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Collagenous xenografts made from kangaroo tail tendon cross-linked with glutaraldehyde have a potential application in the reconstruction of massive digital tendon deficits. However, a limitation to the clinical use of these xenografts has been the optimization of collagen cross-linking, and subsequent bio-incorporation and retention of mechanical properties following implantation. The purpose of this study was to evaluate the effect of nitrous acid on modulating the biologic and mechanical properties of tendon xenografts cross-linked with glutaraldehyde. Tendon xenografts were pretreated with 0.1 or 0.01 M nitrous acid solution, prior to cross-linking in 2% glutaraldehyde and sterilization by gamma irradiation. Xenografts were implanted intramuscularly in rabbits to examine biocompatability, and also used to repair ovine digital extensor tendon deficits to evaluate functional incorporation. Histologically, intramuscularly implanted nitrous acid pretreated xenografts in rabbits had a greater degree of diffuse cellular infiltration into interstitial splits in the graft than controls after 12 weeks. Xenografts implanted in an ovine extensor tendon deficit were evaluated after 26 and 52 weeks. Rate of failure of tenorrhaphies between host tendon and xenografts overall (15/21) was significantly greater (P < 0.05) than for autografts (1/21), suggesting that the holding power of sutures in xenografts was inferior to that obtained in autografts. Tensile failure stress of midsections of both nitrous acid pretreated and control xenografts was about 100 MPa prior to implantation (time zero). After 26 and 52 weeks, failure stress of both types of xenografts was significantly less than at time zero (P < 0.05). At 52 weeks, failure stress of nitrous acid pretreated xenografts (47.4 ± 3.1 MPa) was significantly less than control xenografts (63.7 ± 5.4 MPa); (P < 0.05). However, nitrous acid pretreated xenografts were similar to control xenografts in failure load (357 ± 29 and 354 ± 26 N, respectively), but they tended to have larger cross-sectional areas (7.6 ± 0.5 versus 5.7 ± 0.6 mm2, respectively) which were responsible for the lower calculated value for failure stress. Histologically, autografts maintained their normal tissue architecture and evoked a more limited cellular response in surrounding tissues than xenografts (P < 0.05). Both types of xenograft were surrounded by a thicker cuff of cellular response than autografts. However, compared to control xenografts, nitrous acid pretreated xenografts had more extensive fragmentation and splitting of collagen bundles, and more diffuse cellular and vascular infiltration into these interstitial splits, and these alterations were apparently contributing to the greater 'swelling' of these xenografts. It was concluded that pretreatment of tendon xenografts with nitrous acid modulated their biologic and material properties. Further studies are needed to elucidate the mechanism of these effects, and to determine if the protocol for tendon xenograft preparation could be optimized for improved clinical performance.

Resorbable (poly-L-lactide) and non-resorbable (polyethylene terephathalate) tendon augmentation devices (TAD) in conjunction with a pericardial adhesion barrier are designed to strengthen tenorrhaphies and are evaluated in an ovine extensor tendon deficit model in a short term study. Fifteen centimeters of tendon were resected and replaced with kangaroo tail tendon xenografts that had been cross-linked with 0.075 percent glutaraldehyde (GA) at a certain temperature for one or seven days. Compared with tenorrhaphies performed with Kesler sutures alone, both types of TAD were more effective at preventing tenorrhaphy dehiscence, and thus maintaining tendon function. The increase in tensile strength of TAD tenorrhaphies were also noted. Evaluation of the performance of tenorrhaphy augmentation devices with xenografts is required to further understand their usefulness for reconstruction of traumatic tendon injuries.

Plasma exchange (PE) and ex vivo immunoadsorption (IA) may be applicable to the removal of anti-insulin antibodies (AI-Ab) from diabetic patients. However, the removal of antibodies may prompt an increase in their rate of synthesis and an overshoot of antibody levels which may be deleterious to the patient. The effects of both PE and IA on AI-Ab synthesis were studied in a rabbit model. Rabbits were immunized with insulin and the resulting AI-Abs removed by both plasma exchange and specific immunoadsorption. Following AI-Ab removal by PE no increase in AI-Ab synthesis or antibody overshoot occurred. However a large increase in AI-Ab synthesis and overshoot occurred following specific AI-Ab removal by immunoadsorption. Despite similar reductions in AI-Ab levels by PE and IA, no increase in antibody synthesis occurred due solely to antibody removal. It is likely that antigen released from the immunoadsorbent stimulated the increase in antibody synthesis following immunoadsorption. These findings are relevant to the clinical application of both PE and IA.

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.

Plasma exchange therapy is currently used to remove antibody from the circulation in a number of autoimmune diseases. It has been suggested that the decrease in antibody level may affect synthesis rate by the removal of inhibitory feedback. This would then cause a rapid rise in antibody levels to or beyond those prior to depletion. Based on this supposition immunosuppression is nearly always used concomitantly with plasma exchange to prevent the expected increase in synthesis rates. An assessment of the effect of specific antibody removal by immunoadsorption on synthesis and catabolic rates was undertaken to clarify the nature of the response. Rabbits were immunized to bovine serum albumin (BSA) injected with 125I-anti-BSA IgG and later underwent extracorporeal immunoadsorption with BSA-Sepharose. At least 60% of circulating anti-BSA-IgG was removed. Mathematical analysis of 125I-anti-BSA IgG and anti-BSA-IgG levels demonstrated a reduction in catabolic clearance following immunoadsorption. Conversely synthesis rate was not altered. No significant overshoot of anti-BSA-IgG beyond pre-removal levels occurred. Based on these findings it is postulated that an increase in antibody synthesis does not generally occur following plasma exchange. The rise in antibody levels seen following plasma exchange probably reflect a reduction of catabolism combined with an unchanged rate of synthesis.

In order to overcome the continuing infection rate associated with biomaterials, the use of covalently bound furanones as an antibiofilm coating for biomaterials has been investigated. Furanones have previously been shown to inhibit growth of Gram-positive and Gram-negative bacteria. The aim of these studies were to covalently bind furanones to polymers and to test their efficacy for inhibiting biofilm formation of Staphylococcus epidermidis and in vivo infection rate. Two methods of covalent attachment of furanones were used. The first, a co-polymerisation with a styrene polymer, and second, a plasma-1-ethyl-3-(dimethylaminopropyl) carbodiimide (EDC) reaction to produce furanone-coated catheters. Biofilm formation by S. epidermidis in vitro was inhibited by 89% for polystryene-furanone disks and by 78% by furanone-coated catheters (p