Ex vivo comparison of different thoracoabdominal stapler sizes for typhlectomy in canine cadavers.

OBJECTIVE: To determine the influence of staple size on leakage pressure of typhlectomy sites in canine cadavers. STUDY DESIGN: Randomized, experimental cadaveric study. ANIMALS: Twenty-four fresh canine cadavers. METHODS: Ileocecocolic segments were exteriorized following right paracostal laparotomy after euthanasia. Cecal base length and wall thickness were measured. Each cecum was randomly assigned to 1 of 3 groups (TA 30 V3 2.5 mm, TA 60 3.5 mm, and TA 60 4.8 mm). The cecal base was stapled and the cecum was removed. A 10 cm segment including the stapled cecal excision site was tested for initial leak pressure. RESULTS: The mean ± standard deviation body weights across the groups were 18.7 ± 6.1 kg, 16.2 ± 7.5 kg, and 14.2 ± 5.5 kg for the TA 30 V3 2.5 mm, TA 60 3.5 mm, and TA 60 4.8 mm groups, respectively (P = .48). There were no differences for mean cecal base length or wall thickness. Mean initial leak pressure (ILP) across groups was 182 ± 111 mmHg (TA 30 V3 2.5 mm), 112 ± 57 mmHg (TA 60 3.5 mm), and 77 ± 60 mmHg (TA 60 4.8 mm) (P = .78). CONCLUSION: Each stapler size that was evaluated resulted in a mean ILP in excess of typical intraluminal pressures under normal circumstances. There were no differences among groups. CLINICAL SIGNIFICANCE: The results of this cadaveric study support the use of any of the stapler sizes evaluated in similarly sized dogs. A prospective study is needed to be able to correlate stapler size and clinical outcome.

Multimodal imaging of bacterial-host interface in mice and piglets with Staphylococcus aureus endocarditis.

Acute bacterial endocarditis is a rapid, difficult to manage, and frequently lethal disease. Potent antibiotics often cannot efficiently kill Staphylococcus aureus that colonizes the heart's valves. S. aureus relies on virulence factors to evade therapeutics and the host's immune response, usurping the host's clotting system by activating circulating prothrombin with staphylocoagulase and von Willebrand factor-binding protein. An insoluble fibrin barrier then forms around the bacterial colony, shielding the pathogen from immune cell clearance. Targeting virulence factors may provide previously unidentified avenues to better diagnose and treat endocarditis. To tap into this unused therapeutic opportunity, we codeveloped therapeutics and multimodal molecular imaging to probe the host-pathogen interface. We introduced and validated a family of small-molecule optical and positron emission tomography (PET) reporters targeting active thrombin in the fibrin-rich environment of bacterial colonies. The imaging agents, based on the clinical thrombin inhibitor dabigatran, are bound to heart valve vegetations in mice. Using optical imaging, we monitored therapy with antibodies neutralizing staphylocoagulase and von Willebrand factor-binding protein in mice with S. aureus endocarditis. This treatment deactivated bacterial defenses against innate immune cells, decreased in vivo imaging signal, and improved survival. Aortic or tricuspid S. aureus endocarditis in piglets was also successfully imaged with clinical PET/magnetic resonance imaging. Our data map a route toward adjuvant immunotherapy for endocarditis and provide efficient tools to monitor this drug class for infectious diseases.

Successful management of cutaneous paralagenidiosis in a dog treated with mefenoxam, minocycline, prednisone, and hyperbaric oxygen therapy.

Cutaneous oomycotic infections are a rare dermatological disease primarily affecting horses and dogs. Response to medical management with antifungal therapies is poor because these organisms are not true fungi. Complete cure is unlikely if the infected tissue is unable to be completely surgically excised. This is a case report of successfully-managed cutaneous paralagenidiosis infection of the perianal tissue in an 11-month-old male intact Labrador retriever utilizing hyperbaric oxygen therapy, corticosteroids, minocycline, mefenoxam, and surgery.

Partial splenectomy for incidentally detected non-ruptured splenic lesions in dogs: 18 cases (2004-2018).

The objective of this retrospective study was to describe the outcome and incidence of splenic malignancy in 18 dogs undergoing partial splenectomy for incidentally detected, non-ruptured splenic lesions. Incidence of splenic malignancy in the present study was 5.6% [95% confidence interval (CI): 0.14% to 27.65%]. Median diameter of splenic nodules was 2 cm (range: 1.5 to 4 cm). Splenic hemangiosarcoma was diagnosed in 1 dog, while the remaining 17 dogs had benign splenic lesions. There was a higher incidence of non-splenic malignancy (50%) than splenic malignancy (5.6%) in the study population. Overall median survival time after surgery was 300 days (range: 4 to 1332 days). Median survival time in dogs with malignant disease (splenic and non-splenic) was 67 days (range: 4 to 425 days) and for non-malignant disease was 727 days (range: 8 to 1332 days). In conclusion, partial splenectomy may be appropriate for small, incidental non-ruptured splenic lesions in dogs.

Splénectomie partielle pour des lésions spléniques non-rupturées détectées de manière fortuite chez des chiens : 18 cas (2004­2018). L'objectif de cette étude rétrospective était de décrire l'issue et la fréquence de malignité splénique chez 18 chiens soumis à une splénectomie partielle pour des lésions spléniques non-rupturées détectées de manière fortuite. La fréquence de malignité splénique dans la présente étude était de 5,6 % [intervalle de confiance de 95 % (CI) : 0,14 % à 27,65 %]. Le diamètre médian des nodules spléniques était de 2 cm (écart : 1,5 à 4 cm). Un hémangiosarcome splénique fut diagnostiqué chez un chien, alors que les 17 autres chiens avaient des lésions spléniques bénignes. Il y avait une plus grande fréquence de malignité non-splénique (50 %) que de malignité splénique (5,6 %) dans la population étudiée. Globalement, le temps de survie médian après la chirurgie était de 300 jours (écart : 4 à 1332 jours). Le temps de survie médian chez les chiens avec une condition maligne (splénique et non-splénique) était de 67 jours (écart : 4 à 425 jours) et pour ceux avec une condition non-maligne il était de 727 jours (écart : 8 à 1332 jours). En conclusion, une splénectomie partielle peut être appropriée pour des petites lésions spléniques secondaires non-rupturées.(Traduit par Dr Serge Messier).

Description of a novel technique for surgical placement of gastrostomy tubes in dogs.

BACKGROUND: Early enteral nutrition in dogs with critical illnesses, including septic peritonitis, has been shown to have a positive influence on patient outcome. Surgical placement of a gastrostomy tube (GT) is one option for providing early enteral nutrition. Complications, including premature tube removal or separation of the stomach from the body wall, can result in leakage of gastric contents into the abdominal cavity and subsequent peritonitis. A safe and reliable technique for the placement of a GT is desirable to minimize such complications. KEY CONCEPTS: A modified method for surgical placement of a GT is described. A thoracic trocar catheter (TTC) with an attached Pezzer tube is inserted through a gastrotomy incision and exited through the left gastric body and body wall. A left-sided tube gastropexy is performed using an interlocking box (ILB) pattern. SIGNIFICANCE: GT placement using a TTC is efficient, requiring minimal additional anesthesia time. The gastric defect created by the TTC conforms well with the Pezzer tube. As such, placement and utilization of the ILB suture pattern enables removal of the GT in the early postoperative period, if appropriate.

Sentinel lymph node mapping of the canine anal sac using lymphoscintigraphy: A pilot study.

Sentinel lymph node mapping and biopsy are important parts of oncologic staging in human medicine. Sentinel lymph node mapping enables identification of the first lymph node to receive lymphatic drainage while avoiding unnecessary lymph node dissection. Anal sac adenocarcinoma is the most common malignant neoplasm of the canine perineal area. For dogs with anal sac adenocarcinoma, lympadenectomy and metastasis to the iliosacral lymphocentrum are negative prognostics indicators. The objectives of this prospective, two by two, crossover pilot study were to establish the feasibility of lymphoscintigraphy using Technetium-99 sulfur colloid of the canine anal sac of healthy dogs, compare two injection techniques, and the time for identification of sentinel lymph nodes using each technique. We hypothesized that both intramural and perimural injections of the canine anal sac would identify similar sentinel lymph node drainage. The sentinel lymph node was identified in all dogs using either technique. Intramural injection of the canine anal sac showed radiopharmaceutical uptake faster than perimural injection technique (P = 0.040). There was concordance between intramual and perimural techniques for the sentinel lymph node identified in 50% of cases. A sacral lymph node was identified as sentinel in three of eight dogs (37.5%). Lymphoscintigraphy of the canine anal sac is safe and feasible in normal dogs; however, the method of injection technique seems to have a significant effect on the sentinel lymph node identified.

High-resolution CT evaluation of bronchial lumen to vertebral body, pulmonary artery to vertebral body and bronchial lumen to pulmonary artery ratios in Dirofilaria immitis-infected cats with and without selamectin administration.

Objectives The bronchial lumen to pulmonary artery (BA) ratio is utilized to evaluate pulmonary pathology on CT images. The BA ratio may be unreliable when changes are present in bronchial and pulmonary arteries concurrently. Bronchial lumen to vertebral body (BV) and pulmonary artery to vertebral body (AV) ratios have been established in normal cats and may serve as an alternative. This study aimed to evaluate the BV, AV and BA ratios in cats before and after infection with Dirofilaria immitis, with and without selamectin administration, and to characterize the distribution of disease. Methods Archived CT images were reviewed from three groups of cats: D immitis-infected untreated (n = 6); infected pretreated with selamectin (n = 6); and uninfected untreated (n = 5). The BV, AV and BA ratios were calculated for all lung lobes for baseline (D0) and day 240 (D240) postinfection. Ratios and percentage change from baseline were compared between lobes and between groups. Results BV and AV ratios were more consistent in identifying abnormalities when disease was present in bronchial and arteries concurrently than BA ratios. Infected untreated cats had significant changes in both BV and AV ratios and percentage change from baseline. Abnormal BV and AV ratios were noted in the infected selamectin group, although less widely distributed. Conclusions and relevance The BV and AV ratios more accurately identified bronchial and pulmonary artery abnormalities in D immitis-infected cats. Both bronchial and pulmonary artery changes were present in infected cats, decreasing the diagnostic application of the BA ratio. Pulmonary artery changes were more widely distributed than bronchial changes in the lung. Heartworm-infected cats receiving selamectin had bronchial and pulmonary artery changes but to a lesser extent than untreated heartworm-infected cats. The CT-derived BV and AV ratios are a useful measure to evaluate lung disease of cats.

High-resolution computed tomography evaluation of the bronchial lumen to vertebral body diameter and pulmonary artery to vertebral body diameter ratios in anesthetized ventilated normal cats.

Objectives Bronchial lumen to pulmonary artery diameter (BA) ratio has been utilized to investigate pulmonary pathology on high-resolution CT images. Diseases affecting both the bronchi and pulmonary arteries render the BA ratio less useful. The purpose of the study was to establish bronchial lumen diameter to vertebral body diameter (BV) and pulmonary artery diameter to vertebral body diameter (AV) ratios in normal cats. Methods Using high-resolution CT images, 16 sets of measurements (sixth thoracic vertebral body [mid-body], each lobar bronchi and companion pulmonary artery diameter) were acquired from young adult female cats and 41 sets from pubertal female cats. Results Young adult and pubertal cat BV ratios were not statistically different from each other in any lung lobe. Significant differences between individual lung lobe BV ratios were noted on combined age group analysis. Caudal lung lobe AV ratios were significantly different between young adult and pubertal cats. All other lung lobe AV ratios were not significantly different. Caudal lung lobe AV ratios were significantly different from all other lung lobes but not from each other in both the young adult and pubertal cats. Conclusions and relevance BV ratio reference intervals determined for individual lung lobes could be applied to both young adult and pubertal cats. Separate AV ratios for individual lung lobes would be required for young adult and pubertal cats. These ratios should allow more accurate evaluation of cats with concurrent bronchial and pulmonary arterial disease.

Biomechanical comparison of two ostectomy configurations for partial mandibulectomy.

OBJECTIVE: To determine the stiffness and load to failure of two different ostectomy configurations using canine mandibles. STUDY DESIGN: Cadaveric biomechanical assessment. ANIMALS: Paired mandibles (n = 30). METHODS: Standardized partial ostectomies were created on the alveolar surface of 30 mandibles. Samples were randomly assigned to right-angled (n = 15) or crescentic ostectomy (n = 15). Excision spanned the mesial aspect of the fourth premolar tooth to the distal aspect of first molar tooth. Mandibles were loaded to failure in three-point bending. The stiffness, displacement at maximum load, and load to failure were measured. RESULTS: There was no significant difference in stiffness (p = 0.59), displacement at maximum load (p = 0.16) and load to failure (p = 0.76) between right-angled or crescentic ostectomy. Right-angled and crescentic ostectomy failed mostly by fracture through an empty alveolus (11/15 and 13/15, respectively). CLINICAL RELEVANCE: No significant differences in load to failure or stiffness between ostectomy techniques were observed. Crescentic ostectomy did not improve the acute load to failure for partial mandibulectomy. The empty alveolus served as a focal stress concentration point eliminating the potential mechanical advantage of a crescentic ostectomy.

Effect of histologic processing on dimensions of skin samples obtained from cat cadavers.

OBJECTIVE To determine changes in dimensions of feline skin samples as a result of histologic processing and to identify factors that contributed to changes in dimensions of skin samples after sample collection. SAMPLE Cadavers of 12 clinically normal cats. PROCEDURES Skin samples were obtained bilaterally from 3 locations (neck, thorax, and tibia) of each cadaver; half of the thoracic samples included underlying muscle. Length, width, and depth were measured at 5 time points (before excision, after excision, after application of ink to mark tissue margins, after fixation in neutral-buffered 10% formalin for 36 hours, and after completion of histologic processing and staining with H&E stain). Measurements obtained after sample collection were compared with measurements obtained before excision. RESULTS At the final time point, tissue samples had decreased in length (mean decrease, 32.40%) and width (mean decrease, 34.21%) and increased in depth (mean increase, 54.95%). Tissue from the tibia had the most shrinkage in length and width and that from the neck had the least shrinkage. Inclusion of underlying muscle on thoracic skin samples did not affect the degree of change in dimensions. CONCLUSIONS AND CLINICAL RELEVANCE In this study, each step during processing from excision to formalin fixation and histologic processing induced changes in tissue dimensions, which were manifested principally as shrinkage in length and width and increase in depth. Most of the changes occured during histologic processing. Inclusion of muscle did not affect thoracic skin shrinkage. Shrinkage should be a consideration when interpreting surgical margins in clinical cases. 945).

Thoracic surgery; important considerations and practical steps.

Thoracic surgery is a challenge for any veterinary surgeon. A review of several important articles on topics relative to thoracotomy procedures is presented. Discussion also includes an evaluation of availability of appropriate surgical facilities, necessary equipment before undertaking thoracic surgical procedures, and the essentials and pitfalls to making an approach and effectively closing the thoracic cavity of a dog or cat. This article reviews the 3 primary types of thoracotomy: lateral (intercostal) thoracotomy, median sternotomy, and transdiaphragmatic thoracotomy. Essential anatomy, surgical approach, and various techniques to ensure effective and durable thoracotomy closure are presented.

Chronic ß1-adrenergic blockade enhances myocardial ß3-adrenergic coupling with nitric oxide-cGMP signaling in a canine model of chronic volume overload: new insight into mechanisms of cardiac benefit with selective ß1-blocker therapy.

The ß1-adrenergic antagonist metoprolol improves cardiac function in animals and patients with chronic heart failure, isolated mitral regurgitation (MR), and ischemic heart disease, though the molecular mechanisms remain incompletely understood. Metoprolol has been reported to upregulate cardiac expression of ß3-adrenergic receptors (ß3AR) in animal models. Myocardial ß3AR signaling via neuronal nitric oxide synthase (nNOS) activation has recently emerged as a cardioprotective pathway. We tested whether chronic ß1-adrenergic blockade with metoprolol enhances myocardial ß3AR coupling with nitric oxide-stimulated cyclic guanosine monophosphate (ß3AR/NO-cGMP) signaling in the MR-induced, volume-overloaded heart. We compared the expression, distribution, and inducible activation of ß3AR/NO-cGMP signaling proteins within myocardial membrane microdomains in dogs (canines) with surgically induced MR, those also treated with metoprolol succinate (MR+ßB), and unoperated controls. ß3AR mRNA transcripts, normalized to housekeeping gene RPLP1, increased 4.4 × 10(3)- and 3.2 × 10(2)-fold in MR and MR+ßB hearts, respectively, compared to Control. Cardiac ß3AR expression was increased 1.4- and nearly twofold in MR and MR+ßB, respectively, compared to Control. ß3AR was detected within caveolae-enriched lipid rafts (Cav3(+)LR) and heavy density, non-lipid raft membrane (NLR) across all groups. However, in vitro selective ß3AR stimulation with BRL37344 (BRL) triggered cGMP production within only NLR of MR+ßB. BRL induced Ser (1412) phosphorylation of nNOS within NLR of MR+ßB, but not Control or MR, consistent with detection of NLR-specific ß3AR/NO-cGMP coupling. Treatment with metoprolol prevented MR-associated oxidation of NO biosensor soluble guanylyl cyclase (sGC) within NLR. Metoprolol therapy also prevented MR-induced relocalization of sGCß1 subunit away from caveolae, suggesting preserved NO-sGC-cGMP signaling, albeit without coupling to ß3AR, within MR+ßB caveolae. Chronic ß1-blockade is associated with myocardial ß3AR/NO-cGMP coupling in a microdomain-specific fashion. Our canine study suggests that microdomain-targeted enhancement of myocardial ß3AR/NO-cGMP signaling may explain, in part, ß1-adrenergic antagonist-mediated preservation of cardiac function in the volume-overloaded heart.

Effect of vascular seal configuration using the LigaSure on arterial challenge pressure, time for seal creation, and histologic features.

OBJECTIVE: To determine the effectiveness of a vascular sealing technology on canine carotid arteries using various seal configurations to achieve maximal vessel security. STUDY DESIGN: Ex-vivo study. ANIMALS: Dogs (n = 20). METHODS: Carotid arteries (n = 40) were removed from the mid-cervical region of recently euthanatized dogs. Harvested vessels were closed with 2 circumferential ligatures (Group 1) or a vascular sealing device using 1 of 4 seal configurations of 1 or 2 seals combined with 1 or 2 machine activations/seal. The artery was instrumented to measure intraluminal pressure to evaluate the security of each seal during saline infusion. Maximum intraluminal pressure was recorded for each group, and time for application of each sealing protocol was compared using 1-way ANOVA and Tukey's test for multiple comparisons. Histologic features of the sealing protocols were evaluated. RESULTS: Arterial closures for each group were effective in preventing leakage up to 300 mmHg. There was no significant difference in maximum intraluminal pressure between any group. A significant difference (P ≤ .001) was observed for time to seal creation between the groups using 1 and 2 seals. Histologic evaluation showed no differences between the different sealing protocols. CONCLUSION: Vessel sealing using a single seal created with a single activation cycle was adequate for sealing canine carotid arteries. Histologic examination did not demonstrate any disadvantages to multiple seals or multiple cycle activations.

Isometric responses of isolated intrapulmonary bronchioles from cats with and without adult heartworm infection.

OBJECTIVE: To determine the isometric responses of isolated intrapulmonary bronchioles from cats with and without adult heartworm infection. ANIMALS: 13 purpose-bred adult cats. PROCEDURES: Cats were infected with 100 third-stage larvae or received a sham inoculation, and the left caudal lung lobe was collected 278 to 299 days after infection. Isometric responses of intrapulmonary bronchiolar rings were studied by use of a wire myograph. Three cycles of contractions induced by administration of 10 µM acetylcholine were followed by administration of the contractile agonists acetylcholine, histamine, and 5-hydroxy-tryptamine. To evaluate relaxation, intrapulmonary bronchiolar rings were constricted by administration of 10 µM 5-hydroxytryptamine, and concentration-response curves were generated from administration of sodium nitroprusside, isoproterenol, and substance P. RESULTS: Compared with tissues from control cats, contractile responses to acetylcholine and 5-hydroxytryptamine were reduced in tissues from heartworm-infected cats. Relaxation to isoproterenol was significantly reduced in tissues from heartworm-infected cats. Relaxation to substance P was increased in tissues from heartworm-infected cats, but relaxation to sodium nitroprusside was unchanged. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that despite increased bronchiolar wall thickness in heartworm-infected cats, a hyperreactive response of the bronchiolar smooth muscle is not the primary mechanism of respiratory tract clinical signs. Reduced response of the airway to isoproterenol may indicate refractoriness to bronchiolar relaxation in heartworm-infected cats.

Proteasome inhibitors enhance gene delivery by AAV virus vectors expressing large genomes in hemophilia mouse and dog models: a strategy for broad clinical application.

Delivery of genes that are larger than the wild-type adeno-associated virus (AAV) 4,681 nucleotide genome is inefficient using AAV vectors. We previously demonstrated in vitro that concurrent proteasome inhibitor (PI) treatment improves transduction by AAV vectors encoding oversized transgenes. In this study, an AAV vector with a 5.6 kilobase (kb) factor VIII expression cassette was used to test the effect of an US Food and Drug Administration-approved PI (bortezomib) treatment concurrent with vector delivery in vivo. Intrahepatic vector delivery resulted in factor VIII expression that persisted for >1 year in hemophilia mice. Single-dose bortezomib given with AAV2 or AAV8 factor VIII vector enhanced expression on average ~600 and ~300%, respectively. Moreover, coadministration of AAV8.canineFVIII (1 × 10(13) vg/kg) and bortezomib in hemophilia A dogs (n = 4) resulted in normalization of the whole blood clotting time (WBCT) and 90% reduction in hemorrhages for >32 months compared to untreated hemophilia A dogs (n = 3) or dogs administered vector alone (n = 3). Demonstration of long-term phenotypic correction of hemophilia A dogs with combination adjuvant bortezomib and AAV vector expressing the oversized transgene establishes preclinical studies that support testing in humans and provides a working paradigm to facilitate a significant expansion of therapeutic targets for human gene therapy.

Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy.

Preclinical studies and initial clinical trials have documented the feasibility of adenoassociated virus (AAV)-mediated gene therapy for hemophilia B. In an 8-year study, inhibitor-prone hemophilia B dogs (n = 2) treated with liver-directed AAV2 factor IX (FIX) gene therapy did not have a single bleed requiring FIX replacement, whereas dogs undergoing muscle-directed gene therapy (n = 3) had a bleed frequency similar to untreated FIX-deficient dogs. Coagulation tests (whole blood clotting time [WBCT], activated clotting time [ACT], and activated partial thromboplastin time [aPTT]) have remained at the upper limits of the normal ranges in the 2 dogs that received liver-directed gene therapy. The FIX activity has remained stable between 4% and 10% in both liver-treated dogs, but is undetectable in the dogs undergoing muscle-directed gene transfer. Integration site analysis by linear amplification-mediated polymerase chain reaction (LAM-PCR) suggested the vector sequences have persisted predominantly in extrachromosomal form. Complete blood count (CBC), serum chemistries, bile acid profile, hepatic magnetic resonance imaging (MRI) and computed tomography (CT) scans, and liver biopsy were normal with no evidence for tumor formation. AAV-mediated liver-directed gene therapy corrected the hemophilia phenotype without toxicity or inhibitor development in the inhibitor-prone null mutation dogs for more than 8 years.

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.

Gallbladder agenesis in a Maltese dog.

This report describes the diagnostic evaluation of a 7-month-old, female Maltese dog with elevated liver enzymes. Marked elevations of alanine transferase were the significant clinical findings. A diagnosis of gallbladder agenesis was made, based on lack of a gallbladder on ultrasonography and on surgical exploration. Gallbladder agenesis is a rare condition described in humans but not previously reported in dogs.

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.