Biomedical subjects

J Kessler

Publications and source records attributed to J Kessler.

At least 37 records · Page 2Linked to original sources

PubMed2000

Piracetam improves activated blood flow and facilitates rehabilitation of poststroke aphasic patients.

BACKGROUND AND PURPOSE: In a prospective, double-blind, placebo-controlled study, it was investigated whether piracetam improves language recovery in poststroke aphasia assessed by neuropsychological tests and activation PET measurement of cerebral blood flow. METHODS: Twenty-four stroke patients with aphasia were randomly allocated to 2 groups: 12 patients received 2400 mg piracetam twice daily, 12 placebo. Before and at the end of the 6-week treatment period in which both groups received intensive speech therapy, the patients were examined neuropsychologically and studied with H(2)(15)O PET at rest and during activation with a word-repetition task. Blood flow was analyzed in 14 language-activated brain regions defined on reconstructed surface views from MRI coregistered to the PET images. RESULTS: Before treatment, both groups were comparable with respect to performance in language tasks and to type and severity of aphasia. In the piracetam group, increase of activation effect was significantly higher (P:<0.05) in the left transverse temporal gyrus, left triangular part of inferior frontal gyrus, and left posterior superior temporal gyrus after the treatment period compared with the initial measures. The placebo group showed an increase of activation effect only in the left vocalization area. In the test battery, the piracetam group improved in 6 language functions, the placebo group only in 3 subtests. CONCLUSIONS: Piracetam as an adjuvant to speech therapy improves recovery of various language functions, and this effect is accompanied by a significant increase of task-related flow activation in eloquent areas of the left hemisphere.

Adolescent↗

PubMed2000

Neuroimaging and behavioral correlates of recovery from mnestic block syndrome and other cognitive deteriorations.

OBJECTIVE: We conducted a follow-up study on a patient with enduring psychic shock-induced cognitive impairment to study by neuropsychological and functional imaging methods the degree of his recovery process on the brain and cognitive levels. BACKGROUND: Based on the assumption that trauma and stress conditions can alter the functions of the nervous systems, we report on a patient whom we studied 2 and 12 months after he suffered "mnestic block syndrome" and additional cognitive deterioration symptoms. METHODS: We report on a patient studied 2 and 12 months after he suffered "mnestic block syndrome" and additional cognitive deterioration symptoms. Magnetic resonance imaging and fluorodeoxyglucose positron emission tomography were used for neural and detailed neuropsychological testing for cognitive deficits. RESULTS: The patient initially manifested severe intellectual decline, including severe anterograde and retrograde amnesia. His symptoms were correlated with major, although selective, reductions in his brain metabolism (2-3 SD below those of controls). Presently, he shows a normal brain metabolism and has regained parts of his memory and many of his other intellectual capabilities. Nevertheless, he still has long-term memory impairments. CONCLUSIONS: This case demonstrates a close relation between brain metabolism and cognitive performance, with major deficits of both at 2 months and major recovery of both at 12 months after a shocking event. It can serve as an example for possible stress-related deteriorations in certain brain regions, which can be partly corrected by psychotherapeutic interventions, passing time, and favorable environmental conditions.

Amnesia↗

PubMed2000

Heterogeneous populations of ES cells in the generation of a floxed Presenilin-1 allele.

Generation of a floxed Presenilin-1 (PS1) allele involved two recombination events in the embryonic stem (ES) cells. First, a targeting vector containing a loxP site in intron 1 and a floxed CMV-HYG/TK double selection cassette in intron 3 was integrated into the PS1 locus by homologous recombination. The use of a negative selection cassette, PGK-DTA, dramatically increased the recombination efficiency within the targeted locus (75-fold). Second, an expression vector encoding Cre recombinase was introduced to excise the floxed CMV-HYG/TK cassette via site-specific recombination. However, all five ES cell clones testing positive for the proper removal of the CMV-HYG/TK cassette also contained a proportion of ES cells in which recombination had occurred between the distal loxP sites in introns 1 and 3, resulting in excision of the entire floxed region. It is therefore critical to screen for possible recombination events involving all 3 loxP sites, in order to identify ES cells clones bearing high proportions of the desired ES cells. genesis 26:5-8, 2000.

Alleles↗

PubMed1999

Host-cell positive transcription elongation factor b kinase activity is essential and limiting for HIV type 1 replication.

HIV-1 gene expression and viral replication require the viral transactivator protein Tat. The RNA polymerase II transcriptional elongation factor P-TEFb (cyclin-dependent kinase 9/cyclin T) is a cellular protein kinase that has recently been shown to be a key component of the Tat-transactivation process. For this report, we studied the requirement for P-TEFb in HIV-1 infection, and we now show that P-TEFb is both essential and limiting for HIV-1 replication. Attenuation of P-TEFb kinase activity either by expression of a dominant-negative cyclin-dependent kinase 9 transgene or through the use of small-molecule inhibitors suppresses HIV-1 gene expression and HIV-1 replication. Inhibition of HIV-1 replication is affected in a manner consistent with a direct and specific effect on P-TEFb and the known functional role of P-TEFb in Tat-activated transcription. Tat-activated expression of HIV-1 genes seems uniquely dependent on P-TEFb, as inhibition of P-TEFb activity and HIV-1 replication can be achieved without compromising cell viability or RNA polymerase II-dependent cellular gene transcription. Selective inhibition of the P-TEFb kinase may therefore provide a novel approach for developing chemotherapeutic agents against HIV-1.

Cell Line↗

PubMed1999

Differential capacity of left and right hemispheric areas for compensation of poststroke aphasia.

As previous functional neuroimaging studies could not settle the controversy regarding the contribution of dominant and subdominant hemisphere to recovery from poststroke aphasia, language performance was related to H2(15)O-positron emission tomographic activation patterns in 23 right-handed aphasic patients 2 and 8 weeks after stroke. In patients classified according to the site of lesion (frontal, n = 7; subcortical, n = 9; temporal, n = 7) and in 11 control subjects, flow changes caused by a word repetition task were calculated in 14 regions representing eloquent and contralateral homotopic areas. These areas were defined on coregistered magnetic resonance imaging scans and tested for significance (Bonferroni corrected t test, alpha = 0.0036). At baseline, differences in test performance were only found between the subcortical and temporal group. The extent of recovery, however, differed and was reflected in the activation. The subcortical and frontal groups improved substantially; they activated the right inferior frontal gyrus and the right superior temporal gyrus (STG) at baseline and regained left STG activation at follow-up. The temporal group improved only in word comprehension; it activated the left Broca area and supplementary motor areas at baseline and the precentral gyrus bilaterally as well as the right STG at follow-up, but could not reactivate the left STG. These differential activation patterns suggest a hierarchy within the language-related network regarding effectiveness for improvement of aphasia; ie, right hemispheric areas contribute, if left hemispheric regions are destroyed. Efficient restoration of language is usually only achieved if left temporal areas are preserved and can be reintegrated into the functional network.

Adult↗

PubMed1999

Mnestic block syndrome.

The case of a patient with largely preserved intelligence, but severe and persistent memory impairments is reported. FA, a 46-year-old patient with the diagnosis of prolonged depression was investigated repeatedly over a two year period with neuroradiological, neuropsychological, neuromonitoring and other methods. While no brain damage was detectable in FA, he manifested continued and severe anterograde and retrograde memory disorders together with an inhibition in his thinking processes. Otherwise, his intellectual capabilities were in the normal range, that is he was not pseudo-demented. Various approaches with drug treatment and psychotherapy failed to improve his condition. The condition is interpreted as 'mnestic block syndrome' and is considered to be related to an altered brain metabolism which may include changes in various transmitter and hormonal systems (GABA-agonists, glucocorticoids, acetylcholine). Whether depression contributes to this syndrome is uncertain from FA's cognitive performance, but may be a possibility.

Amnesia, Retrograde↗

PubMed1999

EEG power changes are related to regional cerebral glucose metabolism in vascular dementia.

OBJECTIVE: In patients with vascular dementia (VD), the relationship between the EEG power within the 4 frequency bands and the regional metabolic disturbances was investigated. METHODS: Twenty-eight patients (age 69.0+/-6.54 years) with VD according to NINDS-AIREN criteria underwent quantitative EEG recording, according to the 10-20 system, and fluodeoxyglucose F18 positron emission tomography (PET) at resting condition within 24 h. EEG power FFT-analysis was performed for delta (2-3.5 Hz), theta (4-7.5 Hz), alpha (8-13 Hz) and beta (13.5-20 Hz) frequency bands. Regional EEG power bands were related to regional glucose metabolism in anatomically defined regions corresponding to locations of the 10-20 system. RESULTS: Correlation between slow frequency band power and glucose metabolism was found. A widespread inverse relationship of delta power to metabolism was found between various regions; additionally, delta power was negatively correlated to cerebral glucose metabolism in individual regions. Frontal theta power correlated especially with thalamic CMRglc. Alpha power correlated directly with metabolism in the occipital lobe. No significant relationships were found between beta power and metabolism. CONCLUSION: We conclude that EEG power in VD is linked to glucose metabolism, indicating specific regional dependencies.

Aged↗

PubMed1999

Properties of an enzyme-based low-level iodine disinfectant.

An enzyme-based iodine (EBI) disinfectant that continuously generates free molecular iodine in a controlled fashion was developed and evaluated for use in disinfecting flexible fibreoptic endoscopes (FFEs). EBI is a powder concentrate that produces iodine from sodium iodide and calcium peroxide when catalyzed by horseradish peroxidase. After dissolution in water, it delivers relatively high concentrations of free molecular iodine (> 15 ppm) at relatively low concentrations of total iodine (30-40 ppm). It demonstrates the ability to function as an effective low level iodine disinfectant by rapidly inactivating bacteria, fungi and viruses. A unique feature of the EBI system is the ability to reoxidize reduced iodine which results in a constant level of active (free molecular) iodine during use. EBI inactivates Mycobacterium bovis var BCG more rapidly than 2% glutaraldehyde (Cidex-7). Its sporicidal activity, however, was found to be slower than the aldehyde formulation. The qualification of EBI for use as a practical disinfectant was shown by its negligible toxicity in dermal, ocular, oral and inhalation studies on animals, which is attributed to the low level of total iodine in the solution.

Animals↗

PubMed1999

Short-term memory deficit after focal parietal damage.

The neuropsychological symptomatology is reported for a 44-year-old patient of normal intelligence, EE, after removal of a circumscribed left hemispheric tumor the major part of which was located in the angular gyrus and in the subcortical white matter. EE had a distinct and persistent short-term memory impairment together with an equally severe impairment in transcoding numbers. On the other hand, his performance was flawless in calculation tasks and in all other tests involving number processing. Impairments in language tests could be attributed to his short-term memory deficit, which furthermore was characterized by a strong primacy effect in the absence of a recency effect. His graphomotoric output was temporarily inhibited. The patient, with a strong left-sided dominance, manifested a bi-hemispherical activation of the Broca and Wernicke regions in a positron-emission-tomographic investigation when required to produce verbs which he was to derive from nouns. The findings in EE suggest that unilateral and restricted lateral parietal damage can result in a profound short-term memory deficit together with a transcoding deficit for stimuli extending over only a few digits or syllables in the absence of any symptoms of the Gerstmann syndrome.

Adult↗

PubMed1999

A biosphere modeling methodology for dose assessments of the potential Yucca Mountain deep geological high level radioactive waste repository.

Recent developments in performance standards for proposed high level radioactive waste disposal at Yucca Mountain suggest that health risk or dose rate limits will likely be part of future standards. Approaches to the development of biosphere modeling and dose assessments for Yucca Mountain have been relatively lacking in previous performance assessments due to the absence of such a requirement. This paper describes a practical methodology used to develop a biosphere model appropriate for calculating doses from use of well water by hypothetical individuals due to discharges of contaminated groundwater into a deep well. The biosphere model methodology, developed in parallel with the BIOMOVS II international study, allows a transparent recording of the decisions at each step, from the specification of the biosphere assessment context through to model development and analysis of results. A list of features, events, and processes relevant to Yucca Mountain was recorded and an interaction matrix developed to help identify relationships between them. Special consideration was given to critical/potential exposure group issues and approaches. The conceptual model of the biosphere system was then developed, based on the interaction matrix, to show how radionuclides migrate and accumulate in the biosphere media and result in potential exposure pathways. A mathematical dose assessment model was specified using the flexible AMBER software application, which allows users to construct their own compartment models. The starting point for the biosphere calculations was a unit flux of each radionuclide from the groundwater in the geosphere into the drinking water in the well. For each of the 26 radionuclides considered, the most significant exposure pathways for hypothetical individuals were identified. For 14 of the radionuclides, the primary exposure pathways were identified as consumption of various crops and animal products following assumed agricultural use of the contaminated water derived from the deep well. Inhalation of dust (11 radionuclides) and external irradiation (1 radionuclide) were also identified as significant exposure modes. Contribution to the total flux to dose conversion factor from the drinking water pathway for each radionuclide was also assessed and for most radionuclides was found to be less than 10% of the total flux to dose conversion factor summed across all pathways. Some of the uncertainties related to the results were considered. The biosphere modeling results have been applied within an EPRI Total Systems Performance Assessment of Yucca Mountain. Conclusions and recommendations for future performance assessments are provided.

Computer Simulation↗

PubMed1999

Relationship between the histopathology of the endocrine-exocrine pancreas parenchyma and beta-cell function in the Chinese hamster CHIG/Han subline.

To investigate pancreatic histopathology in relation to islet function in type 2 diabetes, pancreatic tissue was examined at disease onset and after death in the genetically diabetic Chinese hamster CHIG/Han subline. The pancreatic islets displayed vacuolation, intraislet fibrosis, variable stages of degranulation, and beta-cell necrosis, but no insulitis. These lesions were associated with changes in immunostaining of major islet peptides, impaired glucose-stimulated (10 mM) insulin secretion, reduced islet insulin content, and the severity of hyperglycemia. The exocrine pancreas was characterized by peri- and intrapancreatic fat and mononuclear cell infiltration. Biopsy of the pancreas had a marked effect on plasma glucose such that at 2 weeks after excision, in 9 and 18% of the severely hyperglycemic hamsters, plasma glucose levels decreased to <7.2 and 15 mM, respectively, and 45% of the mildly hyperglycemic hamsters became transiently normoglycemic (<7.2 mM). The results showed that insulitis is not involved in beta-cell failure of diabetic CHIG/Han hamsters. Vacuolation of islets was the most prominent lesion associated with a functional islet abnormality and development of hyperglycemia. Attenuation of hyperglycemia after biopsy suggests that the pancreas, in type 2 diabetes, maintains the ability to respond to impairment with amelioration of the diabetic state.

Animals↗

PubMed1998

Apolipoprotein E polymorphism influences the cerebral metabolic pattern in Alzheimer's disease.

In 49 patients with the clinical diagnosis of probable Alzheimer's disease (AD) apoE genotyping as well as regional cerebral glucose metabolism (rCMRGI) using positron emission tomography (PET) of [18F]2-fluoro-2-deoxy-D-glucose (FDG) were studied. The metabolic pattern was condensed to a ratio by dividing the rCMRGI of typically affected regions (temporo-parietal and frontal association cortex) by the rCMRGI of the least affected regions (primary cortical areas, basal ganglia, cerebellum and brainstem). Epsilon4-heterozygotes and epsilon4-homozygotes were grouped together, and also those lacking the epsilon4-allele (non-epsilon4). For the metabolic pattern we found a significant correlation to severity of dementia in both groups (epsilon4: r = 0.49, P = 0.05; non-epsilon4: r = 0.59, P = 0.006). On ANCOVA severity of dementia and epsilon4 status were independent predictors of the cerebral metabolic pattern (P = 0.01). These differences may be attributed to epsilon4 dependent histopathologic changes.

Age Factors↗

PubMed1998

Leukocyte differentials predict short-term clinical outcome following antipsychotic treatment in schizophrenia.

BACKGROUND: The majority of patients with schizophrenia and many of their unaffected siblings exhibit a relative granulocytosis and lymphopenia. To characterize these abnormalities better, we examined leukocyte differentials and organ nonspecific autoantibodies in relationship to intake phenomenology and short-term clinical outcome. METHODS: We studied patients with schizophrenia (n = 81) and their siblings (n = 18). At intake assessment, about one-half of the probands (n = 38) were neurolepticnaive first-episode patients; the remainder were medication-free for at least 2 weeks. Hematologic indices were obtained at intake assessment, and psychiatric symptomatology was assessed at baseline and following 6 months of clinically determined treatment. RESULTS: A relative granulocytosis and lymphopenia prospectively predicted poorer recovery in positive, but not negative, symptoms after 6 months of antipsychotic treatment. Abnormal leukocyte proportions were specific to patients who presented with clinically significant positive symptomatology at intake. In contrast, clinically significant negative symptoms were only evident in a small subgroup of patients who were positive for antinuclear autoantibodies and/or rheumatoid factor. CONCLUSIONS: Future research should further test the hypothesis that a relative granulocytosis and lymphopenia reflect genetic loading for the pathophysiologic determinants of positive symptoms. Future research also should determine the etiologic significance of organ nonspecific autoimmunity in predominantly negative symptom schizophrenia.

Adult↗

PubMed1998

Propentofylline enhances cerebral metabolic response to auditory memory stimulation in Alzheimer's disease.

To evaluate efficacy, safety, metabolic and clinical effects of propentofylline in Alzheimer's disease (AD), a prospective, randomized, double-blind, placebo-controlled trial was performed in 30 patients with mild to moderate AD who underwent pretreatment and posttreatment 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography under resting conditions and during stimulation with an auditory memory paradigm. Twenty-eight subjects completed the 3-month study. The drug was well tolerated. In the active treatment group, a significant increase of cerebral metabolic response to the memory task was observed (multiple measurement ANOVA P = 0.02). The placebo group showed a significantly decline in the MMSE score (P = 0.02) while there was no change in the treatment group. This suggests a protective role for propentofylline in slowing the progression of AD.

Acoustic Stimulation↗

PubMed1998

Early-onset cerebellar ataxia (EOCA) with retained reflexes: reduced cerebellar benzodiazepine-receptor binding, progressive metabolic and cognitive impairment.

A family with two members who had early-onset cerebellar ataxia (EOCA) with retained tendon reflexes had, in addition to their motor deficits, a progressive impairment of cognitive and visuospatial abilities. We used positron emission tomography (PET) with 11C-flumazenil to study gamma-aminobutyric type A/benzodiazepine receptor binding (BZR) and 18F-2-fluoro-2-deoxy-D-glucose to analyze longitudinally regional cerebral glucose metabolism. Flumazenil-PET demonstrated loss of BZR binding that has not been shown in Friedreich's ataxia and olivopontocerebellar atrophy. These findings may be useful for differentiation of EOCA from other types of cerebellar ataxia. In comparison to age-matched control subjects, these patients showed a global metabolic decline and predominant hypometabolism in the thalamus and cerebellum. The progressive metabolic derangement may be explainable by a disturbed integrity of cognition-related networks resulting from secondary degeneration of cerebello-thalamo-cortical projections.

Adult↗

PubMed1998

Brain plasticity in poststroke aphasia: what is the contribution of the right hemisphere?

The brain may use two strategies to recover from poststroke aphasia: the structural repair of primarily speech-relevant regions or the activation of compensatory areas. We studied the cortical metabolic recovery in aphasic stroke patients with positron emission tomography (PET) at rest and during word repetition. The left supplementary motor area (SMA) showed the most prominent compensatory activation in the subacute state of stroke. The restitution of the left superior temporal cortex determined the long-term prognosis of aphasia. The brain recruited right-hemispheric regions for speech processing, when the left-hemispheric centers were permanently impaired. This strategy, however, was significantly less effective than the repair of the original speech-relevant network.

Adult↗

PubMed1998

Localization of language-related cortex with 15O-labeled water PET in patients with gliomas.

Measurement of relative cerebral blood flow (CBF) with 15O-labeled water PET has been widely used for brain mapping experiments on language functions in normal volunteers and patients with epilepsy. We focused on the question of whether PET during speech activation is an appropriate method for noninvasive determination of language-related cortex in patients with brain tumors. Furthermore, the suitability of the method for determination of hemispheric language dominance was examined and compared to the results of the Edinburgh Handedness Inventory. Ten right-handed and six left-handed patients with gliomas were examined prior to surgery while repeatedly performing word repetition and verb generation tasks. A set of volumes of interest (VOIs) was drawn on coregistered MRI in order to account for anatomic variability as well as anatomical alterations due to tumor mass effect. Repetition of nouns did not produce significant hemispheric differences. During stimulation by verb generation, reliable lateralized activations of Broca's area and supplementary motor area were detected in all right-handed patients. Of the left-handed patients, two showed clear right lateralization, two activated Broca's area bilaterally, and two had a pattern similar to that of right-handers. Patients with bilateral activations showed the strongest tendency toward bihandedness according to the handedness inventory. Lateralization of supplementary motor area in left-handers corresponded to lateralized activity in Broca's area. Tumors in the vicinity of language-related regions did not alter activation responses. In conclusion, measurement of CBF changes during verb generation permits identification of language-related areas in patients with gliomas with strong lateralization related to hemispheric dominance. These findings may be of particular clinical interest for left-handed patients.

Adult↗

PubMed1998

[Copying and free drawing by patients with Alzheimer disease of different dementia stages].

In this study we assessed the drawing abilities in 37 patients with probable Alzheimer's disease according to NINCDS-ADRDA criteria. Drawing abilities (drawing: house, flower, clock; Rey-Osterrieth figure; copying: MMST-figure; Rey-Osterrieth figure) were quantified with different rating schemes and related to other neuropsychological assessments. All patients underwent a positron emission tomography with 18-FDG. Drawing performance was highly correlated with severity of dementia--expressed in MMST scores (r = 0.78; p < 0.0001)--with visuo-spatial short-term memory (r = -0.69; p = 0.001), and writing abilities (r = -0.77; p < 0.0001). The summarized drawing score showed a statistically significant correlation with the rate of temporoparietal glucose metabolism measured with positron emission tomography and 18-FDG (r = 0.39; p = 0.017). In the drawings of AD patients omittings and simplifications were typical, whereas perseverations rarely occurred. In severely demented patients closing-in phenomenons could be described, too. A subgroup of AD patients with visuo-constructive impairment as the leading symptom could not be identified.

Aged↗