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A Thiel

Publications and source records attributed to A Thiel.

At least 73 records · Page 4Linked to original sources

Which targets are relevant for therapy of acute ischemic stroke?

BACKGROUND: The efficiency of various strategies of neuroprotection is well documented in animal experiments but is thus far disappointing in ischemic stroke, for which only early reperfusion induced by thrombolysis has improved clinical outcome. This discrepancy between expectation from experimental research and clinical reality may be related to differences in the pathogenetic factors contributing to infarction. SUMMARY OF COMMENT: Positron emission tomography cerebral blood flow studies within 3 hours of onset were used to identify the various compartments of the infarct outlined on MRI 2 to 3 weeks after a hemispheric stroke in 10 patients. Critical hypoperfusion below the viability threshold accounted for the largest proportion (mean, 70%) of the final infarct, whereas penumbral tissue (18%) and initially sufficiently perfused tissue (12%) were responsible for considerably smaller portions of the final infarct. CONCLUSIONS: These results indicate that early critical flow disturbance leading to rapid cell damage is the predominant cause of infarction, while secondary and delayed pathobiochemical processes in borderline or initially sufficiently perfused regions contribute only little to the final infarct. Therefore, emerging therapeutic strategies should be targeted to the initially critically perfused tissue subcompartments. Clinical drug trials might benefit from stratification of patients for target tissue compartments applying functional imaging.

Acute Disease↗

[Not Available].

OBJECTIVE: The present study examines the question of whether concomitant narcissistic self-disorders indicate a poorer prognosis in patients with anorexia nervosa (AN) and bulimia nervosa (BN). METHOD: Ninety-one female inpatients who met the DSMIV criteria fo AN or BN were investigated during inpatient treatment by using: a semistructured diagnostic interview, the Eating Disorder Inventory (EDI), the Narcissism Inventory (NI), the Hamburg Obsession-Compulsion Inventory, and the Inventory of Interpersonal Problems (IIP). The patients were divided into two groups: those with and those without narcissistic self-disorders as measured by the NI. Seventy-five patients were assessed at follow-up thirty months after discharge. RESULTS: Fifty-one percent of the follow-up group no longer fulfilled the DSM-IV criteria for AN or BN, and there was no significant correlation with the earlier presence of concomitant narcissistic self-disorders. At follow-up, patients with narcissistic self-disorders had significantly more pathological mean scores than patients without such disorders on four of the eight EDI scales and on four of the eight IIP scales. ANOVA for repeated measures revealed significant improvement over time on seven of the eight EDI scales in both groups. However, significant group-by-time interactions demonstrated that patients with narcissistic self-disorders had improved more over time than patients without selfdisturbances. Furthermore, the obsessive-compulsive Symptoms of those patients with narcissistic self-disorders who no longer fulfilled DSM-IV criteria for AN or BN had significantly decreased. CONCLUSION: Our findings indicate that the improvement of eating disorder Symptoms corresponds to a decrease in obsessive-compulsive Symptoms. In addition, there is a certain degree of independence between the severity of narcissistic self-disorders and the outcome of AN or BN. The results suggest that concomitant narcissistic self-disorders do not indicate a significantly poorer prognosis in patients with AN and BN.

Anorexia nervosa↗

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↗

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↗

["I have killed my child". Experiences with severe depression in mothers after sudden infant death from the psychiatric and legal medicine viewpoint].

Grief and depressive syndrome belong to normal reaction by parents after a sudden infant death (SID). In the following we report on two cases from the point of view of psychiatry and forensic medicine in which, subsequent to SID, mothers reacted with extremely grave depression and accused themselves of having killed the child. Furthermore, some recommendations are given for the care of parents affected.

Delusions↗

Evaluation of a porcine internal mammary artery (No-React II) as a small-diameter conduit.

BACKGROUND: The patency of biologic small-diameter vascular grafts in the aortocoronary position is still unsatisfactory. Most of the studies suggest that xenografts are to be avoided as an aortocoronary bypass. METHODS: The porcine internal mammary artery treated by the No-React II procedure was developed for use as an alternative coronary artery bypass conduit. The attempt of this study was to evaluate the patency and histologic changes of the porcine internal mammary artery in animals. Five calves underwent coronary artery bypass grafting with a porcine internal mammary artery graft to the right coronary artery. After euthanasia of the animals 103 days later, the samples of these grafts were studied morphologically for patency, structural changes, calcifications, and inflammatory and immunologic response. RESULTS: One animal died during the procedure as result of acute thrombosis of the porcine internal mammary artery graft. In the other 4 animals all grafts became occluded. In the histologic sections of the grafts we noted multiple calcifications and a host-graft immunologic reaction (severe chronic rejection). CONCLUSIONS: The present study demonstrates a very poor experience with the porcine internal mammary artery (No-React II) conduit. We do not recommend this prosthesis for clinical use in humans.

Animals↗

[Development of the AMDP module for identification of obsessive- compulsive symptoms. Conceptualization and empirical results].

Results of epidemiology and comorbidity studies have recently demonstrated the psychopathological relevance of obsessive-compulsive symptoms. Therefore the "Arbeitsgemeinschaft für Methodik und Diagnostik in der Psychiatrie" (AMDP) has started to develop a rating scale for a quick and precise assessment of obsessive-compulsive symptoms. The actual version of the scale comprises 20 items on the dimensions "description", "distress and impairment" and "emotion and cognition". The results of a first empirical study (n = 137, psychiatric in- and outpatients) demonstrated excellent internal consistency (Cronbach's alpha = 0.92), a split-half reliability of 0.89 (Spearman-Brown), a test-retest reliability of r = 0.86 and good convergent validity with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Hamburger Zwangsinventar (HZI). The factor-analytical distribution of the 20 items revealed a 4-factor structure of the scale. The results are presented and their implications on further steps of the development of the scale are discussed.

Adult↗

Survival of long-lived plasma cells is independent of antigen.

Recent studies have shown that persistent specific antibody titer is provided by long-lived plasma cells (PC) which constitute a new kind of 'memory-providing cells'. In the present study, we examine the role of antigen for the long-term survival of PC and the maintenance of specific serum antibody titers. Using a novel cytometric technology, to identify and isolate antigen-specific PC, we analyzed long-lived PC of BALB/c mice, during their development (between day 1 and 10) after secondary immunization with ovalbumin (OVA) and in the phase of the established immune reaction. Most if not all OVA-specific PC were generated within a few days after immunization. Within approximately 3 weeks, they matured, as indicated by down-regulation of expression of MHC class II. These PC are long lived and located in spleen and bone marrow. Upon adoptive transfer, OVA-specific PC from bone marrow, but not memory B cells, conferred specific and long-lasting antibody titers to antigen-free IgH syngeneic recipients. In response to antigenic challenge, new OVA-specific antibody-secreting cells were generated from transferred memory B cells. Antibody secretion by long-lived PC was not affected. Our results confirm that persistent antibody titers are provided by long-lived PC, independent of memory B cells and demonstrate that this humoral memory is inert to antigen.

Adoptive Transfer↗

Tissue at risk of infarction rescued by early reperfusion: a positron emission tomography study in systemic recombinant tissue plasminogen activator thrombolysis of acute stroke.

Thrombolytic therapy of acute ischemic stroke can be successful only as long as there is penumbral tissue perfused at rates between the thresholds of normal function and irreversible structural damage, respectively. To determine the proportion of tissue at risk of infarction, cerebral perfusion was studied in 12 patients with acute ischemic stroke who underwent treatment with systemic recombinant tissue plasminogen activator (0.9 mg/kg body weight according to National Institute of Neurological Disorders and Stroke protocol) within 3 hours of onset of symptoms, using [15O]-H2O positron emission tomography (PET) before or during, and repeatedly after thrombolysis. The size of the regions of critically hypoperfused gray matter were identified on the initial PET scans, and changes of perfusion in those areas were related to the clinical course (followed by the National Institutes of Health stroke scale) and to the volume of infarcted gray matter demarcated on magnetic resonance imaging 3 weeks after the stroke. Whereas the initial clinical score was unrelated to the size of the ischemic area, after 3 weeks there was a strong correlation between clinical deficit and volume size of infarcted gray matter (Spearman's rho, 0.96; P < 0.001). All patients with a severely hypoperfused (< 12 mL/100 g/min) gray matter region measuring less than 15 mL on first PET showed full morphologic and clinical recovery (n = 5), whereas those with ischemic areas larger than 20 mL developed infarction and experienced persistent neurologic deficits of varying degree. Infarct sizes, however, were smaller than expected from previous correlative PET and morphologic studies of patients with acute stroke: only 22.7% of the gray matter initially perfused at rates below the conventional threshold of critical ischemia became necrotic. Actually, the percentage of initially ischemic voxels that became reperfused at almost normal levels clearly predicted the degree of clinical improvement achieved within 3 weeks. These sequential blood flow PET studies demonstrate that critically hypoperfused tissue can be preserved by early reperfusion, perhaps related to thrombolytic therapy. The results correspond with experimental findings demonstrating the prevention of large infarcts by early reperfusion to misery perfused but viable tissue.

Acute Disease↗

Disposition and elimination of meropenem in cerebrospinal fluid of hydrocephalic patients with external ventriculostomy.

The broad antibacterial spectrum and the low incidence of seizures in meropenem-treated patients qualifies meropenem for therapy of bacterial meningitis. The present study evaluates concentrations in ventricular cerebrospinal fluid (CSF) in the absence of pronounced meningeal inflammation. Patients with occlusive hydrocephalus caused by cerebrovascular diseases, who had undergone external ventriculostomy (n = 10, age range 48 to 75 years), received 2 g of meropenem intravenously over 30 min. Serum and CSF were drawn repeatedly and analyzed by liquid chromatography-mass spectroscopy. Pharmacokinetics were determined by noncompartmental analysis. Maximum concentrations in serum were 84.7 +/- 23.7 microg/ml. A CSF maximum (CmaxCSF) of 0.63 +/- 0.50 microg/ml (mean +/- standard deviation) was observed 4.1 +/- 2.6 h after the end of the infusion. CmaxCSF and the area under the curve for CSF (AUCCSF) depended on the AUC for serum (AUCS), the CSF-to-serum albumin ratio, and the CSF leukocyte count. Elimination from CSF was considerably slower than from serum (half-life at beta phase [t1/2beta] of 7.36 +/- 2.89 h in CSF versus t1/2beta of 1.69 +/- 0.60 h in serum). The AUCCSF/AUCS ratio for meropenem, as a measure of overall CSF penetration, was 0.047 +/- 0.022. The AUCCSF/AUCS ratio for meropenem was similar to that for other beta-lactam antibiotics with a low binding to serum proteins. The concentration maxima of meropenem in ventricular CSF observed in this study are high enough to kill fully susceptible pathogens. They may not be sufficient to kill bacteria with a reduced sensitivity to carbapenems, although clinical success has been reported for patients with meningitis caused by penicillin-resistant pneumococci and Pseudomonas aeruginosa.

Aged↗

Permanent cortical damage detected by flumazenil positron emission tomography in acute stroke.

BACKGROUND AND PURPOSE: Therapy of acute ischemic stroke can only be effective as long as neurons are viable and tissue is not infarcted. Since gamma-aminobutyric acid receptors are abundant in the cortex and sensitive to ischemic damage, specific radioligands to their subunits, the central benzodiazepine receptors (BZR), may be useful as indicators of neuronal integrity and as markers of irreversible damage. To test this hypothesis we studied the binding of the BZR ligand [11C]flumazenil (FMZ) early after ischemic stroke in comparison to the extent of final infarcts and hypometabolic cortical areas. METHODS: In 10 patients cerebral blood flow, cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and FMZ binding were studied by positron emission tomography 3.5 to 16 hours after onset of their first hemispheric stroke. Early changes in flow, oxygen metabolism, and FMZ binding were compared with permanent disturbances in glucose metabolism, and the size of the final infarcts was determined on MRI or CT 12 to 22 days after the stroke. RESULTS: In all patients except one cerebral blood flow was disturbed, with marked decreases in eight and a hyperperfusion in one patient corresponding to the location of neurological deficits. In these areas CMRO2 was also reduced but to a variable degree, inducing highly variable OEF. Areas with markedly decreased CMRO2 (<60 micromol/100 g per minute) corresponded to regions with decreased FMZ binding (<4.0 times the mean value in the white matter). In all patients the final cortical infarcts were visible on the early FMZ images. Infarcts could be discriminated from noninfarcted cortex by decreased FMZ binding despite a wide range of OEF. In finally hypometabolic cortex FMZ binding was initially decreased or normal, with OEF covering a wide range; this suggested neuronal loss and/or deactivation as the cause of metabolic disturbance. Additionally, a highly significant correlation was found between FMZ distribution within the first 2 minutes after injection and regional cerebral blood flow. CONCLUSIONS: These results demonstrate that permanently and irreversibly damaged cortex can be detected by reduced FMZ binding early after stroke. Since FMZ distribution additionally images regional cerebral perfusion, BZR radioligands have a potential as clinically useful tracers in patients with acute ischemic stroke. The evidence of tissue damage furnished by these tracers might be of relevance for the selection of individual therapeutic strategies.

Aged↗

Thirty-month outcome in patients with anorexia or bulimia nervosa and concomitant obsessive-compulsive disorder.

OBJECTIVE: The present study examines whether concomitant obsessive-compulsive disorder (OCD) indicates a poorer prognosis for patients with anorexia or bulimia nervosa. METHOD: Seventy-five female inpatients who met DSM-IV criteria for anorexia or bulimia nervosa took part in the follow-up study; 29 of these patients met criteria for concomitant OCD. All patients were investigated twice: during inpatient treatment and at follow-up 30 months after discharge. A semistructured diagnostic interview was used as well as the Eating Disorder Inventory and the Hamburg Obsession-Compulsion Inventory--Short Form. RESULTS: At follow-up, 51% (N = 38) of the patients no longer fulfilled DSM-IV criteria for anorexia or bulimia nervosa, but this improvement was not significantly correlated with the earlier presence of concomitant OCD. Analysis of variance for repeated measures revealed significant improvement over time on six of the eight Eating Disorder Inventory subscales for all patients regardless of OCD presence. Furthermore, no significant group effects or group-by-time interactions were identified. Clinically significant change, as reflected by improvement in scores on the Eating Disorder Inventory, was seen somewhat more often in patients without concomitant OCD, but this trend was not statistically significant. The patients whose eating disorders were most improved at follow-up also showed the highest reduction of obsessions and compulsions. CONCLUSIONS: The results suggest that concomitant OCD does not indicate a significantly poorer prognosis for patients with anorexia or bulimia nervosa.

Adult↗

Higher prevalence of obsessive-compulsive symptoms in patients with blepharospasm than in patients with hemifacial spasm.

OBJECTIVE: The prevalences of obsessive-compulsive symptoms in patients suffering from blepharospasm and in those with hemifacial spasm were determined. The two conditions have similar symptoms, but only blepharospasm is etiologically linked to basal ganglia dysfunction. METHOD: After being interviewed with the Structured Clinical Interview for DSM-III-R, 13 patients with blepharospasm and 13 with hemifacial spasm completed the SCL-90-R and the Hamburg Obsession/Compulsion Inventory-Short Form. RESULTS: Patients in the blepharospasm group had significantly more obsessive-compulsive symptoms, as indicated by higher scores on the Hamburg Obsession/Compulsion Inventory-Short Form, than the patients with hemifacial spasm. SCL-90-R scores were in the normal range for nine and eight categories, respectively (out of nine). CONCLUSIONS: The findings provide additional support for the hypothesis that obsessive-compulsive symptoms are related to basal ganglia dysfunction.

Aged↗

11C-methionine PET for differential diagnosis of low-grade gliomas.

Management of low-grade gliomas continues to be a challenging task, because CT and MRI do not always differentiate from nontumoral lesions. Furthermore, tumor extent and aggressiveness often remain unclear because of a lack of contrast enhancement. Previous studies indicated that large neutral amino acid tracers accumulate in most brain tumors, including low-grade gliomas, probably because of changes of endothelial and blood-brain barrier function. We describe 11C-methionine uptake measured with PET in a series of 196 consecutive patients, most of whom were studied because of suspected low-grade gliomas. Uptake in the most active lesion area, relative to contralateral side, was significantly different among high-grade gliomas, low-grade gliomas, and chronic or subacute nontumoral lesions, and this difference was independent from contrast enhancement in CT or MRI. Corticosteroids had no significant effect on methionine uptake in low-grade gliomas but reduced uptake moderately in high-grade gliomas. Differentiation between gliomas and nontumoral lesions by a simple threshold was correct in 79%. Recurrent or residual tumors had a higher uptake than primary gliomas. In conclusion, the high sensitivity of 11C-methionine uptake for functional endothelial or blood-brain barrier changes suggests that this tracer is particularly useful for evaluation and follow-up of low-grade gliomas.

Adult↗

CD45RA-expressing memory/effector Th cells committed to production of interferon-gamma lack expression of CD31.

It has been considered before that human naive and memory/effector CD4+ T-cells cannot be subdivided solely according to the differential expression of CD45 isoforms. By the lack of expression of CD31 we have identified a subset of CD4+ CD45RA+ CD31- cells which show distinct features of antigen-experienced Th1 cells. Short term stimulation of highly purified human peripheral blood CD4+ T-cells with PMA/ionomycin, followed by the cytometric analysis of intracellular cytokines, showed that a minor subpopulation of CD4+ CD45RA+ CD45RO- cells is able to produce interferon-gamma (IFN-gamma) rapidly, a characteristic of antigen-experienced Th1 cells. Whereas among CD45RA+ CD4+ T-cells both CD31+ and CD31- subsets produce interleukin-2 (IL-2) upon PMA/ionomycin stimulation, only the CD31- subpopulation is able to produce IFN-gamma. Thus, our phenotypic and functional characterization of CD45RA+ CD45RO- Th cells shows that CD45RA+ CD45RO- cells do not represent a homogeneous population of antigen-unexperienced, naive T-cells. We speculate that a certain subset of human CD4+, CD45RO+ memory T-cells reverts to expression of the CD45RA isoform, and that this subset can be identified by the lack of CD31 expression.

Animals↗