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Biomedical subjects

E Schneider

Publications and source records attributed to E Schneider.

At least 19 recordsLinked to original sources
PubMed2006

Osseointegration of hollow cylinder based spinal implants in normal and osteoporotic vertebrae: a sheep study.

INTRODUCTION: Osteoporosis is not only responsible for an increased number of metaphyseal and spinal fractures but it also complicates their treatment. To prevent the initial loosening, we developed a new implant with an enlarged implant/bone interface based on the concept of perforated, hollow cylinders. We evaluated whether osseointegration of a hollow cylinder based implant takes place in normal or osteoporotic bone of sheep under functional loading conditions during anterior stabilization of the lumbar spine. MATERIALS AND METHODS: Osseointegration of the cylinders and status of the fused segments (ventral corpectomy, replacement with iliac strut, and fixation with testing implant) were investigated in six osteoporotic (age 6.9 +/- 0.8 years, mean body weight 61.1 +/- 5.2 kg) and seven control sheep (age 6.1 +/- 0.2 years, mean body weight 64.9 +/- 5.7 kg). Osteoporosis was introduced using a combination protocol of ovariectomy, high-dose prednisone, calcium and phosphor reduced diet and movement restriction. Osseointegration was quantified using fluorescence and conventional histology; fusion status was determined using biomechanical testing of the stabilized segment in a six-degree-of-freedom loading device as well as with radiological and histological staging. RESULTS: Intact bone trabeculae were found in 70% of all perforations without differences between the two groups (P = 0.26). Inside the cylinders, bone volume/total volume was significantly higher than in the control vertebra (50 +/- 16 vs. 28 +/- 13%) of the same animal (P<0.01), but significantly less (P<0.01) than in the near surrounding (60 +/- 21%). After biomechanical testing as described in Sect. "Materials and methods", seven spines (three healthy and four osteoporotic) were classified as completely fused and six (four healthy and two osteoporotic) as not fused after a 4-month observation time. All endplates were bridged with intact trabeculae in the histological slices. CONCLUSIONS: The high number of perforations, filled with intact trabeculae, indicates an adequate fixation; bridging trabeculae between adjacent endplates and tricortical iliac struts in all vertebrae indicates that the anchorage is adequate to promote fusion in this animal model, even in the osteoporotic sheep.

Animals↗
PubMed2006

Mechanical performance of cylindrical and dual core pedicle screws in calf and human vertebrae.

INTRODUCTION: Failure of pedicle screws by loosening and back out remains a significant clinical problem. Pedicle screw fixation is determined by bone mineral density, pedicle morphology and screw design. The objective of this study was to compare the holding strength of newly developed dual core pedicle screws having a cylindrical design in terms of outer diameter and two cylindrical inner core regions connected by a conical transition with conventional cylindrical pedicle screws. MATERIALS AND METHODS: Fifty bovine lumbar vertebrae and 40 human lumbar vertebrae were used. Five different screws were tested in nine experimental "settings" and ten specimens each. The screws were tested for cranial displacement and pullout strength before and after 5,000 cycles of cranio-caudal loading. The tests included a setting with fully inserted and 4 mm backed out screws. For statistical analysis the incomplete balanced block design was used. RESULTS: Cyclic loading led to a decrease of pullout force between 24 and 31% and a 9% increase of displacement. The cylindrical screw designs were affected more than the dual core designs. The pullout force of cylindrical screws was smaller than of dual core screws. Even in a backed out condition dual core screws showed a significantly smaller displacement than cylindrical screws. CONCLUSION: Pedicle screws with the dual core design provide good anchorage in the vertebra.

Animals↗
PubMed2006

Cognition and motor control as a function of Delta9-THC concentration in serum and oral fluid: limits of impairment.

Cannabis use has been associated with increased risk of becoming involved in traffic accidents; however, the relation between THC concentration and driver impairment is relatively obscure. The present study was designed to define performance impairment as a function of THC in serum and oral fluid in order to provide a scientific framework to the development of per se limits for driving under the influence of cannabis. Twenty recreational users of cannabis participated in a double-blind, placebo-controlled, three-way cross-over study. Subjects were administered single doses of 0, 250 and 500 microg/kg THC by smoking. Performance tests measuring skills related to driving were conducted at regular intervals between 15 min and 6h post smoking and included measures of perceptual-motor control (Critical tracking task), motor impulsivity (Stop signal task) and cognitive function (Tower of London). Blood and oral fluid were collected throughout testing. Results showed a strong and linear relation between THC in serum and oral fluid. Linear relations between magnitude of performance impairment and THC in oral fluid and serum, however, were low. A more promising way to define threshold levels of impairment was found by comparing the proportion of observations showing impairment or no impairment as a function of THC concentration. The proportion of observations showing impairment progressively increased as a function of serum THC in every task. Binomial tests showed an initial and significant shift toward impairment in the Critical tracking task for serum THC concentrations between 2 and 5 ng/ml. At concentrations between 5 and 10 ng/ml approximately 75-90% of the observations were indicative of significant impairment in every performance test. At THC concentrations >30 ng/ml the proportion of observations indicative of significant impairment increased to a full 100% in every performance tests. It is concluded that serum THC concentrations between 2 and 5 ng/ml establish the lower and upper range of a THC limit for impairment.

Adult↗
PubMed2006

Effect of BMP-2 gene transfer on bone healing in sheep.

Critical size defects of bone and delayed fracture healing due to metabolic disorders are still problems in orthopaedic surgery. Adenoviral vectors encoding bone morphogenetic protein-2 (Ad.BMP-2) have been used to stimulate bone formation in small animals. The present study evaluated the use of direct adenoviral gene transfer for inducing bone formation in a large animal. Standardized iliac crest defects were created surgically on both sides of the pelvic bone of white mountain sheep. The efficiency of gene transfer was evaluated using recombinant adenoviruses carrying the cDNA for luciferase. High levels of transgene expression, restricted to the site of injection, were found for the 1st week. Transgene expression then fell considerably, but could still be detected for up to 5 weeks. To investigate the effect on bone healing, Ad.BMP-2 (10(11) particles in 200 mul saline) was unilaterally injected into iliac crest defects and into tibial osteotomies. The contralateral defects remained untreated to evaluate possible systemic effects. The controls were treated with saline solution. Bone formation within the defect, assessed by micro-computed tomography (CT) measurement at 8 weeks, and callus formation after osteotomy were significantly reduced following direct application of Ad.BMP-2. The retardation compared to untreated control animals was additionally found at the contralateral iliac crest indicating a systemic inhibitory effect. Histological analysis confirmed the CT measurement and showed an increased number of inflammatory cells within both defects. Antibodies against the adenovirus and the transgene product were detected in all treated animals. These data show a systemic retardation of bone formation following a single local injection of Ad.BMP-2 in sheep. This finding stands in contrast to the data obtained from small animal models. Further studies are needed to determine the contribution of the immune response to these results, and whether a lower dose of Ad.BMP-2 would be advantageous.

Adenoviridae↗
PubMed2006

Improved anchorage in osteoporotic vertebrae with new implant designs.

The goal of our study was to evaluate two newly developed implant designs and their behavior in terms of subsidence in lumbar vertebral bodies under cyclic loading. The new implants were evaluated in two different configurations (two small prototypes vs. one large prototype with similar load-bearing area) in comparison to a conventional screw-based implant (MACS TL). A pool of 13 spines with a total of 65 vertebrae was used to establish five testing groups of similar bone mineral density (BMD) distribution with eight lumbar vertebrae each. In additional to BMD assessment via dual-energy X-ray absorptiometry, cancellous BMD and structural parameters were determined using a new generation in vivo 3D-pQCT. The specimens were loaded sinusoidally in force control at 1 Hz for 1000 cycles at three load levels (100, 200, and 400 N). A survival analysis using the number of cycles until failure (Cox regression with covariates) was applied to reveal differences between implant groups. All new prototype configurations except the large cylinder survived significantly longer than the control group. The number of cycles until failure was significantly correlated with the structural parameter Tb.Sp. and similarly with the cancellous BMD for three of five implants. In both large prototypes the cycle number until failure significantly correlated with the preoperative distance to the upper endplates. Although the direct relationship between bone structure or density and mechanical breakage behavior cannot be conclusively proven, all the prototypes adapted for poor bone structure performed better than the comparable conventional implant.

Aged↗
PubMed2006

Development of testicular inflammation in the rat involves activation of proteinase-activated receptor-2.

Mast cells are involved in early events crucial to inflammation and autoimmune disease. Recently, proteinase-activated receptor-2 (PAR(2)), a G-protein coupled receptor important to injury responses, was shown to be activated by mast cell tryptase. To investigate whether mast cells and PAR(2) are involved in the development and/or aggravation of testicular inflammation, we studied acute and chronic inflammatory models in the rat. In normal testes, PAR(2) was detected immunohistochemically in macrophages, in peritubular cells (PTCs) and in spermatid acrosomes. In experimentally induced autoimmune orchitis (EAO), PAR(2) was strongly upregulated in macrophages and peritubular-like cells, forming concentric layers around granulomas. Mast cells increased 10-fold in number, were more widely distributed throughout the interstitial tissue, and were partially degranulated. Isolated PTCs expressed functional PAR(2), responded to PAR(2) activation by phosphorylating extracellular signal-regulated kinases 1/2 (ERK1/2) and activating protein kinase c, and increased intracellular Ca(2+) concentrations as well as monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta(2) (TGFbeta(2)), and cyclooxygenase-2 (COX-2) mRNA expression. Expression of these inflammatory mediators, together with iNOS, also increased significantly in testes 50 days after EAO. In vivo, expression of cytokines and inflammatory mediators was upregulated after injection of recombinant tryptase (MCP-1, TGFbeta(2), and COX-2) and a specific PAR(2) peptide agonist (MCP-1, TGFbeta(2)) in the testis after 5 h. These results suggest that PAR(2) activation elicited on PTCs by mast cell tryptase contributes to acute testicular inflammation and that this pathogenetic mechanism may also play a role in autoimmune orchitis.

Acute Disease↗
PubMed2006

[Progress in ambulatory anesthesia applied to gynecological surgery].

Ambulatory gynecological surgery enables fast recovery of vital functions, ambulation and a relational life of quality. Patients whose disease is well-controlled at the anesthesia consultation can benefit from ambulatory procedures. Improved material and surgical practices broaden potential indications, limiting the risk of postoperative pain which can be controlled with simple analgesic protocols. The choice of the anesthesic techniques or the agents used during the intervention ensures fast recovery of higher functions. Nausea and vomiting, which may develop after returning home and compromise oral drug intake, must be prevented. More ambulatory gynecological procedures can be expected in the near future, pointing out the importance of developing more adapted medical structures.

Ambulatory Surgical Procedures↗
PubMed2006

Direct adenoviral transfer of bone morphogenetic protein-2 cDNA enhances fracture healing in osteoporotic sheep.

Osteoporosis, a major public health burden, is associated with increased fracture risk. Fracture healing in osteoporosis is delayed, with reduced callus formation and impaired biomechanical properties of newly formed bone leading to high risk of fixation failure. Adenoviral gene transfer of bone morphogenetic protein-2 (BMP-2) has been shown to enhance fracture healing. This study evaluated the ability of gene transfer to enhance bone healing in osteoporosis. An established sheep model of osteoporosis with well-characterized alterations in fracture healing was used. Osteotomies were created surgically in the tibias of adult female sheep and monitored for 8 weeks, using radiographic, biomechanical, and histological methods. For pilot experiments, primary ovine osteoblasts and mesenchymal stem cells were transduced with a recombinant adenovirus carrying BMP-2 cDNA (Ad.BMP-2). Large increases in alkaline phosphatase production and mineralization confirmed the ability of human BMP-2 to stimulate osteoblastic differentiation in sheep. In vivo bending stiffness measurements during fracture healing as well as ex vivo torsional stiffness measurements demonstrated stiffer callus tissue after treatment with Ad.BMP-2. The differences were found mainly in the early fracture-healing period. Computed tomography demonstrated that animals receiving the BMP-2 cDNA had larger cross-sectional callus area and higher callus density. Histological examination of the tibias confirmed enhanced callus formation. Direct, local adenoviral delivery of an osteogenic gene thus led to enhanced healing of fractures in an ovine model of osteoporosis. These promising data encourage the further development of genetic approaches to enhance bone healing in patients suffering osteoporosis-associated fractures.

Adenoviridae↗
PubMed2006

Shear does not necessarily inhibit bone healing.

Interfragmentary shear has been perceived as inhibitory to bone healing. We think this is because of inadequate balance between stimulatory and disruptive interfragmentary displacement magnitudes in the shear direction. We hypothesized that pure shear is not necessarily detrimental to bone healing. This was investigated by comparing bone healing under interfragmentary torsional shear, axial compression, and no applied motion. Applied motion was controlled carefully with similar interfragmentary principal strain magnitudes found to stimulate healing under axial compression. The observation period was 8 weeks. Torsional rotation stimulated intercortical mineralized callus formation with greater area than the group without applied motion, and led to a stiffness and rate of bony bridging similar to that of the no motion group. Axial compression stimulated less intercortical mineralized callus of a lower density than the no motion group, and there also was little bridging. These results support the hypothesis that interfragmentary shear does not necessarily inhibit bone healing.

Animals↗
PubMed2006

Comparison of tolerance of facemask vs. mouthpiece for non-invasive ventilation.

This prospective, single centre, randomised, cross-over study compares patient tolerance of the facemask and mouthpiece for delivery of non-invasive ventilation in an intensive care unit. Twenty-seven patients with acute respiratory failure were scheduled for two 45-min sessions of non-invasive ventilation with facemask and mouthpiece. The order of the sessions was chosen at random. Nurses and patients assessed the tolerance of both techniques using a visual analogue scale. The time spent by nurses and the changes in respiratory parameters were recorded. The facemask was better tolerated than the mouthpiece; all the cases of non-invasive ventilation withdrawal (n = 5) occurred with mouthpieces (p = 0.026). Less nursing time was required using the facemask for the 22 patients who underwent both procedures (p = 0.01). However, the difference in tolerance scores was not significant. Non-invasive ventilation with both facemask and mouthpiece improved the P(a)o(2)/F(i)o(2) ratio, increased the pH and decreased the P(a)co(2). Only non-invasive ventilation with the facemask lowered the respiratory rate. The facemask appears to be a better initial choice for non-invasive ventilation when compared to mouthpiece, but both can be effective.

Adult↗
PubMed2006

Magnetic resonance spectroscopy for measuring the biodistribution and in situ in vivo pharmacokinetics of fluorinated compounds: validation using an investigation of liver and heart disposition of tecastemizole.

BACKGROUND AND OBJECTIVE: The study of biodistribution and in situ pharmacokinetics is a challenging, but sometimes very important, aspect of premarketing characterization of drugs. We aimed to develop a non-invasive fluorine magnetic resonance (MR) spectroscopic method for the absolute quantitation of a mono-fluorinated compound and of its metabolites in the heart and liver of healthy subjects for this purpose. METHOD: We used fluorine MR spectroscopy (MRS) at 4 T (Tesla) and external standardization in an open label multiple-dose study. Twenty-three healthy adult subjects were enrolled in the study. The surface coil localized fluorine MR spectrum was monitored in the heart and liver at baseline and after oral administration of multiple doses of tecastemizole. Steady-state measurements were made at set time points that depended upon dose, and washout measurements were made only on subjects in which in vivo fluorine signal was observed. RESULTS AND DISCUSSION: At 4 T, under the given experimental conditions, the method had a lower limit of quantitation (LLOQ) of about 2.6 microm and a limit of detection (LOD) of about 0.3 microm for solution state samples (linewidth approximately 15 Hz). The measurement reproducibility was 6.4% using a 50 microm phantom. The effect of MR operator and spectral analyst on the calculated calibration curve slope was small, with inter-rater correlation coefficients of 0.999 and 0.998 respectively. MR signal from fluorine-containing tecastemizole-related moieties was observed in situ only at day 8 in the liver of three of five subjects dosed at 270 mg/day. The average in situ concentration was estimated to be 58+/-22 microm, with an average test-retest reproducibility of 216%. Extrapolating the in vitro results to human measurements, with an approximate linewidth of 250 Hz, predicts in situ LOD and LLOQ values of approximately 6 and 44 microm respectively. However, the human study had a fluorine MRS LOD of approximately 20 microm. The decrease in sensitivity and the increase in variability of the in vivo, in situ measurements compared with the validation study most likely arose from coil placement and incomplete rephasing of the MR signal by the respiratory phase compensation method. CONCLUSION: The measured concentrations were the lowest ever recorded for a multi-dose exogenous mono-fluorinated compound in the human liver using a validated fluorine MR quantitation method. The proposed non-invasive MR method for studying the biodistribution and in situ pharmacokinetics of mono-fluorinated compounds in the liver and heart should have broader application to the development of non-invasive biomarkers.

Adult↗
PubMed2006

Principles of fixation of osteoporotic fractures.

Despite advances in the prevention and treatment of osteoporotic fractures, their prevalence continues to increase. Their operative treatment remains a challenge for the surgeon, often with unpredictable outcomes. This review highlights the current aspects of management of these fractures and focuses on advances in implant design and surgical technique.

Algorithms↗
PubMed2005

Double echo steady state magnetic resonance imaging of knee articular cartilage at 3 Tesla: a pilot study for the Osteoarthritis Initiative.

BACKGROUND: Quantitative magnetic resonance imaging (qMRI) may provide valuable measures of cartilage morphology in osteoarthritis (OA) but has been confined to sequences with relatively long acquisition times at 1.5 Tesla (T). OBJECTIVE: To test the accuracy and precision of knee cartilage qMRI with a fast double echo, steady state (DESS) sequence with water excitation (we) at 3 T. METHODS: As a pilot study for the Osteoarthritis Initiative, test-retest MR images were acquired in the knees of 19 participants with no OA to moderate degrees of clinical OA. Two double oblique coronal fast low angle shot (FLASHwe) sequences (1.5 mm slice thickness) were acquired at 3 T, and two sagittal DESSwe sequences (0.7 mm slice thickness). Double oblique coronal multiplanar reformats (MPR) were performed (1.5 mm slice thickness) from the sagittal DESSwe. Knee joint cartilage plates were quantified unpaired in random order with blinding to subject identification. RESULTS: In the femorotibial joint, precision errors (root mean square coefficient of variation in % for unpaired analysis) for cartilage volume and thickness were 3.0-6.4% with coronal FLASHwe, 2.4-6.2% with coronal MPR DESSwe, and 2.3-8.2% with sagittal DESSwe. Correlation coefficients between DESSwe and FLASHwe ranged from r = 0.88 to 1.0. In the femoropatellar joint, precision errors (sagittal DESSwe) were 3.4-8.5%. CONCLUSIONS: DESSwe permits accurate and precise analysis of cartilage morphology in the femorotibial joint at 3 T. Further studies are needed to examine the accuracy of DESSwe in the femoropatellar joint and its ability to characterise sensitivity to longitudinal changes in cartilage morphology.

Adult↗
PubMed2005

How the eyes move the body.

The increased postural sway of patients with disorders of the vestibular system improves with vision. The suppression of pathologic nystagmus also reduces sway. Because the latter effect cannot be attributed to retinal slip as a relevant feedback for postural control, the authors investigated how eye movements rather than retinal slip affect balance. They found that slow eye movements increase sway, possibly by an efference copy, which explains why spontaneous nystagmus causes postural imbalance.

Adult↗
PubMed2005

Significance of osteoporosis in craniomaxillofacial surgery: a review of the literature.

Osteoporosis is a common problem in orthopedic surgery. The purpose of this review of the literature was to examine whether osteoporosis is also an important factor in patient treatment in the field of craniomaxillofacial surgery. Emphasis was given to the consequences of osteoporosis for the maxilla and mandible, the influence of osteoporosis on fracture treatment, the use of dental implants, the importance of soft tissues and the effect of osteoporosis therapies. It was found that osteoporosis does affect the bones of the skull. The effect of osteoporosis on treatment, however, is controversial and necessitates better ways of quantifying bone loss. Large inter-individual and site-specific differences in bone density, as well as other effects such as removal of teeth, periodontitis, implant insertion, augmentation procedures and altered loading with dystrophic consequences need to be considered in future studies. Special attention should be given to osteoporosis during fracture treatment.

Alveolar Bone Loss↗
PubMed2005

Animal models for fracture treatment in osteoporosis.

Demographic changes in the age structure of occidental populations are giving rise to osteoporosis and associated fractures, which are becoming a major public health burden. Various animal models have been established and used to investigate the pathogenesis of osteoporosis and to facilitate the preclinical testing of new treatment options such as antiresorptive drugs. Although osteoporosis can be induced in animals, spontaneous fractures without adequate trauma were only found in nonhuman primates. An animal model designed to investigate new ways to treat fractures of osteoporotic bone has to fulfill requirements that are very different from those of pharmacological testing. The aspects of major interest in orthopedic applications are bone fragility, efficacy of implant fixation and bone healing. Existing animal models for osteoporosis were critically reviewed focusing on these aspects. The advantages and disadvantages of the models with regard to their application in the testing of new fracture-fixation devices or biological approaches to stimulate bone healing are discussed. Ovariectomy alone does not cause the bone loss seen in osteoporotic human patients. New models to simulate fracture of osteoporotic bone need to be explored and used to address the specific aims of an experiment.

Animals↗
PubMed2005

The potential of gene therapy for fracture healing in osteoporosis.

Osteoporosis-associated fractures impair a patient's function and quality of life and represent one of the major public health burdens. Demographic changes predict a dramatic increase in osteoporotic fractures. Experimental data have shown that osteoporosis impairs fracture healing. Clinical observations demonstrate high failure rates of implant fixation in osteoporosis. The reduced healing capacity, including impaired bone formation, in osteoporotic humans might be due to defects in mesenchymal stem cells that lead to reduced proliferation and osteoblastic differentiation. Growth factors show remarkable promise as agents that can improve the healing of bone or increase the proliferation and differentiation capacities of mesenchymal stem cells. Their clinical utility is limited by delivery problems. The attraction of gene-transfer approaches is the unique ability to deliver authentically processed gene products to precise anatomical locations at therapeutic levels for sustained periods of time. Unlike the treatment of chronic diseases, it is neither necessary nor desirable for transgene expression to persist beyond the few weeks or months needed to achieve healing. This review presents different approaches of gene therapy to enhance fracture healing and summarizes the promising results of preclinical studies. It focuses on applications of this new technique to fracture healing in osteoporosis. In our opinion, these applications represent some of the few examples in which gene therapy has a good chance of early clinical success.

Adenoviridae↗