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Biomedical subjects

F Weber

Publications and source records attributed to F Weber.

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

Comparative follow-up of enhancement phenomena with MRI and Proton MR Spectroscopic Imaging after intralesional immunotherapy in glioblastoma--Report of two exceptional cases.

The morphologic pattern of contrast enhancement in magnetic resonance imaging (MRI) of glioblastoma patients could be non specific and metabolic investigations can be useful for the differentiation of tumorous and non tumorous enhancement. Following initial therapy secondary tissue changes can occur and non specific non tumorous enhancement phenomena have been observed after local immuno- and gene therapy strategies. Magnetic resonance spectroscopic imaging (MRSI) has the potential to give more specific information on the metabolism of the suspective tissue and to differentiate enhancing phenomena. We demonstrate two cases of patients suffering from a glioblastoma with simultaneous MRI and MRSI follow-up after multimodal treatment with surgery, radiation, intralesional immunotherapy (IL-4 toxin) and ongoing chemotherapy. MRI demonstrated extensive and increasing enhancement. This was highly suspicious of rapid progressive local tumor recurrency in both patients. Simultaneously obtained MRSI did not show the expected result of extensive and increasing choline concentration within these enhancing areas. This indicated that the enhancement did most likely not reflect vital tumor tissue. Chemotherapy treatment was continued and further MRI follow up revealed nearly complete regression of all enhancement. In pretreated glioblastoma metabolic data of MRSI seem to be potentially helpful to differentiate tumorous and non tumorous enhancement phenomena after local immunotherapy, which might be useful for further treatment decisions.

Adult↗
PubMed2002

Endovascular treatment of thoracic aortic dissection and its variants.

The acute aortic syndrome (AAS) is described. Its pathophysiology is discussed for each of the three entities (penetrating aortic ulcer, intramural hematoma and aortic dissection). The natural history of these three pathologies is reviewed. Diagnostic features and investigation imaging techniques are summarized. The technique of stentgraft-placement is described in detail. The authors report their clinical experience with 127 patients, presenting acute type B aortic dissection or its variants, and treated with an endovascular stent-graft-device. These results are in part compared with a group of control patients with acute type B dissection, submitted to medical non-invasive therapy.

Acute Disease↗
PubMed2002

[Primary stenting of thrombotic occluded main coronary artery in cardiogenic shock].

Acute left main coronary artery (LMCA) occlusion is associated with a high mortality rate. The majority of patients with this clinical condition die suddenly or from cardiogenic shock. We report a case of cardiogenic shock resulting from acute main coronary occlusion. Emergency cardiac catheterization was performed and coronary angiography showed a totally occluded LMCA. Prompt revascularization by means of primary LMCA stenting was successful and the patient was discharged 16 days later without neurological deficit or clinical signs of heart failure. We suggest that the rapid coronary angiography followed by angioplasty and primary stent implantation was instrumental in saving this patient's life.

Angioplasty, Balloon, Coronary↗
PubMed2001

CSF filtration is an effective treatment of Guillain-Barré syndrome: a randomized clinical trial.

OBJECTIVE: To compare CSF filtration (CSFF) and plasma exchange (PE) in the treatment of patients with Guillain-Barré syndrome (GBS). METHODS: In a prospective controlled clinical trial, 37 patients with acute GBS were randomized to receive either CSFF or PE. Inclusion criteria were fulfillment of National Institute of Neurological and Communicative Disorders and Stroke criteria and disability to walk >5 m unassisted. RESULTS: With similar baseline features in both groups (initial disability grades on the six-point grading scale of the GBS Study Group) the primary outcome variable (improvement within 28 days after randomization) was almost identical (test for equivalence p = 0.0014), the mean grade values being 0.82 in the CSFF group and 0.80 in the PE group. After 56 days, 56% (9 of 16 patients) of the CSFF group and 37% (7 of 19 patients) of the PE group had reached grade 2 (i.e., ability of unassisted walking >5 m). After 6 months, the probability to reach grade 2 was about 80% in both groups. In the CSFF group, transient pleocytosis occurred without apparent clinical complications. Clinically relevant complications were higher in the PE-treated group. CONCLUSIONS: Although the number of patients was small, the authors found that the treatment of GBS with CSFF is at least as effective as with PE. CSFF might work by removing from the CSF inflammatory mediators, autoantibodies, or other factors.

Adult↗
PubMed2001

Development of an ultrasensitive enzyme immunoassay for the determination of matrix metalloproteinase-9 (MMP-9) levels in normal human cerebrospinal fluid.

Determination of matrix metalloproteinase-9 (MMP-9) in human cerebrospinal fluid (CSF) to study blood-brain barrier impairment and immune cell migration in inflammatory neurological diseases recently became a matter of major interest. Regularly, MMP-9 was determined qualitatively or semi-quantitatively by zymography (gelatin gel electrophoresis) or quantitatively by enzyme immunoassay (EIA). As yet, it was not possible by either method to detect MMP-9 in CSF of controls (patients without pathologically increased CSF parameters). We developed an ultrasensitive two-side enzyme-linked immunosorbent assay (ELISA) which allows for the first time to measure reliably MMP-9 concentrations in CSF of controls. This ELISA uses a monoclonal as capture and a polyclonal as detector antibody. The detection limit of the assay is below 10 pg/ml and the assay range is 15-2000 pg/ml. Intra-assay precision is 2.5% for low and 3.7% for high, inter-assay precision is 11% for low and 10.7% for high values, respectively. The determination of the MMP-9 concentration in 50 control CSF gave the following results: range, 22-146 pg/ml; median, 76 pg/ml. The measurement of native and recombinant MMP-9 was carried out with three commercially available ELISAs, most widely employed in MMP-9 research, and compared to the newly developed one. All ELISAs recognize recombinant MMP-9 by factors of 5-20 less sensitively than native MMP-9.

Adult↗
PubMed2001

Migration of human granulocytes through reconstituted basement membrane is not dependent on matrix metalloproteinase-9 (MMP-9).

Transmigration of human granulocytes across a basal lamina equivalent was studied in vitro. Transwell inserts were coated with Matrigel, a reconstituted basement membrane. Granulocytes (2x10(6)) were applied to the upper chamber. As chemoattractant interleukin-8 (IL-8; 25 ng/ml) was added to the lower chamber. After 1 h of migration, cells were counted in the lower chamber. Specific hydroxamate inhibitors of MMPs (BB-3103, Ro 31-9790) or of serine proteases (Pefabloc, leupeptin) were added at various concentrations to both chambers before the start of migration. Additional experiments were performed with alpha(2)-macroglobulin, a natural inhibitor of MMPs and a monoclonal antibody which specifically blocks the activity of MMP-9. Migration of granulocytes through Matrigel could not be reduced significantly by any of the MMP inhibitors. A dose-dependent impairment of transmigration was only found with Pefabloc, however, this substance also induced severe morphological changes of the cells. The other inhibitor of serine proteases, leupeptin, did not influence migration at all.

Basement Membrane↗
PubMed2001

Characterization of the human T cell response against the neuronal protein synapsin in patients with multiple sclerosis.

Although multiple sclerosis (MS) is considered primarily as a demyelinating disease, neuronal damage is abundant and correlates with the neurological deficit. Therefore, we investigated the frequency and characteristics of human T cells specific for synapsin-a neuronal protein highly conserved among species. Synapsin specific T cell responses were detected at a frequency similar to that of MBP specific T cells in MS patients, one patient with acute demyelinating encephalomyelitis (ADEM) and controls. Long-term T cell lines specific for synapsin exhibited a CD3(+), CD4(+), CD8(-) phenotype and produced high amounts of tumor-necrosis-factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) after antigen specific stimulation, whereas lymphotoxin (LT), interleukin-4 (IL-4) and interleukin-10 (IL-10) were detectable in smaller quantities.

Acute Disease↗
PubMed2001

The Bunyamwera virus nonstructural protein NSs inhibits viral RNA synthesis in a minireplicon system.

The small (S) genomic segment of Bunyamwera virus (family Bunyaviridae, genus Bunyavirus) encodes the nucleocapsid protein, N, and a nonstructural protein, NSs, in overlapping reading frames. In order to elucidate the function of NSs, we established a plasmid-based minireplicon system using mammalian cells that express large amounts of T7 RNA polymerase. Expression of N, the viral polymerase protein (L), and a minireplicon containing a reporter gene was sufficient to reconstitute functional virus nucleocapsids. Coexpression of NSs, however, led to a dose-dependent decrease in reporter activity without affecting expression of controls. The inhibition could not be reversed by overexpression of N, L or the minireplicon, indicating that the NSs effect was not caused by a reduction in virus gene expression. The NSs proteins of two other members of the Bunyavirus genus, Guaroa virus and Lumbo virus, were also inhibitory in our system. The intracellular localisation of Bunyamwera virus NSs was investigated and found to be predominantly cytoplasmic, but intranuclear inclusion was also detected. Taken together, these data suggest that, in mammalian cells, the bunyavirus NSs protein controls the activity of the viral polymerase by a highly conserved mechanism.

Amino Acid Sequence↗
PubMed2001

Analysis of interleukin-4 receptor alpha chain variants in multiple sclerosis.

A recent candidate gene study employing microsatellite markers suggested a possible linkage of multiple sclerosis (MS) with the interleukin-4 receptor (IL4R) gene. Consequently, we investigated the association of different IL4R variants with MS in 341 German MS patients and 305 healthy controls. Analysis of the first 100 MS patients for six IL4R variants showed an increased frequency of the R551 variant in MS patients versus healthy controls and carriage of the same IL4R variant was weakly associated with myelin oligodendrocyte glycoprotein (MOG) autoantibody production. However, further analysis of all 341 MS patients did not confirm the finding that this IL4R variant represents a general genetic risk factor for MS but revealed an increased frequency of the R551 variant in MS patients with primary progressive MS (PPMS, n=48) as compared to patients with relapsing remitting MS or secondary progressive MS (RR/SPMS n=284; P=0.005 for genotype differences) and to 305 healthy controls (P=0.001 for genotype differences). This association was statistically independent of the presence of the well-known MS susceptibility allele HLA-DRB1*15. After correction for multiple comparisons only the genotype differences between PPMS patients and healthy controls remained statistically significant. These results indicate, that the IL4R variant R551 may influence the genetic predisposition for PPMS but does not represent a general genetic risk factor for MS.

Adult↗
PubMed2001

Bunyamwera bunyavirus nonstructural protein NSs is a nonessential gene product that contributes to viral pathogenesis.

Bunyamwera virus (family Bunyaviridae, genus Bunyavirus) contains a tripartite negative-sense RNA genome. The smallest RNA segment, S, encodes the nucleocapsid protein N and a nonstructural protein, NSs, in overlapping reading frames. We have generated a mutant virus lacking NSs, called BUNdelNSs, by reverse genetics. Compared with the wild-type (wt) virus, BUNdelNSs exhibited a smaller plaque size and generated titers of virus approximately 1 log lower. In mammalian cells, the mutant expressed greatly increased levels of N protein; significantly, the marked inhibition of host cell protein synthesis shown by wt virus was considerably impaired by BUNdelNSs. When inoculated by the intracerebral route BUNdelNSs killed BALB/c mice with a slower time course than wt and exhibited a reduced cell-to-cell spread, and titers of virus in the brain were lower. In addition, the abrogation of NSs expression changed Bunyamwera virus from a noninducer to an inducer of an interferon-beta promoter. These results suggest that, although not essential for growth in tissue culture or in mice, the bunyavirus NSs protein has several functions in the virus life cycle and contributes to viral pathogenesis.

Aedes↗
PubMed2001

[Acute compartment syndrome. Results of a clinico-experimental study of pressure and time limits for emergency fasciotomy].

BACKGROUND: Acute compartment syndrome of the leg is to be regarded as a traumatological emergency. Most specialists already agree that only a timely operative decompression of the afflicted compartment can prevent serious tissue damage. What still remains subject to discussion, however, is the precise tissue pressure above which the operation becomes imperative. Experimental human studies focusing on tissue pressure and muscle oxygenation have not yet been carried out. It was thus the aim of the present study to analyze oxygen partial pressure of the anterior tibial muscle and peroneal action potential in a model compartment syndrome in man. METHODS: In 22 healthy, normotensive volunteers, constant pressure values from 0 to 100 mmHg were induced in the anterior tibial muscle with antishock trousers. Over a period of up to 6 h measurements were made of (1) tissue pressure, (2) intramuscular oxygen partial pressure (pO2), and (3) muscle response potential (MRP) of the n. peroneus profundus by electroneurography. RESULTS: We achieved a 97.7% (Q25%/Q75%: 89.2/99.8) transfer of the pneumatic pressure to the lower leg. Already at intramuscular tissue pressures of 30-40 mmHg, hypoxia and reduction of MRP appeared. A reduction of the MRP to zero and pO2 < 1 mmHg was observed from a pressure of 50 mmHg. Tissue pressure values of over 75 mmHg resulted almost without exception in anoxia of the muscle. CONCLUSIONS: Even under normal perfusion conditions, already slight increases in pressure of above 30 mmHg lead to reduced tissue oxygenation and neural function. We have to consider that with additionally traumatized muscle the ischemic tolerance is markedly reduced and due to unknown influences such as local vasoreactivity and capacity of autoregulation the nutritive perfusion cannot be determined. In the case of a severely injured muscle, to be on the safe side decompressive fasciotomy should therefore be carried out if pressure values remain above 30 mmHg.

Adult↗
PubMed2001

Intracerebral neurocysticercosis mimicking glioblastoma multiforme: a rare differential diagnosis in Central Europe.

A 47-year-old Greek man presented with a 4-week history of speech difficulties. CT and MRI revealed a low-density multilobulated cystic frontal mass with peripheral ring contrast enhancement adjacent to the sylvian fissure. Examination was normal. Blood tests revealed leucocytosis (16,000 cells/microl) and an elevated erythrocyte sedimentation rate (30/52). A malignant brain tumour was suspected and surgically removed. Histological examination disclosed intracerebral neurocysticercosis.

Brain Diseases↗
PubMed2001

3-[123I]Iodo-alpha-methyl-L-tyrosine uptake in cerebral gliomas: relationship to histological grading and prognosis.

3-[123I]Iodo-alpha-methyl-L-tyrosine (IMT) is employed clinically as a tracer of amino acid transport in brain tumours using single-photon emission tomography (SPET). This study investigates the role of IMT SPET in the non-invasive histological grading and prognostic evaluation of cerebral gliomas. The files of patients investigated by IMT SPET in our clinic between 1988 and 1996 were evaluated retrospectively. Complete follow-up was available for 58 patients with cerebral gliomas investigated by IMT SPET shortly after tumour diagnosis. Seventeen patients had low-grade gliomas (WHO grade II), 14 had anaplastic gliomas (WHO grade III) and 27 had glioblastomas (WHO grade IV). Thirty-six cases were primary tumours and 22 cases, recurrences. Maximal and mean tumour-to-brain (T/B) ratios of IMT uptake at the first IMT SPET investigation were related to histological grading and survival time. Patients with low-grade gliomas showed significantly longer survival than patients with high-grade (grade III or IV) tumours. Gliomas without contrast enhancement on computed tomography or magnetic resonance imaging scans were associated with longer patient survival than tumours with contrast enhancement. The T/B ratios of IMT SPET showed no differences in relation to histological grading [WHO grade II: 1.73+/-0.59; WHO grade III: 1.74+/-0.38; WHO grade IV: 1.59+/-0.35, (mean+/-SD, T/B ratios of mean tumour uptake)]. The median survival time of patients with a high T/B ratio on IMT SPET was not significantly different from that of patients with a low T/B ratio (T/B ratio <1.6, 14.8 months; T/B ratio > or =1.6, 13.0 months). Thus, no evidence could be found for a relationship between IMT uptake in cerebral gliomas and either histological grading or survival time. Nevertheless, IMT SPET constitutes a useful method for the detection of primary and recurrent gliomas, determination of tumour extent and individual follow-up.

Adult↗
PubMed2001

Catamenial hemoptysis.

Catamenial hemoptysis is a rare result of thoracic endometriosis. The long-term treatment of this condition remains controversial. An operation to remove the offending parenchymal endometrial tissue by pulmonary sparing, such as wedge resection, segmentectomy affords satisfactory treatment without the disadvantage of long-term hormone therapy and with the consequent suppression of normal menses and alteration of secondary sexual characteristics in a young woman.

Adult↗
PubMed2001

Local inflammation and devascularization--in vivo mechanisms of the "bystander effect" in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma.

Somatic gene therapy with the herpes simplex virus type I thymidine kinase gene/ganciclovir (HSV-Tk/GCV) system and murine retroviral vector producer cells (VPCs) was introduced as a new adjuvant treatment modality to treat tumor bulk and to prevent tumor recurrence in patients harboring malignant glioma. The single-center experience after treatment of 27 patients undergoing tumor resection followed by intracerebral VPC injection for HSV-Tk suicide gene therapy will be presented focused on findings of systematic and close MRI follow-up and a few histological specimens. The data indicate that hemorrhagic necrosis due to endothelial cell transfection mediated vessel necrosis and that local inflammatory immune response occurs frequently after gene therapy. These phenomena seem to be specific because none of the patients of a control group showed any similar features. The prognosis (time to progression, survival) of the patients with "bystander effects" after gene therapy was better, but compared to those patients without bystander effects, they were also privileged by a favorable constellation of prognostic factors. Therefore, the appearance of these neuroradiologic features cannot serve as an indicator for treatment effectiveness and outcome.

Adolescent↗
PubMed2001

Pathogenesis of the permeability barrier abnormality in epidermolytic hyperkeratosis.

Epidermolytic hyperkeratosis is a dominantly inherited ichthyosis, frequently associated with mutations in keratin 1 or 10 that result in disruption of the keratin filament cytoskeleton leading to keratinocyte fragility. In addition to blistering and a severe disorder of cornification, patients typically display an abnormality in permeability barrier function. The nature and pathogenesis of the barrier abnormality in epidermolytic hyperkeratosis are unknown, however. We assessed here, first, baseline transepidermal water loss and barrier recovery kinetics in patients with epidermolytic hyperkeratosis. Whereas baseline transepidermal water loss rates were elevated by approximately 3-fold, recovery rates were faster in epidermolytic hyperkeratosis than in age-matched controls. Electron microscopy showed no defect in either the cornified envelope or the adjacent cornified-bound lipid envelope, i.e., a corneocyte scaffold abnormality does not explain the barrier abnormality. Using the water-soluble tracer, colloidal lanthanum, there was no evidence of tracer accumulation in corneocytes, despite the fragility of nucleated keratinocytes. Instead, tracer, which was excluded in normal skin, moved through the extracellular stratum corneum domains. Increasing intercellular permeability correlated with decreased quantities and defective organization of extracellular lamellar bilayers. The decreased lamellar material, in turn, could be attributed to incompletely secreted lamellar bodies within granular cells, demonstrable not only by several morphologic findings, but also by decreased delivery of a lamellar body content marker, acid lipase, to the stratum corneum interstices. Yet, after acute barrier disruption a rapid release of preformed lamellar body contents was observed together with increased organelle contents in the extracellular spaces, accounting for the accelerated recovery kinetics in epidermolytic hyperkeratosis. Accelerated recovery, in turn, correlated with a restoration in calcium in outer stratum granulosum cells in epidermolytic hyperkeratosis after barrier disruption. Thus, the baseline permeability barrier abnormality in epidermolytic hyperkeratosis can be attributed to abnormal lamellar body secretion, rather than to corneocyte fragility or an abnormal cornified envelope/cornified-bound lipid envelope scaffold, a defect that can be overcome by external applications of stimuli for barrier repair.

Adolescent↗