Characterisation of biomarkers of intestinal barrier function in response to a high fat/high carbohydrate meal and corticotropin releasing hormone.

BACKGROUND: Variation of circulating concentrations of putative biomarkers of intestinal barrier function over the day and after acute physiological interventions are poorly documented on humans. This study aimed to examine the stability and pharmacokinetics of changes in plasma concentrations of intestinal Fatty-acid -binding -protein (IFABP), Lipopolysaccharide-binging-protein (LBP), soluble CD14, and Syndecan-1 after acute stress and high fat-high-carbohydrate meal. METHODS: In a single-blinded, cross-over, randomised study, healthy volunteers received on separate days corticotropin-releasing hormone (CRH, 100 µg) or normal saline (as placebo) intravenously in random order, then a HFHC meal. Participants were allowed low caloric food. Markers of intestinal barrier function were measured at set timed intervals from 30 minutes before to 24 hours after interventions. RESULTS: 10 participants (50% female) completed all three arms of the study. IFABP decreased by median 3.6 (IQR 1.4-10)% from -30 minutes to zero time (p = 0.001) and further reduced by 25 (20-52)% at 24 hours (p = 0.01) on the low caloric diet, but did not change in response to the meal. Syndecan-1, LBP and sCD14 were stable over a 24-hour period and not affected acutely by food intake. LBP levels 2 hours after CRH reduced by 0.61 (-0.95 to 0.05) µg/ml compared with 0.16 (-0.3 to 0.5) µg/ml post placebo injection (p = 0.05), but other markers did not change. CONCLUSION: Concentrations of IFABP, but not other markers, are unstable over 24 hours and should be measured fasting. A HFHC meal does not change intestinal permeability. Transient reduction of LPB after CRH confirms acute barrier dysfunction during stress.

Comparison of gastrointestinal landmarks using the gas-sensing capsule and wireless motility capsule.

BACKGROUND: Accurate definition of the gastroduodenal and ileocaecal junctions (GDJ, ICJ) is essential for the measurement of regional transit times. AIMS: To compare the assessment of these landmarks using the novel gas-sensing capsule and validated wireless motility capsule (WMC), and to evaluate intra-subject variance in transit times METHODS: Healthy subjects ingested the gas-sensing capsule and WMC tandemly in random order. Inter-observer agreement was evaluated by intra-class correlation coefficient (ICC). Agreement between the paired devices' transit times was assessed using Bland-Altman analysis; coefficient of variation was performed to express intra-individual variance in transit times. Similar analyses were completed with tandemly ingested gas-sensing capsules. RESULTS: The inter-observer agreement for landmarks for both capsules was excellent (mean ICC ≥0.97) in 50 studies. The GDJ was identifiable in 92% of the gas-sensing capsule studies versus 82% of the WMC studies (p = 0.27); the ICJ in 96% versus 84%, respectively (p = 0.11). In the primary cohort (n = 26), median regional transit times differed by less than 6 min between paired capsules. Bland-Altman revealed a bias of -0.12 (95% limits of agreement, -0.94 to 0.70) hours for GDJ and - 0.446 (-2.86 to 2.0) hours for ICJ. Similar results were found in a demographically distinct validation cohort (n = 24). For tandemly ingested gas-sensing capsules, coefficients of variation of transit times were 11%-35%, which were similar to variance between the paired gas-sensing capsule and WMC, as were the biases. The capsules were well tolerated. CONCLUSIONS: Key anatomical landmarks are accurately identified with the gas-sensing capsule in healthy individuals. Intra-individual differences in transit times between capsules are probably due to physiological factors. Studies in populations with gastrointestinal diseases are now required.

Acute unilateral submandibular gland swelling associated with the laryngeal mask airway.

We describe a rare complication of acute unilateral submandibular gland swelling following the use of laryngeal mask airway (LMA) in two patients with otherwise uneventful perioperative airway management. This is likely to be a consequence of the pressure exerted by the airway cuff on the tissues within the submandibular triangle. As this complication is rarely reported, its true incidence may in fact be higher, suggesting a need for greater attention on LMA cuff pressures and degree of cuff inflation. We discuss the presenting clinical features, pathophysiology and utilisation of ultrasonographic confirmation of sialadenopathy, and review the current anaesthetic literature to raise awareness of this unusual and under-reported complication of LMA. This complication can be mitigated by incorporating routine manometric checks and limiting intracuff pressures to < 60 cmH2O, potentially avoiding LMA insertions in patients with sialolithiasis and avoiding the use of nitrous oxide.

Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence.

BACKGROUND & AIMS: Observational studies suggest dietary fructose restriction might lead to sustained symptomatic response in patients with irritable bowel syndrome (IBS) and fructose malabsorption. The aims of this study were first to determine whether the efficacy of this dietary change is due to dietary fructose restriction and second to define whether symptom relief was specific to free fructose or to poorly absorbed short-chain carbohydrates in general. METHODS: The double-blinded, randomized, quadruple arm, placebo-controlled rechallenge trial took place in the general community. The 25 patients who had responded to dietary change were provided all food, low in free fructose and fructans, for the duration of the study. Patients were randomly challenged by graded dose introduction of fructose, fructans, alone or in combination, or glucose taken as drinks with meals for maximum test period of 2 weeks, with at least 10-day washout period between. For the main outcome measures, symptoms were monitored by daily diary entries and responses to a global symptom question. RESULTS: Seventy percent of patients receiving fructose, 77% receiving fructans, and 79% receiving a mixture reported symptoms were not adequately controlled, compared with 14% receiving glucose (P < or = 0.002, McNemar test). Similarly, the severity of overall and individual symptoms was significantly and markedly less for glucose than other substances. Symptoms were induced in a dose-dependent manner and mimicked previous IBS symptoms. CONCLUSIONS: In patients with IBS and fructose malabsorption, dietary restriction of fructose and/or fructans is likely to be responsible for symptomatic improvement, suggesting efficacy is due to restriction of poorly absorbed short-chain carbohydrates in general.

Time to tracheal extubation after coronary artery surgery with isoflurane, sevoflurane, or target-controlled propofol anesthesia: a prospective, randomized, controlled trial.

OBJECTIVES: To determine if anesthesia with sevoflurane or target-controlled propofol reduced the time to tracheal extubation after coronary artery bypass graft surgery compared with isoflurane anesthesia. DESIGN: A 3-arm (isoflurane, sevoflurane, or propofol), randomized, controlled trial with patients and intensive care staff blinded to the drug allocation. SETTING: A single, tertiary referral hospital affiliated with the University of Melbourne. PARTICIPANTS: Three hundred sixty elective coronary artery surgery patients. INTERVENTIONS: Patients received either isoflurane (control group, 0.5%-2% end-tidal concentration), sevoflurane (1%-4% end-tidal concentration), or target-controlled infusion of propofol (1-8 microg/mL plasma target concentration) as part of a balanced, standardized anesthetic technique including 15 microg/kg of fentanyl. MEASUREMENTS AND MAIN RESULTS: The primary outcome was time to tracheal extubation. The median time to tracheal extubation for the propofol group was 10.25 hours (interquartile range [IQR] 8.08-12.75), the sevoflurane group 9.17 hours (IQR 6.25-11.25), and the isoflurane group 7.67 hours (IQR 6.25-9.42). Intraoperatively, the propofol group required less vasopressor (p = 0.002) and more vasodilator therapy (nitroglycerin p = 0.01, nitroprusside p = 0.002). There was no difference among the groups in time to intensive care unit discharge. CONCLUSIONS: The median time to tracheal extubation was significantly longer for the target-controlled propofol group. A significantly greater number in this group required the use of a vasodilator to control intraoperative hypertension.