Validation of a model of feline ureteral obstruction as a tool for teaching microsurgery to veterinary surgeons.

OBJECTIVE: To assess the content and face validity of a model of an obstructed feline ureter as a tool for teaching ureteral microsurgery. STUDY DESIGN: Prospective, experimental study. SAMPLE POPULATION: Seven expert and 11 novice microsurgeons. METHODS: The model was created from latex rubber with an inner diameter of 0.8 mm and an outer diameter of 5 mm. The "ureter" was created with an inner compartment, a thin wall, and a soft, outer layer mimicking periureteral fat. A "ureterolith" 0.8-1.2 mm in diameter was placed inside the inner compartment by using a blunt-tipped cannula. A standardized "ureterotomy" was performed by 7 expert and 11 novice microsurgeons. Both groups completed questionnaires evaluating the content and face validity of the model using subjective measures and a 5-point Likert scale. Reliability was analysed by calculation of Cronbach's α for all questions to ensure α ≥ .7. The median responses to each question were compared between groups with a nonparametric independent samples median test. P < .05 was considered significant. RESULTS: The Cronbach's α for the experts and the novices for content validity questions was .7 and .9, respectively, and for the face validity questions it was .7 and .8, respectively. The model was rated to have excellent content validity and very good face validity. CONCLUSION AND IMPACT: The model elicited positive responses from expert and novice microsurgeons and can be recommended as a tool for teaching ureteral microsurgery. A model validated by face and content measures should next be scrutinized by determination of construct, concurrent, and predictive validity by using objective measures.

The Ca²âº-activated K⁺ channel KCa3.1 as a potential new target for the prevention of allograft vasculopathy.

Allograft vasculopathy (AV) remains one of the major challenges to the long-term functioning of solid organ transplants. Although its exact pathogenesis remains unclear, AV is characterized by both fibromuscular proliferation and infiltration of CD4(+) memory T cells. We here tested whether two experimental immunosuppressants targeting K(+) channels might be useful for preventing AV. PAP-1 inhibits the voltage-gated Kv1.3 channel, which is overexpressed on CCR7(-) memory T cells and we therefore hypothesize that it should suppress the memory T cell component of AV. Based on its previous efficacy in restenosis and kidney fibrosis we expected that the KCa3.1 blocker TRAM-34 would primarily affect smooth muscle and fibroblast proliferation and thus reduce intimal hyperplasia. Using immunohistochemistry we demonstrated the presence of Kv1.3 on infiltrating T cells and of KCa3.1 on lymphocytes as well as on proliferating neointimal smooth muscle cells in human vasculopathy samples and in a rat aorta transplant model developing chronic AV. Treatment of PVG rats receiving orthotopically transplanted aortas from ACI rats with TRAM-34 dose-dependently reduced aortic luminal occlusion, intimal hyperplasia, mononuclear cell infiltration and collagen deposition 120 days after transplantation. The Kv1.3 blocker PAP-1 in contrast did not reduce intima hyperplasia despite drastically reducing plasma IFN-γ levels and inhibiting lymphocyte infiltration. Our findings suggest that KCa3.1 channels play an important role in the pathogenesis of chronic AV and constitute an attractive target for the prevention of arteriopathy.

Outcome after renal transplantation in 26 dogs.

OBJECTIVES: To evaluate clinical outcome in dogs after renal transplantation and determine predictors of outcome. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 26) that had renal allograft transplantation. METHODS: Medical records (1994-2006) of 26 consecutive cases of dogs that had kidney transplantation were reviewed. History, signalment, pre- and postoperative clinicopathologic and monitoring variables, postoperative complications, immunosuppressive therapy, and survival were recorded. RESULTS: Median survival was 24 days (range, 0.5 to 4014 days) with a probability of survival to 15 days of 50% and the 100-day survival probability was 36%. Cause of death was attributed to thromboembolic disease in 8 dogs, infection in 6 dogs, and rejection in 1 dog. The only factor significantly associated with an increased likelihood of death was increasing age at time of surgery (P = .024). CONCLUSIONS: Canine renal transplantation in clinical patients is associated with a high morbidity and mortality and increasing recipient age has a negative association with outcome. Thromboembolic complications are a major cause of death in the immediate postoperative period and effective anticoagulation protocols may greatly improve survival in the future.

Hypophosphatemia in cats after renal transplantation.

OBJECTIVE: To report the prevalence of hypophosphatemia after renal transplantation in a historical cohort of cats. DESIGN: Case series. ANIMALS: Cats (n=86) that received a renal allograft. METHODS: Medical records (January 200-June 2006) were reviewed. Signalment, clinical signs, pre- and postoperative diet, pre- and postoperative clinicopathologic variables, renal histopathology, and outcome were retrieved. Prevalence, onset, duration, treatment and associated clinical signs of hypophosphatemia were recorded. A chi(2) test was used to compare hemolysis frequency between cats with normal serum phosphorus concentration or a single spurious low serum phosphorus concentration for <24 hours duration (group 1) and confirmed hypophosphatemia for >24 hours (group 2). A Cox proportional hazards model was used to evaluate the effects of hypophosphatemia on survival while controlling for other potentially confounding variables (age, sex, weight, body condition score, and pre- and 24 hours postoperative clinicopathologic variables). RESULTS: Eighty-six cats (mean age, 7.7 years) were identified. Hypophosphatemia occurred in 32 cats (37%), with a median onset of 2 days and median duration of 4 days. Treatment was initiated in 48 (56%) of hypophosphatemic cats. Survival and hemolysis frequency was not significantly different between groups, and no risk factors were identified. CONCLUSION: Hypophosphatemia occurs in cats after renal transplantation and does not affect survival. CLINICAL RELEVANCE: The clinical importance of hypophosphatemia in renal transplant recipients remains unknown.

Outcome of permanent tracheostomy for treatment of upper airway obstruction in cats: 21 cases (1990-2007).

OBJECTIVE: To determine clinical outcome of permanent tracheostomy in cats with upper airway obstruction. DESIGN: Retrospective case series. ANIMALS: 21 cats. PROCEDURES: Medical records were reviewed for information on history, signalment, clinical signs, results of preoperative clinicopathologic testing, cause of upper airway obstruction, surgical procedure, postoperative complications, and outcome. RESULTS: Causes of upper airway obstruction included neoplasia (squamous cell carcinoma [n = 6] or malignant lymphoma [2]), inflammatory laryngeal disease (5), laryngeal paralysis (4), trauma (3), and a laryngeal mass of unknown cause (1). Fourteen cats had dyspnea in the immediate postoperative period; dyspnea most often resulted from mucous plugs at the stoma or elsewhere in the respiratory tract. Eleven cats died, including 6 cats that died while hospitalized after surgery and 5 cats that died after discharge; 7 cats were euthanatized, most often because of progression of neoplasia; and 2 were still alive at the time of the study. The remaining cat was lost to follow-up after discharge from the hospital. Overall, median survival time for the 20 cats for which information was available was 20.5 days (range, 1 day to 5 years). Cats that underwent permanent tracheostomy because of inflammatory laryngeal disease were 6.61 times as likely to die as cats that underwent permanent tracheostomy for any other reason. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that permanent tracheostomy was an uncommon procedure in cats with upper airway obstruction that was associated with high complication and mortality rates.

Outcome of laryngeal web resection with mucosal apposition for treatment of airway obstruction in dogs: 15 cases (1992--2006).

OBJECTIVE: To evaluate long-term clinical outcome in dogs with upper airway obstruction treated with laryngeal web resection and mucosal apposition. DESIGN: Retrospective case series. ANIMALS: 15 client-owned dogs with laryngeal web formation. PROCEDURES: Medical records of dogs with laryngeal webs treated with a single procedure of web resection with mucosal apposition by use of a ventral laryngotomy were reviewed. Signalment, history, clinical signs, intraoperative complications, postoperative complications, and hospitalization time were recorded. Owners were interviewed 6 months to 6 years after surgery. RESULTS: Most dogs had a history of oral ventriculocordectomy. Duration of clinical signs ranged from 3 months to 3 years. The most common clinical sign reported was exercise intolerance. Postoperative complications were observed in 4 dogs. Follow-up information was available in 10 dogs, and clinical outcome was classified as excellent in 7 and good in 3. CONCLUSIONS AND CLINICAL RELEVANCE: A single surgical procedure of web resection with mucosal apposition for the treatment of laryngeal web formation in dogs resulted in low morbidity and was associated with a good to excellent outcome.

In vitro effects of the active metabolite of leflunomide, A77 1726, on feline herpesvirus-1.

OBJECTIVE: To determine whether the active metabolite of leflunomide, A77 1726 (A77), inhibits replication of feline herpesvirus-1 (FHV-1) in cell culture. STUDY POPULATION: Crandell Rees feline kidney (CRFK) cell cultures. PROCEDURES: Cell cultures were inoculated with FHV-1 and treated simultaneously with concentrations of A77 ranging from 0 to 200microM. The antiviral effect of A77 was determined by use of conventional plaque reduction assays. The effect of A77 on viral load was determined via real-time PCR analysis, and transmission electron microscopy was used to evaluate the effect of A77 on viral morphology. To determine whether the antiviral effect was attributable to alterations in CRFK cell viability and number, CRFK cells were treated with various concentrations of A77 and stained with Annexin V and propidium iodide to assess apoptosis and a mitochondrial function assay was used to determine cell viability. RESULTS: Concentrations of A77 > or = 20microM were associated with substantial reduction in plaque number and viral load. Concentrations > or = 100microM were associated with complete suppression of plaque formation. At low concentrations of A77, clusters of intracytoplasmic virus particles that appeared to lack tegument and an external membrane were detected. Treatment of uninfected CRFK cell monolayers with A77 was associated with reduction in mitochondrial function with minimal evidence of apoptosis. CONCLUSIONS AND CLINICAL RELEVANCE: Leflunomide may be an alternative to current calcineurin-based immunosuppressive protocols used in feline organ transplantation because of its antiherpesviral activity.

Incidence of and risk factors for diabetes mellitus in cats that have undergone renal transplantation: 187 cases (1986-2005).

OBJECTIVE: To compare incidence of diabetes mellitus in cats that had undergone renal transplantation with incidence in cats with chronic renal failure, compare mortality rates in cats that underwent renal transplantation and did or did not develop diabetes mellitus, and identify potential risk factors for development of posttransplantation diabetes mellitus (PTDM) in cats. DESIGN: Retrospective case series. ANIMALS: 187 cats that underwent renal transplantation. PROCEDURES: Medical records were reviewed. RESULTS: 26 of the 187 (13.9%) cats developed PTDM, with the incidence of PTDM being 66 cases/1,000 cat years at risk. By contrast, the incidence of diabetes mellitus among a comparison population of 178 cats with chronic renal failure that did not undergo renal transplantation was 17.9 cases/1,000 cat years at risk, and cats that underwent renal trans-plantation were 5.45 times as likely to develop diabetes mellitus as were control cats with chronic renal failure. The mortality rate among cats with PTDM was 2.38 times the rate among cats that underwent renal transplantation but did not develop PTDM. Age, sex, body weight, and percentage change in body weight were not found to be significantly associated with development of PTDM. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats that undergo renal transplantation have an increased risk of developing diabetes mellitus, compared with cats with chronic renal failure, and that mortality rate is higher for cats that develop PTDM than for cats that do not.

Surgical management of left-divisional intrahepatic portosystemic shunts: outcome after partial ligation of, or ameroid ring constrictor placement on, the left hepatic vein in twenty-eight dogs (1995-2005).

OBJECTIVES: To evaluate outcome in dogs with left divisional intrahepatic portosystemic shunts (PSS) treated by partial ligation (PL) or ameroid ring constrictor (ARC) placement on the left hepatic vein. DESIGN: Retrospective study. ANIMALS: Dogs (n=28) with left divisional intrahepatic PSS. METHODS: Retrieved data from medical records of dogs with left divisional intrahepatic PSS that had PL (n=17) or ARC (n=11) were signalment, history, clinical signs, preoperative blood work, portal pressure measurements, ARC size, complications and postoperative technetium scintigraphy. Outcome assessed by owner interview 6 months-10 years after surgery was classified as excellent, good or poor. Differences were tested by exact chi2 test. RESULTS: Major complications occurred in 3 dogs: coagulopathy (1 PL dog died), ascites (1 PL dog survived) and seizures (1 ARC dog died). Eight PL dogs had technetium portal scintigraphy; 1 dog was negative and 7 dogs positive for persistent shunting. Seven ARC dogs had scintigraphy; 4 dogs were negative and 3 positive for persistent shunting. In PL dogs, long-term clinical outcome was excellent (92%) or good (8%) whereas, in ARC dogs it was excellent (20%), good (50%) or poor (30%). This outcome difference between treatment groups was significant (P=.0012). CONCLUSION: Dogs treated by PL had significantly better long-term outcome compared with ARC treated dogs. CLINICAL RELEVANCE: Based on these data, ARC placement on the left hepatic vein in dogs with left-divisional intrahepatic PSS cannot be recommended.

Evaluation of the effects of ischemic injury and ureteral obstruction on delayed graft function in cats after renal autotransplantation.

OBJECTIVE: To determine the relative importance of ischemic injury to delayed graft function (DGF) in cats. STUDY DESIGN: Experimental study. ANIMALS: Six intact female cats. METHODS: Cats had renal autograft transplantation without ureteral transection and reimplantation and a contralateral nephrectomy. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured regularly and abdominal ultrasound was performed before surgery, the day after surgery and twice weekly thereafter. Ultrasound-guided renal biopsy was performed on day 7. Cats were euthanatized on day 21. Histology of the autograft, ureter, bladder, vascular anastomoses sites, and contralateral kidney were performed. Observations were compared with those from an historic group of research cats that had extravesicular ureteroneocystostomy and contralateral nephrectomy. RESULTS: Five cats completed the study. Serum creatinine and BUN concentrations increased after surgery, peaking at 3.2+/-0.8 and 77.6+/-15.9 mg/dL, respectively, 1-2 days after surgery. Serum creatinine concentration returned to the reference interval by 6 days after surgery. BUN gradually decreased in all cats but did not return to the reference interval by study end. Serum creatinine and BUN concentrations were consistently lower but not significantly so (P=.29 and .56, respectively) compared with the historic ureteroneocystostomy group. No ultrasonographic abnormalities or renal biopsy histologic abnormalities were observed. At necropsy, 1 autograft had generalized interstitial fibrosis. CONCLUSION: Harvesting the renal graft and the ischemia before revascularization causes impaired renal function after engraftment. CLINICAL RELEVANCE: The process of harvesting and reimplanting the renal graft can contribute to DGF in cats, independent of ureteral obstruction.

In vitro evaluation of the effect of a novel immunosuppressive agent, FTY720, on the function of feline neutrophils.

OBJECTIVE: To use in vitro assays to evaluate the effects of a novel immunosuppressive agent, FTY720, on biological functions (migration, phagocytosis, and production of reactive-oxygen species [ROS]) of feline peripheral neutrophils and determine the cytotoxic effects of FTY720 on feline peripheral neutrophils. SAMPLE POPULATION: Peripheral neutrophils obtained from 8 healthy cats. PROCEDURE: Peripheral neutrophils were isolated from blood samples obtained from the 8 cats and exposed to the phosphorylated form of FTY720 (FTY720-P). A fluorescence-based in vitro evaluation of migration was performed. Phagocytosis of microbes and production of ROS were evaluated by use of a 2-color flow cytometry system. Samples of whole blood obtained from the cats were incubated with various concentrations of FTY720-P, fluorescein-labeled Staphylococcus aureus, and dihydroethidium. Cytotoxic effects were evaluated by use of propidium iodide staining. RESULTS: Addition of FTY720-P caused a slight non-significant decrease in phagocytosis and production of ROS by feline peripheral neutrophils. Migration activity of feline peripheral neutrophils was significantly increased by the addition of FTY720-P. Addition of FTY720-P at concentrations considered for clinical use did not increase the death rate of feline peripheral neutrophils. CONCLUSIONS AND CLINICAL RELEVANCE: FTY720 does not inhibit critical functions of feline peripheral neutrophils in vitro.

Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes.

BACKGROUND: The use of porcine cells and organs as a source of xenografts for human patients would vastly increase the donor pool; however, both humans and Old World primates vigorously reject pig tissues due to xenoantibodies that react with the polysaccharide galactose alpha (1,3) galactose (alphaGal) present on the surface of many porcine cells. We previously examined the xenoantibody response in patients exposed to porcine hepatocytes via treatment(s) with bioartficial liver devices (BALs), composed of porcine cells in a support matrix. We determined that xenoantibodies in BAL-treated patients are predominantly directed at porcine alphaGal carbohydrate epitopes, and are encoded by a small number of germline heavy chain variable region (VH) immunoglobulin genes. The studies described in this manuscript were designed to identify whether the xenoantibody responses and the IgVH genes encoding antibodies to porcine hepatocytes in non-human primates used as preclinical models are similar to those in humans. Adult non-immunosuppressed rhesus monkeys (Macaca mulatta) were injected intra-portally with porcine hepatocytes or heterotopically transplanted with a porcine liver lobe. Peripheral blood leukocytes and serum were obtained prior to and at multiple time points after exposure, and the immune response was characterized, using ELISA to evaluate the levels and specificities of circulating xenoantibodies, and the production of cDNA libraries to determine the genes used by B cells to encode those antibodies. RESULTS: Xenoantibodies produced following exposure to isolated hepatocytes and solid organ liver grafts were predominantly encoded by genes in the VH3 family, with a minor contribution from the VH4 family. Immunoglobulin heavy-chain gene (VH) cDNA library screening and gene sequencing of IgM libraries identified the genes as most closely-related to the IGHV3-11 and IGHV4-59 germline progenitors. One of the genes most similar to IGHV3-11, VH3-11cyno, has not been previously identified, and encodes xenoantibodies at later time points post-transplant. Sequencing of IgG clones revealed increased usage of the monkey germline progenitor most similar to human IGHV3-11 and the onset of mutations. CONCLUSION: The small number of IGVH genes encoding xenoantibodies to porcine hepatocytes in non-human primates and humans is highly conserved. Rhesus monkeys are an appropriate preclinical model for testing novel reagents such as those developed using structure-based drug design to target and deplete antibodies to porcine xenografts.

Renal transplantation in cats with calcium oxalate urolithiasis: 19 cases (1997-2004).

OBJECTIVE: To determine outcome of renal transplantation in cats with renal failure associated with calcium oxalate urolithiasis. DESIGN: Retrospective case series. ANIMALS: 19 cats. PROCEDURE: Medical records were reviewed for evaluation of signalment, preoperative clinical signs, physical examination results, dietary history, clinicopathologic data, abdominal imaging, postoperative diet, complications, and long-term outcome. RESULTS: The domestic shorthair was the most common breed represented. There were 13 spayed females and 7 castrated males. Mean age was 6.8 years. Clinical signs included weight loss, lethargy, vomiting, anorexia, polyuria, and polydipsia. Before surgery, cats received commercially available canned or dry food (n = 10), a prescription renal failure diet (5), a commercial diet to manage struvite crystalluria (1), or an unknown diet (3). Seventeen cats were anemic. All cats were azotemic. Hypercalcemia was detected in 7 cats. Abdominal imaging revealed nephrolithiasis, ureterolithiasis, or both in all cats. Median duration of survival of all cats was 605 days. Eight cats were alive 282 to 2,005 days (median, 1,305 days) after surgery. Eleven cats died 2 to 1,197 days (median, 300 days) after surgery. Five cats formed calculi in their allograft (120 to 665 days). Two of the 5 cats that formed calculi were hypercalcemic. Four of the 5 cats died following complications associated with formation of calculi. CONCLUSIONS AND CLINICAL RELEVANCE: Renal transplantation appears to be a viable option for cats in renal failure secondary to calcium oxalate urolithiasis. In addition to reported complications in renal transplant recipients, formation of calculi within the allograft may also occur.

Results of clinical renal transplantation in 15 dogs using triple drug immunosuppressive therapy.

OBJECTIVE: To evaluate outcome of renal transplantation in dogs administered cyclosporine, azathioprine, and prednisolone immunosuppression. STUDY DESIGN: Prospective clinical study. ANIMALS: Fifteen dogs with chronic renal failure. RESULTS: Nine dogs died within 1 month of surgery; 5 died from complications associated with generalized thromboembolism. Three dogs survived for 6-25 months. Three dogs alive at the time of this report have survived 22-48 months; however, all 3 dogs have had bacterial infections that responded to antibiotic therapy. There was no biochemical evidence of acute allograft rejection in any dog. Perioperative use of enoxaparin may have prevented thromboembolism in 5 dogs. CONCLUSIONS: Triple drug immunosuppressive therapy used in this study prevented acute renal allograft rejection in 6 dogs that survived >4 weeks; however, immunosuppression was excessive, resulting in an unacceptable frequency of infection and other drug-related complications. Perioperative anticoagulation therapy seem to be warranted. CLINICAL RELEVANCE: Survival time and quality of life for this group of dogs was poor; however, there was no evidence of acute rejection in the dogs surviving >4 weeks. This protocol should only be used if the degree of immunosuppression is reduced, and early evidence of allograft rejection is monitored by renal biopsy or markers of lymphocyte activation.

Human tissue-engineered blood vessels for adult arterial revascularization.

There is a crucial need for alternatives to native vein or artery for vascular surgery. The clinical efficacy of synthetic, allogeneic or xenogeneic vessels has been limited by thrombosis, rejection, chronic inflammation and poor mechanical properties. Using adult human fibroblasts extracted from skin biopsies harvested from individuals with advanced cardiovascular disease, we constructed tissue-engineered blood vessels (TEBVs) that serve as arterial bypass grafts in long-term animal models. These TEBVs have mechanical properties similar to human blood vessels, without relying upon synthetic or exogenous scaffolding. The TEBVs are antithrombogenic and mechanically stable for 8 months in vivo. Histological analysis showed complete tissue integration and formation of vasa vasorum. The endothelium was confluent and positive for von Willebrand factor. A smooth muscle-specific alpha-actin-positive cell population developed within the TEBV, suggesting regeneration of a vascular media. Electron microscopy showed an endothelial basement membrane, elastogenesis and a complex collagen network. These results indicate that a completely biological and clinically relevant TEBV can be assembled exclusively from an individual's own cells.

Use of nonpenetrating vascular closure staples in feline renal transplantation.

Renal transplantation is a potential treatment for irreversible renal failure in pet cats. Our aim is to reduce warm ischemic time by using nonpenetrating vascular closure staples (VCS), thereby improving graft survival. Experimental cats were divided into the VCS group (n = 4; autotransplantation) or suture group (n = 6; allotransplantation). The renal artery was anastomosed with the external iliac artery in an end-to-end fashion, and the renal vein was attached to the external iliac vein in an end-to-side fashion. Warm ischemic time as well as arterial and venous anastomotic times were measured. Cats in the suture group were administrated cyclosporine and prednisolone orally after transplantation. Ischemic and anastomotic times in the VCS group were significantly reduced compared with the suture group. Two of 6 allografts had a ureteral anastomotic stricture, and 4 allografts were rejected. Histological findings of autografts showed normal structure. In conclusion, VCS staples were useful in feline renal transplantation.

Evaluation of the prevalence of infections in cats after renal transplantation: 169 cases (1987-2003).

OBJECTIVE: To determine the prevalence of infections developing postoperatively, document the contribution of infection to increased risk of death, and identify risk factors associated with the development of infectious complications in cats after renal transplantation. DESIGN: Retrospective study. ANIMALS: 169 cats that received renal allograft transplants. PROCEDURES: Medical records of cats receiving renal transplants at the University of California from January 1987 through December 2003 were reviewed. RESULTS: 47 infections developed in 43 of 169 cats. Bacterial infections were most common (25/47 cats), followed by viral (13/47), fungal (6/47), and protozoal (3/47) infections. The median duration from transplant surgery to development of infection was 2.5 months. Infection was the second most common cause of death after acute rejection of the transplant, accounting for 14% of deaths overall. Cats with concurrent diabetes mellitus had a significantly increased risk of developing an infection after renal transplantation. Sex, increasing age, concurrent neoplasia, and previous treatment for transplant rejection were not associated with development of infection. CONCLUSIONS AND CLINICAL RELEVANCE: Infection was a common complication and an important cause of death or euthanasia in cats after renal transplantation. Development of diabetes mellitus after transplantation significantly increased the risk of infection.

Identification of the V genes encoding xenoantibodies in non-immunosuppressed rhesus monkeys.

The major immunological barrier that prevents the use of wild-type pig xenografts as an alternative source of organs for human xenotransplantation is antibody-mediated rejection. In this study, we identify the immunoglobulin variable region heavy (IgV(H)) chain genes encoding xenoantibodies to porcine heart and fetal porcine islet xenografts in non-immunosuppressed rhesus monkeys. We sought to compare the IgV(H) genes encoding xenoantibodies to porcine islets and solid organ xenografts. The immunoglobulin M (IgM) and IgG xenoantibody response was analysed by enzyme-linked immunosorbent assay and cDNA libraries from peripheral blood lymphocytes were prepared and sequenced. The relative frequency of IgV(H) gene usage was established by colony filter hybridization. Induced xenoantibodies were encoded by the IGHV3-11 germline progenitor, the same germline gene that encodes xenoantibodies in humans mounting active xenoantibody responses. The immune response to pig xenografts presented as solid organs or isolated cells is mediated by identical IgV(H) genes in rhesus monkeys. These animals represent a clinically relevant model to identify the immunological basis of pig-to-human xenograft rejection.

Evaluation of ameroid ring constrictors for treatment for single extrahepatic portosystemic shunts in dogs: 168 cases (1995-2001).

OBJECTIVES: To evaluate use of an ameroid ring constrictor (ARC) for treatment for single extrahepatic portosystemic shunts (PSSs) and identify factors associated with postoperative death, continued portosystemic shunting, and long-term outcome in dogs. DESIGN: Retrospective study. ANIMALS: 168 dogs with a single extrahepatic PSS. PROCEDURE: Medical records of dogs that had a single extrahepatic PSS and were treated with an ARC were reviewed. Signalment, history, clinical signs, results of preoperative blood analyses and portal pressure measurements, PSS location, ARC size, postoperative complications, and postoperative scintigraphy results were recorded. Owners were interviewed 6 months to 6 years after surgery. Results-Postoperative complications developed in 10% of dogs. Postoperative mortality rate was 7.1%. Predictive factors for postoperative death included high preoperative WBC count and postoperative complications. Twenty-one percent of dogs in which portal scintigraphy was performed 6 to 10 weeks after surgery had continued shunting. Predictive factors for persistent shunting included low preoperative plasma albumin concentration, high portal pressure after complete occlusion, and high portal pressure difference (postocclusion minus baseline). Clinical outcome in 108 dogs was classified as excellent (80%), good (14%), or poor (6%). Predictive factors for excellent long-term clinical outcome included high preoperative plasma albumin concentration, low preoperative leukocytosis, low portal pressure after complete occlusion, absence of postoperative seizures, and absence of continued shunting. CONCLUSIONS AND CLINICAL RELEVANCE: Use of an ARC for treatment for a single extrahepatic PSS resulted in low morbidity and mortality rates. Certain preoperative factors were associated with increased risk of postoperative death, continued portosystemic shunting, and long-term outcome.