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Biomedical subjects

J Kessler

Publications and source records attributed to J Kessler.

At least 127 records · Page 7Linked to original sources

Impaired metabolic activation in Alzheimer's disease: a PET study during continuous visual recognition.

Regional cerebral metabolic rate of glucose (rCMRGl) was studied in 21 patients with probable Alzheimer's disease (AD) and nine age-matched normal controls by positron emission tomography (PET) of 2(18F)-fluoro-deoxy-D-glucose (FDG) at rest and during stimulation with a continuous visual recognition task. While global metabolism at rest was comparable in both groups, rCMRGl in the temporo-parietal junction area, the mid-temporal and the frontal cortex was typically decreased in the AD patients. The continuous visual recognition task adapted to the individual performance capacity increased the global metabolic rate in the controls by 21 +/- 18%, while in the AD patients the metabolic change (5.7 +/- 11.1%) during activation was significantly weaker (P = 0.023). Due to the tasks chosen the activation of rCMRGl in both groups was most prominent in the visual cortex and the temporo-parietal association areas, although the recognition task additionally involved widespread brain structures with varying rCMRGl. A significant correlation was found between rCMRGl in areas usually severely affected by AD pathology, e.g. the temporo-parietal cortex, and GDS scores, and became stronger during metabolic activation. Neither at rest nor during stimulation was there a relationship between the rCMRGl of structures usually less involved in AD, e.g. the sensorimotor cortex, and the severity of dementia as assessed by the global deterioration scale (GDS). From these results it can be concluded that metabolic rate at rest reflects the extent of morphologic damage, while PET studies during activation indicate the brain's reserve capacity to respond to functional tasks. Since metabolism in AD patients during activation is more severely impaired than at rest, PET studies during functional tests could help in the selection of patients with a potential to benefit from therapeutic intervention.

Alzheimer Disease↗

Abnormalities of energy metabolism in Alzheimer's disease studied with PET.

Positron emission tomography (PET) is currently the only technology affording three-dimensional measurement of the brain's energy metabolism which is closely coupled to brain function. Studies of glucose metabolism by PET of (18F)-2-fluoro-2-deoxy-D-glucose are therefore widely applied to show the contribution of various brain structures in the performance of a variety of tasks or their participation in functional deficits associated with various diseases. Although glucose metabolism decreases slightly with age to a regionally different degree, most types of dementia show severe changes in glucose metabolism. Alzheimer's disease (AD) is characterized by metabolic disturbances most prominent in the parietotemporal association cortex and later in the frontal lobe, whereas primary cortical areas, basal ganglia, thalamus, brainstem, and cerebellum are not affected. It is this typical pattern that distinguishes AD from other dementia syndromes. A ratio calculated from the metabolic rates of glucose of "affected" and "nonaffected" brain regions was able to separate patients with AD from age-matched controls and permitted the discrimination of patients with cognitive impairment of other origin in 85%. The discriminative power can be further improved by activation studies. A continuous visual recognition task increased the metabolic rate in normal subjects by 21% and in patients with AD by 6% on average, with significant regional differences. During activation the significant relation between severity of disease and temporoparietal metabolic rate became even stronger. In the assessment of effects of treatment on disturbed metabolism, PET studies demonstrated an equalization of metabolic heterogeneities in patients responding to a muscarinergic cholinagonist, whereas general increases in glucose utilization were observed with piracetam, pyritinol, and phosphatidyl-serine. The therapeutic relevance of such metabolic effects, however, must be proved in controlled clinical trials.

Adult↗

Complex sensory cross integration deficits in a case of corpus callosum agenesis with bilateral language representation: positron-emission-tomography and neuropsychological findings.

A 45-year-old right-handed patient with total callosal agenesis and absence of the anterior commissure was examined neuropsychologically and with magnetic resonance and positron emission tomography (PET with 18FDG) of the brain. PET results showed, in the resting state, a bilateral metabolic reduction in the hippocampal formation and a left hemispheric reduction in the amygdala, thalamus and in the occipital and temporoparietal junction areas of the cerebral cortex. Under speech activation hypermetabolic glucose activity was observed bilaterally in the region of the Wernicke area and within the left Broca area. Neuropsychologically, on the whole the patient behaved normally, the exceptions being an inability to associate olfactory stimuli with words, a clear left ear advantage in dichotic listening, and a similar high performance in recognizing verbal stimuli presented tachistoscopically to either hemisphere. From comparing the patient's behavior with that of other acallosals it appears that highly individual variants of cerebral organization and/or reorganization result from the lack of the brain's main commissural system and that the processing of sensory information deviates considerably especially in cases in whom the two main telencephalic commissures--corpus callosum and anterior commissure--are absent.

Brain↗

Positron emission tomography findings relevant to neurosurgery for epilepsy.

Using the 2-[F-18]fluorodeoxyglucose method, 213 positron emission tomographic (PET) studies of local brain glucose metabolism (CMRglu) were performed in 124 patients with various forms of epilepsy. Interictal PET scans of primary epileptics typically showed some global metabolic depression and decreased functional activity of insular, basal and anterior temporal cortex. Epilepsia partialis continua Kozevnikov was characterized by hypo- or hyper-metabolism of perirolandic cortex. Tuberous sclerosis was distinguished by neocortical foci of significantly decreased glucose consumption. Even in the interictal resting state, with regard to sensitivity (greater than 90%) and accuracy of focus localization. PET was superior to other diagnostic methods in typical temporal lobe epilepsy. Averaging 23% below normal CMRglu, the majority of hypometabolic foci were found in mesial temporal structures. Improved distinction between the epileptogenic area and the surrounding tissue showing comparatively normal functional responsiveness, was achieved by psychophysical activation using emotional speech or continuous visual recognition during PET scanning. In patients who had undergone total cerebral hemispherectomy because of uncontrolled epilepsy, remarkable recruitment of association areas was observed on both motor and speech activation.

Blood Glucose↗

Antibody-mediated in vitro neutralization of human immunodeficiency virus type 1 abolishes infectivity for chimpanzees.

This study was undertaken to establish whether antibody directed against the human immunodeficiency virus type 1 (HIV-1) principal gp120 type-specific neutralization determinant can abolish the infectivity of HIV-1 in chimpanzees. Challenge inocula of the IIIb virus isolate were mixed in vitro with either immunoglobulin G (IgG) from an uninfected chimpanzee, nonneutralizing IgG from an HIV-seropositive human, a virus-neutralizing murine monoclonal antibody directed against the HIV-1 IIIb isolate, or virus-neutralizing IgG from a chimpanzee infected with the IIIb isolate. Both neutralizing antibodies were directed against the principal neutralization determinant of the challenge isolate. Establishment of infection following inoculation of each virus-antibody mixture into chimpanzees was assessed by virus-specific antibody development and by virus isolation. No protective effect was noted either with the control IgG or with the nonneutralizing anti-HIV IgG. By contrast, the polyclonal chimpanzee virus-neutralizing IgG prevented HIV-1 in vivo infection, while the neutralizing monoclonal antibody notably decreased the infectivity of the challenge virus. Hence, antibody to the gp120 principal neutralization determinant is able both to prevent HIV-1 infection in vitro and to inhibit infection in vivo.

Animals↗

Challenges of a P & T Committee in a community teaching hospital.

Lutheran General Hospital, a 650-bed, tertiary care and trauma center in Park Ridge, Illinois, has had a P & T Committee in place for 11 years. In this exclusive Hospital Formulary interview, David Cooke, MD, and Jackie Kessler, MS, the respective chairman and secretary of that committee, discuss the challenges their committee faces. Somewhat unique to a community hospital, this committee manages a relatively restricted formulary. They attribute their success to dedicated P & T Committee members and a committed pharmacy. Among the more difficult issues still to be resolved at Lutheran General are relationships between pharmaceutical companies and P & T members and the possible institution of a conflict-of-interest disclosure policy, as well as the never-ending battle of evaluating drug use in their institution.

Drug Industry↗

The biology of human immunodeficiency virus-1 IIIB infection in the chimpanzee: in vivo and in vitro correlations.

Human immunodeficiency virus (HIV)-1 IIIB infection of chimpanzees leads to a compartmentalized, nonpathogenic in vivo and in vitro relationship with the virus. The absence of an acquired immunodeficiency syndrome (AIDS)-like disease in over 100 chimpanzees persistently infected may be related to some or all of the findings reported here. Further characterizing these possible host adapative mechanisms may be critical in both understanding pathogenesis, as well as elucidating novel mechanisms for therapeutic and/or the preventive strategies for AIDS in humans.

Acquired Immunodeficiency Syndrome↗

Cognitive functioning of juveniles with Down syndrome and other forms of mental retardation.

The performance of juvenile Down syndrome individuals and two groups of oligophrenes was compared in several cognitive tests. All three groups of subjects were of the same CA, the Down's and one group of mentally retarded non-Down's had an average MA of 62, the other group an MA of 86 months. Though the group with the highest mental age usually outperformed the other two, significant differences were rare. It is concluded that at this age Down's and mentally retarded with different etiologies generally have rather similar cognitive abilities and that the intellectual deterioration of Down's, which at a later age inevitably leads to Alzheimer's disease, indeed starts only at a later CA.

Adolescent↗

Primate learning tasks reveal strong impairments in patients with presenile or senile dementia of the Alzheimer type.

Eight subjects with the likely diagnosis of presenile or senile dementia of the Alzheimer type were tested on two frequently used primate learning tasks: a concurrent object discrimination task and a delayed non-match-to-sample task. In addition, various tests for cognitive, mnemonic, perceptual, and language functions were applied. The results suggest a severe decline of the Alzheimer subjects in all measures when compared with 10 control subjects matched for age, gender, and education. The two animal learning tasks revealed strong impairments, thus demonstrating a high sensitivity for the detection and assessment of human amnesic disorders. Implications of these findings for human neuropsychological, and especially comparative neuropsychological, research are discussed.

Aged↗

Korsakoff and alcoholic subjects are severely impaired in animal tasks of associative memory.

Korsakoff subjects, members of the Alcoholics Anonymous, and alcoholics with 1 week or 5-6 months of abstinence were tested in a concurrent object discrimination task with 10 and 20 pairs of objects and compared to control subjects matched for age and education. The anonymous alcoholics were moderately Korsakoff subjects strongly impaired, whereas alcoholics with 1 week or 5-6 months abstinence performed similar to control subjects. The results are discussed with respect to current research on human amnesia and comparative neuropsychological topics.

Adult↗

[Possibilities and weaknesses of psychopathometric diagnosis of dementia].

As cognitive deficiencies in aged people constitute a growing factor in our societies, the possibilities for diagnosing dementia are described and analyzed critically. Based on a discussion of those changes in intellectual performance which are typical for normal aging (e.g., reduction in so-called fluid intelligence combined with preservation of so-called crystallized intelligence), the pathological forms of aging, especially Alzheimer's disease, are outlined. The present, internationally favored psychometrical measures for recording dementia in the aged and for evaluating and diagnosing it differentially are listed. Finally, certain requirements which have to be imposed on a diagnostic test for dementia are discussed.

Aged↗

Enkephalin and capsaicin-resistant substance P-like immunoreactivities in intra-ocular grafts of different fetal spinal cord areas.

Fetal spinal cord tissue was grafted to the anterior chamber of the eye of adult rats in order to evaluate survival and distribution of substance P- and enkephalin-immunoreactive neurons. Capsaicin treatment was used to evaluate any possible contribution of host iris-derived substance P fibres to the innervation of the grafts and to check for capsaicin sensitivity of graft substance P-positive systems. Substance P- and enkephalin-immunoreactive nerve fibres were present in grafts of half-transverse segments of the spinal cord and were clearly co-distributed throughout the grafts. Areas with a high density of substance P- and enkephalin-positive fibres resembling substantia gelatinosa were seen. Grafts of the dorsal horn alone had a moderate to high density of substance P- and enkephalin-positive fibres, while ventral horn grafts contained a low amount of such fibres. Capsaicin eliminated the substance P innervation of the host iris and the dorsal root ganglion-derived substance P innervation of the host spinal cord, while sparing the intrinsic substance P innervation of both host spinal cord and spinal cord grafts. These experiments show that intra-ocular grafts of defined spinal cord areas express relatively organotypic amounts of substance P- and enkephalin-positive nerve fibres, and thus emphasize the importance of intrinsic genetic determinants for spinal cord development.

Animals↗

Recognition memory and psychophysiological responses to stimuli with neutral or emotional content: a study of Korsakoff patients and recently detoxified and longterm abstinent alcoholics.

Possible relations between chronic alcohol abuse and impairments in cognitive functioning were tested in six groups of subjects, groups A1, A2, CGy, AA, KO, and CGo: The first three groups were about 35 years old, the last three about 50 years. Groups A1 and A2 each consisted of ten men hospitalized for the treatment of alcohol dependency, group A1 having been detoxified for less than one week, and group A2 for more than five months. Group CGy constituted the matched control group. Group AA consisted of six Alcoholics Anonymous, sober for more than five years, nine Korsakoff patients made up group KO, and group CGo was the control group matched for groups AA and KO. As the main tests, all subjects were given a number of slides showing scenes, humans, or animals, half of which had been rated as neutral while the other half was emotionally arousing (in either a negative or a positive way). In two tests, one after ten minutes, and one after two days, the subjects were required to reidentify those slides which they had seen before, and their galvanic skin response was measured simultaneously. Several psychological tests including one for paired associate learning were given as well. The main results were that alcoholics, whether they had been abstinent for a longer time or not, were inferior to nonalcoholics, but that a prolonged period of soberness nevertheless most likely leads to the recovery of cognitive functions. Though the underlying causes of the cognitive deficits found in the four experimental groups (A1, A2, AA, KO) may be due at least in part to different or even contradictory underlying causes, they provide support for "simple versions" of the so-called continuity and premature aging hypotheses.

Adult↗

Memory related role of the posterior cholinergic system.

In order to establish a model for the possible neuropathology of patients with Alzheimer's disease, various behaviors of rats with different chemical lesions in cholinergic regions were studied and compared with those of sham-operated control rats. A battery of neurological tests was used as well as activity measurements and two learning tasks: a positively reinforced place-learning task with delay periods of Os, 1 min, 15 min, and 2h, and a shock-motivated two-way active avoidance task. While in general no intergroup differences were obtained in performance on the neurological test battery or the rats' activity in an open field, there were marked impairments in the three lesioned groups compared to the control group in the two learning tasks. These deficits were less severe in the two groups with lesions of the medial septal/vertical diagonal band of Broca region and the nucleus basalis of Meynert region, but rather marked in the group with lesions of neurons situated in the pontomesencephalic region, although the amount of ibotenic acid injected had been the same for all groups. We conclude from these data that changes in mesencephalic cholinergic regions might play a significant role in the pathology of Alzheimer's disease. The existence of such regions was recently established for primates as well, thus providing a basis for justifying an animal model of this human disease.

Alzheimer Disease↗