Alvimopan Is Associated With a Reduction in Length of Stay and Hospital Costs for Patients Undergoing Radical Cystectomy.

OBJECTIVE: To evaluate the impact of alvimopan in patient undergoing radical cystectomy (RC) for bladder cancer. We hypothesize that alvimopan can decrease cost for RC by reducing length of stay (LOS). METHODS: We identified patients who underwent elective RC for bladder cancer from 2009 to 2015 in the Premier Healthcare Database, a nationwide, all-payer hospital-based database, and compared patients who received and did not receive alvimopan in the perioperative period. Hospitals that had no record of administering alvimopan for patients undergoing RC were excluded. The primary outcomes were LOS and the direct hospital costs. The secondary outcomes were 90-day readmission for ileus and major complications. RESULTS: After applying the inclusion criteria, the study cohort consisted of 1087 patients with 511 patients receiving perioperative alvimopan. Alvimopan was associated with a reduction in hospital costs by -$2709 (95% confidence interval: -$4507 to -$912, P = .003), decreased median LOS (7 vs 8 days, P < .001), and lower likelihood of readmission for ileus (adjusted odds ratio: 0.63, P = .041). While alvimopan use led to higher pharmacy costs, this was outweighed by lower room and board costs due to the reduced LOS. There was no significant difference between 2 groups regarding major complications. These results were robust across multiple adjusted regression models. CONCLUSION: Our data show that alvimopan is associated with a substantial cost-saving in patients undergoing RC, and suggest that routine use of alvimopan may be a potential cost-effective strategy to reduce the overall financial burden of bladder cancer.

How the Beneficial Effects of Alvimopan Differ With Surgical Approach for Radical Cystectomy.

OBJECTIVE: To assess whether the beneficial perioperative effects of alvimopan differ with surgical approach for patients who undergo open radical cystectomy (ORC) vs robot-assisted radical cystectomy (RARC). METHODS: This retrospective study reviewed all patients who underwent cystectomy with urinary diversion at our institution between January 1, 2007, and January 1, 2018. Data were collected on demographic characteristics, comorbidities, surgical approach, alvimopan therapy, hospital length of stay (LOS), days until return of bowel function (ROBF), and complications. Outcomes and interactions were evaluated through regression analysis. RESULTS: Among 573 patients, 236 (41.2%) underwent RARC, 337 (58.8%) underwent ORC, and 205 (35.8%) received alvimopan. Comparison of 4 cohorts (ORC with alvimopan, ORC without alvimopan, RARC with alvimopan, and RARC without alvimopan) showed that patients who underwent ORC without alvimopan had the highest rate of postoperative ileus (25.6%, P = .02), longest median hospital LOS (7 days, P < .001), and longest time until ROBF (4 days, P < .001). On multivariable analysis, the interaction between surgical approach and alvimopan use was significant for the outcome of ROBF (estimate, 1.109; 95% confidence interval, 0.418-1.800; P = .002). In the RARC cohort, multivariable analysis showed no benefit of alvimopan with respect to ileus (P = .27), LOS (P = .09), or ROBF (P = .36). Regarding joint effects of robotic approach and alvimopan, RARC had no effect on gastrointestinal tract outcomes. CONCLUSION: We observed a diminished beneficial effect of alvimopan among patients undergoing RARC and a statistically significant benefit of alvimopan among patients undergoing ORC. The implications of these findings may permit more selective medication use for patients who would benefit the most from this drug.

Potential Strategies in the Prevention of Nonsteroidal Anti-inflammatory Drugs-Associated Adverse Effects in the Lower Gastrointestinal Tract.

With the increasing use of nonsteroidal anti-inflammatory drugs (NSAIDs), the incidence of lower gastrointestinal (GI) complications is expected to increase. However, unlike upper GI complications, the burden, pathogenesis, prevention and treatment of NSAID-associated lower GI complications remain unclear. To date, no cost-effective and safe protective agent has been developed that can completely prevent or treat NSAID-related lower GI injuries. Selective COX-2 inhibitors, misoprostol, intestinal microbiota modulation, and some mucoprotective agents have been reported to show protective effects on NSAID-induced lower GI injuries. This review aims to provide an overview of the current evidence on the prevention of NSAID-related lower GI injuries.

The first in vivo application of synthetic polymers based on methacrylic acid as an aflatoxin sorbent in an animal model.

This study attempts to evaluate the potential aflatoxin binder activity of a molecularly imprinted polymer (TMU95) synthesized to target the aflatoxin B1 (AFB1) analog molecule in comparison to a commercial toxin binder (CTB). Adsorption experiments were carried out to assess the ability to bind to AFB1 at various pH values. The strength of binding was investigated by the chemisorption index. The isothermal analysis was used to determine the maximum adsorption capacity values. The ability of TMU95 and CTB to adsorb essential minerals was evaluated and the obtained data suggested that CTB would significantly reduce availability of them compared to TMU95. The in vivo efficacy of TMU95 as an aflatoxin (AF) binder in duckling exposed to aflatoxin-contaminated feed from 4 to 18 days of age in comparison to the CTB was also assessed. TMU95 and CTB were effective in reducing the adverse effects caused by AFs on feed conversion ratio of duckling (p ≤ 0.01), and also showed a minor reduction of injuries caused by AFs on visceral organs enlargement (p ≤ 0.01). It was concluded that TMU95 could absorb AFB1 in vitro efficiently and had beneficial health effects that could alleviate some of the toxic effects of AFs on growing duckling performance similar to CTB.

The Ever-Changing Landscape of Drug-Induced Injury of the Lower Gastrointestinal Tract.

CONTEXT: -There is an ever-growing armamentarium of pharmacologic agents that can cause gastrointestinal (GI) mucosal injury, the most common symptoms being diarrhea, constipation, nausea, and vomiting. These are often self-limiting and without serious sequelae, but some symptoms are of greater concern, like drug-induced mucosal ulceration that can manifest as GI hemorrhage, stricture formation, and even perforation. Histologically, there is significant overlap between drug-induced injuries and various disease entities. A single type of medication may cause multiple patterns of injury, which can involve the entire GI tract or just some parts of it. OBJECTIVE: -To review the most common drug-induced injury patterns affecting the colon, which may be recognized by the surgical pathologist on colonic mucosal biopsies. This review does not address the injuries occurring in the upper GI tract. DATA SOURCES: -A PubMed review of English-language literature, up to December 2015, on drug-induced injury of GI tract was performed. CONCLUSIONS: -There are numerous drugs that damage the colonic mucosa. The most common drugs are included in this review according to their histologic pattern of injury. It is important for the pathologist to keep in mind that a single drug type can induce many histologic patterns of mucosal injury that can mimic many disease entities. Although there are some histologic clues helpful in the diagnosis of drug-induced colonic injury, correlation with clinical history and especially medication history is essential to improve diagnostic accuracy.

Protons pump inhibitor treatment and lower gastrointestinal bleeding: Balancing risks and benefits.

Proton pump inhibitors (PPIs) represent a milestone in the treatment of acid-related diseases, and are the mainstay in preventing upper gastrointestinal bleeding in high-risk patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin. However, this beneficial effect does not extend to the lower gastrointestinal tract. PPIs do not prevent NSAID or aspirin-associated lower gastrointestinal bleeding (LGB). PPIs may increase both small bowel injury related to NSAIDs and low-dose aspirin treatment and the risk of LGB. Recent studies suggested that altering intestinal microbiota by PPIs may be involved in the pathogenesis of NSAID-enteropathy. An increase in LGB hospitalization rates may occur more frequently in older patients with more comorbidities and are associated with high hospital resource utilization, longer hospitalization, and increased mortality. Preventive strategies for NSAID and aspirin-associated gastrointestinal bleeding should be directed toward preventing both upper and lower gastrointestinal damage. Future research should be directed toward identifying patients at low-risk for gastrointestinal events associated with the use of NSAIDs or aspirin to avoid inappropriate PPI prescribing. Alternatively, the efficacy of new pharmacologic strategies should be evaluated in high-risk groups, with the aim of reducing the risk of both upper and lower gastrointestinal bleeding in these patients.

Prophylaxis Versus Treatment Use of Laxative for Paralysis of Lower Gastrointestinal Tract in Critically Ill Patients.

GOALS: To evaluate the prevalence of lower gastrointestinal tract paralysis and to compare the success to achieve defecation between treatment and prophylaxis strategies. BACKGROUND: Laxatives use is commonly the first-level measure to achieve defecation in critically ill patients with lower gastrointestinal tract paralysis. Studies comparing prophylaxis versus treatment of lower gastrointestinal tract paralysis have not been performed yet. STUDY: We designed 3 sequential phases of 4 months each: observational phase, treatment phase, and prophylaxis phase. First-level measure was intermittent polyethylene glycol (PEG) 4000 by nasogastric tube. Second-level measures were enema, neostigmine, and continuous PEG. Primary endpoints were the prevalence of constipation for the observational phase and the number of patients that failed to achieve defecation with first-level measures for the treatment and prophylaxis phases. RESULTS: Paralysis of lower gastrointestinal tract in the observational phase was found in 57 of 63 patients (90.5%). Failure to achieve defecation with the first-level measure occurred in 16 of 64 patients (25%) in the treatment phase and in 6 of 70 patients (8.6%) in the prophylaxis phase (P=0.01). Eighteen measures of second level were applied in the treatment phase and 6 in the prophylaxis phase. CONCLUSIONS: Paralysis of the lower gastrointestinal tract in mechanically ventilated ICU patients is common. PEG given as prophylaxis on the first day after mechanical ventilation is associated with faster resolution of paralysis of gastrointestinal tract than PEG given as a treatment on day 4.

Epidemiology of Low Dose Aspirin Damage in the Lower Gastrointestinal Tract.

Low dose aspirin (ASA), commonly defined as the cardiovascular (CV) dose of 75 to 325 mg daily, is one of the most widely prescribed drugs in the world and the cornerstone of therapy and prophylaxis for CV disease. However, the use of low dose ASA is well known to be associated with an increased risk of different upper and lower gastrointestinal (GI) complications, such as peptic ulceration and bleeding. In the recent past, clinical research was mainly focused on ASA-related injury of the upper GI tract. However, the introduction of new endoscopic techniques, such as capsule endoscopy and balloon-assisted endoscopy for the evaluation of small bowel lesions have resulted in an increasing interest among gastroenterologists about the side effects of ASA on the large and small bowel. Furthermore, it has been demonstrated that chronic use of low dose ASA results in a variety of lesions in the lower GI tract, including multiple petechiae, erosions, ulcers, diverticular bleeding and even circumferential ulcers with stricture. The ideal treatment for small bowel injury in low dose ASA users would be withdrawal of ASA, however, this withdrawal could increase the risk of CV/cerebrovascular morbidity and mortality in high percentage of patients. Therefore, several drugs have been evaluated to identify the best choice to prevent or treat ASA-induced small bowel injury with different results. Nevertheless, further specifically designed studies with more sample size are needed to determine the best treatment for low dose ASA related GI injury.

Outcomes of trimodality approach in the management of T2N0M0 bladder cancer.

AIMS AND BACKGROUND: The main objective of this study is to evaluate outcomes of bladder preservation treatment for patients with muscle-invasive bladder cancer. METHODS AND STUDY DESIGN: 38 patients with histologically proven muscle-invasive bladder cancer treated at our department between January 2008 and December 2013 were analyzed retrospectively. Age, gender, pathology, stage, 3-year overall survival, 3-year disease-free survival, radiotherapy (RT) dose, genitourinary and gastrointestinal toxicity scores and response evaluation of the patients were recorded. 3-year overall survival and 3-year disease-free survivals were calculated by Kaplan-Meier method along with the analysis of gender, pathology, stage and therapy response of the study group. RESULTS: 33 patients (86.8%) were managed with concomitant chemoradiotherapy whereas 5 patients (13.2%) received only radiation therapy due to renal insufficency and comorbid diseases. 6 (15.8%) out of 38 patients had partial response (PR) and remaining 32 (84.2%) patients experienced complete response (CR). The PR group underwent salvage cystectomy and CR group had been followed-up after radical radiotherapy. Mean age of the group was 70.9 (range 45-90) years. 26 of all patients were male (68.4%) and 12 were female (31.6%). Mean follow-up time after completion of radiotherapy was 24.7 months (range 12-40). Mean RT dose was 64 Gy (range 60-66). 3-year overall survival was 64% and 3-year disease free survival was 73%. CONCLUSIONS: Bladder preserving approach is an alternative definitive therapy solution to radical cystectomy in the treatment of muscle-invasive bladder cancer with less morbidity, preserved natural bladder, and high quality of life.

Exploring the effects of galacto-oligosaccharides on the gut microbiota of healthy adults receiving amoxicillin treatment.

In the present double-blind, randomised, parallel intervention study, the effects of the intake of galacto-oligosaccharides (GOS) on the gut microbiota of twelve healthy adult subjects (aged 18-45 years with a normal BMI (18-25 kg/m²)) receiving amoxicillin (AMX) treatment were determined. All the subjects were treated with AMX (375 mg; three times per d) for 5 d and given either GOS (n 6) or placebo (maltodextrin, n 6) (2·5 g; three times per d) during and 7 d after AMX treatment. Faecal samples were collected twice before starting the treatment and on days 2, 5, 8, 12, 19 and 26. Due to AMX treatment, a decrease in the abundance of Bifidobacterium spp., an overgrowth of Enterobacteriaceae, and a disruption of the metabolic activity of the microbiota (increase in succinate, monosaccharide and oligosaccharide levels in the faecal samples) were observed in both groups (P< 0·05). Positive effects of GOS intake were observed on the levels of bifidobacteria, although not found to be significant. Data revealed that the levels of bifidobacteria were higher upon GOS intake than upon placebo intake, especially after AMX treatment. The activity of bifidobacteria and subsequent cross-feeding activity of the microbiota upon GOS intake compared with those upon placebo intake were reflected by the significant increase in butyrate levels (P< 0·05) in the faecal samples after AMX treatment. Despite the small number of subjects, our findings confirm previous results obtained in vitro, namely that GOS intake supports the recovery of the beneficial bifidobacteria and, indirectly, the production of butyrate after AMX treatment.

Gastrointestinal lesions and complications of low-dose aspirin in the gastrointestinal tract.

Low dose aspirin (ASA) use has been associated with a wide range of adverse side effects in the upper gastrointestinal (GI) tract, which range from troublesome symptoms without mucosal lesions to more serious toxicity, including ulcers, GI bleeding, perforation and even death. Upper GI symptoms in low dose ASA users are common but often careless or misinterpreted and they are not always related to the presence of mucosal injury. Usually, low dose ASA related ulcers are reasonably small and asymptomatic, and probably heal over a period of weeks to a few months. But, the real clinical problem occurs when the ulcer results in a GI complication (mostly bleeding). The estimated average excess risk of symptomatic or complicated ulcer related to low dose ASA is five cases per 1000 ASA users per year. Death is the worst outcome of GI complications in low dose ASA users, but data about this aspect are scarce. Current evidence indicates that low dose ASA can damage the lower GI tract also, but the real size of the problem is still unknown.

The APC and PreSAP trials: a post hoc noninferiority analysis using a comprehensive new measure for gastrointestinal tract injury in 2 randomized, double-blind studies comparing celecoxib and placebo.

BACKGROUND: Previous gastrointestinal (GI) outcomes of nonsteroidal anti-inflammatory drug (NSAID) trials have focused on upper GI events, although recent evidence suggests NSAID-related lower GI effects are important and clinically relevant. OBJECTIVE: We assessed the long-term GI adverse event (AE) profile of celecoxib in a nonarthritis population. The aim of this post hoc analysis was to determine the incidence of serious GI AEs, using a new Clinically Significant Upper and/or Lower GI Events end point. METHODS: Patients from 2 colorectal adenoma recurrence studies were included. Patients received celecoxib 200 mg/400 mg BID, 400 mg once daily, or placebo over 3 years. The analysis measured noninferiority, using a prespecified definition of noninferiority. Celecoxib was predefined to be noninferior to placebo if the upper limit of the 95% CI for the hazard ratio (HR) with celecoxib was <1.25, at any dose, compared with the placebo (calculated using the Cox proportional hazards model). RESULTS: A total of 3588 patients were included; in the primary analysis, the HR for celecoxib (any dose) compared with placebo was 1.22 (95% CI: 0.69-2.18; P = 0.4948). In the secondary dose analyses, the HR associated with a 400-mg daily dose, compared with placebo, was 1.04 (95% CI: 0.55-1.96; P = 0.9149); for 800 mg/d, the HR was 1.79 (95% CI: 0.82-3.89; P = 0.1427). In a third covariate analysis, low-dose aspirin use (HR = 2.33; 95% CI: 1.33-4.08) and age ≥65 years (HR = 1.82; 95% CI, 1.05-3.15) was suggested to have a statistically significant association with increased risk of GI AEs. Study limitations include retrospective evaluation and small sample size of patients with GI AEs. CONCLUSIONS: The noninferiority of celecoxib to placebo was not established because the HR for the time to the first Clinically Significant Upper and/or Lower GI Event was greater than the prespecified upper limit of 95% CI for noninferiority. In addition, HRs associated with daily doses of 400 or 800 mg celecoxib compared with placebo were not significant. However, a significantly increased risk of clinically significant upper and/or lower GI events was observed in low-dose aspirin users (≤162.5 mg average daily use) and in patients ≥65 years of age.

Guinea pig ileum motility stimulation elicited by N-formyl-Met-Leu-Phe (fMLF) involves neurotransmitters and prostanoids.

In guinea-pig ileum (GPI), the chemotactic peptide N-formyl-Met-Leu-Phe-OH (fMLF) possesses spasmogenic properties through the activation of formyl peptide receptors (FPRs). Despite this, the mediators involved remain to be elucidated. fMLF (1nM-1µM) induced a dose-dependent contraction of GPI (EC(50)=24nM), that is blocked by pre-treatment with the FPRs antagonist Boc(2). The pre-treatment with tetrodotoxin (TTX) atropine or with SR140333 reduced the fMLF-induced contraction, whereas with hexamethonium, MEN10627, SB222200, mepyramine, cimetidine, thioperamide or methysergide did not produce any effect. With DuP697 pre-treatment, but not with piroxicam, reduced the fMLF-induced contraction. After stimulation with 24nM fMLF, a strong increase in the PGE(2) levels was observed. Finally, the concomitant blocking of the NK(1) receptor, the muscarinic receptors and COX-2 abolished the GPI contractions induced by fMLF. fMLF induced a concentration-dependent contraction of guinea-pig jejunum (EC(50)=11nM), proximal colon (EC(50)=3.5nM) and distal colon (EC(50)=2.2nM), with a time-course similar to that observed in GPI. In these preparations as well, the co-administration of atropine, SR140333 and DuP697 abolished the contractions induced by fMLF. Intraperitoneal injection of fMLF (0.1 or 1µmol/kg) enhanced the gastrointestinal motility in mice, abolished by the co-administration of atropine, SR140333 and DuP697. In conclusion, we showed that fMLF exerts spasmogenic actions on guinea-pig intestine both in vitro and in vivo through the release of acetylcholine and substance P from myenteric motorneurons and through prostanoids, probably from the inflammatory cells of the enteric immune system.

Effects of the mycotoxin destruxin A on Locusta migratoria visceral muscles.

Destruxins, a family of cyclic peptides, are produced by various species of entomopathogenic fungi. These peptides have been shown to influence calcium-dependent processes in insect cell lines and tissues, such as skeletal muscles. To better understand the mechanism of action of these peptide toxins on insect muscular tissues, we have evaluated the effects of destruxin A on the contractions of oviducts and hindgut of Locusta migratoria. In oviducts, destruxin A increased the frequency of spontaneous contractions and induced a dose-dependent tonic contraction; the EC(50) for lower lateral and upper lateral oviducts was 0.7 microM and 8.7 microM, respectively. In hindgut, destruxin A also caused an increase in the frequency of spontaneous contractions; the EC(50) was 3.2 microM. The action of destruxin A was abolished in Ca(2+)-free saline or when the Ca(2+) channel blocker CoCl(2) was added to the incubation saline. Likewise, the presence of 50 microM nifedipine or 100 microM verapamil in the medium reduced the magnitude of destruxin A's effect, particularly in hindgut. The depolarization of muscle membranes by 100 mM K(+) saline prevented the action of destruxin A. Preincubation of lower lateral oviducts in the intracellular Ca(2+) antagonist TMB-8 did not have any effect on destruxin A action; however, preincubation in the calmodulin inhibitor trifluoperazine greatly reduced the effect of destruxin A. Taken together, these results show that destruxin A has an excitatory effect on contractions of insect visceral muscles of L. migratoria. Destruxin A-induced contractions appear to be dependent on extracellular, but not on intracellularly-released Ca(2+), which suggest that this peptide toxin might be acting on insect visceral muscle by facilitating an influx of extracellular Ca(2+).

Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): a randomised trial.

BACKGROUND: Cyclo-oxygenase (COX)-2-selective non-steroidal anti-inflammatory drugs (NSAIDs) and non-selective NSAIDs plus a proton-pump inhibitor (PPI) have similar upper gastrointestinal outcomes, but risk of clinical outcomes across the entire gastrointestinal tract might be lower with selective drugs than with non-selective drugs. We aimed to compare risk of gastrointestinal events associated with celecoxib versus diclofenac slow release plus omeprazole. METHODS: We undertook a 6-month, double-blind, randomised trial in patients with osteoarthritis or rheumatoid arthritis at increased gastrointestinal risk at 196 centres in 32 countries or territories. Patients tested negative for Helicobacter pylori and were aged 60 years and older or 18 years and older with previous gastroduodenal ulceration. We used a computer-generated randomisation schedule to assign patients in a 1:1 ratio to receive celecoxib 200 mg twice a day or diclofenac slow release 75 mg twice a day plus omeprazole 20 mg once a day. Patients and investigators were masked to treatment allocation. The primary endpoint was a composite of clinically significant upper or lower gastrointestinal events adjudicated by an independent committee. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00141102. FINDINGS: 4484 patients were randomly allocated to treatment (2238 celecoxib; 2246 diclofenac plus omeprazole) and were included in intention-to-treat analyses. 20 (0.9%) patients receiving celecoxib and 81 (3.8%) receiving diclofenac plus omeprazole met criteria for the primary endpoint (hazard ratio 4.3, 95% CI 2.6-7.0; p<0.0001). 114 (6%) patients taking celecoxib versus 167 (8%) taking diclofenac plus omeprazole withdrew early because of gastrointestinal adverse events (p=0.0006). INTERPRETATION: Risk of clinical outcomes throughout the gastrointestinal tract was lower in patients treated with a COX-2-selective NSAID than in those receiving a non-selective NSAID plus a PPI. These findings should encourage review of approaches to reduce risk of NSAID treatment. FUNDING: Pfizer Inc.

Pretreatment with diphenoxylate hydrochloride/atropine sulfate (Lomotil) does not decrease physiologic bowel FDG activity on PET/CT scans of the abdomen and pelvis.

PURPOSE: Physiologic uptake of 2-[(18)F]-fluoro-2-deoxy-D: -glucose (FDG) by bowel can confound positron emission tomography/computed tomography (PET/CT) assessment for abdominal pathology, particularly within the bowel itself. We wished to determine if oral administration of the antimotility agent, Lomotil (5 mg diphenoxylate hydrochloride/0.05 mg atropine sulfate; G.D. Searle and Company, a division of Pfizer), prior to PET/CT scanning would reduce physiologic uptake of FDG by the small bowel and colon (lower gastrointestinal [GI] tract). PROCEDURES: Patients undergoing PET/CT scans for lymphoma were enrolled in a prospective, randomized, double-blinded study and received either 10 mL water (control group) or 10 mL Lomotil (experimental group) orally 30-60 min prior to scanning. Scans were reviewed independently by two blinded experienced readers and scored for the degree of FDG activity in the lower GI tract relative to liver activity. RESULTS: The administration of Lomotil prior to PET/CT scanning did not reduce physiologic FDG activity in the small bowel and colon. In contrast, increased radiotracer uptake by the lower GI tract was observed in the Lomotil group compared to the control group. CONCLUSIONS: Pretreatment with Lomotil prior to PET/CT scanning confers no benefit toward the reduction of physiologic FDG uptake by the small bowel and colon.

Palliative care and pain: new strategies for managing opioid bowel dysfunction.

Opioid analgesics are a cornerstone of pain therapy in the hospice and palliative care population. However, opioid-induced bowel dysfunction (OBD) is a commonly associated condition that frequently compromises the usefulness of these agents. Although its most common and debilitating symptom is constipation, the impact of OBD extends beyond constipation to encompass a myriad of gastrointestinal (GI) signs and symptoms, ranging from decreased gastric emptying and reflux to abdominal pain, cramping, bloating, nausea, and vomiting. Even after aggressive therapies to improve bowel function have been implemented, many patients continue to experience symptoms of OBD. To avoid these unwanted effects, some even choose to decrease or discontinue therapy with opioid analgesics, and experience inadequate pain control. The net result of OBD is a seriously negative impact on quality of life (QOL). For these reasons, it is important that palliative care practitioners have an adequate understanding of normal GI function and the underlying mechanisms responsible for OBD, the burden of OBD in the context of appropriate and effective pain management, and the benefits provided by effective pharmacotherapy. Several real-world cases are discussed to illustrate the application of optimal symptom management and the use of strategies that minimize the effects of OBD and improve patient QOL.

Significance of salicylate intolerance in diseases of the lower gastrointestinal tract.

Salicylate intolerance is defined as a nonspecific antigen-induced pseudo-allergic hypersensitivity reaction which can occur upon contact of an organism with salicylic acid, its derivatives or other related organic or inorganic acids of similar chemical structure. Since the effects of nonsteroidal anti-inflammatory drugs (NSAID) intolerance are by no means always severe or life-endangering but may just as well present as oligosymptomatic or local disorders (e.g. abdominal pain, diarrhea, we decided to evaluate the characteristics of patients with salicylate intolerance on the basis of gastroenterological case material of Medical Department I of Erlangen University. On the basis of the findings from the Erlangen interdisciplinary data register of chronic inflammatory gastrointestinal disease, the signs and symptoms of NSAID intolerance were found to constitute a diagnosis of great practical import to clinical medicine (allergology, dermatology, immunology, other disorders etc.) including gastroenterology. For approx. 2-7% of all patients with inflammatory bowel syndrome and food allergies this poses a new diagnostic and therapeutic challenge which may concern physicians from any of the disciplines involved. When presented with patients with chronic active disease who are suffering from these symptoms one should, therefore, in future give greater thought to the possibility of salicylate intolerance, all the more as there are meaningful dietetic, diagnostic and therapeutic options available for these persons.

Regional intestinal adaptations in Na+,K+-ATPase in experimental colitis and the contrasting effects of interferon-gamma.

AIMS: This study evaluated Na+,K+-ATPase activity and the abundance of alpha1 subunit Na+,K+-ATPase in experimental colitis and gathered evidence on the effects of interferon-gamma (IFN-gamma) on intestinal Na+,K+-ATPase. METHODS: Colitis was induced by the intrarectal administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS, 30 mg/250 microL). Na+,K+-ATPase activity was determined as the difference between total and ouabain-insensitive ATPase. The abundance of Na+,K+-ATPase was analysed by immunoblotting. RESULTS: Na+,K+-ATPase activity was markedly reduced in the proximal colonic mucosa of TNBS-treated rats, whereas upstream in the terminal ileal mucosa a marked increase in sodium pump activity was observed. At the jejunal level no significant changes in Na+,K+-ATPase activity were observed between TNBS-treated rats and corresponding controls (ethanol-treated rats). No changes were observed in the abundance of alpha1 subunit Na+,K+-ATPase in the proximal colon, terminal ileum and jejunum. The administration of IFN-gamma (50,000 U) 48 h before sacrifice reduced both Na+,K+-ATPase activity and the abundance of alpha1 subunit Na+,K+-ATPase in the proximal colon. Dexamethasone prevented colonic inflammation and decreases in proximal colonic Na+,K+-ATPase activity in TNBS-treated rats, but did not affect the INF-gamma-induced decrease in colonic Na+,K+-ATPase activity. CONCLUSIONS: The increase in ileal Na+,K+-ATPase activity upstream to the lesioned colonic mucosa, where Na+,K+-ATPase activity was markedly reduced, might indicate a compensatory process to counteract the decrease in water and electrolyte absorption at the colonic level. This decrease in colonic Na+,K+-ATPase activity is likely not related to INF-gamma-induced downregulation of Na+,K+-ATPase.