International Perspectives on Management of Inflammatory Bowel Disease: Opinion Differences and Similarities Between Patients and Physicians From the IBD GAPPS Survey.

Background: Inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), are complex disorders with multiple comorbidities. We conducted international patient and physician surveys to evaluate current experiences and perceptions of patients with CD or UC and physicians who treat IBD.

Methods: The IBD Global Assessment of Patient and Physician Unmet Need Surveys comprised a patient survey and a physician survey, fielded in North America and Europe between August 16, 2019, and November 10, 2019.

Change in erythrocyte mean corpuscular volume during combination therapy with azathioprine and infliximab is associated with mucosal healing: a post hoc analysis from SONIC.

Background: The adequacy of exposure of purine analogs as measured by 6-thioguanine nucleotides concentrations in the setting of combination therapy remains poorly understood. The aim of this study was to investigate the relationship between the mean corpuscular volume (MCV) value (as a surrogate marker of 6-thioguanine nucleotides concentration) and Crohn's disease outcomes in the setting of combination therapy with infliximab.

Methods: The SONIC trial was a randomized controlled trial comparing infliximab to azathioprine and to infliximab plus azathioprine in 508 Crohn's disease patients.

Optimizing immunomodulators and anti-TNF agents in the therapy of Crohn disease.

Randomized trials support the use of the thiopurines and anti-TNF monoclonal antibodies in treating Crohn disease. New therapeutic approaches and laboratory assays have helped optimize the use of these agents. Thiopurine methyltransferase activity should always be determined to avoid thiopurines in individuals with absent enzyme activity.

Once-daily dosing of delayed-release oral mesalamine (400-mg tablet) is as effective as twice-daily dosing for maintenance of remission of ulcerative colitis.

Background & Aims: The practice of dosing mesalamines in divided doses for the treatment of ulcerative colitis (UC) began with sulfasalazine and was driven by sulfapyridine toxicity. This convention and the assumption that dosing multiple times a day is necessary to treat UC had not been challenged until recently. This study was conducted to determine the efficacy and safety of once-daily dosing of delayed-release mesalamine (Asacol 400-mg tablets) compared with twice-daily dosing for maintaining remission in UC patients.

Risk factors for hepatitis C virus infection among patients receiving health care in a Department of Veterans Affairs hospital.

A cross-sectional, seroepidemiological study was conducted to determine the prevalence and risk factors for hepatitis C virus (HCV) infection among veterans receiving health care from the VA. Among 274 evaluated outpatients, anti-HCV was found in 27 (9.9%).

Prevention of acetic acid-induced colitis by desferrithiocin analogs in a rat model.

Iron contributes significantly to the formation of reactive oxygen species via the Fenton reaction. Therefore, we assessed whether a series of desferrithiocin analogs, both carboxylic acids and hydroxamates, could (1) either promote or diminish the iron-mediated oxidation of ascorbate, (2) quench a model radical species, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+), and (3) when applied topically, prevent acetic acid-induced colitis in rats. Surprisingly, most of the desferrithiocin analogs inhibited the Fenton reaction to an approximately equivalent degree; however, substantial differences were observed in the capacity of the analogs to scavenge the model radical cation.

Long-term response to subtotal colectomy in colonic inertia.

The purpose of this study was to determine the long-term outcome of patients who had previously undergone subtotal colectomy for severe idiopathic constipation at the University of Florida between 1983 and 1987. In addition, we aimed to determine whether preoperative motility abnormalities of the upper gastrointestinal tract are more common among those patients who have significant postoperative complications after subtotal colectomy. We evaluated 13 patients who underwent subtotal colectomy for refractory constipation between 1983 and 1987 at the University of Florida.

Altering the natural history of Crohn's disease?

With the medical advances achieved in Crohn's disease (CD) over the past several years, treatment goals have expanded to include not only improvement in clinical outcomes, but also potential alteration of underlying disease processes and modification of the clinical course. A reliable prospective predictive model for the clinical course of CD is presently lacking. However, preliminary evidence suggests that the clinical expression of CD may reflect at least in part transmural and superficial mucosal inflammatory changes.

Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn's disease. North American Azathioprine Study Group.

Background & Aims: Azathioprine is effective for Crohn's disease but acts slowly. A loading dose may decrease the time to response.

Methods: A placebo-controlled study was conducted in patients with active Crohn's disease despite prednisone treatment.

Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease.

Background & Aims: Recombinant human interleukin 11 (rhIL-11) is a cytokine with thrombocytopoietic activity and anti-inflammatory and mucosal protective effects. The objectives of this study were to investigate the safety and tolerability of rhIL-11 in patients with Crohn's disease and to explore the effects of dose and schedule on platelet count and Crohn's disease activity.

Methods: A multicenter, double-masked, placebo-controlled, dose-escalation study of 76 patients with active Crohn's disease was performed.

Prevention and treatment of osteoporosis in patients with inflammatory bowel disease.

Osteopenia or osteoporosis is common in patients with inflammatory bowel disease. The use of corticosteroids contributes to the decline in bone loss; however, osteoporosis may develop in patients with inflammatory bowel disease independent of corticosteroid use. Risk factors for the development of low bone mass in patients with inflammatory bowel disease include the general risk factors for osteoporosis as well as additional factors such as the presence of chronic inflammation, use of corticosteroids and other pharmaceuticals, and nutritional deficiencies as the result of small bowel disease or small bowel resections.

Diabetes and the gastrointestinal tract.

Gastrointestinal motility disorders are common in patients with diabetes. The entire gastrointestinal tract may be involved from the esophagus to the anal sphincter. Before instituting therapy, people with diabetes first require a careful diagnostic evaluation.

Disruption in neuropeptide Y and leptin signaling in obese ventromedial hypothalamic-lesioned rats.

Electrolytic lesions placed in the ventromedial hypothalamus (VMH) of rats induce instant hyperphagia and excessive weight gain. Since neuropeptide Y (NPY) is a potent hypothalamic orexigenic signal, and leptin secreted by adipocytes regulates NPY output, we tested the hypothesis that altered NPYergic-leptin signaling may underlie hyperphagia in VMH-lesioned rats. VMH-lesioned rats exhibiting hyperphagia and excessive weight gain in a time-related fashion were sacrificed on days 2, 7, and 21 post-surgery.

A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis.

Objectives: The aim of this study was to compare the efficacy of mesalamine rectal suspension enema (Rowasa) alone, oral mesalamine tablets (Asacol) alone, and the combination of mesalamine enema and mesalamine tablets in patients with active mild-to-moderate distal ulcerative colitis.

Methods: Sixty outpatients with ulcerative colitis at least 5 cm above the anal verge and not more than 50 cm, inclusive, and a total disease activity index (DAI) score between 4 and 10, inclusive, were randomized to either mesalamine rectal enema (n = 18) once nightly, oral mesalamine 2.4 g/day (n = 22), or a combination of both treatments (n = 20).

Colchicine is an effective treatment for patients with chronic constipation: an open-label trial.

Chronic constipation is a common clinical condition that frequently does not respond to routine therapeutic measures. We hypothesized that colchicine would be effective in this condition because we reported that it stimulates intestinal motility in rats and commonly causes diarrhea in patients taking the drug for either gouty arthritis or Familial Mediterranean fever. We prospectively studied seven patients with chronic constipation who were refractory to medical therapy and treated them with oral colchicine 0.

Gastrointestinal myoelectric activity in a child with gastroschisis and ileal atresia.

Gastroschisis is frequently associated with intestinal atresia and alterations in gastrointestinal function. The authors studied gastric and small bowel myoelectric activity in a child who had a complex course and prolonged inability to tolerate oral intake after staged repair of gastroschisis and an associated ileal atresia. The child remained unable to tolerate oral intake after repair of the atresia and was reexplored 3 months later to rule out a partial small bowel obstruction, with simultaneous placement of serosal electrodes on the stomach and proximal small bowel.

Evidence that hypothalamic neuropeptide Y gene expression and NPY levels in the paraventricular nucleus increase before the onset of hyperphagia in experimental diabetes.

Neuropeptide Y (NPY) is the most potent endogenous orexigenic signal. Several lines of evidence indicate that the site of NPY action in transducing feeding signal may reside in the paraventricular nucleus (PVN) and neighboring sites in the hypothalamus. To test the hypothesis that an increase in NPY activity in the ARC-PVN pathway precedes the onset of diabetic hyperphagia, we evaluated NPY levels in seven hypothalamic nuclei and NPY gene expression in the hypothalamus at 48, 72 or 96 h after streptozotocin (STZ) treatment in rat.

Metabolically programmed polyamine analogue antidiarrheals.

The design, synthesis, and testing of a novel class of antidiarrheal drugs based on a tetraamine pharmacophore are reported. While N1,N14-diethylhomospermine (DEHSPM) (5 mg/kg) completely prevents diarrhea in rodents, tissue distribution studies demonstrated that the principal metabolite of DEHSPM, homospermine (HSPM), accumulates and persists in tissues for a protracted period of time. This accumulation accounts for a large part of the chronic toxicity of DEHSPM.

Metabolism and pharmacokinetics of N1,N14-diethylhomospermine.

The pharmacokinetics and metabolism of N1,N14-diethylhomospermine (DEHSPM) is described. Analysis of 15 min constant rate intravenous infusion data in dogs gave mean values of: plasma t1/2 = 1.04 hr; Vd = 0.

Differential increase in neuropeptide Y-like levels and myenteric neuronal staining in diabetic rat intestine.

Neuropeptide Y is a regulatory peptide found in adrenergic and non-adrenergic neurons. Diabetes, which may cause autonomic neuropathy, induces an increase in hypothalamic neuropeptide Y (NPY) levels; thereby we measured the effects of chronic diabetes on neuropeptide Y in the intestine. Rats were injected with streptozotocin (65 mg/kg) and maintained for up to 20 weeks.

Salsalate, morphine, and postoperative ileus.

Background: Previously, we demonstrated that ketorolac, a nonsteroidal antiinflammatory drug (NSAID), prevented postoperative small bowel ileus in a rodent model. The aim of this study was to evaluate the effect of salsalate, an NSAID without antiplatelet effect, on postoperative ileus alone or in combination with morphine.

Methods: Forty-eight rats underwent placement of duodenal catheters and were then randomly assigned to one of eight groups (n = 6).

Insulin and insulin-like growth factor II suppress neuropeptide Y release from the nerve terminals in the paraventricular nucleus: a putative hypothalamic site for energy homeostasis.

It has been recently recognized that a distinct signaling pathway in the hypothalamus is involved in the stimulation of feeding in mammals. Neuropeptide Y (NPY), a member of the pancreatic polypeptide family, is the most potent orexigenic signal, and its secretion in discrete hypothalamic sites increases in response to insulinopenia produced by food deprivation or experimental diabetes. To establish the site of interaction between the hypothalamus and the pancreas, we examined the effects of insulin on NPY release in vivo and in vitro from hypothalamic sites known to be involved in feeding behavior.

The impact of polyamine analogues on the blood pressure of normotensive and hypertensive rats.

The impact of the antineoplastic polyamine analogues N1N14-diethylhomospermine (DEHSPM) and N1N11-diethylnorspermine (DENSPM) on the blood pressure and heart rate of normotensive and hypertensive rats are described. DEHSPM was administered to both normotensive and spontaneously hypertensive rats (SHR), while the DENSPM analogue was given only to the normotensive animals. The intravenous administration of DEHSPM at doses of 5 or 10 mg/kg resulted in a profound and long-lasting drop in the test animals' blood pressure, with no appreciable change in their heart rate.