Small bowel transit and gastric emptying after biliodigestive anastomosis using the uncut jejunal loop

BACKGROUND: The Roux-en-Y loop is an effective procedure for biliodigestive drainage. However, up to 15% of patients suffer from postoperative cholangitis or blind loop syndrome. A new technique to prevent motility abnormalities has been developed. METHODS: Male Lewis rats were used to compare gastric emptying and transit in the small bowel after either a standard Roux-en-Y anastomosis or a new biliodigestive anastomosis technique which involves creating an "uncut" jejunal loop with luminal occlusion. Unoperated rats served as controls. (99)Technetium HIDA and (111)Indium-tagged amberlite were respectively used to investigate small bowel transit and gastric emptying. RESULTS: Histopathology showed distinctive abnormalities only in the liver of conventional Roux-en-Y animals. No recanalization of the obliterated gut lumen occurred in uncut Roux animals. Distribution of (99)Tc-HIDA and (111)In showed were similar in both groups. Gastric emptying is slowed in both groups. CONCLUSIONS: The uncut proximal jejunum loop is a good alternative to the conventional Roux-en-Y loop and showed preserved small bowel motility and adequate jejunal transit. Gastric emptying is slowed in both groups.     

Predictors of mortality and management of patients with traumatic inferior vena cava injuries

The aim of this study was to determine factors that predict mortality in patients with traumatic inferior vena cava (IVC) injuries and to review the current management of this lethal injury. A 7-year retrospective review of all trauma patients with IVC injuries was performed. Factors associated with mortality were assessed by univariate analysis. Significant variables were included in a multivariate regression analysis model to determine independent predictors of mortality. Statistical significance was determined at P < or = 0.05. A literature review of traumatic IVC injuries was performed and compared with our institutional experience. Thirty-six IVC injuries were identified (mortality, 56%; mechanisms of injury, 28% blunt and 72% penetrating). There was no difference in mortality based on mechanism of injury. Injuries with closer proximity to the heart were associated with increased mortality (P < 0.001). Univariate analysis demonstrated that nonsurvivors had a higher injury severity scale, a lower systolic blood pressure in the emergency department, a lower Glasgow coma score (GCS), and were more likely to have thoracotomies performed in the emergency department or operating room. Multivariate analysis revealed that only GCS (P = 0.03) was an independent predictor of mortality. Typical factors predicting mortality were identified in our cohort of patients, including GCS. The mechanism of injury is not associated with survival outcome, although mortality is higher with injuries more proximal to the heart. The form of management by IVC level is reviewed in our patient population and compared with the literature.     

Dynamic cervical plates: biomechanical evaluation of load sharing and stiffness.

STUDY DESIGN: An in vitro biomechanical study using a simulated cervical corpectomy model to compare the load-sharing properties and stiffnesses of two static and two dynamic cervical plates. OBJECTIVES: To evaluate the load-sharing properties of the instrumentation with a full-length graft and with 10% graft subsidence and to measure the stiffness of the instrumentation systems about the axes of flexion-extension, lateral bending, and axial torsion under these same conditions. SUMMARY OF BACKGROUND DATA: No published reports comparing conventional and dynamic cervical plates exist. METHODS: Six specimens of each of the four plate types were mounted on ultra-high molecular weight polyethylene-simulated vertebral bodies. A custom four-axis spine simulator applied pure flexion-extension, lateral bending, and axial torsion moments under a constant 50 N axial compressive load. Load sharing was calculated through a range of applied axial loads up to 120 N. The stiffness of each construct was calculated in response to +/-2.5 Nm moments about each axis of rotation with a full-length graft, a 10% shortened graft, and no graft. ANOVA and Fisher's post hoc test were used to determine statistical significance (alpha < or = 0.05). RESULTS: The two locked cervical plates (CSLP and Orion) and the ABC dynamic plate were similar in flexion-extension, lateral bending, and torsional stiffness. The DOC dynamic plate was consistently less stiff. The Orion plate load shared significantly less than the other three plates with a full graft. Both the ABC and the DOC plates were able to load share with a shortened graft, whereas the conventional plates were not. CONCLUSIONS: All plates tested effectively load share with a full-length graft, whereas the two dynamic cervical plates tested load share more effectively than the locked plates with simulated graft subsidence. The effect of dynamization on stiffness is dependent on plate design.     

Does Thumb Immobilization Contribute to Scaphoid Fracture Stability?

Immobilization protocols for nondisplaced scaphoid fractures have included the elbow, wrist, and thumb. This study attempts to demonstrate whether or not immobilization of the thumb makes a difference in preventing motion at the scaphoid fracture site. Using six fresh frozen forearm specimens, a transverse waist scaphoid fracture was created through a dorsal approach. Metallic markers were imbedded on either side of the fracture. Sutures were secured to the flexor pollicus longus (FPL) and extensor pollicus longus (EPL). Each specimen was loaded in extension and flexion by attaching 50-g weights to the EPL and FPL, first with no casting, then with a short arm cast, and finally a short arm thumb spica cast. Angulation and displacement at the fracture site were measured in the coronal, sagittal, and axial planes utilizing image reconstructions from computed tomography. One-way ANOVA with repeated measures and Tukey–Kramer multiple comparison test post hoc analysis were used for statistical evaluation. There was no significant difference in fracture angulation or rotation between spica and short arm casts. There was a significant difference in angulation and rotation in all three planes when comparing between casting and no casting, p < 0.05. In our cadaveric model, wrist immobilization is crucial for nondisplaced scaphoid waist fractures, and short arm casting was just as effective as thumb spica casting in preventing fracture displacement.     

Modulation of metastasis phenotypes of non-small cell lung cancer cells by 17-allylamino 17-demethoxy geldanamycin

Background. Cancer cells that overexpress c-erbB oncogenes exhibit resistance to chemotherapy, enhanced tumorigenicity, as well as increased propensity for metastasis. The aim of this study was to investigate if depletion of erbB-1/EGFR and erbB-2/HER2neu oncogene products by 17-allylamino 17-demethoxy Geldanamycin (17AAGA) could diminish the metastatic potential of non-small cell lung cancer (NSCLC) cells that express varying levels of the erbB1/erbB2 oncogenes.

Methods. NSCLC cell lines (H460, H358, H322, or H661) were assayed for expression of erbB1 and erbB2, the cell adhesion molecule E-cadherin, secretion of the matrix metalloproteinase 9 (MMP-9), and vascular endothelial cell growth factor (VEGF), as well as their ability to invade Matrigel after 48-hour exposure to 17AAGA.

Results. 17AAGA significantly depleted erbB1 or erbB2 levels in NSCLC cells expressing high levels of these proteins, and effectively inhibited their growth with IC₅₀ values ranging from 50 to 90 nmol/L. Moreover, drug treatment enhanced E-cadherin expression in H322 and H358 cells, and inhibited secretion of MMP-9 and VEGF secretion by tumor cells. 17AAGA diminished hypoxia-induced upregulation of VEGF expression as well as growth factor-mediated augmentation of MMP-9 secretion, and profoundly inhibited the ability of H322 and H358 cells to migrate through Matrigel in response to chemoattractants.

Conclusions. In addition to its known antiproliferative and chemosensitization effects, 17AAGA inhibits the metastatic phenotype of lung cancer cells. 17AAGA may be a novel pharmacologic agent for specific molecular intervention in lung cancer patients.     

A simple and highly effective method for the stable transduction of uncultured porcine hepatocytes using lentiviral vector

Gene therapy is an attractive approach for the treatment of a wide spectrum of liver diseases. Lentiviral vectors allow the stable integration of transgenes into the genome of nondividing differentiated cells including hepatocytes and could provide long-lasting expression of a therapeutic gene. To develop such approaches, preclinical studies in large animal models such as pigs are necessary to evaluate the feasibility and safety of stable lentiviral integration and long-term vector expression. In addition, effective lentivector-mediated gene transfer onto porcine hepatocytes could advance in cell-based therapies for acute liver failure. To investigate this issue, porcine hepatocytes were transduced in suspension immediately after their isolation in University of Wisconsin (UW) solution containing vitamin E. Up to 80% of hepatocytes stably expressed a GFP transgene after a single exposure to lentiviral vector coding for GFP under the control of either liver-specific or ubiquitous promoters. Moreover, porcine hepatocytes cryopreserved in UW solution containing fetal bovine serum, dimethyl sulfoxide, and vitamin E remained highly transducible with lentiviral vector after thawing. When thawed, transduced in suspension, and immediately transplanted into the spleen of immunodeficient mice, ex vivo lentivirally transgene marked xenogeneic hepatocytes were detected in murine liver. We demonstrated that porcine hepatocytes are highly susceptible to lentiviral vector and describe an easy methodology to efficiently, rapidly, and stably introduce transgenes into uncultured porcine hepatocytes.     

Neuregulin‐1 positively modulates glial response and improves neurological recovery following traumatic spinal cord injury

Spinal cord injury (SCI) results in glial activation and neuroinflammation, which play pivotal roles in the secondary injury mechanisms with both pro‐ and antiregeneration effects. Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin‐1 (Nrg‐1) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg‐1 dysregulation on glial and immune cell reactivity following SCI. Using complementary in vitro approaches and a clinically‐relevant model of severe compressive SCI in rats, we demonstrate that immediate delivery of Nrg‐1 (500 ng/day) after injury enhances a neuroprotective phenotype in inflammatory cells associated with increased interleukin‐10 and arginase‐1 expression. We also found a decrease in proinflammatory factors including IL‐1β, TNF‐α, matrix metalloproteinases (MMP‐2 and 9) and nitric oxide after injury. In addition, Nrg‐1 modulates astrogliosis and scar formation by reducing inhibitory chondroitin sulfate proteoglycans after SCI. Mechanistically, Nrg‐1 effects on activated glia are mediated through ErbB2 tyrosine phosphorylation in an ErbB2/3 heterodimer complex. Furthermore, Nrg‐1 exerts its effects through downregulation of MyD88, a downstream adaptor of Toll‐like receptors, and increased phosphorylation of Erk1/2 and STAT3. Nrg‐1 treatment with the therapeutic dosage of 1.5 μg/day significantly improves tissue preservation and functional recovery following SCI. Our findings for the first time provide novel insights into the role and mechanisms of Nrg‐1 in acute SCI and suggest a positive immunomodulatory role for Nrg‐1 that can harness the beneficial properties of activated glia and inflammatory cells in recovery following SCI.