Biomedical subjects

R Schober

Publications and source records attributed to R Schober.

81 records · Page 5Linked to original sources

PubMedDate not supplied

Secreting germ cell tumors of the central nervous system (CNS). First results of the cooperative German/Italian pilot study (CNS sGCT).

BACKGROUND: Secreting germ cell tumors are an invariably fatal subgroup within the malignant pediatric brain tumors. Thus in 1993, an international working group was initiated to establish a cooperative study for diagnostic and treatment of intracranial secreting germ cell tumors of the CNS. To pilot this protocol, since 1994 German and Italian patients are treated in accordance with the established guidelines. METHODS: Regarding to the achieved consensus within the international protocol committee a characteristical diagnostic imaging (CT/MRI scan) of head and spine and a significant increase of tumor markers beta-HCG (> 50 IU/l) and/or AFP (> 25 ng/ml) are defined as sufficient diagnostic criteria. Additionally staging procedures include an initial CSF cytology. Treatment consists of 4 courses PEI: platinum (20 mg/m2 day 1-5), VP16 (100 mg/ m2 day 1-3), and ifosfamide (1.5 g/m2 day 1-5). Surgery of the residual tumor is administered after chemotherapy, if resection is possible, followed by craniospinal irradiation (30 Gy with tumor boost 24 Gy). RESULTS: Until September 96, 19 patients (16 boys and 3 girls) aged 8 to 19 years are registered and have finished their treatment. Seven children are diagnosed by elevated tumor markers. Six of 7 children with stereotactic fine needle biopsy and histology of germinoma have a significant marker increase as a specific characteristic for secreting non-germinomatous germ cell tumors. In 6 patients, the tumor is primarily resected, 2 children are biopsied. In 2 children spinal metastases are diagnosed initially. Tumor marker response is evaluated in 16 children. Thirteen of 16 patients show a clear marker normalization after 2 courses of PEI. One boy with a slight increase of the tumor marker after the 4th course developed an early spinal relapse and died. One girl showed a spinal recurrence during focal radiotherapy. She is still under relapse treatment. A significant decrease of tumor volume after chemotherapy is documented in 10/13 children, who have a definite signal tumor at start of therapy. In 3 children tumor volume does not change despite of marker normalization. Histology of these tumors is teratoma. One of these children died postoperatively because of tumor bleeding. 17/19 patients are alive, 16 of them are in complete remission with a median follow-up of 11 months. CONCLUSION: These results show a further significant increase of event-free survival (EFS 81%). The piloted chemotherapy is proven to be effective and the protocol is now open as an international SIOP CNS GCT study that is started in October 1996.

Adolescent↗

PubMedDate not supplied

MRI-guided laser-induced interstitial thermotherapy of cerebral neoplasms.

OBJECTIVE: Laser-induced interstitial thermotherapy (LITT) using a neodymium:yttrium aluminum garnet (Nd: YAG) laser is a new therapeutic approach in the treatment of brain tumors. The purpose of our study was to determine the value of MRI in monitoring LITT. MATERIALS AND METHODS: Eight patients with intracerebral tumors were treated with LITT. The light guide was inserted via an applicator sheath that was implanted stereotaxically with CT guidance. The laser irradiation was performed within the MR unit and monitored by repetitive measurements of a T1-weighted 2D-FLASH sequence. RESULTS: During therapy in all patients, typical changes of signal intensity were seen. A gradually increasing central zone of high signal intensity was surrounded by an increasing peripheral area of reduced signal intensity. The diameter of an enhancing rim at the outer border of the peripheral area after Gd-DTPA was considered as the total lesion size. The lesion size as determined on 2D-FLASH scans during LITT accounted for 88-100% (mean 93.5%) of total lesion size on T1-weighted images after Gd-DTPA acquired immediately after therapy. On T2-weighted images the signal intensities of the two zones were vice versa. Follow-up studies showed a decrease of total lesion size (15-87%). CONCLUSION: Our results demonstrate that MRI is feasible and effective in monitoring LITT. However, the role of LITT in the therapeutic workup of brain tumors still has to be defined in future clinical studies.

Adult↗

PubMedDate not supplied

Immunocytochemical study of P0 glycoprotein, P1 and P2 basic proteins, and myelin-associated glycoprotein (MAG) in lesions of idiopathic polyneuritis.

To investigate the mechanism of myelin breakdown in idiopathic polyneuritis, paraffin and Epon sections of lesions were immunostained with antisera to four proteins in myelin sheaths. Three of these (P0, P2, and BP) are constituents of compact myelin whereas myelin-associated glycoprotein (MAG) is restricted to membranes near Schwann cell cytoplasm in periaxonal and paranodal regions and in Schmidt-Lanterman clefts. In early lesions, there were focal abnormalities in P2, P0, and BP immunostaining of paranodal and internodal myelin. No single protein was affected selectively and lesions occurred in fibres of all sizes, not just in larger fibres selectively stained by P2 antiserum. Early changes in MAG immunostaining occurred only in regions where myelin immunostaining also was abnormal. More severe, late changes in the distribution of P0, P2, and BP and MAG were consistent with the sequence of myelinated fibre alterations seen in segmental demyelination and Wallerian degeneration. In regenerating fibres, MAG antiserum stained periaxonal regions intensely; thin regenerating myelin sheaths were stained by P0, and BP antisera, but not by P2 antiserum. The results show that myelin sheath changes are identified more easily in immunostained sections than in conventional histological preparations. Our data also suggest that in idiopathic neuritis, myelin sheaths are the primary target and that the breakdown of myelin and its proteins is not secondary to Schwann cell damage.

Adult↗

PubMedDate not supplied

Diffuse plaques in the molecular layer show intracellular A beta(8-17)-immunoreactive deposits in subpial astrocytes.

The presence of A beta protein- (A beta) containing astrocytes in diffuse plaques of the cortical layers II-VI has recently been demonstrated with antibodies directed against A beta(17-23) and C-terminal epitopes, of A beta. We here confirm and extend this finding by use of immunocytochemical double-labeling and preembedding immune-electron microscopy. Diffuse subpial plaques are associated with both anti-A beta(8-17) and anti-A beta(17-23)-positive granules in astrocytes. The ultrastructural nature of these intracellular deposits has been demonstrated to be lysosomal and the deposits have a lipofuscin-like appearance. These data point to a role of subpial astrocytes in the degradation of A beta by lysosomal processing.

Adult↗

PubMedDate not supplied

Clinical significance and neuropathology of primary MADD in C34-T and G468-T mutations of the AMPD1 gene.

OBJECTIVE: Primary myoadenylate deaminase deficiency (MADD) is probably the most frequent inborn metabolic myopathy with a prevalence of up to 2%. It is the result of mutations in the AMPDI gene, the most common of which is a C34-T transition in exon 2. The importance of the more rare mutation G468-T in exon 5 is uncertain. Primary objective was to elucidate the clinical significance of the enzyme disorder, which remains unclear since its first description in 1978. We further examined the existence of an association of MADD with other muscle disorders, such as malignant hyperthermia and rhabdomyolysis, as was suspected in earlier studies. MATERIAL AND METHODS: In a large collection of 1673 muscle biopsies that had been stored deep frozen we identified 33 cases of primary MADD, 12 of which without any other coinciding muscle diseases, by histochemical, biochemical and molecular genetic examinations. Clinical and laboratory data was collected. By additional examination of randomly chosen blood samples we identified one person carrying the rare compound heterozygosity C34-T/ G468-T, who was examined in clinical respects and a muscle biopsy was taken. RESULTS: As underlying mutation, the most common transition C34-T/C 143-T was detected in 33 cases. One patient carried the compound heterozygosity C34-T/G468-T. The overall frequency of MADD in the contingent was 1.8%. Only three patients out of 12 with isolated primary MADD suffered from muscle complaints, one of whom did not experience the typical symptoms of exercise related myalgia, muscle cramps and weakness as described by Fishbein. The patient carrying C34-T/G468-T was a fully healthy female. She had never experienced any muscle complaints. Any association with other neuromuscular disorders, if not completely ruled out, was found to be very unlikely. CONCLUSION: The results suggest that MADD itself is unlikely to be solely responsible for the manifestation of muscular symptoms. It is probable that either the loss of a compensation mechanism or coexistent disturbances in muscle metabolism which are unidentified so far are required for the emergence of complaints.

AMP Deaminase↗

PubMedDate not supplied

Cystic changes and vascular permeability in meningiomas.

A retrospective study of 397 human meningiomas revealed microcystic and cystic changes in about 10% of tumors, predominantly meningiomas of the meningotheliomatous subtype. The biological behavior of these tumors corresponded to those of meningiomas in general, while one tumor singled out from the microcystic variant and separately described as myxomatous meningioma was characterized by a high recurrency rate. Histochemical and immunohistochemical examination with serum proteins of variable size indicated that the microcystic alterations are associated with local vascular permeability disturbances. Hyaline vascular changes and increased numbers of mast cells were further intriguing observations with respect to the pathogenesis of microcyst formation. Possible clinical implications, in particular in regard to the sometimes severe peritumoral edema, are discussed. Since surgical material is insufficient in this respect due to sampling limitations, an unoperated autopsy case is included in this study.

Adult↗

PubMedDate not supplied

The epidermal growth factor receptor in glioblastoma: genomic amplification, protein expression, and patient survival data in a therapeutic trial.

Human glioblastomas were evaluated for overexpression of the epidermal growth factor receptor (EGFR) in a therapeutic trial with the anti-EGFR antibody EMD 55900. A total of 55 cases were examined by immunohistochemistry using 4 different monoclonal antibodies on frozen or on paraffin sections: EGFR-1 (Amersham), E 62 (Merck), E 30 (Merck), and EMD 55900 (MAB 425, Merck). Definition for inclusion in clinical trials of EMD 55900 was an immunohistochemical overexpression of grade 4+ or 3+ in a scale of 4 grades of staining quality. The use of the 4 different antibodies gave essentially equal results. In 21 cases, the immunohistochemical results were supplemented by molecular genetic analysis of EGFR amplification on the corresponding locus of chromosome 7, using frozen tissue from the same blocks after screening for vital tumor areas. Since no other material was available, the differential polymerase chain reaction technique was applied. Interferon-gamma (IFN-gamma) served as a reference gene. In a preliminary experimental series with cases of known EGFR amplification, a densitometric EGFR/IFN-gamma ratio higher than 3 was determined as indicator for amplification of the EGFR gene. With this experimental approach we were able to identify an amplified EGFR gene in 13 specimens including 2 from recurrent glioblastomas in the same patients. All of these showed an increased immunoreactivity for EGFR protein. The degree of EGFR amplification (EGFR/IFN-gamma ratio as measured by DNA densitometry) showed a positive correlation with the grade of immunohistochemical protein expression, both in regard to the fraction of positive cells and to the overall staining intensity.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMedDate not supplied

The stromal Schwann cell during maturation of peripheral neuroblastomas. Immunohistochemical observations with antibodies to the neuronal class III beta-tubulin isotype (beta III) and S-100 protein.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III; analogous to the beta' 1-/beta 2-tubulin isoform) to the Schwann cell-associated S-100 protein focusing on topographic relationships of Schwann-like cells to differentiating neuronal phenotypes during stromal development in human peripheral neuroblastomas. The earliest appearance of Schwann cells in poorly differentiated (classical) neuroblastomas is heralded by S-100 protein-immunoreactive cells in close association with tumor blood vessels. In subsequent stages of maturation, i.e. maturing neuroblastoma (ganglioneuroblastoma and gangliocytoma), S-100 protein-positive cells are mostly confined to the connective tissue septa dividing tumor into lobules, and are not freely interspersed with beta III-immunoreactive neoplastic neurons. Significant ensheathment of individual axon-like processes by Schwann cells occurs only in mature ganglioneuromas. beta III is localized in a full spectrum of neoplastic neuronal phenotypes, ranging from poorly-differentiated apolar neuroblasts (often signaling ensuing neuritogenesis) to mature ganglion cells, but not in Schwann cells, or other cell types of the stroma. Our observations suggest that Schwann cells in peripheral neuroblastomas are stroma-derived cells and not an expression of divergent neoplastic differentiation.

Adolescent↗

PubMedDate not supplied

Carotid artery dissection in a young adult: cystic medial necrosis associated with an increased elastase content.

A dissecting aneurysm of the right internal carotid artery was found in a 22-year-old man, who rapidly became unconscious and hemiparetic after an accident occurring during sport. The dissection was limited to the intima and internal elastic lamina. Patterns of cystic medial necrosis with mucoid degeneration were present in the right internal carotid artery proximal to the site of dissection, in the thoracic aorta, and in several visceral arteries. In the region of the right internal carotid artery affected with cystic medial necrosis, calcification and also splitting of the internal elastic lamina was found. Such calcification was also present at the site of the dissection, at the tip of the ruptured and recoiled elastic lamina. These changes, dissection as well as cystic medial necrosis, were associated with an elevated elastase content, a decrease of desmin and an increase of vimentin expression. Ultrastructurally, in areas affected by cystic medial necrosis a corresponding transformation of medial smooth muscle cell phenotype from the contractile to the metabolic state was found. The topographical relation of dissecting aneurysm, cystic medial necrosis, and an increased elastase content is suggestive of a causal relation, and the possibility of common etiological factors is discussed.

Adult↗