Management of the lower gastrointestinal system in burn: A comprehensive review.

BACKGROUND: Burn produces complex gastrointestinal (GI) responses. Treatment, including large volume fluid resuscitation and opioid analgesia, may exacerbate GI dysfunction. Complications include constipation and opioid-induced bowel dysfunction (OBD), acute colonic pseudo-obstruction (ACPO), bacterial translocation and sepsis, and abdominal compartment syndrome (ACS). Contamination of perineal burns contributes to delayed healing, skin graft failure and sepsis and may impact upon morbidity and mortality. The authors carried out a literature review on management of the lower GI system in burn. This study aimed to explain: current prevention and treatment modalities; drawbacks and complications associated with available treatments, and to provide direction for development of best practice guidelines. ACS is associated with high mortality and should be treated with careful fluid resuscitation and diuresis, to minimise and remove oedema. METHODS: A comprehensive search of English language literature was performed on PubMed, Medline and Embase. Both MeSH and keywords searches were used. RESULTS: Evidence available on the management of lower gastrointestinal system in burn is summarised. Levels of evidence available are generally low (level III-IV). CONCLUSION: Structured, graded interventions are required for prevention and treatment of constipation and OBD. Correction of electrolyte imbalance, adequate enteral intake and mobilisation are pre-requisites. Laxatives should be used according to World Gastroenterology Organisation recommendations. Resistant constipation may respond to changes in medication, but ACPO should be suspected and treated when present. Other complications, such as bacterial translocation and ACS are common in major burns. There is evidence that selective digestive tract decontamination reduces mortality and infectious episodes in major burns. ACS is associated with high mortality and should be treated with careful fluid resuscitation and diuresis. Surgery is reserved for non-responsive and severe cases. Perineal burns present challenges in wound and bowel management. Faecal management systems and negative pressure wound therapy (NPWT) may improve wound control and hygiene, but diversion colostomy will still be beneficial in some cases. There is a clear need for rigorous studies to guide practice more effectively in these challenging conditions.

Physical activity, inflammation, and volume of the aging brain.

Physical activity influences inflammation, and both affect brain structure and Alzheimer's disease (AD) risk. We hypothesized that older adults with greater reported physical activity intensity and lower serum levels of the inflammatory marker tumor necrosis factor α (TNFα) would have larger regional brain volumes on subsequent magnetic resonance imaging (MRI) scans. In 43 cognitively intact older adults (79.3±4.8 years) and 39 patients with AD (81.9±5.1 years at the time of MRI) participating in the Cardiovascular Health Study, we examined year-1 reported physical activity intensity, year-5 blood serum TNFα measures, and year-9 volumetric brain MRI scans. We examined how prior physical activity intensity and TNFα related to subsequent total and regional brain volumes. Physical activity intensity was measured using the modified Minnesota Leisure Time Physical Activities questionnaire at year 1 of the study, when all subjects included here were cognitively intact. Stability of measures was established for exercise intensity over 9 years and TNFα over 3 years in a subset of subjects who had these measurements at multiple time points. When considered together, more intense physical activity intensity and lower serum TNFα were both associated with greater total brain volume on follow-up MRI scans. TNFα, but not physical activity, was associated with regional volumes of the inferior parietal lobule, a region previously associated with inflammation in AD patients. Physical activity and TNFα may independently influence brain structure in older adults.

Body mass index, but not FTO genotype or major depressive disorder, influences brain structure.

Obesity and major depressive disorder (MDD) are highly prevalent and often comorbid health conditions. Both are associated with differences in brain structure and are genetically influenced. Yet, little is known about how obesity, MDD, and known risk genotypes might interact in the brain. Subjects were 81 patients with MDD (mean age 48.6 years) and 69 matched healthy controls (mean age 51.2 years). Subjects underwent 1.5T magnetic resonance imaging, genotyping for the fat mass and obesity associated (FTO) gene rs3751812 polymorphism, and measurements for body mass index (BMI). We conducted a whole brain voxelwise analysis using tensor-based morphometry (TBM) to examine the main and interaction effects of diagnosis, BMI and FTO genotype. Significant effects of BMI were observed across widespread brain regions, indicating reductions in predominantly subcortical and white matter areas associated with increased BMI, but there was no influence of MDD or FTO rs3751812 genotype. There were no significant interaction effects. Within MDD patients, there was no effect of current depressive symptoms; however the use of antidepressant medication was associated with reductions in brain volume in the frontal lobe and cerebellum. Obesity affects brain structure in both healthy participants and MDD patients; this influence may account for some of the brain changes previously associated with MDD. BMI and the use of medication should ideally be measured and controlled for when conducting structural brain imaging research in MDD.

The efficacy of indapamide in hypertensive patients failing to respond to a beta-blocker alone.

A double-blind, placebo-controlled, cross-over study was carried out to evaluate the efficacy and safety of 2.5 mg indapamide in 24 hypertensive patients failing to respond to oxprenolol alone. An additional 6 patients were assessed by ambulatory blood pressure recordings over a 15-hour period with a Remler M2,000 semi-automatic sphygmomanometer. On average, indapamide reduced supine blood pressure by 18.5/10 mmHg and standing blood pressure by 19.6/8.9 mmHg. The ambulatory recordings carried out in 6 patients detected a fall in diastolic pressure not observed using clinic readings in these 6 patients, suggesting that this is a more sensitive method of detecting antihypertensive effect. These responses were not associated with significant changes in heart rate or body weight and there was no significant postural fall in blood pressure. No serious side-effects were reported. Changes in serum potassium, chloride and urate similar to those seen with diuretics were observed. These results suggest that indapamide is a useful and safe adjunct to beta-adrenoceptor blocking therapy for uncontrolled hypertension.

The clinical pharmacology of tolmesoxide. A new vasodilator antihypertensive agent.

The haemodynamic response and pharmacokinetics of single dose oral tolmesoxide were studied at various dose levels in 4 patients with severe hypertension. There was a reproducible fall in mean arterial pressure from baseline of 24.2% and a rise in heart rate of 37.6% following administration of tolmesoxide. The onset of antihypertensive action occurred within 1 h, with a peak effect at 3 h after dosing. The mean duration of action was up to 12.0 h. Tolmesoxide had a mean half-life of 3.0 h. It was rapidly absorbed with a mean peak plasma level occurring at 1.0 h. Plasma levels correlated well with the doses administered. Side-effects include mild nausea, facial flushing and postural symptoms.

Malignant islet-cell tumour of the pancreas presenting with non-bacterial thrombotic endocarditis and eosinophilia.

A case of severe persistent eosinophilia and non-bacterial thrombotic endocarditis complicating a malignant islet-cell tumour of the pancreas is documented. Although these are well recognized complications of malignant tumours, they do not appear to have been previously documented from the same patient. These complications probably reflect ectopic synthesis and are unlikely to be causally interrelated.

Clinical pharmacology of tolmesoxide in refractory heart failure.

The haemodynamic effects and pharmacokinetics of single intravenous doses of tolmesoxide, a new vasodilator agent, were studied in 6 patients with severe cardiac failure secondary to ischaemic cardiomyopathy and refractory to conventional therapy. The mean (+ SEM) baseline cardiac index (CI) and pulmonary artery diastolic pressure (PADP) were 1.7 +0.11/min/m2 and 30.5 +4.1 mm Hg respectively. The mean % rise in CI was 78.8 +23.3 and the mean % fall in PADP was 35.2 +5.2. The mean half life of tolmesoxide in these patients was markedly prolonged at 15.6 +6.6h. Side effects were minimal - vomiting was seen in 1 patient. This agent warrants further study in the long term management of refractory cardiac failure.