Disseminated Rhodococcus equi in an Anglo-Nubian goat.

Disseminated Rhodococcus equi infection was diagnosed in an Anglo-Nubian goat presenting for non-weight bearing lameness of the right pelvic limb. Radiographs showed a moth-eaten osteolytic lesion in the proximal tibia suggestive of an aggressive bone lesion. Two pulmonary nodules were also present on thoracic radiographs. Initial antemortem cytology of the tibial lesion was suggestive of Rhodococcosis and the goat was sent to necropsy. Necropsy and bacterial culture confirmed the diagnosis of disseminated R. equi infection in the right tibia, lungs, and liver.

Identification of Heterobilharzia americana infection in a dog residing in Indiana with no history of travel.

CASE DESCRIPTION: A 1-year-old castrated male dog residing in Indiana was examined because of intermittent vomiting of 4 months' duration. CLINICAL FINDINGS: The dog's condition did not resolve with medication. Diagnostic imaging revealed a possible partial obstruction at the ileocecal junction. An exploratory laparotomy was performed. The jejunum contained diffusely distributed, nodular, intramural lesions; 2 biopsy specimens were collected from representative lesions. The pancreas was grossly swollen, and pancreatitis was presumed present. No other abnormalities were observed in the abdomen. Histologic examination of the submitted biopsy specimens revealed infection with Heterobilharzia americana. TREATMENT AND OUTCOME: After diagnosis, the dog was treated with fenbendazole suspension (48 mg/kg [21.8 mg/lb], PO, q 24 h) for 10 days. This treatment was subsequently repeated 11 and 80 days later. One week after the end of the last fenbendazole treatment, several H americana eggs were detected in a fecal sample via saline sedimentation, and the dog was given praziquantel (25 mg/kg [11.4 mg/lb], PO, q 8 h) for 2 days. No gastrointestinal signs were evident 4 months after that treatment. CLINICAL RELEVANCE: The dog described in this report was the first autochthonous canine case of H americana infection in Indiana, to the authors' knowledge; this case has confirmed that the distribution of this parasite in the Midwestern United States is broader than previously known. Increased awareness of the distribution of H americana should aid veterinarians in early, noninvasive diagnosis and appropriate treatment of affected animals. Repeated treatments and recheck fecal examinations may be necessary when managing these cases.

DNA-epitope vaccine provided efficient protection to mice against lethal dose of influenza A virus H1N1.

Swine influenza virus (SIV) is a fast-evolving viral pathogen in pig populations. However, commercial vaccines, based on inactivated viruses, cannot provide complete protection with induced humoral immunity only and require frequent updates to fight against current isolates. A DNA vaccine delivering conservative epitopes was designed in this study in the hope of meeting the need. In this study, a B-cell epitope (HA2.30-130), a quadruplicated Th-cell epitope (NP55-69), and a quadruplicated CTL epitope (NP147-158) were fused separately to the C-terminal of VP22c gene in the modified pcDNA3.1 plasmid. The expression of epitopes was confirmed by in vitro transfection of 293FT cells. The DNA vaccine administered intramuscularly stimulated epitope-specific immunity against the two T-cell epitopes in all ten mice before the virus challenge. Only two out of ten mice were ELISA positive against the B-cell epitope. All vaccinated mice survived a lethal dose of virus challenge, while all mice in the challenge control group died. The DNA vaccine delivering epitopes in this study showed promising protection against influenza virus in an animal model; however, more work needs to be done to evaluate the best conserved protective epitopes which can be applied in developing a universal DNA vaccine.

Goats are a potential reservoir for the herpesvirus (MCFV-WTD), causing malignant catarrhal fever in deer.

In the recent investigation of malignant catarrhal fever in a red brocket deer (Mazama americana) from a Texas zoo, the viral DNA from the herpesvirus termed MCFV-WTD, which causes disease in white-tailed deer (Odocoileus virginianus), was detected. The epidemiology information revealed that the red brocket deer had been associated with a herd of pygmy goats (Capra hircus) at the zoo. MCFV-WTD DNA was also detected in one of these 12 goats that were malignant catarrhal fever viral antibody positive. The amplified herpesviral sequences from the affected deer and the MCFV-WTD-positive goat were identical, and matched the sequence in GenBank. Three of 123 DNA samples from various breeds of goats from different geographic locations in the United States were positive for MCFV-WTD DNA. The study shows that MCFV-WTD is capable of causing malignant catarrhal fever in other species of deer besides white-tailed deer and suggests that goats are a potential reservoir for the virus.

DNA-vaccine platform development against H1N1 subtype of swine influenza A viruses.

Swine influenza virus (SIV) is an important viral pathogen in pig populations. However, commercial vaccines cannot provide complete protection with induced humoral immunity only, and require frequent updates to fight against current isolates. DNA vaccination is an effective means of eliciting both arms of the immune system, the humoral and cellular immune responses. In this study, DNA vector pcDNA3.1 was inserted with a chimeric intron downstream of the CMV promoter region followed by a Kozak sequence to enhance the expression of gene inserts. The C-terminal of the VP22 gene (VP22c), encoding the tegument protein of bovine herpesvirus-1, was fused separately to the N-terminal of four quadruplicated epitopes: two B-cell epitopes (HA91-108 and M2e), and two T-cell epitopes (NP366-374 and NP380-393), which were conserved, at least among the three SIV subtypes prevailing in pig populations in North America. Linker -KK- was used to space between each copy of the two B-cell epitopes, and -RVKR- was used for the two T-cell epitopes, in order to enhance the presentation of epitopes to the immune system. The expression of epitopes was confirmed in in vitro transfection of 293FT cells, and higher percentages of epitope-positive cells were achieved from the plasmids containing VP22c than those without. After the DNA plasmids were administered to mice intramuscularly in combination or separately, or boosted with recombinant proteins of quadruplicated epitopes fused to VP22c, the vaccine stimulated the desired epitope-specific humoral immunity to the two B-cell epitopes, and cellular immunity to the epitope NP380-393. Our results indicate that plasmids with quadruplicated epitopes fused to the VP22c may be a potential vehicle in developing epitopes as vaccines against SIV.

Experimental co-infection of pigs with Bovine viral diarrhea virus 1 and Porcine circovirus-2.

The role of Bovine viral diarrhea virus (BVDV) in the development of Porcine circovirus-2 (PCV-2)-associated disease (PCVAD) was investigated in 2 experimental studies. In the first, separate groups of germ-free pigs were inoculated with filtered tissue homogenate (from diseased pigs) containing PCV-2b + BVDV-1-like virus (group 1), PCV-2a + BVDV-1-like virus (group 4), BVDV-1-like virus only (group 3), or PCV-2b + BVDV-1-like virus following a BVDV vaccination protocol (group 2). This last group was used to test if BVDV vaccination would prevent clinical PCVAD in this model. Many of the inoculated pigs had mild multisystemic inflammation consistent with classic PCVAD. One vaccinated, dually inoculated pig had acute respiratory distress followed by death at 21 days postinfection. Lesions in this pig resembled the severe form of PCVAD observed in the field since the fall of 2004, suggesting a role of ruminant pestiviruses and/or vaccination in the development of this disease. In the second study, cesarean-derived, colostrum-deprived pigs were inoculated with PCV-2b and a cytopathic strain of BVDV-1 (cpBVDV-NADL) either alone or in combination. Clinical signs of PCVAD were seen in a single animal inoculated only with PCV-2b. This pig had growth retardation followed by acute respiratory distress leading to death 30 days postinfection. Pulmonary lesions in this animal were similar to those seen in the pig that died in the first study. Infection with cpBVDV-NADL did not enhance PCV-2b replication or lesion formation.

Pilot evaluation of a vacuum-assisted biopsy instrument for percutaneous renal biopsy in dogs.

Kidney biopsies in dogs are commonly obtained using automated spring-loaded biopsy instruments. Interpretation of biopsies from dogs with glomerular disease requires examination of at least 5-10 glomeruli, with at least two biopsies usually required for full evaluation. The purpose of this study was to compare quality and interpretability of renal biopsies obtained from healthy dogs with a large-gauge, vacuum-assisted biopsy instrument versus two biopsies obtained with a spring-loaded biopsy needle. Twenty dogs were randomized into two groups, and percutaneous, ultrasound-guided renal biopsies were evaluated using standard criteria. There were no significant differences in the number of biopsies that contained renal tissue, cortex, or medulla. Biopsies obtained with either instrument contained an adequate number of glomeruli and an equivalent number of arterioles and severity of tissue compression. Differences included easier penetration of the renal capsule and collection of sufficient tissue for interpretation with only one instrument pass when using the vacuum-assisted device (vs two passes required with the spring-loaded instrument). Before use in client-owned dogs, future studies should evaluate whether these differences are clinically relevant advantages in the diagnostic evaluation of dogs with kidney disease, and determine the prevalence and severity of complications when using this larger gauge device.

An alternative pathway electrosurgical unit injury in a dog.

OBJECTIVE: To report esophageal perforation, caused by alternative current pathway from the use of a monopolar electrosurgery unit (ESU), during routine orthopedic surgery in a dog. STUDY DESIGN: Clinical report. ANIMALS: Two-year-old male Labrador retriever. METHODS: Medial meniscectomy and lateral suture stabilization were performed on a healthy Labrador retriever with a ruptured cranial cruciate ligament. Monopolar electrosurgery was used during the procedure for hemostasis and tissue dissection. Anesthetic monitoring was augmented with an esophageal electrocardiogram (ECG) probe. The day after surgery, the dog appeared dehydrated. After intravenous fluid therapy, respiratory distress was noted and thoracic radiography and contrast fluoroscopy revealed an esophageal perforation. RESULTS: Exploratory surgery was planned to repair the defect. Cardiac arrest occurred after induction. Gross necropsy findings and histopathologic examination revealed lesions consistent with thermal necrosis of the esophagus and myocardial degeneration. An internal investigation of this medical device accident revealed that multiple factors may have contributed to the injury. CONCLUSIONS: An alternative current pathway from the monopolar ESU to the esophageal ECG probe resulted in a full-thickness esophageal thermal injury and cardiac failure.

Hypertrophic osteopathy associated with a renal adenoma in a cat.

Hypertrophic osteopathy is a hyperostotic syndrome of the appendicular skeleton that is most commonly associated with intrathoracic neoplasia or inflammation. The condition is rarely associated with intra-abdominal lesions. The majority of cases have occurred in dogs and human beings, with fewer cases reported in cats, horses, and other species. A 15-year-old male neutered Domestic Shorthair cat presented for swollen limbs and difficulty in ambulation. Radiographs and gross postmortem revealed severe periosteal hyperostosis of the diaphysis and metaphysis of all 4 limbs, including the humerus, radius, ulna, carpi, metacarpi, femur, tibia, tarsi, metatarsi, and phalanges. The axial skeleton was spared. Hyperostotic lesions were characterized microscopically by lamellar bony trabeculae separated by adipocytes and scant hematopoietic tissue. In several areas, fibrovascular connective tissue, woven bone, and islands of cartilage were also present. A 2.5 cm × 2.5 cm perirenal neoplasm compressed the left kidney and adrenal gland. This mass consisted of well-differentiated tubules of cuboidal epithelial cells and was most consistent with a renal tubular adenoma, because mitotic figures were rare, and no distant metastases were found. Thoracic pathology was absent. Hyperostosis was consistent with hypertrophic osteopathy secondary to the renal adenoma. The pathogenesis of hypertrophic osteopathy is uncertain, but predominant theories point to increased peripheral circulation and angiogenesis as a key initiating event. Recent literature highlights the potential role of vascular endothelial growth factor and platelet-derived growth factor in the human condition. The mechanism by which this renal adenoma caused hypertrophic osteopathy is unknown.

Infection of cesarean-derived colostrum-deprived pigs with porcine circovirus type 2 and Swine influenza virus.

Porcine circovirus type 2 (PCV2) and swine influenza virus (SIV) are important pathogens for porcine respiratory disease complex, which is economically significant worldwide. The pathogenesis of PCV2-SIV coinfection is unknown. In this study, we focused on establishing a challenge model for PCV2 to determine whether SIV influences PCV2 replication and increases the severity of PCV2-associated disease. Cesarean-derived colostrum-deprived pigs were inoculated intratracheally with cell culture medium only (negative control group), PCV2 only, or PCV2 followed 1 wk later with SIV H1N1. Two pigs from each group were necropsied at 12, 21, 28, and 35 d after inoculation. Coinfection with SIV did not increase the number of PCV2 genomic copies in serum or target tissues or the severity of microscopic lesions associated with PCV2 in lung or lymph node. The antibody titer to PCV2 did not differ significantly between PCV2-SIV- and PCV2-infected groups. In conclusion, SIV H1N1 did not influence PCV2 replication in dually infected pigs in this study.

Multimodal treatment of recurrent sinonasal cryptococcal granulomas in a horse.

CASE DESCRIPTION: A 7-year-old 509-kg (1,120-lb) Tennessee Walking Horse mare was evaluated because of bilateral mucosanguinous nasal discharge, intermittent right-sided epistaxis, and worsening dyspnea of 9 months' duration. CLINICAL FINDINGS: Multiple masses in the nasopharynx were detected via endoscopic and radiographic examinations. Cytologic and histologic examinations of biopsy specimens of 1 mass revealed round yeasts with thick nonstaining capsules and occasional narrow-based budding that resembled cryptococcal organisms. TREATMENT AND OUTCOME: Oral administration of fluconazole and organic ethylenediamine dihydriodide and intermittent intralesional injections with fluconazole, amphotericin B, and formalin resulted in resolution of lesions for a period of 2.5 years. The horse then developed exophthalmos, recurring clinical signs, and extensive nasopharyngeal masses. The masses were surgically debulked via a large frontonasal bone flap, and the horse was treated with IV injections of amphotericin B and long-term oral administration of fluconazole. Clinical signs did not recur in the following 2-year period. A presumptive diagnosis of cryptococcosis was made following cytologic and histologic evaluations of the masses; results of serologic analysis and fungal culture confirmed infection with Cryptococcus neoformans. CLINICAL RELEVANCE: Cryptococcal infection of the upper respiratory tract in horses has previously been described as a uniformly fatal disease. As this case report illustrates, medical and surgical treatment of sinonasal cryptococcal granulomas in horses may be successful, but the importance of long-term follow-up and the potential for disease recrudescence should be considered. As efficacious antifungal agents become less expensive, their increased use will likely decrease mortality rates in horses with fungal infections.

Requirement for p85alpha regulatory subunit of class IA PI3K in myeloproliferative disease driven by an activation loop mutant of KIT.

OBJECTIVE: Oncogenic activation loop mutations of KIT are observed in acute myeloid leukemia (AML) and in myeloproliferative disorders (MPD); however, the signaling pathways that contribute to transformation via these mutations in vivo are not known. Previous studies have demonstrated hyperactivation of p85alpha regulatory subunit of class IA phosphatidylinositol-3-kinase (PI3K) in cell lines expressing the activation loop mutant of KIT (KITD816V [human] and KITD814V [murine]). Although p85alpha is hyperphosphorylated and constitutively bound to KITD814V in cell-line models; the physiologic significance of this biochemical phenomenon in KITD814V-induced transformation is not known. MATERIALS AND METHODS: Here, we describe the generation of a new mouse model to study KITD814V-induced transformation in myeloid cells as opposed to previously described models that primarily result in the generation of disease resembling acute lymphocytic leukemia. RESULTS: Our results show that transplantation of KITD814V expressing bone marrow cells from C57/BL6 strain of mice into syngeneic recipients results in a fatal MPD. Importantly, in this model, transplantation of KITD814V expressing p85alpha-deficient bone marrow cells rescues the MPD phenotype. CONCLUSIONS: Our results describe the generation of a new murine transplant model to study KITD814V-induced transformation and identify p85alpha as potential therapeutic target for the treatment of KITD814V-bearing diseases.

Evaluation of clinical status, renal function, and hematopoietic variables after unilateral nephrectomy in canine kidney donors.

OBJECTIVE: To determine clinical status and renal and hematopoietic function after kidney donation and identify risks associated with kidney donation in dogs. DESIGN: Prospective study. ANIMALS: 14 dogs that underwent unilateral nephrectomy for kidney donation. PROCEDURES: Records were reviewed retrospectively to collect data regarding prenephrectomy clinicopathologic variables. Dogs were reexamined prospectively at various times after nephrectomy, and pre- and postnephrectomy CBC, serum biochemical analyses, urinalysis, and urine protein-to-urine creatinine ratio were compared. Six dogs had postnephrectomy renal volume determined ultrasonographically, and 4 of those dogs also underwent scintigraphic determination of glomerular filtration rate and renal biopsy. RESULTS: All dogs were clinically normal at the time of reevaluation. There were no significant differences between prenephrectomy and postnephrectomy values for BUN concentration or urine specific gravity. Mean postnephrectomy serum creatinine concentration was significantly greater than prenephrectomy concentration. Mean serum phosphorus concentration was significantly decreased after nephrectomy, and mean Hct, corpuscular volume, and corpuscular hemoglobin concentration were significantly increased after nephrectomy. Postnephrectomy renal volume was greatest in dogs < 12 months old at the time of surgery. Mean postnephrectomy glomerular filtration rate was 2.82 +/- 1.12 mL/kg/ min (1.28 +/- 0.51 mL/lb/min). Renal biopsy specimens obtained during and after nephrectomy were histologically normal. CONCLUSIONS AND CLINICAL RELEVANCE: Renal and hematopoietic variables were within reference ranges in dogs examined up to 2.5 years after unilateral nephrectomy. Compensatory renal hypertrophy was greatest in dogs < 1 year of age at donation. Donor age, along with histocompatability, may be an important factor in selecting dogs for kidney donation.

Hematopoietic chimerism induces renal and skin allograft tolerance in DLA-identical dogs.

OBJECTIVE: Hematopoietic chimerism, a state where donor and recipient bone marrow cells coexist, is associated with donor-specific tolerance. Nonmyeloablative bone marrow transplantation (BMT) has been shown to induce stable mixed hematopoietic chimerism in dog leukocyte antigen (DLA)-matched dogs. The potential for inducing renal and skin allograft tolerance with nonmyeloablative BMT was investigated in DLA-identical and DLA-haploidentical dogs in this study. MATERIALS AND METHODS: Renal allografts were performed in 8 DLA-identical and 4 DLA-haploidentical dogs with nonmyeloablative conditioning (200 cGy TBI) and transient immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF) with (n = 8) and without (n = 4) simultaneous BMT. Skin allografts were performed in 2 DLA-identical and 4 DLA-haploidentical dogs after stopping CSP and MMF. Two DLA-identical control dogs received renal allografts without TBI, BMT, or immunosuppression with CSP and MMF. Molecular chimerism was determined with a PCR-based DNA microsatellite assay. Serum creatinine (Cr) concentration, urine specific gravity, and sequential renal biopsies were monitored to assess renal allograft function. RESULTS: Donor-type blood cells were first detected 4 weeks posttransplantation in both the myeloid and lymphoid lineages. Donor chimerism was present for at least 76 weeks in the DLA-identical dogs. Mixed chimerism was not observed in the DLA-haploidentical dogs or DLA-identical dogs that did not undergo BMT. The renal allografts were acutely rejected within 14 days in the 2 DLA-identical control dogs. There was long-term (> 5 yrs) renal allograft survival as evidenced by a normal (< 2.0 mg/dL) serum Cr concentration in both the DLA-identical and DLA-haploidentical dogs that underwent 200 cGy TBI and transient immunosuppression with CSP and MMF either with or without simultaneous BMT. Renal allograft inflammation was severe in the control dogs, mild to moderate in the DLA-haploidentical dogs, and minimal in the DLA-identical dogs. Donor-specific skin grafts were accepted in the DLA-identical dogs but rejected in the DLA-haploidentical dogs. Nonmyeloablative conditioning (200 cGy TBI) and transient immunosuppression with CSP and MMF induce renal and skin allograft tolerance in DLA-identical and permit long-term renal allograft survival in DLA-haploidentical dogs. These findings suggest it may possible to obtain long-term allograft survival in DLA-identical and -haploidentical dogs without the need for chronic immunosuppressive therapy.

Renal allograft histopathology in dog leukocyte antigen mismatched dogs after renal transplantation.

OBJECTIVE: To evaluate allograft histopathology in dog leukocyte antigen (DLA)-mismatched dogs undergoing renal transplantation, with transient immunosuppression. STUDY DESIGN: Prospective study. ANIMALS: Ten healthy adult mongrel dogs. METHODS: Reciprocal renal transplantation and bilateral nephrectomy were performed. Immune conditioning consisted of nonmyeloablative (200 cGy), total body irradiation (TBI), bone marrow transplantation (BMT; 7 dogs), cyclosporine (CSA; 15 mg/kg every 12 hours), mycophenolate mofetil (MMF; 10 mg/kg every 12 hours) and intermittent prednisone (1 mg/kg every 12-24 hours). Biopsies were collected at transplantation, during full immunosuppression (44-90 days), and once medications were reduced or discontinued (228-580 days). Biopsies were evaluated for interstitial, tubular, vascular, and glomerular lesions. Blood urea nitrogen, creatinine, serum CSA concentrations, and clinical score were determined at each biopsy. RESULTS: Seven dogs survived >200 days (mean, 380 days). Transient CSA toxicity was suspected in 6 dogs. Lymphocytic, plasmacytic interstitial inflammation, and tubulitis progressed when immunosuppressive medications were decreased. All 7 dogs had histologic lesions consistent with some degree of allograft rejection at study end. CONCLUSION: Nonmyeloablative TBI, BMT, and short-term immunosuppression with CSA, MMF, and prednisone allowed renal allograft function and dog survival for >200 days. It appears unlikely that total drug withdrawal will be possible in unrelated DLA-mismatched dogs using this protocol. CLINICAL RELEVANCE: Transient immunosuppression with MMF, CSA, and prednisone along with BMT and nonmyeloablative TBI may make kidney transplantation a clinical reality for treatment of kidney failure in dogs. Initiating both MMF and CSA at lower dosages may potentially eliminate early renal allograft injury.

Leukocyte emigration in the early stages of laminitis.

The mechanisms that initiate the pathophysiologic changes in the digital laminae in equine laminitis are poorly understood. Due to the fact that (1) the horse at risk of laminitis has many similarities clinically to the human sepsis patient and (2) our recent finding of marked laminar proinflammatory cytokine expression at the developmental time point of the black walnut extract (BWE) model of laminitis, we tested the possibility that, similar to organ damage in human sepsis, leukocyte emigration is an early event in laminitis. Using immunoperoxidase methods with an anti-equine CD13 monoclonal antibody that recognizes neutrophils and monocytes, we discovered that, whereas the dermal microvasculature of the skin commonly has a marginal pool of leukocytes, the normal laminar dermal microvasculature has minimal to no perivascular leukocytes. However, increases in leukocyte numbers occurred around the dermal vasculature of both the laminae and the skin in the majority of BWE-treated horses in the developmental stage and at the onset of clinical signs of lameness in the BWE model. These findings indicate that, similar to organ failure in human sepsis, leukocyte emigration is likely to play a significant role in initiating numerous pathophysiologic mechanisms that lead to the development of laminitis.

The quantity of nitric oxide released by macrophages regulates Chlamydia-induced disease.

Intracellular bacteria of the genus Chlamydia cause numerous typically chronic diseases, frequently with debilitating sequelae. Genetic determinants of disease susceptibility after infection with Chlamydia bacteria are unknown. C57BL/6 mice develop severe pneumonia and poor immunity against Chlamydia after moderate respiratory infection whereas BALB/c mice are protected from disease and develop vigorous Th1 immunity. Here we show that infected C57BL/6 macrophages release more NO synthesized by NO synthase 2 (NOS2) than BALB/c macrophages and have lower mRNA concentrations of arginase II, a competitor of NOS2 for the common substrate, l-arginine. Reduction, but not elimination, of NO production by incomplete inhibition of NOS2 abolishes susceptibility of C57BL/6 mice to Chlamydia-induced disease. Thus, the quantity of NO released by infected macrophages is the effector mechanism that regulates between pathogenic and protective responses to chlamydial infection, and genes controlling NO production determine susceptibility to chlamydial disease.

Evaluation of small-intestinal submucosa implants for repair of meniscal defects in dogs.

OBJECTIVE: To assess the effects of porcine small intestinal submucosa (SIS) implants on the healing of meniscal lesions in dogs. ANIMALS: 16 adult Greyhounds of both sexes. PROCEDURE: Unilateral osteotomy was performed at time 0 to disrupt the medial collateral ligament attachment, and two (1 cranial and 1 caudal) 4-mm circular defects were created in the avascular portion of the medial meniscus. One defect was filled with an SIS graft, and the other defect remained empty (control). Three months later, the identical procedure was performed on the contralateral limb. Three months after the second surgery, dogs were euthanatized, and meniscal tissue specimens from both stifle joints were collected for gross, histologic, biomechanical, and biochemical evaluations. RESULTS: Regenerative tissue was evident in 4 (2 SIS-implanted and 2 control) of 16 defects examined histologically. In 3 defects, this thin bridge of tissue was composed of immature haphazardly arranged fibrous connective tissue with a relatively uniform distribution of fibroblasts. Aggregate modulus, Poisson ratio, permeability, and shear modulus were not significantly different between control and SIS-implanted defects either 3 or 6 months after surgery. Hydroxyproline content also did not differ between SIS-implanted and control defects at 3 or 6 months. CONCLUSIONS AND CLINICAL RELEVANCE: Implantation of porcine SIS into experimentally induced meniscal lesions in dogs did not promote tissue regeneration.