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Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 145 records · Page 8Linked to original sources
PubMed2000

Changes in cerebral blood volume and cerebral oxygenation during periodic breathing in term infants.

The present study is an analysis of changes in cerebral oxygenation and cerebral blood volume (CBV) during periodic breathing in healthy term infants by means of near infrared spectroscopy (NIRS). Polygraphy included electrocardiogram, electrooculogram, heart rate, oxygen saturation, side stream capnography, two respiratory effort sensors, a movement sensor, and NIRS. During periodic breathing analysis of behaviour of total haemoglobin (cHbtot), deltaCBV, the haemoglobin oxygenation index (cHbD), and cytochrome oxidase (CytOx) was performed. In ten healthy term infants 30 cycles of periodic breathing with a mean of 10 apnoeas per cycle were analysed. Corresponding cyclical variations of cHbD appeared in 98%, cyclical variations of cHbtot appeared in 42% of all apnoeas. During phases of apnoea, a mean decrease of cHbD of -3.45 micromol/l occurred 1.75 seconds after onset of apnoea, and a mean decrease of cHbtot of -0.79 micromol/occurred 0.74 seconds after onset of apnoea. During these apnoeas, the deltaCBV was -44 microl/100 g brain. During phases of ventilation, there was an increase of cHbD and cHbtot to the pre-apnoeic levels. There was a tendency that CytOx values decreased during periodic breathing, the amount of decrease was -0.32 micromol/l. In conclusion, the present study was able to show for the first time that there is cyclical desaturation and reoxygenation of cerebral blood during periodic breathing. Cyclical changes in CBV in association with periodic apnoea occurred only in 42% of apnoea.

Blood Volume↗
PubMed2000

Effect of tropisetron on circulating catecholamines and other putative biochemical markers in serum of patients with fibromyalgia.

OBJECTIVE: The aim of the study was to assess the influence of the 5HT3-receptor antagonist tropisetron on circulating catecholamines as biochemical markers of the activity of the sympathoadrenal system in fibromyalgia. Moreover, serum concentrations of serotonin, somatomedin C, oxytocin, calcitonin-gene-related-peptide, calcitonin and cholecystokinin were assayed as putative markers in pain-related disorders like primary fibromyalgia. METHODS: In 96 patients, who met the ACR classification criteria for fibromyalgia, and in 20 sex and age matched controls concentrations of dopamine, noradrenaline, adrenaline, serotonin and tropisetron were assayed in serum by HPLC with electrochemical detection. All other transmitters were determined by ELISA. RESULTS: There was with the exception of tropisetron, calcitonin and dopamine, no correlation between doses of tropisetron 5, 10, 15 mg respectively and significant changes in circulating transmitters or other transmitters as putative biochemicals markers in primary fibromyalgia. Regarding the prediction of pain reduction to tropisetron, patients with elevated dopamine and/or reduced plasma 5-HT concentrations tended to show a higher response rate. CONCLUSION: Despite these partly disappointing results another prospective pilot study with selected patients vs. age and sex matched controls, double blind and with comparison of other 5HT3-receptor antagonists e.g. dolasetron and granisetron e.g. after i.v. bolus injection is suggested. Still the data obtained in this preliminary paper provide some evidence regarding the present discussion on subgroups of patients with primary fibromyalgia.

Analysis of Variance↗
PubMed2000

Efficacy and tolerability of tropisetron in primary fibromyalgia--a highly selective and competitive 5-HT3 receptor antagonist. German Fibromyalgia Study Group.

OBJECTIVE: Based on a potential role for serotonin receptors in fibromyalgia, we investigated the efficacy and tolerability of treatment with tropisetron, a highly selective, competitive inhibitor of the 5-HT3 receptor. METHODS: In this prospective, multicenter, double-blind, parallel-group, dose-finding study, 418 patients suffering from primary fibromyalgia (ACR criteria) were randomly assigned to receive either placebo, 5 mg, 10 mg or 15 mg tropisetron once daily, respectively. The duration of treatment was 10 days. The clinical response was measured by changes in pain-score, visual analog scale (VAS), and the number of painful tender-points. RESULTS: Treatment with 5 mg tropisetron resulted in a significantly higher response rate (39.2%) when compared with placebo (26.2%) (p=0.033). The absolute reduction in pain-score was -13.5% for 5 mg tropisetron, -13.0% for 10 mg tropisetron, and -6.3% for placebo (p<0.05). The effects of 15 mg tropisetron were similar to placebo, thus suggesting a bell-shaped dose-response curve. Compared with placebo, treatment with 5 mg tropisetron led to a significant improvement (p<0.05) in VAS, while a clear trend in terms of clinical benefit was seen with 10 mg tropisetron. The number of painful tender-points was also reduced significantly (p=0.002) in the 5 mg tropisetron group. Of interest, during the 12-month follow-up period, pain intensity of responders on 5 mg and 10 mg tropisetron was still markedly below baseline. The treatment was well tolerated, with gastro-intestinal complaints being the most frequently reported side effects, in keeping with the known safety profile for 5-HT3 receptor antagonists. CONCLUSIONS: This study demonstrates the efficacy of short-term treatment with 5 mg tropisetron once daily in primary fibromyalgia. Treatment was well tolerated and prolonged clinical benefits were seen.

Adolescent↗
PubMed2000

Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain.

The 5-HT3 receptor antagonists are a novel therapy for patients suffering from fibromyalgia, although the optimal duration of treatment is still unclear. The objective of this phase II study was to evaluate whether prolonging treatment with tropisetron to 4 weeks is tolerable and correlated with an improved clinical benefit. Thirty female patients with fibromyalgia received oral tropisetron (5 mg) daily for 28 days in an open-label fashion. Treatment resulted in significantly decreased pain as measured by visual analog scale (VAS), with a mean reduction of 59.7% and an absolute median change of -25.0 from baseline to day 28 (p<0.0001). A similar, significant reduction of 55.7% and absolute median change of -31.0 was observed in the painscore (p<0.0001). The response rate with patients showing a > or = 35% reduction in individual pain scores was 72.4% at day 28. The pressure tolerance of tender-points was slightly increased at the end of the treatment period. In addition, significant improvements were observed in the State-Trait-Anxiety-Inventory (STAI), scales of von Zerssen (Bf-S) and Beck Depression Index (BDI). Functional symptoms were compared with the results from a 10-day, randomized, double-blind phase III study of tropisetron in 418 fibromyalgia patients. In both studies several functional symptoms such as sleep disturbances and dizziness improved significantly (p<0.05). In the 28 days study, the number and extent of improvement in functional symptoms was increased compared with the shorter trial. Tolerability and safety of tropisetron was good, and typically for 5-HT3-receptor antagonists, gastrointestinal symptoms and headache were the most frequently reported events. In conclusion, 28 days treatment of fibromyalgia patients with 5 mg tropisetron resulted in significant pain reduction, which was most pronounced after 10 days with a further reduction up to day 28. Psychometric tests showed significant improvements in depression and anxiety state scores, while functional symptoms improved with extended tropisetron treatment.

Administration, Oral↗
PubMed2000

Results of the intravenous administration of tropisetron in fibromyalgia patients.

The observed effects on the symptoms of fibromyalgia of daily oral administration of 5 mg of the 5-HT3 receptor antagonist, tropisetron, for 10 days, could be maintained or exceeded with intravenous administration of only 2 mg of the formulation. Following a single i.v. injection of 2 mg tropisetron, a more rapid and profound reduction in pain was achieved than with 5 mg oral tropisetron per day. In individual cases, patients who had previously experienced no reduction in pain from 10 days of 5 mg oral tropisetron daily responded to i.v. therapy. A more favourable and persistent effect on pain, combined with a simultaneous significant improvement in various vegetative and functional symptoms was achieved with five days treatment with 2 mg tropisetron i.v. per day. The results outlined and the possibility for rapid improvements with drug treatment of fibromyalgia should be confirmed in randomised, placebo controlled trials.

Administration, Oral↗
PubMed2000

Do predictors exist for the therapeutic effect of 5-HT3 receptor antagonists in fibromyalgia?

From the findings outlined below, there are no reliable predictors of the therapeutic effect of the 5-HT3-receptor antagonists in fibromyalgia. Neither clinical change in pain and vegetative symptoms, nor alterations in biochemical parameters are appropriate predictors of response. The accompanying psychological changes in the form of depressive disorders appear to be somewhat predictive of decreased therapeutic effect, if such definitive statements can be applied to individual cases. If, following new trials, it becomes possible to judge the response of patients to therapy after 3-5 days treatment with 2 mg intravenous tropisetron then predictors will be unnecessary in practice.

Depression↗
PubMed2000

The use of 5-HT3 receptor antagonists in various rheumatic diseases--a clue to the mechanism of action of these agents in fibromyalgia?

In a pilot study, the action of the 5-HT3 receptor antagonist, tropisetron, on different types of local rheumatic pain and inflammatory effects was studied. With intra-articular injection of tropisetron, an improvement in inflammation and pain was obtained in inflammatory rheumatic diseases and activated osteoarthrosis. Also, the majority of patients with localized soft-tissue rheumatic diseases (periarthritis) demonstrated an obvious decrease in their pain following local infiltration of tropisetron. Chronic low back pain and cervical pain responded somewhat to i.v. treatment with tropisetron. The effect of the 5-HT3 receptor antagonists is probable primarily to limit the release of substance P, which acts as a pain and inflammatory mediator, and is itself released by the neurogenic inflammation that occurs after the binding of serotonin to its corresponding receptor. These results should be backed up with placebo controlled studies, which if confirmed, might imply that 5-HT3 receptor antagonists could supplement or replace the local administration of corticosteroids.

Arthritis, Rheumatoid↗
PubMed2000

Saline-enhanced radiofrequency ablation of breast tissue: an in vitro feasibility study.

RATIONALE AND OBJECTIVES: The feasibility of radiofrequency (RF) ablation for the treatment of breast tumors was investigated in vitro. The best parameters for ablation of breast tissue were chosen. METHODS: Saline-enhanced RF ablation was performed in human breast tissue specimens and cow udder tissue. Temperature profiles were measured depending on RF power (20, 28, 36 W) and NaCl infusion rate (15, 30, 60 mL/h) using eight thermocouples. Lesion development was monitored by ultrasound. Thermolysis efficiency was measured by tissue weight determinations before and after ablation. RESULTS: After RF ablation of tissue samples, 73.6% turned into a fat/saline emulsion. Ultrasound monitoring showed a cone-shaped hyperechoic area during the first 2 minutes of RF ablation, followed by an irregular expansion of the area. Time-dependent spatial temperature curves were more homogeneous at low infusion rates (15 mL/h). Peak temperatures up to 160 degrees C were measured. CONCLUSIONS: Controlled RF ablation of breast tissue is feasible. The irregular expansion of RF lesions in fatty breast tissue is due to liquefied fat. Low saline interstitial infusion rates result in better control of lesioning.

Animals↗
PubMed2000

Epitope mapping of immunogenic and adhesive structures in repetitive domains of Mycoplasma bovis variable surface lipoproteins.

The family of variable surface lipoproteins (Vsps) of the bovine pathogen Mycoplasma bovis includes some of the most immunogenic antigens of this microorganism. Vsps were shown to undergo high-frequency phase and size variations and to possess extensive reiterated coding sequences extending from the N-terminal end to the C-terminal end of the Vsp molecule. In the present study, mapping experiments were conducted to detect regions with immunogenicity and/or adhesion sites in repetitive domains of four Vsp antigens of M. bovis, VspA, VspB, VspE, and VspF. In enzyme-linked immunosorbent assay experiments, sera obtained from naturally infected cattle showed antibodies to different repeating peptide units of the Vsps, particularly to units R(A)1, R(A)2, R(A)4.1, R(B)2.1, R(E)1, and R(F)1, all of which were found to contain immunodominant epitopes of three to seven amino acids. Competitive adherence trials revealed that a number of oligopeptides derived from various repeating units of VspA, VspB, VspE, and VspF partially inhibited cytoadhesion of M. bovis PG45 to embryonic bovine lung cells. Consequently, putative adherence sites were identified in the same repeating units (R(A)1, R(A)2, R(A)4.1, R(B)2.1, R(E)1, and R(F)1) and in R(F)2. The positions and lengths of the antigenic determinants were mostly identical to those of adhesion-mediating sites in all short repeating units, whereas in the considerably longer R(F)1 unit (84 amino acid residues), there was only one case of identity among four immunogenic epitopes and six adherence sites. The identification of epitopes and adhesive structures in repetitive domains of Vsp molecules is consistent with the highly immunogenic nature observed for several members of the Vsp family and suggests a possible function for these Vsp molecules as complex adherence-mediating regions in pathogenesis.

Amino Acid Sequence↗
PubMed2000

Blockade of the integrin alphaLbeta2 but not of integrins alpha4 and/or beta7 significantly prolongs intestinal allograft survival in mice.

BACKGROUND: Small bowel transplantation remains a difficult therapeutic option endangered by a high rate of rejection and infectious complications. To improve these clinical results, it is mandatory to set up animal models to test alternative immunosuppressive regimens which may lead to immunotolerance. AIMS: To determine the value of blockade of alphaLbeta2 (LFA-1) and alpha4 and beta7 integrins (alpha4beta1, alpha4beta7, and alphaEbeta7) in the prevention of rejection of fetal small bowel grafts in mice and the effect of the association of calcineurin dependent drugs in anti-LFA-1 treated mice. METHODS: Adult recipient mice engrafted with allogeneic fetal small bowel received a short course of anti-alpha4 and/or anti-LFA-1 monoclonal antibodies (mAb) with or without FK506 or cyclosporin A. In addition, in a set of experiment, beta7-/- mice were used as recipients. Graft biopsies were performed and processed for standard histology. RESULTS: Blockade of the pathways of the integrins alpha4 and beta7 had a modest or no effect on intestinal graft survival. In contrast, transitory, short administration of anti-LFA-1 monoclonal antibody alone, when started before engraftment (day -1), allowed long term survival of intestinal grafts, even when associated with calcineurin dependent drugs. However, early withdrawal of FK506 reversed the immunosuppressive effect of anti-LFA-1 treatment. CONCLUSION: These results suggest that firstly, anti-LFA-1, but not anti-alpha4 mAb treatment, may be useful in improving the results of intestinal transplantation, and secondly, that this treatment is not incompatible with long term administration of tacrolimus currently used in the prevention of small bowel graft rejection in humans.

Animals↗
PubMed2000

alpha(4)beta(7) independent pathway for CD8(+) T cell-mediated intestinal immunity to rotavirus.

Rotavirus (RV), which replicates exclusively in cells of the small intestine, is the most important cause of severe diarrhea in young children worldwide. Using a mouse model, we show that expression of the intestinal homing integrin alpha(4)ss(7) is not essential for CD8(+) T cells to migrate to the intestine or provide immunity to RV. Mice deficient in ss7 expression (ss7(-/-)) and unable to express alpha(4)ss(7) integrin were found to clear RV as quickly as wild-type (wt) animals. Depletion of CD8(+) T cells in ss7(-/-) animals prolonged viral shedding, and transfer of immune ss7(-/-) CD8(+) T cells into chronically infected Rag-2-deficient mice resolved RV infection as efficiently as wt CD8(+) T cells. Paradoxically, alpha(4)ss(7)(hi) memory CD8(+) T cells purified from wt mice that had been orally immunized cleared RV more efficiently than alpha(4)ss(7)(low) CD8(+) T cells. We explained this apparent contradiction by demonstrating that expression of alpha(4)ss(7) on effector CD8(+) T cells depends upon the site of initial antigen exposure: oral immunization generates RV-specific CD8(+) T cells primarily of an alpha(4)ss(7)(hi) phenotype, but subcutaneous immunization yields both alpha(4)ss(7)(hi) and alpha(4)ss(7)(low) immune CD8(+) T cells with anti-RV effector capabilities. Thus, alpha(4)ss(7) facilitates normal intestinal immune trafficking to the gut, but it is not required for effective CD8(+) T cell immunity.

Adoptive Transfer↗
PubMed2000

Chronic colitis in IL-10-/- mice: insufficient counter regulation of a Th1 response.

IL-10-deficient (IL-10-/-) mice, generated by a gene-targeted mutation, develop abnormal immune responses as a result of uncontrolled interactions between antigen presenting cells and lymphocytes. The studies reviewed herein have focused on the enterocolitis that spontaneously develops in IL-10-/- mice. Not unexpectedly, heightened production of proinflammatory mediators accompanied pathologic changes in the gastrointestinal tract of young mutants. In a series of studies, the proinflammatory mediators responsible for initiating the pathogenic response were distinguished from those that were elicited as a consequence of persistent inflammation. We have also investigated the possibility that different mediators are involved in the inductive versus the maintenance phase of disease. The findings of these mechanistic studies as they relate to our understanding of progressive inflammatory disease and the role of IL-10 in controlling the acute and chronic stages are discussed.

Animals↗
PubMed2000

[Follow-up after histologically verified radical resection of early cancers of the mouth cavity: results of a prospective multicenter study].

INTRODUCTION: Early stage oral cavity carcinoma is curable in most cases. This study follows the course of early stage squamous cell carcinoma of the oral cavity after radical surgical resection, in order to assess the necessity of further treatment modalities. MATERIAL AND METHODS: In a prospective multicentric study, 110 patients with T1-T2 and N0-N1 (without capsular invasion) squamous cell carcinoma of the oral cavity were enrolled. All patients were treated exclusively by surgical resection with histopathologically proven negative margins. RESULTS: Among 96 patients (14 excluded because of positive margins), followed-up for 3 years, 18 presented a local or regional recurrence. In 12 of these 18 loco-regional control was reestablished by second treatment. Overall, the 4-year disease-specific survival probability was 94%. Patients treated initially by selective neck dissection had significantly lower recurrence rates than those without neck surgery. CONCLUSION: Early (T1-2, N0-1) squamous cell carcinoma of the oral cavity is adequately treated by surgery alone. The surgical procedure should include margin-free resection of the primary combined with selective neck dissection. Systematic postoperative radiotherapy does not appear necessary. Neck dissection is advocated in N0 patients as well.

Carcinoma, Squamous Cell↗
PubMed2000

[Surgical therapy concept in primary hyperparathyroidism].

INTRODUCTION: Primary hyperparathyroidism is a relatively rare disease caused in 80-85% of cases by solitary adenoma of the parathyroid glands. The laboratory findings are hypersecretion of PTH and hypercalcaemia. We distinguish between asymptomatic and symptomatic primary hyperparathyroidism. 25 patients of our clinic who underwent surgery in 1996 and 1997 are presented to illustrate our surgical concept of therapy. METHODS: 7 patients were asymptomatic and 18 symptomatic with regard to primary hyperparathyroidism. Preoperative localisation was facilitated by ultrasonography of the neck, which was used in all cases. Bilateral exploration of the neck under general anaesthesia similarly to thyroidectomy was the gold standard. Monitoring the inferior laryngeal nerve helped to protect it. In 6 cases intraoperative parathyroid hormone monitoring (rapid PTH assay) was applied. RESULTS: More than a third of the symptomatic group of patients had neurological or psychiatric diseases, followed by symptoms of the musculoskeletal and urological systems. Possible reasons for surgical intervention were persistent hypercalcaemia, age over 50, radiological findings of kidney stones or decreased kidney function. In 17 patients the preoperative ultrasonographic localisation was consistent with the intraoperative clinical findings. The sensitivity of this method was 68%. Intraoperative pathology showed 17 patients with a solitary adenoma, 4 ectopic, 2 cases had double adenoma, and 2 others hyperplasia with enlargement of all glands. After resection of the pathological parathyroid glands there was a decrease of parathyroid hormone in intraoperative hormone monitoring of approximately 60%. The preoperative hypercalcaemia (mean 2.99 mmol/l) usually normalised 4 hours postoperatively. There was no severe intraoperative bleeding and the inferior laryngeal nerve was preserved in all cases. All patients were monitored at 3-month intervals for parathyroid hormone and serum calcium during the first year after operation. One patient had persistently elevated parathyroid hormone without clinical findings. DISCUSSION: Parathyroidectomy is an efficient and safe operation with excellent normalisation of serum calcium and parathyroid hormone and a high rate of patient satisfaction. In this study assessment of ultrasonography was the preferred method of locating enlarged parathyroid glands before operation. However, this method is not based on unilateral exploration of the glands. Therefore, we prefer to locate all four glands, an approach based on the literature [1, 2]. Intraoperative monitoring of parathyroid hormone facilitates assessment of the operative result [3]. Normalisation of calcium in serum and the effectiveness and safety of the surgical method are confirmed in other publications [4-8]. In 24 of our patients normocalcaemia resulted within 12 hours after operation and in one patient within 4 days. One year after operation and endocrinological checkup all 25 patients were asymptomatic and normocalcaemic, while one patient had persistently high parathyroid hormone of unknown origin.

Adenoma↗
PubMed2000

Planning system for computer assisted total knee replacement.

Total knee replacement (TKR) is a common orthopaedic surgical intervention and includes the removal of bone sections from the end of the femur and the top of the tibia for replacement by prosthetic components. Pain relief and functional improvement are predictable clinical results. But the accuracy of the alignment affects the surgical outcome and the longevity of the prosthesis. Hence, current total knee implantation systems attempt to align the knee joint in the mechanical axis for placement of the total knee components. These approaches use templates and plain radiographs for preoperative planning and alignment devices for bone cuts. To overcome the inherent inaccuracy of the presently used systems a computer-assisted planning system has been developed delivering the necessary control data for the intraoperative surgical robot system.

Arthroplasty, Replacement, Knee↗
PubMed2000

LAHYSTOTRAIN intelligent training system for laparoscopy and hysteroscopy.

Rapid developments in the medical field, as an expanding knowledge base and emerging new technologies require continuing medical education to achieve life long learning and to keep the surgeons up to date. Consequently, specific training is necessary to guarantee qualification of the surgeons. The goal of LAHYSTOTRAIN is to overcome the current drawbacks of traditional training methods for laparoscopic/hysteroscopic procedures. A computer-assisted simulator for training and quality control in laparoscopy and hysteroscopy is developed using Virtual Reality (VR), Multimedia (MM) technology, and Intelligent Tutoring Systems (ITS).

Artificial Intelligence↗