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The female cardioprotective advantage, present in mammals of a reproductively competent age, is lost during the transition to a postreproductive state. The role of reproductive hormones in this transition is most evident in women with premature ovarian failure, where reduced estrogen production has been associated with an increased incidence of early death from cardiovascular disease. Previously, we reported that postreproductive-aged mice that received young ovaries displayed an increased life span. Subsequent histopathological analysis suggested the presence of a cardioprotective effect associated with the restoration of ovarian influence. This restoration in postreproductive-aged mice produced a sharp decrease in evidence of significant cardiomyopathy at death, compared with sham-transplanted mice (36.0% vs. 73.3%, respectively). Within the intact transplant group, evidence of cardiomyopathy at death was decreased in mice that were reproductively cycling at the time of transplant, compared with acyclic mice (26.7% vs. 50.0%, respectively). This observation reflects the importance of timing in restoration of ovarian influence in this study. Transplantation of young ovaries to intact, postreproductive-aged female mice provided significant, long-term restoration of a cardioprotective benefit, similar to that previously present during a reproductively competent age. In these mice, restoration of ovarian influence through ovarian transplantation may, in effect, have postponed the advance of age-associated cardiomyopathy to a point where the disease did not reach a clinically relevant threshold during the lifetime of the recipients. These results offer support for previous clinical observations suggesting that hormone replacement therapy can produce divergent results if initiated during the perimenopausal period, compared with the postmenopausal ages.

Monoallelic RUNX1 mutations cause familial platelet disorder with predisposition for acute myelogenous leukemia (FPD/AML). Sporadic mono- and biallelic mutations are found at high frequencies in AML M0, in radiation-associated and therapy-related myelodysplastic syndrome and AML, and in isolated cases of AML M2, M5a, M3 relapse, and chronic myelogenous leukemia in blast phase. Mutations in RUNX2 cause the inherited skeletal disorder cleidocranial dysplasia (CCD). Most hematopoietic missense mutations in Runx1 involve DNA-contacting residues in the Runt domain, whereas the majority of CCD mutations in Runx2 are predicted to impair CBFbeta binding or the Runt domain structure. We introduced different classes of missense mutations into Runx1 and characterized their effects on DNA and CBFbeta binding by the Runt domain, and on Runx1 function in vivo. Mutations involving DNA-contacting residues severely inactivate Runx1 function, whereas mutations that affect CBFbeta binding but not DNA binding result in hypomorphic alleles. We conclude that hypomorphic RUNX2 alleles can cause CCD, whereas hematopoietic disease requires more severely inactivating RUNX1 mutations.

Objective— To compare 3 techniques for ureteroneocystostomy in cats. Study Design— Experimental surgical study. Animals— Fifteen adult cats. Methods— Cats (15) had ureteroneocystostomy with ureteronephrectomy of the contralateral kidney: 5 cats had an intravesical mucosal apposition technique (modified Leadbetter-Politano; intravesical-MA group), 5 cats had extravesical ureteroneocystostomy (modified Lich Gregoir) using a simple continuous suture pattern (extravesical-SC group) and 5 cats had an extravesical technique using a simple interrupted suture pattern (extravesical-SI group). Renal function was evaluated by measuring serum creatinine concentration. Ultrasonographic assessment of the kidney and ureteroneocystostomy site was performed the day after surgery, twice weekly for 3 weeks and once weekly for the remainder of the study. Cats were euthanatized 50 days after surgery. The kidney and ureter removed at surgery, the remaining kidney, ureter, ureteroneocystostomy site, and bladder were examined histologically. Results— Two extravesical-SC cats were euthanatized because of azotemia and uroabdomen, and 1 died acutely at day 4 for unknown reasons. In the intravesical-MA and extravesical-SI cats, the serum creatinine concentration increased after surgery, peaking at a mean (±SD) of 9.4±2.4 mg/dL and 4.9±3.3 mg/dL on day 3, and decreasing to 3.4±5.7 mg/dL and 1.5±0.4 mg/dL on day 7, respectively. The extravesical-SI technique was associated with consistently lower serum creatinine concentrations for the first week after surgery compared with the other techniques. The mean serum creatinine concentration was within the reference range in cats in the intravesical-MA and extravesical-SI groups by days 10 and 5, respectively. Renal pelvic dilatation occurred in all cats but resolved more rapidly in cats after extravesical techniques. There was no significant difference in serum creatinine concentrations or renal pelvic dilation between the intravesical-MA and extravesical-SI techniques. Bladder mass height at the anastomosis site was significantly larger and persisted for longer with intravesical-MA technique. Conclusion— An extravesical-SI technique is seemingly the choice for ureteroneocystostomy in cats with undilated ureters. Renal pelvic dilation on ultrasound examination should be expected after ureteroneocystostomy in cats. Clinical Relevance— An extravesical ureteroneocystostomy technique using a simple interrupted pattern for anastomosis should be considered in cats undergoing renal transplantation.

Objectives— To evaluate the mechanism of vascular occlusion after placement of an ameroid constrictor (AC) on a large intra-abdominal vein and document changes in blood flow. Study Design— Experimental study. Animals— Six adult dogs. Methods— Six 6.5 mm ACs were digitally scanned to measure area and circumference of the ameroid and inner lumen before surgery. ACs were surgically positioned around the left common iliac vein (CIV) in each dog. Peri-vascular ultrasonic flow probes were positioned on the left CIV cranial to the AC, and on the right CIV as an internal control. Blood flow measurements were recorded daily until there was no, or prolonged minimal, blood flow, at which time the dogs were euthanatized. Left and right CIVs were removed for histologic evaluation, and the ACs re-scanned to evaluate degree and direction of expansion of the ameroid. Results— Reduction in blood flow occurred within 10 days in all dogs. Three dogs had complete occlusion by day 10 from thrombus formation. One dog damaged the flow probes at 13 days when blood flow was approximately 50% of intra-operative values; the dog was euthanatized at 37 days; there was partial occlusion from thrombosis. Two dogs had persistent low blood flow and occlusion from thrombus formation when euthanatized at 59 and 98 days. There was a significant increase in total AC area and outer circumference, and decrease in luminal area and inner circumference when presurgical and postocclusion measurements were compared. Conclusions— Vascular occlusion after placement of an AC on a large intra-abdominal vein occurred from thrombus formation. Clinical Relevance— A similar pattern of venous occlusion may occur after placement of an AC on a portosystemic shunt, which may lead to both short- and long-term complications associated with portal hypertension.

Objectives— To determine whether the microemulsified formulation of cyclosporine (MCsA; Neoral; Novartis A.G.), combined with azathioprine (Imuran; Glaxo Wellcome), and prednisolone (Delta-Cortef; Upjohn), would be effective in preventing acute renal allograft rejection in unrelated mongrel dogs. To document any toxic effects associated with this drug combination. Study Design— Prospective, pilot study. Animals— Four healthy, adult, mongrel, canine renal allograft recipients. Methods— Heterotopic renal transplantation, with bilateral nephrectomy, was performed in 4 dogs. Allografts were harvested from 2 unrelated dogs that were to be euthanatized for reasons unrelated to this study. The dogs were treated for 100 days or until signs of illness or allograft rejection required euthanasia. Microemulsified cyclosporine (20 mg/kg/day), azathioprine (5 mg/kg every other day), and prednisolone (1 mg/kg/day) were administered for the prevention of acute rejection. Body weight, serum biochemistry profiles, complete blood counts, and trough whole-blood cyclosporine concentrations were measured throughout the study. Cyclosporine dose was adjusted to maintain a trough concentration of 400–500 ng/mL. Azathioprine dose was decreased if evidence of hepatotoxicity developed or if the total blood white cell count was

Immunohistochemistry was used to examine feline lymphoid tumors for bcl-2 and MIB- I expression. Tumor tissues from 29 cats were selected to represent 2 groups-cats that did not respond to chemotherapy and cats that responded to therapy. Median bcl-2 immunoreactivity was 60%, and median MIB-1 reactivity was 47%. There was no significant difference in median survival time between cats with tumors with high levels of bcl-2 expression and those with low levels of expression. There was no significant difference in median survival time between cats with tumors with high levels of MIB-1 expression and those with low levels of expression. Mean bcl-2 immunoreactivity was significantly (P = .0004) higher in low-grade (73.2%) than in high-grade (16.9%) lymphomas, whereas the mean MIB-1 immunoreactivity was significantly (P = .0201) higher in high-grade (61.2%) lymphomas than in low-grade (35.0%) lymphomas. The mean bcl-2 immunoreactivity was significantly (P = .0042) greater in T-cell lymphomas (66.8%) than in B-cell lymphomas (22.8%), whereas the mean MIB-1 immunoreactivity was significantly (P = .0052) lower in T-cell lymphomas (36.4%) than in B-cell lymphomas (65.2%). Although expression of bcl-2 and MIB-1 did not appear to be linked to responses to chemotherapy in cats with lymphoma, the data suggest a possible role for these regulatory proteins in the biology of feline lymphomas.

Two hyperplastic parathyroid glands and three solitary parathyroid adenomas were identified using high-resolution ultrasonography in five adult dogs with persistent hypercalcemia. Ultrasonographic features of parathyroid adenomas included visualization of a round or oval, 5 mm or larger, hypoechoic mass in the cranial pole of one thyroid lobe. Each mass had well-defined margins between the thyroid gland and parathyroid adenoma, reduced echogenicity of the adenoma compared to surrounding thyroid parenchyma, and distal enhancement. Ultrasonographic features of the hyperplastic parathyroid glands included hypoechogenicity, compared to surrounding thyroid parenchyma, and a size of approximately 2 mm. Hyperplastic parathyroids were well marginated in one dog and poorly marginated in another dog.