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Biomedical subjects

R Müller

Publications and source records attributed to R Müller.

At least 253 records · Page 14Linked to original sources
PubMed1997

Quantitative gait analysis after bilateral total knee arthroplasty with two different systems within each subject.

The functional behavior of two kinematically different knee arthroplasty systems within each subject was studied by gait analysis (three-dimensional kinematics, kinetics, dynamic electromyography) in five elderly patients, 2 to 5 years after bilateral surgery. Clinical results were good, yet gait velocity was reduced (range, 0.57-1.1 m/s), with a shortened stride length and a decreased duration of single-limb stance in all subjects. Force plate recordings revealed an undynamic gait with slow loading, reduced modulation of the vertical forces, and poor fore/aft shears. Sagittal plane knee motion during gait was reduced in all subjects, with trunk and pelvic compensation patterns for foot clearance. Muscle activity around the knee was prolonged bilaterally, with activity modulation related to the motion pattern. Although the stride parameters were quite symmetric, there was a marked asymmetry of the motion pattern, with a side-to-side difference of peak knee flexion during stance and swing phase of up to 15 degrees. This finding, however, was not clearly related to the type of prosthesis. Even within one subject, significant side-to-side variability may persist, which leads to asymmetry of the motion pattern, unrelated to the kinematic design of the implant. Other factors, such as the patella-extensor mechanism, ligament balancing, leg-length discrepancy, proprioception, continuation of a preoperative habit, or a contralateral influence, may explain part of the asymmetry seen in these subjects.

Aged↗
PubMed1997

27Al and 29Si MAS NMR investigations of cordierite glass, mu- and alpha-cordierite.

27Al and 29Si Magic-Angle Spinning NMR results are reported for conventionally prepared glass of cordierite stoichiometry (2MgO.2Al2O3.5SiO2), the metastable high-quartz solid solution (mu-cordierite) and the high-temperature polymorph of cordierite (alpha-cordierite). Both, 27Al two-dimensional (2D) quadrupole nutation experiments and 27Al satellite transition spectroscopy (SATRAS) have been applied to identify two different tetrahedrally-coordinated aluminium sites (AlO4). SATRAS has been used to extract the quadrupole interaction parameters and their distribution, the isotropic chemical shifts and the relative populations of the different Al sites. Both, the 27Al and 29Si NMR results, lead to the conclusion that a perfect Si/Al disorder does not exist in these investigated cordierite samples.

Aluminum↗
PubMed1997

Reference resistance indices of the umbilical, fetal middle cerebral and uterine arteries at 24-42 weeks of gestation.

The objective of this cross-sectional study was to construct new reference ranges for Doppler flow velocity waveform resistance indices for the fetal umbilical artery, middle cerebral artery, placental and non-placental uterine arteries and the placentocerebral ratio in a large and minimally selected population attending a single clinic. Study design and data analysis adhered to a number of stringent and validated methodological recommendations derived both from the recent literature and from a review of earlier publications in this field. The final database comprised initial routine Doppler velocimetry at 24-42 weeks' gestation in 1675 pregnancies. Separate regression models were fitted to estimate the mean and standard deviation at each gestational age for each vessel. New charts, centile tables and regression equations are presented for the resistance indices of the fetal umbilical artery, middle cerebral artery, placental and non-placental uterine arteries and the mean of both uterine arteries and for the placentocerebral ratio.

Adult↗
PubMed1997

[Conversion from peridural to transdermal opiate analgesia in abdominal tumor pain syndrome].

In a 32 years old patient with advanced gastric cancer epidural analgesia with local anaesthetic and morphine via a thoracic epidural catheter was required because of intractable pain and intolerable side effects of intravenous morphine. In spite of good efficacy it was decided to remove the catheter because of technical problems and the risk of infection during chemotherapy. Analgesic therapy proceeded to non-invasive transdermal fentanyl, using an intravenous fentanyl pca-pump during transition. The equipotent daily dose ratio of epidural morphine to transdermal fentanyl was calculated as 2.25:1.

Adult↗
PubMed1997

Acceleration in dental development: fact or fiction.

The aim of this investigation was to determine whether an actual acceleration in dental development has taken place over the last 30 years in a European population group, as is so readily observable in relation to body height. In this study, radiographs of 1038 healthy European children, 516 boys and 522 girls, were evaluated. The methodology and norms given by Nolla (1960) for both sexes were used and compared with the tooth developmental stages in our subjects. In girls, no difference to Nolla's norms could be detected. However, in boys, dental development has accelerated. This difference was most apparent in the 3- to 9-year-old age group and was statistically significant. Thus, over the last 30 years, a small acceleration in dental development has taken place in very young males.

Adolescent↗
PubMed1997

Significant reduction of human monocyte chemotactic response to monocyte-chemotactic protein 1 in patients with primary and metastatic malignant melanoma.

The recruitment of leukocytes from the peripheral blood is a key event for the development and composition of the inflammatory infiltrate in solid tumors and tumor metastases like malignant melanoma. Tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) are thought to play a crucial rôle in tumor immunosurveillance. In malignant melanoma expression and secretion of monocyte-chemotactic protein 1 (MCP-1) have been demonstrated. MCP-1 serves as an attractant for monocytes and activated T-cells. In this study we addressed the question whether circulating monocytes show altered chemotaxis to MCP-1. Therefore the chemotactic responsiveness of monocytes towards MCP-1 was investigated in patients with primary and metastatic melanoma and compared to patients with basal cell carcinoma and healthy persons. The results show that monocytes from melanoma patients showed a significantly decreased chemotactic migration towards MCP-1 while chemotaxis to the stimulus N-formyl-methionyl-leucyl-phenylalanine (FMLP) remained normal. Patients with basal cell carcinoma showed normal monocyte chemotaxis to all stimuli tested. In primary melanoma, there was no relation of the number of TAM or TIL to the decreased chemotaxis of circulating monocytes to MCP-1. From these data it can be concluded that circulating monocytes from patients with primary and metastatic melanoma show a MCP-1-specific decrease in chemotactic migration. This may be due to deactivation or modulation of the MCP-1-receptor expression on these cells.

Adult↗
PubMed1997

A novel, transformation-relevant activation domain in Fos proteins.

We have previously demonstrated that transformation by Fos is critically dependent on an intact DNA-binding domain (bZip) and a functional N-terminal transactivation motif (N-TM). We now show that a novel motif (C-terminal transactivation motif [C-TM]) near the C terminus also plays an important role in both transformation and the activation of AP1-dependent transcription and that the hydrophobic amino acids in the C-TM are functionally essential. The C-TM is the most crucial element in the C-terminal transactivation domain in Fos, as indicated by its relative strength and context-independent function. The C-TM is clearly different from the previously identified HOB2 domain, located N terminally to the C-TM, and the C-terminally positioned TATA-binding protein-binding domain. We also show that the C-terminal transactivation domain strongly synergizes with the HOB1-like N-TM, even when both domains are present on different proteins within a dimeric complex, and that the C-TM plays a crucial role in this cooperation. These observations can be corroborated in a model in which multiple contacts with the basal machinery are established either to stabilize the transcription complex or to facilitate its sequential assembly.

3T3 Cells↗
PubMed1997

Micro-tomographic imaging for the nondestructive evaluation of trabecular bone architecture.

The structural properties of trabecular bone have been shown to vary significantly with age, anatomic location, and metabolic condition. Micro-computed tomography (microCT) is an emerging technique for the nondestructive assessment and analysis of the three-dimensional trabecular bone architecture. Within the framework of the European Union BIOMED I project "Assessment of Bone Quality in Osteoporosis," a total of 350 bone biopsies from five different anatomical locations were harvested post mortem from 70 donors (aged 23 to 92 years). These biopsies were measured using a newly devised compact micro-tomographic system, also referred to as desk-top microCT. Samples with a diameter from a few millimeters to a maximum of 18 mm and a length of up to 55 mm can be measured. For this study fresh, untreated bone biopsies with a diameter of 8 mm were measured micro-tomographically with a nominal isotropic resolution of 14 microns. For all samples, the volumes of interest (4 x 4 x 4 mm3) were binarized using a uniform threshold. Subsequently, standard structural indices such as bone volume density (BV/TV), bone surface density (BS/BV), trabecular plate number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) and the degree of anisotropy (DA) were computed for all specimens incorporating mean intercept length (MIL) measurements. Regression analysis was used to estimate the correlations of single structural parameters with age or with a second parameter and also among different measurement sites. The nondestructive microCT measurements allowed not only to perform quantitative bone morphometry but also to assess other important microstructural features in the determination of the mechanical integrity of trabecular bone such as the incidence and prevalence of microcallus formations. The findings from the BIOMED I study are expected to improve our understanding of the relative importance of bone architecture, damage accumulation, and bone mineralization in the characterization of bone quality in the progress of age- and disease-related bone loss.

Adult↗
PubMed1997

The quality of trabecular bone evaluated with micro-computed tomography, FEA and mechanical testing.

Most standard methods to predict bone quality are merely based on apparent density measurements. However, apparent density alone does neither explain all variation of the mechanical properties nor does it account for the structural anisotropy of trabecular bone. Thus, apparent density alone might not be sufficient to accurately predict the quality of bone. This study investigates if a new approach based on microstructural computer models can provide additional and relevant information on bone quality. 58 human trabecular bone samples from the femoral head were measured with a 3-D micro-Computed Tomography (micro-CT) system providing a voxel representation of the bone microarchitecture with a resolution of 28 microns. Based on such representations, the orthotropic stiffness matrices and the principal directions were computed for 5 mm cubes with microstructural Finite Element Analysis (FEA). For a subset of six samples the moduli were then validated with tri-axial mechanical compression tests. The results show that on average 15% of the variation of the elastic properties are not explained by bone volume fraction. Differences of elastic properties between samples with the same bone volume fraction range up to 53%. The variation of the degree of anisotropy is unrelated to that of the bone volume fraction. Finally, the direction-dependent stiffness of the trabecular bone differs by a factor of four, indicating that one single (isotropic) modulus as predicted from apparent density measurements might not be adequat. It is concluded that micro-CT-based FEA provides new and additional information about anisotropy and mechanical properties in a direct and non-destructive way, and thus will be important in the future for advanced failure risk prediction. An extension to patient examinations using high-resolution CT or MRI techniques is envisaged.

Biomechanical Phenomena↗
PubMed1997

The CliniCon framework for context representation in electronic patient records.

A well-known problem of current electronic patient records in that they usually fail to represent the semantic relationships between the involved clinical data. This has to be viewed as a problem especially in the domains characterized by a complex and long-term treatment, as the medical decision making process may not be comprehensible anymore from the data entries themselves. Context representation can overcome these limitations, enabling the record to express causality, revisions, conflicts, or individual heuristics explicitly. This article introduces CLINICON which is a formal framework for domain-independent context representation based on Sowa's conceptual graphs.

Artificial Intelligence↗
PubMed1997

The incidence of complications associated with local anesthesia in dentistry.

Local anesthetics are frequently administered in dentistry and thus can be expected to be a major source of drug-related complications in the dental office. Additionally, the dentist will more often be confronted with the treatment of risk patients; thus, the incidence of side effects can be expected to rise. In this study, 2731 patients receiving dental anesthesia were evaluated by questionnaire for risk factors, type and dosage of local anesthetic applied, type and duration of treatment, and complications associated with the administration of the local anesthetic. Of all patients, 45.9% had at least one risk factor in their medical histories, with cardiovascular diseases and allergies being the most frequent. The overall incidence of complications was 4.5%. It was significantly higher in risk patients (5.7%) than in nonrisk patients (3.5%). The most frequently observed complications (dizziness, tachycardia, agitation, nausea, tremor) were transient in nature and did not require treatment. Severe complications (seizure, bronchospasm) occurred in only two cases (0.07%). Articaine was found to be administered in over 90% of all dental anesthesias in Germany despite the great variety of local anesthetics available. Articaine 1:100,000 caused more sympathomimetic side effects than did articaine 1:200,000. Additionally, doses of local anesthetics proved not to be strictly determined according to body weight, especially for patients weighing less than 50 kg. In summary, it can be stated that dental local anesthesia can be considered safe. Nevertheless, the incidence of complications due to dental anesthesia can be expected to be further reduced if (a) patients are routinely evaluated for risk factors with an adequate medical history prior to dental treatment, (b) doses of local anesthetics are strictly determined according to body weight, (c) anesthetics with low concentrations of epinephrine are used, and (d) the concept of a differentiated dental anesthesia is applied.

Adult↗
PubMed1996

Uncoupling of DNA replication and cell cycle progression by human cyclin E.

The G1-specific D- and E-type cyclins are among the most crucial factors controlling cell cycle progression in mammalian cells and are therefore thought to play an important role in tumorigenisis. D-type cyclins have indeed been shown to be endowed with an oncogenic potential. Here, we report that the ectopic expression of human cyclin E, but not cyclin D1, deregulates DNA synthesis in both yeast and mammalian cells. In yeast, induction of DNA synthesis by cyclin E occurs even under conditions of cell cycle arrest in G1 or G2/M, indicating an uncoupling of DNA replication from cell cycle progression. In rat embryo fibroblasts, the cooperative action of Ras and cyclin E induces transformation. These cells, in contrast to those transformed by Ras and cyclin D1, show aberrant levels of DNA synthesis. Since cyclin E is commonly overexpressed in a variety of human tumors, these findings may point to a link between the uncontrolled proliferation and the genomic instability typically seen in malignant tumors. Furthermore they reveal significant differences in the functional properties of cyclin E and D1.

Animals↗
PubMed1996

A T cell controlled molecular pathway regulating the IgH locus: CD40-mediated activation of the IgH 3' enhancer.

Immunoglobulin heavy chain (IgH) class switch recombination and regulation of IgH expression levels are processes suggested to be controlled by the IgH 3' enhancer. Here we demonstrate that CD40 or IgM receptor stimulation of primary B cells results in transactivation of this enhancer. 4-Hydroxy-3-nitrophenylacetyl (NIP)-BSA induction of a K46 B cell line expressing a chimeric NIP-specific CD40 single chain receptor results in a ligand receptor-dependent response of a 3' enhancer ETS/AP-1 minimal promoter construct. Gel retardation analysis and genomic footprinting experiments reveal that CD40 or IgM induction recruits NFAB (nuclear factors of activated B cells) to the ETS/AP-1 motif. While IgM signalling recruits c-Fos, JunB and Elf-1 (NFAB-I), only JunB and Elf-1 were observed following CD40 signalling (NFAB-II). CD40 signalling, however, induces a Fos family-related partner for JunB, which may account for the transcriptional activity observed by NFAB-II in K46 cells. We propose a model whereby CD40 and IgM receptor-mediated signalling converge in the process of 3' enhancer activation in B lymphocytes. Our data provide a putative molecular explanation as to why CD40L-deficient mice, and possibly patients with hyper-IgM syndrome, are unable to undergo T cell-dependent class switch recombination but respond properly upon lipopolysaccharide-induced switch recombination.

Animals↗
PubMed1996

[Percutaneous suture closure of the femoral artery access after diagnostic heart catheter examination or coronary intervention].

BACKGROUND AND OBJECTIVE: Alternative methods to the conventional one of external compression with a pressure bandage over the site of arterial puncture after percutaneous catheter introduction for coronary angiography or transluminal balloon coronary angioplasty have failed to reduce the rate of vascular complications. This study was undertaken to assess the complication rate of a percutaneously introduced suturing device (Techstar, Perclose). PATIENTS AND METHODS: To achieve immediate haemostasis and thus shorten post-interventional immobilisation the technique of percutaneous suturing of the femoral artery was used in 1030 consecutive patients (793 men, 237 women; mean age 58.6 years) without obstructive vascular disease or local vascular complications. RESULTS: Percutaneous suture closure with primary haemostasis was successful after 137 of 153 coronary angioplasties (89.5%) and after 786 of 977 left heart catheterisations (89.6%). Early mobilisation, after at most 4 hours, was possible in 923 patients with successful suture closure (89.6%). The overall complication rate was 0.78%. CONCLUSION: Percutaneous suture repair of the femoral artery after cardiac catheterisation is a safe and effective method to achieve immediate haemostasis. However, controlled studies are needed to demonstrate harmlessness of early mobilisation.

Angioplasty, Balloon, Coronary↗
PubMed1996

Surface antigen expression on CD34+ cord blood cells: comparative analysis by flow cytometry and limiting dilution (LD) RT-PCR of chymopapain-treated or untreated cells.

Expression of antigens coexpressed on cord blood (CB) CD34+ cells was evaluated by flow cytometry analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Antigen expression was also comparatively analyzed by flow cytometry and limiting dilution (LD) RT-PCR to investigate effects of chymopapain on epitopes of several cell surface markers: LD RT-PCR allows detection of the expression of antigens degraded by chymopapain which are not identified by flow cytometry. Monoclonal antibodies (MoAbs) that recognize chymopapain resistant epitopes on several coexpressed cell surface markers were identified: these included MoAbs directed against CD11a, CD13, CD18, CD38, CD45RO, CD51, HLA-DR, Thy-1, c-kit, flt-3 (STK-1), and mdr-1. Interestingly, chymopapain treatment caused enhanced staining with MoAbs against HLA-DR, Thy-1, flt-3, mdr-1, and CD51. The frequency (LD RT-PCR) of CD18, CD38, Thy-1, and c-kit RT-PCR signals on pure sorted CD34+ CD18-, CD34+ CD38-, CD34+ Thy-1-, and CD34+ c-kit- cells, respectively, was similar in corresponding subsets treated or not with chymopapain. In contrast, the frequency of CD33 RT-PCR signals on sorted CD34+ CD33- cells was higher in chymopapain-treated samples than in untreated samples and thus confirmed at the transcriptional level that the epitope recognized by anti-CD33 is chymopapain sensitive. Our findings extend data on the phenotypic profile of CB CD34+ cells and show that several key cell surface markers of hematopoietic progenitor cells are chymopapain resistant. In addition, the results of the present study demonstrate that the RT-PCR can be applied to the analysis of multiple RNA species in small numbers of hematopoietic progenitor cells and show that LD RT-PCR allows the identification and frequency determination of rare cells which are undetectable by flow cytometry.

Antibodies, Monoclonal↗
PubMed1996

Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway.

We have previously shown that the persistent activation of p42/p44(MAPK) is required to pass the G1 restriction point in fibroblasts (Pagès, G., Lenormand, P., L'Allemain, G., Chambard, J. C., Meloche, S., and Pouysségur, J. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 8319-8323) and postulated that MAPKs control the activation of G1 cyclin-dependent complexes. We examined the mitogen-dependent induction of cyclin D1 expression, one of the earliest cell cycle-related events to occur during the G0/G1 to S-phase transition, as a potential target of MAPK regulation. Effects exerted either by the p42/p44(MAPK) or the p38/HOGMAPK cascade on the regulation of cyclin D1 promoter activity or cyclin D1 expression were compared in CCL39 cells, using a co-transfection procedure. We found that inhibition of the p42/p44(MAPK) signaling by expression of dominant-negative forms of either mitogen-activated protein kinase kinase 1 (MKK1) or p44(MAPK), or by expression of the MAP kinase phosphatase, MKP-1, strongly inhibited expression of a reporter gene driven by the human cyclin D1 promoter as well as the endogenous cyclin D1 protein. Conversely, activation of this signaling pathway by expression of a constitutively active MKK1 mutant dramatically increased cyclin D1 promoter activity and cyclin D1 protein expression, in a growth factor-independent manner. Moreover, the use of a CCL39-derived cell line that stably expresses an inducible chimera of the estrogen receptor fused to a constitutively active Raf-1 mutant (DeltaRaf-1:ER) revealed that in absence of growth factors, activation of the Raf > MKK1 > p42/p44MAPK cascade is sufficient to fully induce cyclin D1. In marked contrast, the p38(MAPK) cascade showed an opposite effect on the regulation of cyclin D1 expression. In cells co-expressing high levels of the p38(MAPK) kinase (MKK3) together with the p38(MAPK), a significant inhibition of mitogen-induced cyclin D1 expression was observed. Furthermore, inhibition of p38(MAPK) activity with the specific inhibitor, SB203580, enhanced cyclin D1 transcription and protein level. Altogether, these results support the notion that MAPK cascades drive specific cell cycle responses to extracellular stimuli, at least in part, through the modulation of cyclin D1 expression and associated cdk activities.

Animals↗
PubMed1996

Cell cycle-regulated repression of B-myb transcription: cooperation of an E2F site with a contiguous corepressor element.

B-myb belongs to a group of cell cycle genes whose transcription is repressed in G0/early G1 through a binding site for the transcription factor E2F. Here, we show that the B-myb repressor element is specifically recognised by heterodimers consisting of DP-1 and E2F-1, E2F-3 or E2F-4. Surprisingly, E2F-mediated repression is dependent on a contiguous corepressor element that resembles the CHR previously established as a corepressor of the CDE in cell cycle genes derepressed in S/G2, such as cyclin A, cdc2 and cdc25C. A factor binding to the B-myb CHR was identified in fractionated HeLa nuclear extract and found to interact with the minor groove, as previously shown by in vivo footprinting for the cyclin A CHR. The B-myb and cdc25C CHRs are related with respect to protein binding but are functionally clearly distinct. Our results support a model where both E2F- and CDE-mediated repression, acting at different stages in the cell cycle, are dependent on promoter-specific CHR elements.

3T3 Cells↗