EXOGENOUS PHOSPHOLIPASE C STIMULATES EPITHELIAL CELL MIGRATION AND INTEGRIN EXPRESSION IN VITRO

Phospholipase C secreted by bacterial pathogens has been identified as a virulence factor in several human diseases and has been implicated in impeding wound healing. The role of phospholipase C in the intracellular signal control of epithelial growth was studied in normal human skin keratinocytes cultured in conditions simulating aspects of wound healing. Bacillus cereus phospholipase C decreased cell-cell contact and increased cell migration resulting in disruption of the advancing epithelial sheet. Phospholipase C-induced migration was blocked by inhibitor of the phosphoinositol signal transduction pathway neomycin sulfate and protein kinase C inhibitor RO-31-8220. Induced migration was associated with elevated levels of matrix metalloproteinase-9 which, when blocked by tissue inhibitor of metalloproteinase-1, was accompanied by a loss of migration. Adhesion studies showed that phospholipase C treatment enhanced cell binding to fibronectin, vitronectin and collagen IV. Immunostained phospholipase C-stimulated cells cultured on fibronectin showed enhanced expression and relocation of the integrin subunits alpha(v), alpha5 and beta1. Confocal microscopy showed that phospholipase C-induced levels of integrin subunit beta1 were predominantly deposited on the basal surface of the cell apparently in focal contacts and associated with actin stress fibers. These results indicate that exogenous phospholipase C signaling from a bacterial source may play an important role in perturbing normal reepithelialization via altered expression of integrins and matrix metalloproteinase-9.     

Short- and long-term outcomes of combined cardiac and renal transplantation with allografts from a single donor

Coexisting end-stage heart and kidney failure can be treated by combined cardiac and renal transplantation. This study reviews the short- and long-term outcomes after such a procedure over a 16-year period at a single institution.All patients who underwent single-donor simultaneous heart and kidney transplantation during the period of March 1986 to April 2002 (including heart retransplantation) were included (n = 13). They were listed for combined heart and kidney transplantation as they fulfilled our criteria for irreversible end-stage organ failure. Retrospective review of patient data from the transplant database, patient case notes and post-mortem reports were carried out.The mean (SD) recipient age was 45 (12) years and there were 2 females. The mean pre-operative creatinine level was 724 (415) micromol/liter with 9 patients (69.2%) on continuous ambulatory peritoneal dialysis and 2 patients (15.4%) on hemodialysis prior to transplantation. The 30-day mortality rate was 15.4% (2 of 13). For surviving patients the mean creatinine level at hospital discharge was 158 (93) micromol/liter. The mean number of acute cardiac rejection episodes per 100 patient-days was significantly lower (p = 0.01) than that for the heart-only transplant group (n = 760) during the same period. The median (interquartile range) post-operative survival was 1,969 (620 to 3,468) days. The actuarial survival rates (95% confidence interval) at 1 and 10 years were 77% (54% to 100%) and 67% (40% to 94%), respectively, and were not significantly different from the isolated heart transplant population (p = 0.68). Only 1 episode of acute renal rejection was diagnosed on clinical grounds, which was treated accordingly. There was no renal allograft loss in the long-term survivors.Combined cardiac and renal transplantation with allografts from the same donor has acceptable short- and long-term outcomes for patients with coexisting end-stage cardiac and renal failure. This group of patients may also experience fewer acute rejection episodes post-operatively.     

Physical fitness in people with posttraumatic stress disorder: a systematic review

Purpose: People with posttraumatic stress disorder (PTSD) have an increased risk of cardiovascular diseases (CVD). Physical fitness is a key modifiable risk factor for CVD and associated mortality. We reviewed the evidence-base regarding physical fitness in people with PTSD.

Methods: Two independent reviewers searched PubMed, CINAHL, PsycARTICLES, PEDro, and SPORTDiscus from inception until May 2016 using the key words “fitness” OR “exercise” AND “posttraumatic stress disorder” OR “PTSD”.

Results: In total, 5 studies involving 192 (44 female) individuals with PTSD met the inclusion criteria. Lower baseline physical fitness are associated with greater reductions in avoidance and hyperarousal symptoms, as well as with total, physical, and social symptoms of anxiety sensitivity. Rigorous data comparing physical fitness with age- and gender matched general population controls are currently lacking.

Conclusions: The research field regarding physical fitness in people with PTSD is still in its infancy. Given the established relationships between physical fitness, morbidity and mortality in the general population and the current gaps in the PTSD literature, targets for future research include exploring: (a) whether people with PTSD are at risk of low physical fitness and therefore in need of intensified assessment, treatment and follow-up, (b) the relationships among physical fitness, overall health status, chronic disease risk reduction, disability, and mortality in individuals PTSD, (c) psychometric properties of submaximal physical fitness tests in PTSD, (d) physical fitness changes following physical activity in PTSD, and (e) optimal methods of integrating physical activity programs within current treatment models for PTSD.

• Implications for Rehabilitation

• People with PTSD should aim to achieve 150?minutes of moderate or 75?minutes vigorous physical activity per week while also engaging in resistance training exercises at least twice a week.

• Health care professionals should assist people with PTSD to overcome barriers to physical activity such as physical pain, loss of energy, lack of interest and motivation, generalized fatigue and feelings of hyperarousal.

     

Prognostic value of resting and submaximal exercise radionuclide ventriculography after acute myocardial infarction in high-risk patients with single and multivessel disease

In patients who survive the acute phase of myocardial infarction, those with multivessel coronary artery disease generally have a worse prognosis than those with single-vessel disease. However, some patients with significant multivessel stenoses have a good prognosis, whereas some with a significant single-vessel stenosis have a poor prognosis. Thus, although definition of coronary anatomy may be helpful, it is a not a fail-safe prognosticator. In this retrospective analysis, the association of abnormalities at rest and during submaximal exercise testing with radionuclide ventriculography after acute myocardial infarction with major cardiac complications (death, recurrent infarction, severe angina or congestive heart failure) in the ensuing 6 months was assessed in patients with single and multivessel disease. Coronary angiography and submaximal exercise testing with radionuclide ventriculography were performed within 3 months of each other in 42 patients. Eleven of the 16 patients with single-vessel coronary stenosis had major cardiac complications. The subsequent course of these 16 patients was correctly predicted by left ventricular ejection fraction (LVEF) ≤ 0.40 in 8 patients, by LVEF < 0.55 in 7 patients, by failure of LVEF to increase by 0.05 units in 13 patients, and by an increase in left ventricular end-systolic volume index (LVESVI) during exercise >5% above baseline in 11 patients. Of the 26 patients with multivessel coronary artery disease, 24 had major cardiac complications. The subsequent course of these 26 patients was correctly predicted in 13 by LVEF ≤ 0.40, in 20 by LVEF < 0.55, in 25 by a failure of LVEF to increase by 0.05 units during exercise, and in 20 by an increase in LVESVI by > 5% during exercise. Thus, submaximal exercise testing with radionuclide ventriculography may provide valuable prognostic information concerning the occurrence of major cardiac events after myocardial infarction not only in patients with multivessel disease, but also in those with single-vessel disease. Exercise-induced abnormalities of left ventricular function may have greater prognostic importance than the delineation of coronary arterial anatomy or the assessment of residual left ventricular function at rest.