Search

The case report describes a novel technique of pre-emptive plasma "reconstitution" prior to disengagement from cardiopulmonary bypass (CPB) to minimize RV volume overload. The concomitant use of hemoconcentration facilitates volume and blood product management in cardiac transplant after previous left ventricular assist device implant surgery.

Objectives: To describe the use of closed reduction and minimally invasive fixation for treatment of a central tarsal bone luxation in a six-year-old spayed female, mixed breed dog with acute onset non-weight bearing right hindlimb lameness., Methods: Physical examination and tarsal radiographs resulted in a diagnosis of central tarsal bone luxation. Closed reduction and minimally invasive screw stabilization were performed with fluoroscopic guidance. External coaptation for six weeks was followed by a gradual return to full function., Results: Follow-up examination at 34 months post-surgery revealed the patient to be fully functional on the surgically repaired limb. Radiographs revealed ankylosis of the intertarsal joints., Clinical Significance: Minimally invasive ankle surgery is commonly performed in humans but is uncommon in dogs. Based on the results of this single case, minimally invasive reduction and stabilization of central tarsal bone luxation is feasible.

Bone plating has been used as a method of fracture management for many years. Recently, a trend toward the use of fracture fixation techniques which preserve the local fracture environment, known as biological osteosynthesis, has evolved. This trend has resulted in the development of a less traumatic method of bone plating referred to as minimally invasive plate osteosynthesis (MIPO), or percutaneous plating. During MIPO fracture stabilisation, plates are inserted through short incisions and a communicating epiperiosteal tunnel. Typically, bone plates applied in this fashion have a bridging function. Promising outcomes have been reported in human patients undergoing MIPO fracture stabilisation, and limited reports of the use of this technique in dogs and cats have yielded positive results as well. Careful case selection, pre-operative planning, and appropriate instrumentation are necessary when performing the technique. Rapid time to union, low complication rates and good return to function have been noted in human patients. Additional research is needed to define selection criteria and outline the definitive benefits of MIPO in dogs and cats.

The microbially derived antiproliferative agent rapamycin inhibits cell growth by interfering with the signaling functions of the mammalian target of rapamycin (mTOR). In this study, we demonstrate that interleukin-3 stimulation induces a wortmannin-sensitive increase in mTOR kinase activity in a myeloid progenitor cell line. The involvement of phosphoinositide 3'-kinase (PI3K) in the regulation of mTOR activity was further suggested by findings that mTOR was phosphorylated in vitro and in vivo by the PI3K-regulated protein kinase, AKT/PKB. Although AKT phosphorylated mTOR at two COOH-terminal sites (Thr2446 and Ser2448) in vitro, Ser2448 was the major phosphorylation site in insulin-stimulated or -activated AKT-expressing human embryonic kidney cells. Transient transfection assays with mTOR mutants bearing Ala substitutions at Ser2448 and/or Thr2446 indicated that AKT-dependent mTOR phosphorylation was not essential for either PHAS-I phosphorylation or p70S6K activation in HEK cells. However, a deletion of amino acids 2430-2450 in mTOR, which includes the potential AKT phosphorylation sites, significantly increased both the basal protein kinase activity and in vivo signaling functions of mTOR. These results demonstrate that mTOR is a direct target of the PI3K-AKT signaling pathway in mitogen-stimulated cells, and that the identified AKT phosphorylation sites are nested within a "repressor domain" that negatively regulates the catalytic activity of mTOR. Furthermore, the activation status of the PI3K-AKT pathway in cancer cells may be an important determinant of cellular sensitivity to the cytostatic effect of rapamycin.

Objective attempts to characterize postural control in subjects with cerebellar (Cb) pathology have focused primarily on sagittal plane responses to static standing, semi-dynamic standing, and platform perturbation. Repeated, dynamic, functional movement may provide a better opportunity to study the effects of ataxia on frontal plane postural stability. The purpose of this investigation was to quantify lateral stability using center of gravity (CG) and center of pressure (CP) movement analysis, and to examine motor responses necessary to complete a repetitive stepping task. Whole body kinematic and kinetic data were collected as patients with Cb degeneration and non-disabled volunteers repeatedly ascended forward and descended backward from a 7.6-cm step to the beat of a metronome. Cb subjects demonstrated significantly greater lateral CG instability, consistent with increased CG velocity and displacement variability in the frontal plane compared to non-disabled subjects. Significantly greater lateral CP displacement was found in subjects with Cb degeneration. Phase plot patterns from patients with Cb degeneration showed poor movement quality, indicated by abruptly changing CG phase plot patterns and abnormal CG acceleration and deceleration phases. Ataxic postural reactions were observed consistently during lateral weight shifting phases toward the stance limb. We hypothesized that lateral postural instability in Cb subjects stems from altered lower extremity intersegmental coordination and inadequate lateral CG velocity control. Frontal plane CG instability may necessitate a wide-based gait. Despite the varied neuroanatomic sites of degenerative Cb pathology, subjects with Cb pathology demonstrated similar CG movement patterns and altered motor strategies to avoid destabilization. Dynamic assessment provides important information regarding frontal plane instability not revealed by static assessment methods. These findings suggest that a dynamic, constrained stepping task effectively differentiates Cb and non-disabled volunteers, contributing to our knowledge of the effect of ataxic movement disturbances on frontal plane postural stability and lower limb coordination.

The immunosuppressant rapamycin interferes with G1-phase progression in lymphoid and other cell types by inhibiting the function of the mammalian target of rapamycin (mTOR). mTOR was determined to be a terminal kinase in a signaling pathway that couples mitogenic stimulation to the phosphorylation of the eukaryotic initiation factor (eIF)-4E-binding protein, PHAS-I. The rapamycin-sensitive protein kinase activity of mTOR was required for phosphorylation of PHAS-I in insulin-stimulated human embryonic kidney cells. mTOR phosphorylated PHAS-I on serine and threonine residues in vitro, and these modifications inhibited the binding of PHAS-I to eIF-4E. These studies define a role for mTOR in translational control and offer further insights into the mechanism whereby rapamycin inhibits G1-phase progression in mammalian cells.