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Biomedical subjects

D Wahl

Publications and source records attributed to D Wahl.

At least 19 recordsLinked to original sources
PubMed2000

[Biomechanics of interlocked nailing in humeral shaft fractures. Comparison of 2 nail systems and the effect of interfragmentary compression with the unreamed humeral nail].

In this biomechanical study the implanted Unreamed Humeral Nail (UHN) has been tested concerning bending and torsional stiffnesses. In literature other intramedullary implants have been criticized for insufficient rotatory stability especially in transverse and short oblique fractures of the humeral shaft. This study examined, whether the implanted UHN, as well as the UHN implanted with interfragmentary compression through a specific compression device, is able to augment torsional stiffness significantly. To evaluate bending and torsional stiffnesses, the UHN has been compared biomechanically to the Russell-Taylor humeral nail (RT) in paired mid-shaft osteotomized cadaveric humeri. Identic paired comparison has been performed with the UHN without and UHN with interfragmentary compression. In anterior-posterior, as well as medio-lateral direction stiffness under four-point-bending is significantly higher in stabilizing with the RT. Under torsional loading with moments of 4 Nm, 6 Nm and 8 Nm the UHN reached more than the double torsional stiffness. The RT, which is only dynamically interlocked, owns a high initial "play" between bolts and nail itself. Through additional interfragmentary compression stiffness of the UHN under four-point-bending in anterior-posterior, as well as medio-lateral direction augments significantly. Also under torsional loading with moments of 4 Nm, 6 Nm und 8 Nm torsional stiffness increases with interfragmentary compression significantly. In comparison to other biomechanical studies of different authorship it is clear, that this statically interlocked intramedullary nailing of the humeral shaft is superior to non-statically interlocked types of nailing concerning their stabilizing potency in torsion and serves especially for fracture types, which are critically under rotation, as transverse or short oblique humeral shaft fractures.

Biomechanical Phenomena↗
PubMed2000

[Comparative in vitro studies of self-boring and self-tapping screws. Histomorphological and physical-technical studies of bone layers].

Self-drilling screws are gaining increasing importance in maxillofacial surgery. This study assesses which screw design, self-drilling or self-tapping, is best suited to various locations of the human skull. With regard to different areas in the human midface, mandible, and cranium, the thickness of cortical bone varies as well as the relative proportion of cortical to cancellous bone. Criteria used to judge the success of screws were minimal insertion torque and minimum temperature, maximum pullout strength, and minimum deformation and destruction of the bone. To mimic the variations in anatomical conditions, 1-mm and 3-mm-thick cortical bone specimens and cancellous bone blocks were prepared. Eight screws of three types (self-tapping, self-drilling/self-tapping, conically shaped self-drilling) were inserted into the different bone specimens. Torque and temperature were measured during the insertion procedure. Subsequently, the screws were carefully removed and the specimens were processed for histological evaluation. The same insertion protocol was used to test the pull-out strength of the screws. The conically shaped screw showed best results in cancellous bone for all parameters. The self-tapping screw with a pilot hole performed best in thick cortical bone and the self-drilling/self-tapping screw performed better than did the others in thin bone. The results suggest the three screw designs to be optimal for different locations of the human skull. This project provides the data for a planned in vivo study that will evaluate the long-term influence of deformation and temperature on stability and osseointegration of the screws.

Animals↗
PubMed2000

Monovalent binding of autoantibodies to beta2-glycoprotein I, detected using surface plasmon resonance at low antigen density.

The precise mechanism of interaction between autoantibodies and beta2-glycoprotein I (beta2GPI) and the experimental conditions to be used for their detection are still under debate. Until now, these interactions have been studied under static conditions. We have investigated the interactions of purified IgG from 25 lupus anticoagulant-positive patients with immobilized beta2GPI under flow conditions by real-time analysis based on surface plasmon resonance technology. Sensor chips were coated with purified human beta2GPI coupled to dextran via amino groups at low densities (1.4, 1.8 or 2. 4 ng beta2GPI/mm2). Four patients' IgG displayed efficient binding and had the highest so-called antiphospholipid IgG levels by enzyme-linked immunosorbent assay (ELISA) and the highest absorbance values in an anti- beta2GPI ELISA at a beta2GPI density reported to be around 12 ng/mm2. Binding of antibodies to the beta2GPI sensor chips proved to be dependent upon the IgG concentration and beta2GPI density and was inhibited by a rabbit antibody against beta2GPI. Similar association and dissociation profiles were observed for the four efficient binders. The fast rate of dissociation limited the binding of autoantibodies to beta2GPI and was highly suggestive of a monovalent association, confirmed by binding of Fab fragments under similar experimental conditions. In conclusion, monovalent binding of low-affinity antibodies to beta2GPI immobilized at a density as low as 1.8 ng/mm2 could be detected using surface plasmon resonance.

Animals↗
PubMed2000

Comparison of the in vitro holding strengths of conical and cylindrical pedicle screws in a fully inserted setting and backed out 180 degrees.

Previous investigations have suggested that conical and cylindrical pedicle screws have comparable holding strengths. So far, the remaining performance in screws turned back or loose as a result of other reasons has not been determined. Twenty-four cadaveric spines from 6- to 8-week-old calves were examined. After bone mineral density was determined, four pedicle screws (two conical and two cylindrical screws) were inserted. The screws were fully inserted and half of them turned back 180 degrees. Twenty-four axial pullout and 24 cyclic loading tests with subsequent pullout tests were conducted. The pullout strengths of conical screws turned back 180 degrees are significantly smaller (1.8 kN) than those of cylindrical screws (4.3 kN). After cyclic loading, the displacement of conical screws is significantly greater (6.9 mm) than that of cylindrical screws (4.7 mm). Pedicle screws, especially conical ones, need to be placed to a correct depth, and they should not have to be backed out.

Animals↗
PubMed2000

Interaction of anti-phospholipid antibodies with late endosomes of human endothelial cells.

Anti-phospholipid antibodies (APLAs) are associated with thrombosis and/or recurrent pregnancy loss. APLAs bind to anionic phospholipids directly or indirectly via a cofactor such as beta(2)-glycoprotein 1 (beta(2)GPI). The lipid target of APLA is not yet established. Recently, we observed that APLAs in vitro can bind lysobisphosphatidic acid (LBPA). The internal membranes of late endosomes are enriched in this phospholipid. The current study was undertaken to determine to what extent binding of APLA to LBPA is correlated with binding to cardiolipin and to beta(2)GPI and to determine whether patient antibodies interact with late endosomes of human umbilical vein endothelial cells (HUVECs) and thus modify the intracellular trafficking of proteins. Binding of patient immunoglobulin G (n=37) to LBPA was correlated significantly with binding to cardiolipin. Although LBPA binding was correlated to a lesser extent with beta(2)GPI binding, we observed that beta(2)GPI binds with high affinity to LBPA. Immunofluorescence studies showed that late endosomes of HUVECs contain LBPA. Patient but not control antibodies recognized late endosomes, but not cardiolipin-rich mitochondria, even when we used antibodies that were immunopurified on cardiolipin. Incubation of HUVECs with patient plasma samples immunoreactive toward LBPA resulted in an accumulation of the antibodies in late endosomes and led to a redistribution of the insulinlike growth factor 2/mannose-6-phosphate receptor from the Golgi apparatus to late endosomes. Our results suggest that LBPA is an important lipid target of APLA in HUVECs. These antibodies are internalized by the cells and accumulate in late endosomes. By modifying the intracellular trafficking of proteins, APLA could contribute to several of the proposed pathogenic mechanisms leading to the antiphospholipid syndrome.

Antibodies, Antiphospholipid↗
PubMed1999

[Improvement in prevention of venous thromboembolism in medical environment. Mission impossible?].

PURPOSE: In France, low molecular weight heparins are widely used for prophylaxis of venous thromboembolism. This practice is not based on strong evidence supporting the use of this technique, thus leading to important difficulties in defining accurate guidelines. Improvement in the prophylaxis must focus on the process leading to prescription or non-prescription. Our primary objective was to identify and describe this process. We also analyzed the causes for dysfunction and implemented corrective actions. METHODS: Basic tools and methods specific to improvement of quality were used including: flow charting for process description, causes-effect diagram for updating and analysis of dysfunction, weighted vote for decisions regarding corrective actions, and agenda and designation of leaders for the implementation of corrective actions. RESULTS: The theoretical process beginning with the recognition of a risk and ending with the adequate treatment or prevention of this risk was demonstrated. The most important dysfunction was the lack of epidemiological and clinical trials. Key corrective actions were the following: standardization of practices where evidence was available; if not, collaborative efforts to collect valid epidemiological data through multicenter surveys and clinical trials; systematic appraisal of the quality of published data; assessment of the risk for venous thromboembolism during hospitalization. To achieve real improvement in practice, priority was given to repeated measures of the risk for thromboembolism. The use of low molecular weight heparins has been so wide however, that it has led to some difficulties. We must draw lessons from this experience. CONCLUSION: Improvement of quality in terms of healthcare is not only based on auditing the practices or modifying the defective processes, but also on our ability not to use new drugs before fully assessing their validity.

Anticoagulants↗
PubMed1999

A fragment of alpha-actinin promotes monocyte/macrophage maturation in vitro.

Conditioned media (CM) from cultures of HL-60 myeloid leukemia cells grown on extracellular bone marrow matrix contains a factor that induces macrophage-like maturation of HL-60 cells. This factor was purified from the CM of HL-60 cells grown on bone marrow stroma by ammonium sulfate precipitation, then sequential chromatography on DEAE, affi-gel blue affinity, gel exclusion, and wheat germ affinity columns, followed by C-4 reverse phase HPLC, and SDS-PAGE. The maturation promoting activity of the CM was identified in a single 31 kD protein. Amino acid sequence analysis of four internal tryptic peptides of this protein confirmed significant homology with amino acid residues 48-60, 138-147, 215-220, and 221-236 of human cytoskeletal alpha-actinin. An immunoaffinity purified rabbit polyclonal anti-chicken alpha-actinin inhibited the activity of HL-60 conditioned media. A 27 kD amino-terminal fragment of alpha-actinin produced by thermolysin digestion of chicken gizzard alpha-actinin, but not intact alpha-actinin, had maturation promoting activity on several cell types, including blood monocytes, as measured by lysozyme secretion and tartrate-resistant acid phosphatase staining. We conclude that an extracellular alpha-actinin fragment can promote monocyte/macrophage maturation. This represents the first example of a fragment of a cytoskeletal component, which may be released during tissue remodeling and repair, playing a role in phagocyte maturation.

Actinin↗
PubMed1999

HL-60 cells degrade alpha-actinin to produce a fragment that promotes monocyte/macrophage maturation.

An amino-terminal fragment of alpha-actinin can promote monocyte/macrophage maturation. This fragment was initially isolated from media of HL-60 myeloid leukemia cells cultured on extracellular bone marrow matrix. To determine the source of this fragment in this culture system, we investigated whether HL-60 cells grown on bone marrow stroma have increased intracellular levels of alpha-actinin that may be released into the media during cell apoptosis. HL-60 cells grown on matrix showed no evidence of increased cellular alpha-actinin compared to cells grown on plastic substrata as measured by flow cytometry. In addition, there was no evidence of increased apoptosis as determined by DNA fragmentation assays or flow cytometry. However, 100 kD alpha-actinin was found in the extracellular matrix of bone marrow stroma by Western blot analysis and immunofluorescence microscopy. The alpha-actinin content in the stroma was markedly decreased after exposure to HL-60 cells. Furthermore, lysates of HL-60 cells or of peripheral blood monocytes can degrade exogenous alpha-actinin to produce a 31 kD fragment, which promotes monocyte/macrophage maturation. We conclude that when alpha-actinin is present in the extracellular matrix, it can be modified by HL-60 cells to produce a maturation promoting 31 kD fragment.

Actinin↗
PubMed1998

Cyclosporine A-induced decrease in calbindin-D 28 kDa in rat kidney but not in cerebral cortex and cerebellum.

Recently, we reported that in rat, cyclosporine A (CsA) markedly decreases the levels of calbindin-D (CABP-D) 28 kDa in kidney. CABP-D 28 kDa is a calcium-binding protein which is highly expressed in calcium-transporting tissues such as kidney or brain. In this study, we investigated whether, in addition to the kidney, CsA also has an effect on CABP-D 28 kDa in rat brain. Three groups of male Wistar rats received 15 mg/kg/day or 50 mg/kg/day of CsA orally for 12 days, whereas controls received vehicle solution for the same period. CABP-D 28-kDa protein and CsA were quantified in homogenates of kidney, cerebral cortex and cerebellum, and the localization of CABP-D 28 kDa was assessed in the different tissue sections by immunohistochemistry. In kidney, CABP-D 28 kDa was strongly and dose dependently decreased, and was located in tubular epithelial cells. In brain, CABP-D 28 kDa was not changed and was mainly located in pyramidal cells of the cortex and in cerebellum exclusively in Purkinje cells. High CsA concentrations were measured in kidney, more than 17-fold greater than those found in cortex. In cerebellum, CsA was below the limit of detection. These data suggest that at clinically relevant doses, CsA may not affect CABP-D 28-kDa levels in brain.

Animals↗
PubMed1998

[Prevention of venous thromboembolism. Survey of in-hospital medical practice].

OBJECTIVES: In an effort to improve the prevention of venous thromboembolism, the Nancy University Hospitals conducted a survey of medical practice concerning indications for preventive therapy and surveillance of platelet counts and anti Xa activity. METHODS: The survey involved 163 medical files. Questionnaires were filled out in 6 units (3 medical wards and 3 intensive care units). RESULTS: Indications for preventive therapy were found to be quite variable with the exception of very low risk of thromboembolism where the treat/do not treat ratio was 0.1/1, indicating a clear tendency for abstention. This ratio was 0.77/1 and 0.38/1 respectively for low and moderate risk and 2/1 for high risk. There was undoubtedly a ward effect. The attitudes in practice tended toward non-prevention in patients without limited mobility. For platelet counts, an initial count was performed in 95% of the cases and during treatment in 38% although the specific rates were not the same for different types of units. Anti-Xa activity, which according to prevention recommendations need not to be determined, was not monitored in 88% of the cases. In accordance with prevention recommendations, anti-Xa activity was not determined in 88% of the cases. CONCLUSION: Further progress is needed in the prevention of venous thromboembolism and should be based on wider use of existing methods.

France↗
PubMed1998

New insights into cyclosporine A nephrotoxicity by proteome analysis.

Using two-dimensional gel electrophoresis (2-DE), we recently discovered an association between decreased calcium-binding protein, calbindin-D 28 kDa, urinary calcium wasting and intratubular corticomedullary calcifications in rat kidney. This observation prompted us to investigate kidney tissues of other species, including man. In this paper we show that in dogs and monkeys, which are generally devoid of cyclosporine A (CsA)-mediated nephrotoxicity, renal calbindin levels were not affected by the CsA treatment whereas in CsA-treated human kidney-transplant recipients with renal vascular or tubular toxicity, a marked decrease in renal calbindin-D 28 kDa protein level was found in most of the kidney biopsy sections. The present results strongly suggest that calbindin is a marker for CsA-nephrotoxicity. The discovery of calbindin-D 28 kDa being involved in CsA toxicity has evolved from the application of 2-DE and has not been reported previously, proving that proteomics can provide essential information in mechanistic toxicology. Considering the current improvements in proteome methods it is expected that high throughput proteomics will become an indispensable tool in preclinical safety testing.

Animals↗
PubMed1998

Biomechanical behaviour at the distal third of the femur: possible use of a medial metaphyseal plate.

The incidence of fractures in the distal femur is becoming more frequent and they are often associated to complex lesions with potential complications. Operative treatment is mandatory for elderly people and several methods of internal fixation with appropriate implants have been developed, generally approaching the lateral aspect of the femur. An alternative antero-medial access was proposed several years ago but the biomechanical aspects of its application must be debated. The aim of the present study is to establish if adverse biomechanical effects should be expected when the plate is affixed at the medial side of the femur metaphysis, by analysing the strain pattern of a human cadaver femur submitted to loads simulated in different experimental conditions. Application of load resulted, as expected, in tension in the lateral aspect and compression in the medial aspect of the femur diaphysis but it turned more and more toward the anterior aspect and the compression turned toward the posterior aspect when the levels measured changed from proximal to distal. The plate was next to the neutral axis and produced a moderate stress protection effect (approx. 70 per cent). No biomechanical disadvantages have been observed as a result of the plate being apposed at the medial aspect instead of the conventional lateral aspect of the distal femur.

Aged↗
PubMed1998

Changes in the liver protein pattern of female Wistar rats treated with the hypoglycemic agent SDZ PGU 693.

SDZ PGU 693 acts as a hypoglycemic agent by stimulating glucose utilisation in insulin-sensitive peripheral tissues, such as skeletal muscle and fat. In a 28 day toxicity study the compound was found to induce hepatocellular hypertrophy in Wistar rats treated with 300 mg/kg/day. To gain insights into the pathomechanism of these alterations, aliquots of liver samples from control and treated female Wistar rats were separated by two-dimensional protein gel electrophoresis and the digitized images of the protein patterns were searched for protein abundance changes. Significant treatment-related quantitative changes (P < 0.001) were found in 29 liver proteins. Major increases were observed in several microsomal proteins, including NADPH cytochrome P-450 reductase, cytochrome b5 and serine protease inhibitor. The changes in the cytochrome related enzymes, both known co-factors of the P-450 enzyme system, strongly suggest that SDZ PGU 693 induces microsomal proliferation and induction of the P-450 enzyme system. Decreases were observed in a series of mitochondrial proteins, such as F1ATPase-delta subunit and ornithine aminotransferase precursor as well as in several cytosolic proteins such as the liver fatty acid binding protein, arylsulfotransferase and the senescence marker protein-30. The changes in F1ATPase-delta subunit and liver fatty acid binding protein together suggest a down-regulation of the mitochondrial liver fatty acid metabolism, likely reflecting the pharmacological action of the compound. These results show that SDZ PGU 693 produces a complex pattern of gene expression changes which give insights into the molecular mechanisms of both its pharmacological action and a toxic response.

Animals↗
PubMed1998

Gastric versus duodenal feeding and gastric tonometric measurements.

OBJECTIVE: To compare the influence of gastric and postpyloric enteral feeding on the gastric tonometric PCO2 gap (tonometric PCO2 - PaCO2). DESIGN: A prospective, clinical trial. SETTING: Two intensive care units in a university hospital. PATIENTS: Twenty patients undergoing mechanical ventilation and enteral feeding without catecholamines, sepsis, or sign of hypoxia. INTERVENTIONS: Patients were randomized to receive feeding through the tonometer (gastric group), or through a postpyloric tube (postpyloric group). MEASUREMENTS AND MAIN RESULTS: The patients received tube feeding at a rate of 50 mL/hr during 4 hrs. Baseline measurements included: mean arterial pressure, heart rate, tonometric parameters, arterial gases, and arterial lactate concentration. Except for lactate concentration, these measurements were repeated after 1 and 4 hrs of enteral feeding and 2 hrs after stopping enteral feeding. During the study, arterial pH and PaCO2 did not change. During enteral feeding, the PCO2 gap increased in the gastric group from a mean of 7+/-5 to 17+/-14 (SD) torr (0.9 0.7 to 2.3+/-1.9 kPa) (p< .O01) and did not change in the postpyloric group (5+/-5 to 3+/-1 torr [0.7+/-0.7 to 0.4+/-0.1 kPa]). Two hours after stopping enteral feeding, the PCO2 gap was still increased in the gastric group (15+/-9 vs. 7+/-5 torr [2.0+/-1.2 vs. 0.9+/-0.7 kPa]) (p < .01). CONCLUSION: The results indicate that gastric enteral feeding increased the PCO2 gap. However, postpyloric enteral feeding does not interact with gastric tonometric measurements and should be used when using gastric tonometry in enterally fed patients.

Aged↗
PubMed1998

Spinal and bulbar muscular atrophy (SBMA): somatic stability of an expanded CAG repeat in fetal tissues.

Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked motor neuron degenerative disease caused by an expanded trinucleotide repeat. Unlike most other trinucleotide repeat diseases, SBMA shows limited meiotic instability, and evidence thus far indicates absence of somatic instability in adults. Data regarding the presence of fetal tissue somatic mosaicism is unavailable. We present a family in which a woman whose father had SBMA requested prenatal testing. After informed consent. molecular genetic evaluation showed the male fetus to carry the SBMA repeat elongation. Testing of fetal tissues after elective pregnancy termination showed no somatic mosaicism in the CAG repeat length. This is the first report of molecular genetic analysis of multiple tissues in an affected fetus, and only the second report of prenatal diagnosis in SBMA.

Abortion, Induced↗
PubMed1998

[Method for measuring the comparative stability of osteosynthesis in the dorsal pelvic ring].

In the past, biomechanical investigations on the dorsal pelvic ring have generally been performed on a small number of cadaveric pelves in various non-standardized procedures. Significant differences in stability between different internal fixation methods of unstable pelvic ring fractures were not found. The experimental design presented here was based as closely as possible on the physiological loading of the pelvis in one-leg stance. This method made it possible to carry out standardized, reproducible tests on different osteosytheses of the sacroiliac joint. Furthermore, the suitability of artificial bones for such investigations can be assessed on the basis of a larger number of similar experiments on artificial and human pelves and the number of human pelves required for such studies could be reduced.

Biomechanical Phenomena↗