Long term outcomes of biomaterial-mediated repair of focal cartilage defects in a large animal model.

The repair of focal cartilage defects remains one of the foremost issues in the field of orthopaedics. Chondral defects may arise from a variety of joint pathologies and left untreated, will likely progress to osteoarthritis. Current repair techniques, such as microfracture, result in short-term clinical improvements but have poor long-term outcomes. Emerging scaffold-based repair strategies have reported superior outcomes compared to microfracture and motivate the development of new biomaterials for this purpose. In this study, unique composite implants consisting of a base porous reinforcing component (woven poly(ε-caprolactone)) infiltrated with 1 of 2 hydrogels (self-assembling peptide or thermo-gelling hyaluronan) or bone marrow aspirate were evaluated. The objective was to evaluate cartilage repair with composite scaffold treatment compared to the current standard of care (microfracture) in a translationally relevant large animal model, the Yucatan minipig. While many cartilage-repair studies have shown some success in vivo, most are short term and not clinically relevant. Informed by promising 6-week findings, a 12-month study was carried out and those results are presented here. To aid in comparisons across platforms, several structural and functionally relevant outcome measures were performed. Despite positive early findings, the long-term results indicated less than optimal structural and mechanical results with respect to cartilage repair, with all treatment groups performing worse than the standard of care. This study is important in that it brings much needed attention to the importance of performing translationally relevant long-term studies in an appropriate animal model when developing new clinical cartilage repair approaches.

Successful use of ReFacto continuous infusion in two paediatric patients with severe haemophilia A undergoing orthopaedic surgery.

In this report we describe the successful use of B-domain-deleted recombinant factor VIII (ReFacto) administered by continuous infusion during orthopaedic procedures in two children with severe haemophilia A. Both patients underwent ankle synovectomy and in patient 2, a medial patello-femoral ligament repair was performed in the same operative session. Patient 2 developed septic arthritis A in his knee joint and arthroscopic joint irrigation and debridement was performed 2 weeks after the initial procedure. Surgical cover was initiated with a bolus dose of ReFacto 50 IU kg(-1) followed by continuous infusion at 3.3-4.8 IU kg(-1) h(-1) which was maintained for up to 9 days postoperatively. Patient 2 received an additional bolus dose of 15 IU kg(-1) during the infusion period. All procedures were performed without haemostatic complications and long-term orthopaedic outcomes were good in both patients.

Differential scanning calorimetry of albumin solders: interspecies differences and fatty acid binding effects on protein denaturation.

BACKGROUND AND OBJECTIVE: Understanding albumin solder denaturation is important for laser tissue soldering. Human (HSA), bovine (BSA), porcine (PSA), and canine (CSA) albumin both fatty acid containing (FAC) and fatty acid free (FAF) were evaluated by using differential scanning calorimetry (DSC). STUDY DESIGN/MATERIALS AND METHODS: DSC was used to measure difference thermograms to determine the irreversible thermal denaturation profile for 50% albumin solutions. The denaturation transition's onset, end and peak temperatures, and enthalpy were measured. RESULTS: All FAC species, except BSA, exhibited twin peaked endotherms. Single endotherms were observed for all FAF species and BSA-FAC. Onset and end temperatures were significantly [P < 0.001] lower for all FAF species (except BSA's end temperature). There was a 30% decrease in the denaturation enthalpy between FAF and FAC groups. CONCLUSION: FAF albumin solders were found to denature at significantly lower temperatures, while also having a 30% reduction in enthalpy when compared with their FAC counterparts.

Laser-assisted demucosalized gastrocystoplasty with autoaugmentation in a canine model.

OBJECTIVES: Laser-assisted autoaugmentation gastrocystoplasty has been performed successfully. Experiments were performed to determine the optimal laser for tissue welding during demucosalized autoaugmentation gastrocystoplasty using both a 1.9-microm diode and a 1.32-microm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser with and without thermal control. METHODS: Autoaugmentation gastrocystoplasty was performed on 18 female mongrel dogs. Anastomoses were performed by either suture or laser welding with a 50% human albumin solution. A 1.9-microm diode laser was compared with a 1.32-microm Nd:YAG laser with and without thermal control. In vivo canine bladder capacity measurements were performed both before gastrocystoplasty and at euthanasia. The animals were studied on days 4 and 14. Samples of the anastomotic area from each group were taken to measure tensile strength. Histologic samples were assessed for tissue damage. RESULTS: There was a significant increase in bladder volume in the 4-day group compared with pregastrocystoplasty values. Both the 1.9-microm diode laser and suture control dogs with the 14-day repairs had significantly more tensile strength than their 4-day counterparts. In contrast, no statistical difference was found between the 4 and 14-day 1.32-microm Nd:YAG groups. The suture control group had evidence of minor tissue devitalization at the anastomosis at both 4 and 14 days. The 1.9 and 1.32-microm laser groups both had evidence of tissue devitalization at 4 and 14 days. The 1.32-microm laser group had primarily severe tissue injury. The laser groups at 14 days demonstrated an inflammatory reaction that was localized to the albumin. CONCLUSIONS: Demucosalized gastrocystoplasty with autoaugmentation can be safely and successfully performed with a 1.9-microm diode laser without significant differences in tensile strength when compared with suture controls. The 1.32-microm Nd:YAG laser can also be successfully used; however, the long-term results appear to be inferior to the 1.9-microm diode laser.

Treatment of thrombotic thrombocytopenic purpura. Plasmapheresis, plasma transfusion, and vincristine.

In four patients with thrombotic thrombocytopenic purpura (TTP), the administration of plasma exchange and vincristine sulfate was associated with reversal of clinical and hematologic evidence of disease. Plasmapheresis with fresh frozen plasma replacement appears effective in acutely improving neurologic and hematologic abnormalities of patients with TTP and provides time for vincristine to become effective and induce lasting remissions. One patient with early relapse responded to a second short course of vincristine without other therapy. These data suggest that these treatment modalities should be considered as the initial treatment of TTP.

Effect of local arterial hypotension on cat intestinal capillary permeability.

The effects of local arterial hypotension on lymph flow, lymphatic protein flux, and capillary permeability were analyzed in an isolated vascularly perfused cat ileum preparation. Reductions in perfusion pressure to 30-40 mmHg (60 min) resulted in a lowering of lymph flow and an increase in the lymph to p lasma protein concentration ratio. Release of the partial arterial occlusion caused lymph flow and lymph to plasma protein concentration ratio to increase above their control values. Venous outflow pressure was then increased in 10 mmHg increments to 30 mmHg. The capillary osmotic reflection coefficient was estimated from the relationship between lymph to plasma protein concentration ratio and lymph flow. Values of the osmotic reflection coefficient for total proteins and individual protein fractions were significantly lower than control values. The results of this study indicate that 1 hr of regional ischemia significantly increases the permeability of intestinal capillaries. The increased capillary permeability accounts, at least in part, for the enhanced capillary filtration and interstitial fluid accumulation which occurs in the posthypotensive small intestine.