Search PubMed⌕ Search

Biomedical subjects

W Paulus

Publications and source records attributed to W Paulus.

At least 109 records · Page 6Linked to original sources
PubMed2000

Radiation therapy approach in gliomatosis cerebri--case reports and literature review.

Gliomatosis cerebri is defined as a remarkably diffuse glioma, characterized by widespread infiltration of the central nervous system. Clinicopathologic characteristics and imaging findings have been published but valid classification remains controversial. Few reports exist regarding therapeutic options in gliomatosis cerebri. Here we review data on 17 patients treated with radiation therapy extracted from the literature, in which we focus our attention on available details of irradiation and clinical outcome and present the results of three additional patients treated at our two institutions. Radiologic-pathologic correlation in gliomatosis cerebri indicates that tumor delineation should be based on T2-weighted MRI. Radiation therapy in gliomatosis cerebri is associated with a temporary improvement in or stabilization of clinical symptoms in the majority of cases. Duration of improvement was > or = 6 months in 50% of treated patients. Survival from onset of symptoms was 23.8 months (range 8-42). Considerable variation in the natural course of the disease precludes conclusions regarding the impact of radiation therapy on survival.

Adolescent↗
PubMed2000

Comparative genomic hybridization in pineal germ cell tumors.

Fifteen primary pineal germ cell tumors (8 germinomas, 4 mixed teratomas-germinomas, 2 immature teratomas, and 1 yolk sac tumor) and 2 recurrences of the yolk sac tumor were studied by comparative genomic hybridization (CGH). An average of 1.8 chromosomal changes per germinoma (0.5 gains vs 1.3 losses), 5.5 per mixed teratoma-germinoma (3.0 gains vs 2.5 losses), 3.5 per immature teratoma (2.0 gains vs 1.5 losses), and 2.0 in the yolk sac tumor (2 gains vs 0 losses) were found; the first recurrence showed 7 (4 gains vs 3 losses), the second 13 imbalances (8 gains vs 5 losses). The most frequent imbalances were gains on 12p (40%), 8q (27%), and 1q (20%) as well as losses on 13q (47%), 18q (33%), 9q and 11q (20% each). Among germinomas, the most common chromosomal changes were -13q and -18q (38% each), in mixed teratomas-germinomas +8q (100%), +12p (75%), -13q (75%) and -9q (50%). Seven high-level gains were identified: 5 in mixed teratomas-germinomas (+8q: 3 cases, + 12p: 2 cases), 1 each in a germinoma (+2p) and an immature teratoma (+12p). Minimal common regions of over- and underrepresentation were found on +8q11.22-21.1, +12p11.1-12.1, -9q32-qter, -11q23.2-qter, -13q32-qter and -18q22-qter. Our findings suggest, that imbalances in cerebral germ cell tumors affect the same chromosomes as among their extracerebral counterparts, albeit in a considerably lower frequency among cerebral germinomas where +12p does not seem to play a major role.

Adolescent↗
PubMed2000

Motor cortex fatigue in sports measured by transcranial magnetic double stimulation.

PURPOSE: Besides peripheral mechanisms, central fatigue is an important factor limiting the performance of exhausting exercise in sport. The mechanisms responsible are still in discussion. Using noninvasive transcranial magnetic stimulation (TMS) in a double-pulse technique, we sought to assess fatigue of the motor cortex after exhaustive anaerobic strain. METHODS: 23 male subjects (22-52 yr) taking part in the study were requested to accomplish as many pull-ups as possible until exhaustion. The amount of physical lifting work was recorded. Before and immediately after the task, intracortical inhibition (ICI) and facilitation (ICF) were measured by a conditioned-test double-pulse TMS method for the right brachioradialis (BR) and abductor pollicis brevis muscle (APB). RESULTS: After exercise, ICF was significantly reduced in the BR but not in the APB. ICI was not altered. Changes tended to normalize within 8 min after the task. The amount of lifting work accomplished showed significant correlation to the values of ICF reduction (r = 0.73). Moreover, the baseline values of ICF before exercise were also significantly correlated to the lifting work (r = 0.63). CONCLUSIONS: Because double-pulse TMS gives access to the motor cortex independently of spinal or peripheral mechanisms, reduced ICF reflects decreased excitability of interneuronal circuits within the motor cortex. We suggest that ICF measures motor cortex fatigue after exhausting strain specifically for the muscles performing the task. Gamma-aminobutyric acid (GABA)-ergic neurotransmission is possibly involved in the mechanisms mediating central fatigue. Double-pulse TMS may be a useful tool in the control of training in sports as well as in the detection of pathological central fatigue in overreaching and in the prevention of overtraining.

Adult↗
PubMed2000

Source reconstruction of mesial-temporal epileptiform activity: comparison of inverse techniques.

PURPOSE: To evaluate whether advanced source reconstruction such as current density reconstruction (CDR) provides additional hints for clinical presurgical evaluation, different source reconstruction techniques with idealized spherical as well as realistically shaped head models (boundary element method, BEM) were applied on interictal and ictal epileptiform activity in presurgical evaluated patients with temporal lobe epilepsy. It is discussed whether CDR and BEM give additional information for presurgical evaluation compared to "conventional" strategies, such as single moving, and spatio-temporal dipole modeling with spherical head models. METHODS: A variety of source reconstruction procedures were applied to the data of five patients with pharmacoresistent temporal lobe epilepsy with probable mesial origin: (1) single-moving dipole in a spherical head model and (2) in BEM, (3) spatio-temporal dipole modeling in a spherical head model and (4) in BEM; and (5) deconvolution with fixed locations and orientations and (6) with cortically constrained L1-norm CDR in BEM. In addition, simulated sources of temporal lobe origin were calculated in each subject with CDR to prove the basic feasibility of this technique in the particular application. RESULTS: Source activity was correctly localized within the affected temporal lobe by all source reconstruction techniques used. Neither single moving dipole, spatio-temporal modeling, nor CDR was able to localize sources at a sublobar level. In the case of two sources, single moving dipole solutions showed changes in dipole orientation in time and spatio-temporal modeling separated two sources, whereas CDR at the peak latency failed to distinguish among different origins. BEM enhanced localization accuracy. CONCLUSION: There was no advantage of using CDR. Single moving dipole as well as spatio-temporal dipole modeling in BEM leads to more precise localization within the individual anatomy and provides a simple algorithm, which is capable of indicating both the time course and the number of sources.

Brain Mapping↗
PubMed2000

Dipole-source analysis in a realistic head model in patients with focal epilepsy.

PURPOSE: By the use of three different head models in EEG dipole analysis, we tried to model the origin of interictal and ictal epileptic activity as precisely as possible. Further, as a control, a second evaluation was made by an independent group to control for interindividual reliability of the dipole source analysis. With the realistic head model (CURRY) considering cortex, skull, and skin segmentation, the spike source was located. METHODS: In five patients with mesial temporal epileptogenesis, confirmed by successful epilepsy surgery, the spike source was close to the hippocampus, with a mean distance of the dipole source from the hippocampus of 13.6 mm (range, 9-17.2 mm). In one case the ictal EEG also could be analyzed and resulted in a dipole-source localization comparable to the interictal source. RESULTS: In both head models using either pure cortex segmentation only or a concentric three-shell model, the dipole source was systematically dislocated in a more superior position. Data analysis by a second group with independently chosen EEG samples and identical individual head model resulted in deviations of <5.3 mm. Data analysis using independently selected spikes and independently segmented head models resulted in deviations < or =16.7 mm. CONCLUSIONS: In four cases of extratemporal epileptogenesis, the origin of interictal epileptiform discharges was localized to the suspected primary epileptogenic zone.

Adult↗
PubMed1999

Deficient motor control in children with tic disorder: evidence from transcranial magnetic stimulation.

Decreased motor inhibition was reported in adult patients with tic disorder (TD) using the technique of transcranial magnetic stimulation. Since tics usually begin during childhood, motor threshold, cortical silent period (CSP) and intracortical inhibition/facilitation were measured in 21 TD children and 25 healthy children aged 10-16 years. In TD children motor threshold was normal. The CSP was significantly shortened compared to healthy controls but did not depend on tic localization. Intracortical inhibition and facilitation did not differ between the two groups. This study confirms that the finding of decreased motor control in adult patients also holds true for children wherever the tics in the latter group were located.

Adolescent↗
PubMed1999

Characterization and regional distribution of nitric oxide synthase in the human brain during normal ageing.

Nitric oxide (NO) is a highly diffusible cellular mediator generated from L-arginine by the enzyme nitric oxide synthase (NOS). As little is known about the regional distribution of NOS in the human brain, we examined the distribution pattern of nitric oxide synthase activity in 28 regions of the human brain using the [(3)H]L-citrulline formation assay. To elucidate which isoforms contribute to the total NOS activity we performed Western blot analysis of neuronal, inducible and endothelial NOS. We further determined brain levels of arginine and citrulline as a potential index of NOS activity pre mortem. NOS activity appears to remain unaltered during ageing and is independent of post mortem delay, gender or sample storage time. We identified a regional pattern of NOS distribution with highest levels of NOS activity in the substantia innominata, cerebellar cortex, nucleus accumbens and subthalamicus, whereas lowest levels were measured in the corpus callosum, thalamus, occipital cortex, and dentate nucleus. nNOS was measured throughout the brain, in contrast iNOS and eNOS were not detectable. We therefore conclude that primarily nNOS is responsible for NOS activity in the human brain. Levels of citrulline were higher than those of arginine, but did not correlate with the enzyme activity, suggesting that these parameters are unsuitable for testing NOS activity premortem. The characterization and topographical pattern of NOS in the human brain during normal ageing may assist our understanding of the physiological role of NO and its relevance in Parkinson's and Alzheimer's disease, alcoholism, schizophrenia and AIDS.

Adolescent↗
PubMed1999

Changes in 5-HT1A and NMDA binding sites by a single rapid transcranial magnetic stimulation procedure in rats.

The effects of a single rapid-rate transcranial magnetic stimulation (rTMS) exposure on neurotransmitter binding sites in the rat brain 24 h after the stimulation were examined. Quantification by in vitro-autoradiography showed no differences for 3H-paroxetine binding (5-HT uptake sites) between rTMS-treated, sham and control animals. In contrast, the number of 5-HT1A binding sites (labeled with 3H-8-OH-DPAT) were selectively increased in the rTMS-group with significantly higher BMAX values in the frontal cortex, the cingulate cortex, and the anterior olfactory nucleus. A non-specific increase in NMDA binding sites (labeled with 125I-MK-801) in rTMS and sham animals was observed in the hippocampal formation. A selective increase of these binding sites after rTMS was detected in the ventromedial hypothalamus, the basolateral amygdala and layers 5-6 of the parietal cortex. These findings imply that a single rTMS exposure can result in persistent effects on NMDA and 5-HT1A binding sites even 24 h after stimulation and therefore may be of relevance with respect to the therapeutic action of rTMS reported from clinical studies.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Differential inhibition of chromatic and achromatic perception by transcranial magnetic stimulation of the human visual cortex.

The magnocellular visual pathway is devoted to low-contrast achromatic and motion perception whereas the parvocellular pathway deals with chromatic and high resolution spatial vision. To specifically separate perception mediated by these pathways we have used low-contrast Gaussian filtered black-white or coloured visual stimuli. By use of transcranial magnetic stimulation (TMS) over the visual cortex inhibition of magnocellular stimuli was achieved distinctly earlier by about 40 ms compared with parvocellular information. A nonspecific inhibition of all stimuli could be seen peaking at 75-90 ms, significantly higher for magnocellular stimuli. The particular vulnerability of magnocellular stimuli to TMS is correlated with distinct physiological properties of this pathway such as faster conduction velocity and non-linear stimulus encoding.

Analysis of Variance↗
PubMed1999

Motor system excitability in patients with restless legs syndrome.

In 18 patients with idiopathic restless legs syndrome (RLS), intracortical inhibition by paired transcranial magnetic stimulation (TMS) was significantly reduced for both foot and hand muscles, suggesting that the entire motor cortex is disinhibited in RLS. Decreased intracortical facilitation in the foot muscle but not in the hand muscle may be due to subliminal activation of the symptomatic lower limbs. Motor excitability measurements of single TMS were not altered. These results support a subcortical origin of RLS.

Aged↗
PubMed1999

Riluzole does not have an acute effect on motor thresholds and the intracortical excitability in amyotrophic lateral sclerosis.

Intracortical excitability in amyotrophic lateral sclerosis (ALS) is impaired. The effectiveness of the glutamate antagonist riluzole (Rilutek, Rhône-Poulenc Rorer) in ALS has been shown in clinical studies. In healthy subjects it modifies intracortical excitability in a frequently used double-stimulus paradigm of transcranial magnetic stimulation (TMS). Under riluzole intracortical inhibition is enhanced in healthy individuals, although not always significantly, whereas intracortical facilitation has been described as reduced [10, 11]. We wanted to find out whether riluzole affects and potentially rebalances impaired intracortical excitability in ALS. We, therefore, enrolled 13 patients with clinically and electromyographically confirmed ALS into this study. Five patients had to be excluded because motor thresholds were too high to get reliable motor evoked potentials (MEPs). In the remaining 8 patients, mean age was 59.9 +/- 11.9 years (+/- standard deviation) and mean symptom duration 9.6 +/- 2.5 months. Intracortical excitability was assessed before and 1.5 hours after the first intake of a loading dose of 100 mg of riluzole using a conventional paired-pulse TMS paradigm with interstimulus intervals (ISI) ranging from 1-30 ms and intensities adjusted to yield MEPs of 1.0 mV for test pulses and of 90% active motor threshold for conditioning pulses. Patients' baseline results were compared to those of 9 age-matched, healthy control subjects. Before drug intake, motor thresholds did not differ between groups, but there was significantly less intracortical inhibition in the ALS patient group. Riluzole intake did not significantly alter motor thresholds or intracortical excitability in the ALS patients. We conclude that riluzole does not immediately influence intracortical excitability in ALS. Our results are in contrast to the findings of Stefan et al (1998) [14] where a partial normalization of intracortical inhibition in ALS was observed after at least 5 days of drug intake. The difference between that study and our result may indicate a delayed onset of riluzole's influence on intracortical excitability.

Aged↗
PubMed1999

Complete suppression of voluntary motor drive during the silent period after transcranial magnetic stimulation.

To evaluate changes in the motor system during the silent period (SP) induced by transcranial magnetic stimulation (TMS) of the motor cortex, we investigated motor thresholds as parameters of the excitability of the cortico-muscular pathway after a suprathreshold conditioning stimulus in the abductor digiti minimi muscle (ADM) of normal humans. Since the unconditioned motor threshold was lower during voluntary tonic contraction than at rest (31.9+/-5.4% vs. 45.6+/-7.5%), it is suggested that the difference between active and resting motor threshold indicates the magnitude of the voluntary drive on the cortico-muscular pathway. Therefore, we compared conditioned resting and active motor threshold (cRMT and cAMT) during the SP. cRMT showed an intensity-dependent period of elevation of more than 200 ms in duration and approximately 17% of the maximum stimulator output above the unconditioned threshold, due to decreased excitability of the cortico-muscular pathway after the conditioning stimulus. Some 3040 ms after the conditioning stimulus, cAMT approximated cRMT, indicating complete suppression of the voluntary motor drive. This suppression did not start directly after the conditioning stimulus since cAMT was still significantly lower than the cRMT within the first 30-40 ms. Threshold elevation was significantly longer than the SP (220+/-41 vs. 151+/-28 ms). Recovery of the voluntary motor drive started late in the SP and was nearly complete at the end of the SP, although thresholds were still significantly elevated. We conclude that the SP is largely due to a suppression of voluntary motor drive, while the threshold elevation is a different inhibitory phenomenon that is of less importance for the generation of the SP, at least in its late part. It is argued that the pathway of fast cortico-spinal fibers activated by TMS is partially different from the pathway involved in the maintenance of tonic voluntary muscle activation.

Adult↗
PubMed1999

Intrasellar malignant lymphoma developing within pituitary adenoma.

A mixed lymphoblastic T cell lymphoma and gonadotroph cell pituitary adenoma occurred 25 years after first resection of the adenoma. Within 1 year the lymphoma overgrew the adenoma, but was still restricted to the sellar region. Histologically, lymphoma and adenoma components were tightly admixed. Possible pathogenetic pathways for intra-adenomatous lymphoma development include monoclonal expansion of T cell infiltrates, expression of adhesion molecules specific for adenoma endothelium, and production of mitogenic pituitary hormones.

Adenoma↗
PubMed1999

Xanthogranuloma of the sellar region: a clinicopathological entity different from adamantinomatous craniopharyngioma.

Xanthogranulomatous change of craniopharyngioma, consisting of cholesterol clefts, macrophages, chronic inflammatory infiltrates, necrotic debris and hemosiderin deposits, has been traditionally considered a hallmark of the adamantinomatous variant, even in the absence of epithelium. Based on a series of 110 craniopharyngioma patients undergoing primary surgery, we found 37 specimens with a predominating xanthogranulomatous component. Only 3 of these cases (8%) exhibited additional histological features of adamantinomatous craniopharyngioma, while 13 cases (35%) contained non-adamantinomatous epithelium composed of squamous or ciliated cuboidal cells. Subsequent clinical analysis revealed that these 37 xanthogranulomatous lesions differed from 59 classical adamantinomatous craniopharyngiomas with respect to preferential occurrence in adolescents and young adults (mean age 27 years), predominant intrasellar location, smaller tumor size, more severe endocrinological deficits, longer preoperative history, lower frequency of calcification and visual disturbances, better resectability, and a more favorable outcome. On the other hand, xanthogranulomatous and adamantinomatous lesions did not differ with respect to sex, amount of cystic components, or the intraoperative aspect, considered by the neurosurgeon as being typical for craniopharyngioma in all cases. We suggest that xanthogranuloma (cholesterol granuloma) of the sellar region is clinically and pathologically distinct from the classical adamantinomatous craniopharyngioma.

Adolescent↗
PubMed1999

Chromosomal imbalances in primary lymphomas of the central nervous system.

Twenty-two primary central nervous system lymphomas of immunocompetent adults were studied by comparative genomic hybridization. All were high-grade diffuse large B cell lymphomas. Comparative genomic hybridization revealed an average of 5.5 chromosomal changes per tumor, with gains being more common than losses (3.5 vs. 2.0). The most frequent DNA copy number changes were gains on chromosomes 1, 12, 18 (41% each), 7 (23%), and 11 (18%) and losses involving chromosomes 6 (59%), 18, and 20 (18% each). Commonly involved regions were +12q (41%), +18q (36%), +1q (32%), and +7q (23%), as well as -6q (50%), -6p (18%), -17p, and -18p (14% each). High-level gains were found on 7 chromosomes, mainly involving chromosomes 18q (23%), 12q (18%), and 1q (14%). Minimal common regions of over- and underrepresentation were found on +1q25-31, -6q16-21, +7q11.2, +12p11.2-13, +12q12-14, +12q22-24.1, and +18q12.2-21.3. A significant correlation between loss of DNA copy numbers on chromosome 6q and shorter survival could be established (10.2 vs. 22.3 months; P < 0.05). Our findings suggest that chromosomal imbalances of primary central nervous system lymphomas are similar to those of diffuse large B cell lymphomas at other locations and are probably not related to cerebral presentation; however, they may be prognostically relevant.

Adult↗
PubMed1999

Tetracycline-controlled expression but not toxicity of an attenuated diphtheria toxin mutant.

Tight transcriptional regulation of transferred bacterial toxin genes represents a potential approach for gene therapy of cancer. We have previously shown that the gene for wild type diphtheria toxin A chain (DT-A) placed under transcriptional control of a tetracycline-responsive promoter cannot be silenced due to its extreme toxicity. We now have explored a tetracycline-regulated DT-A mutant involving the histidine-21 catalytic domain (H21A) which shows 120-fold reduced ADP-ribosylation activity. Cellular toxicity was determined in NIH 3T3 fibroblasts and C6 glioma cells after triple transfections with the DT-A construct, the Tet transactivator gene and a luciferase plasmid as the reporter. Marked toxicity, i.e. reduced luciferase expression by more than 98%, was observed both in the absence and in the presence of tetracycline, suggesting leakiness of the Tet system, and absence of regulation, possibly due to inhibition of DT-A synthesis by activated DT-A itself. In contrast, the lacZ gene which was driven by the same promoter could be regulated by up to 49-fold. We conclude that (1) expression but not toxicity of the DT-A mutant can be sufficiently controlled by a tetracycline-responsive promoter, and (2) tight regulation of transferred genes encoding toxins remains a challenge for gene therapy of cancer.

3T3 Cells↗