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W Paulus

Publications and source records attributed to W Paulus.

At least 91 records · Page 5Linked to original sources
PubMed2000

Diminution of training-induced transient motor cortex plasticity by weak transcranial direct current stimulation in the human.

Training of a thumb movement in the opposite direction of a twitch in response to transcranial magnetic stimulation (TMS) induces a transient directional change of post-training TMS-evoked movements towards the trained direction. Functional synaptic mechanisms seem to underlie this rapid training-induced plasticity. Transcranial direct current stimulation (tDCS) induces outlasting changes of cerebral excitability, thus presenting as promising tool for neuroplasticity research. We studied the influence of tDCS, applied over the motorcortex during training, on angular deviation of post-training to pre-training TMS-evoked thumb movements. With tDCS of anodal and cathodal polarity the training-induced directional change of thumb movements was significantly reduced during a 10 min post-training interval, indicating an interference of tDCS with mechanisms of rapid training-induced plasticity.

Adult↗
PubMed2000

Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.

In this paper we demonstrate in the intact human the possibility of a non-invasive modulation of motor cortex excitability by the application of weak direct current through the scalp. Excitability changes of up to 40 %, revealed by transcranial magnetic stimulation, were accomplished and lasted for several minutes after the end of current stimulation. Excitation could be achieved selectively by anodal stimulation, and inhibition by cathodal stimulation. By varying the current intensity and duration, the strength and duration of the after-effects could be controlled. The effects were probably induced by modification of membrane polarisation. Functional alterations related to post-tetanic potentiation, short-term potentiation and processes similar to postexcitatory central inhibition are the likely candidates for the excitability changes after the end of stimulation. Transcranial electrical stimulation using weak current may thus be a promising tool to modulate cerebral excitability in a non-invasive, painless, reversible, selective and focal way.

Adult↗
PubMed2000

Variability of transcriptional regulation after gene transfer with the retroviral tetracycline system.

Inducible transcription and position-independent expression are critical issues after gene transfer. To gain insight into the amount of variability of transcriptional regulation due to random proviral integration, we analyzed a total of 200 C6 glioma and rat-1 fibroblast clones retrovirally infected with the conventional and reverse tet systems where a luciferase reporter gene was placed under control of a tetracycline-responsive promoter. Repressed luciferase activities differed by up to 81000-fold among individual clones. Repressed activities close to baseline levels were observed in eight clones, all of them transduced with the conventional tet system. Regulation factors ranged from less than two-fold (indicating absence of regulation), observed in 17 clones to 90-fold. Regulation was higher with the conventional tet system as compared with the reverse tet system. Our data show that even under these standardized conditions there was a very high variability in absolute expression levels and regulability between individual clones, and they suggest that homogeneous transcriptional regulation in a cellular population remains a challenge for research in biotechnology.

Animals↗
PubMed2000

Human post-mortem striatal alpha4beta2 nicotinic acetylcholine receptor density in schizophrenia and Parkinson's syndrome.

The density of nicotinic alpha4beta2 receptors, which are believed to largely mediate nicotine's effects, has been reported to be decreased in post-mortem hippocampus of patients with schizophrenia. In the present study, using [(3)H]cytisine as a radioligand, we observed a significant 30% decrease in post-mortem striatum of patients with schizophrenia (n=12) as compared to controls (n=12). A 25% decrease of striatal alpha4beta2 receptor density in patients with Parkinson's syndrome (n=12) was not significant. As an upregulation of alpha4beta2 receptors has been observed due to nicotine consumption, the beneficial effects of nicotine described in patients with schizophrenia may be partly due to a compensation for a decrease in alpha4beta2 nicotinic acetylcholine receptors.

Aged↗
PubMed2000

Lasting influence of repetitive transcranial magnetic stimulation on intracortical excitability in human subjects.

We studied the effects of a train of 30 pulses of repetitive transcranial magnetic stimulation (rTMS) at frequencies of 5 and 15 Hz and at an intensity of 120% of resting motor threshold on human motor cortex excitability. Intracortical inhibition (ICI) and intracortical facilitation (ICF) after rTMS were tested by a conditioning-test designed paired-pulse paradigm. After 15 Hz rTMS, ICI was significantly reduced for 3.2 min, ICF was enhanced for 1.5 min, muscle evoked potentials from single TMS were increased in the first 30 s only. After 5 Hz rTMS ICI was significantly reduced in the first 32 s. We conclude that high-frequency suprathreshold rTMS transiently suppresses the activity of the intracortical inhibitory circuitry and, with a different time course, increases the excitability of the excitatory circuitry.

Adult↗
PubMed2000

Suppression of proteasome C2 contralateral to ischemic lesions in rat brain.

Functional as well as structural reorganization takes place in the surrounding and remote brain areas after focal ischemic lesions. In particular, reactive or regenerative processes have been described to occur in the contralateral hemisphere. We used mRNA differential display to gain more insight into the molecular mechanisms underlying this type of neuronal plasticity. Circumscribed unilateral infarcts consistently affecting the forelimb area of the primary motor cortex were induced photochemically in adult male Wistar rats. The lesion produced significant behavioral asymmetry with subsequent partial recovery within 1 week. Cloning the genes with altered expression profiles identified the 20S proteasome subunit C2 as a gene whose expression level is decreased in contralateral homotopic cortex. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed approximately twofold lower proteasome C2 mRNA levels in the lesion group as compared with the sham-operated group. The proteasome serves as the central enzyme of non-lysosomal protein degradation. It is responsible for intracellular protein turnover and is critically involved in a variety of regulation processes, such as cell cycle, metabolism and differentiation. Our results suggest that proteasome activity may play also a role in contralateral cortical plasticity occurring after focal cerebral ischemia.

Animals↗
PubMed2000

Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo.

Dendrimers are highly branched macromolecules of low polydispersity that provide many exciting opportunities for design of novel drug-carriers, gene delivery systems and imaging agents. They hold promise in tissue targeting applications, controlled drug release and moreover, their interesting nanoscopic architecture might allow easier passage across biological barriers by transcytosis. However, from the vast array of structures currently emerging from synthetic chemistry it is essential to design molecules that have real potential for in vivo biological use. Here, polyamidoamine (PAMAM, Starburst), poly(propyleneimine) with either diaminobutane or diaminoethane as core, and poly(ethylene oxide) (PEO) grafted carbosilane (CSi-PEO) dendrimers were used to study systematically the effect of dendrimer generation and surface functionality on biological properties in vitro. Generally, dendrimers bearing -NH(2) termini displayed concentration- and in the case of PAMAM dendrimers generation-dependent haemolysis, and changes in red cell morphology were observed after 1 h even at low concentrations (10 microg/ml). At concentrations below 1 mg/ml CSi-PEO dendrimers and those dendrimers with carboxylate (COONa) terminal groups were neither haemolytic nor cytotoxic towards a panel of cell lines in vitro. In general, cationic dendrimers were cytotoxic (72 h incubation), displaying IC(50) values=50-300 microg/ml dependent on dendrimer-type, cell-type and generation. Preliminary studies with polyether dendrimers prepared by the convergent route showed that dendrimers with carboxylate and malonate surfaces were not haemolytic at 1 h, but after 24 h, unlike anionic PAMAM dendrimers they were lytic. Cationic 125I-labelled PAMAM dendrimers (gen 3 and 4) administered intravenously (i.v.) to Wistar rats ( approximately 10 microg/ml) were cleared rapidly from the circulation (<2% recovered dose in blood at 1 h). Anionic PAMAM dendrimers (gen 2.5, 3.5 and 5.5) showed longer circulation times ( approximately 20-40% recovered dose in blood at 1 h) with generation-dependent clearance rates; lower generations circulated longer. For both anionic and cationic species blood levels at 1 h correlated with the extent of liver capture observed (30-90% recovered dose at 1 h). 125I-Labelled PAMAM dendrimers injected intraperitoneally were transferred to the bloodstream within an hour and their subsequent biodistribution mirrored that seen following i.v. injection. Inherent toxicity would suggest it unlikely that higher generation cationic dendrimers will be suitable for parenteral administration, especially if they are to be used at a high dose. In addition it is clear that dendrimer structure must also be carefully tailored to avoid rapid hepatic uptake if targeting elsewhere (e.g. tumour targeting) is a primary objective.

Animals↗
PubMed2000

Exploration of motor cortex excitability in a diabetic patient with hemiballism-hemichorea.

Hemiballism-hemichorea in older patients with hyperglycemia, associated with high signal intensity in the contralateral striatum on T1-weighted magnetic resonance scans, is now an accepted clinical entity. We present an additional patient with this disorder. Using transcranial magnetic stimulation, we show that intracortical inhibition in the motor cortex contralateral to hemiballism-hemichorea is increased. This finding is discussed in the context of current models of basal ganglia-thalamo-cortical connectivity.

Aged↗
PubMed2000

Supratentorial low-grade glioma: results and prognostic factors following postoperative radiotherapy.

BACKGROUND AND PURPOSE: To assess treatment outcome and prognostic factors following postoperative external radiotherapy in 77 patients with low-grade glioma. PATIENTS AND METHODS: Between 1977 and 1996, 45 patients with astrocytoma, 14 with oligodendroglioma and 18 with mixed glioma received postoperative radiotherapy with a median total dose of 52 Gy (range, 45 to 61 Gy). Sixty-seven patients were treated immediately following surgery, 10 patients with tumor progression. The influence of various factors including histology, gender, age, seizures, duration of symptoms (< or = 6 weeks vs > 6 weeks), CT pattern (enhancement vs no enhancement), type of surgery, total radiotherapy dose and timing of radiotherapy on relapse-free survival and overall survival was investigated. RESULTS: The median overall survival time was 81 months, the 5- and 10-year survival rates were 54% and 31%, respectively. The median time to progression was 56 months, while the 5- and 10-year progression-free survival rates were 45% and 24%. Univariate analyses identified the total radiotherapy dose (p = 0.01), duration of symptoms (p = 0.05), the presence of seizures (p = 0.04), and the CT pattern following intravenous contrast (p = 0.005) as significant prognostic factors for overall survival. Progression-free survival rates were influenced by the total dose (p = 0.04), the duration of symptoms (p = 0.01) and CT pattern (p = 0.006). On multivariate analysis, only the CT pattern (enhancement vs no enhancement) remained as independent prognostic factors for both progression-free survival and overall survival. CONCLUSIONS: A minimum total dose of 52 Gy is recommended for the postoperative radiotherapy in low-grade glioma. Tumors with CT enhancement seem to need further intensification of treatment.

Adult↗
PubMed2000

Evaluation of the extension of cerebral gliomas by scintigraphy.

BACKGROUND: Single photon emission computed tomography (SPECT) with 201Tl and 123I-alpha-methyl tyrosine (123I-IMT) are routine methods for the evaluation of brain tumors. 123I-IMT transport across the blood brain barrier is mediated by an amino acid carrier, 201Tl accumulation is analogous to cerebral potassium uptake. PATIENTS AND METHODS: To determine the differences in glioma extension as shown by the 2 methods, 17 patients with malignant gliomas were included in this comparative imaging study: astrocytoma III: n = 6, ependymoma III: n = 1, oligodendroglioma III: n = 1, glioblastoma IV: n = 9. The tomographic image sets were matched anatomically and the slices showing maximal tumor extension were identified in both image sets respectively. Tumor spread was compared visually and the tumor extension was quantified. RESULTS: In gliomas WHO III tumor extension was delineated significantly larger by 123I-IMT-SPECT than by 201Tl-SPECT (mean +/- SD: 816 +/- 281 pixels vs 600 +/- 220 pixels, n = 8, p < 0.05). The size of glioblastomas was shown in a comparable manner by the 2 methods (977 +/- 571 vs 1.051 +/- 588, n = 9, ns, p = 0.57), but there were considerable regional differences between the area of 201Tl uptake and amino acid retention. In the whole group a weak but significant negative correlation between intensity of 201Tl uptake on the one hand and a ratio of the area as depicted by 123I-IMT vs area as depicted by 201Tl on the other hand, was found (n = 17, r = 0.49, p < 0.05). Thus the differences in the delineation of areas became smaller with increasing 201Tl uptake. CONCLUSIONS: These preliminary data indicate that the extension of gliomas is depicted differently by the 2 methods. 123I-IMT-SPECT shows a larger tumor extension especially in gliomas WHO III. Since 201Tl uptake has previously been shown to correlate with disruption of the blood brain barrier, 123I-IMT-SPECT may delineate tumor parts without endothelial leakage. This additional information may be helpful in planning surgical or radiation therapy. The advantages of 123I-IMT in this respect decrease with increasing 201Tl uptake and with increasing malignancy.

Adult↗
PubMed2000

Sequential scintigraphic strategy for the differentiation of brain tumours.

Both thallium-201 and iodine-123 alpha-methyltyrosine (123I-IMT) have been shown to be useful in the diagnostic evaluation of brain tumours. The aim of this study was to investigate the respective contributions of 201Tl and 123I-IMT single-photon emission tomography (SPET) in the non-invasive evaluation of intracerebral tumours. We analysed 65 patients with the following brain tumours: 8 non-neoplastic lesions, 4 meningiomas, 12 low-grade gliomas, 28 high-grade gliomas, 11 metastases and 2 high-grade lymphomas. 201Tl SPET and 123I-IMT SPET were performed [start of 201Tl SPET: 15 min p.i. (early) and 180 min p.i. (delayed); start of 123I-IMT SPET: 15 min p.i.]. The intensity of uptake was quantified as the ratio between tracer accumulation in the tumour and in the contralateral hemisphere. None of the non-neoplastic lesions or low-grade gliomas expressed marked 201Tl uptake. All malignant tumours except one small metastasis and all meningiomas except one small, cystic and degenerated lesion showed significant 201Tl accumulation [Tl(15')>2.0]; 123I-IMT uptake was either absent or intermediate in non-malignant lesions except in two low-grade gliomas; the highest levels were observed in high-grade gliomas followed by metastases and lymphomas (mean IMT: 2.7 vs. 2.1 vs. 1.8), with metastases showing a high variability in 123I-IMT uptake (range: 0.8-3.6). Using 201Tl to distinguish non-neoplastic lesions from malignant tumours and meningiomas, 63 of 65 patients were characterised correctly. In the latter group, high-grade gliomas were correctly identified in 27 of 28 cases by their amino acid uptake. It is concluded that the combination of 201Tl and 123I-IMT surpasses the accuracy of each single test in the differentiation of space-occupying lesions of the brain. Based on these preliminary results, a sequential strategy is proposed involving an initial 201Tl SPET study and an additional 123I-IMT SPET study in the event of positive 201Tl uptake.

Adult↗
PubMed2000

Cerebral malakoplakia associated with Escherichia coli infection.

Malakoplakia is an unusual chronic inflammatory disease occurring predominantly in the bladder and only rarely affecting other organs. For the urinary tract, its aetiology has been ascribed to the presence of Escherichia coli, while the very few cases of cerebral malakoplakia which have been reported so far, have mostly occurred in infants in the clinical setting of neonatal herpes virus infection or otherwise in adults in areas of cerebral infarction. We here report a case of E. coli-associated malakoplakia of the brain. It occurred in a 53-year-old man who had undergone long-term corticosteroid therapy and had previously been operated on a cerebral E. coli-associated abscess. This case indicates that malakoplakia of the brain might also be a histiocytic reaction against bacterial antigens of the E. coli family.

Abscess↗
PubMed2000

In vivo glioma model enabling regulated gene expression.

Experimental investigation of glioma biology and therapy requires a representative model and a convenient technique for regulating gene expression. We have established an in vivo model in which genetically modified rat C6 glioma cells (C6TL cells) are transplanted into nude mice brain, followed by specific transcriptional control of a transgene. Histologically, the tumors exhibit an astrocytic phenotype and closely resemble human malignant gliomas including diffuse brain invasion. Due to a stably integrated lacZ gene, individual tumor cells can be unequivocally identified in tissue sections by histochemistry for beta-galactosidase. Since C6TL cells carry the tet transactivator (tTA) gene, any additional gene under control of a tetracycline/tTA-responsive promoter can be transcriptionally regulated by the concentration of tetracycline. C6TL cells stably transfected with a tetracycline/tTA-responsive luciferase reporter gene showed 23-fold regulation of luciferase activity in vitro. After intracerebral transplantation a regulation of 4.5- to 8.3-fold was obtained, dependent on the concentration and the type of tetracycline in the drinking water. This model should be useful for studying the functional role of candidate genes in tumor biology as well as for experimental gene therapy studies.

Animals↗
PubMed2000

Cavernous hemangioma of the internal auditory canal arising from the inferior vestibular nerve: case report and review of the literature.

OBJECTIVE: To describe a case of cavernous hemangioma arising from the inferior vestibular nerve, limited to the internal auditory canal. STUDY DESIGN: Retrospective case review and review of literature. SETTING: A tertiary referral clinic. INTERVENTIONS: Extended middle cranial fossa surgery. RESULTS: The hemangioma was completely resected through the extended middle cranial fossa approach. No serious complications occurred, and the hearing and the facial nerve function were preserved. CONCLUSIONS: Originating from the capillary plexus surrounding Scarpa's ganglion, this hemangioma has to be differentiated from intratemporal hemangioma at the geniculate ganglion. Because of extrinsic growth pattern, the potential for preservation of the facial nerve function is high if surgery is performed early. Complete resection through the extended middle fossa approach is the treatment of choice for cavernous hemangioma with limited extension into the cerebellopontine angle. It remains difficult to distinguish preoperatively from the more common tumors, and surgery is usually planned on assumption of vestibular schwannoma.

Adult↗
PubMed2000

Artifacts caused by transcranial magnetic stimulation coils and EEG electrodes in T(2)*-weighted echo-planar imaging.

We investigated the effects of transcranial magnetic stimulation (TMS) coils and electroencephalographic (EEG) electrodes on T(2)*-weighted echo-planar images (EPI) at 2.0 T (gradient-echo EPI, mean TE = 53 ms, 2x2x4 mm(3)). In comparison with anatomic gradient-echo images (3D FLASH, TE = 4 ms, 1x1x1 mm(3)), T(2)*-weighted EPI acquisitions of a water-filled spherical phantom revealed severe signal losses and geometric distortions in the vicinity of TMS coils. Even remote effects were observed for image orientations perpendicular to the coil plane. EEG electrodes and the fixation gel caused milder localized distortions. In humans, complications were avoided by the large distance between the TMS coil and the cortical surface and when using an EPI orientation parallel to the plane of the coil. It is concluded that T(2)*-weighted EPI studies of human brain function may be performed without distortions caused by TMS coils and EEG electrodes.

Artifacts↗
PubMed2000

Laparoscopic surgery for complex ovarian masses.

STUDY OBJECTIVE: To assess the value of laparoscopy in managing complex ovarian masses. DESIGN: Retrospective, observational analysis (Canadian Task Force classification II-2). SETTING: University-based, tertiary level center for endoscopic surgery. PATIENTS: Two hundred eleven consecutive women. INTERVENTIONS: Laparoscopic surgery including ovary-preserving surgery, salpingo-oophorectomy, adhesiolysis, and pelvic lymphadenectomy. MEASUREMENTS AND MAIN RESULTS: Patients were selected on the basis of preoperative ultrasound findings. Intraoperative appearance of the tumors as well as results from frozen section examinations were compared with histologic results. Two hundred sixteen pelvic masses were benign. In 10 patients, early ovarian cancer, borderline tumors, tubal cancer, or secondary ovarian, nongynecologic pathology was managed primarily by laparoscopy and confirmed histologically. Three of these 10 women underwent standard radical open surgery within 1 week. The true nature of masses was not recognized at the time of laparoscopy in three patients with malignant findings. Patients with malignant tumors were followed for 5 years. CONCLUSION: Although most complex ovarian masses can be managed by laparoscopy, the possibility of overlooking malignancy remains, even with frozen section examination. Whether or not laparoscopy compromises clinical outcome compared with laparotomy is not fully understood. Prospective studies to address this important clinical question are urgently needed.

Adolescent↗
PubMed2000

Modification of the silent period by double transcranial magnetic stimulation.

OBJECTIVES: To study the time course of the changes of the inhibitory network of the human motor system, we investigated the silent period (SP) in 7 healthy subjects by double suprathreshold transcranial magnetic stimulation (TMS). METHODS: SPs and motor evoked potentials (MEPs) were recorded from the voluntarily activated right abductor digiti minimi muscle. Conditioning and test stimuli were delivered with equal intensity, which was set to yield a baseline SP duration of 130 ms by a single pulse, and with various interstimulus intervals (ISIs). In addition, a control experiment with adjustment of the intensity of single stimuli was performed. RESULTS: At ISIs of 20 and 30 ms the test pulse SP duration was prolonged, without increasing the MEP amplitude. The SP duration shortened at longer ISIs and showed a significant depression between ISIs of 60-110 ms. The shortened SP was accompanied by a diminished MEP. The control experiment revealed that the SPs evoked by the adjusted pulses were significantly shorter than the test pulse SPs. CONCLUSIONS: A conditioning stimulus can prolong and shorten the test pulse SP duration at different ISIs. The prolongation is probably cortically generated, whereas the shortening is likely to occur at a cortical and spinal level.

Adult↗