Impact of PI3Kα (Phosphoinositide 3-Kinase Alpha) Inhibition on Hemostasis and Thrombosis.

Objective- PI3Kα (phosphoinositide 3-kinase alpha) is a therapeutic target in oncology, but its role in platelets and thrombosis remains ill characterized. In this study, we have analyzed the role of PI3Kα in vitro, ex vivo, and in vivo in 2 models of arterial thrombosis. Approach and Results- Using mice selectively deficient in p110α in the megakaryocyte lineage and isoform-selective inhibitors, we confirm that PI3Kα is not mandatory but participates to thrombus growth over a collagen matrix at arterial shear rate.

Bronchial aspirates glucose level as indicator for methicillin-resistant Staphylococcus aureus (MRSA) in intubated mechanically ventilated patients.

This study evaluated if the level of glucose in bronchial aspirate serves as indicator for the risk of MRSA infection in intubated mechanically ventilated ICU patients. A total of 50 critically ill patients was enrolled and were under tight glycemic control to abolish the effect of hyperglycemia on bronchial secretion, if they were expected to require mechanical ventilation for more than 48 hours. Bronchial aspirates were detected for glucose and sent twice weekly for microbiological analysis and whenever an MRSA was expected.

Prevalence of extramucosal fungal elements in sinonasal polyposis: a mycological and pathologic study in an Egyptian population.

Objective And Hypothesis: The objective of the study was to define the true incidence of fungal elements in the nasal and sinus mucous in cases of chronic rhinosinusitis (CRS) with bilateral polyposis compared with normal controls-in an Egyptian African population-via mycological and histologic techniques.

Study Design: This study was conducted prospectively on 100 patients with the clinical diagnosis of CRS with bilateral nasal polyposis. Fifty volunteers with no history of nasal or paranasal sinus disease served as a control group.

Evaluation of cartilage growth following sustained delivery of tgf-? Using a rat degenerated disc model - biomed 2010.

The current modalities of treating symptomatic degenerative disc disease are either conservative non-surgical or surgical modalities. However, none of these modalities is a true cure for the degenerative process. Ideally, the best treatment would be preventing the progression of degeneration.

Dynamic anterior cervical plating for multi-level spondylosis: Does it help?

Study Design:  Randomized controlled trial.

Objective:  To compare fusion rates, time to fusion, complication rates and subsidence between 1) a static, 2) a dynamic angulation, and 3) a dynamic translation plate in anterior cervical discectomy and fusion for symptomatic degenerative cervical disease.

Methods:  Thirty-six patients with two level, symptomatic cervical degenerative changes requiring surgery were randomized in a blinded fashion to receive a statically locked plate, Cervical Spine Locking Plate (CSLP) (Synthes, Paoli, PN, USA), an Atlantis Vision(®) Anterior Cervical Plate System (Medtronic, Memphis, TN, USA) which allows angular dynamization, or a Premier(®) Anterior Cervical Plate System (Medtronic) which allows translational dynamization.

Conditional TPM3-ALK and NPM-ALK transgenic mice develop reversible ALK-positive early B-cell lymphoma/leukemia.

NPM-ALK (nucleophosmin-anaplastic lymphoma kinase) and TPM3-ALK (nonmuscular tropomyosin 3-anaplastic lymphoma kinase) are oncogenic tyrosine kinases implicated in the pathogenesis of human ALK-positive lymphoma. We report here the development of novel conditional mouse models for ALK-induced lymphomagenesis, with the use of the tetracycline regulatory system under the control of the EmuSRalpha enhancer/promoter. The expression of either oncogene resulted in the arrest of the differentiation of early B cells and lymphomagenesis.

A preliminary report on the effects of sustained administration of corticosteroid on traumatized disc using the adult male rat model.

Study Design: A novel degenerative disc disease model and sustained delivery method for corticosteroid in male Sprague-Dawley albino rats.

Objectives: To develop a model of degenerative disc disease and to determine the effect of continuous sustained release of corticosteroid on the process of degeneration within the traumatized disc.

Summary Of Background Data: The current modalities of treating symptomatic degenerative disc disease are either conservative or surgical.

Effect of low power laser treatment on a traumatized disc in a rat model.

This study investigated the effects of low power laser on the healing process of a traumatized disc in an animal model. The experimental design consisted of 14 rats divided into the following three groups: Animals in group I (n = 5) served as controls with no surgery. Animals in group II (n = 5), the sham group, received a surgically created defect in the disc at L4/L5 level and received no other treatment.

Management of back pain in patients with previous back surgery.

The 80,000 or so patients a year who continue to have chronic, disabling back pain after one or more spinal surgeries are said to have failed back surgery syndrome. There are no controlled studies to guide physicians in the management of these patients. Six anatomical abnormalities of the spine most commonly result in back surgery, and 7 undesirable outcomes lead to failed back surgery syndrome.

Characterization of a femoral segmental nonunion model in laboratory rats: report of a novel surgical technique.

The literature is lacking conclusive results regarding the exact mechanism of maximizing the fracture healing stages with minimal traumatic side effects. This observation mandates the development of a novel surgical procedure using small animals as a model to study fracture healing in the presence of osteoinductive agents. Previously, stabilization of osteotomies in small animal models has mainly been accomplished using Kirschner wires, but the rat's tremendous ability to heal an osteotomy stabilized by this method has masked the effects of osteoinductive agents.

Roles of the C-terminal tyrosine residues of LAT in GPVI-induced platelet activation: insights into the mechanism of PLC gamma 2 activation.

Linker for activation of T cells (LAT) is an adaptor protein required for organization of the signaling machinery downstream of the platelet collagen receptor, the glycoprotein VI (GPVI). Here, we investigated the effect of LAT mutations on specific signaling pathways and on platelet functions in response to GPVI triggering by convulxin (Cvx). Using mice containing tyrosine to phenylalanine mutations of the adaptor, we show the crucial role played by the tyrosine residues at positions 175, 195, and 235 in the phosphorylation of LAT and in the whole pattern of protein tyrosine phosphorylation in response to Cvx.

A quantitative analysis of strain at adjacent segments after segmental immobilization of the cervical spine.

Study Design: A biomechanical study on human cadaveric cervical spines with segmental fixation.

Objectives: To quantify the strains across all segments of the spine after simulated fusion.

Summary Of Background Data: Clinical evidence suggests that degenerative changes occur at adjacent levels after cervical fusion.

Targeted sustained delivery of tobramycin at the site of a femoral osteotomy.

Complex fractures are difficult to manage because of the increased risk of secondary infection. Traditional treatments include debridment and local administration of antibiotics. Local antibiotic therapy is a safe technique resulting in high local concentration of antibiotics with minimal systemic levels.

SHP1 tyrosine phosphatase negatively regulates NPM-ALK tyrosine kinase signaling.

Anaplastic large-cell lymphoma (ALCL) is frequently associated with the 2;5 translocation and expresses the NPM-ALK fusion protein, which possesses a constitutive tyrosine kinase activity. We analyzed SHP1 tyrosine phosphatase expression and activity in 3 ALK-positive ALCL cell lines (Karpas 299, Cost, and SU-DHL1) and in lymph node biopsies (n = 40). We found an inverse correlation between the level of NPM-ALK phosphorylation and SHP1 phosphatase activity.

Evaluation of insulin-like growth factor-1 and parathyroid hormone on growth characteristics of MG-63 cells.

Insulin-like Growth Factor-1 (IGF-1) and Parathyroid hormones (PTH) are major endocrine secretions that contribute to bone formation. The purpose of this experiment was to examine MG-63 bone like cells after treatment with PTH and IGF-1 in low (1 ug), medium (5 ug), and high (50 ug) dosage levels. MG-63 cells were plated onto a 24 well tissue culture plate at a density of 1 x 1--5 cells per well.

Endoscopic removal of an implant from the maxillary sinus: a case report.

Slippage of an implant into the maxillary sinus is an exceptional complication that may occur during immediate implant placement. In this study, removal of a displaced implant into the maxillary sinus with the aid of endoscopy via buccal window approach is reported. Management of such a rare complication is also addressed.

Does endotoxin contribute to aseptic loosening of orthopedic implants?

Aseptic loosening of orthopedic implants caused by wear particles is a major clinical problem. This review examines the hypothesis that bacterial endotoxin contributes to aseptic loosening. Clinical findings support this hypothesis: bacterial biofilms exist on many implants from patients with aseptic loosening and antibiotics in bone cement reduce the rate of aseptic loosening.

Stimulation of osteogenesis by means of sustained delivery of various natural androgenic hormones.

Sex steroids play an essential role in the maintenance of bone health throughout life, and the mechanisms by which these effects are mediated in a subject of much controversy. Osteoblast cells appear to be stimulated by androgens in vitro, however their use in vivo is limited due to the virilizing side effects as well as alterations in the lipoprotein profiles. The use of targeted sustained release of anabolic steroids may stimulate fracture healing without untoward side effects.

The tyrosine phosphatase 1B regulates linker for activation of T-cell phosphorylation and platelet aggregation upon FcgammaRIIa cross-linking.

Human platelets express the receptor for immunoglobulin G, FcgammaRIIa, that triggers cell aggregation upon interaction with immune complexes. Here, we report that the rapid tyrosine phosphorylation of the Linker for Activation of T-cell (LAT) in human platelets stimulated by FcgammaRIIa cross-linking was followed by its complete dephosphorylation in an alphaIIb/beta3 integrin-dependent manner. Concomitant to LAT dephosphorylation, the protein tyrosine phosphatase 1B (PTP1B) was activated through a mechanism involving its proteolysis by calpains downstream of integrins.

Validity of self-assessment outcome questionnaires: patient-physician discrepancy in outcome interpretation.

Patient outcome following total hip arthroplasty (THA) was evaluated using a previously described patient assessment outcome index questionnaires. The questionnaire was distributed to 263 patients who underwent cementless THA. One hundred and three patients responded to the self-administered questionnaire and had updated clinical evaluation.

Surgery of the lumbar spine for spinal stenosis in 118 patients 70 years of age or older.

Study Design: A consecutive case retrospective chart review and an outcome satisfaction questionnaire were used in this study.

Objective: To provide a surgical reference for surgeons and elderly patients who may have concerns regarding the safety and outcome of lumbar spine surgery in their age population.

Summary Of Background Data: Elderly patients scheduled for spine surgery have a major concern about the safety and outcome of the procedure in light of their advanced age.

A critical role of lipid rafts in the organization of a key FcgammaRIIa-mediated signaling pathway in human platelets.

The involvement of platelet FcgammaRIIa in heparin-associated thrombocytopenia (HIT) is now well established. However, the precise sequence of molecular events initiated by FcgammaRIIa cross-linking in platelets remains partly characterized. We investigated here the role of lipid rafts in the spatio-temporal organization of the FcgammaRIIa-dependent signaling events.

Implications of subtalar joint anatomic variation in calcaneal lengthening osteotomy.

The purpose of this study was to identify the percentage of individuals with distinct anterior and middle calcaneal facets. Calcaneal lengthening osteotomy, as popularized by Mosca, is extra-articular, with its site being the interval between the anterior and middle calcaneal facets. For individuals without a distinct anterior and middle facet, the subtalar joint must be violated to perform this operation.

Cytokines synergistically induce osteoclast differentiation: support by immortalized or normal calvarial cells.

Conditionally immortalized murine calvarial (CIMC) cells that support differentiation of precursors into mature osteoclasts were isolated. All six CIMC cell lines supported osteoclast differentiation in response to 1,25-dihydroxyvitamin D(3) or interleukin (IL)-11. CIMC-4 cells also supported osteoclast differentiation in response to tumor necrosis factor (TNF)-alpha, IL-1beta, or IL-6.

Selective dephosphorylation of the threonine(183) residue of ERK2 upon (alpha)llb(beta)3 engagement in platelets.

Thrombin-induced extracellular signal-regulated kinase 2 (ERK2) activation is negatively regulated in conditions of all bP3 integrin engagement and platelet aggregation. Here we show by Western blotting with antibodies against mono- and biphosphorylated forms of ERK2 that the dephosphorylation of ERK2 by alpha llb beta 3 engagement affects threonine183 and not tyrosine185. Addition of a potent serine/threonine phosphatase inhibitor, okadaic acid (OA), restored thrombin-induced threonine phosphorylation of ERK2 in conditions of platelet aggregation, whereas OA had no effect in the absence of alpha llb beta 3 engagement.