Effect of zoledronate on bone quality in the treatment of aseptic loosening of hip arthroplasty in the dog.

Periprosthetic bone loss, which is a direct cause of aseptic loosening in total hip arthroplasty (THA), can be suppressed by bisphosphonates. It is unknown how the quality of this bone is affected in the presence of both wear debris (from implant) and bisphosphonates. The objective of this study was to evaluate the effect of zoledronate (ZLN) on bone quality in the presence of wear debris [polyethylene (PE) particles] in a canine model of uncemented THA. Thirty dogs underwent THA, and aseptic loosening was induced via implantation of PE particles packed into the femoral component. For 26 weeks until sacrifice, two groups (each n = 10) received weekly injections of ZLN (low dose 2 mug/kg, high dose 10 mug/kg) and the third group (control) received saline. Histological and radiographic examinations were performed to evaluate the degree of implant reaction. Histomorphometry (static/dynamic) was performed to evaluate bone turnover. Back-scattered electron imaging was used to quantify the newly formed bone and to evaluate the mineralization distribution. Density fractionation and X-ray diffraction were used to evaluate mineral properties, while four-point bending was used to determine mechanical properties. A dose-dependent presence of newly formed subperiosteal bone was found, which appeared to be less mineralized than the adjacent cortical bone. The high-dose ZLN group showed decreased cortical porosity and turnover and increased mineralization profile, failure strength, and modulus. We conclude that ZLN affects some of the material properties of cortical bone and allows the newly formed subperiosteal bone to remain and therefore affect the overall quality of the bone.

Osseointegration of hydroxyapatite porous-coated femoral implants in a canine model.

This study evaluated the quality and quantity of osseointegration of two thicknesses of hydroxyapatite coating on press-fit, porous-coated titanium implants in a canine hip model. In 12 dogs, titanium press-fit porous-coated prostheses were implanted. The stems had a 50-microm thickness hydroxyapatite coating, 100-microm thickness hydroxyapatite coating, or no hydroxyapatite coating. The animals were randomized into one of three groups and received one of the three implants. The implants were retrieved and examined 4 months after implantation. Direct juxtaposition of bone to the surface of the hydroxyapatite-coated implants with no intervening fibrous tissue layer was observed. There was no histologic evidence that hydroxyapatite initiated any foreign body reaction, nor was there any irregularity or resorption of the hydroxyapatite coating. There was a statistically significant greater degree of total bone apposition and bone ingrowth in the implants coated with hydroxyapatite at the level of the isthmus and the calcar. No statistical difference was found between the two groups with hydroxyapatite coatings in the degree of bone ingrowth or bone apposition.

Clinical observations of the treatment of canine perianal fistulas with topical tacrolimus in 10 dogs.

Tacrolimus ointment, a potent immunosuppressive medication, was evaluated for efficacy in the treatment of perianal fistulas in dogs. Ten dogs with perianal fistulas were treated with topical tacrolimus ointment once to twice daily for 16 weeks. Full healing of the fistulas occurred in 50% and was noticeably improved in 90% of dogs.

Cementless acetabular fixation in total hip arthroplasty using polyglycolide-lactide screws: an in vivo canine study.

Bone ingrowth into cementless acetabular components was evaluated in a canine total hip arthroplasty model, comparing components initially stabilized with polyglycolide-lactide screws with those initially stabilized with titanium screws. The acetabular shell was anchored with 2 polyglycolide-lactide screws in 16 dogs and with 2 titanium screws in 12 dogs. The dogs were followed and sacrificed at 7 weeks, 14 weeks, 10 months, or 15 months. Histomorphometric analysis of bone ingrowth into the weight-bearing dome of the acetabular shell was conducted. No difference was detected in mean bone ingrowth into the acetabular shell comparing the 2 screw groups. The results of this study do not support a significant advantage to the use of biodegradable screws for the initial stabilization of cementless acetabular components in canine total hip arthroplasty.

Use of a polyglycolide lactide cement plug restrictor in total hip arthroplasty.

The use of a polyglycolide lactide cement plug restrictor in cemented femoral fixation during total hip arthroplasty was evaluated. Femoral cement pressurization was evaluated in vitro in a cadaveric model and the host response to polymer degradation was evaluated in vivo in a canine total hip arthroplasty model. Sixteen embalmed anatomic specimen femurs were prepared for cement femoral fixation. The intramedullary canal was plugged with either an ultrahigh molecular weight polyethylene cement plug restrictor or a polyglycolide lactide cement plug restrictor. Peak pressures in the proximal, mid, and distal portions of the cement mantle were recorded during cement insertion, cement pressurization, and implant insertion. There was no difference between the two plug groups in peak pressures throughout the cement mantle during cement insertion, pressurization, or implant insertion. Total hip arthroplasty using a cementless acetabular component and a cemented femoral stem was performed in 24 dogs. The femoral intramedullary canal was plugged with a polyethylene or a biodegradable cement plug restrictor. The dogs were sacrificed at 7 weeks, 10 months, or 15 months. Radiographically, no osteolytic lesions were seen around either plug type. Histomorphometrically, the polyglycolide lactide plugs appeared intact at 7 weeks and partially degraded by 10 and 15 months. In both plug groups, a mild fibrohistiocytic reaction with infiltration of fibrocytes, histocytes, and endothelial cells was seen. No osteolysis was observed. The results of the current study show that femoral cement pressurization can be attained in vitro using a biodegradable cement plug restrictor and that for as long as 15 months in the in vivo canine model there were no adverse reactions associated with use of these plugs compared with conventional ultrahigh molecular weight polyethylene plugs.

A Corethane/polyester composite vascular prosthesis for vascular access. Comparison with expanded polytetrafluoroethylene grafts in a canine model.

An important need in hemodialysis is a self-sealing prosthesis for vascular access with at least equivalent patency and biostability to expanded polytetrafluoroethylene (ePTFE) alternatives. The authors have developed a Corethane/polyester composite (CPC) graft with an inner blood interfacing layer of spun Corethane fibers (10-15 microns diameter; pore size 30-60 microns) impregnated with a gelatin-heparin complex and an outer soft tissue interfacing warp-knitted polyester sheath. Twenty-six CPC grafts (6 mm internal diameter; 25-30 cm length) and eight Gore-Tex ePTFE grafts (same dimensions) were implanted as femoral artery-to-vein shunts in dogs on low dose (162 mg/day) aspirin, and subjected to weekly dialysis needle punctures for up to 52 weeks. Patency was 73% (19/26 with 15 at 52 weeks) for the CPC grafts and 63% (5/8 at 52 weeks) for the ePTFE controls, with more favorable healing (e.g., less extensive mural thrombi) of the CPC grafts. The hemostasis time per needle pair after removal (3.1 min mean for CPC versus 21.2 min mean for ePTFE) and the blood loss in achieving hemostasis (5.7 g mean for CPC versus 47.9 g for ePTFE) documented the significant (p < 0.0001) performance advantages of the CPC prosthesis.

The effect of the medial collar in total hip arthroplasty with porous-coated components inserted without cement. An in vivo canine study.

We performed an in vivo study in a canine model to compare the results of the use of a porous-coated collared femoral component with those of the use of a porous-coated collarless femoral component in total hip arthroplasties without cement. Our study focused on the comparative proximal strain pattern, bone ingrowth, and cortical porosity of the two types of prostheses. We used a trochanteric wire marker to measure subsidence. The use of the limb was assessed with gait analysis. Twelve weeks after the operation, the collarless components had significantly greater bone ingrowth proximally (p = 0.003) and were associated with significantly lower cortical porosity (p = 0.006). There were no differences between the groups with regard to either axial or hoop strain. While the group that had a collarless prosthesis had significantly less proximal-medial radiolucency (p = 0.03), there were no differences between the groups with regard to subsidence.

Migration of polyethylene wear debris in hip arthroplasties: a canine model.

The distal migration of polyethylene wear debris appears to be a major cause of loosening and osteolysis of cementless total hip arthroplasties. The use of modern cementing techniques, circumferential porous or hydroxyapatite (HA) coating has been advocated as a means of preventing access of the particles to the bone-implant interface. The purpose of this study was to compare the ability of different methods of implant fixation to prevent wear debris migration. Three each of smooth, porous-coated, HA-coated, and cemented hemiarthroplasties were implanted in the right hip of 12 dogs. Polyethylene particles were injected into the hip once a month for 4 months and then the femurs were sectioned. The percentage bone ingrowth was 8% for the smooth, 38% for the porous, and 83% for the HA-coated sections. Infiltration of the interface membrane by histiocytes containing polyethylene particles, and endosteal scalloping or osteolysis were found on all sections of the smooth prostheses. No particles or osteolysis were found on any sections of the other three types of prostheses. Capsular and lymph node sections from all dogs revealed histiocytic infiltration with numerous polyethylene particles present. It is concluded that the use of cement, porous, or HA coating prevents or delays access of the polyethylene wear debris to the bone-implant interface. No one of these methods of fixation proved more advantageous in the 5-month limit of this study.

The effect of occlusive and semi-occlusive dressings on the healing of acute full-thickness skin wounds on the forelimbs of dogs.

This project compared the effects of hydrocolloid (HC) and hydrogel (HG) occlusive dressings and a polyethylene (PE) semi-occlusive dressing on the healing of acute full-thickness skin wounds on the forelimbs of 10 dogs. All treatments resulted in a similar degree of healing at postoperative days 4 and 7. No significant differences existed in the number of wounds that were more than 90% healed at postoperative day 28 between the group treated with the HG dressing and the group treated with the PE dressing. There were significantly fewer wounds more than 90% healed at postoperative day 28 in the group treated with the HC dressing. Wounds under the HG dressing had the largest mean percentage of contraction at postoperative days 21 and 28. Wounds under the HG dressing also had the largest contraction/re-epithelialization ratio (postoperative days 21 and 28) compared with wounds under the PE and HC dressings. Wounds under the PE dressing had a significantly higher mean percentage of re-epithelialization than wounds under both occlusive dressings on postoperative days 14, 21, and 28. Wounds under the two occlusive dressings had exuberant granulation tissue present more often than wounds under the PE dressing. The two occlusive dressings had significantly higher bacterial counts on wounds compared with wounds under the PE dressing; analysis of variance (ANOVA), P = .0008. Wounds under the HC dressing showed the poorest healing in all parameters.

Renal allograft survival in outbred mongrel dogs using rabbit anti-dog thymocyte serum in combination with immunosuppressive drug therapy with or without donor bone marrow.

Therapeutic renal transplantation in dogs is currently being investigated as a treatment for endstage renal disease. This pilot study examines the effect of donor bone marrow (DBM) infusion and antithymocyte serum (ATS) in combination with immunosuppressive drug therapy in prolonging renal allograft survival in dogs. Seven normal outbred mongrel dogs received an unmatched renal allograft. All dogs received rabbit anti-dog thymocyte serum (RADTS), prednisone (Pr), cyclosporine-A (CsA) and azathioprine (Aza). In addition, three dogs (group 1 test) received DBM and four dogs (group 2 control) did not receive DBM. Serum CsA levels were measured throughout the study. Immunosuppressive therapy was gradually reduced with Pr, CsA, and Aza withdrawn at 200, 450, and 680 days, respectively. Allograft rejection was treated with prednisolone sodium succinate. One dog in group 1 and one in group 2 died as a result of infectious canine rhinotracheitis and rejection early in the study. Renal allograft torsion occurred in one group 1 dog. The remaining four dogs survived the 2 years of the study. The dogs in group 2 (three dogs) all rejected the renal allograft after total drug withdrawal, the surviving dog in group 1 did not. This study demonstrates that RADTS, Pr, CsA, and Aza in combination can prolong renal allograft survival in mongrel dogs, whereas DBM may enhance the unresponsive state.

Fixation with biodegradable devices of acetabular components in a canine model.

Cementless total hip arthroplasty was performed in 13 dogs. The acetabular component was anchored with two biodegradable devices (polylactic acid) in seven dogs and with two titanium screws in six dogs. At 14 weeks, histomorphometric determinations of bony ingrowth into the porous coating of the acetabular weight bearing dome was 54.4% when fixed with the biodegradable devices and 58.9% when fixed with the titanium screws (no statistically significant difference; p = 0.556). At the sites of fixation, less bony ingrowth occurred with the biodegradable devices. The use of biodegradable devices in total hip arthroplasty should overcome the potential metal corrosion of titanium screws that can lead to polyethylene wear.

Functional osseointegration of hydroxyapatite-coated implants in a weight-bearing canine model.

That hydroxyapatite (HA) can form a strong chemical bond with bone has been confirmed by several precedent workers using unloaded implants. The relationship between the histomorphometric measurements of the interface of the cementless femoral stems with and without HA coating and their mechanical properties in a weight-bearing canine model was evaluated in this study. Seven HA-coated and seven uncoated titanium (Ti6Al4V) hemiarthroplasties were implanted in the right hip of 14 dogs for a 5-month period. The specimens were taken to conduct mechanical testing and morphometric measuring. The average interface shear strength of 2.13 MPa for the HA-coated specimens was significantly higher than 0.93 MPa for the uncoated specimens (P < .05). There was greater bone apposition with the HA coating (72.39%) than without the coating (15.96%). Bone interfaces were divided into two types histomorphometrically: type A, simple bony shell without supporting trabeculae and type B, buttressed bony shell with supporting trabeculae. A positive correlation between the type B HA-bone interface and interface shear strength was found (r = .81).

A compliant Corethane/Dacron composite vascular prosthesis. Comparison with 4-mm ePTFE grafts in a canine model.

We have developed a composite vascular prosthesis with the inner blood interfacing layer made of a porous elastomeric membrane of spun Corethane fibers (10-15 microns in diameter, pore size 30-60 microns) impregnated with a gelatin-heparin complex and an outer soft tissue interfacing warp knitted Dacron sheath. Forty-eight Corethane/Dacron composite (CDC) vascular grafts, 4 mm in diameter and 5 cm in length, and 48 expanded polytetrafluoroethylene (ePTFE) vascular grafts of similar size were implanted bilaterally as end to end interposition grafts on opposite sides in the carotid and femoral arteries in dogs on low dose (162 mg/day) aspirin. Patency at 3 months was 37/48 (77%) for the ePTFE grafts and 44/48 (91.7%) for the CDC grafts. Fisher's exact test (two-tailed comparison) indicates the probability of superior CDC graft patency to be 95.5%. In the seven pairs of grafts in which one graft was occluded and the contralateral graft of another type was patent, the CDC graft was patent and the ePTFE graft was occluded in every instance. Explant histology and scanning electron microscopy showed greater collagenization, less residual platelet-fibrin and red blood cell deposits, and more frequent mid-graft endothelialization in the CDC grafts than in the ePTFE grafts.

Hydroxyapatite coating on carbon composite hip implants in dogs.

In 33 dogs we implanted femoral stems made either of carbon composite, some coated with hydroxyapatite, or of titanium alloy with a porous coating. Osseointegration was greater in the hydroxyapatite-coated than in the un-coated stems (p less than 0.001). Push-out tests, at an average of 7.2 months after implantation, showed a six-fold increase in interface shear strength and a twelve-fold increase in shear stiffness in the hydroxyapatite-coated group compared with noncoated implants. The highest shear-strength values were found in the porous-coated titanium alloy stems, around which there was also the most resorptive bone remodelling.

The intestinoprostatic capsule anastomosis: functional and anatomic results in a canine model.

Because of its potential application to intestinal bladder reconstructions, the authors studied the functional and anatomic results of a modification of the Camey procedure. In this modification the enteric bladder replacement is sutured to the periphery of the prostatic capsule after the inner two-thirds of the prostate gland have been removed. In eight dogs postoperative functional studies revealed that all were continent and potent. Autopsy examination of the area of the intestinoprostatic anastomosis revealed that the prostatic fossa was lined by a transitional epithelial layer originating from the urethral stump and not by intestinal mucosa as might be expected. The results indicated that this modification is simpler technically than the original procedure, that it shortens the operating time and that it gives excellent functional results. If used in the context of bladder cancer, however, the procedure should be undertaken only in the presence of negative biopsies and brushings of the urethra before surgery, because the transitional epithelium lining the prostatic fossa represents a new area at risk later malignant transformation. Moreover, because of the potential importance of the area of prostatic fossa resurfaced postoperatively by urothelium, even patients with normal preoperative urethral biopsies and brushings who undergo such a procedure require careful follow-up with endoscopic examination, urethral biopsy and brushings and cytologic examination of the urine.

Renal disease in carrier female dogs with X-linked hereditary nephritis. Implications for female patients with this disease.

Male dogs with X-linked hereditary nephritis (HN) serve as a model for studying male patients with this disease. In the present study, carrier female dogs were found to resemble female patients in showing a broad range of renal dysfunction. Of 37 carrier female dogs studied, all were healthy up to 5 years of age; however, all had proteinuria develop at 2 to 3 months, and focal segmental glomerulosclerosis (FSGS) was detected after 7 months. After 5 years, 4 of 13 dogs remained healthy and showed mild FSGS on renal biopsy; 4 had mild renal dysfunction develop and their kidneys showed extensive FSGS; 5 died prematurely of renal failure with end-stage kidneys. By immunofluorescence, using antibody to the NC1 domain of collagen type IV, segmental staining of glomerular basement membranes (GBM) was seen in all dogs before 3 to 4 years, and lesions of FSGS were negative. Thereafter, a transition to global staining of GBM was noted and lesions of FSGS became positive. Lens capsule and basement membranes in lung and choroid plexus showed discontinuous staining in two young carrier female dogs and continuous staining in one older carrier female dog. By electron microscopy, multilaminar splitting of some GBM was seen up to 4 years, and thereafter, splitting took on a compressed appearance, with the layers becoming apposed though still detectable. The authors conclude that: 1) carrier female dogs with X-linked HN are mosaics for an abnormality in the NC1 domain of GBM and other basement membranes; 2) FSGS develops in all carrier female dogs in glomerular capillary loops that possess an abnormal NC1 domain, and progresses to a variable extent in different dogs; and 3) the abnormality of NC1 in GBM of carrier female dogs appears to diminish with age, but this does not prevent progression of renal disease. Similar conclusions may apply to females with X-linked HN.

The composite Corethane/Dacron vascular prosthesis. Canine in vivo evaluation of 4 mm diameter grafts with 1 year follow-up.

Polyurethane vascular prostheses offer the potential of superior thromboresistance and reduced anastomotic hyperplasia compared to existing Dacron and ePTFE alternatives, but have suffered from susceptibility to biodegradation, with resulting mechanical failure. To address this problem, the authors have developed and evaluated a composite prosthesis comprised of: 1) an inner blood interfacing elastomeric porous membrane made from Corethane, a proprietary Shore 80A polyurethane like material substantially devoid of ether/ester linkages, with superior biostability over conventional polyether urethanes, spun into a nonwoven structure with fiber diameters 10-15 microns and pore sizes 30-60 microns filled with gelatin +/- heparin; and 2) an outer soft, tissue interfacing, warp knitted Dacron mesh bonded to the inner layer to assure long-term dimensional stability. Twenty 4 mm ID x 5 cm L composite prostheses, half with heparinized gelatin (the remainder nonheparinized) were implanted as femoral interposition grafts in 10 dogs. Four of the 10 nonheparinized grafts occluded. All 10 with heparin remained widely patent, with two explanted at 6 months showing vascularized connective tissue growth through the graft, in contrast to the giant cell inflammatory response to the Dacron mesh, with a substantially endothelialized neointima and no Corethane biodegradation. Of the 10 patent grafts at 1 year follow-up, none showed aneurysm formation. This vascular prosthesis provides compliance superior to ePTFE and Dacron alternatives, with excellent suture retention and good kink resistance, while combining the superior thromboresistance and tissue ingrowth properties of polyurethanes with the proven biostability of Dacron.

Enterocystoplasty with cystectomy and subtotal intracapsular prostatectomy in the male dog.

Urinary diversion by implantation of the ureters into an isolated segment of jejunum was evaluated in eight clinically normal male dogs. Total cystectomy and subtotal intracapsular prostatectomy were performed, and the intestinal loop was sutured to the prostatic remnant. General health, renal function, acid-base balance, urinary tract infection, and urinary continence were monitored during observation periods of 4 to 30 weeks. All dogs survived the observation period and seven were in excellent general health at the time of euthanasia. Six of the 16 ureterointestinal anastomoses were complicated by complete ureteral obstruction. Absorption of urea from the intestinal loop was speculated as the reason for significant increases in serum urea nitrogen concentrations in all of the dogs. Serum creatinine concentrations generally remained within the normal range, but were significantly increased from preoperative baseline values by week 30. There was dilation of 12 renal pelves and ureters in seven dogs. Urine bacterial cultures were positive in six dogs, but histologic evidence of pyelonephritis was present in only five kidneys. Ejaculation was not affected by the procedure, but epididymitis was present in five dogs. The dogs could urinate consciously and did not dribble urine continuously; however, they urinated hourly. While the procedure was well tolerated by the dogs, the frequency of urination makes this technique unacceptable for most household pets.

Effect of stem modulus in a total hip arthroplasty model.

The purpose of this study was to determine the biological effects of the elastic modulus of the femoral stem in canine hip arthroplasty. Cementless total hip arthroplasty was performed in 12 dogs, six had a low elastic modulus polyacetal resin stem and six had a high modulus stainless steel stem. The components were otherwise similar. At six and 12 months after operation, radiographic and histomorphometric analysis showed that those with steel implants had more cortical porosity than did the other group (p less than 0.01). We suggest that the elastic modulus of the implant is an important factor in controlling cortical bone resorption. A low modulus femoral prosthesis can significantly decrease bone resorption which might otherwise eventually lead to implant failure.

The NC1 domain of collagen type IV in neonatal dog glomerular basement membranes. Significance in Samoyed hereditary glomerulopathy.

Patients with hereditary nephritis (HN) present with renal disease after infancy, suggesting that the lesion of glomerular basement membranes (GBM) may not be congenital. Therefore, the NC1 domain of collagen type IV in normal neonatal dog GBM was compared with NC1 in normal adult GBM by SDS-PAGE and Western blotting, using two anti-NC1 antibodies. Similar results were obtained, indicating that the NC1 domain is present and immunoreactive in the neonatal period. Next, serial renal biopsies were performed on a family of Samoyed dogs with hereditary glomerulopathy (SHG), an animal model of HN, and assessed by immunofluorescence. One of the anti-NC1 antibodies produced global staining of GBM in unaffected dogs, and global/segmental staining in carrier females; however, no staining was seen in affected males as early as the neonatal period. Electron microscopy (EM) failed to demonstrate any lesion of GBM in neonatal dogs. Thus, in SHG, and presumably in human HN, the abnormality in the NC1 domain is congenital, and precedes the changes seen by EM in GBM.