Habitual physical activity is associated with the maintenance of neutrophil migratory dynamics in healthy older adults.

BACKGROUND: Dysfunctional neutrophils with advanced age are a hallmark of immunosenescence. Reduced migration and bactericidal activity increase the risk of infection. It remains unclear why neutrophil dysfunction occurs with age. Physical activity and structured exercise have been suggested to improve immune function in the elderly. The aim of this study was to assess a comprehensive range of neutrophil functions and determine their association with habitual physical activity. METHOD: Physical activity levels were determined in 211 elderly (67±5years) individuals by 7-days of accelerometry wear. Twenty of the most physically active men and women were matched for age and gender to twenty of the least physically active individuals. Groups were compared for neutrophil migration, phagocytosis, oxidative burst, cell surface receptor expression, metabolic health parameters and systemic inflammation. Groups were also compared against ten young participants (23±4years). RESULTS: The most active group completed over twice as many steps/day as the least active group (p<0.001), had lower BMI's (p=0.007) and body fat percentages (p=0.029). Neutrophils migrated towards IL-8 better in the most active group compared to the least active (p<0.05) and was comparable to that of the young (p>0.05). These differences remained after adjusting for BMI, body fat and plasma metabolic markers which were different between groups. Correlations revealed that steps/day, higher adiponectin and lower insulin were positively associated with migratory ability (p<0.05). There was no difference in expression of the chemokine receptors CXCR1 or CXCR2 (p>0.05 for both). CD11b was higher in the most active group compared to the least active (p=0.048). No differences between activity groups or young controls were observed for neutrophil phagocytosis or oxidative burst in response to Escherichia coli (p>0.05). The young group had lower concentrations of IL-6, IL-8, MCP-1, CRP, IL-10 and IL-13 (p<0.05 for all) with no differences between the two older groups. CONCLUSION: These data suggest that impaired neutrophil migration, but not bactericidal function, in older adults may be, in part, the result of reduced physical activity. A 2-fold difference in physical activity is associated with better preserved neutrophil migratory dynamics in healthy older people. As a consequence increasing habitual physical activity may be beneficial for neutrophil mediated immunity.

The Effect of Adjuvant Chemotherapy on Stoma-Related Complications After Surgery for Colorectal Cancer: A Retrospective Analysis.

PURPOSE: To assess stoma-related complications of colorectal cancer patients undergoing surgery with curative intent who received adjuvant chemotherapy compared to those who underwent surgery alone. DESIGN: A retrospective analysis of a prospectively maintained colorectal cancer clinical audit database was completed. SUBJECTS AND SETTINGS: Patients undergoing curative surgery for colorectal cancer with the formation of a stoma (end ileostomy, loop ileostomy, end colostomy) between 1999 and 2011 at a single hospital in Lanarkshire, United Kingdom. Patients who underwent neo-adjuvant chemotherapy were excluded. Two hundred twenty-two patients comprised the study sample; 130 (59%) were male. Seventy-five (34%) patients comprised the chemotherapy group and 147 (66%) made up the surgery-only group. Patients in the chemotherapy group were younger (61.6 vs 65.4 years; P = .001) and had higher stage colorectal cancer (P < .001). There was no difference in baseline (day 10) stoma scores between the chemotherapy or surgery-only groups. METHODS: Postoperative stoma-related complications were serially assessed using a stoma complication scoring tool; scores were calculated at 10 days and 3 months postoperatively. Scores of patients receiving adjuvant chemotherapy were compared to scores of participants who underwent surgery alone. INSTRUMENT: A composite stoma function score was calculated for each patient after assessment of stoma-related complications. The overall score included a global assessment of stoma quality (stoma retraction, prolapse, stenosis, parastomal hernia, skin changes) and patient-reported stoma function (leakage, soiling, nighttime emptying, odor). RESULTS: At 3 months, the mean loop ileostomy stoma function score was poorer among the chemotherapy group when compared to the surgery-only group (4.55 vs 1.53; P = .041). No differences were found when colostomy (2.00 vs 2.62; P = .411) or end ileostomy (1.00 vs 2.00; P = .170) function scores were compared at 3 months. CONCLUSION: Patients undergoing curative surgery for colorectal cancer resulting in a loop ileostomy who received adjuvant chemotherapy had higher stoma complication scores at 3 months compared to those who underwent surgery with no chemotherapy. This difference was not seen in patients with colostomies or end ileostomies. Patients, WOC nurses, and medical staff must be alert to the potential of increased loop ileostomy-related complications with adjuvant chemotherapy. Fully informed patient consent coupled with timely support and advice may reduce stoma-related morbidity and improve quality of life for such patients.

Effect of muscle metaboreflex activation on central hemodynamics and cardiac function in humans.

We sought to determine how the mode of muscle metaboreflex activation influences the central hemodynamic response and cardiac inotropic and lusotropic function in healthy humans. Ten healthy males performed (i) isometric handgrip (IHG) with and without post-exercise ischemia (PEI) to examine the influence of isolated muscle metaboreflex activation and (ii) rhythmic handgrip (RHG) with and without ischemia to examine the influence of enhanced muscle metaboreflex activation. Heart rate (HR) and blood pressure (BP) were continuously monitored. Stroke volume (SV, Doppler echocardiography) was measured, cardiac output (CO = HR × SV) and total peripheral resistance (TPR = mean BP/CO) calculated, and indices of left ventricular systolic and diastolic function were obtained (tissue Doppler imaging). During isolated muscle metaboreflex activation with PEI following IHG, mean BP (+23 ± 3 mm Hg) and TPR were elevated from baseline (p < 0.05), whereas HR, SV, and CO were unchanged. Enhanced muscle metaboreceptor activation during ischemic RHG augmented the increase in mean BP, CO, and HR (p < 0.05 ischemic vs. free-flow RHG), whereas SV and TPR were unchanged from baseline. Neither isolated (PEI) nor enhanced muscle metaboreflex activation altered left ventricular systolic function (systolic myocardial velocity), but left atrial systolic function (late diastolic myocardial velocity) was enhanced. These findings indicate that the mode of muscle metaboreceptor activation (during vs. post handgrip) determines whether the resultant pressor response is flow (CO) or vasoconstriction (TPR) mediated, and that although left ventricular systolic function is unchanged, enhanced left atrial systolic function likely aids the preservation of SV during muscle metaboreflex engagement.

Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals.

We evaluated cerebral perfusion, oxygenation and metabolism in 11 young (22 ± 1 years) and nine older (66 ± 2 years) individuals at rest and during cycling exercise at low (25% W(max)), moderate (50% Wmax), high (75% W(max)) and exhaustive (100% W(max)) workloads. Mean middle cerebral artery blood velocity (MCA V(mean)), mean arterial pressure (MAP), cardiac output (CO) and partial pressure of arterial carbon dioxide (P(aCO2)) were measured. Blood samples were obtained from the right internal jugular vein and brachial artery to determine concentration differences for oxygen (O2), glucose and lactate across the brain. The molar ratio between cerebral uptake of O2 versus carbohydrate (O2-carbohydrate index; O2/[glucose + 1/2 lactate]; OCI), the cerebral metabolic rate of O2 (CMRO2) and changes in mitochondrial O2 tension ( P(mitoO2)) were calculated. 100% W(max) was ~33% lower in the older group. Exercise increased MAP and CO in both groups (P < 0.05 vs. rest), but at each intensity MAP was higher and CO lower in the older group (P < 0.05). MCA V(mean), P(aCO2) and cerebral vascular conductance index (MCA V(mean)/MAP) were lower in the older group at each exercise intensity (P < 0.05). In contrast, young and older individuals exhibited similar increases in CMRO2 (by ~30 µmol (100 g(-1)) min(-1)), and decreases in OCI (by ~1.5) and (by ~10 mmHg) during exercise at 75% W(max). Thus, despite the older group having reduced cerebral perfusion and maximal exercise capacity, cerebral oxygenation and uptake of lactate and glucose are similar during exercise in young and older individuals.

Views of child psychiatrists on physical contact with patients.

The appropriateness and therapeutic value of physical contact with children is under increasing scrutiny. We conducted a postal questionnaire and telephone survey of consultant child and adolescent psychiatrists within Great Britain to investigate attitudes of specialists towards physical contact with their patients in different clinical contexts. Here we report that psychiatrists tend to restrict physical contact to the minimum essential for patient comfort or safety. Decision-making about contact is primarily influenced by professional experience and training. This conservative approach to physical contact with patients has implications for clinical practice and requires to be better informed by evidence.

Expression of and functional responses to protease-activated receptors on human eosinophils.

Eosinophil recruitment to airway tissue is a key feature of asthma, and release of a wide variety of toxic mediators from eosinophils leads to the tissue damage that is a hallmark of asthma pathology. Factors that control the release of these toxic mediators are targets for potential therapeutic intervention. Protease-activated receptors (PARs) are a novel class of receptors that are activated by cleavage of the N terminus of the receptor by proteases such as thrombin or trypsin-like enzymes. To date, PAR1-4 have been identified, and there are several studies that have demonstrated the expression of PARs in airway tissue, particularly the respiratory epithelium. We have investigated whether eosinophils express PARs and if activation of these receptors will then trigger a functional response. Using a combination of reverse transcriptase-polymerase chain reaction, Western blotting, and flow cytometry analysis, we have demonstrated that eosinophils express PAR1 and PAR2. FACS analysis showed that PAR1 could be clearly detected on the surface of the cells, whereas PAR2 appeared to be primarily intracellular. Trypsin and the PAR2 agonist peptide were seen in trigger shape change, release of cysteinyl leukotrienes, and most obviously, generation of reactive oxygen species. In contrast, thrombin had no effect on eosinophil function. The PAR1 agonist peptide did have a minor effect on eosinophil function, but this was most likely down to its ability to activate PAR1 and PAR2. These results demonstrate that PAR2 is the major PAR receptor that is capable of modulating eosinophil function.