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Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 235 records · Page 13Linked to original sources

[Patellar substitution in total knee prosthesis--is it important?].

As shown in long term follow-up studies of Total Knee Arthroplasty (TKA), the femoropatellar joint is an important problem. We report our experience over the past seven years not having resurfaced the patella at the primary TKA at all. Between 1990 and 1997 more than 700 consecutive TKA with the De Puy New Jersey LCS prosthesis were performed. A standardised lateral approach with osteotomy of the tibial tuberosity was used. The patella was redressed, either denervated or left untouched. In no case a primary patellar resurfacing was performed. X-rays of the patello-femoral joint showed a remodelling of the patella over the years, nicely matching the condylar design of the femoral prosthesis. Using a blood-supply-preserving approach and a biomechanically adequate implant, TKA without patellar replacement gives excellent long-term results.

Arthroplasty, Replacement, Knee↗

Expression of p21WAF1 predicts outcome of esophageal cancer patients treated by surgery alone or by combined therapy modalities.

The p21WAF1 protein is an important regulator of the cell cycle. Its expression and prognostic significance were investigated immunohistochemically in samples of normal esophageal squamous epithelium (n = 10), severe squamous cell dysplasia (n = 20), carcinoma in situ (n = 14), permanent esophageal squamous cell carcinoma cell lines (n = 3), and invasive squamous cell carcinomas treated either by potentially curative resection (n = 172) or by combined modality therapy (radiochemotherapy +/- surgery; n = 38). Whereas p21WAF1 expression in the normal epithelium was restricted to a few cells adjacent to the basal cell layer, p21WAF1 overexpression was frequently found in preneoplasias and invasive carcinomas. Expression of p21WAF1 in invasive carcinomas was not correlated with tumor differentiation, pT category, or pN category. Among carcinomas treated by potential curative resection, univariate (P = 0.0025) and multivariate (P = 0.0081) survival analysis showed significant correlation of strong p21WAF1 expression (> or =50% p21WAF1-positive tumor cells) with poor overall survival. Univariate survival analysis (P = 0.0006) revealed the same prognostic influence in the group of patients treated by combined modality therapy. We conclude that overexpression of p21WAF1 protein is a frequent event in preneoplasias and neoplasias of the esophagus. Immunohistochemical examination of p21WAF1 expression may provide important prognostic information for decision-making in the treatment of patients with esophageal cancer.

Adult↗

[Kinetic therapy of severe meconium aspiration syndrome].

Recent studies showed the possible positive effect of body position changes during mechanical ventilation of severe lung diseases in adult patients. In neonatology kinetic therapy is still rarely used, therefore we present this case report. A full term newborn suffering from severe MAS and peripartal asphyxia was transferred to our NICU to perform extracorporeal lung support, if necessary. After application of a natural porcine surfactant and start of inhalative nitric oxide therapy (10 ppm) a clinical stabilisation was possible. Because of hypercapnia, high frequency oscillation ventilation was introduced later on. The PaCO2 values decreased quickly. A few days later severe pulmonary secretion problems occurred, which led to atelectasis and barotrauma due to local hyperinflation. After several different ventilation strategies had failed to improve the situation, kinetic therapy in combination with conventional mechanical ventilation was started. Under this therapy-concept it was possible to reventilate the atelectatic lung areas, and quickly an improvement of oxygenation was seen. Weaning from the respirator was possible within one week. In conclusion, we think that an important progress in therapy was due to kinetic therapy.

Adult↗

[Protein expression of hMSH2 and hMLH1 in HNPCC: evaluation of a prescreening method].

We show that immunohistochemistry for hMSH2 and hMLH1 is an easy and reproducible routine procedure. The interpretation of the staining results is unequivocal and investigator-independent. It is now necessary to validate the specificity and sensitivity of the method in a multicenter study with tumors of known mutations. As a consequence perhaps MIN testing may be replaced by immunohistochemistry as a first-line pretesting for HNPCC, reducing cost and time required.

Adaptor Proteins, Signal Transducing↗

Analysis of granuloma formation in double cytokine-deficient mice reveals a central role for IL-10 in polarizing both T helper cell 1- and T helper cell 2-type cytokine responses in vivo.

In response to i.v.-injected eggs of Schistosoma mansoni, normal mice develop a dominant type 2 response, whereas IL-10-deficient animals generate a mixed type 1/type 2 cytokine profile and show reduced pulmonary granuloma formation. IL-4-deficient mice, while displaying diminished type 2 responses and granulomatous inflammation, also do not fully default to a type 1 cytokine profile. Strikingly, mice doubly deficient in IL-4 and IL-10 are completely defective in pulmonary granuloma formation and develop a highly polarized type 1 cytokine pattern. In analogous fashion, mice deficient in both IL-12 and IL-10 generate highly exacerbated type 2 cytokine responses, whereas in wild-type animals, IL-12 depletion minimally effects egg-induced cytokine production. Together, these results argue first that IL-10 is an important endogenous down-regulator of type 2 as well as type 1 cytokine synthesis, and second, that its induction is critical for type 2 response polarization in vivo.

Animals↗

Generation of Cre recombinase-specific monoclonal antibodies, able to characterize the pattern of Cre expression in cre-transgenic mouse strains.

Transgene-encoded Cre recombinase can target alteration of loxP-tagged genes to specific cell types and developmental stages in mice, depending on the pattern of transgene expression. To facilitate determination of the latter, we have generated monoclonal anti-Cre antibodies which are specific for distinct epitopes on the recombinase and detect Cre both on immunoblots and intracellularly by immunofluorescence. We demonstrate the usefulness of these antibodies by an analysis of Cre expression in mice carrying a cre-transgene under B cell-specific control.

Animals↗

[The diagnostic value of IgG galactosylation in rheumatoid arthritis].

Glycosylation is the main posttranslational modification of protein molecules. Human immunoglobulin G (IgG) is unique among serum glycoproteins because it is associated with at least 30 different biantennary oligosaccharide moieties. Elevated ratio of circulating IgG molecules lacking galactose from the oligosaccharides on the CH2 domain correlates with severity of the disease in a number of different autoimmune illnesses. Moreover, it may be helpful in differential diagnosis of rheumatoid arthritis (RA). By that we may try to predict outcome of RA. Its seems that agalactosyl IgG is distinctively connected with rheumatoid arthritis and may be involved in its immunopathogenesis.

Arthritis, Rheumatoid↗

Assessment of lung function in neonates during extracorporeal membrane oxygenation.

We report our experience with pulmonary function testing in 11 out of 22 full-term neonates with severe respiratory failure, treated at the ECMO center Graz (Austria) during the period from 1990 to 1995. Altogether 17 out of 22 patients survived ECMO and all of them were successfully weaned from ECMO. Pulmonary function was assessed by monitoring expiratory tidal volume on the ventilator and estimating respiratory system compliance from the ratio tidal volume/(PIP-PEEP). In addition, compliance, and functional residual capacity were measured using a computerized pulmonary function system (PEDS). Compliance (mean +/- SD) decreased markedly after 24 hours of ECMO, compared with baseline values (0.20 +/- 0.12 vs 0.12 +/- 0.13 ml/cmH2O/kg) and was significantly higher (0.43 +/- 0.14 ml/cmH2O/kg, p < 0.01) before ECMO stop. When tidal volumes increased continuously ECMO blood flow could be decreased, indicating lung recovery. Most patients had a tidal volume of > 7 ml/kg prior to decannulation. Functional residual capacity and corresponding dynamic compliance, measured in 5 patients, ranged from 18.6 to 29.6 ml/kg and 0.49 to 0.57 ml/cmH2O/kg at this time. Functional residual capacity (mean +/- SD) increased significantly when surfactant was administered to promote weaning from ECMO (8.28 +/- 0.9 vs 19.0 +/- 1.0 ml/kg, p < 0.01). We conclude that the assessment of lung function has improved our understanding of pulmonary recovery during ECMO. Its clinical significance in determining the optimum time of weaning from ECMO needs further evaluation.

Extracorporeal Membrane Oxygenation↗

[Lithotripsy in the conservative treatment of salivary stones].

Otolaryngologists and generalists as well are commonly involved in the evaluation and management of salivary gland stones. Most patients present with a history of recurrent swelling and pain in the gland, associated with eating. Up to date conservative therapy was limited to the treatment of the acute sialadenitis, which may develop as a consequence of the obstruction and often recurs until the function of the salivary gland ceases. Surgical treatment depends on the location of the calculus. Distal stones can be removed trans-orally by dilatation or incision of the duct, whereas those near the hilus and intraglandular stones required excision of the gland, including the disadvantage of a scar and the risk of injury to cranial nerves. Extracorporal shock wave lithotripsy is a new noninvasive method, which allows to destroy intra- and extraglandular salivary stones, mostly without the need of local or general anesthesia. Reported disintegration rates vary from 14% to 85%, depending on site and size of the calculus. About 80% of the patients remain symptomless Lithotripsy of salivary stones is a cost-effective, additional treatment modality to surgery and may be employed on an outpatient basis.

Diagnostic Imaging↗

Impaired Ca-signaling in astrocytes from the Ts16 mouse model of Down syndrome.

The trisomy 16 mouse model of Down syndrome has been used to compare calcium (Ca)-homeostasis and Ca-signaling in astrocytes from trisomic mice and from diploid littermates. Ratio calcium-imaging of Fura-2/AM loaded primary astroglial cultures prepared from the hippocampus shows that resting Ca levels are on average significantly higher in trisomic than in the control astrocytes (280 vs. 120 nM). Serotonin (3 microM) and glutamate (30-300 microM) evoked transient Ca-increases from 400 to 600 nM in euploid but from only 20 to 150 nM in trisomic astrocytes. Imaging of ATP-driven Ca-accumulation in cellular organelles revealed a significantly stronger uptake of Ca in trisomic astrocytes that might buffer cytosolic Ca-increases. Our results demonstrate major disturbances in Ca-signaling in trisomic astrocytes that are likely to be of pathophysiological relevance.

Adenosine Triphosphate↗

Detection of the induction of Salmonella enterotoxin gene expression by contact with epithelial cells with RT-PCR.

All strains of Salmonella enterica investigated were found to carry the Salmonella enterotoxin gene (stn) as determined by PCR and hybridization studies. However, when using CHO-K1 cells for testing the toxicity of the strains, not all strains showed a toxic effect (cell elongation) on the cells or did so only at a low level. The cultivation of Salmonella in contact with epithelial cells (IEC-6) led to an increase in the production of toxin. The stn gene expression was detectable with the help of the RT-PCR after 3 h of incubation. The RNA of the strains was isolated, transcribed into cDNA (with MMLV-reverse transcriptase) and amplified using PCR. The PCR products were separated electrophoretically using a polyacrylamide gel and detected by silver staining.

Animals↗

Interleukin-4 protects against a genetically linked lupus-like autoimmune syndrome.

Interleukin-4 (IL-4) provides support for humoral immune responses through upregulation of T helper (Th) type 2 cell differentiation, but it is not known whether IL-4 promotes antibody-mediated autoimmune diseases such as systemic lupus erythematosus (SLE). Here, we show that the constitutive expression of an IL-4 transgene by B cells completely prevents the development of lethal lupus-like glomerulonephritis in the (NZW x C57BL/6.Yaa)F1 murine model of SLE. This was associated with marked changes in the serum levels of IgG subclasses, rather than in the total levels of anti-DNA antibodies, with a lack of IgG3, a decrease of IgG2a, and an increase in IgG1 subclasses, and by a strong reduction in the serum levels of gp70-anti-gp70 immune complexes. This effect of the transgene appears to result from a modulation of the Th1 versus Th2 autoimmune response, since the protected mice displayed comparably modified IgG2a and IgG3 antibody response against exogenous T cell-dependent antigen, but not against T cell-independent antigens. Thus, IL-4 prevents the development of this lupus-like autoimmune disease, most likely by downregulating the appearance of Th1-mediated IgG subclasses of autoantibodies such as the IgG3 autoantibodies which have been shown to be especially nephritogenic.

Animals↗

IMGT, the international ImMunoGeneTics database.

IMGT, the international ImMunoGeneTics database, is an integrated database specializing in immunoglobulins, T-cell receptors (TcR) and major histocompatibility complex (MHC) of all vertebrate species, initiated and co-ordinated by Marie-Paule Lefranc, CNRS, Montpellier II University, Montpellier, France (lefranc@ligm.crbm.cnrs-mop.fr). IMGT includes two databases: LIGM-DB (for immunoglobulins and TcR) and MHC/HLA-DB. IMGT comprises expertly annotated sequences and alignment tables. LIGM-DB contains more than 19 000 immunoglobulin and TcR sequences from 78 species. MHC/HLA-DB contains class I and class II human leukocyte antigen alignment tables. An IMGT tool, DNAPLOT, developed for immunoglobulins, TcR and MHC sequence alignments, is also available. IMGT works in close collaboration with the EMBL database. IMGT goals are to establish a common data access to all immunogenetics data, including sequences, oligonucleotide primers, gene maps and other genetic data of immunoglobulins, TcR and MHC molecules, and to provide a graphical user-friendly data access. IMGT will have important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutical approaches (antibody engineering), genome diversity and genome evolution studies. IMGT can be accessed at http://imgt.cnusc.fr:8104 and http://www.ebi.ac.uk/IMGT

Amino Acid Sequence↗

Expression and prognostic value of the CD44 splicing variants v5 and v6 in gastric cancer.

In the present study, the expression and prognostic role of the CD44 splicing variants v5 and v6 were immunohistochemically investigated in 418 curatively resected gastric carcinomas. CD44v5 was expressed in 65.3 per cent (n = 273) and CD44v6 in 77.0 per cent (n = 322) of the tumours. Whereas the expression of CD44v5 was correlated with advanced pT categories, with lymph node involvement, and with the presence of blood and lymphatic vessel invasion, such a correlation could not be found for the variant v6. As shown by univariate analysis, patients with CD44v5-positive tumours had a significantly shorter overall survival than patients with CD44v5-negative tumours (P = 0.049). In contrast, expression of CD44v6 had no impact on prognosis (P = 0.574). In a multivariate analysis including the prognostic parameters pT category and pN category, as well as blood and lymphatic vessel invasion, the prognostic impact of CD44v5 expression could not, however, be maintained. Although in the present study the expression of CD44v5 was correlated with a more aggressive tumour type, these data suggest that neither CD44v5 nor CD44v6 can predict survival in patients with gastric cancer, nor is their expression a suitable tool for identifying subgroups of patients who may be at higher risk.

Adult↗

Tissue oxygen measurement and 31P magnetic resonance spectroscopy in patients with muscle tension and fibromyalgia.

Muscle tissue oxygen tension was measured by a polarographic oxygen fine-needle probe, and inorganic phosphate and creatine phosphate spectra were recorded using magnetic resonance spectroscopy in patients with chronic low back pain and in patients with fibromyalgia. Results were compared with healthy controls. The tissue oxygen tension was markedly higher in those with tense muscles than in normal subjects. Magnetic resonance spectra for inorganic phosphate were higher in patients demonstrating muscle contraction, and intracellular pH was shifted in the alkaline direction in cases with increased muscle tension. Results show that hypoxia is not the result of increased muscle tension, as was thought previously, but results from oversupply of oxygen demanded by the muscle, leading to increased capillary perfusion and rising oxygen tension.

Adult↗

Tender points, depressive and functional symptoms: comparison between fibromyalgia and major depression.

The degree of symptomatic overlap between fibromyalgia and major depression should be estimated by assessing the amount of local tenderness and the frequency and severity of depressive and functional symptoms. Tender points were assessed by palpation and symptoms by psychometric scales in 30 patients with fibromyalgia and 26 patients with major depression. The patients with fibromyalgia had markedly more tender points (16.5) than the depressive patients (1.3). In contrast, depressive and functional symptoms were present in both groups of patients, and some depressive patients (26%) also suffered from clinical pain. An increased sensitivity to pressure pain clearly distinguishes fibromyalgia from depression even if there is an overlap of other symptoms.

Adult↗

[Electromyography studies for objective assessment of loss of function of the lateral pterygoid muscles after dislocation fractures of the mandibular processes].

The aim of treatment for luxation fractures of the mandibular articular processes is not only complete anatomical restitution but also restoration of the mobility. In a retrospective study on 242 patients after operative and conservative treatment, it was possible to demonstrate that there are no correlations between fragment position and functional result. Functional restitution was observed after conservative treatment in 65% of cases and after operative treatment in 57%. In order to establish the causes for dysfunction of the lateral pterygoid muscle an electromyographical technique was developed to dissipate the action potentials of the muscle. Another retrospective study, performed in 23 patients with dysfunction of the mandible revealed loss of activity of the lateral pterygoid muscle after fracture treatment, independent of the treatment method, in 11.5% of cases (two patients). Without any connection to the treatment method, the remaining results permit to conclude that there are preoperative neurological defects. Therefore the pre- and posttherapeutic functions of muscles and nerves were investigated in a prospective study on 18 patients. Before the treatment 16.6% of the patients (n = 3) showed defects of the lateral pterygoid nerve with a resulting loss of muscle function. According to the findings, residual dysfunction of the lateral pterygoid muscle is determined by the extend of the traumatic nerve injury, independent of the treatment method. In the case of axonal defects of the pterygoid nerve, there can be no expectation of a restitutio ad integrum after the operative fragment position.

Adolescent↗

The effect of intravenous cyclophosphamide pulse on peripheral blood lymphocytes in lupus erythematosus patients.

In the present study we investigated the long-term effect of intravenous pulse cyclophosphamide (CY) on lymphocyte surface antigens in systemic lupus erythematosus (SLE) patients. Blood samples derived from 17 lupus erythematosus patients were analysed using two- and three-colour flow cytometry. During the CY therapy, the total number of T lymphocytes (CD3+) was reduced by 31.4%, B lymphocytes (CD19+) by 67.4% and NK cells (CD16+) by 27.4%. Six months after the end of the CY regimen, these values recovered to entry levels. At the onset of the study we observed increased percentages of CD3+ CD25+, CD3+ CD4- CD8-, CD4+ CD29+, CD19+ and CD19+ CD5+ cells. The CY treatment regimen decreased the CD3+ CD25+, CD3+ CD4- CD8-, CD19+ and CD19+ CD5+ cells, but increased the CD3+ CD8+ subpopulation. Taken together, a deficiency of CD8+ T cells associated with CD4+ CD29+ predominance may imply an immune regulatory imbalance leading to abnormal CD4+ cell activation and in consequence to autoimmunity. Depletion of CD19+ cells combined with an enlargement of CD8 cells as a result of CY therapy may reduce the enhanced immune response in SLE patients.

Adult↗