Biomedical subjects

K Schindhelm

Publications and source records attributed to K Schindhelm.

At least 37 records · Page 2Linked to original sources

PubMed1995

Shielding of augmented tendon--tendon repair.

Strength and function of autogenic and xenogenic reconstruction of digital extensor tendons was examined in an ovine model. In this study, tendon-graft junctions were formed by either suture augmented with a woven polyester tube (A), or augmented and shielded from surrounding tissues by chemically-treated bovine pericardium (S). By 12 wk, both A and S sheep had returned to full range of motion. Mechanical strength of both the autograft-host and xenograft-host repair sites was similar, with a pooled strength of 131 +/- 25 N (n = 15). Similarly, the mid-portion xenograft strengths were constant at approximately 366 +/- 97 N (n = 7). In contrast, mid-portion autograft strengths decreased from 380 +/- 110 N (N = 4) to 120 +/- 66 N (n = 4) if shielding was omitted. The loss in autograft strength was attributed to loss of function associated with adhesions. The use of the augmentation device coupled with an adhesion barrier gives higher initial reconstruction strength and improved function during the host repair period up to 12 wk.

Animals↗

PubMed1994

An experimental model of affinity cell separation.

Cell affinity separations are based on the selective attachment of cell phenotype using antibody or lectins specific for cell surface markers. The major physicochemical factors which influence ligand-mediated cell adhesion dynamics and the efficiency of cell affinity separation have been examined. Uniform cell detachment forces were generated with a parallel-plate flow cell (plate separation 100 microns, surface area 3 cm2). Hydrodynamic shear stress was used to measure cell adhesion strength and to separate cells on the basis of surface affinity. Human cell lines grown in tissue culture were separated on a flat derivatised glass immunoadsorbent which formed the floor of the flow chamber. Flow-cell residence time, detachment shear stress, temperature, and ligand density were shown to influence cell attachment probability. An understanding of the physical basis of ligand-mediated cell adhesion provided a rationale for optimisation of affinity cell separation. At room temperature attachment of positive cells was rapid (< 2 min) and adhesion strength was directly related to immunoadsorbent ligand density. Purity and recovery of enriched fractions were dependent on the separation shear stress and could be optimised using this parameter. Enrichment factors were greater than 100-fold, with at least 90% of positive cells recovered in enriched fractions. Enrichment purity and yields did not decline at higher loading densities (10(5) cells/cm2). Selective immunoadsorbent surface chemistry is a prerequisite for efficient affinity cell separation. Purity and recovery may be optimised by fractionating enriched and depleted cell populations with uniform fluid shear stress.

Antibody Affinity↗

PubMed1994

In vivo evaluation of polyurethanes based on novel macrodiols and MDI.

A series of novel polyurethane elastomers based on methylenediphenyl diisocyanate, 1,4-butanediol and the macrodiols, poly(hexamethylene oxide), poly(octamethylene oxide), and poly(decamethylene oxide) were implanted subcutaneously in sheep for periods of 3 and 6 months. The specimens that were subjected to 3 months of implantation were strained to 250% of their resting length, while those implanted for 6 months had no applied external strain. SEM examination of the explanted specimens revealed that the novel materials displayed resistance to environmental stress cracking. Proprietary materials, Pellethane 2363-80A, Biomer and Tecoflex EG-80A, which had been implanted under identical conditions, showed evidence of significant stress cracking. The extent of stress cracking in the 3-month strained experiment was similar to that from the 6-month unstrained experiment. Stress cracking was also observed in Pellethane 2363-55D, when implanted for 6 months (unstrained). Neither changes in molecular weight nor in tensile properties provided a clear indication of early susceptibility to degradation by environmental stress cracking.

Animals↗

PubMed1993

Degradation of medical-grade polyurethane elastomers: the effect of hydrogen peroxide in vitro.

Treatment of Pellethane 2363-80A--a medical-grade poly(tetramethylene oxide)-based polyurethane elastomer--with 25% (w/w) hydrogen peroxide at 100 degrees C for times ranging from 24 h to 336 h led to significant decreases in ultimate tensile properties and decreases in molecular weight, both at the surface and in the bulk. IR spectral changes were similar to those observed after degradation in vivo. Differential scanning calorimetry showed that hydrogen-peroxide-induced degradation was associated with greater order in the hard domain and greater mobility in the soft domain. Studies conducted with low-molecular-weight model compounds for the hard and soft segments confirmed that methylene groups adjacent to oxygen were susceptible toward oxidation. The extent of degradation of a series of commercial polyurethanes on treatment with hydrogen peroxide (25%, 24 h, 100 degrees C) correlated well with their reported susceptibility to environmental stress cracking in vivo.

Hydrogen Peroxide↗

PubMed1992

Phagocytosis of carbon particles by macrophages in vitro.

Particles of known size ranges of carbon fibre-reinforced carbon were presented to in vitro cultures of murine macrophages. Particles of up to 20 microns diameter were phagocytosed. Larger particles were not phagocytosed but became surrounded by aggregations of macrophages, some of which migrated on to the particle surfaces. Mean rates of phagocytosis up to 2.5 particles per hour were observed. Cells presented with a large excess of particles became rounded, detached from the substrate and some underwent lysis. The implications of these findings for the fate of particulates released from implanted medical devices is discussed. It is argued that a mechanism exists where particles in the size range 8-20 microns, released from medical devices, are small enough to be phagocytosed by macrophages and transported to the lymphatics and subsequently to the vascular circulation but large enough to lodge in capillary beds of tissues remote from the implant site.

Animals↗

PubMed1992

The effect of gamma irradiation on a xenograft tendon bioprosthesis.

Radiation sterilisation of xenograft prostheses has been shown to cause damage to the material. Such damage has been imputed to affect the mechanical and biological properties and may contribute to long-term failure. This study has examined the effect of 25 kGy (2.5 Mrad) of gamma radiation on the mechanical and physicochemical properties and the biological function of a xenograft tendon bioprosthesis derived from glutaraldehyde cross-linked kangaroo tail tendon. The ultimate tensile stress of nonirradiated glutaraldehyde cross-linked tendon was greater than that of fresh frozen tendon, but irradiated cross-linked tendon did not differ. Irradiation did not alter the response to prolonged collagenase exposure. There was a decrease in overall apparent cross-link density (as determined by thermal denaturation temperature). After 12 months implantation, there was a slightly more active cellular response around irradiated tendon and the very peripheral fibres were infiltrated, but the mechanical properties of the retrieved implants were the same for irradiated and nonirradiated material. Gamma irradiation would appear to be a satisfactory method of sterilisation for glutaraldehyde cross-linked tendon materials. However, as damage to the cross-linked structure was detected in this study, it may not be appropriate in other applications.

Animals↗

PubMed1992

In vivo patency of endothelial cell-lined expanded polytetrafluoroethylene prostheses in an ovine model.

The performance of small-diameter vascular prostheses may be improved by implantation of grafts lined with endothelial cells. Expanded polytetrafluoroethylene (ePTFE) prostheses (4 mm x 40 mm) were coated with fibronectin (20 micrograms/ml), seeded with endothelial cells, and cultured for 48 h to produce a confluent, autologous endothelial cell lining. They were implanted as carotid interposition grafts in sheep. Seeded ePTFE grafts were compared with nonseeded ePTFE grafts and autologous carotid artery grafts. No anticoagulant or antiplatelet therapy was administered, making this a stringent test model for the thromboresistance of a small-diameter prosthesis. After 13 weeks the patencies of seeded, nonseeded, and autologous artery grafts were 16% (1/6), 0% (0/6), and 100% (6/6), respectively. The one seeded graft that was patent was fully lined with endothelial cells and showed no stenosis. The remaining five seeded grafts were occluded by fibrous tissue and displayed substantial spindle cell hyperplasia. There was no apparent difference between the autologous artery grafts and normal arterial tissue, and the anastomoses showed no stenosis. The ovine model provides a conservative test of prosthesis survival and may be useful for study of graft failure.

Anastomosis, Surgical↗

PubMed1991

Treated xenografts as gliding tendon prostheses in an ovine model.

A model for testing the properties of gliding tendon grafts has been developed that allows anastomoses to be evaluated separately from the mid-portion of the graft. In addition, two different graft materials may be implanted in one sheep foreleg whilst maintaining control (not operated) tendons in both the operated leg and contralateral foreleg. The model has been used to evaluate the response of xenografts made from chemically treated kangaroo tail tendon (KTT) compared with autografts. At 3 month the mid-sections of the glutaraldehyde-fixed xenografts maintained between 57 and 82% of their initial ultimate tensile strength whereas lyophilized KTT dropped to 10% and autografts retained 91% of initial strength. Sterilization by gamma-radiation of wet xenografts did not affect the material and implant properties significantly. Longer term studies are necessary to determine the resorption behaviour of the xenografts. Anastomosis strengths were found to be about the same for all grafts, at about 25% of the strength of the original tendon. Alternatives need to be investigated to improve this strength.

Anastomosis, Surgical↗

PubMed1991

Comparative evaluation of treated bovine pericardium as a xenograft for hernia repair.

Two forms of bovine pericardium (BPC) were assessed as hernia repair materials: non-cross-linked (lyophilized) and cross-linked through treatment with glutaraldehyde (GA). These were compared with polypropylene mesh (Marlex) in a rabbit model. Over 52 wk implantation, the GA BPC grafts developed a strong, stable, fibrous tissue replacement with good incorporation into the abdominal muscle wall. The lyophilized BPC grafts were substantially resorbed within 12 wk of implantation, however the thin, fibrous replacement tissue was inadequate for abdominal wall support. Marlex grafts provided sufficient abdominal support, however these grafts were associated with extensive adhesion formation and, in this model, fat deposition around the perimeter of the graft. Control (ungrafted) rabbit abdominal muscle in the transverse orientation had an ultimate tensile load (UTL) of 11.4 +/- 5.1 N (x +/- s.d.) and a strain at UTL of 35 +/- 12% (n = 169). At 52 weeks the UTL of the repair sites was 7.3 +/- 4.5 N (n = 6), 5.1 +/- 3.5 N (n = 6) and 5.6 +/- 2.7 N (n = 6) for GA BPC, lypophilized BPC and Marlex grafts, respectively.

Animals↗

PubMed1991

Beta 2-microglobulin kinetics in end-stage renal failure.

The kinetics of beta 2-microglobulin (beta 2m) were studied in five anephric or anuric hemodialysis patients. Human beta 2m was isolated from peritoneal dialysate using ion-exchange and gel chromatography and radiolabeled with 125I. Patients were injected with 10 microCi labeled beta 2m. In one study (N = 4), plasma activity was measured over 72 hours. In a second study (N = 4), patients received low-flux dialysis 24 hours after injection and high-clearance dialysis (Bellco BL655) at 48 hours. Plasma activities were fitted to a three-compartment, variable volume model. Endogenous beta 2m levels (radioimmunoassay) were 56 +/- 6 mg/liter. The beta 2m distribution volume was 12.7 +/- 2.0 liter (0.20 +/- 0.03 liter/kg) and the non-renal clearance was 3.0 +/- 0.4 ml/min. The generation rate, 9.9 +/- 1.7 mg/hr (0.16 +/- 0.04 mg/kg/hr), was similar to that measured in subjects with normal renal function. The three compartment model derived from the turnover data gave an adequate fit of the arterial concentrations of endogenous and exogenous beta 2m during low-flux (nil beta 2m clearance) and high-clearance (beta 2m clearance of 19 ml/min) dialysis. Simulations based on this model indicate that extracorporeal treatment can at best remove about 50% of weekly production. These results suggest that beta 2m production is not increased in dialysis patients, that there is substantial non-renal beta 2m clearance, and that the amount of beta 2m that can be removed by extracorporeal therapy is therefore limited.

Adult↗

PubMed1991

Autograft and Leeds-Keio reconstructions of the ovine anterior cruciate ligament.

This study compared the Leeds-Keio prosthesis with grafting of autogeneic patellar tendon for the reconstruction of the ovine anterior cruciate ligament under controlled conditions. Reconstructed knees from six sheep of each group were evaluated at 12, 26, and 52 weeks postreconstruction with respect to clinical assessment, gross pathology, mechanical properties, and histology. Although no difference in clinical assessment (anteroposterior draw, range of motion, and function) was noted between the prosthesis reconstruction and the autograft reconstruction, the prosthesis provided a higher strength initially, which remained relatively constant over the one-year study. However, prosthesis wear was observed, with up to 50% of Dacron fibers ruptured in some cases. Histologic sections indicated that in the ovine model, the Leeds-Keio prosthesis should be considered an artificial device and not a scaffold or stent that supports aligned collagenous growth. The autograft had low strength at 12 weeks, which increased over the study period. Despite acceptable clinical performance and adequate mechanical properties up to one year postimplantation, neither reconstruction approached the clinical or mechanical performance of the normal anterior cruciate ligament in the ovine model.

Animals↗

PubMed1990

Measurement of the mechanical properties of the ovine anterior cruciate ligament bone-ligament-bone complex: a basis for prosthetic evaluation.

The reported ultimate tensile stress of the anterior cruciate ligament varies greatly, ranging from 13 to 147 MPa. This study shows that the orientation and degree of flexion of the bone-ligament-bone complex significantly alter the apparent ultimate tensile properties (ultimate tensile stress ranging from 60 +/- 3 to 123 +/- 15 MPa, ultimate specific extension from 37 +/- 7 to 93 +/- 20%), whilst the method chosen for measuring extension also affects the calculated specific extension of the bone-ligament-bone complex. It is suggested that, for considerations of prosthesis design and evaluation, the mechanical properties of the bone-ligament-bone complex should be measured in anterior draw and extension measured using points as close as possible to the positions of the ligamentous attachment sites.

Animals↗

PubMed1990

Endothelial cell seeding of small diameter vascular grafts.

This study examines, under flow conditions, the adhesion of endothelial cells to 3 mm diameter fibronectin (Fn)-coated expanded polytetrafluoroethylene (PTFE) vascular grafts. Cultured ovine carotid artery endothelial cells were labelled with 35S-methionine. The grafts were seeded with endothelial cells (1.5 x 10(6)/ml) by rolling for 1 h at 37 degrees C and then either cultured to confluence for 48 h or flow tested immediately. Cell attachment to grafts (n = 5) was evaluated in an in vitro flow circuit, using flows of up to 330 ml/min. Ex vivo studies (n = 5 grafts) were conducted without anticoagulant using autologous cells in a sheep model. Grafts were inserted into an externalized carotid-jugular shunt and exposed to blood flows of approximately 150 ml/min for 3 h. One hour seeded and 48 h cultured grafts demonstrated greater than 95% cell retention following in vitro flow studies. Ex vivo studies of 48 h cultured grafts gave endothelial cell retention of 81% with no sign of thrombogenicity. Furthermore, a preliminary 24 h ex vivo study has shown greater than 95% retention. This study demonstrates the firm attachment of seeded endothelial cells to Fn-coated PTFE grafts in the sheep model.

Animals↗

PubMed1990

Collagen cross-linking and resorption: effect of glutaraldehyde concentration.

Cross-linked collagen bioprostheses usually are designed to be inert and nonresorbable, resulting in fatigue and wear failure in high-stress environments. Eventual replacement of the implant, although minimizing strength loss during resorption, would result in a graft with reparative ability. Kangaroo tail tendon (KTT) partially cross-linked with glutaraldehyde (GA) was evaluated in vitro for resistance to bacterial collagenase digestion and in vivo for biocompatibility and resorbability in an intramuscular implant assay. Cross-linking was quantified by thermal denaturation studies. Incomplete cross-linking was achieved with concentrations of GA less than 0.1% (w/v). KTT cross-linked in greater than or equal to 0.05% GA were collagenase resistant being incompletely digested after 240 h. Cross-linking of KTT with low concentrations of GA resulted in partial collagenase resistance and slowed resorption.

Animals↗

PubMed1989

Transport and kinetics in synthetic and immunospecific adsorption columns.

Immunological or physicochemical adsorption can be used to remove specific proteins from plasma. The most common adsorption systems are based on the principle of affinity or adsorption chromatography. An adsorption column can be considered to be analogous to a packed bed, and transport is modeled by accounting for solute convection, accumulation, uptake, and axial dispersion within the bed. Adsorption kinetics and transport within particles of the packed bed need to be described. The solution of model equations is solute specific and generally requires numerical methods. The application of column adsorption systems to on-line therapeutic adsorption is constrained by flow considerations, which influence processing time; adsorbent capacity, which dictates column volume and hence design; and adsorbent stability, which may impact on patient safety.

Adsorption↗

PubMed1989

IgG immunoadsorption in experimental allergic neuritis: effect on antibody levels and clinical course.

The effect of IgG immunoadsorption upon the course of chronic experimental allergic neuritis (EAN) is described. Miniature membrane plasma separators coupled with a Protein A (PA)-Sepharose immunoadsorbent column were used to perform upon conscious rabbits 5 IgG immunoadsorption treatments over 6 days. Quantitation of anti-myelin IgG and IgM by ELISA revealed that 55-65% of plasma IgG was removed per treatment. Rapid post-treatment antibody rebound was observed for anti-myelin IgG although no antibody overshoot above control levels could be observed. Anti-myelin IgM levels remained relatively unaffected by PA immunoadsorption. Comparisons of clinical scores between control and treatment animals showed that IgG immunoadsorption was significantly beneficial (day 1 post-treatment p less than 0.001; day 2 post-treatment p less than 0.05). However, rapid relapse was observed in all treatment animals such that by day 3 post-treatment no significant clinical difference between control and treatment groups could be observed. IgG immunoadsorption suppresses the clinical progression of chronic EAN in a manner similar to that seen with plasma exchange. This finding suggests that antibody modulates early disease pathogenesis.

Animals↗

PubMed1989

Mixed-mode therapy: kinetic analysis and acute clinical evaluation.

A mixed therapeutic modality was devised in which patients with chronic renal failure were treated with a combination of continuous ambulatory peritoneal dialysis (CAPD; two daily 4-hour exchanges per day; 16 h dry belly) and hemodialysis (1 session per week). Kinetic modeling analysis indicated that a time-averaged urea concentration equivalent to CAPD could be obtained with a Kt/V value of 1.2-1.6, depending on patient parameters, for the single-weekly hemodialysis. The therapy format was acutely evaluated in a 2-week clinical trial on 4 patients. Excursions in small-solute concentration were virtually equivalent to those predicted from theory. Adequate fluid removal was obtained in the 2 CAPD exchanges and blood pressure was well controlled. As a result of the success of the acute trials, and since this format may offer potential lifestyle advantages to patients who possess dual access, a chronic trial of mixed-mode therapy seems advised.

Aged↗

PubMed1989

Experimental allergic neuritis: effect of plasma infusions.

The effect of intravenous fresh frozen plasma (FFP) and artificial plasma infusions upon the clinical course of chronic experimental allergic neuritis (EAN) in the rabbit was investigated. A total of 12 animals allocated to treatment groups received rabbit FFP or a gelatin plasma expander Haemaccel (Hoechst) and were compared to 13 control non-treated animals. Animals receiving Haemaccel at a rate of 15 ml/kg/day for 7 days showed no significant clinical benefit at any stage. However, animals receiving 15 ml/kg/day FFP for 8 days showed significant clinical benefit during treatment initiated at the onset of definite neurological symptoms of EAN (Mann-Whitney U test, day 4 post-allocation P less than 0.05; day 6 post-allocation P less than 0.01; day 8 post-allocation P less than 0.05). Relapse was observed after cessation of treatment such that comparisons of clinical scores at day 14 and 22 post-allocation revealed no significant differences. Analysis of plasma anti-myelin IgG levels by ELISA showed that non-immunogenic plasma volume expansion decreased anti-myelin IgG concentrations immediately by an average of 34% but had no long-term effect. In contrast, anti-myelin IgG concentrations in FFP infused animals were significantly decreased, compared to controls, when measured 24 h after the last infusion (Student's t-test P less than 0.05). Identical percentage weight losses for both control and treatment groups post-allocation indicated that this decrease was immunologically mediated and not due to plasma dilution. Similar plasma cortisol concentrations measured in both groups showed no significant artifactual induction of endogenous steroid production. Infusions of FFP during early disease progression are able to mediate clinical remission in animals with chronic EAN.

Animals↗