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Biomedical subjects

M Westphal

Publications and source records attributed to M Westphal.

At least 55 records · Page 3Linked to original sources
PubMed2002

Head injury by gunshots from blank cartridges.

BACKGROUND: Blank cartridge handguns are generally underestimated in their capacity to inflict serious and potentially life threatening injuries. The predominant reasons for these injuries are suicide or suicide attempts, followed by accidental injuries. METHODS: A series of 26 gas gunshots to the neurocranium is presented. The injury pattern relevant to neurosurgical practice is illustrated in a case summary of 7 selected cases and the clinical courses as well as outcomes are presented. RESULTS: The injury pattern demonstrates that the energy density of the gas jet and the high temperatures of the exploding gas volume cause extensive soft tissue injuries. In close-range shots the gas jet takes on physical properties of a projectile. In these injuries impression fractures and dislocation of bone fragments are common. CONCLUSIONS: Gas handguns, contrary to public opinion, are dangerous weapons and may inflict potentially fatal injuries to the neurocranium when fired at close range. These weapons are frequently used in criminal or careless activities predominantly by young males. Extensive CNS injuries including hematomas, subarachnoid hemorrhage, foreign body contamination, and increased intracranial pressure are frequently observed.

Adolescent↗
PubMed2002

Stability of a sufentanil-ropivacaine mixture in a glass and a PVC reservoir.

BACKGROUND AND OBJECTIVE: Drug mixtures containing sufentanil may be unstable owing to absorption into the drug reservoirs of patient-controlled epidural analgesia systems that contain polyvinylchloride. The stability of sufentanil in a mixture of ropivacaine 0.2% in a 750 mL reservoir was therefore investigated. METHODS: During simulated epidural infusions of 5 mLh(-1) at 25 degrees C, sufentanil concentrations were measured for 96 h. Samples were taken from the reservoir and from the end of the epidural catheter under the following conditions: into glass or polyvinylchloride reservoirs containing ropivacaine 0.2% with sufentanil 1, 0.75 or 0.5 microg mL(-1); and into polyvinylchloride reservoirs with ropivacaine 0.2% and sufentanil 1 microg mL(-1) which were stored for 4 weeks at 8 degrees C. RESULTS: The different solutions remained stable over the observation period of 96 h. Using the same solutions, independent samples' ANOVA showed no difference in the sufentanil concentrations between the glass and polyvinylchloride reservoirs, or between the polyvinylchloride reservoirs when stored for 4 weeks. Correlations between the concentrations at the different measurement times were extremely high for the reservoir (r(min) = 0.98, r(max) = 1.00) and the catheter end (rmin = 0.86, r(max) = 1.00). CONCLUSIONS: Sufentanil citrate at 0.5-1.0 microg mL(-1) in an admixture of ropivacaine 0.29 for 5 days, which is the usual period for postoperative epidural analgesia, remains stable in a polyvinylchloride reservoir. There is no change in the drug concentration even if the reservoir is stored for 4 weeks at 8 degrees C.

Amides↗
PubMed2002

[Diagnostic and therapeutical considerations in the treatment of giant aneurysms].

The treatment of giant aneurysms requires a thorough surgical and endovascular planning as this entity is accompanied by complex vascular and blood flow particularities. Even in experienced neurovascular centers the clinical outcome varies considerably. Within a series of 1386 aneurysm patients 72 (5%) giant (>25 mm) aneurysms were treated in our institution. Their age ranged between 26 and 81 years (medium age 52 years). 22 patients were suffering of a subarachnoid hemorrhage (SAH). Additionally there were 50 patients with nerve palsies or unspecific symptoms due to unruptured giant aneurysms (UGA). Treatment modalities included surgical clipping (n = 35), balloon occlusion of the ICA (n = 12), endovascular coiling (n = 7) or a combined regimen of balloon occlusion, surgical clipping and EC-IC bypass (n = 8). 10 patients could not be treated on due to their high age or minor clinical status (H&H IV and V). 6 of 15 (40%) SAH-patients were discharged without any complaints compared to 26% (12 of 47 patients) in the group of unruptured aneurysms. 1 SAH-patients (7%) versus 13 UGA (28%) patients suffered persisting nerve palsies or minor neurological disorders. 32% (n = 15) of the UGA-patients were suffering of major neurological deficits and required further professional help. 5 patients remained in a vegetative state, 3 of these had been admitted with an incidental finding of an UGA. 6 of 15 (40%) SAH-patients died, 5 of them admitted with H&H grade IV or V. However only 3 of 47 (6%) UGA patients died. 2 of these had a fatal SAH before treatment, 1 underwent EC-IC bypass surgery with insufficient hemispheric vascularization followed by gross infarction. The clinical status and age of the patient are significant factors influencing treatment associated morbidity and mortality. The individual vascular situation may lead to a complex therapeutical regimen thereby predisposes higher complication rates. We believe that surgical clipping is the first choice of treatment allowing temporarily clipping and reconstruction of the normal anatomy by shrinking or/and reconstructive clipping while reducing the mass effect. Whereas endovascular coiling alone is less favorable due to the packing of the coils a combined endovascular and surgical approach have to be considered in selected cases.

Adult↗
PubMed2001

Multimodal fetal transesophageal echocardiography for fetal cardiac intervention in sheep.

BACKGROUND: The overall performance of available mechanical intravascular ultrasound catheters for fetal transesophageal echocardiography during fetoscopic fetal cardiac interventions in sheep has been limited by radioelectronic interference, low system frame rates, and low acoustic outputs. Therefore, a more reliable device is desired for human fetoscopic surgical procedures. METHODS AND RESULTS: We assessed the potential of a newly available 10-French phased-array intravascular ultrasound catheter for multimodal fetal transesophageal echocardiography in 5 fetal sheep between 78 and 98 days of gestation (term, 145 to 150 d). The intravascular ultrasound catheter was easily inserted through the mouth into the esophagus in all 5 sheep fetuses (mean weight, 600 g), and it permitted high-quality 2D imaging of the fetal heart in vertical imaging planes that were validated by MRI. Color Doppler and pulsed Doppler imaging permitted clear assessment of fetal cardiovascular flows and recording of velocity-time integral tracings of the fetal heart and great vessels. The vertical imaging planes were particularly useful to demonstrate interventional material inside the fetal heart and great vessels. CONCLUSIONS: Our early experience with the phased-array intravascular ultrasound catheter indicates that multimodal fetal transesophageal echocardiography has now become possible in these smallest of patients.

Animals↗
PubMed2001

Inhibition of glioma angiogenesis and growth in vivo by systemic treatment with a monoclonal antibody against vascular endothelial growth factor receptor-2.

Using an orthotopic intracerebral model, we investigated whether systemic treatment with DC101, a monoclonal antibody against vascular endothelial growth factor receptor (VEGFR)-2, could inhibit angiogenesis and the growth of human glioblastoma cells in severe combined immunodeficient mice. Intraperitoneal treatment with DC101, control IgG, or PBS was initiated either on day 0 or, in another series, on day 6 after tumor cell implantation, and animals were killed approximately 2 weeks after tumor cell injection. Tumor volumes in animals treated with DC101 were reduced by 59 and 81% compared with IgG and PBS controls, respectively (P < 0.001), when treatment was initiated immediately, and similar results were obtained when treatment started on day 6. Microvessel density in tumors of DC101-treated animals was reduced by at least 40% compared with animals treated with control IgG or PBS (P < 0.01). We observed a reduction in tumor cell proliferation and an increase in apoptosis in DC101-treated animals (P < 0.001). However, in mice treated with DC101, we also noticed a striking increase in the number and total area of small satellite tumors clustered around, but distinct from, the primary. These satellites usually contained central vessel cores, and tumor cells often had migrated over long distances along the host vasculature to eventually reach the surface and spread leptomeningeally. We conclude that systemic antagonization of VEGFR-2 can inhibit glioblastoma neovascularization and growth but can lead to increased cooption of preexistent cerebral blood vessels. Therefore, a combination of different treatment modalities which also include anti-invasive therapy may be needed for an effective therapy against glioblastoma, and the use of an antibody against VEGFR-2 may be one effective component.

Animals↗
PubMed2001

Molecular genetic alterations on chromosomes 11 and 22 in ependymomas.

Ependymomas arise from the ependymal cells at different locations throughout the brain and spinal cord. These tumors have a broad age distribution with a range from less than 1 year to more than 80 years. In some intramedullary spinal ependymomas, mutations in the neurofibromatosis 2 (NF2) gene and loss of heterozygosity (LOH) on chromosome arm 22q have been described. Cytogenetic studies have also identified alterations involving chromosome arm 11q, including rearrangements at 11q13, in ependymomas. We analyzed 21 intramedullary spinal, 14 ventricular, 11 filum terminale and 6 intracerebral ependymomas for mutations in the MEN1 gene, which is located at 11q13, and mutations in the NF2 gene, which is located at 22q12, as well as for LOH on 11q and 22q. NF2 mutations were found in 6 tumors, all of which were intramedullary spinal and all of which displayed LOH 22q. Allelic loss on 22q was found in 20 cases and was significantly more frequent in intramedullary spinal ependymomas than in tumors in other locations. LOH 11q was found in 7 patients and exhibited a highly significant inverse association with LOH 22q (p<0.001). A hemizygous MEN1 mutation was identified in 3 tumors, all of which were recurrences from the same patient. Interestingly, the initial tumor corresponded to WHO grade II and displayed LOH 11q but not yet a MEN1 mutation. In 2 subsequent recurrences, the tumor had progressed to anaplastic ependymoma (WHO grade III) and exhibited a nonsense mutation in exon 10 of MEN1 (W471X) in conjunction with LOH 11q. This suggests that loss of wild-type MEN1 may be involved in the malignant progression of a subset of ependymomas. To conclude, our findings provide evidence for different genetic pathways involved in ependymoma formation and progression, which may allow to define genetically and clinically distinct tumor entities.

Adolescent↗
PubMed2001

Dictyostelium cells' cytoplasm as an active viscoplastic body.

We applied a recently developed microrheology technique based on colloidal magnetic tweezers to measure local viscoelastic moduli and active forces in cells of Dictyostelium discoideum. The active transport of nonmagnetic beads taken up by phagocytosis was analyzed by single particle tracking, which allowed us to measure the length of straight steps and the corresponding velocities of the movements. The motion consists of a superposition of nearly straight long-range steps (step length in the micrometer range) and local random walks (step widths about 0.1 microm). The velocities for the former type of motion range from 1 to 3 microm/s. They decrease with increasing bead size and are attributed to rapid active transport along microtubuli. The short-range local motions exhibit velocities of less than 0.5 microm/s and reflect the internal dynamics of the cytoplasm. Viscoelastic response curves were measured by application of force pulses with amplitudes varying between 50 pN and 400 pN. Analysis of the response curves in terms of mechanical equivalent circuits yielded cytoplasmic viscosities varying between 10 and 350 Pa s. Simultaneous analysis of the response curves and of the bead trajectories showed that the motion of the beads is determined by the local yield stress within the cytoplasmic scaffold and cisternae, which varies between sigma = 30 Pa and 250 Pa. The motion of intracellular particles is interpreted in terms of viscoplastic behavior and the apparent viscosity is a measure of the reciprocal rate of bond breakage within the cytoplasmatic network. The viscoelastic moduli are interpreted as dynamic quantities which depend sensitively on the amplitude of the forces, and the rate of bond breakage is determined by the Arrhenius-Kramers law with the activation energy being reduced by the work performed by the applied force. In agreement with previous work, we provide evidence that the myosin II-deficient cells exhibit higher yield stresses, suggesting that the function of myosin II as a cross-linker is taken over by the other (non-active) cross-linkers.

Animals↗
PubMed2001

Treatment of malignant glioma: a problem beyond the margins of resection.

The treatment of malignant glioma remains problematic. Surgical removal followed by external beam irradiation represents a standard treatment that has demonstrated a prolonged time to progression and survival. However, the capacity to locally invade normal brain invariably leads to formation of a recurrent tumor most often immediately adjacent to the site of resection. This clinical everyday experience prompts the hypothesis that improved local control of the tumor may translate into a delayed time to progression and possibly survival, specifically because systemic chemotherapy for most of these tumors has failed to significantly improve survival. Local treatment strategies including chemotherapy, gene therapy, and immunotherapy are rapidly developing and progressing to clinical trials. Several theoretical considerations suggest that these approaches may be promising in the treatment of brain tumors.

Genetic Therapy↗
PubMed2001

Tamoxifen sensitivity-testing of glioblastomas: comparison of in vitro and in vivo results.

BACKGROUND: Only less than half of the patients with malignant gliomas respond to a continuous high dose Tamoxifen (TAM) and/or Carboplatin (CP)-treatment. Therefore, a method for predicting the efficacy of TAM-treatment would be desirable. METHODS: Paralleling a clinical study, the predictive value of in vitro-sensitivity testing of TAM and TAM's metabolite 4-OH-TAM in primary cultures of tumour explants from 15 of a total of 50 patients was examined. Additionally, the influence of TAM, 4-OH-TAM, and CP on the proliferation of established glioblastoma cell lines and of those explanted from athymic nude mice and re-established in cell culture was investigated. Human glioblastomas xenotransplanted subcutaneously into athymic nude mice and subsequently treated with TAM and/or CP were examined in a parallel in vivo-study. FINDINGS: TAM-chemosensitivity-testing of glioblastomas failed to predict the clinical response to TAM-treatment in our patients and did not correlate with the in vivo-TAM-response of tumours xenotransplanted into nude mice. TAM's and 4-OH-TAM's ability to inhibit growth of various glioblastoma cell lines in vitro in very similar concentrations was shown to be a consistent phenomenon which seems to be independent of the in vivo response in either patients or mice as previous hosts. However, CP's antiproliferative effect on glioblastomas in vivo was paralleled by respective in vitro results. Whereas TAM showed to mediate its in vitro antiproliferative effect by inducing apoptosis in most cell lines examined, CP-treatment lead to necrosis of cells. INTERPRETATION: Combining the results obtained from our human and mouse studies, it has to be postulated that host factors other than the sensitivity to TAM of the individual cell, determine the efficacy of TAM-treatment in vivo.

Adult↗
PubMed2001

(E)-5-(2-bromovinyl)-2'-deoxyuridine potentiates ganciclovir-mediated cytotoxicity on herpes simplex virus-thymidine kinase--expressing cells.

Tumor cells expressing the thymidine kinase gene of the herpes simplex virus (HSV-tk) are rendered highly susceptible to the cytotoxic effects of different antiherpes drugs. In an attempt to enhance cytotoxicity of this therapeutic approach in glioma and other tumor cell lines transduced with the HSV-tk gene, we evaluated tumor cell killing following co-administration of two different prodrugs metabolized by HSV-tk, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), and ganciclovir (GCV). In 8 of 12 cell lines investigated, addition of BVDU in concentrations showing no cytotoxic effect or only limited cytotoxicity could enhance GCV-mediated cell killing by as much as one order of magnitude. In co-cultures consisting of HSV-tk(+) (9L STK) and HSV-tk(-) (9L wild-type) cells, we also observed potentiation of GCV-mediated cytotoxicity in the presence of BVDU, suggesting strongly enhanced bystander cell killing. BVDU is thought to exert its cytotoxic effect through inhibition of thymidylate synthase activity or by incorporation into replicating DNA. Both effects could be observed in all HSV-tk--expressing cells investigated, including cell lines which did not exhibit cytotoxicity after incubation with BVDU. These findings argue against current concepts of BVDU-mediated cytotoxicity in HSV-tk--expressing cells. Taken together, our data suggest that gene therapy utilizing prodrug activating enzymes may be rendered more effective by simultaneous treatment with two different prodrugs metabolized by the same enzyme.

Animals↗
PubMed2001

Expression and localization of scatter factor/hepatocyte growth factor in human astrocytomas.

Scatter factor/hepatocyte growth factor (SF/HGF) is a pleiotropic cytokine that has been implicated in glioma invasion and angiogenesis. The SF/HGF receptor, MET, has been found to be expressed in neoplastic astrocytes as well as in endothelial cells of the tumor vasculature. Both SF/HGF and MET expression have also been described to correlate with the malignancy grade of human gliomas. However, most glioblastoma cell lines lack SF/HGF expression, raising the question of the cellular origin of SF/HGF in vivo. Using in situ hybridization, we analyzed glioblastomas, anaplastic astrocytomas, diffuse astrocytomas, pilocytic astrocytomas, and normal brain for the expression of SF/HGF mRNA. We detected strong SF/HGF expression by the majority of the tumor cells and by vascular endothelial cells in all glioblastoma specimens analyzed. Combined use of in situ hybridization with fluorescence immunohistochemistry confirmed the astrocytic origin of the SF/HGF-expressiong cells. In contrast, CD68-immunoreactive microglia/macrophages, as well as vascular smooth muscle cells reactive to alpha-smooth muscle actin, lacked SF/HGF expression. In anaplastic, diffuse, and pilocytic astrocytomas, SF/HGF expression was confined to a subset of tumor cells, and signals were less intense than in glioblastomas. In addition, we detected SF/HGF mRNA in cortical neurons. SF/HGF expression was not up regulated around necroses or at tumor margins. MET immunoreactivity was observed in GFAP-expressing astrocytic tumor cells and endothelial cells as well as in a subset of microglia/macrophages. We conclude that in vivo, both autocrine and paracrine stimulation of tumor cells and endothelium through the SF/HGF-MET system are likely to contribute to tumor invasion and angiogenesis. Lack of SF/HGF expression by most cultured glioblastoma cells is not representative of the in vivo situation and most likely represents a culture artifact.

Astrocytoma↗
PubMed2001

The IGF/IGFBP system in CNS malignancy.

The insulin-like growth factor (IGF) system includes IGF-I and IGF-II, the type I and type II IGF receptors, and specific IGF binding proteins (IGFBP-1 to IGFBP-6). These factors regulate both normal and malignant brain growth. Enhanced expression of IGF-I and IGF-II mRNA transcripts has been demonstrated in gliomas, meniningiomas, and other tumours. Abnormal imprinting of IGF-II occurs in gliomas, medulloblastomas, and meningiomas. Both types of IGF receptor are expressed in gliomas and, in particular, the type I IGF receptor appears to be upregulated in malignant brain tissue. Antisense IGF-I receptor mRNA induces an antitumour response, resulting in complete brain tumour regression. Clinical trials for the treatment of brain tumours in humans based on a gene transfer protocol using IGF-I receptor antisense are under way. All six IGFBPs are expressed to a variable extent in brain tumours. High concentrations of IGFBP-2 are found in cerebrospinal fluid from patients with malignant central nervous system tumours; therefore, IGFBP-2 might be a useful marker for these tumours. IGFBP-4 appears to be a negative regulator of tumour proliferation. Both in vitro and in vivo experiments suggest that the IGF system represents an important target for the treatment of malignant central nervous system tumours and the ongoing trials should provide valuable information for future therapeutic approaches.

Biomarkers↗
PubMed2000

Retention of imprinting of the human apoptosis-related gene TSSC3 in human brain tumors.

Genomic imprinting is the result of a gamete-specific modification leading to parental origin-specific gene expression in somatic cells of the offspring. Several embryonal tumors show loss of imprinting of genes clustered in human chromosome 11p15.5, an important tumor suppressor gene region, harboring several normally imprinted genes. TSSC3, a gene homologous to mouse TDAG51, implicated in Fas-mediated apoptosis, is also located in this region between hNAP2 and p57 (KIP2). TSSC3 is the first apoptosis-related gene found to be imprinted in placenta, liver and fetal tissues where it is expressed from the maternal allele in normal human development. This study investigated the imprinting status of TSSC3 in human normal, adult brain and in human neuroblastomas, medulloblastomas and glioblastomas. A polymorphism in exon 1 at position 54 was used to analyze the allelic expression of the TSSC3 gene by a primer oligo base extension (PROBE) assay using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). We found that the TSSC3 gene is not imprinted in human normal, adult brain and blood. In contrast, strong allelic bias resembling imprinting could be detected in most examined tumor specimens. The results demonstrate for the first time that the tumors under investigation are associated with a retention of imprinting of a potential growth inhibitory gene.

Animals↗
PubMed2000

Growth factors in gliomas revisited.

Overexpression or untimely expression of wild-type or mutated protein growth factors and their receptors is associated with the biology of malignant gliomas and other types of cancer. It may result in unchecked tumour cell proliferation, migration/invasion into normal tissue, tumour angiogenesis, escape from immune surveillance, and decreased apoptotic cell death, i.e. after treatment with cytotoxic agents. This often involves activation of growth factor receptors either by simultaneous production of growth factors and corresponding receptors on the same or adjacent tumour cells or by constitutive receptor activation due to mutations. In several instances, the cellular genes encoding these growth factors and receptors are homologous to transforming genes/oncogenes from tumourigenic retroviruses and have thus been regarded as cellular proto-oncogenes. In recent years much progress has been made towards a better understanding of the function of these molecules and how they lead to the aggressive phenotype of malignant gliomas and its inherent resistance to adjuvant therapies. This, still insufficient, knowledge is a prerequisite for the development of novel therapies for this non-curable disease. The aim of this review is to address relevant growth factor receptor systems with emphasis on their particular role in glioma biology.

Apoptosis↗
PubMed2000

Ultrasound-guided surgery of deep seated brain lesions.

OBJECTIVE: Computer aided navigation systems have been introduced to optimize the neurosurgical strategies minimizing the damage to the healthy brain tissue. As the loss of cerebrospinal fluid and surgical manipulation alter the position of the lesion in the external reference system, there is a risk of being misguided to deep seated brain tumors. In this context we present our experiences with intraoperative ultrasound which represents a real-time navigation system. PATIENTS AND METHODS: 45 patients with subcortical intracerebral lesions were operated on with the support of ultrasound imaging. Tumor depth from the surface measured 5 (superficial) to 68 mm. The minimum size of a cavernoma was 8 mm. Histopathological diagnoses included 17 cavernomas, 12 metastases and 16 gliomas. Ultrasound localization was achieved by two perpendicular projections and the surgical trajectory of the lesion secured by catheter placement. RESULTS: Intraoperative ultrasound allowed an easy identification of all brain lesions. Additionally, a reliable localization of the tumor margins, including gliomas and metastases, was reached in 23 of 28 (82%) cases. The remaining 17 cavernomas were located all by intraoperative ultrasound, even the deep seated brain lesions of less than 10 mm in diameter could be easily detected. The real-time mode enabled a control of the surgical procedure. Technical problems arose from irregular and vaulted cortex surface, head positioning and surgical manipulation causing air artefacts with distal reduction of the signal intensity. CONCLUSION: Intraoperative ultrasound is a reliable intraoperative guidance tool in the localization of deep seated brain tumors because it operates in real-time, thus increasing the safety of the surgical procedure and of the tumor resection.

Adolescent↗
PubMed2000

Genomic imprinting of IGF2 and H19 in human meningiomas.

A number of genes, including IGF2 and H19, are normally imprinted with preferential expression of the paternal or maternal allele, respectively. Loss of imprinting (LOI) of IGF2 and H19 is found in a number of tumours, suggesting that LOI of IGF2 and/or H19 may play an important role in tumorigenesis. The IGF2 gene codes for a fetal growth factor and the H19 gene is likely to act as an RNA with an antitumour effect. We investigated the imprinting status of IGF2 and H19 in human meningiomas. The normally imprinted IGF2 gene lacks imprint in the leptomeninges and choroid plexus of the brain. To examine the imprinting status of IGF2 and H19 in human meningiomas we used the ApaI polymorphism in exon 9 for the IGF2 gene and the AluI polymorphism in exon 5 for the H19 gene. In total, 24 meningiomas of WHO grade I, II and III were analysed. 15 meningiomas (63%) were informative for the ApaI polymorphism in the IGF2 gene. Monoallelic expression (MAE) for IGF2 was found in 11 out of 15 tumours (73%) which is in contrast to the lack of imprinting status of IGF2 in leptomeninges. Ten cases (42%) were heterozygous for the H19 gene and biallelic expression was found in 3 out of 10 meningiomas (30%). These results indicate that modulation of the imprinting status of IGF2 and H19 may play an important role for the development of meningiomas.

Adolescent↗
PubMed2000

Allelic losses in neurofibromatosis 2-associated meningiomas.

More than 50% of patients with neurofibromatosis 2 (NF2) develop meningiomas. Recently, a higher proliferative activity, more mitotic figures, and greater nuclear pleomorphism have been described for NF2-associated meningiomas compared with sporadic ones. To analyze whether such histological differences could reflect underlying genetic differences, we examined 30 meningiomas from 22 NF2 patients for allelic losses on those chromosome arms that are frequently affected by deletions in sporadic meningiomas. In addition, we assessed the proliferative activity of the tumors and studied NF2 germline mutations. Twenty-three meningiomas corresponded to WHO grade I (10 fibrous, 6 psammomatous, 4 transitional, 3 meningothelial) and 7 to WHO grade II. The average MIB-1 index was 1.60 +/- 0.85 (WHO grade I: 1.41 +/- 0.80, WHO grade II: 2.13 +/- 0.82). When compared with several published studies of sporadic meningiomas, the MIB-1 index in NF2-associated meningiomas was not higher. Loss of heterozygosity (LOH) flanking or within the NF2 locus at 22q12 was detected in 100% of the tumors. LOH on 1p was the second most frequent abnormality (40%), followed by losses on 10q (27%), 6q and 14q (24%), 18q (23%), and 9p (17%). LOH on 19q and 17p, which is not commonly seen in sporadic meningiomas, was also only rarely detected in NF2-associated meningiomas. NF2 gene mutations were detected in 8 of 15 patients analyzed and were located in exons 2, 5, 6, 7, and 8. We conclude that sporadic and NF2-associated meningiomas share a common spectrum and frequency of allelic deletions as well as, in contrast to previous observations, a similar proliferative activity.

Adolescent↗