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Biomedical subjects

R Firsching

Publications and source records attributed to R Firsching.

At least 37 records · Page 2Linked to original sources
PubMed2000

Immunohistochemical determination of five somatostatin receptors in meningioma reveals frequent overexpression of somatostatin receptor subtype sst2A.

Meningioma is one of a variety of human tumors that exhibit a very high density of somatostatin receptors and in many cases show a true positive somatostatin receptor scintigraphy. However, the level of expression of individual somatostatin receptor proteins in meningioma has not been investigated. We have recently developed a panel of somatostatin receptor subtype-specific antibodies that effectively stain formalin-fixed, paraffin-embedded tumor tissue (S. Schulz et al., Clin. Cancer Res., 4: 2047-2052, 1998). In the present study, we have used these antibodies to determine the somatostatin receptor status of 40 randomly selected meningiomas. Immunoreactive staining for all somatostatin receptors was clearly located at the plasma membrane of the tumor cells and completely blocked with antigenic peptide. The vast majority of tumors (29 cases; 70%) were positive for sst2A immunoreactivity; among these, 20 (69%) tumors showed high levels of sst2A immunoreactivity. In contrast, all other somatostatin receptors were only detected sporadically, and none of these cases revealed a particularly strong staining. However, it is uncertain to what extent somatostatin receptor-immunoreactive staining intensity may translate into somatostatin receptor protein expression on the tumor cells. Therefore, in a prospective study, 16 surgically removed meningiomas were collected, and the level of sst2A expression was determined using Western blot analysis. Whereas sst2A was readily detectable as a broad band migrating at Mr 70,000 in 12 (75%) of these tumors, 8 tumors (50%) showed particularly high levels of immunoreactive sst2A receptors. There was an excellent correlation (P < 0.001) between the level of sst2A protein expression detected in Western blots and the sst2A- immunoreactive staining seen in tissue sections. Thus, the frequent overexpression of the sst2A receptor may explain the high tracer uptake often observed in meningioma patients during somatostatin receptor scintigraphy. Moreover, this simple immunohistochemical method could prove useful in identifying those cases of recurrent disease that may possibly respond to therapy with sst2-selective agonists.

Adult↗
PubMed1999

Measles virus spread by cell-cell contacts: uncoupling of contact-mediated receptor (CD46) downregulation from virus uptake.

CD46, which serves as a receptor for measles virus (MV; strain Edmonston), is rapidly downregulated from the cell surface after contact with viral particles or infected cells. We show here that the same two CD46 complement control protein (CCP) domains responsible for primary MV attachment mediate its downregulation. Optimal downregulation efficiency was obtained with CD46 recombinants containing CCP domains 1 and 2, whereas CCP 1, alone and duplicated, induced a slight downregulation. Using persistently infected monocytic/promyelocytic U937 cells which release very small amounts of infectious virus, and uninfected HeLa cells as contact partners, we then showed that during contact the formation of CD46-containing patches and caps precedes CD46 internalization. Nevertheless, neither substances inhibiting capping nor the fusion-inhibiting peptide Z-D-Phe-L-Phe-Gly-OH (FIP) blocked CD46 downregulation. Thus, CD46 downregulation can be uncoupled from fusion and subsequent virus uptake. Interestingly, in that system cell-cell contacts lead to a remarkably efficient infection of the target cells which is only partially inhibited by FIP. The finding that the contact of an infected with uninfected cells results in transfer of infectious viral material without significant (complete) fusion of the donor with the recipient cell suggests that microfusion events and/or FIP-independent mechanisms may mediate the transfer of MV infectivity from cell to cell.

Animals↗
PubMed1999

[Risk factors for posttraumatic fits and epilepsy].

There is still a considerable controversy about the usefulness of antiepileptic prophylaxis after traumatic brain injury. Overall incidence of posttraumatic fits and epilepsy's is well known, but an individual decision on prophylaxis requires knowledge about the individual risk. We performed a prospective observational study on 612 patients with traumatic brain injury of every degree of severity. Follow-up by phone call included 96.2% of the study population after 6 month and 91.2% after 36 month, respectively. The overall incidence for early fits (within 7 days after trauma), late fits (up to 36 month) and epilepsy (as defined by the International League Against Epilepsy) was 4.2%, 3.7% and 2.5%, respectively. These incidences increased according to the severity of the trauma, but the most powerful single predictor was intracranial hemorrhage. There was no significant difference related to the hemorrhage localisation. Development of epilepsy was much more common after late fits (48%) than after early fits (17%). These features established a hierarchy of risks for the development of epilepsy: no intracranial hemorrhage/no fit: 1% (4/437), intracranial hemorrhage/no fit: 8% (10/122), intracranial hemorrhage/early fit: 16% (3/19), intracranial hemorrhage/late fit: 53% (7/13). If prophylactic antiepileptic treatment is desired, but should be restricted to patients at high risk. These are patients with intracranial hemorrhage--are a well defined high risk group--when their first fit is a late fit.

Brain Injuries↗
PubMed1998

Efficiency of the Glasgow Outcome Scale (GOS)-Score for the long-term follow-up after severe brain injuries.

The Glasgow Outcome Scale (GOS)-Score is the most widely used instrument for measuring outcome in head injury research. Its reliability is seen controversial because of its simplicity. The study analyzes the correlation between the levels 3 to 5 of recovery to medical data, psychology and quality of life (QOL) 4 to 8 years after the accident. 34 patients, suffered from a severe brain injury (BI) 4 to 8 years ago, were reexamined by a psychological test battery and by evaluating of QOL (using self developed items for private and social activity). Test results and GOS-Score additionally were correlated to data from the phase of intensive care. Patients, still alive 4 to 8 years after injury, ranged mainly between the GOS-Scores 3 to 5 of recovery. Consequently, other scores (like Ranchos los Amigos, Barthel Index, GOAT) failed in measuring the outcome after such a long time. Different parameters from the phase of intensive care correlate significantly with the patients GOS-Score: coma length, isolated brain injury versus additional extracranial injury, compression of the basal cisternes on the initial CCT. Different psychological test results and the patients quality of life correlate significantly with the GOS-Scores from 3-5. These correlations could be shown in xy and yx-direction by different mathematical models. It is concluded, that GOS-levels 3-5 of recovery correlate to the essential medical data from the initial phase after the accident and to a detailed psychological evaluation years after injury.

Adult↗
PubMed1998

Long-term follow up in lumbar spinal stenosis.

In a retrospective study the charts of 72 patients who had decompressive surgery for lumbar stenosis between 1987 and 1990 were evaluated. Mean first follow up was 2.5 years (range 1.5 years to 3.5 years). A second follow up was done 8 years after surgery via mail. The mean age was 59.7 years (females 63.7, males 55 years). The average interval between the onset of complaints to surgery was 6 years. Claudicatio intermittens was found in 34.7% of cases. Patients were divided into four groups according to the classification by Arnoldi from 1976. Laminectomy of hemilaminectomy was performed in 73.6% of cases. In 68.1% nucleotomy was performed. In the first follow up outcome of patients was good in 73.6%. Complete recovery was noted in 61.1%. 11% were not satisfied with operative results. Old patients especially benefitted from the operation. In the second follow up after 8 years only 62.1% of the patients mentioned that their results were unchanged, good or better than at the first evaluation. The other 37.9% complained of a poorer result.

Aged↗
PubMed1998

Differential receptor usage by measles virus strains.

Recently, we demonstrated that infection of cells with all measles virus (MV) strains tested was inhibited by antibodies against CD46, although not all strains caused downregulation of the MV receptor CD46 from the surface of human cells. We now show that infection of cells with MV strain WTFb, a variant of wild-type isolate WTF which has been isolated and propagated on human BJAB cells, is not inhibited by antibodies against CD46. In contrast, infection of cells with the closely related strain WTFv, a Vero cell-adapted variant of WTF, is inhibited by antibodies against CD46. This observation led us to investigate the interaction of these viruses and the vaccine strain Edmonston (Edm) with CD46 and target cells. Cellular receptors with high affinity binding for WTFb are present on BJAB cells, but not on transfected CD46-expressing CHO cells. In contrast to the Edm strain, virus particles and solubilized envelope glycoproteins of WTFb have a very limited binding capacity to CD46. Furthermore, we show that recombinant soluble CD46 either does not bind, or binds very weakly, to WTFb glycoproteins expressed on the cell surface. Our findings indicate that wild-type MV strain WTFb and vaccine strain Edm use different binding sites on human cells. In addition, the results suggest that MV strains may alternatively use CD46 and an unknown molecule as receptors, and that the degree of usage of both receptors may be MV strain-specific.

Animals↗
PubMed1998

Early magnetic resonance imaging of brainstem lesions after severe head injury.

OBJECT: The availability of magnetic resonance (MR) imaging data obtained in comatose patients after head injury is scarce, because MR imaging is somewhat cumbersome to perform in patients requiring ventilation and because, in the first hours after injury, its relevance is clearly inferior to computerized tomography (CT) scanning. The authors assessed the value of MR imaging in the early postinjury period. METHODS: In this prospective study MR imaging was performed in 61 consecutive patients within 7 days after they suffered a severe head injury. An initial CT scan had already been obtained. To understand the clinical significance of the lesions whose morphological appearance was identified with MR imaging, brainstem function was assessed by registration of somatosensory and auditory evoked potentials. Brainstem lesions were visualized in 39 patients (64%). Bilateral pontine lesions proved to be 100% fatal and nonbrainstem lesions carried a mortality rate of 9%. In singular cases circumstances allowed for a clear clinical distinction between primary and secondary brainstem lesions. On MR imaging all lesions were hyper- and hypointense after intervals longer than 2 days. Within shorter intervals (< 2 days) after the injury, primary lesions appeared isointense on MR imaging. In one secondary brainstem lesion there were no traces of blood. CONCLUSIONS: Because mean intracranial pressure (ICP) levels in patients without brainstem lesions were similar to those in patients with brainstem lesions, the authors conclude that it was not mainly increased ICP that accounted for the high mortality rates in patients with brainstem lesions. The authors also conclude that brainstem lesions are more frequently found in severe head injury than previously reported in studies based on neuropathological or CT scanning data. Early MR imaging after head injury has a higher predictive value than CT scanning.

Adult↗
PubMed1997

Immunohistochemical detection of vascular growth factors in angiomatous and atypical meningiomas, as well as hemangiopericytomas.

The arachnoideal compartment provides the vascular sources for three different tumor types rich in vessels: angiomatous meningioma, some atypical meningioma with high vascularity and meningeal hemangiopericytoma. We investigated immunohistochemically the expression and distribution of vascular mitogenes in 7 angiomatous meningiomas, 8 atypical meningiomas with high vasculature and 4 hemangiopericytomas. On the one hand it should be studied which vascular growth factors such as VPF/VEGF-1, VPF/VEGF-2, bFGF, PDGF and TGF-alpha could be responsible for the close meshwork of vessels within the tumors. On the other hand we were interested in whether or not there are differences in vascular mitogens between slowly growing angiomatous meningiomas and both other types with their increased tendency to recur. PDGF and TGF-alpha were extensively expressed in the endothelium and smooth muscle cells of the vessels, as well as tumor cells. VEGF-2 could only be found in endothelial cells of all three tumor entities. bFGF was localized in some vessels of angiomatous meningiomas and VEGF-1 revealed a very low expression with a localization comparable with VEGF-2. Moreover, uPAR was diffusely expressed in nearly all tumor cells and endothelial cells. The fact that tumor cells of hemangiopericytomas and meningiomas did not show any immunohistochemical reaction with VEGF's could indicate a lower priority of these growth factors for neovascularization in this type of neoplasm. A different expression of vascular mitogens between benign angiomatous meningiomas and atypical meningiomas as well as hemangiopericytomas with their tendency for recurrence could not be observed. The morphological evidence for extravasates of IgG-proteins, Fibrin and Fibronectin due to VPF-effects seems not to be a renouncable condition for neoangiogenesis in the tumors investigated.

Adult↗
PubMed1997

Early dynamics of acute extradural and subdural hematomas.

In a retrospective study volumes of 42 extradural and 102 subdural traumatic hematomas were evaluated. Results were related with the time interval between injury and initial CT scan, outcome, coma grade and subject age. Mean volumes were found to increase with time after the injury. In the first hour volumes of 8 intracranial hematomas were hardly space consuming, while they became clearly space consuming in the second and in later hours after the injury. It was therefore concluded that it should not take longer than one hour until a CT scan be performed when an intracranial post-traumatic hematoma is suspected in the comatose patient.

Acute Disease↗
PubMed1997

Clinical predictors of the psychosocial long-term outcome after brain injury.

The correlation of clinical with psychological and social data is an attempt to find predictors of the definite long-term outcome after brain injury. 34 patients were reexamined 3 to 8 years after the accident using a number of psychological tests. Additionally, life quality was defined and evaluated. Only patients with an initial Glasgow Coma Scale-Score of 3-12, an intracranial traumatic lesion on computertomography and age 16-65 years at the time of accident were included in this study. Patients exhibited a uniform pattern of disturbances in psychosocial long-term outcome. These disturbances were compared with initial clinical data: memory, attention and learning were significantly correlated with the duration of coma and the presence of additional extracerebral injuries. From the initial computerized tomography, the findings 'compression of basal cisterns' and 'intracerebral contusion' showed to be predictors of the cerebral function. Late social status and behavior, defined as quality of life, were clearly related with initial clinical findings. In conclusion, there are early clinical predictors of the long term social and psychological outcome after brain injury.

Adolescent↗
PubMed1997

Guidelines for treatment of head injury in adults. Opinions of a group of neurosurgeons.

There are a number of parallel activities world wide to devise guidelines for the treatment of head injuries. A Group of neurosurgeons from various European countries worked on guidelines during three informal meetings, which may serve as a base for discussion of national or local protocols. Three levels of certainty were distinguished: Measures that must be taken which such a high degree of certainty, that they have not seriously been challenged-principles. Measures, that should be taken, as there is reasonable evidence in the literature about its efficacy-recommendations and measures that may be taken, but proof of its efficacy is lacking-optional measures. Protocols based on these guidelines are felt to help young neurosurgeons in training, define neurosurgical needs for other specialities and enhance the general efficacy of care for the head injured patient including multiple injuries.

Adult↗
PubMed1996

Penetration of M cells and destruction of Peyer's patches by Yersinia enterocolitica: an ultrastructural and histological study.

Yersinia enterocolitica is enteropathogenic for man and rodents. Previous studies provided evidence that Y. enterocolitica invades the lymphoid follicles of the Peyer's patches (PP) of the small intestine. In this study Y. enterocolitica-induced tissue alterations of the follicle-associated epithelium (FAE) and the underlying PP tissue were analysed by scanning (SEM) and transmission electron microscopy (TEM) as well as by conventional histological examination. For this purpose, an experimental mouse infection model including orogastric infections as well as ileal loop experiments were used. A rapid and selective colonisation of the FAE after orogastric yersinia infection was observed by SEM. TEM studies confirmed that Y. enterocolitica adhered closely to the FAE including M cells and enterocytes. Histological studies and TEM revealed that Y. enterocolitica selectively invaded the PP via M cells but not via other cells of the FAE. One day after Y. enterocolitica infection the FAE was altered and small micro-abscesses comprising yersiniae expressing the major outer-membrane protein YadA were observed immediately beneath the FAE. Adjacent villi were dilated from lymphangiectasis and transmigrating polymorphonuclear leucocytes (PMNL) were found within the epithelium. At 5-7 days after infection the FAE and parts of PP were destroyed. Profound alterations of the cyto-architecture of the PP were due to the enormous recruitment of PMNL. By day 5 after infection, abscesses were found in the mesenteric lymph nodes. However, TEM studies revealed evidence that Y. enterocolitica may disseminate from the PP not only via the lymphatics but also by invasion of blood vessels. Taken together, the results of this study demonstrate that the FAE is the primary site of host-pathogen interaction in Y. enterocolitica infection and that this pathogen penetrates M cells and subsequently induces destruction of the PP.

Animals↗
PubMed1996

Intratumorous heterogeneity of chromosome 10 and 17 in meningiomas using non-radioactive in situ hybridization.

Contrary to classical cytogenetics non-radioactive chromosomal in situ hybridization (CISH) may be performed within 24 hours while the morphological structure of paraffin-embedded tumor material is preserved. Slides of 34 formalin fixed and paraffin-embedded meningiomas were hybridized with a biotinylate alpha-satellite DNA-probe for chromosome 10 and 17. According to the distribution of hybridization signals per nucleus we found five meningiomas with signs of trisomy 17 whereby all of them exhibited intratumorous heterogeneity. Trisomy 10 was found in five tumors. Monosomy 17 was assumed in two cases and monosomy 10 in one meningioma. As a control six meningiomas were karyotyped by G-banding. Formalin fixed and paraffin-embedded tissue of the same tumors was hybridized against chromosome X and Y. In five of six cases the result of conventional karyotyping could be confirmed by in situ hybridization. CISH of paraffin-embedded tissue is new tool for the analysis of intratumorous cytogenetical heterogeneity with potential prognostic significance.

Adult↗
PubMed1996

Considerations on the tendency for calcification in meningiomas.

Calcifications in meningotheliomatous and fibromatous meningiomas were demonstrated after maceration under the scanning electron microscope and by pluck preparation. In five predominantly meningotheliomatous and five fibromatous meningiomas vascular features were studied after injection of Indian ink. The influx of calcium into the tumor parenchyma is thought to be related to long vessel loops and parallel coursing vessels which act as a countercurrent multiplication system similar to the loops of Henle in the kidney. Abruptly changing of diameter of vessels reduces the flow rate and enhances the transport of ions across vessels walls. Furthermore, the fine structure of endothelium favors the escape of ions into vessel walls and into parenchyma. Possible consequences of an intratumoral Ca overload are briefly discussed.

Calcinosis↗