Evaluation of complications and short-term outcome after unilateral or single-session bilateral tibial tuberosity advancement for cranial cruciate rupture in dogs.

OBJECTIVE: To compare the resulting complications, short-term results, and client satisfaction for treatment of cranial cruciate ligament rupture using either unilateral or bilateral single-session tibial tuberosity advancement (TTA) in dogs. METHODS: Medical records of 68 dogs (101 stifles) undergoing unilateral or bilateral single-session TTA were evaluated. Data gathered included signalment, history, physical examination findings, anaesthesia and surgical time, type of cranial cruciate ligament rupture and meniscal injury, implants, and intra-operative and postoperative complications. A mixed effect logistic regression analysis was performed to determine if complications were grouped by surgical procedure. Linear regression was performed to determine the influence of the variables on the occurrence of complications. Values of p <0.05 were considered significant. RESULTS: No major intra-operative complications occurred. Twenty stifles (20%) developed a complication after surgery (11 minor, 9 major). There was no significant difference in occurrence of complications between dogs undergoing unilateral (n = 8) or bilateral single-session (n = 12) TTA (p = 0.69). The only risk factor found to be associated with complication occurrence was age. CLINICAL SIGNIFICANCE: This is the first report evaluating the use of bilateral simultaneous TTA. There was no significant difference in complication rates between unilateral and bilateral single-session TTA. Additional evaluation is needed to fully determine the extent of complications and long-term outcome of bilateral single-session TTA.

Extracellular signal-regulated kinase 1 and 2 are not required for GnRH neuron development and normal female reproductive axis function in mice.

BACKGROUND/AIMS: Selective deletion of extracellular signal-regulated kinase (ERK) 1 and ERK2 in the pituitary gonadotrope and ovarian granulosa cells disrupts female reproductive axis function. Thus, we asked if ERK1 and ERK2 are critical for GnRH neuron ontogeny or the central control of female reproductive function. METHODS: GnRH-Cre-recombinase (Cre+) expressing mice were crossed with mice with a global deletion of ERK1 and a floxed ERK2 allele (Erk1-/Erk2fl/fl) to selectively delete ERK2 in GnRH neurons. RESULTS: Cre-recombinase mRNA was selectively expressed in the brain of Cre+ mice. GnRH neuron number and location were determined during embryogenesis and in the adult. GnRH neuron counts at E15 did not differ between experimental and control groups (1,198 ± 65 and 1,160 ± 80 respectively, p = NS). In adults, numbers of GnRH neurons in the GnRHCre+Erk1-/Erk2- mice (741 ± 157) were similar to those in controls (756 ± 7), without alteration in their distribution across the forebrain. ERK1 and 2 deficiency did not alter the timing of vaginal opening, age at first estrus, or estrous cyclicity. CONCLUSIONS: Although ERK1 and 2 are components of a dominant signaling pathway in GnRH neuronal cells that modulates survival and control of GnRH gene expression, other signaling pathways compensate for their deletion in vivo to allow GnRH neuron survival and targeting and normal onset of female sexual maturation and reproductive function. In contrast to effects at the pituitary and the ovary, ERK1 and ERK2 are dispensable at the level of the GnRH neuron.

Striated myogenesis and peristalsis in the fetal murine esophagus occur without cell migration or interstitial cells of Cajal.

Esophageal striated myogenesis progresses differently from appendicular myogenesis, but the mechanism underlying this process is incompletely understood. Early theories of transdifferentiation of smooth muscle into striated muscle are not supported by transgenic fate-mapping experiments; however, the origin of esophageal striated muscle remains unknown. To better define the process of striated myogenesis, we examined myogenesis in murine fetal cultured esophageal whole-organ explants. Embryonic day 14.5 (E14.5) esophagi maintained a functional contractile phenotype for up to 7 days in culture. Striated myogenesis, as evidenced by myogenin expression, proceeded in a craniocaudal direction along the length of the esophagus. Esophageal length did not change during this process. Complete, but not partial, mechanical disruption of the rostral esophagus inhibited myogenesis distally. Addition of fibroblast growth factor-2 (FGF-2) to the culture media failed to inhibit striated myogenesis, but attenuated smooth muscle actin expression and reduced peristaltic activity. Inhibition of c-kit failed to inhibit peristalsis. These results suggest that striated myogenic precursors are resident along the entire length of the esophagus by day 14.5 and do not migrate along the esophagus after E14.5. Induction of myogenesis craniocaudally appears to require physical continuity of the esophagus and is not inhibited by FGF-2. Finally, peristalsis in E14.5 esophagi appears not to be regulated by interstitial cells of Cajal.

Genetic structure of susceptibility traits for hip dysplasia and microsatellite informativeness of an outcrossed canine pedigree.

An outcrossed canine pedigree was developed for quantitative trait locus (QTL) mapping of hip dysplasia by breeding dysplastic Labrador retrievers to trait-free greyhounds. Measured susceptibility traits included age at onset of femoral capital chondroepiphyseal ossification (OSS), maximum hip distraction (laxity) index (DI), and the dorsolateral subluxation (DLS) score. The pedigrees consisted of 147 dogs representing four generations. For 59 dogs genotyped with 65 microsatellites, the median heterozygosity and polymorphic information content (PIC) values of the F(1) generation were 0.82 and 0.68, respectively. Seventy-seven percent of microsatellites had a PIC greater than 0.59 in the F(1)s. Ninety-six percent of alleles showed Mendelian inheritance. Based on marker informativeness, approximately 350 randomly selected markers would be required for genome-wide screening to obtain an average interval between informative markers of 10 cM. Heritability was estimated as 0.43, 0.5, and 0.61 for OSS, DI, and the DLS score, respectively. Biometric estimates of the mean (+/- variance) effective number of segregating QTLs was 1.2 (+/- 0.05), 0.8 (+/- 0.02), and 1.0 (+/- 0.03) for OSS, DI, and the DLS score, respectively. The distributions of simulated backcross trait data suggested that the loci controlling these traits acted additively and that the DI may be controlled by a major locus. When combined with previous power and quantitative genetic analyses, these estimates indicate that this pedigree is informative for QTL mapping of hip dysplasia traits.

Fetal oxygen content is restored after maternal hemorrhage and fluid replacement with polymerized bovine hemoglobin, but not with hetastarch, in pregnant sheep.

UNLABELLED: We investigated the ability of hemoglobin-based oxygen carrying solutions (HBOCs) to alleviate fetal hypoxemia from maternal hemorrhage. Fifteen pregnant ewes (132-day gestational age) were hemorrhaged 20 mL/kg over 1 h; they were randomized to receive 20 mL/kg IV of HBOC, hetastarch (HTS), or autologous blood (BLD) (n = 5 each) over 30 min and were monitored for 2 h. Hemorrhage significantly (P < or = 0.05) decreased maternal mean blood pressure (from 98 to 48 mm Hg, median), arterial oxygen content (from 12.2 to 11.1 mL/dL), and fetal arterial oxygen content (from 8.1 to 3.9 mL/dL). Fluid replacement restored maternal blood pressure in all groups, although maternal oxygen content immediately returned to baseline only after BLD or HBOC. Maternal oxygen saturation decreased after HBOC (from 98% to 88%). Fetal oxygen content rapidly returned to baseline with either BLD (7.1 mL/dL) or HBOC (8.0 mL/dL) but was never restored with HTS (4.7 mL/dL), and, 60 min after fluid replacement, it was higher with HBOC (8.3 mL/dL) than with HTS (4.7 mL/dL). Fetal plasma-free hemoglobin did not change after HBOC. In conclusion, maternal fluid replacement with HBOC or BLD effectively restored fetal oxygenation, primarily by restoring maternal oxygen content, whereas HTS did not. IMPLICATIONS: Hemoglobin solutions eliminate many limitations of blood transfusions. Our results show that fluid replacement with either blood or a hemoglobin solution, compared with hetastarch, restored fetal oxygenation in pregnant ewes after hemorrhage. If applicable to women, these results suggest a potential for the use of hemoglobin solutions in obstetrics.