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M Glatzel

Publications and source records attributed to M Glatzel.

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

[Eosinophilia and polyneuropathy after percutaneous transluminal coronary angioplasty].

HISTORY AND CLINICAL FINDINGS: A 76-year-old man was admitted for a coronary angiography because of a postinfarction angina. Clinical examination was normal except a grade 2/6 systolic murmur and a slightly impaired vibration sense. INVESTIGATIONS: A slight anaemia, a slightly impaired renal function, and a slightly elevated cholesterol level could be found. The ECG showed a chronic anterior myocardial infarction. In the coronary angiography a double vessel disease was seen. TREATMENT AND COURSE: A percutaneous transluminal coronary angioplasty of the left anterior descending artery was performed and four stents were implanted. During the procedure a rush occurred in both legs following an appearance of livedo reticularis. Renal function deteriorated and there was an markedly increased number of eosinophils. With a new neurological check a marked peripheral neuropathy could be found. A biopsy of the sural nerve showed a necrotizing granulomatous inflammation of the nerve and the surrounding small arteries. Several small arteries contained needle shaped crystal clefts in their walls. The appearances were of multiple cholesterol emboli. Besides treatment of pain an immunosuppressive therapy with prednisone (100 mg/d) and cyclophosphamide (50 mg/d) showed no improvement. The patient died 2 months after the diagnosis of cholesterol emboli. CONCLUSION: Typically, cholesterol embolism occurs in elderly men within the eight weeks after arterial procedure. Diagnosis can be made only by histological examination. Cholesterol emboli syndrome may mimic systemic vasculitis. Therapy trial of cholesterol emboli syndrome usually fails and mortality rate is high.

Aged↗
PubMed2000

Impaired prion replication in spleens of mice lacking functional follicular dendritic cells.

In scrapie-infected mice, prions are found associated with splenic but not circulating B and T lymphocytes and in the stroma, which contains follicular dendritic cells (FDCs). Formation and maintenance of mature FDCs require the presence of B cells expressing membrane-bound lymphotoxin-alpha/beta. Treatment of mice with soluble lymphotoxin-beta receptor results in the disappearance of mature FDCs from the spleen. We show that this treatment abolishes splenic prion accumulation and retards neuroinvasion after intraperitoneal scrapie inoculation. These data provide evidence that FDCs are the principal sites for prion replication in the spleen.

Animals↗
PubMed2000

Adenoviral and adeno-associated viral transfer of genes to the peripheral nervous system.

Targeted expression of foreign genes to the peripheral nervous system is interesting for many applications, including gene therapy of neuromuscular diseases, neuroanatomical studies, and elucidation of mechanisms of axonal flow. Here we describe a microneurosurgical technique for injection of replication-defective viral vectors into dorsal root ganglia (DRG). Adenovirus- and adeno-associated virus-based vectors with transcriptional competence for DRG neurons led to expression of the gene of interest throughout the first neuron of the sensory system, from the distal portions of the respective sensory nerve to the ipsilateral nucleus gracilis and cuneatus, which contains the synapses to the spinothalamic tracts. Use of Rag-1 ablated mice, which lack all B and T lymphocytes, allowed for sustained expression for periods exceeding 100 days. In immunocompetent mice, long-term (52 days) expression was achieved with similar efficiency by using adeno-associated viral vectors. DRG injection was vastly superior to intraneural injection into the sciatic nerve, which mainly transduced Schwann cells in the vicinity of the site of inoculation site but only inefficiently transduced nerve fibers, whereas i.m. injection did not lead to any significant expression of the reporter gene in nerve fibers. The versatile and efficient transduction of genes of interest should enable a wide variety of functional studies of peripheral nervous system pathophysiology.

Adenoviridae↗
PubMed2000

Prions: from neurografts to neuroinvasion.

Spongiform encephalopathies are infectious neurodegenerative diseases caused by pathogens that seem to be devoid of any informational nucleic acids. Histopathologically, these diseases are characterized by spongiform degeneration of the central nervous system. Although the main pathological changes during the course of the disease occur in the brain, the infectious agent accumulates early in lymphoid tissue. The consecutive development of clinical disease depends on the presence of an intact immune system including mature B-cells and follicular dendritic cells. In this article we review the state of knowledge on the routes of neuroinvasion used by the infectious agent in order to gain access to the central nervous system upon entry into extracerebral sites.

Animals↗
PubMed2000

[Prevention of radiation-induced diarrhea by smectite. Results of a double-blind randomized, placebo-controlled multicenter study].

PURPOSE: Diarrhea and abdominal pain are well-known side effects abdominal or pelvic of radiation therapy that may lead to interruption of treatment in serious cases. In recent trials the silicate smectite has proven a promising drug in the prophylaxis of these adverse events. The presented trial aimed at the verification of earlier studies and the evaluation of a dose-effect relationship. PATIENTS AND METHODS: Between April 1994 and May 1995, a total of 176 patients obtaining radiotherapy of the pelvis or the abdomen were evaluated in a double-blind, randomized placebo-controlled investigation regarding the prophylactic effect of smectite (= Colina) against radiotherapy-induced diarrhea. During the whole period of radiotherapy 85 patients obtained 2 x 6 g smectite daily and 91 patients received 2 x 6 g placebo. The primary end point of the analysis was the time to the first appearance of diarrhea (> or = 3 pappy stools). RESULTS: All 176 patients were evaluated according to an intent-to-treat analysis. There was no significant difference between the prophylactic effects of smectite and placebo. For an explorative post-hoc analysis the total study group was split up into 2 subgroups, one with an irradiated small bowel volume < or = 837.5 ml, the other with a small bowel volume > 837.5 ml (median); the analysis indicated that the first subgroup showed a benefit for the smectite-treated patients in contrast to the placebo treatment (32 vs. 18 calendar days to the first appearance of diarrhea). This benefit was statistically not significant. CONCLUSION: Prophylactic application of smectite during irradiation of the pelvis and the abdomen can delay the development of radiotherapy-induced diarrhea, a statistical significance could not be verified neither in the total study group nor in the post-hoc subgroup analysis.

Abdomen↗
PubMed2000

Gene expression of TNF-receptors in peripheral blood mononuclear cells of patients with alcoholic cirrhosis.

BACKGROUND/AIMS: Elevated concentrations of tumor necrosis factor receptors have been detected in alcoholic cirrhosis, but it remains unknown whether or not peripheral blood mononuclear cells are a source of tumor necrosis factor receptors and reflect the clinical disease activity of patients with advanced alcoholic liver disease. METHODS: Twenty-two abstinent patients in different stages of alcohol-induced cirrhosis according to the criteria of the Child-Pugh classification (Child-Pugh stage A: 4, Child-Pugh stage B: 10, Child-Pugh stage C: 8) were compared with four healthy individuals. Semi-quantitative reverse transcriptase-polymerase chain reaction was used for the measurement of the expression of tumor necrosis factor-alpha, soluble tumor necrosis factor receptors-p55, -p75, interleukin-10 and inducible nitric oxide synthase in unstimulated peripheral blood mononuclear cells. RESULTS: Unstimulated peripheral blood mononuclear cells of patients with alcoholic cirrhosis demonstrate a stage-dependent enhanced RNA expression of tumor necrosis factor-alpha (healthy controls 0/4, Child-Pugh stage A 2/4, stage B 10/10, stage C 8/8; p<0.01). The mRNA expression of TNF-receptors-p55/-p75 is significantly higher in patients with severe alcoholic cirrhosis (Child-Pugh stage B or C patients) than healthy controls (p<0.05), while peripheral blood mononuclear cells from patients with Child-Pugh stage A show a similiar pattern of gene expression to healthy controls. No significant up-regulation of interleukin-10 was found. Inducible nitric oxide synthase was detectable in Child-Pugh stage C (p<0.05). CONCLUSIONS: Unstimulated peripheral blood mononuclear cells of patients with severe alcoholic cirrhosis (Child-Pugh stage B and C) demonstrate a systemic leukocyte activation and gene expression of tumor necrosis factor-alpha and tumor necrosis factor receptors-p55/-p75, which is correlated with the activity of the disease. Our data confirm previous studies that reported a correlation between plasma levels of pro-inflammatory cytokines and the severity of alcoholic cirrhosis. The role of interleukin-10 and inducible nitric oxide synthase in the pathogenesis of alcoholic cirrhosis remains to be fully elucidated.

Antigens, CD↗
PubMed2000

Peripheral pathogenesis of prion diseases.

Prions are infectious pathogens that cause a group of neurodegenerative diseases characterized by spongiform degeneration of the central nervous system. Prions appear to lack any informational nucleic acid. The most notable prion diseases include bovine spongiform encephalopathy, scrapie in sheep and Creutzfeldt-Jakob disease of humans. Transmission is thought to be achieved through conversion of a normal host protein into a pathological isoform. Although the main pathological changes during the course of the disease occur in the brain, the infectious agent accumulates early in lymphoid tissue. The subsequent development of clinical disease depends on the presence of an intact immune system including mature B-cells. In this article we review the state of knowledge on the routes of neuroinvasion used by the infectious agent in order to gain access to the central nervous system upon entry into extracerebral sites.

Animals↗
PubMed2000

Deletions in the spinal muscular atrophy gene region in a newborn with neuropathy and extreme generalized muscular weakness.

A newborn presented with respiratory insufficiency requiring artificial ventilation, inability to swallow, lack of spontaneous movements including the facial muscles, and areflexia. Nerve conduction velocities were not recordable. Molecular analysis showed a homozygous deletion in the spinal muscular atrophy (SMN) gene region on chromosome 5q. Pathological and neuropathological examination revealed a normal number of anterior horn cells, hypomyelinated axons in peripheral nerves and some atrophy of skeletal muscle fibres in combination with sarcoplasmic glycogen accumulation. This observation illustrates that severe congenital neuropathy can result from deletions in the SMN gene.

Axons↗
PubMed2000

Neuroinvasion of prions: insights from mouse models.

The prion was defined by Stanley B. Prusiner as the infectious agent that causes transmissible spongiform encephalopathies. A pathological protein accumulating in the brain of scrapie-infected hamsters was isolated in 1982 and termed prion protein (PrPSc). Its cognate gene Prnp was identified more than a decade ago by Charles Weissmann, and shown to encode the host protein PrP(C). Since the latter discovery, transgenic mice have contributed many important insights into the field of prion biology, including the understanding of the molecular basis of the species barrier for prions. By disrupting the Prnp gene, it was shown that an organism that lacks PrP(C) is resistant to infection by prions. Introduction of mutant PrP genes into PrP-deficient mice was used to investigate the structure-activity relationship of the PrP gene with regard to scrapie susceptibility. Ectopic expression of PrP in PrP knockout mice proved a useful tool for the identification of host cells competent for prion replication. Finally, the availability of PrP knockout mice and transgenic mice overexpressing PrP allows selective reconstitution experiments aimed at expressing PrP in neurografts or in specific populations of haemato- and lymphopoietic cells. The latter studies have allowed us to clarify some of the mechanisms of prion spread and disease pathogenesis.

Animals↗
PubMed2000

Prions: pathogenesis and reverse genetics.

Spongiform encephalopathies are a group of infectious neurodegenerative diseases. The infectious agent that causes transmissible spongiform encephalopathies was termed prion by Stanley Prusiner. The prion hypothesis states that the partially protease-resistant and detergent-insoluble prion protein (PrPsc) is identical with the infectious agent, and lacks any detectable nucleic acids. Since the latter discovery, transgenic mice have contributed many important insights into the field of prion biology. The prion protein (PrPc) is encoded by the Prnp gene, and disruption of Prnp leads to resistance to infection by prions. Introduction of mutant PrPc genes into PrPc-deficient mice was used to investigate structure-activity relationships of the PrPc gene with regard to scrapie susceptibility. Ectopic expression of PrPc in PrPc knockout mice proved a useful tool for the identification of host cells competent for prion replication. Finally, the availability of PrPc knockout and transgenic mice overexpressing PrPc allowed selective reconstitution experiments aimed at expressing PrPc in neurografts or in specific populations of hemato- and lymphopoietic cells. The latter studies helped in elucidating some of the mechanisms of prion spread and disease pathogenesis.

Animals↗
PubMed2000

[Radiotherapy of hidradenitis suppurativa--still valid today?].

PURPOSE: In a retrospective analysis the efficacy of radiotherapy in the treatment of hidradenitis suppurativa was assessed. PATIENTS AND METHODS: Data from 231 patients undergoing radiotherapy for hidradenitis suppurativa in the last years in 2 hospitals were analyzed. The patients were treated with an orthovoltage therapy unit with 175 kV, 0.5 mm copper-filtering. The single doses reached from 0.5 Gy to 1.5 Gy up to total doses between 3.0 Gy and 8.0 Gy in one series. In chronic recurrent disease 2 or more series with a total dose of more than 10.0 Gy were given. RESULTS: Complete relief of symptoms at the end of radiotherapy was achieved in 89 patients (38%). In 92 patients (40%) there was clear improvement of symptoms. Only 2 patients did not react to radiotherapy. No side effects of radiotherapy occurred. CONCLUSION: Radiotherapy should be given more consideration as a treatment option for hidradenitis suppurativa.

Adult↗
PubMed1999

Antimicroglia antibodies in sera of Alzheimer's disease patients.

BACKGROUND: Immune mechanisms seem to contribute to the degenerative process in Alzheimer's disease. Antibodies directed against animal brain tissue were found in sera of Alzheimer's patients. METHODS: Antibodies were measured in sera of 25 Alzheimer's patients and a comparison group of 25 age- and sex-matched controls. Sera were tested for their immunological response to various brain structures of postmortem human brain tissue. RESULTS: In 8 patients with Alzheimer's disease perinuclear antibodies directed against microglia were found in amygdala and frontal cortex. In the control group 1 subject showed antibody binding to microglia. CONCLUSIONS: Perinuclear antibodies to microglia may play a role in tissue destruction of Alzheimer's disease. These data add to the evidence that immune mechanisms play a role in the pathophysiology of Alzheimer's disease.

Aged↗
PubMed1999

No complementation between TP53 or RB-1 and v-src in astrocytomas of GFAP-v-src transgenic mice.

Human low-grade astrocytomas frequently recur and progress to states of higher malignancy. During tumor progression TP53 alterations are among the first genetic changes, while derangement of the p16/p14ARF/RB-1 system occurs later. To probe the pathogenetic significance of TP53 and RB-1 alterations, we introduced a v-src transgene driven by glial fibrillary acidic protein (GFAP) regulatory elements (which causes preneoplastic astrocytic lesions and stochastically astrocytomas of varying degrees of malignancy) into TP53+/- or RB-1+/- mice. Hemizygosity for TP53 or RB-1 did not increase the incidence or shorten the latency of astrocytic tumors in GFAP-v-src mice over a period of up to 76 weeks. Single strand conformation analysis of exons 5 to 8 of non-ablated TP53 alleles revealed altered migration patterns in only 3/16 tumors analyzed. Wild-type RB-1 alleles were retained in all RB-1+/-GFAP-v-src mice-derived astrocytic tumors analyzed, and pRb immunostaining revealed protein expression in all tumors. Conversely, the GFAP-v-src transgene did not influence the development of extraneural tumors related to TP53 or RB-1 hemizygosity. Therefore, the present study indicates that neither loss of RB-1 nor of TP53 confer a growth advantage in vivo to preneoplastic astrocytes expressing v-src, and suggests that RB-1 and TP53 belong to one single complementation group along with v-src in this transgenic model of astrocytoma development. The stochastic development of astrocytic tumors in GFAP-v-src, TP53+/- GFAP-v-src, and RB-1+/- GFAP-v-src transgenic mice indicates that additional hitherto unknown genetic lesions of astrocytes contribute to tumorigenesis, whose elucidation may prove important for our understanding of astrocytoma initiation and progression.

Animals↗
PubMed1999

[Cytoprotection with amifostine in the framework of radiochemotherapy in previously irradiated head and neck carcinoma].

PURPOSE: The radiotherapeutic possibilities are limited for patients with a recurrent or second head and neck cancer if the patient was already irradiated in the first therapy. In the presented study we investigated the changes of this situation due to the usage of amifostine in the case of re-irradiation (simultaneous radio-chemotherapy). PATIENTS AND METHODS: Between 1995 and 1997 we treated 14 patients with a recurrent or second malignancy of the head and neck region by a simultaneous radio-chemotherapy (20 x 1.5 Gy, Carboplatin 70 mg/m2 BSA on days 1 to 5 and 16 to 20, 500 mg amifostine prior to every carboplatin infusion). Six out of 14 patients got an additional brachytherapy (10 to 15 Gy) to increase the local dose because of a residual tumor. In 4 cases the treatment was an adjunctive one, following the surgical tumor debulking. RESULTS: We have seen 3 complete remissions (21.4%), and 8 partial remissions (57.1%). The median time of observation is 13 months now. Three out of 14 patients died, 2 because of the tumor. Hematological toxicities: side effects Grade 2 WHO were seen only in 1 patient. Acute non-hematological toxicities: mucositis Grade 0/1 in 7 patients, mucositis Grade 2 in 7 patients, dysphagia Grade 0/1 in 9 patients, dysphagia Grade 2 in 5 patients, xerostomia Grade 1 in 9 patients, xerostomia Grade 2 in 3 patients. We registrated only 1 serious late toxicity due to radio-chemotherapy: 4 months after brachytherapy a patient (with laryngectomy) developed a submental fistula. CONCLUSION: These first results suggest that the usage of amifostine offers new potential ways for re-irradiation of patients with recurrent or second malignancies in the head neck region.

Adult↗
PubMed1998

Radiochemotherapy with amifostine cytoprotection for head and neck cancer.

A randomized study was conducted to evaluate the protective activity of amifostine (A) against the dose-limiting toxicities of radiochemotherapy (RCT). Patients with head and neck cancer received radiotherapy (2 Gy/day 5 days a week up to 60 Gy) with carboplatin 70 mg/m2 on days 1-5 and 21-25 inclusive. Patients either received RCT alone (n = 14) or RCT + A at a dose of 500 mg prior to treatment with carboplatin (n = 25). There was a significant reduction in the incidence of grade 3/4 mucositis (P < 0.0001), acute grade 2 xerostomia (P < 0.0001) and grade 3/4 thrombocytopenia (P = 0.012) in these patients who received A. The incidence of grade 2 late xerostomia at 12 months is 16.7% and the incidence of loss of taste is 0% in patients treated with A, as opposed to 54.5% and 63.6% in patients who received RCT alone. There were 18 (72%) complete responses (CR) and 6 (24%) partial responses (PR) in patients who received A, compared with 6 (43%) CR and 6 PR (43%) in patients treated with RCT alone. The disease-free survival at 12 months is 85.7% in the RCT + A arm and 78.6% in the RCT alone arm. The use of amifostine reduces the incidence and severity of acute and late toxicities associated with RCT whilst preserving antitumour activity.

Adult↗
PubMed1998

Selective cytoprotection with amifostine in concurrent radiochemotherapy for head and neck cancer.

BACKGROUND: Amifostine has reduced toxicities associated with radiation therapy and platinum-based chemotherapy. In a phase II randomized trial, we investigated the ability of amifostine to reduce the toxicity of carboplatin plus radiotherapy (RCT) in patients with head and neck cancer. PATIENTS AND METHODS: Thirty-nine patients with stage III or IV squamous cell carcinomas of the head and neck received RCT (following surgery or as primary treatment). Radiotherapy was given five days per week with daily fractions of 2 Gy, up to a total dose of 60 Gy in conjunction with carboplatin 70 mg/m2 on days 1 through 5 and days 21 through 26. Eligible patients were randomised to receive RCT alone or preceded by a rapid infusion of amifostine (500 mg) on the days when carboplatin was administered. RESULTS: Patients receiving amifostine + RCT (n = 25) had significantly reduced mucositis (P = 0.0001) and xerostomia (P = 0.0001) in comparison with patients receiving RCT alone (n = 14). Additionally, patients receiving amifostine + RCT had significantly less thrombocytopenia (P = 0.001) and leukopenia (P = 0.001). At 12 months following therapy, 79% of patients receiving amifostine + RCT had no evidence of disease compared with 64% of those receiving RCT alone. CONCLUSIONS: Amifostine reduces the RCT-induced toxicities in patients with head and neck cancer and has no negative impact on antitumour efficacy.

Adult↗
PubMed1995

[Therapy trends in the prevention of radiation-induced diarrhea after pelvic and abdominal irradiation. Results of a tricenter study].

PURPOSE: Radiotherapy induced diarrhea and convulsive pain are severe side-effects of irradiation of the pelvis and the abdomen leading often to an interruption of the treatment. Up to now these side-effects were only treated symptomatically, prophylactic therapies are not known. PATIENTS AND METHODS: During the years 1992 and 1993 174 patients who obtained radiotherapy in the pelvis or the abdomen because of different malignancies were observed referring to the diarrhea-prophylactic effect of Smectite (= Skilpin). 80 patients received Smectite at the beginning of radiotherapy, 94 patients of the control group were treated with motility modifying drugs when diarrhea appeared. The following parameters were compared: Frequency, consistence and incontinence of stool, tenesmus and the onset of diarrhea. RESULTS: 67.0% (n = 63) of the patients in the control group developed diarrhea, whereas in the pretreated Smectite-group only 37.5% of the cases (n = 30) developed diarrhea. The first appearance of diarrhea was at day 17 in the pretreated group and averagely at day 11 in the control group. 44% of the patients in the control group suffered from tenesmus versus 25% in the Smectite-group. CONCLUSION: In comparison to the symptomatic treatment of radiation enteritis the prophylactic application of Smectite is able to reduce the diarrhea from the beginning of radiotherapy or at least to reduce the pathological frequency of stool and therefore to increase the quality of life.

Abdomen↗