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Biomedical subjects

J Kessler

Publications and source records attributed to J Kessler.

At least 73 records · Page 4Linked to original sources

Impaired episodic memory retrieval in a case of probable psychogenic amnesia.

A patient with severe, selective retrograde amnesia for personal material diagnosed as probable psychogenic amnesia, was investigated intensively neuropsychologically with cranial computed tomography (CCT), magnetic resonance imaging (MRI), and single photon emission tomography (SPECT). The patient was of average intelligence and memory with no anterograde amnesia. No evidence for structural brain damage was detected in CCT and MRI. SPECT, performed about 3 weeks after the onset of symptoms, demonstrated reduced perfusion in right temporal and frontal areas, that is, in areas which have been suggested as critical for episodic memory retrieval. To study episodic memory retrieval, positron-emission-tomography (PET) blood flow (rCBF) measurements were performed 6 months after the onset of symptoms. During episodic memory retrieval bilateral neuronal activations were observed in the precuneus, the lateral parietal and the right dorsolateral and polar prefrontal cortex. Compared to the results of previous functional imaging studies on episodic memory retrieval, our findings suggest an underlying functional disturbance of brain areas previously demonstrated to be involved in episodic memory retrieval.

Adult↗

Tyrosine phosphorylation-dependent activation of phosphatidylinositide 3-kinase occurs upstream of Ca2+-signalling induced by Fcgamma receptor cross-linking in human neutrophils.

The effect of wortmannin on IgG-receptor (FcgammaR)-mediated stimulation of human neutrophils was investigated. The Ca2+ influx induced by clustering of both Fcgamma receptors was inhibited by wortmannin, as was the release of Ca2+ from intracellular stores. Wortmannin also inhibited, with the same efficacy, the accumulation of Ins(1,4,5)P3 observed after FcgammaR stimulation, but did not affect the increase in Ins(1,4,5)P3 induced by the chemotactic peptide, formyl-methionine-leucine-phenylalanine. Because wortmannin is, in the concentrations used here, an inhibitor of PtdIns 3-kinase, these results suggested a role for PtdIns 3-kinase upstream of Ca2+ signalling, induced by FcgammaR cross-linking. Support for this notion was obtained by investigating the effect of another inhibitor of PtdIns 3-kinase, LY 294002, and by studying the kinetics of PtdIns 3-kinase activation. We found translocation of PtdIns 3-kinase to the plasma membrane and increased PtdIns 3-kinase activity in the membrane as soon as 5 s after FcgammaR cross-linking, even before the onset of the Ca2+ response. Moreover, the translocation of PtdIns 3-kinase to the plasma membrane was inhibited by co-cross-linking of either FcgammaRIIa and FcgammaRIIIb with the tyrosine phosphatase, CD45, indicating a requirement for protein tyrosine phosphorylation in the recruitment of PtdIns 3-kinase to the plasma membrane. Taken together, our results suggest a role for PtdIns 3-kinase in early signal transduction events after FcgammaR cross-linking in human neutrophils.

Androstadienes↗

Speech-induced cerebral metabolic activation reflects recovery from aphasia.

Six stroke patients with clinically significant aphasia were studied 4 weeks and again 12-18 months after their first left hemispheric ictus. The regional cerebral metabolic rate of glucose (rCMRglc) was measured repeatedly by PET at rest and during word repetition, and severity of speech impairment was assessed by a neuropsychologic test battery. The patterns of speech-associated activation of glucose metabolism were related to improvement in language performance as measured by the Token test. Three patients experienced significant recovery from aphasia (Token test: 47 to 3, 45 to 12, and 37 to 5 points, respectively), whereas 3 patients had poor outcome (Token test from 48 to 45, and from 47 to 39 and 24, respectively). Good recovery was related to activation of left hemispheric speech areas surrounding the infarct, especially left superior temporal gyrus. In contrast, the 3 patients with persistent aphasia showed rCMRglc recruitment in right hemispheric regions and were unable to activate left hemispheric speech areas on follow-up. These results indicate that favorable outcome is related to partial sparing of speech areas of the dominant hemisphere that can be (re-) activated. Predominant recruitment of contralateral areas is not efficacious for a considerable recovery from aphasia. It rather indicates unspecific involvement of widespread networks in the effort to perform a complex task.

Adult↗

Functional effects of striatal dysfunction in Parkinson disease.

BACKGROUND: Concepts of basal ganglia organization suggest structually and functionally segregated pathways that link putamen and caudate function to motor and cognitive performance, respectively. OBJECTIVE: To investigate whether motor and cognitive impairment in Parkinson disease is attributable to selective disturbance in nigrostriatal, dopaminergic function and regional cerebral glucose metabolism. DESIGN: Twenty patients with probable Parkinson disease underwent positron emission tomographic measurements of dopaminergic, nigrostriatal function (positron emission tomography with fluorodopa F 18), regional glucose metabolism (positron emission tomography with fludeoxyglucose F 18), memory testing, and evaluation of locomotor disability. RESULTS: Memory performance in the patient cohort strongly correlated with the individual disease duration and degree of locomotor disability (P < .05). Striatal uptake rates of fluorodopa F 18 were significantly reduced in all patients (P < .05) compared with those in normal control subjects, and putaminal rates correlated significantly with the patients' degree of locomotor disability (P < .01) but not with memory performance. In the patients with an advanced stage of disease, there was a significant correlation between reduced caudate uptake rates of fluorodopa F 18 and the patients' impairment in delayed recall performance of the memory task (P < .05) but not with the individual degree of locomotor disability. No changes were found for regional glucose metabolic rates in the patients compared with the controls. CONCLUSIONS: The present study provides evidence for the hypothesis that on the level of the striatum, motor impairment in Parkinson disease may be assigned to altered dopamine neuronal integrity in the putamen but not in the caudate, whereas memory impairment in the more advanced cases may be attributed to caudate but not putaminal dysfunction.

Aged↗

Differential impairments in recalling people's names: a case study in search of neuroanatomical correlates.

The case of a patient with selective left hemispheric medial and lateral temporal lobe damage is described. The patient was of slightly supra-average intelligence and had no problems in normal memory functions, but was severely anomic with respect to people's names. One month post-onset, this deficit held for names of colleagues and friends she had gotten to know during the last 10 years prior to the infarct and for all names confronted with post-infarct. On the other hand, learning of face-name associations was preserved and was independent of the ability to generate context-specific information for the subjects whose names were requested. The results support the existence of category-specific naming impairments, and, moreover, indicate a deficit that has to be differentiated with regard to memory systems. A time-limited, but prolonged engagement of interconnected left medial and adjacent lateral temporal lobe structures in ecphory is stressed for context-restricted information such as proper names.

Anomia↗

Massive and persistent anterograde amnesia in the absence of detectable brain damage: anterograde psychogenic amnesia or gross reduction in sustained effort?

The case of a young patient with severe and persistent anterograde amnesia of no known cause is reported. Anterograde amnesia arose within a 1-month period and has persisted for more than 1 year. Although a wide variety of neurological and neuroradiological assessments were completed (EEG, evoked potential recordings, Doppler sonography, MRI, PET), no evidence of brain damage was detected. Neuropsychologically, the patient was of high intelligence, had average to above-average short-term memory, and normal retrograde memory abilities, but severe and persistent anterograde amnesia in both verbal and nonverbal domains. Furthermore, he demonstrated grossly reduced long-term concentration. It is likely that a complex chain of interacting variables can produce a syndrome that appears phenomenologically as anterograde amnesia without organically measurable correlates.

Adult↗

Preoperative activation and intraoperative stimulation of language-related areas in patients with glioma.

OBJECTIVE: Evaluation of the accuracy of preoperative localization of language-related cortex by magnetic resonance imaging-guided positron emission tomography. METHODS: Patients with gliomas in the left dominant hemisphere were examined preoperatively with magnetic resonance imaging-guided positron emission tomography and intraoperatively by electrical stimulation of cortex. RESULTS: A verb generation task yielded more intense and better lateralized local increases of cerebral blood flow in the positron emission tomographic examination than did a naming task. Significant correspondence of preoperative and intraoperative findings was observed for the verb generation task. Cortical sites with aphasic disturbance during electrical stimulation had a significantly higher cerebral blood flow increase during preoperative activation than did sites without intraoperative language impairment. Areas with cerebral blood flow increases above an optimum threshold had 73% sensitivity and 81% specificity to predict aphasic disturbance during intraoperative stimulation. CONCLUSION: The data suggest that with further technical improvements, imaging of language function may become a preoperative diagnostic tool for patients with tumors close to language-related brain structures.

Adult↗

Widespread functional deficits in perception-related networks demonstrated by PET in a case with simple visual seizures.

PURPOSE: To study benzodiazepine receptor (BZR) density and functional deficits in occipital lobe epilepsy. METHODS: A 39-year-old man who had simple partial visual seizures after neurosurgical transtentorial extirpation of a pinealoma was studied by EEG, magnetic resonance imaging (MRI), and positron emission tomography (PET) of [18F]2-fluoro-2-deoxy-D-glucose (FDG) at rest and during visual activation task and[11C]flumazenil (FMZ). RESULTS: Electroencephalographic recordings were nonspecific, and MRI did not reveal any morphologic anomaly in the occipital lobe. Flumazenil-PET demonstrated a small epileptogenic region in the right visual association cortex and FDG-PET showed hypometabolism in a corresponding location and thalamic diaschisis. Stimulation of occipital metabolism by a continuous visual recognition task improved significantly the contrast between the dysfunctional zone and its surround. CONCLUSIONS: As BZR deficits are restricted to a small region, widespread hypometabolism in networks involved in visual information processing indicates an extensive functional deactivation by the epileptogenic focus.

Adult↗

Control of the amount of free molecular iodine in iodine germicides.

Horseradish peroxidase has been used to generate iodine compositions that comprised principally free molecular iodine. The concentration of free molecular iodine in these enzyme-based compositions ranged from 44 to 63% of the thiosulphate titratable iodine; this is substantially higher than the corresponding value for the povidone-iodine preparation betadine. The biocidal efficacy of these compositions was proportional to the concentration of free molecular iodine. Iodine compositions with relatively low total iodine concentrations but high levels of free molecular iodine (20-175 ppm) killed Staphylococcus aureus and spores of Bacillus subtilis more rapidly than betadine. The effects of normal saline and these enzyme-based iodine compositions on the rate of epidermal regeneration in superficial swine wounds were comparable. These results suggest that an effective germicide containing a high level of molecular iodine need not be irritating or toxic.

Animals↗

Leukocytes and organ-nonspecific autoantibodies in schizophrenics and their siblings: markers of vulnerability or disease?

To determine whether leukocyte counts and organ-nonspecific autoantibodies mark familial vulnerability for schizophrenia and/or the disease itself, we examined 92 patients with schizophrenia and 94 unrelated, demographically balanced, healthy individuals. In addition, for 19 of the probands, one of their nonschizophrenia, full siblings also was recruited. At the time of the blood draw, most probands (87%) had been free of medications for a minimum of 2 weeks and about half were neuroleptic-naive, first-episode patients. Results indicate that a relative lymphopenia in the context of a relative granulocytosis appears to mark familial vulnerability for schizophrenia, whereas an absolute monocytosis appears to mark spectrum manifestations of the clinical phenotype. The former observation is consistent with the hypothesis that the etiology of schizophrenia is immunologically mediated, whereas the latter is consistent with emerging evidence that an inflammatory process is associated with the expression of the disorder. Neither antinuclear antibody nor rheumatoid factor emerged as liability or disease markers.

Adult↗

Propentofylline improves regional cerebral glucose metabolism and neuropsychologic performance in vascular dementia.

In a double-blind, placebo-controlled trial in thirty patients with mild to moderate vascular dementia (VD) according to DSM-III-R criteria, the effects of the adenosine uptake blocker propentofylline (HWA 285) on regional cerebral glucose metabolism (rCMRGl) was studied using positron emission tomography of 2-[18F]fluoro-2-deoxy-D-glucose (FDG). 25 subjects completed the 3-months study. Propentofylline significantly improved relative rCMRGl in the motor cortex, while relative rCMRGl in the placebo treated group worsened significantly. Neuropsychologically, visual information processing was improved in the propentofylline group and we observed a trend towards a slowing of the progression of cognitive deterioration in patients with VD. The results of the longitudinal analysis showed further that neuropsychological and metabolic changes are closely related. These findings justify a large-scale clinical trial to prove therapeutic efficacy.

Aged↗

Cerebral representation of one's own past: neural networks involved in autobiographical memory.

We studied the functional anatomy of affect-laden autobiographical memory in normal volunteers. Using H2 15O positron emission tomography (PET), we measured changes in relative regional cerebral blood flow (rCBF). Four rCBF measurements were obtained during three conditions: REST, i.e.,, subjects lay at rest (for control); IMPERSONAL, i.e., subjects listened to sentences containing episodic information taken from an autobiography of a person they did not know, but which had been presented to them before PET scanning (nonautobiographical episodic memory ecphory); and PERSONAL, i.e., subjects listened to sentences containing information taken from their own past (autobiographical episodic memory ecphory). Comparing IMPERSONAL with REST (nonautobiographical episodic memory ecphory) resulted in relative rCBF increases symmetrically in both temporal lobes including the temporal poles and medial and superior temporal gyri. The same loci, however, with a stronger lateralization to the right hemisphere were activated in the comparison PERSONAL to REST (autobiographical episodic memory ecphory). In addition, the right temporomesial, right dorsal prefrontal, right posterior cingulate areas, and the left cerebellum were activated. A comparison of PERSONAL and IMPERSONAL (autobiographical vs nonautobiographical episodic memory ecphory) demonstrated a preponderantly right hemispheric activation including primarily right temporomesial and temporolateral cortex, right posterior cingulate areas, right insula, and right prefrontal areas. The right temporomesial activation included hippocampus, parahippocampus, and amygdala. These results suggest that a right hemispheric network of temporal, together with posterior, cingulate, and prefrontal, areas is engaged in the ecphory of affect-laden autobiographical information.

Adult↗

Visual versus auditory memory stimulation in patients with probable Alzheimer's disease. A PET study with 18 FDG.

Patients with probable Alzheimer's disease were either stimulated with a continuous visual recognition task (n = 18) or with a continuous auditory recognition task during PET measurement with 18 FDG. The PET scanner was a Siemens CTI, ECAT EXACT with 5 mm transaxial and 6 mm axial resolution. The global stimulation effects were nearly identical in both groups and increased of 4.17 +/- 8.14% in the auditory stimulated group and of 4.03 +/- 11.78% in the visual stimulated group. Beyond regional stimulation effects in both groups a common cerebellar stimulation effect was measured. It is concluded that the cerebellar stimulation effect reflects a modality independent cognitive process and that the only small enhancement of global glucose metabolism indicates disturbed stimuli processes and finally explained the patient's failure in memory tasks.

Aged↗

MRI-guided flumazenil- and FDG-PET in temporal lobe epilepsy.

In temporal lobe epilepsy (TLE) patients without lesions, major hippocampal sclerosis, or atrophy on magnetic resonance imaging (MRI), the localizing power of [11C]flumazenil (FMZ) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was compared using high-resolution positron emission tomography (PET) studies and individually coregistered MRI scans. Following complete clinical, neuropsychological, and electrophysiological evaluation, benzodiazepine receptor density was assessed using the FMZ equilibrium method. Thirty minutes later, interictal FDG-PET was performed under resting conditions. PET images were matched to three-dimensionally coregistered, T1-weighted MRI. Each temporal lobe (TL) was divided into 12 volumes of interest. The regional FMZ data were normalized with respect to average cortical values. For each patient the right-left asymmetries of rCMRGlc and normalized FMZ data were calculated. In 7 to 10 patients, mesial TL structures showed reduced FMZ binding, with a decrease by at least 10% in the affected TL. Reductions of 10% or more of rCMRGlc usually were more widespread than FMZ reductions and often involved lateral temporal cortex. The regions of most pronounced disturbances are not necessarily identical in both methods. Three patients had a complex correspondence of lateralization with PET, neuropsychological, and EEG data. In 4 patients, lateralization was less clear from EEG or neuropsychological results but was still consistent with lateralization by PET. In 3 of 10 patients, however, major discrepancies were found. These data suggest that the combination of neuropsychological testing, EEG, and MRI-guided FMZ- and FDG-PET will help to select patients with clearly defined epileptogenic foci especially in mesial TLE. Even in cases without MRI lesions, TL epileptic foci can be lateralized with consistency across the methods; FMZ-PET shows the pathologic focus more circumscribed than FDG-PET.

Adult↗

Individual functional anatomy of verb generation.

Examination of the individual functional anatomy of language is of particular interest in clinical neurology to explain the variability of aphasic symptoms after focal lesions and to avoid damage of language-related brain areas by surgery. For a silent verb generation task, we examined whether activation PET with 3D data acquisition, multiple replication of conditions, and coregistration with MRI provides results that are consistent and reproducible enough to be useful clinically. Visual analysis was performed on PET-MRI fusion images, including renderings of the brain surface. Quantitative analysis was based on volumes of interest. In seven right-handed normals, activation of the triangular part of the left inferior frontal cortex [Brodman area (BA) 45] was the most significant finding that was present in each subject. Two subjects showed minor anatomical variants of the ascending or horizontal ramus of the sylvian fissure that were associated with the least activation of BA 45. In the left hemisphere the other frontal gyri, the superior temporal and posterior part of the middle temporal gyrus, and the paracingulate gyrus were also significantly activated. There was significant bilateral cerebellar activation, but it was significantly more intense on the right than on the left side. The consistency and high interindividual reproducibility of these findings suggest that this technique may be useful for clinical assessment of language-related areas.

Acoustic Stimulation↗

Vascular dementia: perfusional and metabolic disturbances and effects of therapy.

Positron emission tomography (PET) has elucidated basic pathophysiological mechanism that produce the cognitive decline in vascular dementia (VD). The typical pattern of glucose metabolism seen in VD with scattered areas of focal cortical and subcortical hypometabolism differs from that in AD with marked hypometabolism affecting the association areas. The total volume of metabolically inactive tissue is significantly related to severity of dementia. Rather than the quantity of tissue destruction, the critical effect may be the quantity of cortical hypometabolism caused by subcortically induced disconnection. Studies with HMPAO SPECT have shown focal deficits in VD and AD patients that are comparable to those seen with FDG PET. In mildly demented patients performance for the classification AD versus VD is much better by PET because it might be more sensitive for imaging small functional pathological changes. A longitudinal analysis of rCMRGl in VD showed that the progression of dementia can be delayed by the adenosine uptake blocker propentofylline and that neuropsychological and metabolic changes are closely related.

Brain↗