Intestinal fatty-acid binding protein and gut permeability responses to exercise

Purpose Intestinal cell damage due to physiological stressors (e.g. heat, oxidative, hypoperfusion/ischaemic) may contribute to increased intestinal permeability. The aim of this study was to assess changes in plasma intestinal fatty acid-binding protein (I-FABP) in response to exercise (with bovine colostrum supplementation, Col, positive control) and compare this to intestinal barrier integrity/permeability (5 h urinary lactulose/rhamnose ratio, L/R). Methods In a double-blind, placebo-controlled, crossover design, 18 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac). For each arm participants performed two baseline (resting) intestinal permeability assessments (L/R) pre-supplementation and one post-exercise following supplementation. Blood samples were collected pre- and post-exercise to determine I-FABP concentration. Results Two-way repeated measures ANOVA revealed an arm?×?time interaction for L/R and I-FABP (P?<?0.001). Post hoc analyses showed urinary L/R increased post-exercise in Plac (273% of pre, P?<?0.001) and Col (148% of pre, P?<?0.001) with post-exercise values significantly lower with Col (P?<?0.001). Plasma I-FABP increased post-exercise in Plac (191% of pre-exercise, P?=?0.002) but not in the Col arm (107%, P?=?0.862) with post-exercise values significantly lower with Col (P?=?0.013). Correlations between the increase in I-FABP and L/R were evident for visit one (P?=?0.044) but not visit two (P?=?0.200) although overall plots/patterns do appear similar for each. Conclusion These findings suggest that exercise-induced intestinal cellular damage/injury is partly implicated in changes in permeability but other factors must also contribute

The effect of bovine colostrum supplementation on intestinal injury and circulating intestinal bacterial DNA following exercise in the heat

Purpose Exercise-induced changes in intestinal permeability are exacerbated in the heat. The aim of this study was to determine the effect of 14 days of bovine colostrum (Col) supplementation on intestinal cell damage (plasma intestinal fatty acid-binding protein, I-FABP) and bacterial translocation (plasma bacterial DNA) following exercise in the heat. Methods In a double-blind, placebo-controlled, crossover design, 12 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac) consisting of 60 min treadmill running at 70% maximal aerobic capacity (30 ??C, 60% relative humidity). Blood samples were collected pre-exercise (Pre-Ex), post-exercise (Post-Ex) and 1 h post-exercise (1 h Post-Ex) to determine plasma I-FABP concentration, and bacterial DNA (for an abundant gut species, Bacteroides). Results Two-way repeated measures ANOVA revealed an arm ?~ time interaction for I-FABP (P = 0.005, with greater Post- Ex increase in Plac than Col, P = 0.01: Plac 407 ?} 194% of Pre-Ex vs Col, 311 ?} 134%) and 1 h Post-Ex (P = 0.036: Plac 265 ?} 80% of Pre-Ex vs Col, 229 ?} 56%). There was no interaction (P = 0.904) but there was a main effect of arm (P = 0.046) for plasma Bacteroides/total bacterial DNA, with lower overall levels evident in Col. Conclusion This is the first investigation to demonstrate that Col can be effective at reducing intestinal injury following exercise in the heat, but exercise responses (temporal pattern) of bacterial DNA were not influenced by Col (although overall levels may be lower).publishersversionPeer reviewe

Home-based Reach-to-Grasp training for people after stroke is feasible: A pilot randomised controlled trial

© The Author(s) 2016. Objective: To determine feasibility of a randomised controlled trial (RCT) of home-based Reach-to-Grasp training after stroke. Design: single-blind parallel group RCT. Participants: Residual arm deficit less than 12 months post-stroke. Interventions: Reach-to-Grasp training in 14 one-hour therapist's visits over 6 weeks, plus one hour self-practice per day (total 56 hours). Control: Usual care. Main Measures: Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), pre-randomisation, 7, 12, 24 weeks post-randomisation. Results: Forty-seven participants (Reach-to-Grasp=24, usual care=23) were randomised over 17 months. Reach-to-Grasp participants received a median (IQR) 14 (13,14) visits, and performed 157 (96,211) repetitions per visit; plus 30 minutes (22,45) self-practice per day. Usual care participants received 10.5 (5,14) therapist visits, comprising 38.6 (30,45) minutes of arm therapy with 16 (6,24) repetitions of functional tasks per visit. Median ARAT scores in the reach-to-grasp group were 8.5 (3.0,24.0) at baseline and 14.5 (3.5,26.0) at 24 weeks compared to median of 4 at both time points (IQR: baseline (3.0,14.0), 24 weeks (3.0,30.0)) in the usual-care group. Median WMFT tasks completed at baseline and 24 weeks were 6 (3.0,11.5) and 8.5 (4.5,13.5) respectively in the reach-to-grasp group and 4 (3.0,10.0), 6 (3.0,14.0) in the usual care group. Incidence of arm pain was similar between groups. The study was stopped before 11 patients reached the 24 weeks assessment. Conclusions: An RCT of home-based Reach-to-Grasp training after stroke is feasible and safe. With ARAT being our preferred measure it is estimated that 240 participants will be needed for a future two armed trial

Association between alcohol intoxication and mortality in severe traumatic brain injury in the emergency department: a retrospective cohort

BackgroundAcute alcohol intoxication is very common in patients with severe traumatic brain injury (TBI). Whether there is an independent association between alcohol intoxication and mortality is debated. This study hypothesized that alcohol intoxication is independently associated with less mortality after severe TBI (sTBI).MethodsThis retrospective observational cohort study included all patients with sTBI [head-Abbreviated Injury Score (AIS) >= 3, corresponding to serious head injury or worse] admitted from 1 January 2011 to 31 December 2016 in an academic level I trauma center. Patients were classified as with alcohol intoxication or without intoxication based on blood alcohol concentration or description of alcohol intoxication on admission. The primary endpoint was in-hospital mortality. Multivariable logistic regression analysis, including patient and injury characteristics, was used to assess independent association with alcohol intoxication.ResultsOf the 2865 TBI patients, 715 (25%) suffered from alcohol intoxication. They were younger (mean age 46 vs. 68 years), more often male (80 vs. 57%) and had a lower median Glasgow Coma Scale upon arrival (14 vs. 15) compared to the no-intoxication group. There was no difference in injury severity by head AIS or Rotterdam CT. Alcohol intoxication had an unadjusted association with in-hospital mortality [unadjusted odds ratio (OR) 0.51; 95% confidence interval (CI), 0.38-0.68]; however, there was no independent association after adjusting for potentially confounding patient and injury characteristics (adjusted OR 0.72; 95% CI, 0.48-1.09).ConclusionIn this retrospective study, there was no independent association between alcohol intoxication and higher in-hospital mortality in emergency patients with sTBI.Trauma Surger

Molecular clustering of genes related to the atopic syndrome

Background: The atopic syndrome consists of heterogeneous manifestations, in which multiple associated genetic loci have recently been identified. It is hypothesized that immune dysregulation plays a role in the pathogenesis. In primary immunodeficiency diseases (PIDs), which are often monogenic immunodysregulation disorders, the atopic syndrome is a frequently occurring comorbidity. Based on the genetic defects in PIDs, novel gene/pathway-targeted therapies have been evaluated, which could be relevant in the atopic syndrome as well. Therefore, we aimed to define subclasses within the atopic syndrome based on the expression profiles of immune cell lineages of healthy mice. Methods: Overlap between known atopy-related genes as described in the Human Gene Mutation Database and disease-causing genes of monogenic PIDs was evaluated. Clusters of atopy-related genes were based on the overlap in their co-expressed genes using the gene expression profiles of immune cell lineages of healthy mice from the Immunological Genome Project. We analyzed pathways involved in the atopic syndrome using Ingenuity Pathway Analysis. Results: Twenty-two (5.3%) genes were overlapping between the atopy-related genes (n = 160) and PID-related genes (n = 278). We identified seven distinct clusters of atopy-related genes. Functional pathway analysis of all atopy-related genes showed relevance of T helper cell-mediated pathways. Conclusions: This study shows a model to define clusters within the atopic syndrome based on gene expression profiles of immune cell lineages. Our results support the hypothesis that both genetic mechanisms and immune dysregulation play a role in the pathogenesis. It also opens up the possibility for novel therapeutic targets and a more tailored approach towards personalized medicine

Prolonged Antibiotic Treatment does not Prevent Intra-Abdominal Abscesses in Perforated Appendicitis

Contains fulltext : 89619.pdf (publisher's version ) (Open Access)BACKGROUND: Children with perforated appendicitis have a relatively high risk of intra-abdominal abscesses. There is no evidence that prolonged antibiotic treatment after surgery reduces intra-abdominal abscess formation. We compared two patient groups with perforated appendicitis with different postoperative antibiotic treatment protocols. METHODS: We retrospectively reviewed patients younger than age 18 years who underwent appendectomy for perforated appendicitis at two academic hospitals between January 1992 and December 2006. Perforation was diagnosed during surgery and confirmed during histopathological evaluation. Patients in hospital A received 5 days of antibiotics postoperatively, unless decided otherwise on clinical grounds. Patients in hospital B received antibiotics for 5 days, continued until serum C-reactive protein (CRP) was <20 mg/l. Univariate logistic regression analysis was performed on intention-to-treat basis. p < 0.05 was considered significant. RESULTS: A total of 149 children underwent appendectomy for perforated appendicitis: 68 in hospital A, and 81 in hospital B. As expected, the median (range) use of antibiotics was significantly different: 5 (range, 1-16) and 7 (range, 2-32) days, respectively (p < 0.0001). However, the incidence of postoperative intra-abdominal abscesses was similar (p = 0.95). Regression analysis demonstrated that sex (female) was a risk factor for abscess formation, whereas surgical technique and young age were not. CONCLUSIONS: Prolonged use of antibiotics after surgery for perforated appendicitis in children based on serum CRP does not reduce postoperative abscess formation.1 december 201

Rapid Low-Cost Microarray-Based Genotyping for Genetic Screening in Primary Immunodeficiency

Background: Genetic tests for primary immunodeficiency disorders (PIDs) are expensive, time-consuming, and not easily accessible in developing countries. Therefore, we studied the feasibility of a customized single nucleotide variant (SNV) microarray that we developed to detect disease-causing variants and copy number variation (CNV) in patients with PIDs for only 40 Euros. Methods: Probes were custom-designed to genotype 9,415 variants of 277 PID-related genes, and were added to the genome-wide Illumina Global Screening Array (GSA). Data analysis of GSA was performed using Illumina GenomeStudio 2.0, Biodiscovery Nexus 10.0, and R-3.4.4 software. Validation of genotype calling was performed by comparing the GSA with whole-genome sequencing (WGS) data of 56 non-PID controls. DNA samples of 95 clinically diagnosed PID patients, of which 60 patients (63%) had a genetically established diagnosis (by Next-Generation Sequencing (NGS) PID panels or Sanger sequencing), w

Study design and methods of the BoTULS trial: a randomised controlled trial to evaluate the clinical effect and cost effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A

Background Following a stroke, 55–75% of patients experience upper limb problems in the longer term. Upper limb spasticity may cause pain, deformity and reduced function, affecting mood and independence. Botulinum toxin is used increasingly to treat focal spasticity, but its impact on upper limb function after stroke is unclear. The aim of this study is to evaluate the clinical and cost effectiveness of botulinum toxin type A plus an upper limb therapy programme in the treatment of post stroke upper limb spasticity. Methods Trial design : A multi-centre open label parallel group randomised controlled trial and economic evaluation. Participants : Adults with upper limb spasticity at the shoulder, elbow, wrist or hand and reduced upper limb function due to stroke more than 1 month previously. Interventions : Botulinum toxin type A plus upper limb therapy (intervention group) or upper limb therapy alone (control group). Outcomes : Outcome assessments are undertaken at 1, 3 and 12 months. The primary outcome is upper limb function one month after study entry measured by the Action Research Arm Test (ARAT). Secondary outcomes include: spasticity (Modified Ashworth Scale); grip strength; dexterity (Nine Hole Peg Test); disability (Barthel Activities of Daily Living Index); quality of life (Stroke Impact Scale, Euroqol EQ-5D) and attainment of patient-selected goals (Canadian Occupational Performance Measure). Health and social services resource use, adverse events, use of other antispasticity treatments and patient views on the treatment will be compared. Participants are clinically reassessed at 3, 6 and 9 months to determine the need for repeat botulinum toxin type A and/or therapy. Randomisation : A web based central independent randomisation service. Blinding : Outcome assessments are undertaken by an assessor who is blinded to the randomisation group. Sample size : 332 participants provide 80% power to detect a 15% difference in treatment successes between intervention and control groups. Treatment success is defined as improvement of 3 points for those with a baseline ARAT of 0–3 and 6 points for those with ARAT of 4–56

The PINE study: rationale and design of a randomised comparison of epidural injection of local anaesthetics and steroids versus care-as-usual to prevent postherpetic neuralgia in the elderly [ISRCTN32866390]

BACKGROUND: Postherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients. METHODS / DESIGN: The PINE study is an open, multicenter clinical trial in which 550 elderly (age ≥ 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness. CONCLUSION: The PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN

Cost effectiveness of epidural steroid injections to manage chronic lower back pain

Background The efficacy of epidural steroid injections in the management of chronic low back pain is disputed, yet the technique remains popular amongst physicians and patients alike. This study assesses the cost effectiveness of injections administered in a routine outpatient setting in England. Methods Patients attending the Nottingham University Hospitals’ Pain Clinic received two injections of methylprednisolone plus levobupivacaine at different dosages, separated by at least 12 weeks. Prior to each injection, and every week thereafter for 12 weeks, participants completed the EQ-5D health-related quality of life instrument. For each patient for each injection, total health state utility gain relative to baseline was calculated. The cost of the procedure was modelled from observed clinical practice. Cost effectiveness was calculated as procedure cost relative to utility gain. Results 39 patients provided records. Over a 13-week period commencing with injection, mean quality adjusted life year (QALY) gains per patient for the two dosages were 0.028 (SD 0.063) and 0.021 (SD 0.057). The difference in QALYs gained by dosage was insignificant (paired t-test, CIs -0.019 – 0.033). Based on modelled resource use and data from other studies, the mean cost of an injection was estimated at £219 (SD 83). The cost utility ratio of the two injections amounted to £8,975 per QALY gained (CIs 5,480 – 22,915). However, at costs equivalent to the tariff price typically paid to providers by health care purchasers, the ratio increased to £27,459 (CIs 16,779 – 70,091). Conclusions When provided in an outpatient setting, epidural steroid injections are a short term, but nevertheless cost effective, means of managing chronic low back pain. However, designation of the procedure as a day case requires the National Health Service to reimburse providers at a price which pushes the procedure to the margin of cost effectiveness