Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis.

BACKGROUND: Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. METHODS: A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. KEY RESULTS: Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04). CONCLUSIONS & INFERENCES: Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.

Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum.

BACKGROUND: Animal studies have increasingly highlighted the role of macrophages in the development of delayed gastric emptying. However, their role in the pathophysiology of human gastroparesis is unclear. Our aim was to determine changes in macrophages and other cell types in the gastric antrum muscularis propria of patients with diabetic and idiopathic gastroparesis. METHODS: Full thickness gastric antrum biopsies were obtained from patients enrolled in the Gastroparesis Clinical Research Consortium (11 diabetic, 6 idiopathic) and 5 controls. Immunolabeling and quantitative assessment was done for interstitial cells of Cajal (ICC) (Kit), enteric nerves protein gene product 9.5, neuronal nitric oxide synthase, vasoactive intestinal peptide, substance P, tyrosine hydroxylase), overall immune cells (CD45) and anti-inflammatory macrophages (CD206). Gastric emptying was assessed using nuclear medicine scintigraphy and symptom severity using the Gastroparesis Cardinal Symptom Index. RESULTS: Both diabetic and idiopathic gastroparesis patients showed loss of ICC as compared to controls (Mean [standard error of mean]/hpf: diabetic, 2.28 [0.16]; idiopathic, 2.53 [0.47]; controls, 6.05 [0.62]; P=.004). Overall immune cell population (CD45) was unchanged but there was a loss of anti-inflammatory macrophages (CD206) in circular muscle (diabetic, 3.87 [0.32]; idiopathic, 4.16 [0.52]; controls, 6.59 [1.09]; P=.04) and myenteric plexus (diabetic, 3.83 [0.27]; idiopathic, 3.59 [0.68]; controls, 7.46 [0.51]; P=.004). There was correlation between the number of ICC and CD206-positive cells (r=.55, P=.008). Enteric nerves (PGP9.5) were unchanged: diabetic, 33.64 (3.45); idiopathic, 41.26 (6.40); controls, 46.80 (6.04). CONCLUSION: Loss of antral CD206-positive anti-inflammatory macrophages is a key feature in human gastroparesis and it is associates with ICC loss.

Early satiety and postprandial fullness in gastroparesis correlate with gastroparesis severity, gastric emptying, and water load testing.

BACKGROUND: Early satiety (ES) and postprandial fullness (PPF) are often present in gastroparesis, but the importance of these symptoms in gastroparesis has not been well-described. The aims were: (i) Characterize ES and PPF in patients with gastroparesis. (ii) Assess relationships of ES and PPF with etiology of gastroparesis, quality of life, body weight, gastric emptying, and water load testing. METHODS: Gastroparetic patients filled out questionnaires assessing symptoms (PAGI-SYM) and quality of life (PAGI-QOL, SF-36v2). Patients underwent gastric emptying scintigraphy and water load testing. KEY RESULTS: 198 patients with gastroparesis (134 IG, 64 DG) were evaluated. Early satiety was severe or very severe in 50% of patients. Postprandial fullness was severe or very severe in 60% of patients. Severity scores for ES and PPF were similar between idiopathic and diabetic gastroparesis. Increasing severity of ES and PPF were associated with other gastroparesis symptoms including nausea/vomiting, satiety/early fullness, bloating, and upper abdominal pain and GERD subscores. Increasing severity of ES and PPF were associated with increasing gastroparesis severity, decreased BMI, decreased quality of life from PAGI-QOL and SF-36 physical health. Increasing severity of ES and PPF were associated with increasing gastric retention of a solid meal and decreased volume during water load test. CONCLUSIONS & INFERENCES: Early satiety and PPF are commonly severe symptoms in both diabetic and idiopathic gastroparesis. Early satiety and PPF severity are associated with other gastroparesis symptom severities, body weight, quality of life, gastric emptying, and water load testing. Thus, ES and PPF are important symptoms characterizing gastroparesis. ClinicalTrials.gov number: NCT NCT01696747.

Nausea and vomiting in gastroparesis: similarities and differences in idiopathic and diabetic gastroparesis.

BACKGROUND: Nausea and vomiting are classic symptoms of gastroparesis. It remains unclear if characteristics of nausea and vomiting are similar in different etiologies of gastroparesis. The aims of this article were as follows: to describe characteristics of nausea and vomiting in patients with gastroparesis and to determine if there are differences in nausea and vomiting in diabetic (DG) and idiopathic gastroparesis (IG). METHODS: Gastroparetic patients enrolling in the NIDDK Gastroparesis Registry underwent assessment with history and questionnaires assessing symptoms, quality of life, and a questionnaire characterizing nausea and vomiting. KEY RESULTS: Of 159 gastroparesis patients (107 IG, 52 DG), 96% experienced nausea, whereas 65% experienced vomiting. Nausea was predominant symptom in 28% and vomiting was predominant in 4%. Nausea was severe or very severe in 41%. PAGI-SYM nausea/vomiting subscore was greater with increased vomiting severity, but not nausea severity in DG than IG. Nausea was related to meals in 71%; lasting most of the day in 41%. Increasing nausea severity was related to decreased quality of life. Nausea often preceded vomiting in 82% of patients and vomiting often relieved nausea in 30%. Vomiting was more common in DG (81%) compared to IG (57%; p = 0.004). Diabetic patients more often had vomiting in the morning before eating, during the night, and when not eating. CONCLUSIONS & INFERENCES: Nausea is present in essentially all patients with gastroparesis irrespective of cause and associated with decreased quality of life. In contrast, vomiting was more prevalent, more severe, and occurred more often in DG than IG. Thus, characteristics of vomiting differ in IG vs DG.

Baseline features and differences in 48 week clinical outcomes in patients with gastroparesis and type 1 vs type 2 diabetes.

BACKGROUND: In studies of diabetic gastroparesis, patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM) are often combined for analyses. We compared gastroparesis severity, healthcare utilization, psychological function, and quality of life in T1DM vs T2DM gastroparesis patients. METHODS: Questionnaire, laboratory, and scintigraphy data from patients with gastroparesis and T1DM and T2DM from seven centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry were compared at enrollment and after 48 weeks. Multiple regression models assessed baseline and follow-up differences between diabetes subtypes. KEY RESULTS: At baseline, T1DM patients (N = 78) had slower gastric emptying, more hospitalizations, more gastric stimulator implantations, higher hemoglobin A1c (HbA1c), and more anxiety vs T2DM patients (N = 59). Independent discriminators of patients with T1DM vs T2DM included worse gastroesophageal reflux disease, less bloating, more peripheral neuropathy, and fewer comorbidities (p ≤ 0.05). On follow-up, gastrointestinal (GI) symptom scores decreased only in T2DM (p < 0.05), but not in T1DM patients who reported greater prokinetic, proton pump inhibitor, anxiolytic, and gastric stimulator usage over 48 weeks (p ≤ 0.03). Gastrointestinal symptoms at baseline and 48 weeks with both subtypes were not associated with HbA1c, peripheral neuropathy, psychological factors, or quality of life. CONCLUSIONS & INFERENCES: Baseline symptoms were similar in T1DM and T2DM patients, even though T1DM patients had worse gastric emptying delays and higher HbA1c suggesting other factors mediate symptom severity. Symptom scores at 48 weeks decreased in T2DM, but not T1DM patients, despite increased medical and surgical treatment utilization by T1DM patients. Defining causes of different outcomes in diabetic gastroparesis warrants further investigation.

Evaluation of the pylorus with concurrent intraluminal pressure and EndoFLIP in patients with nausea and vomiting.

BACKGROUND: Nausea and vomiting occurs in gastroparesis due to diabetes mellitus or unknown causes. The aim of this study was to compare (i) pyloric distensibility to pyloric manometric pressure in patients with nausea and vomiting and (ii) to correlate distensibility with delays in gastric emptying. METHODS: Sleeve manometry and EndoFLIP were performed sequentially during the same endoscopy on 114 patients with nausea and vomiting (47 with diabetes mellitus and 67 with idiopathic cause) after a standardized gastric emptying study. The sleeve manometer was positioned fluoroscopically, and the EndoFLIP was placed endoscopically. Manometric pressure using a water-perfused catheter and distensibility using an EndoFLIP filled with 40 cc of saline were measured from the pylorus. KEY RESULTS: The basal pyloric pressure was elevated (>10 mmHg) in 34 patients and was normal in 80 patients. The basal and peak pressures were similar in patient with normal and delayed gastric emptying (p > 0.05). There was a significant decrease in distensibility (8.0 ± 1.0 mm(2) /mmHg) in patients with gastric retention (>20% at 4 h) compared with patients (12.4 ± 1.4 mm(2) /mmHg) (p < 0.01) with normal gastric retention (<10%). Pressure measurements from the sleeve manometer and the EndoFLIP correlated (r = 0.29) (p < 0.002), and increased EndoFLIP balloon pressure (19.4 ± 1.4 mmHg) (p < 0.01) was associated with a severe delay in gastric emptying. CONCLUSIONS & INFERENCES: Elevated basal pyloric pressure occurs in 42% of patients with nausea and vomiting and delayed emptying. Decreased pyloric distensibility occurs with nausea, vomiting, and delayed gastric emptying. The EndoFLIP is a useful tool in the evaluation of pyloric function in symptomatic patients.

Association of low numbers of CD206-positive cells with loss of ICC in the gastric body of patients with diabetic gastroparesis.

BACKGROUND: There is increasing evidence for specific cellular changes in the stomach of patients with diabetic (DG) and idiopathic (IG) gastroparesis. The most significant findings are loss of interstitial cells of Cajal (ICC), neuronal abnormalities, and an immune cellular infiltrate. Studies done in diabetic mice have shown a cytoprotective effect of CD206+ M2 macrophages. To quantify overall immune cellular infiltrate, identify macrophage populations, and quantify CD206+ and iNOS+ cells. To investigate associations between cellular phenotypes and ICC. METHODS: Full thickness gastric body biopsies were obtained from non-diabetic controls (C), diabetic controls (DC), DG, and IG patients. Sections were labeled for CD45, CD206, Kit, iNOS, and putative human macrophage markers (HAM56, CD68, and EMR1). Immunoreactive cells were quantified from the circular muscle layer. KEY RESULTS: Significantly fewer ICC were detected in DG and IG tissues, but there were no differences in the numbers of cells immunoreactive for other markers between patient groups. There was a significant correlation between the number of CD206+ cells and ICC in DG and DC patients, but not in C and IG and a significant correlation between iNOS+ cells and ICC in the DC group, but not the other groups. CD68 and HAM56 reliably labeled the same cell populations, but EMR1 labeled other cell types. CONCLUSIONS & INFERENCES: Depletion of ICC and correlation with changes in CD206+ cell numbers in DC and DG patients suggests that in humans, like mice, CD206+ macrophages may play a cytoprotective role in diabetes. These findings may lead to novel therapeutic options, targeting alternatively activated macrophages.

Factors related to abdominal pain in gastroparesis: contrast to patients with predominant nausea and vomiting.

BACKGROUND: Factors associated with abdominal pain in gastroparesis are incompletely evaluated and comparisons of pain vs other symptoms are limited. This study related pain to clinical factors in gastroparesis and contrasted pain/discomfort- with nausea/vomiting-predominant disease. METHODS: Clinical and scintigraphy data were compared in 393 patients from seven centers of the NIDDK Gastroparesis Clinical Research Consortium with moderate-severe (Patient Assessment of Upper Gastrointestinal Disorders Symptoms [PAGI-SYM] score ≥ 3) vs none-mild (PAGI-SYM < 3) upper abdominal pain and predominant pain/discomfort vs nausea/vomiting. KEY RESULTS: Upper abdominal pain was moderate-severe in 261 (66%). Pain/discomfort was predominant in 81 (21%); nausea/vomiting was predominant in 172 (44%). Moderate-severe pain was more prevalent with idiopathic gastroparesis and with lack of infectious prodrome (P ≤ 0.05) and correlated with scores for nausea/vomiting, bloating, lower abdominal pain/discomfort, bowel disturbances, and opiate and antiemetic use (P < 0.05), but not gastric emptying or diabetic neuropathy or control. Gastroparesis severity, quality of life, and depression and anxiety were worse with moderate-severe pain (P ≤ 0.008). Factors associated with moderate-severe pain were similar in diabetic and idiopathic gastroparesis. Compared to predominant nausea/vomiting, predominant pain/discomfort was associated with impaired quality of life, greater opiate, and less antiemetic use (P < 0.01), but similar severity and gastric retention. CONCLUSIONS & INFERENCES: Moderate-severe abdominal pain is prevalent in gastroparesis, impairs quality of life, and is associated with idiopathic etiology, lack of infectious prodrome, and opiate use. Pain is predominant in one fifth of gastroparetics. Predominant pain has at least as great an impact on disease severity and quality of life as predominant nausea/vomiting.

Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium.

BACKGROUND: Cellular changes associated with diabetic (DG) and idiopathic gastroparesis (IG) have recently been described from patients enrolled in the Gastroparesis Clinical Research Consortium. The association of these cellular changes with gastroparesis symptoms and gastric emptying is unknown. The aim of this study was to relate cellular changes to symptoms and gastric emptying in patients with gastroparesis. METHODS: Earlier, using full thickness gastric body biopsies from 20 DG, 20 IG, and 20 matched controls, we found decreased interstitial cells of Cajal (ICC) and enteric nerves and an increase in immune cells in both DG and IG. Here, demographic, symptoms [gastroparesis cardinal symptom index score (GCSI)], and gastric emptying were related to cellular alterations using Pearson's correlation coefficients. KEY RESULTS: Interstitial cells of Cajal counts inversely correlated with 4 h gastric retention in DG but not in IG (r = -0.6, P = 0.008, DG, r = 0.2, P = 0.4, IG). There was also a significant correlation between loss of ICC and enteric nerves in DG but not in IG (r = 0.5, P = 0.03 for DG, r = 0.3, P = 0.16, IG). Idiopathic gastroparesis with a myenteric immune infiltrate scored higher on the average GCSI (3.6 ± 0.7 vs 2.7 ± 0.9, P = 0.05) and nausea score (3.8 ± 0.9 vs 2.6 ± 1.0, P = 0.02) as compared to those without an infiltrate. CONCLUSIONS & INFERENCES: In DG, loss of ICC is associated with delayed gastric emptying. Interstitial cells of Cajal or enteric nerve loss did not correlate with symptom severity. Overall clinical severity and nausea in IG is associated with a myenteric immune infiltrate. Thus, full thickness gastric biopsies can help define specific cellular abnormalities in gastroparesis, some of which are associated with physiological and clinical characteristics of gastroparesis.

Long-term safety of tegaserod in patients with constipation-predominant irritable bowel syndrome.

BACKGROUND: Tegaserod is a 5-hydroxytryptamine-4 receptor partial agonist. Oral administration causes gastrointestinal effects resulting in increased gastrointestinal motility and attenuation of visceral sensation. AIM: : To determine the long-term safety and tolerability of tegaserod in patients suffering from irritable bowel syndrome with constipation as the predominant symptom of altered bowel habits. METHOD: A multicentre, open-label study with flexible dose titration of tegaserod in out-patients suffering from constipation-predominant irritable bowel syndrome. RESULTS: A total of 579 patients with constipation-predominant irritable bowel syndrome were treated with tegaserod. Of these, 304 (53%) completed the trial. The most common adverse events, classified as related to tegaserod for any dose, were mild and transient diarrhoea (10.1%), headache (8.3%), abdominal pain (7.4%) and flatulence (5.5%). Forty serious adverse events were reported in 25 patients (4.4% of patients) leading to discontinuation in six patients. There was one serious adverse event, acute abdominal pain, classified as possibly related to tegaserod. There were no consistent differences in adverse events between patients previously exposed to tegaserod and those treated de novo. No pattern-forming tegaserod-related abnormalities in haematological and biochemical laboratory tests, urinalysis, blood pressure, pulse rate or electrocardiograms were found. CONCLUSIONS: Tegaserod appears to be well tolerated in the treatment of patients with constipation-predominant irritable bowel syndrome. The adverse event profile, clinical laboratory evaluations, vital signs and electrocardiogram recordings revealed no evidence of any unexpected adverse events, and suggest that treatment is safe over a 12-month period.

Effect of leuprolide acetate in treatment of abdominal pain and nausea in premenopausal women with functional bowel disease: a double-blind, placebo-controlled, randomized study.

We have previously reported impressive results in using a gonadotropin-releasing hormone analog, leuprolide acetate (Lupron), in the treatment of moderate to severe symptoms (especially abdominal pain and nausea) in patients with functional bowel disease (FBD). Pain is the hallmark of patients with FBD, and there is no consistent therapy for the treatment of these patients. The purpose of the present study was to expand the investigation to study similar patients (menstruating females) in a multicenter, double-blind, placebo-controlled, randomized study using Lupron Depot (which delivers a continuous dose of drug for one month), 3.75 mg (N = 32) or 7.5 mg (N = 33), or placebo (N = 35) given intramuscularly every four weeks for 16 weeks. Symptoms were assessed using daily diary cards to record abdominal pain, nausea, vomiting, early satiety, anorexia, bloating, and altered bowel habits. Additional assessment tools were quality of life questionnaires, psychological profile, oral-to-cecal transit using the hydrogen breath test, antroduodenal manometry, reproductive hormone levels, and global evaluations by both patient and investigator. Patients in both Lupron Depot-treated groups showed consistent improvement in symptoms; however, only the Lupron Depot 7.5 mg group showed a significant improvement for abdominal pain and nausea compared to placebo (P < 0.001). Patient quality of life assessments and global evaluations completed by both patient and investigators were highly significant compared to placebo (P < 0.001). All reproductive hormone levels significantly decreased for both Lupron Depot-treated groups by week 4 and were significantly different compared to placebo at week 16 (P < 0.001). This study shows that leuprolide acetate is effective in controlling the debilitating symptoms of abdominal pain and nausea in patients with FBD.

Role of motility measurements in managing upper gastrointestinal dysfunction.

Nausea, vomiting, and abdominal pain are common symptoms that suggest many diagnoses. The patient's symptoms may be related to an anatomical defect such as a peptic ulcer or a mechanical small bowel obstruction. However, no anatomical abnormality may be identified despite radiological, endoscopic, or laboratory studies. The cause of the patient's symptoms may have significant impact on the patient's quality of life (nonulcer dyspepsia) and life span (intestinal pseudo-obstruction). Abnormal antroduodenal motility may be the underlying cause of the patient's symptoms. Normally, coordinated phasic contractions in the stomach and small intestine maintain digestion and absorption of food. A prolonged set of phasic contractions (phase 3 of the migrating complex) begins in the stomach and propagates down the small intestine to excrete nondigestible foods, bacteria, and dead cells. Any disturbance in the normal motility pattern can lead to maldigestion and symptoms of upper intestinal dysfunction. Objective tests of motility disturbances in the stomach and small intestine include measurement of gastric emptying, intestinal transit, contractions of the stomach and duodenum, and electrogastrography. Abnormal antroduodenal motility may be secondary to an abnormality in the smooth muscle (myopathy) or the nerves in controlling smooth muscle contractions (neuropathy). Antroduodenal motility measurements may help identify a partial small bowel obstruction, the cause of small intestinal overgrowth, and the cause of chronic abdominal visceral pain. Motility studies may suggest useful drugs for correcting the underlying pathophysiology and relieving symptoms.

Managing the patient with atypical chest pain.

Since angina and heartburn can feel the same, excluding cardiac disease may be the first order of business. That done, clinical findings and laboratory tests can help identify the esophageal disturbance. Gastric acid reflux, motility disorders, and visceral nerve hypersensitivity--alone or in combination--can cause chest pain, and each may call for a different pharmacologic regimen.

Clinical considerations in GERD (gastroesophageal reflux disease) therapy: focus on cisapride.

Heartburn, the major symptom of gastrointestinal reflux disease (GERD), is a common condition that is usually self-treated with over-the-counter products. For patients with severe or recurrent symptoms of GERD, pharmacologic therapy includes acid suppression with H2-receptor antagonists and proton pump inhibitors, and, alternatively, the use of prokinetic agents. While all of these are efficacious, given its high efficacy in nonerosive and mild-to-moderate erosive esophagitis, the prokinetic agent cisapride deserves significant consideration in this patient population.

Expression of insulin-like growth factor I receptors and binding proteins by colonic smooth muscle cells.

We recently demonstrated upregulation of insulin-like growth factor I (IGF-I) binding sites in the smooth muscle layer of inflamed rat colon. The increase in binding sites was due to increased expression of IGF binding proteins (IGFBPs), which modulate the effects of IGF. To further study the role of IGF in the colon, we investigated whether cultured colonic smooth muscle cells (SMC) express IGF-I receptors and IGFBPs. SMC were isolated by collagenase digestion from rat colonic smooth muscle and grown in primary culture. Equilibrium binding experiments using (125)I-labeled IGF-I showed the presence of an IGF-I receptor with a dissociation constant of 1.96 nM and a maximal binding constant of 53,000 receptors/cell. Competition binding studies with IGF-II and insulin, together with chemical cross-linking experiments, corroborated this conclusion. Western ligand blotting of conditioned medium and Northern analysis of total RNA demonstrated that the cells expressed and secreted IGFBP-4, -5, and -3 with molecular masses of 25, 31, and 45 kDa, respectively. These results, together with our in vivo studies in the rat, support a role for IGF in tissue fibrosis and stricture formation during chronic intestinal inflammation.

Role of colonic motility in guiding therapy in patients with constipation.

Constipation is a common condition defined by less than three bowel movements per week. Often constipation is secondary to altered motility of the colon. Tests that measure colonic motility lead the clinician to appropriate therapy. Colonic transit measured with either radionuclides or radio-opaque markers determine whether the transit through the colon is truly slow, and then identify the potential region of the colon that impedes the movement of intraluminal contents. Patients with normal colonic transit do not require further evaluation of their colonic motor function. Colonic and anorectal manometry differentiate patients in to 3 groups: (1) functional anal outlet obstruction; (2) uncoordinated distal colonic phasic contractions, and (3) colonic inertia. Functional outlet obstruction may be treated successfully by increasing the water content of their stools and biofeedback. Antispasmodics including anticholinergics, nitrates and calcium channel blockers may decrease the functional obstruction caused by phasic colonic contractions. The prokinetics such as cisapride have successfully improved constipation due to colonic inertia, Parkinson's disease or spinal cord injury as well as idiopathic inertia. Occasionally patients with inertia may require colectomy with ileorectal anastomosis to treat severe constipation.

Antibodies in patients with inflammatory bowel disease and the apparent influence of medications.

Patients with inflammatory bowel disease (IBD) are known to have increased antibodies to several food and bacterial antigens. To assess selected isotype contributions in greater detail, we examined the concentrations of IgA, IgG, IgE, and IgG4 antibodies to five selected antigens, two of bacterial and three of food origin. Thirty patients with IBD and thirty matched healthy controls were studied. Most antibodies were increased in IBD patients compared to controls. Statistically significant increases were more frequent in Crohn's disease (CD) than in ulcerative colitis (UC). An unexpected finding was that IBD patients treated with sulfasalazine had statistically higher levels of most IgA antibodies than healthy controls, while steroid treated patients had lower levels. These findings suggest differing effects on the immune systems of IBD patients by each of these commonly used drugs.

Antroduodenal manometry in children and adults with severe non-ulcer dyspepsia.

BACKGROUND: Nonulcer dyspepsia is common in adults but has been recognized only recently in children. METHODS: We compared signs, symptoms, and antroduodenal motility findings in 34 children and 35 adults with severe nonulcer dyspepsia. RESULTS: Symptoms and signs were similar in the two groups. Ten children (29%) and one adult (3%) required tube feedings (p = 0.01). Abdominal surgery had been performed on 6 of 34 (18%) children and 18 of 35 adults (51%) (p < 0.01), without relief of symptoms. Esophageal manometry was abnormal in 5 of 23 (22%) children and 6 of 31 (19%) adults. Antroduodenal manometry was suggestive of neuropathy in 25 children and 26 adults and of myopathy in 3 children and 2 adults. Absence of phase 3 of the migrating motor complex was found in 4 children and 17 adults (p = 0.01). Antroduodenal manometry was normal in six children and seven adults. CONCLUSION: Signs, symptoms, and discrete manometric abnormalities of childhood nonulcer dyspepsia resembled those of adult nonulcer dyspepsia. Manometric findings in nonulcer dyspepsia resembled those reported in chronic intestinal pseudo-obstruction, suggesting that these conditions are on a continuum of enteric neuromuscular diseases.

Current concepts in the management of the irritable bowel syndrome.

In the irritable bowel syndrome gastrointestinal tract motility is disturbed from the esophagus to the colon, causing pain and altered function. When colonic motility is abnormal, the patient can experience either constipation or diarrhea in addition to abdominal pain and bloating. In constipated patients the postprandial colonic motility can increase normally after eating or the colon can remain motionless. Generally propagating contractions are absent in patients with constipation predominant irritable bowel syndrome. Propagating contractions are increased in frequency in patients with diarrhea, although the phasic contractions are decreased. Questionnaires discriminate between patients with structural disease such as ulcerative colitis and patients with functional disease, however they cannot differentiate between the different subgroups of patients with constipation predominant irritable bowel syndrome. Treatment strategies are beginning to focus on the underlying pathophysiologic abnormality.