Search PubMed⌕ Search

Biomedical subjects

J Meixensberger

Publications and source records attributed to J Meixensberger.

At least 73 records · Page 4Linked to original sources

Prognostic significance of nuclear DNA content in human meningiomas: a prospective study.

Flow cytometric DNA analyses were performed to study the correlation between alterations of nuclear DNA content and clinical aggressive tumour behaviour in 134 cranial meningiomas. Forty-one meningiomas revealed an aneuploid DNA content with a distribution of n = 24 in benign, n = 12 in atypical and n = 5 in anaplastic tumours. Aneuploid DNA content was correlated with a significantly higher amount of histomorphological criteria like evidence of mitoses, necrosis, infiltration and increased cellularity. There was a significantly higher Ki 67 proliferation index in the aneuploid meningiomas in comparison to the diploid tumour group. The rate of aneuploid cell-lines was increased in recurrent tumours. No tumour recurrence could be found in diploid meningiomas during follow up (mean 37 months, range 22-46 months). However eight of forty-one aneuploid tumours showed meningioma recurrence. Nuclear DNA content has an important significance in predicting risk of recurrence and poor clinical outcome after benign meningioma surgery.

Aneuploidy↗

Factors influencing morbidity and mortality after cranial meningioma surgery--a multivariate analysis.

In a retrospective analysis 385 patients with a histologically defined cranial meningioma were studied to analyze the impact of characteristic factors on morbidity and mortality after modern cranial meningioma surgery. Mortality was 4.2% one month and 7.3% six months after operation. 15.6% of the patients stayed more than one month in the hospital (defined as criteria of operative morbidity). Age, poor preoperative clinical condition (ASA score), intra- and postoperative bleeding and CSF disturbances were significantly associated with a subsequent decrease of quality of life. First symptoms like intracranial hypertension, seizures, aphasia and hemiparesis were correlated with an increase of postoperative Karnowsky index. Postoperative quality of life decreased in patients with optic and other cranial nerve disturbances significantly. Tumour size, location (exception: medial sphenoid wing) and histological diagnosis did not influence surgical outcome. This information may be useful in management decisions regarding asymptomatic meningiomas in elderly and high risk patients.

Adolescent↗

Progesterone receptors in tumor fragment spheroids of human meningiomas.

Progesterone receptors (PgR) are detectable in about 60-70% of tissue specimens of human meningiomas. Despite these data, PgR are hardly to be found in monolayer tissue culture of meningiomas. Aim of this study was to elucidate whether PgR might be preserved in tumor fragment spheroids of meningiomas maintained in organ culture since the morphological appearance of the original tumor is preserved by this culture technique. Aliquots of meningioma specimens of 25 patients (17 females) were snap frozen in liquid nitrogen immediately after removal. Additionally, monolayer tissue cultures of the same specimen were obtained as primary culture and passage #3. Tumor fragment spheroids were kept on medium-agar with liquid medium overlay and harvested after 1 and 3 weeks in culture. PgR were detected by immunohistochemistry using a rat monoclonal antibody. 18/25 meningioma tissue specimens were positive for PgR. In 8 out of 15 PgR-positive tumors which formed spheroids we could detect PgR in fragment spheroids after 1 and 3 weeks in culture. In contrast, none of the monolayers depicted PgR. PgR is preserved in a considerable amount of tumor fragment spheroids of PgR-positive meningiomas. They remain detectable after 3 weeks of culture whereas monolayer tissue cultures are PgR-negative. Thus, tumor fragment spheroids seem to be a suitable tool to investigate progesterone/antiprogesterone effects in vitro.

Adult↗

Brain tissue pO2 in relation to cerebral perfusion pressure, TCD findings and TCD-CO2-reactivity after severe head injury.

As a reliable continuous monitoring of cerebral blood flow and/or cerebral oxygen metabolism is necessary to prevent secondary ischaemic events after severe head injury (SHI) the authors introduced brain tissue pO2 (ptiO2) monitoring and compared this new parameter with TCD-findings, cerebral perfusion pressure (CPP) and CO2-reactivity over time on 17 patients with a SHI. PtiO2 reflects the balance between the oxygen offered by the cerebral blood flow and the oxygen consumption by the brain tissue. According to TCD-CO2-reactivity PtiO2-CO2-reactivity was introduced. After initially (day 0) low mean values (ptiO2 7.7 +/- 2.6 mmHg, TCD 60.5 +/- 32.0 cm/sec and CPP 64.5 +/- 16.0 mmHg/, ptiO2 increased together with an increase in blood flow velocity of the middle cerebral artery and CPP. The relative hyperaemic phase on days 3 and 4 was followed by a decrease of all three parameters. Although TCD-CO2-reactivity was except for day 0 (1.4 +/- 1.5%), sufficient, ptiO2-CO2-reactivity sometimes showed so-called paradox reactions from day 0 till day 3, meaning an increase of ptiO2 on hyperventilation. Thereafter ptiO2-CO2-reactivity increased, increasing the risk of inducing ischaemia by hyperventilation. The authors concluded that ptiO2-monitoring might become an important tool in our treatment regime for patients requiring haemodynamic monitoring.

Adolescent↗

Critical increase of blood flow velocities after subarachnoid haemorrhage: vasospasm versus hyperaemia.

Thirty cases of subarachnoid haemorrhage (SAH), who underwent early aneurysm clipping, were studied to clarify the significance of a critical increase of blood flow velocities in correlation to neurological disability and cerebral blood flow. Three different groups of patients could be distinguished: 57% (17) of the cases showed increased TCD-values at the affected side corresponding to secondary neurological deficits (Vasospasm-group). The CBF-results pointed out a side difference according to the flow acceleration. In 7 patients (23%) we detected a similar side difference in blood flow velocity, but no secondary deficit appeared. The corresponding CBF-measurements showed risen values with no side difference (Hyperaemia-group). The third group of patients (20% i.e.6 cases) developed neurological deficits and corresponding side difference in CBF-measurements, but the transcranial Doppler sonography could not detect a significant side difference and even showed normal values (Blind-TCD-group). Critical increased blood flow velocities after SAH without secondary neurological deficits does not indicate vasospasm but hyperaemia.

Adult↗

Continuous monitoring of brain tissue PO2: a new tool to minimize the risk of ischemia caused by hyperventilation therapy.

Secondary ischemic events worsen the outcome of patients with severe head injury. Such a secondary ischemic event may be caused by a forced hyperventilation. A consequence of the induced vasoconstriction is the risk of ischemia with an adverse effect on outcome. As a reliable and on-line technique, brain tissue pO2 (p(ti)O2) is used for monitoring regional microcirculation, to detect critical hypoperfusion. On 22 patients with a severe head injury 70 hyperventilation tests were performed from day 0-9 after trauma, calculating TCD-CO2-reactivity (% change of mean flow velocity per mm Hg paCO2 change). Additionally brain p(ti)O2-CO2-reactivity (% change of brain p(ti)O2 per mm Hg paCO2 change) was calculated and introduced. Group A +2 (p(ti)O2 < or = 15 mm Hg, TCD-CO2-reactivity > or = 2.5%, p(ti)O2-CO2-reactivity > 0%) and group B +2 (p(ti)O2 > 15 mm Hg, TCD-CO2-reactivity > or = 2.5%. p(ti)O2-CO2-reactivity > 0%) was formed. P(ti)O2 values in group A+2 decreased to an ischemic level or ischemia aggravated during hyperventilation. In group B+2 no ischemic events occurred. TCD-CO2-reactivity, p(ti)O2-CO2-reactivity and decrease of paCO2 were not significantly different in both groups. 6 out of 22 patients showed, from day 0-9, at least once a risk of (aggravating) ischemia by hyperventilation therapy.

Brain↗

Metabolic patterns in malignant gliomas.

Changes of mitochondrial and cytoplasm tumor metabolism were studied in malignant gliomas and normal cortex probes in vitro. By spectrophotometric methods marker enzymes of different mitochondrial (whole respiratory chain, citrate acid cycle, fatty oxidation) and cytoplasm (glycolysis, pentose phosphate shunt) metabolic energy pathways were analysed. Generally, the activities of intramitochondrial key enzymes were significantly decreased in gliomas when compared with enzyme activities of normal cortex tissue (p < 0.01). Glycolytic enzymes and a representative of the pentose phosphate shunt were unchanged or increased. Ratios of marker enzymes of the glycolytic pathway (lactate dehydrogenase) and glycose-6-P dehydrogenase revealed a significant difference between glioblastomas (p < 0.05) and grade III (p < 0.05) tumors in comparison to normal astrocytic tissue and astrocytomas WHO grade II. Thus, biochemical analyses allow metabolic grading of gliomas in vitro and may be a useful tool for understanding tumor biology.

Adolescent↗

Disturbances of cerebrospinal fluid (CSF) circulation--neuropsychiatric symptoms and neuroradiological contribution.

The present study aimed at relating dementia, pseudo-neurasthenic and affective organic brain syndromes to underlying type of CSF flow disorder and to subsequent alteration of anatomy. T2*-weighted magnetic resonance imaging (MRI) in the midsagittal plane permitted an analysis of aqueductal CSF flow phenomena and hydrocephalus-induced elevation, thinning and dorsal impingement of the corpus callosum. Furthermore, the width of the third ventricle was measured on the transverse scout images. 72 patients with communicating hydrocephalus (increased aqueductal CSF pulsations) and 26 patients with aqueductal stenosis (absence of aqueductal flow phenomena) were compared with 22 controls. Dementia and affective disorders were distributed equally among both CSF flow subgroups whereas pseudo-neurasthenic syndromes were observed more frequently in non-communicating hydrocephalus (p < 0.03). Alzheimer-type and multiinfarct dementia syndromes were found more frequently in communicating hydrocephalus whereas non-classifiable dementia showed some predilection for non-communicating hydrocephalus. Callosal height, area and third ventricular width did not predict affective or pseudoneurasthenic disorder whereas third ventricular width (p < 0.01) and callosal area (p < 0.05) discriminated between demented and non-demented patients. Dorsal impingement of the corpus callosum by the falx was a non-specific finding.

Cerebral Aqueduct↗

The corpus callosum in communicating and noncommunicating hydrocephalus.

To investigate morphological changes in the corpus callosum in hydrocephalus and to correlate them with clinical findings we studied sagittal T2*-weighted cine MR images of 163 patients with hydrocephalus. The height, length and cross-sectional area of the corpus callosum were measured and related to the type of cerebrospinal fluid flow anomaly and to clinical features, especially dementia. With expansion of the lateral ventricles the corpus callosum showed mainly elevation of its body and, to a lesser degree, increase in length. Upward bowing was more pronounced in noncommunicating than in communicating hydrocephalus. Dorsal impingement on the corpus callosum by the free edge of the falx correlated with the height of the corpus callosum. Cross-sectional area did not correlate with either height, length or impingement; it was, however, the strongest anatomical discriminator between demented and nondemented patients. The area of the corpus callosum was significantly smaller in patients with white matter disease. Our findings suggest that, due to its plasticity, the corpus callosum can to some degree resist distortion in hydrocephalus. Dementia, although statistically related to atrophy of the corpus callosum, is possibly more directly related to white matter disease.

Case-Control Studies↗

Identification of ventricular enlargement and estimation of intracranial pressure by transcranial color-coded real-time sonography.

Transcranial color-coded real-time sonography (TCCS) was applied to 26 patients with ventricular enlargement to quantify the ventricular size and to estimate intracranial pressure. Intracranial pressures, as determined by lumbar, epidural, or ventricular tonometry, ranged from 6.5 to 55 cm H2O (8 patients had pressures > 18 cm H2O). The widths of the third ventricle and the frontal horns of both lateral ventricles depicted by TCCS were compared to corresponding computed tomography data: TCCS and computed tomography findings correlated well for the third ventricle (r = 0.96) and for the right (r = 0.86) and left (r = 0.92) frontal horns. The capability of the septum pellucidum to undulate relative to the ventricular wall during short (20-degree) rotatory movements of the head was related to intracranial pressure. In all patients with intracranial pressure below 17 cm H2O, rotatory head movements induced septum pellucidum undulation; no lateral deflection of the septum pellucidum was found in patients with an intracranial pressure above 21 cm H2O. Therefore, TCCS may be employed to quantify and follow-up ventricular enlargement. Dynamic neurosonographic tests may allow a gross estimation of intracranial pressure.

Adult↗

Studies of tissue PO2 in normal and pathological human brain cortex.

Brain cortex PO2 was measured after craniotomy and opening of the dura mater in 26 patients. We determined the brain tissue PO2 under standard narcotic conditions and after changing arterial PO2 and PCO2. Patients were divided into two groups (normal and pathological), depending on the aspect of their cortex on Ct/MRI and intraoperative appearance of the cortex. No statistical significantly difference was seen between tissue PO2 of the normal and the pathological group. A significant difference was seen only between the normal group and a subgroup with brain swelling (p = 0.0344). In the normal group no correlation was seen between tissue PO2 and arterial PO2 (r = 0.1541, p = 0.3076), whereas in the pathological group and especially in the oedema subgroup there was a highly significant correlation between tissue PO2 and PaO2 (r = 0.754, p = 0.0015 and r = 0.888, p = 0.0007). Breathing 100% oxygen changed tissue PO2 to 137.8 or 352 mmHg in the normal or the pathological group, respectively. Again, there was no correlation between tissue PO2 and PaO2 in the normal group (r = 0.1071, p = 0.392), whereas this correlation was significant in the pathological and the oedema subgroup (r = 0.6291, p = 0.0473 and r = 0.8385, p = 0.0185). This is evidence for regulatory mechanisms of tissue PO2. During hyperventilation no significant difference in tissue PO2 between the normal and the pathological group was seen. Low tissue PO2 values, however, indicate a risk for inducing ischemia.

Adult↗

Xenon 133--CBF measurements in severe head injury and subarachnoid haemorrhage.

The possibility of measuring cerebral blood flow by mobile bedside units with the intravenous 133-Xenon technique increased the interest to monitor haemodynamic changes after head injury and subarachnoid haemorrhage in intensive care. Time course of resting CBF after trauma is variable (reduced CBF, hyperemia) and there is no strong correlation to clinical outcome. Additional studies of CBF/CO2 reactivity show normal and impaired CO2 response in the acute stage after trauma (day 1-8). A permanently impaired CO2 reactivity correlates with severe brain damage and bad outcome (GOS 1,2). A normal or improving CO2 reactivity indicates a favourable outcome (GOS 3-5). There was no significant correlation between CBF and ICP, nor between CBF and CPP. A CPP of more than 70 mmHg did not guarantee a sufficient CBF in every case indicating the variability of the limits of autoregulation. As therapeutic hyperventilation may lead to ischemia, mannitol was preferred to reduce ICP and increased low CBF to normal values. This fact should be considered in the treatment of patients with low CBF and normal CO2 reactivity. Delayed ischemic neurological deficits ("vasospasm") are well-known as significant complications of the clinical course following SAH. Immediately postoperatively performed CBF measurements enable to detect ischemia and allow to start early antiischemic therapy. During "vasospasm" CBF showed a better correlation to the neurological status than blood flow velocity in the basal arteries measured by transcranial doppler sonography. Furthermore hyperemia after SAH could only be verified by CBF measurements.

Adolescent↗

Effect of embolisation of meningioma on Ki-67 proliferation index.

The proliferation indices (PIs) were determined in 33 meningiomas using two monoclonal antibodies to the Ki-67 antigen (Ki-67 and MIB1). PIs obtained using Ki-67 on frozen material were intermediate between the lowest and highest MIB1 PIs determined in paraffin wax sections. Preoperative embolisation did not influence Ki67 PI, but four of the 15 embolised tumours showed substantially increased MIB1 PIs around embolisation necroses. Proliferation can be reliably assessed in routinely processed meningioma tissues using MIB1; and increased perinecrotic PIs may occur in embolised meningiomas without being an indication of malignancy.

Antibodies, Monoclonal↗

Autocrine growth regulation in neuroectodermal tumors as detected with oligodeoxynucleotide antisense molecules.

The cell lines of three neuroectodermal tumors, two glioblastomas (HTZ-146, HTZ-17) and one melanoma (HTZ-19) were established and screened for the expression of growth factors by northern blotting and immunochemical methods. All three tumors were positive for platelet-derived growth factor- (PDGF-) A-, -B-chain, and basic fibroblast growth factor (bFGF) messenger ribonucleic acids. Cultured cells as well as original tumor material were also positive for PDGF-AA-, PDGF-BB, and bFGF protein, as shown by immunochemistry. To investigate the possible pathophysiological role of PDGF and bFGF, antisense technology was employed with chemically modified nuclease-stable 14-mer phosphorothioate oligodeoxynucleotides. Proliferation of all three tumors was reduced to a different extent with antisense phosphorothioate oligodeoxynucleotides in vitro, targeted against PDGF-A-chain-, -B-chain-, and -bFGF-messenger ribonucleic acid. These data indicate autocrine stimulatory loops for PDGF and bFGF, which may be blocked, may have different relevance in neuroectodermal tumors in vitro, and may have conceivable future therapeutic implications.

Biopsy↗

The effect of transforming growth factor-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides in reversing cellular immunosuppression in malignant glioma.

This in vitro study was aimed at restitution of transforming growth factor (TGF)-beta 2-mediated suppression of T-lymphocyte activation within malignant gliomas. In early-passage tumor cell cultures of two glioblastomas (HTZ-153 and HTZ-209) and one malignant astrocytoma classified as World Health Organization Grade III (HTZ-243), autologous peripheral blood mononuclear cells were activated by interleukin-1 alpha and interleukin-2 in vitro (lymphokine-activated killer cells) and tested for cytotoxic and proliferative activity. In expression studies (Western blot and Northern hybridization) of all three tumors, TGF-beta could be detected at the protein and messenger ribonucleic acid (mRNA) levels. A polyclonal anti-TGF-beta neutralizing antibody did not enhance lymphocyte proliferation upon stimulation with tumor targets (3H-thymidine incorporation) and slightly stimulated lymphocyte cytotoxicity against autologous target cells. Preincubation of target cells for 12 hours with TGF-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides (S-ODN's) did, however, enhance lymphocyte proliferation up to 2.5-fold and autologous tumor cytotoxicity up to 60%, compared to controls not treated with S-ODN's. Incubation of tumor cells with TGF-beta 2-specific S-ODN's resulted in decreased TGF-beta-specific immunoreactivity in cultured glioma cells, in reduced TGF-beta 2 protein concentration (Western blot), and in a change in the expression pattern of TGF-beta 2 mRNA's. These observations may have implications for in vivo and in vitro activation of a cellular immune response against autologous malignant glioma cells.

Antigens, CD↗

Sex hormone binding and peritumoural oedema in meningiomas: is there a correlation?

Steroid receptor binding activity was evaluated in specimens of 28 human cerebral meningiomas using a dextran coated charcoal (DCC) assay. Oestrogen receptor (ER) binding activity at significant levels (greater than 10 fmol/mg protein) could be detected only in three postmenopausal females (11% positive cases) at low levels. Positive progesterone receptor (PR) binding was detected in eighteen of the twenty-eight analysed meningioma tissues (64% positive cases). A significantly higher level of PR in male than in female patients could be demonstrated. The degree of peritumoural oedema could be evaluated from CT scans. There was no significant correlation between lack and amount of peritumoural oedema and quantity of cytosolic PR binding activity. Therefore we conclude, that peritumoural oedema is related to other factors and a possible role of PR activity in development of peritumoural oedema and growth control of meningiomas could not be demonstrated.

Adult↗

[Transcranial Doppler sonography with evaluation of CO2 reactivity in craniocerebral trauma].

17 patients with severe head injury were examined by transcranial Doppler sonography. Resting values and CO2 reactivity were determined. The resting measurements had no prognostic value. There was no significant side difference in patients with unilateral intracranial lesions. CO2 reactivity was 2.8 +/- 2.3%/mmHg pCO2 in patients with good outcome, whereas in patients with bad outcome CO2 reactivity was 0.6 +/- 5.1%/mmHg pCO2. However, in the acute situation after the trauma there was no difference between the two. In patients with a unilateral lesion we found a significantly lower CO2 reactivity on the side of the lesion of 1.8 +/- 0.4%/mmHg pCO2, on the non-affected side CO2 reactivity was 4.5 +/- 2.1%/mmHg pCO2. The conclusion is that the CO2 reactivity yields information on the actual haemodynamic situation in brain-injured patients. Repeated measurements are necessary to improve the prognostic value of CO2 reactivity, because this parameter may improve during treatment.

Adult↗

CBF studies with Xenon-133 in arteriovenous malformations: a methodological study.

A new model for the two dimensional rCBF technique using the inhalation of Xenon 133 was tested in patients with arteriovenous malformations. It was hypothetized that, in contrast to the conventional CBF model, it corrects for the artifactual shunt flow through the AVM and thus yields physiological CBF data. Four regions of interest (AVM, contralateral to AVM, ipsilateral hemisphere, contralateral hemisphere) were defined in 17 patients with AVMs and analyzed for differences in grey matter flow (F1). In contrast to the conventional CBF model, the new model shows a decreased flow over the AVM area, corresponding to the results of Xenon CT and SPECT. Furthermore, the blood pool parameter P4 is very sensitive to the location of the AVM. Thus further investigations of the hemodynamics of AVMs with this model are encouraged.

Adult↗