Altered Serum Transforming Growth Factor-ß1 and Monocyte Chemoattractant Protein-1 Levels in Obstructive Jaundice

Impaired immune function has long been documented in patients with obstructive jaundice, and those with jaundice due to extrahepatic biliary obstruction still experience a high rate of postoperative complications and death. Transforming growth factor-ß1 (TGFß1) appears to be an important regulator of both normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1 (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites. We hypothesize that obstructive jaundice may alter serum TGFß1 and MCP-1 expressions in the rat and that oral bile acid or glutamine (or both) can restore the altered serum TGFß1 and MCP-1 expression in rats with obstructive jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (n = 10 in each group). Group 1 underwent a sham operation with oral normal saline administration. Group 2 underwent common bile duct ligation (CBDL) with oral normal saline administration. Group 3 underwent CBDL with oral bile acid replacement. Group 4 underwent CBDL with oral glutamine administration. Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood samples were collected. Serum was obtained after centrifugation for measurement of TGFß1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum TGFß1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral glutamine administration prevented this elevation, but oral bile acid replacement did not. The serum MCP-1 level showed similar changes. After 3 days of obstructive jaundice, the TGFß1 and MCP-1 levels were altered in the rat. Oral glutamine administration, not oral bile acid replacement, was able to prevent these alterations.     

Significance of Toll-like receptors in the pathophysiology of surgical sepsis

The discovery of Toll-like receptors has substantially changed our knowledge of pathogen recognition. 11 Toll-like receptors have so far been described in humans. These recognize distinct pathogen associated molecular patterns, as well as endogenous ligands and small molecular synthetic compounds. TLRs have a multifunctional role in pathogen-triggered immune responses and represent an important connection between the "innate" and "adaptive" immunity. The role of the TLRs in the recognition of pathogens renders them a key figure in the activation of the immune response during surgical sepsis. However, emerging evidence points to a fundamental role in tumorigenesis, transplantation, wound healing, atherogenesis and inflammatory bowel disease. The aim hence was to review experimental data pertaining to the activation of TLR signalling pathways in conditions associated with surgical sepsis. A systematic review of the literature was undertaken by searching the MEDLINE database for the period 1966-2004 without language restriction. The paper also analyses the possible therapeutic utilization of the TLR signalling pathways in surgical sepsis.     

The health and life priorities of individuals with spinal cord injury: a systematic review

Determining the priorities of individuals with spinal cord injury (SCI) can assist in choosing research priorities that will ultimately improve their quality of life. This systematic review examined studies that directly surveyed people with SCI to ascertain their health priorities and life domains of importance. Twenty-four studies (a combined sample of 5262 subjects) that met the inclusion criteria were identified using electronic databases (Medline, EMBASE, CINAHL, and PsycINFO). The questionnaire methods and domains of importance were reviewed and described. While the questionnaires varied across studies, a consistent set of priorities emerged. Functional recovery priorities were identified for the following areas: motor function (including arm/hand function for individuals with tetraplegia, and mobility for individuals with paraplegia), bowel, bladder, and sexual function. In addition, health, as well as relationships, emerged as important life domains. The information from this study, which identified the priorities and domains of importance for individuals with SCI, may be useful for informing health care and research agenda-setting activities.     

Reduced hip bone mineral density is related to physical fitness and leg lean mass in ambulatory individuals with chronic stroke

Following a stroke, the reduced level of physical activity and functional use of the paretic leg may lead to bone loss and muscle atrophy. These factors and the high incidence of falls may contribute to hip fractures in the stroke population. This study was the first to examine total proximal femur bone mineral content (BMC) and bone mineral density (BMD) and their relationship to stroke-specific impairments in ambulatory individuals with chronic stroke (onset >1 year). We utilized dual-energy X-ray absorptiometry (DXA) to acquire proximal femur and total body scans on 58 (23 women) community-dwelling individuals with chronic stroke. We reported total proximal femur BMC (g) and BMD (g/cm²) derived from the proximal femur scans, and lean mass (g) and fat mass (g) for each leg derived from the total body scans. Each subject was evaluated for ambulatory capacity (Six-Minute Walk Test), knee extension strength (hand-held dynamometry), physical fitness [maximal oxygen uptake (VO₂max)] and spasticity (Modified Ashworth Scale). Results showed that the paretic leg had significantly lower proximal femur BMD, lean mass and percent lean mass, but higher fat mass than the non-paretic leg for both men and women. Proximal femur BMD of the paretic leg was significantly related to ambulatory capacity ( r =0.33, P =0.011), muscle strength ( r =0.39, P =0.002), physical fitness ( r =0.57, P <0.001), but not related to spasticity ( r =–0.23, P =0.080). Multiple regression analysis showed that lean mass in the paretic leg was a major predictor ( r ²=0.371, P <0.001) of the paretic proximal femur BMD. VO₂max was a significant predictor of both paretic proximal femur BMD ( r ²=0.325, P <0.001) and lean mass in the paretic leg ( r ²=0.700, P <0.001). Further study is required to determine whether increasing physical fitness and lean mass are important to improve hip bone health in chronic stroke.     

Pharmacologic C5-complement suppression reduces blood loss during on-pump cardiac surgery

BACKGROUND: Inflammation contributes to morbidity following on-pump cardiac surgery. Complement activation during cardiopulmonary bypass has been associated with the postoperative bleeding and tissue injury. This study examines the pharmacology and impact on blood loss of complement C5 suppression with pexelizumab in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Pexelizumab, a humanized monoclonal antibody single-chain fragment that binds to the human C5 complement component, was studied in a Phase II multicentered clinical trial. CABG (n = 800) and CABG with concomitant valve surgery (n = 114) patients were evaluated. Patients were randomized to either: pexelizumab bolus (2.0 mg/kg) + placebo infusion; pexelizumab bolus (2.0 mg/kg) + pexelizumab infusion (0.05 mg/kg/hour for 24 hours); or placebo bolus + placebo infusion. Pharmacology, chest tube drainage, and transfusion requirements were assessed. RESULTS: Mean maximum pexelizumab serum concentration was similar for bolus and bolus + infusion-treated patients. Complement-dependent serum hemolytic activity was completely suppressed within 1 hour following pexelizumab bolus, however, suppression was maintained for a longer duration in the bolus + infusion compared to the bolus-only treated patients. A reduction in chest tube drainage was observed for all pexelizumab-treated patients, although transfusion of blood products was similar across all study groups. CONCLUSION: Pexelizumab administration inhibits complement-dependent hemolytic activity and is associated with a reduction in postoperative chest tube drainage in patients undergoing cardiac surgery requiring cardiopulmonary bypass. Further, clinical studies are needed to assess the value of complement attenuation in this setting.     

Is Minimal Access Surgery for Cancer Associated with Immunologic Benefits?

Minimal-access surgical techniques have been shown to be beneficial to patients in terms of shorter convalescence, reduced pain, and improved cosmesis. Although systemic immune function is better preserved following laparoscopic procedures when compared with their respective open approaches, CO₂ pneumoperitoneum may significantly affect local (i.e., infra-abdominal) cellular immunity by reducing regional macrophage function. Results to date are conflicting with regard to the impact of closed and open methods on intraabdominal immunity. Impaired cellular immunity after CO₂ pneumoperitoneum may have significant undesirable intra-abdominal effects on tumor surveillance after oncological surgery; however, at present, there is no clinical evidence to support this position. The VATS techniques avoid the use of CO₂ insufflation, which may offer some advantages from the immune function perspective over laparoscopic procedures accomplished with CO₂ pneumoperitoneum. Better preservation of early postoperative cellular immune function and attenuated disturbance in the inflammatory mediators are likely contributing factors to the clinical benefits that follow laparoscopic surgery and VATS. Larger multi-center randomized trials are needed to confirm the potential benefits of minimal-access surgery on patient survival after cancer surgery. Future research should focus on the effects of minimal-access surgery on other mediators (such as MMP-9, IGFBP-3, IL-12, IL-17, and IL-23) that may be important in tumor cell dissemination, deposition, and propagation in the early postoperative period. Furthermore, additional searches for other factors or mediators, heretofore unrecognized, should be carried out. Such studies will, we hope, increase our knowledge and understanding of the impact of surgery on immune and other physiologic functions.     

Change in Predicted 10-Year Cardiovascular Risk Following Laparoscopic Roux-en-Y Gastric Bypass Surgery

Background  Bariatric surgery is being conducted more often for morbid obesity, but little evidence exists about how it affects the risk of future cardiovascular events. The goal of this study was to quantify the change in predicted 10-year cardiovascular risk following laparoscopic Roux-en-Y gastric bypass (LRYGBP). Methods  We conducted a prospective clinical study of morbidly obese adults undergoing LRYGBP at a university hospital in the USA. Our primary outcome measure was mean change in 10-year cardiovascular risk at 12 months. We estimated cardiovascular risk by using the Framingham risk equation, which calculates the absolute risk of cardiovascular events for patients with no known history of heart disease, stroke, or peripheral vascular disease by using information on age, sex, blood pressure, total and high-density lipoprotein cholesterol levels, smoking status, and history of diabetes. Results  Ninety-two participants underwent LRYGBP between December 2004 and October 2005. Their predicted baseline 10-year cardiovascular risk was 6.7%. At 6 and 12 months, their predicted risk had decreased to 5.2% and 5.4%, respectively. Assuming no change in risk among untreated patients, this represents an absolute risk reduction of 1.3%; which suggests that 77 morbidly obese patients would have to undergo LRYGBP to avert one new case of cardiovascular disease over the ensuing 10 years (number needed to treat = 77). Conclusion  Our findings indicate that LRYGBP is associated with improvements in cardiovascular risk factors and a corresponding decrease in predicted 10-year risk of cardiovascular disease.     

Designing a workplace return-to-work program for occupational low back pain: an intervention mapping approach

Background  

Despite over 2 decades of research, the ability to prevent work-related low back pain (LBP) and disability remains elusive. Recent research suggests that interventions that are focused at the workplace and incorporate the principals of participatory ergonomics and return-to-work (RTW) coordination can improve RTW and reduce disability following a work-related back injury. Workplace interventions or programs to improve RTW are difficult to design and implement given the various individuals and environments involved, each with their own unique circumstances. Intervention mapping provides a framework for designing and implementing complex interventions or programs. The objective of this study is to design a best evidence RTW program for occupational LBP tailored to the Ontario setting using an intervention mapping approach.