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W Müller

Publications and source records attributed to W Müller.

At least 55 records · Page 3Linked to original sources
PubMed2004

Expression of 5-HT3A receptors in cells of the immune system.

There is evidence from both human and animal research that 5-hydroxytryptamine3 (5-HT3) receptor antagonists, particularly tropisetron, exert analgesic and antiinflammatory effects. However, the underlying mechanisms of these effects including the expression of 5-HT3 receptors in cells of the immune system have not yet been investigated in detail. Therefore, we investigated the expression of the 5-HT3A receptor in primary human monocytes, chondrocytes, T-cells, dendritic cells, and synovial tissue. We found that 5-HT3A receptors are expressed in monocytes, chondrocytes, T-cells, and synovial tissue but not in dendritic cells. Our data show that 5-HT3A receptors are widely expressed in cells of the immune system and that they might play an important role in inflammatory events and in the observed antiphlogistic effects of 5-HT3 receptor antagonists.

Dendritic Cells↗
PubMed2004

Antiinflammatory effects of 5-HT3 receptor antagonists in lipopolysaccharide-stimulated primary human monocytes.

There is evidence from both human and animal research that 5-hydroxytryptamine (5-HT)3 receptor antagonists, particularly tropisetron, exert analgesic and antiinflammatory effects. However, the underlying mechanisms of these effects have not yet been investigated in detail. Therefore, the antiinflammatory effects of tropisetron and ondansetron were investigated in human monocytes. In human monocytes, both lipopolysaccharide (LPS)-stimulated tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta secretion were dose-dependently inhibited by tropisetron starting at a concentration of 5 microg/mL and reaching maximal levels at 25 microg/mL (IC50: 32 microg/mL and 12 microg/mL, respectively). LPS-induced IL-6 and PGE2 release was only slightly inhibited at high doses, whereas LPS-induced release of IL-8 and matrix metalloprotease (MMP)-9 was not affected. In conclusion, our data show that the binding of tropisetron to 5-HT3 receptors results in antiinflammatory effects through inhibition of TNF-alpha/IL-1beta, which might explain the antiphlogistic effects of 5-HT3 antagonists.

Cells, Cultured↗
PubMed2004

Immunomodulatory function of the 5-HT3 receptor antagonist tropisetron.

OBJECTIVE: To characterize the immune modulatory effects of 5-HT3 receptor antagonist treatment in patients with fibromyalgia, autoimmune disorders, and chronic pain. METHODS: Multiplex-assisted cytokine measurements were performed before and during treatment. Whole blood stimulation with TNF-alpha was carried out to determine the proinflammatory response induced by exogenous TNF-alpha. RESULTS: Five of nine patients clinically responded to treatment, and two had a moderate response. All patients had significantly elevated levels of T-H1 cytokines more prominent than TNF-alpha, IL-1beta, and IL-6. Treatment resulted in transient effects on peripheral monocyte counts in all but one patient, a plasma IL-1beta increase in two responder patients, and decreased T-H1 cytokines in two responder patients. Ex vivo TNF-alpha stimulation was transiently reconstituted in three responder patients to a significant level. Three patients showed a marginal reconstitutive response. CONCLUSION: 5-HT3 receptor blockade transiently affects monocyte tissue infiltration, modulates T-H1 cytokines in clinical responders as well as MIP-1beta in moderate responders, and transiently affects the ex vivo response to exogenous TNF-alpha.

Adult↗
PubMed2004

Local treatment of tendinopathies and myofascial pain syndromes with the 5-HT3 receptor antagonist tropisetron.

UNLABELLED: The use of local tropisetron injections improved the treatment of tendinopathies considerably, with the effect being comparable to the topical application of local anaesthetics combined with depot corticosteroids. On the other hand, local injection of prilocaine alone exerted a shorter and weaker effect on the condition. OBJECTIVES: After it had been proven that systemic application of the 5-HT3 receptor antagonist tropisetron exerts an analgesic effect on musculoskeletal pain in fibromyalgia, we investigated the efficacy of the substance in tendinopathies and myofascial pain syndromes. RESULTS: Local injections of tropisetron as a treatment for trigger points in myofascial pain syndrome also brought about rapid and prolonged relief in the majority of cases. The analgesic effect was far superior to the action of local anaesthetics. CONCLUSION: The present findings indicate that the analgesic action of the 5-HT3 receptor antagonist tropisetron sets in rapidly and lasts for a long time. Various mechanisms are under discussion to explain the long duration of the effect. Tropisetron not only has an analgesic but probably also an antiphlogistic effect which can be attributed to the inhibited release of substance P and other neuropeptides from the nociceptors and the blocked release of phlogistic substances from macrophages, monocytes etc.

Adult↗
PubMed2004

Intra-articular treatment of arthritides and activated osteoarthritis with the 5-HT3 receptor antagonist tropisetron. A double-blind study compared with methylprednisolone.

BACKGROUND: Since the good effect of intra-articular injections of the 5-HT3 receptor antagonist tropisetron in patients with arthritides and activated osteoarthritis has already been demonstrated in pilot studies, the effect of tropisetron is compared with that of methylprednisolone here. OBJECTIVES: In a double-blind study, 34 patients with gonarthritides or activated osteoarthritis (18 patients with rheumatoid arthritis, 16 patients with osteoarthritis) were treated with a single intra-articular injection of 10 mg tropisetron (18 patients) or 40 mg methylprednisolone (16 patients). Before treatment as well as one and three weeks later, the intensity of rest pain and pain following exercise was measured with the visual analog scale (VAS) for pain and the clinical findings in the knee joint were recorded. RESULTS: By means of the intra-articular tropisetron treatment, the inflammatory joint process with arthritides and activated arthroses could be influenced in a similar way as with corticosteroid treatment. No significant differences were detected. CONCLUSION: According to the results presented here, the intra-articular treatment with the 5-HT3 receptor antagonist tropisetron in patients with gonarthritides and activated arthroses was about equally effective as those for treatment with corticosteroids. Therefore, it can be used as an alternative in patients for whom concomitant diseases like diabetes and hypertension make it difficult to use corticosteroids. Whether increasing the tropisetron dose may further improve the results remains to be determined in future studies.

Adult↗
PubMed2003

The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting.

Macrophage migration inhibitory factor (MIF) is a mediator of host immunity and functions as a high, upstream activator of cells within the innate and the adaptive immunological systems. Recent studies have suggested a potentially broader role for MIF in growth regulation because of its ability to antagonize p53-mediated gene activation and apoptosis. To better understand MIF's activity in growth control, we generated and characterized a strain of MIF-knockout (MIF-KO) mice in the inbred, C57BL/6 background. Embryonic fibroblasts from MIF-KO mice exhibit p53-dependent growth alterations, increased p53 transcriptional activity, and resistance to ras-mediated transformation. Concurrent deletion of the p53 gene in vivo reversed the observed phenotype of cells deficient in MIF. In vivo studies showed that fibrosarcomas induced by the carcinogen benzo[alpha]pyrene are smaller in size and have a lower mitotic index in MIF-KO mice relative to their WT counterparts. The data provide direct genetic evidence for a functional link between MIF and the p53 tumor suppressor and indicate an important and previously unappreciated role for MIF in carcinogenesis.

Alleles↗
PubMed2003

[The influence of depression on the effect of Tropisetron in the therapy of fibromyalgia].

As described elsewhere the oral administration of 5 mg of the 5-HT3-receptor-antagonist Tropisetron in fibromyalgia exhibited less amelioration of pain in patients with a depression in comparison to patients without depression. Since an intravenous treatment seems to increase the effect of Tropisetron, the question arises whether patients with depression profit from the intravenous therapy. Methods 68 out patients with fibromyalgia according to ACR-criteria were enrolled in the study. The patients filled in a VAS pain and the Beck Depression Inventory (BDI) before and after a bolus i.v. injection of 5 mg Tropisetron for 5 days [Beck AT, Steer Ra. Beck-Depression-Inventory (BDI) In: Hautzinger M (Hrsg der dt. Ausg.). Testhandbuch. 1. Auflage Bern: Verlag Hans Huber, 1994]. In the beginning the patients had to have > or = 40 mm in the VAS pain from 0-100 mm. The patients were divided into three groups: group 1 = patients with a BDI<19 without experience with antidepressive drugs (n=26); group 2=patients with a BDI > or = 19 (n=22) and negative experience with antidepressive substances, and group 3=patients with a BDI > or = 19 and an accompanying antidepressant drug therapy and some benefit under this therapy (n=20). Results Before the therapy there was no significant difference in VAS pain in the groups, but in BDI there was a significant difference between group 1 (BDI mean value 11.5) in comparison to group 2 (BDI mean value 26.1) and group 3 (BDI mean value 24.8). After therapy all three groups had a significant amelioration of pain: group 1: p=0.000023; group 2: p=0.00073; group 3: p=0.0145. There was a significant difference between the group with BDI<19 and the group with antidepressant drug in amelioration of pain (p=0.044). A significant correlation was found in group 2 with Beck > or = 19 between amelioration of pain and BDI after therapy (p=0.008, r=0.666). In this group a pain-reactive depression and in group 3 an endogenous depression must be discussed.

Adjustment Disorders↗
PubMed2003

[Local treatment of rheumatic diseases with the 5-HT3 receptor antagonist tropisetron].

Local injection of the 5-HT3 receptor antagonist tropisetron manifests a distinct analgesic effect in various local diseases of the locomotor system such as tendinopathies, peri-arthropathies,myofascial pain syndrome, in trigger points, and in inflammatory joint processes.This effect corresponds to that exerted by local anesthetics in general use such as lidocaine and prilocaine among others, but the effect lasts considerably longer. The reason for this finding is found in a simultaneous antiphlogistic effect of the 5-HT3 receptor antagonist as evidenced by animal experiments and clinical data.

Humans↗
PubMed2003

Single-injection inulin clearance for routine measurement of glomerular filtration rate in cats.

Glomerular filtration rate (GFR) was determined in 53 cats using an inulin single-injection method. Thirty healthy young adult cats were used to establish normal values. The procedure was also used in 23 cats that were either older than 10 years or had borderline serum creatinine levels. The total clearance was calculated from the decay of the serum inulin concentration after injection of 3000 mg/m(2)body surface area using a two-compartment model. Concomitant inulin and iohexol clearance in nine cats showed excellent correlation between the two methods. Calculated normal values for GFR in 30 healthy cats were 35.9-58.5 (median 46.0) ml/min/m(2)or 2.07-3.69 (median 2.72) ml/min/kg. A few cats with normal creatinine or blood urea nitrogen levels were detected as having reduced GFR and therefore being in a state of early renal dysfunction. The study indicates that single-injection inulin clearance is a valuable tool for routine GFR measurement in cats. An "inulin excretion test" using only one blood sample 3h after the administration of 3000 mg/m(2)body surface area could prove an attractive alternative for the assessment of renal function in daily practice.

Animals↗
PubMed2003

Nuclear BAG-1 expression is a biomarker of poor prognosis in esophageal squamous cell carcinoma.

Apoptosis is one of the critical biological factors that correlate with the biological behavior of malignant tumors including cancer progression and clinical outcome. The present study was performed to clarify the clinical implications of BAG-1, a bcl-2 binding protein in esophageal squamous cell carcinoma (ESCC). Seventy-one cases with ESCC were investigated. Immunohistochemical study of BAG-1 was performed on resected specimens. The expression pattern of BAG-1 in nuclei and/or cytoplasm was analyzed and correlated with TNM classification, vessel invasion, survival period after surgery. BAG-1 expression in the nuclei was related to the depth of tumor invasion (P = 0.0381) but not to any other clinicopathologic parameters. The cytoplasmic staining pattern of BAG-1 exhibited no correlation with clinicopathologic parameters. Univariate analysis (P < 0.05), but not multivariate analysis, revealed significantly poor prognosis for ESCC cases exhibiting positive nucleic staining for BAG-1. Our data suggests that BAG-1 expression in the nuclei of ESCC plays an important role in tumor development and may be useful for predicting the prognosis after surgery.

Biomarkers, Tumor↗
PubMed2003

[Radio-frequency-ablation (RFA) with wet electrodes in the treatment of primary and secondary liver tumours].

INTRODUCTION: The majority of patients with primary and secondary tumours of the liver cannot be treated curatively by surgery. The treatment of these patients with radio-frequency thermoablation using perfused needle applicators (wet electrodes) was evaluated in a feasibility study. METHOD: Patients with primary and secondary tumours of the liver and contraindications against surgery or LTX were included into the feasibility study. RFA was performed percutaneously under ultrasound guidance. The patients were followed up sonographically and by computed tomography. RESULTS: 20 patients (9 male, 11 female) with 35 lesions were treated with RFA. 12 patients (22 tumour locations) suffered from HCC and 8 patients (13 tumour masses) had liver metastases (colorectal, breast, pancreas, carcinoid). The median age was 65.6 years (36 to 83 years). The median tumour size was 33.5 mm. 59 RFTA applications (1.7 applications per tumour mass) were performed. The mean duration of RFTA per patient was 16.2 minutes. During the procedure isotonic saline was injected at a mean flow rate of 6.63 ml/min. All patients received local anaesthesia. In 33 sessions an additional analgosedation was necessary (average dose 63.8 mg Pethidine and 1.4 mg Midazolam). In 2 cases a reduction of the haemoglobin level, occurred, necessitating a blood transfusion. 3/4 of the treated metastases could be eradicated completely. Within a median follow-up of 145 days no intrahepatic local recurrence but 4 distant metastases occurred. 2/3 of the treated HCC could initially be brought into complete remission (CR). After a median follow-up of 329 days 5 of the 8 initially successfully treated patients with HCC were still in complete remission. In 3 cases an intrahepatic local recurrence developed. CONCLUSION: RFA with wet electrodes is a safe, effective and inexpensive treatment for primary and secondary tumours of the liver, measuring less than 4 cm in diameter.

Adult↗
PubMed2003

Substitution for PCP, disruption of prepulse inhibition and hyperactivity induced by N-methyl-D-aspartate receptor antagonists: preferential involvement of the NR2B rather than NR2A subunit.

The non-competitive NMDA receptor antagonist phencyclidine (PCP) is known to produce a discriminative stimulus in rats. The first aim of the present study was to investigate which NMDA receptor subtype(s) is involved in this effect of PCP. Rats were trained to discriminate PCP (2 mg/kg; i.p.) from saline in a two lever operant task. The NMDA channel blocker, (+)MK-801 (0.1 mg/kg; i.p.) and the competitive NMDA receptor antagonist SDZ 220-581 (3 mg/kg; i.p.) produced 76% of PCP-lever selection (ED50=0.045 and 2 mg/kg, respectively), whereas their respective inactive enantiomers (-)MK-801 (0.025-0.1 mg/kg) and SDZ 221-653 (2-5 mg/kg) induced less than 30% of PCP-appropriate responding. Another competitive NMDA antagonist, SDZ EAB-515 (30 mg/kg; i.p.), induced 63% of PCP-lever responding (ED50=23.48 mg/kg). The selective antagonist of NMDA receptors containing the NR1A/NR2B-subunits Ro 25-6981 (20 mg/kg; i.p.) resulted in a complete substitution (more than 80% of PCP-lever selection) for PCP (ED50=8.59 mg/kg). In contrast, the NR1A/NR2A NMDA receptor-preferring antagonist NVP-AAM077 (2-10 mg/kg; i.p.) failed to produce PCP-like discriminative stimuli. At high doses SDZ 220-581 (ED50=2.44), NVP-AAM077 (ED50=8.33) and SDZ EAB-515 (ED50=25.81) decreased the performance of the rats in this operant task. The ability of these NMDA receptor antagonists to disrupt the prepulse inhibition (PPI) of the startle response and to alter locomotor activity was also studied. PCP (0.5-2 mg/kg; s.c.), SDZ 220-581 (0.5-5 mg/kg; s.c.), SDZ EAB-515 (1-30 mg/kg; i.p.) and Ro 25-6981 (5-20 mg/kg; i.p.) disrupted PPI and at high doses produced hyperlocomotion. In contrast, NVP-AAM077 (5-20 mg/kg; i.p.) did not disrupt PPI and reduced locomotor activity. In conclusion, it appears that the NMDA receptor containing the NR2B, rather than the NR2A subunit, may play a major role in the PCP-like discriminative stimulus. In addition, sensory motor gating disturbances associated with NMDA antagonists do not seem to result from a blockade of NR1/NR2A-containing NMDA receptors.

Animals↗
PubMed2003

Radiofrequency ablation of hepatocellular carcinoma with a saline solution perfusion device: a pilot study.

PURPOSE: The majority of patients with hepatocellular carcinoma (HCC) cannot be treated with surgery. This study evaluated the treatment of patients with radiofrequency ablation (RFA) with use of needle applicators perfused with isotonic saline solution. MATERIALS AND METHODS: Twenty patients with a maximum of three HCCs as large as 60 mm and a contraindication to partial liver resection or orthotopic liver transplantation were enrolled in the study. They were treated with ultrasound-guided RFA with use of perfused needle applicators and followed with sonography and computed tomography. RESULTS: Twenty patients (14 men, six women) with a total of 29 HCCs were treated with RFA. In total, 56 RFA treatments were performed. Mean HCC size was 31 mm (range, 10-60 mm). Two cases of self-limiting bleeding requiring transfusion of blood products took place. Complete response (CR) was achieved in 85% of patients (17 of 20). Partial response occurred in three tumors 45 mm in diameter or larger. There was a total of six local recurrences in five patients (25% of patients, 21% of tumors). Six patients (30%) exhibited distant recurrence, two of whom also showed local recurrence. In three patients, repeat treatment led to renewed CR. After a median follow-up of 445 days (range, 114-1,071 days), 12 patients (71% of the 17 patients with initial CR) still showed CR. Twelve patients (60% of all patients, 71% of those with initial CR) survived. Three of the eight patients who died were free of viable tumor at the time of death. CONCLUSIONS: RFA with use of perfused needle applicators shows promise as an effective method for treating inoperable HCC. The most frequent complication was bleeding.

Aged↗
PubMed2003

Assessment of the single-occlusion technique for measurements of respiratory mechanics and respiratory drive in healthy term neonates using a commercially available computerized pulmonary function testing system.

In this study, a critical assessment of the single-occlusion technique as a means of measuring passive respiratory mechanics and respiratory drive (P0.1) was performed in nonintubated spontaneously breathing healthy term neonates using commercially available computerized equipment (PEDS system). In general, we found that quality parameters only partially conformed to the international established standards for measuring passive respiratory mechanics. There was a failure rate of technically acceptable occlusions of about 50% for respiratory mechanics measurements and 20% for P0.1 measurements. Intersubject variability of the data was between 10 and 40%. After studying different lengths of occlusion times (Tocc; 0.2, 0.3, 0.4 and 0.5 s), it was found that acceptable occlusions for passive respiratory mechanics were obtained only if the expiratory Tocc exceeded 0.2 s. Increasing the Tocc had no effect on the absolute values of respiratory mechanics but showed a significant trend towards more technically acceptable occlusions. We speculate that a Tocc of at least 0.4 s may be a prerequisite for obtaining reliable results for respiratory mechanics in healthy term neonates.

Electronic Data Processing↗
PubMed2003

Percutaneous saline-enhanced radiofrequency ablation of unresectable hepatic tumors: initial experience in 26 patients.

OBJECTIVE: The purpose of our study was to evaluate the safety and efficacy of percutaneous saline-enhanced radiofrequency ablation for unresectable primary or metastatic hepatic tumors. SUBJECTS AND METHODS: Twenty-six patients with 15 hepatocellular carcinomas and 33 hepatic metastases (maximum diameter < or = 8.6 cm) were treated; of these, seven tumors in five patients were treated twice. Thus, 44 radiofrequency treatments were performed. Saline-enhanced and impedance-controlled radiofrequency ablation (0.5-1.1 mL/min of saline, 15-mm conductive portion of the electrode tip, 25-60 W, 5-43 min) was performed using MR imaging guidance. Coagulation necrosis, volume indexes, morbidity, and complications were assessed. RESULTS: The volume of coagulation necrosis 1-7 days after radiofrequency ablation was 1.6-126.6 cm(3) (median, 18.9 cm(3)), corresponding to coagulation diameters of 1.5-6.2 cm (median, 3.2 cm). The coagulation volume was significantly larger if there were more than four radiofrequency applications (p = 0.006). Tumors of 3 cm or less in diameter were eight times as likely to be successfully completely ablated (p = 0.01) and volume indexes of lesions treated with the patient under general anesthesia were significantly larger than those treated with the patient under conscious sedation (p < 0.001). Major complications occurred in four patients (15%). Incomplete ablation in 19 (35%) of 54 radiofrequency lesions was due to cooling by a large vessel nearby (n = 2) or to low power applied in painful (n = 11) or critical (n = 6) locations. Residual tumor was observed in 14 (58%) of 24 tumors evaluated 6-8 months after radiofrequency ablation. CONCLUSION: Percutaneous saline-enhanced and impedance-controlled radiofrequency ablation can be effective in the treatment of unresectable hepatic tumors and minimizes potential carbonization. A greater number of radiofrequency applications, general anesthesia, and increasing experience provide significantly better results.

Administration, Cutaneous↗
PubMed2003

[Identification and differentiation of Campylobacter fetus subspecies by PCR].

The species Campylobacter (C.) fetus is divided into the subspecies venerealis and fetus, which differ in epidemiology and clinical importance. The differences between these subspecies make an accurate distinction essential. Differentiation of C. fetus by traditional microbiological methods is only based on two reactions (tolerance to glycin, Na selenite reduction), in which C. fetus ssp. venerealis reacts negatively. However, the value of both reactions is limited. We used a specific PCR-based assay for identifying and differentiating the two C. fetus subspecies, which was recently developed by HUM et al. (1997). In this assay, a 764 bp amplicon is produced using primers MG3F and MG4R for both subspecies of C. fetus. In contrast to HUM et al. (1997), this amplicon was approximately 200 bp smaller. This discrepancy can't be explained. Afterwards, the primers VenSF and VenSR are used for differentiation. The identification of the sub-species venerealis is based on the presence of a 142 bp amplicon, which is not formed with subspecies fetus. The type strains of both C. fetus subspecies were used as positive controls. Non-specific reactions were not observed. In this PCR assay, 73 field strains were investigated (among them 24 C. fetus ssp. veneralis, 26 C. fetus ssp. fetus). In these investigations, the method has proved its diagnostic suitability. The results of the traditional microbiological differentiation of the C. fetus field strains could be confirmed by the PCR assay. In future, the traditional phenotypic characterization of C. fetus subspecies remains indispensable, but this PCR assay constitutes a valuable method for the confirmation of these results.

Animals↗
PubMed2003

Crowding and winter emergency feeding as predisposing factors for kerato-conjunctivitis in semi-domesticated reindeer in Norway.

Due to the hard environmental and climatic situation in late winter 1999, a herd of about 200 free-ranging, semi-domesticated reindeer was gathered in a paddock in northern Norway for emergency feeding. About the same number of reindeer was not corralled but supplementary fed on their winter pastures. The fodder was of relatively good quality but very dusty and fed in a very dry environment. Six weeks later, an outbreak of eye-infection was diagnosed in one third of the corralled reindeer; mild symptoms were observed in most of them, but 11 animals showed severe signs of disease. No signs of disease were found in the non-corralled animals. Ten reindeer died through emaciation, the eleventh was sacrificed. Histopathological diagnosis of two severely affected eyes revealed a severe purulent kerato-conjunctivitis with bacteria and plant particles embedded in purulent exudates on the cornea and conjunctiva. In one eye from the two most affected animals Actinomyces pyogenes, coagulase-negative Staphylococci and Escherichia coli and in the other one Staphylococcus aureus and Escherichia coli were found. The bacteria encountered in this study are not considered the primary cause of disease. They seem rather to be opportunistic infectious agents of eyes that have been irritated mechanically through exposure to dusty fodder in a dry environment. The stress through unfamiliar corralling of the reindeer, that followed an insufficient fodder supply, could be considered as an additional infection supporting factor. This case-report emphasises on the importance of different factors involved in favouring outbreaks of disease in reindeer, under intensified husbandry conditions. Even though crowding and emergency feeding may be, at certain circumstances, the only means of survival for reindeer, a negative impact of implied crowding diseases on their productivity, must be considered, as well.

Animal Feed↗