal cortex. These results suggest that the temporal lobes are the first neocortical regions affected by AD and that other cortical areas become involved as the disease progresses.

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