Biomedical subjects

W Paulus

Publications and source records attributed to W Paulus.

At least 73 records · Page 4Linked to original sources

PubMed2001

Epidemiology of central nervous system tumors in childhood and adolescence based on the new WHO classification.

METHOD: The topography, sex distribution and histology of 340 primary CNS tumors in children up to 17 years of age were investigated and (re-)classified according to the latest WHO classification of nervous system tumors. RESULTS: Overall the prevalence for boys (60.9%) was higher and supratentorial locations predominated (53.3%); there was an even distribution of low-grade WHO I/II (51.5%) and high-grade WHO III/IV (48.5%) tumors. Boys were more commonly affected in all age groups throughout childhood and adolescence. Infratentorial location was more common between the ages of 3 and 11 years (57.5%). High-grade tumors were more frequently encountered up to the age of 5 years (53.2%). The main histological entities were pilocytic astrocytomas (23.5%), followed by medulloblastomas (16.3%), ependymomas (10.1%), anaplastic astrocytomas and glioblastomas (7.2% each), and craniopharyngiomas (5.6%); astrocytomas overall accounted for 47.3% of pediatric brain tumors. Rarer entities included germ cell tumors, gangliogliomas, and meningiomas (2.5% each), supratentorial PNET and pineal parenchymal tumors (1.9% each), atypical teratoid/rhabdoid tumors (1.3%), choroid plexus tumors (0.9%), and desmoplastic infantile astrocytomas and dysembryoplastic neuroepithelial tumors (0.6% each). A meta-analysis of 10,582 childhood brain tumors accumulated from 16 international surveys revealed a male-female ratio of 1.29 and a supra-/infratentorial ratio of 0.92. The most common histological diagnoses were astrocytomas (37.6%), medulloblastomas (17.7%), ependymomas (9.9%), craniopharyngiomas (7.3%), and germ cell tumors (4.4%). CONCLUSIONS: Pediatric brain tumors vary considerably in their histological, topographical and gender distribution throughout childhood and adolescence, reflecting different dynamics of individual tumor entities as well as a susceptibility to their occurrence during certain periods of a child's life. Although at times difficult to characterize, pediatric CNS tumors can be satisfactorily classified according to the latest WHO classification of nervous system tumors.

Adolescent↗

PubMed2001

Rosetted glioneuronal tumor: a case with proliferating neuronal nodules.

Glioneuronal tumors with neuropil-like islands (rosetted glioneuronal tumors) were recently reported as a novel brain tumor entity with characteristic clinicopathological features (Am J Surg Pathol 23: 502, 1999). Here we describe the clinical, histological and genetic features of another case arising in the parietal lobe of a 43-year-old man suffering from focal motor epilepsy. Histologically, nodules of small neuronal tumor cells immunoreactive for synaptophysin and NeuN were embedded within a diffuse astrocytoma. Remarkably, highest proliferative activity was observed within the neuronal nodules. Comparative genomic hybridization revealed a gain of chromosome 7q and a loss on chromosome 9p.

Adult↗

PubMed2001

Postlesional transcriptional regulation of metabotropic glutamate receptors: implications for plasticity and excitotoxicity.

Metabotropic glutamate receptors (mGluRs) seem to be involved both in neuronal excitotoxicity evoked by pathological conditions such as ischemia, and in processes associated with neuronal plasticity and regulation of synaptic strength. Using semiquantitative reverse transcription-polymerase chain reaction, we measured the messenger RNA levels of mGluR2-5, 24 h and 7 days after experimentally induced focal cortical infarcts in rat motor cortex. The mRNA level of mGluR3 was strikingly decreased ipsilaterally after 24 h. On day 7, the expression of mGluR2 was down-regulated both ipsi- and contralaterally. Other receptors of this family showed either a slight or no regulation at both time points. The early changes in the expression pattern of mGluRs might be primarily linked to excitotoxicity processes which occur immediately after an ischemic lesion in cortex, whereas the delayed changes might represent one chain link in the cascade of compensatory mechanisms contributing to functional amelioration.

Animals↗

PubMed2001

Increased chromosomal imbalances in recurrent pituitary adenomas.

Eight pituitary adenomas (four gonadotroph cell adenomas, three prolactin cell adenomas, one null cell adenoma) and their respective recurrences in the same patients were studied by comparative genomic hybridization. Chromosomal imbalances were found in seven of eight patients affecting two of eight primary and seven of eight recurrent tumors. Overall, pituitary adenomas showed an average of 1.6 chromosomal imbalances per primary and 3.4 per recurrent tumor (P < 0.01). Prolactin cell adenomas showed an average of 4.3 chromosomal changes per primary and 6.3 per recurrent tumor, which were significantly more common than in gonadotroph cell adenomas (0 vs 1.7 changes; P < 0.05) and the null cell adenoma (0 vs 1.0 changes; P < 0.05). The most common changes were gains of 4q (in three of eight recurrences), 5q, and 13q (in two of eight recurrences each) as well as losses of chromosome 2 (in both primary and recurring tumors of two patients), 1p, 8q, 10, and 12q (in two of eight recurrences). Minimal common regions associated with recurrent adenomas were gains of 4q31.2-34 (three recurrences), 5q14-23 and 13q21-31 and losses of 12q24.3-qter (two recurrences each). The average MIB-1 proliferation indices were 1.2% for primary and 1.9% for recurrent adenomas (P < 0.005). Our findings suggest that acquisition of certain chromosomal imbalances is related to and may underlie adenoma recurrence.

Adult↗

PubMed2001

Chromosomal aberrations in pituitary carcinoma metastases.

Four pituitary carcinoma metastases [two adrenocorticotropic hormone (ACTH) and prolactin cell tumors each] were studied by comparative genomic hybridization. Chromosomal gains were found in all four carcinoma metastases, but losses only in the two prolactin cell carcinoma metastases. Overall, pituitary carcinoma metastases showed an average of 8.3 chromosomal imbalances per tumor (7 gains vs 1.3 losses), 10 in prolactin cell carcinoma metastases (7.5 gains vs 2.5 losses) and 6.5 in ACTH cell carcinoma metastases (6.5 gains vs 0 loss). The most common changes were gains of chromosome 5, 7p, and 14q (in three tumors each). High-level gains were found on 13q22-qter and 14q (two cases each) and on 1q, 3p, 7, 8, 9p, and 21q (one case each). To date, gains of chromosome 14q have not been reported among pituitary tumors. It remains to be shown whether gain of 14q is associated with malignant progression and metastatic dissemination of pituitary carcinomas.

ACTH Syndrome, Ectopic↗

PubMed2001

Sudden unexpected death in young adults with chronic hydrocephalus.

We present four cases of sudden unexpected death in young adults with chronic hydrocephalus. The patients were between 20 and 28 years of age and had suffered from aqueduct stenosis (two patients), spina bifida in combination with Arnold-Chiari malformation (type II) and fragile X-syndrome. The patients suddenly collapsed with cardiorespiratory failure and could not be resuscitated and none had a history of headache or seizures. The post-mortem examinations revealed no unusual findings and a definite cause of death could not be established. Neuropathological examination revealed chronically hydrocephalic brains without any signs of uncal or tonsillar herniation. We hypothesise that a sudden pressure-induced decompensation of cerebral neuronal pathways involving insular and limbic cortex, hypothalamus and brain stem nuclei, may have caused disturbances of the cardiopulmonary control centres in the reticular formation of the brain stem, which in turn may have led to instantaneous cardiorespiratory arrest resulting in sudden "neurogenic" cardiac death.

Adult↗

PubMed2001

Neglect-associated fatal Marchiafava-Bignami disease in a non-alcoholic woman.

We present the case of an 80-year-old malnourished and non-alcoholic woman who died from neglect-associated Marchiafava-Bignami disease, an illness usually almost exclusively occurring in male alcoholics. The patient had been bedridden for several months and had been looked after by her son. The patient was admitted to hospital in an extremely poor care condition suffering from severe exsiccosis, pressure sores and marasmus and died shortly afterwards. The initial post-mortem examination could not establish a definite cause of death, however, upon neuropathological examination a necrotising cystic lesion in the left cingulate gyrus as well as a central necrosis in the corpus callosum indicative of Marchiafava-Bignami disease were revealed. This is the first known case of Marchiafava-Bignami disease in a non-alcoholic woman and the first case in the forensic setting of neglect.

Aged↗

PubMed2001

Pediatric high-grade astrocytomas show chromosomal imbalances distinct from adult cases.

We studied 23 pediatric high-grade astrocytomas by comparative genomic hybridization. Chromosomal imbalances were found in 10 of 10 anaplastic astrocytomas and 11 of 13 glioblastomas and consisted of +1q (43%), +3q (26%), +1p, +2q, +5q (22%), -22q (34%), -6q, -10q (30%), -9q, -11q, -13q, -16q, and -17p (22%). Anaplastic astrocytomas frequently showed +5q (40%), +1q (30%), -22q (50%), -6q, -9q (40%), and -12q (30%); glioblastomas +1q (54%), +3q (38%), +2q, +17q (23%), -6q, -8q, -10q, -13q, and -17p (31%). Minimal common regions mapped to +1q21-41, +3q27-qter, +2q31-32, +5q14-22, -22q12-qter, -10q23-25, -6q25-qter, -9q34.2, -11q14-22, -16q22-qter, and -17p. High-level gains were located on 1q (7 cases), 2q, 7q (4 cases), 3q (3 cases), 9, 17q (2 cases), 4q, 8q, 18, and 20q (1 case). A significantly shorter survival was found for anaplastic astrocytomas showing +1q (P: < 0.05), MIB-1 proliferation index >25% (P: < 0.001) and glioblastomas (P: < 0.05). Compared with adult cases, +1p, +2q, and +21q as well as -6q, -11q, and -16q were more frequent in pediatric malignant astrocytomas. Among the latter +5q, -6q, -9q, -12q, and -22q were characteristic for pediatric anaplastic astrocytomas and +1q, +3q, +16p, -8q, and -17p for pediatric glioblastomas. Our results show that chromosomal aberrations differ between pediatric anaplastic astrocytomas and glioblastomas as well as between pediatric and adult high-grade astrocytomas, supporting the notion of a different genetic pathway. Furthermore, gains of chromosomal material on 1q might be correlated with a worse prognosis in pediatric anaplastic astrocytomas.

Adolescent↗

PubMed2001

Piracetam affects facilitatory I-wave interaction in the human motor cortex.

OBJECTIVE: To investigate by means of transcranial magnetic stimulation (TMS) the effect of a single oral dose of the GABA derivate piracetam on intracortical facilitatory I-wave interaction. METHODS: The study was performed in 8 healthy volunteers. Before, 1, 3, 6, and 24 h after intake of 4000 mg piracetam, MEPs in the relaxed abductor digiti minimi muscle were elicited by a recently introduced double pulse TMS technique with a suprathreshold first and a subthreshold second stimulus. From interstimulus intervals of 0.5-5.1 ms 3 periods were observed in which MEP facilitation showed maxima - so-called peaks of I-wave interaction - and which were separated by two troughs with no facilitation. We studied the changes in timing and size of the peaks over time. RESULTS: With piracetam, I-wave peaks showed a reduction in size as well as a shortening of the latencies at which the peaks occurred. Both changes were significant at 6 h after drug intake compared to baseline. The effects were partially reversible after 24 h. CONCLUSIONS: The mode of action of piracetam within the nervous system is almost unknown. The peak size reduction was similar to effects that were seen under GABAergic drugs, although GABAergic properties of piracetam have not been observed so far. Shortening of the I-wave peak latencies is a new phenomenon. The results are discussed on the basis of the known therapeutic effects of piracetam in cortical myoclonus and as nootropic agent.

Adult↗

PubMed2001

Simultaneous EEG and functional MRI of epileptic activity: a case report.

OBJECTIVES: Attempts to localize the source of epileptic activity by linking electroencephalographic (EEG) abnormalities to blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) signal alterations are hampered mainly by EEG distortions during MRI, subject motion, and unknown hemodynamic response characteristics. METHODS: Using T2*-weighted echo-planar imaging at 2.0 T (2 s temporal resolution, 2 x 2 x 4 mm(3) spatial resolution), this work demonstrates strategies to alleviate some of these problems while studying a patient who had ideopathic generalized epilepsy with poly-spike and slow-wave complexes. RESULTS: Continuous EEG recordings during dynamic MRI (500 ms scanning, 1500 ms delay) and post-examination derivation of an EEG reference function for MRI analysis revealed positive BOLD MRI responses with temporal characteristics similar to those obtained for functional challenges. CONCLUSIONS: The ability to map focal epileptic activity and/or associated cognitive processing provides new potential for both epilepsy research and clinical patient management.

Adult↗

PubMed2001

Regulated gene expression in glioma cells: a comparison of three inducible systems.

Transcription control systems enable experimental regulation of transgene expression in eukaryotic cells by application of specific repressors or inducers. Currently used inducible systems include tetracycline (tet-off), dimerizer and ecdysone systems. While numerous studies have utilized a single system, their comparative performance under identical conditions remains unclear. We therefore compared the efficiency of these three systems in C6 glioma cells by using transient transfection and the lacZ reporter gene. Highest induced activity was found with the ecdysone system, followed by tet-off and dimerizer systems. Both lowest repressed activity and highest regulation were revealed with the dimerizer system, followed by ecdysone and tet-off systems. Our data suggest that the most appropriate system depends on the experimental procedures, the application and the gene to be regulated.

Animals↗

PubMed2001

Effects of closed traumatic brain injury and genetic factors on the development of Alzheimer's disease.

In order to assess the impact of traumatic brain injury (TBI) and Apolipoprotein E (ApoE) allele frequency on the development of Alzheimer's disease (AD), we examined: (i) the incidence of AD pathology in 55 consecutive autopsy cases (mean age +/- SD 77.6 +/- 7.3 years) with residual closed TBI lesions and (ii) the frequency of TBI residuals in 53 age-matched autopsy proven AD cases. In both series, ApoE was evaluated from archival paraffin-embedded brain material. The results were as follows: (i) In the TBI series, 12.7% showed Consortium to Establish a Registry for Alzheimer's disease (CERAD) definite and 9.1% probable AD, only one with ApoEepsilon4. From the remaining 43 non-AD cases, three had ApoEepsilon4. The prevalence of 21.8% AD in this small autopsy cohort was significantly higher than 3.3% in a recent large clinical series and 14% in the general population over the age of 70. (ii) In the AD cohort with ApoEepsilon4 allele frequency of 30% similar to other AD series, residuals of TBI were seen in 4 brains (7.5%), all lacking the ApoEepsilon4 allele. TBI incidence was slightly higher than 8.5% in the clinical MIRAGE study. The results of this first retrospective autopsy study of TBI, ApoE allele frequency, and AD confirms clinical studies suggesting severe TBI to be a risk factor for the development of AD particularly in subjects lacking ApoEepsilon4.

Aged↗

PubMed2001

Complete inhibition of in vivo glioma growth by oncostatin M.

We describe here the oncostatin M (OSM)-dependent inhibition of in vivo tumour formation after intracerebral inoculation of glioblastoma cells in mice. We generated human glioblastoma cells transfected with the OSM gene under the control of a tetracycline-response promoter. Upon removal of tetracycline from the medium, cells exhibited a differentiated cell morphology, while proliferation was significantly inhibited. After implantation of these cells into nude mice brains, large tumours developed in animals lacking OSM expression, whereas no tumour formation was observed in mice with induced OSM expression. Our results suggest that OSM exerts pronounced antitumorigenic effects on glioblastoma cells in vivo and provide arguments for a therapeutic application of OSM in humans.

Animals↗

PubMed2001

Magnetic resonance spectroscopy and histopathological findings in temporal lobe epilepsy.

PURPOSE: In some patients with temporal lobe epilepsy, histopathological evaluation of resected brain tissue after surgical treatment may reveal several features indicative of discrete cortical malformations. We sought to determine whether these histopathological features were accompanied by hippocampal changes detectable preoperatively by proton magnetic resonance (MR) spectroscopy and to evaluate their relationship with postoperative outcome. METHODS: In 25 consecutive temporal lobe epilepsy patients who were scheduled for surgical treatment, MR spectroscopy was performed, and resected brain tissue was analyzed histopathologically for the presence of discrete cortical malformations (e.g., microdysgenesis). Outcome was assessed in all patients with an average postoperative period of 26 months. RESULTS: In 13 patients, we found subtle, histopathologically detectable signs of cortical malformation: 6 of them with concomitant hippocampal sclerosis (dual pathology) and 7 without. The latter subgroup had a worse surgical outcome and showed enhanced bilateral and/or contralateral pathological changes in the hippocampal formation when investigated by MR spectroscopy. CONCLUSIONS: These data suggest that by showing contralaterally or bilaterally abnormal spectra, MR spectroscopy might be able to indicate pathological changes in subtle developmental disorders that are possibly more widespread over the brain. This observation may improve noninvasive diagnosis in presurgical evaluation and the neurobiological understanding of cortical malformations in pharmacoresistant temporal lobe epilepsy.

Adult↗

PubMed2001

Structure of manganese diacetate tetrahydrate and low-temperature methyl-group dynamics.

We have determined the crystal structure of manganese(II) diacetate tetrahydrate at 300 and 14 K by single-crystal neutron diffraction. Proton density distributions for each of the three crystallographically distinct methyl groups have been calculated by Fourier difference. At room temperature the observed densities are those of quasi-free rotors. At low temperature rather well localized protons are observed. Inelastic neutron scattering measurements performed with single crystals allow us to assign each of the three tunnelling lines to a particular crystal site. Classical molecular dynamics simulations give density distributions in qualitative agreement with the observations. With quantum mechanics proton distributions can be represented with rotational wavefunctions convoluted with static distributions of librational coordinates. The effective rotational potentials are temperature dependent.

Journal Article↗

PubMed2001

Quantitative volumetry in patients with carotid disease--effects of acetazolamide.

The intracranial effects of acetazolamide on flow velocities can be monitored noninvasively by transcranial Doppler (TCD) sonography. Extracranial volume flow changes can now reliably be measured with color duplex M-mode systems. The authors tested the volumetric effects of acetazolamide in patients with high-grade unilateral carotid disease to quantify the amount of flow changes. Patients in group 1 had a high-grade > 70% internal carotid artery (ICA) stenosis, without collateral flow through the ophthalmic artery (OA). Patients with occluded ICA were included in group 2 (patent OA collateralization) or group 3 (no OA collateralization) (n = 6 per group). In group 1, common carotid artery (CCA) volume flow in the stenotic (normal contralateral) side increased from 271 (388) ml/min by 52 (54%) with 1 g aceta-zolamide intravenously. Simultaneously, middle cerebral artery (MCA) flow velocities increased from 54 (56) cm/s by 47 (53%). In group 2, extracranial volume flow increased from 166 (444) ml/min by 19 (52)%. MCA flow velocities increased from 43 (65) cm/s by 13 (30)%. In group 3, volume flow increased from 159 (467) ml/min by 2 (46)%. Intracranial flow velocities rose from 49 (54) cm/s by 27 (41)%. Volume flow data showed the expected decline in patients with high-grade ICA stenosis and even more pronounced in patients with occlusion of the vessel. Cerebral reserve capacity was less sufficient in patients with a patent OA, despite an additional supply of 30 ml/min, indicating a hemodynamically critical situation.

Acetazolamide↗

PubMed2001

Pregnancy and renal failure: the case for application of dosage guidelines.

Pregnancies in women with renal disease, undergoing dialysis treatment or with kidney transplants are increasingly observed. Serious problems with drug dose adjustment may arise in pregnant women with renal impairment. This review gives a practical overview on the risks of drug use during gestation, the recommended drugs of choice (e.g. methyldopa, cyclosporin), and provides some proposals for dosage adjustments in pregnant women with renal impairment. In normal pregnancy, the glomerular filtration rate and plasma volume increase, whereas plasma protein binding and liver function may be impaired. An increase in dosage is needed for cyclosporin and for methadone because of increased hepatic clearance. The dosage of erythropoetin must be increased because of lower potency in pregnant women. Little more is known on the impact of gestation on drug dose, since pharmacokinetic studies are rarely done in pregnant women. The dosages of magnesium, lithium and morphine must be reduced in renal impairment. Dose adjustment to renal function is critical and is essential for anti-infective agents (e.g. ceftazidime, ganciclovir). Basing drug dose on estimated creatinine clearance might be the most practical solution in pregnant women with renal impairment.

Dose-Response Relationship, Drug↗

PubMed2000

COL9A2 allelotypes in intervertebral disc disease.

An allelic variation of the COL9A2 gene encoding the alpha(2)-chain of collagen IX has recently been identified as a genetic risk factor for intervertebral disc prolapse, resulting in a tryptophane (Trp) substitution at position 326 of the protein. To enable quick screening of a large population we established a single enzyme (BsmFI) restriction assay which was validated by screening disc tissue samples of 250 patients (age, 47.1 +/- 13.7 years). Positive results were confirmed by nucleotide sequencing. The Trp allele was found in three patients (1.2%) who suffered from their first prolapse and were significantly older (70.7 +/- 8.5 years) than the other 247 patients. Since the substitution affects a domain covalently linked to collagen II fibrils, we conclude that this allelotype may contribute to reduced collagen crosslinking, disc instability and eventually prolapse in the elderly.

Adolescent↗