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Biomedical subjects

T Czech

Publications and source records attributed to T Czech.

At least 19 recordsLinked to original sources

Histopathological prognostic factors in medulloblastoma: high expression of survivin is related to unfavourable outcome.

Standard postoperative treatment of medulloblastoma consists of craniospinal irradiation and chemotherapy. Currently, only clinical factors are used for therapy stratification. To optimise treatment and patient outcome, biological prognostic markers are needed. In the present study we tested the prognostic influence of four histopathological parameters considered in recent publications as prognostic factors in medulloblastoma. We analysed a series of 82 Austrian medulloblastoma patients who were treated according to the consecutive HIT protocols for medulloblastoma conducted by the German Society of Paediatric Haematology and Oncology. Histological subtype and immunohistochemical expression of erbB-2, TRKC, and survivin were determined on paraffin embedded tumour tissue and correlated with patient outcome. Statistical analysis showed a significant correlation of high expression levels of survivin with decreased survival. None of the other investigated histopathological factors correlated significantly with patient outcome. Our data indicate that high survivin expression is related to unfavourable clinical outcome in medulloblastoma patients.

Adolescent↗

Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE), the most common form of epilepsy, is characterised by cytoarchitectural abnormalities including neuronal cell loss and reactive gliosis in hippocampus. Determination of aberrant cytoskeleton protein expression by proteomics techniques may help to understand pathomechanism that is still elusive. We searched for differential expression of hippocampal proteins by an analytical method based on two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry unambiguously identifying 77 proteins analysed in eight control and eight MTLE hippocampi. Proteins were quantified and we observed 18 proteins that were altered in MTLE. Cytoskeleton proteins tubulin alpha-1 chain, beta-tubulin, profilin II, neuronal tropomodulin were significantly reduced and one actin spot was missing, whereas ezrin and vinculin were significantly increased in MTLE. Proteins of several classes as e.g. antioxidant proteins (peroxiredoxins 3 and 6), chaperons (T-complex protein 1-alpha, stress-induced-phosphoprotein 1), signaling protein MAP kinase kinase 1, synaptosomal proteins (synaptotagmin I, alpha-synuclein), NAD-dependent deacetylase sirtuin-2 and 26S protease regulatory subunit 7 protein, neuronal-specific septin 3 were altered in MTLE. Taken together, the findings may represent or lead to cytoskeletal impairment; aberrant antioxidant proteins, chaperons, MAP kinase kinase 1 and NAD-dependent deacetylase sirtuin-2 may have been involved in pathogenetic mechanisms and altered synaptosomal protein expression possibly reflects synaptic impairment in MTLE.

Adult↗

Evaluation of preoperative high magnetic field motor functional MRI (3 Tesla) in glioma patients by navigated electrocortical stimulation and postoperative outcome.

OBJECTIVES: The validity of 3 Tesla motor functional magnetic resonance imaging (fMRI) in patients with gliomas involving the primary motor cortex was investigated by intraoperative navigated motor cortex stimulation (MCS). METHODS: Twenty two patients (10 males, 12 females, mean age 39 years, range 10-65 years) underwent preoperative fMRI studies, performing motor tasks including hand, foot, and mouth movements. A recently developed high field clinical fMRI technique was used to generate pre-surgical maps of functional high risk areas defining a motor focus. Motor foci were tested for validity by intraoperative motor cortex stimulation (MCS) employing image fusion and neuronavigation. Clinical outcome was assessed using the Modified Rankin Scale. RESULTS: FMRI motor foci were successfully detected in all patients preoperatively. In 17 of 22 patients (77.3%), a successful stimulation of the primary motor cortex was possible. All 17 correlated patients showed 100% agreement on MCS and fMRI motor focus within 10 mm. Technical problems during stimulation occurred in three patients (13.6%), no motor response was elicited in two (9.1%), and MCS induced seizures occurred in three (13.6%). Combined fMRI and MCS mapping results allowed large resections in 20 patients (91%) (gross total in nine (41%), subtotal in 11 (50%)) and biopsy in two patients (9%). Pathology revealed seven low grade and 15 high grade gliomas. Mild to moderate transient neurological deterioration occurred in six patients, and a severe hemiparesis in one. All patients recovered within 3 months (31.8% transient, 0% permanent morbidity). CONCLUSIONS: The validation of clinically optimised high magnetic field motor fMRI confirms high reliability as a preoperative and intraoperative adjunct in glioma patients selected for surgery within or adjacent to the motor cortex.

Adolescent↗

Aberrant cytosolic acyl-CoA thioester hydrolase in hippocampus of patients with mesial temporal lobe epilepsy.

A series of enzyme alterations has been shown to be associated with several forms of epilepsy, in mesial temporal lobe epilepsy (MTLE), however, information is limited. It was therefore the aim of the study to determine brain enzyme protein expression using a proteomic screening approach. Hippocampi of controls and patients with drug-resistant MTLE were used for evaluation of protein expression. We applied two-dimensional electrophoresis (2-DE) with mass spectrometrical identification and immunoblotting. 2-DE revealed a remarkably decreased spot identified as cytosolic acyl-CoA thioester hydrolase (BACH; EC 3.1.2.2) in patients with MTLE. Western blotting showed absence of bands at 37 kDa in MTLEs using an antibody against mouse BACH and at 140 kDa in MTLEs using anti-rat BACH. This study demonstrates that BACHs were deranged in hippocampus of MTLE patients. This finding may well contribute to the understanding of the still elusive pathomechanisms involved in MTLE.

Adult↗

Multiregional sampling reveals a homogenous distribution of Ki-67 proliferation rate in pituitary adenomas.

Ki-67 antigen is used as a marker of proliferative activity that is linked to growth rate, invasiveness and prognosis of pituitary adenomas. So far the distribution of Ki-67 index within an individual adenoma has not been investigated. If Ki-67 antigen expression differs significantly within an individual pituitary adenoma, a sampling error may result when assessing small fragments of adenoma tissue. Such a potential error would diminish the value of Ki-67 as a tool for postoperative patient management considerations. The aim of the present study was to assess Ki-67 proliferation rates in different regions of pituitary adenomas and to statistically analyse these data for potential regional differences within each tumor. Ki-67 proliferation index was assessed in smear preparations of 100 specimens of 26 consecutive patients operated on for pituitary adenoma in the Department of Neurosurgery, Medical University Vienna. Depending on the size and extent of the tumor, a mean of 4 tissue samples (range 2-8) was selected intraoperatively from each adenoma from endosellar, suprasellar, parasellar, and basal sellar dural locations. Overall mean cell proliferation rate measured by Ki-67 was 1.81 +/- 0.90% (range 0.33-3.43%). Histologically invasive adenomas had significantly higher mean Ki-67 proliferation index in all samples from the same tumor than non-invasive adenomas (2.01 +/- 0.91% vs. 1.11 +/- 0.59%; P = 0.024). Multiregional sampling revealed a homogenous distribution of Ki-67 index throughout an individual adenoma with no significant differences between any two different regions on t-test. Our data confirm that location of a biopsy does not influence Ki-67 index. Therefore, Ki-67 index of a single biopsy is representative for the whole individual adenoma. Thus Ki-67 index can be considered a reliable parameter for assessment of cell proliferation rate in adenoma biopsies and may be used for postoperative patient management considerations.

Adenoma↗

Expression of cell proliferation markers in pituitary adenomas--correlation and clinical relevance of MIB-1 and anti-topoisomerase-IIalpha.

Pituitary adenomas represent an inhomogeneous tumor entity in terms of growth rate, invasiveness and recurrence. To improve understanding of their different biological behaviour, tumor cell proliferation markers are applied. The aim of this study was to assess proliferation rates overall and in clinico-pathological subgroups using MIB-1 and the recently introduced cell proliferation marker anti-topoisomerase-IIalpha (Topo-IIalpha). Further, we correlated the two markers, and defined the clinical value of Topo-IIalpha in pituitary adenomas as compared to MIB-1. We analyzed tumor cell proliferation rates using MIB-1 and Topo-IIalpha antibodies on samples of 260 primary pituitary adenomas. We excluded recurrent cases and cases with drug pretreatment. Median patient age at the time of surgery was 47 years (range 14-86 years), the male:female ratio was 1:1. The total cohort comprised 110 non-functioning and 150 functioning cases. Subtyping was performed according to hormonal expression as defined by WHO. Tumor size and invasiveness were noted from surgical and/or radio logical reports in 95% of cases. Overall MIB-1 index was median 1.8% (range 0.2-23.6%), Topo-IIalpha index was median 1.0% (range 0-14.4%) with a strong correlation between the two markers ( R=0.837, P<0.001). As compared to MIB-1, mean Topo-IIalpha values were significantly lower by a factor 1.8. Only MIB-1 was significantly higher in invasive as compared to non-invasive adenomas, in tumors < or =3 cm in diameter, and in the age-group 21-40. Female gender had significantly higher MIB-1 and Topo-IIalpha indices than male. Silent ACTH-cell and PRL-producing adenomas had the highest, null-cell adenomas and gonadotropinomas the lowest proliferation values, respectively. Our data show a strong correlation between MIB-1 and Topo-IIalpha indices in pituitary adenomas. Only MIB-1 but not Topo-IIalpha demonstrated significantly higher values in invasive adenomas. Therefore, MIB-1 seems more useful than Topo-IIalpha for decisions regarding postoperative patient management.

Adenoma↗

Vestibular processing in human paramedian precuneus as shown by electrical cortical stimulation.

The authors describe a 16-year-old patient with recurrent episodes of epileptic linear self-motion perception and occasional body tilts. Intracranial seizure monitoring located the seizure onset, caused by a circumscribed ependymoma, in the right paramedian precuneus. Electrical cortical stimulation of this area could reproduce the same vestibular sensations, which ceased after lesionectomy. The findings implicate the paramedian area of the precuneus in the processing of static and dynamic vestibular, probably otolithic, information.

Adolescent↗

Virtual endoscopy is a useful device for training and preoperative planning of transsphenoidal endoscopic pituitary surgery.

Virtual endoscopy (vE) allows simulated three-dimensional (3-D) visualisation of anatomical structures by computerised reconstruction of radiological images. The aim of this study was to evaluate the feasibility of vE and its potential benefits for endoscopic transsphenoidal pituitary surgery. vE was realised using a commercially available ray-casting software plugin of a picture archiving and communications system (PACS). For this study, the vE system was enhanced with volume segmentation, transparency and cutting tools. The data for vE were derived from high resolution computed tomography (CT) scans of 22 patients with pituitary pathology (20 pituitary adenomas, 2 Rathke's cleft cysts) preoperatively. Anatomic structures were identified on vE images and compared with the intraoperative endoscopic views. The simulated 3-D vE images were found to be comparable to the intraoperative endoscopic anatomy in terms of distortion and angle of view. vE was found to be particularly useful for the preoperative depiction of 1) the nasal anatomy and its variations for choosing the side of the approach, 2) the sphenoid sinus septae and chambers for improved intraoperative orientation, 3) the transparent 3-D simulated visualisation of the pituitary gland, tumour and adjacent anatomic structures in relation to the sphenoid sinus landmarks for planning the opening of the sellar floor. We conclude that vE harbours the potential to become a valuable tool in endoscopic pituitary surgery for training purposes and preoperative planning. Furthermore, vE may add to the safety of interventions in case of anatomic variations.

Endoscopy↗

Microprolactinomas in males treated by transsphenoidal surgery.

OBJECTIVE: To support the opinion that transsphenoidal surgery can be an effective alternative to medical treatment for microprolactinomas in men. DESIGN: Clinical study with retrospective data analysis. PATIENTS AND METHODS: Of 46 men who were operated on for prolactinoma in the Department of Neurosurgery of the University of Vienna General Hospital between 1985 and 2000 a microadenoma was detected 11 times (24%). RESULTS: Median patient age was 41 years (range 32 to 54 years). Symptoms were of endocrine nature in all patients with erectile dysfunction, infertility and gynaecomastia being the initial complaints and having lasted for a median of 13 months (range 7-68 months). Preoperative median serum prolactin (PRL) was elevated to 120 ng/ml (range 41-1000 ng/ml). Radiography by MRI revealed microadenomas with a median diameter of 8 mm (range 4-10 mm). All patients were operated on via the transsphenoidal approach. Endocrine cure as defined by a serum PRL <25 ng/ml was achieved in 8 of 11 patients (73%) after a median follow-up of 7 years (range 2-13 years). In none of the 3 patients with preoperative serum PRL levels >150 ng/ml was a normoprolactinaemia obtained after surgery: 2 require further dopamine-agonist therapy after surgery, 1 after late follow-up. Surgery and medical treatment could restore potency and libido in all but 1 patient, 2 of 3 patients remain infertile. CONCLUSION: Prolactinomas in males are potentially curable by surgery if detected at an early stage. They most commonly present with insidious signs and symptoms of endocrine disturbances such as loss of libido, impotence and sterility. We stress the importance of early determination of serum prolactin and high resolution magnetic resonance tomography of the sella in male patients with hyperprolactinaemia as this may prevent the possible progression to larger tumours which are rarely curable by surgery and necessitate life-long medical therapy.

Adult↗

Early diagnosis of external ventricular drainage infection: results of a prospective study.

OBJECTIVES: The aim of this study was to evaluate the influence of total drainage time on the risk of catheter infection, and the predictive value of standard laboratory examinations for the diagnosis of bacteriologically recorded cerebrospinal fluid (CSF) infection during external ventricular drainage. METHODS: During a three year period, all patients of the neurosurgical intensive care unit (ICU), who received an external ventricular drain, were prospectivly studied. Daily CSF samples were obtained and examined for cell count, glucose and protein content. Bacteriological cultures were taken three times a week, and serum sepsis parameters were determined. RESULTS: 130 patients received a total of 186 external ventricular drains. The ventricular catheters were in place from one to 25 days (mean 7.1 days). In 1343 days of drainage, the authors recorded 41 positive bacteriological cultures in 21 patients between the first and the 22nd drainage day (mean 6.4). No significant correlation was found between drainage time and positive CSF culture. The only parameter that significantly correlated with the occurrence of a positive CSF culture was the CSF cell count (unpaired t test, p<0.05). CONCLUSIONS: Drainage time is not a significant risk factor for catheter infection. Increasing CSF cell count should lead to the suspicion of bacteriological drainage contamination. Other standard laboratory parameters, such as peripheral leucocyte count, CSF glucose, CSF protein, or serum sepsis parameters, are not reliable predictors for incipient ventricular catheter infection.

Adolescent↗

Altered expression of voltage-dependent calcium channel alpha(1) subunits in temporal lobe epilepsy with Ammon's horn sclerosis.

Voltage-dependent calcium channels, the initial components in the calcium signalling cascade, are increasingly being recognised as relevant factors in the pathology of epilepsy. To further characterise their role in temporal lobe epilepsy associated with Ammon's horn sclerosis, we investigated the immunohistochemical distribution of five different voltage-dependent calcium channel alpha(1) subunits (alpha(1A), alpha(1B), alpha(1C), alpha(1D), alpha(1E)) in 14 hippocampal specimens of patients with Ammon's horn sclerosis in comparison with eight autopsy control cases. In epilepsy specimens an increased immunoreactivity was observed for alpha(1A), alpha(1B), alpha(1D) and alpha(1E) in the neuropil of the dentate gyrus molecular layer. Dentate gyrus granule cells and residual CA3 pyramidal neurones showed enhanced immunoreactivity for alpha(1A), while labelling of these neurones was decreased for alpha(1C). Astrocytes in Ammon's horn sclerosis specimens were strongly immunoreactive for the alpha(1C) subunit contrasting with an absent astrocytic alpha(1C) labelling in controls. Our results suggest that the expression of calcium channels in neurones and glial cells is dynamically regulated in temporal lobe epilepsy, supporting the relevance of calcium signalling pathways for this disease.

Adolescent↗

DNA topoisomerase IIalpha expression in optic pathway gliomas of childhood.

DNA topoisomerase IIalpha (Topo IIalpha) is linked to tumour cell growth and chemoresistance. We examined immunohistochemically Topo IIalpha expression levels in a series of 36 consecutive paediatric optic pathway glioma (OPG) patients. Topo IIalpha labelling index (LI) ranged from 0.0 to 11.6 and was significantly associated with patient age, with higher levels of Topo IIalpha in children < or = 3 years (P=0.031). Topo IIalpha expression did not correlate with patient survival. Topo IIalpha LI was not significantly increased in specimens of repeat surgery. Topo IIalpha LI closely correlated with MIB-1 LI (R=0.781, P<0.001). We conclude that Topo IIalpha expression correlates with tumour cell proliferation in paediatric OPGs. Assessment of cell proliferation, however, does not assist in refining prognostic predictions. Enhanced Topo IIalpha expression in children < or = 3.0 years suggests that Topo IIalpha-interfering anticancer compounds for adjuvant treatment of OPGs may be of particular benefit to young children.

Adolescent↗

Posthemorrhagic hydrocephalus in preterm infants: long-term follow-up and shunt-related complications.

INTRODUCTION: A retrospective analysis of 42 preterm infants with intraventricular hemorrhage was performed in order to evaluate shunt-related problems in neonates with posthemorrhagic hydrocephalus. PATIENTS AND METHODS: Within the last 15 years, 76 infants with intraventricular hemorrhage were treated primarily by external ventricular drainage, and 42 needed permanent shunting. Shunting was performed 28-101 days after the patients' birth, ventriculoatrial shunts being placed in 10 patients and ventriculoperitoneal shunts in 32. RESULTS: The mean number of shunt revisions per patient was 1.57. The main reasons for shunt revision were infection (7.1%) and blockage (45.2%). Primary ventriculoperitoneal and ventriculoatrial shunts differed only insignificantly in revision rate and length of shunt survival, whereas ventriculoperitoneal shunts used in shunt revisions required significantly fewer further revisions. CONCLUSIONS: The neurological outcome was not related to the necessity for or to complications of a shunt. Programmable valve systems and neuroendoscopy appear to be helpful in the overall management and in the treatment of complications.

Brain Damage, Chronic↗

Plasticity of Y1 and Y2 receptors and neuropeptide Y fibers in patients with temporal lobe epilepsy.

Marked expression of neuropeptide Y (NPY) and its Y2 receptors in hippocampal mossy fibers has been reported in animal models of epilepsy. Because NPY can suppress glutamate release by activating presynaptic Y2 receptors, these changes have been proposed as an endogenous protective mechanism. Therefore, we investigated whether similar changes in the NPY system may also take place in human epilepsy. We investigated Y1 and Y2 receptor binding and NPY immunoreactivity in hippocampal specimens that were obtained at surgery from patients with temporal lobe epilepsy and in autopsy controls. Significant increases in Y2 receptor binding (by 43-48%) were observed in the dentate hilus, sectors CA1 to CA3, and subiculum of specimens with, but not in those without, hippocampal sclerosis. On the other hand, Y1 receptor binding was significantly reduced (by 62%) in the dentate molecular layer of sclerotic specimens. In the same patients, the total lengths of NPY immunoreactive (NPY-IR) fibers was markedly increased (by 115-958%) in the dentate molecular layer and hilus, in the stratum lucidum of CA3, and throughout sectors CA1 to CA3 and the subiculum, as compared with autopsies. In nonsclerotic specimens, increases in lengths of NPY-IR fibers were more moderate and statistically not significant. NPY mRNA was increased threefold in hilar interneurons of sclerotic and nonsclerotic specimens. It is suggested that abundant sprouting of NPY fibers, concomitant upregulation of Y2 receptors, and downregulation of Y1 receptors in the hippocampus of patients with Ammon's horn sclerosis may be endogenous anticonvulsant mechanisms.

Adolescent↗

Chromogranins as markers of altered hippocampal circuitry in temporal lobe epilepsy.

Chromogranins are polypeptides which are widely expressed in the central nervous system. They are stored in dense core vesicles of nerve terminals, from where they are released upon stimulation. Using immunocytochemistry, we investigated the distribution of chromogranin A, chromogranin B, secretoneurin, and, for comparison, dynorphin in hippocampal specimens removed at routine surgery from patients with drug-resistant mesial temporal lobe epilepsy and in autopsy tissues from nonneurologically deceased subjects. In post mortem controls (n = 21), immunoreactivity for all 4 peptides (most prominently for chromogranin B and dynorphin) was observed in the terminal field of mossy fibers. For chromogranins, staining was observed also in sectors CA1 to CA3 and in the subiculum. Chromogranin B immunoreactivity was found in the inner molecular layer of the dentate gyrus, the area of terminating associational-commissural fibers. Secretoneurin and dynorphin immunoreactivity labeled the outer molecular layer and the stratum lacunosum moleculare of sectors CA1 to CA3, where projections from the entorhinal cortex terminate. In specimens with Ammon's horn sclerosis (n = 25), staining for all 3 chromogranins and for dynorphin was reduced in the hilus of the dentate gyrus. Instead, intense staining was observed in the inner molecular layer, presumably delineating terminals of sprouted mossy fibers. Specimens obtained from temporal lobe epilepsy patients without Ammon's horn sclerosis (n = 4) lacked this pronounced rearrangement of mossy fibers. In the stratum lacunosum moleculare of sector CA1, secretoneurin and dynorphin immunoreactivity was reduced in sclerotic, but not in nonsclerotic, specimens, paralleling the partial loss of fibers arising from the entorhinal cortex. Instead, presumably sprouted secretoneurin-immunoreactive fibers were found in the outer dentate molecular layer in sclerotic specimens. These changes in staining patterns for chromogranins and dynorphin mark profound plastic and functional rearrangement of hippocampal circuitry in temporal lobe epilepsy.

Adult↗

Intracranial hemorrhage from an aneurysm encased in a pilocytic astrocytoma--case report and review of the literature.

The authors present an unusual complication of a recurrent chiasmal/hypothalamic pilocytic astrocytoma. From his second year of life onwards, the patient was repeatedly operated on and also underwent external radiation therapy (54 Gy total dose) 1 month after the first subtotal tumor resection. Nine years after irradiation, the patient was referred to our center with a sudden onset of severe headache, vomiting and neck stiffness. Computed tomography, magnetic resonance imaging, and cerebral angiography demonstrated an intratumoral, intraventricular, and subarachnoidal hemorrhage from an anterior communicating artery aneurysm encased in the pilocytic astrocytoma. The aneurysm was clipped and the patient recovered nicely from the hemorrhage. Three years later, the patient suddenly died of cardiac failure. Autopsy disclosed vessel wall changes compatible with radiation-induced vasculopathy. In light of this finding, the importance of radiation therapy and intracranial neoplasms for aneurysm formation is discussed.

Acute Disease↗

Working memory limitation as a source of confusion in the abstract THOG task.

Limitations of working memory are proposed as a major determinant of problem difficulty in the THOG task. This task is a logical reasoning task which uses an exclusive disjunction and requires hypothetico-deductive reasoning. Four experiments with students of mathematics or psychology were used to test the hypotheses that, first, guiding participants' attention facilitates the task and, second, the use of paper and pencil as external problem representation reliefs working memory load. Focusing participants' attention upon a critical aspect of the task does not improve solution rates. Students of mathematics were better than students of psychology, but only if they were allowed to use paper and pencil or to work on the task repeatedly. These results partially support the working memory hypothesis. They point toward the importance of training and practice in relatively simple meta-cognitive skills in logical reasoning.

Attention↗