Regional gastrointestinal contractility parameters using the wireless motility capsule: inter-observer reproducibility and influence of age, gender and study country.

BACKGROUND: The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. AIMS: To describe normative values for motility/contractility parameters across age, gender and testing centres. METHODS: Healthy participants underwent a standardised wireless motility capsule assessment following an overnight fast and consumption of a meal of known nutritional content. Traces were divided into regions of interest and analysed using 2 software packages (MotiliGI and GIMS Data Viewer). Inter-observer agreement was independently assessed by 2 investigators. RESULTS: Normative data for motility/contractility parameters (maximum amplitude, mean peak amplitude, contraction frequency and motility index) are presented for 107 individuals (62 male, median age 40 years, range 18-78). MotiliGI-Gastric, small bowel and colonic maximal contraction amplitude correlated with age (r = .24, P = .01; r = .22, P = .02; and r = .2, P = .04 respectively). Small bowel motility index was higher in females than males (150.4 ± 12 vs 122 ± 7.6, P = .04). Inter-observer agreement was excellent for transit times, pH and contractility/motility parameters. GIMS Data viewer-Gastric, small bowel and colonic loge motility index correlated with the respective area under the contraction curve, total contractions, sum of amplitudes and contraction frequency (all r>.35, P < .0003) but not with transit times. CONCLUSIONS: Our analysis provides normative data for motility/contractility parameters. Log motility index summarises a number of measures. In future, the measurement of contractile activity with the wireless motility capsule may potentially aid in the diagnosis of disease states such as visceral myopathic disorders.

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.

Regional gastrointestinal transit and pH studied in 215 healthy volunteers using the wireless motility capsule: influence of age, gender, study country and testing protocol.

BACKGROUND: The wireless motility capsule (WMC) offers the ability to investigate luminal gastrointestinal (GI) physiology in a minimally invasive manner. AIM: To investigate the effect of testing protocol, gender, age and study country on regional GI transit times and associated pH values using the WMC. METHODS: Regional GI transit times and pH values were determined in 215 healthy volunteers from USA and Sweden studied using the WMC over a 6.5-year period. The effects of test protocol, gender, age and study country were examined. RESULTS: For GI transit times, testing protocol was associated with differences in gastric emptying time (GET; shorter with protocol 2 (motility capsule ingested immediately after meal) vs. protocol 1 (motility capsule immediately before): median difference: 52 min, P = 0.0063) and colonic transit time (CTT; longer with protocol 2: median 140 min, P = 0.0189), but had no overall effect on whole gut transit time. Females had longer GET (by median 17 min, P = 0.0307), and also longer CTT by (104 min, P = 0.0285) and whole gut transit time by (263 min, P = 0.0077). Increasing age was associated with shorter small bowel transit time (P = 0.002), and study country also influenced small bowel and CTTs. Whole gut and CTTs showed clustering of data at values separated by 24 h, suggesting that describing these measures as continuous variables is invalid. Testing protocol, gender and study country also significantly influenced pH values. CONCLUSIONS: Regional GI transit times and pH values, delineated using the wireless motility capsule (WMC), vary based on testing protocol, gender, age and country. Standardisation of testing is crucial for cross-referencing in clinical practice and future research.

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.

Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies.

BACKGROUND: Disorders of gastrointestinal (GI) transit and motility are common, and cause either delayed or accelerated transit through the stomach, small intestine or colon, and affect one or more regions. Assessment of regional and/or whole gut transit times can provide direct measurements and diagnostic information to explain the cause of symptoms, and plan therapy. PURPOSE: Recently, several newer diagnostic tools have become available. The American and European Neurogastroenterology and Motility Societies undertook this review to provide guidelines on the indications and optimal methods for the use of transit measurements in clinical practice. This was based on evidence of validation including performance characteristics, clinical significance, and strengths of various techniques. The tests include measurements of: gastric emptying with scintigraphy, wireless motility capsule, and (13)C breath tests; small bowel transit with breath tests, scintigraphy, and wireless motility capsule; and colonic transit with radioopaque markers, wireless motility capsule, and scintigraphy. Based on the evidence, consensus recommendations are provided for each technique and for the evaluations of regional and whole gut transit. In summary, tests of gastrointestinal transit are available and useful in the evaluation of patients with symptoms suggestive of gastrointestinal dysmotility, since they can provide objective diagnosis and a rational approach to patient management.

Wireless pH-motility capsule for colonic transit: prospective comparison with radiopaque markers in chronic constipation.

BACKGROUND: Colon transit (CT) measurements are used in the management of significant constipation. The radiopaque marker (ROM) method provides limited information. METHODS: We proposed to validate wireless motility capsule (WMC), that measures pH, pressure and temperature, to ROM measurement of CT in patients with symptomatic constipation evaluated at multiple centers. Of 208 patients recruited, 158 eligible patients underwent simultaneous measurement of colonic transit time (CTT) using ROM (Metcalf method, cut off for delay >67 h), and WMC (cutoff for delay >59 h). The study was designed to demonstrate substantial equivalence, defined as diagnostic agreement >65% for patients who had normal or delayed ROM transit. KEY RESULTS: Fifty-nine of 157 patients had delayed ROM CT. Transit results by the two methods differed: ROM median 55.0 h [IQR 31.0-85.0] and WMC (43.5 h [21.7-70.3], P < 0.001. The positive percent agreement between WMC and ROM for delayed transit was approximately 80%; positive agreement in 47 by WMC/59 by ROM or 0.796 (95% CI = 0.67-0.98); agreement vs null hypothesis (65%) P = 0.01. The negative percent agreement (normal transit) was approximately 91%: 89 by WMC/98 by ROM or 0.908 (95% CI = 0.83-0.96); agreement vs null hypothesis (65%), P = 0.00001. Overall device agreement was 87%. There were significant correlations (P < 0.001) between ROM and WMC transit (CTT [r = 0.707] and between ROM and combined small and large bowel transit [r = 0.704]). There were no significant adverse events. CONCLUSIONS & INFERENCES: The 87% overall agreement (positive and negative) validates WMC relative to ROM in differentiating slow vs normal CT in a multicenter clinical study of constipation.

Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule.

BACKGROUND: The wireless motility capsule (WMC) measures intraluminal pH and pressure, and records transit time and contractile activity throughout the gastrointestinal tract. Our hypothesis is that WMC can differentiate antroduodenal pressure profiles between healthy people and patients with upper gut motility dysfunctions. This study aims to analyze differences in the phasic pressure profiles of the stomach and small intestine in healthy and gastroparetic subjects. METHODS: Data from 71 healthy and 42 gastroparetic subjects were analyzed. The number of contractions (Ct), area under the pressure curve and motility index (MI = Ln (Ct *sum amplitudes +1)) were analyzed for 60 min before gastric emptying of the capsule (GET), (gastric window) and after GET (small bowel window) and results between groups were compared with the Wilcoxon rank sum test. KEY RESULTS: Significant differences were observed between healthy and gastroparetic subjects for Ct and MI (P < 0.05). Median values of the motility parameters in gastric window were Ct = 72, MI = 11.83 for healthy and Ct = 47, MI = 11.12 for gastroparetics. In the small bowel, median values were Ct = 144.5, MI = 12.78 for healthy and Ct = 93, MI = 12.12 for gastroparetics. Diabetic subjects with gastroparesis showed significantly lower Ct and MI compared with healthy subjects in both gastric and small bowel windows while idiopathic gastroparetic subjects did not show significant differences. CONCLUSIONS & INFERENCES: The WMC is able to differentiate between healthy and gastroparetic subjects based on gastric and small bowel motility profiles.

The assessment of regional gut transit times in healthy controls and patients with gastroparesis using wireless motility technology.

BACKGROUND: Wireless pH and pressure motility capsule (wireless motility capsule) technology provides a method to assess regional gastrointestinal transit times. AIMS: To analyse data from a multi-centre study of gastroparetic patients and healthy controls and to compare regional transit times measured by wireless motility capsule in healthy controls and gastroparetics (GP). METHODS: A total of 66 healthy controls and 34 patients with GP (15 diabetic and 19 idiopathic) swallowed wireless motility capsule together with standardized meal (255 kcal). Gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT) and whole gut transit time (WGTT) were calculated using the wireless motility capsule. RESULTS: Gastric emptying time, CTT and WGTT but not SBTT were significantly longer in GP than in controls. Eighteen percent of gastroparetic patients had delayed WGTT. Both diabetic and idiopathic aetiologies of gastroparetics had significantly slower WGTT (P < 0.0001) in addition to significantly slower GET than healthy controls. Diabetic gastroparetics additionally had significantly slower CTT than healthy controls (P = 0.0054). CONCLUSIONS: In addition to assessing gastric emptying, regional transit times can be measured using wireless motility capsule. The prolongation of CTT in gastroparetic patients indicates that dysmotility beyond the stomach in GP is present, and it could be contributing to symptom presentation.

Coupling and propagation of normal and dysrhythmic gastric slow waves during acute hyperglycaemia in healthy humans.

Acute hyperglycaemia in healthy humans disrupts slow wave rhythm similar to that observed in diabetic gastropathy, but hyperglycaemic effects on regional dysrhythmias, power, coupling and propagation are unexplored. Using mucosal mapping, we aimed to demonstrate that hyperglycaemia elicits region-specific tachygastria and evokes slow wave uncoupling between adjacent regions. Catheters with bipolar electrodes were affixed 10.5, 6 and 2 cm from the pylorus during endoscopy with midazolam in 10 healthy humans. Recordings were obtained for 1 h under basal conditions and for 1 h with hyperglycaemic clamping to 250 mg dL(-1). In basal recordings, proximal and distal slow wave frequencies were similar [2.91 +/- 0.05 vs 2.81 +/- 0.09 cycles per minute (cpm)]. Tachygastria (>3.6 cpm) was present 1.7 +/- 1.1% of the time proximally and 3.3 +/- 1.8% distally and localized to one lead 67% of the time. Proximal to distal gradients in signal power and power variability were observed. Coupling between adjacent sites was 78 +/- 2% with propagation velocities of 1.3 +/- 0.1 cm s(-1). 2 +/- 1% of segments showed >50% uncoupling. Hyperglycaemic clamping increased mean proximal (3.18 +/- 0.11 cpm) and distal (3.50 +/- 0.12 cpm) frequencies and proximal (15 +/- 6%) and distal (32 +/- 9%) tachygastria (all P < 0.01) that localized to one lead 80% of the time. During periods of normal frequency, coupling decreased proximally (54 +/- 6%) and distally (47 +/- 4%) (P < 0.01). 55 +/- 8% of segments showed >50% uncoupling (P < 0.01). In conclusion, gastric slow waves show stable, highly coupled rhythms under basal conditions. Hyperglycaemia elicits isolated tachygastrias and uncoupling of normal slow waves that are most prominent distally. These findings provide a foundation for studying slow wave conduction defects in diabetic gastropathy.

Methods of gastric electrical stimulation and pacing: a review of their benefits and mechanisms of action in gastroparesis and obesity.

Development of gastric electrical stimulation techniques for treatment of gastric dysmotility syndromes and obesity has been a long-standing goal of investigators and clinicians. Depending on stimulus parameters and sites of stimulation, such methods have a range of theoretical benefits including entrainment of intrinsic gastric electrical activity, eliciting propagating contractions and reducing symptomatology in patients with gastroparesis and reducing appetite and food intake in individuals with morbid obesity. Additionally, gastric stimulation parameters have extragastrointestinal effects including alteration of systemic hormonal and autonomic neural activity and modulation of afferent nerve pathways projecting to the central nervous system that may represent important mechanisms of action. Numerous case series and smaller numbers of controlled trials suggest clinical benefits in these two conditions, however better controlled trials are mandated to confirm their efficacy. Current research is focusing on novel stimulation methods to better control symptoms in gastroparesis and promote weight reduction in morbid obesity.

American Neurogastroenterology and Motility Society consensus statement on intraluminal measurement of gastrointestinal and colonic motility in clinical practice.

Tests of gastric, small intestinal and colonic motor function provide relevant physiological information and are useful for diagnosing and guiding the management of dysmotilities. Intraluminal pressure measurements may include concurrent measurements of transit or intraluminal pH. A consensus statement was developed and based on reports in the literature, experience of the authors, and discussions conducted under the auspices of the American Neurogastroenterology and Motility Society in 2008. The article reviews the indications, methods, performance characteristics, and clinical utility of intraluminal measurements of pressure activity and tone in the stomach, small bowel and colon in humans. Gastric and small bowel motor function can be measured by intraluminal manometry, which may identify patterns suggestive of myopathy, neuropathy, or obstruction. Manometry may be most helpful when it is normal. Combined wireless pressure and pH capsules provide information on the amplitude of contractions as they traverse the stomach and small intestine. In the colon, manometry assesses colonic phasic pressure activity while a barostat assesses tone, compliance, and phasic pressure activity. The utility of colonic pressure measurements by a single sensor in wireless pressure/pH capsules is not established. In children with intractable constipation, colonic phasic pressure measurements can identify patterns suggestive of neuropathy and predict success of antegrade enemas via cecostomy. In adults, these assessments may be used to document severe motor dysfunction (colonic inertia) prior to colectomy. Thus, intraluminal pressure measurements may contribute to the management of patients with disorders of gastrointestinal and colonic motility.

Cyclic vomiting syndrome in adults.

Cyclic vomiting syndrome (CVS) was initially described in children but can occur in all age groups. Cyclic vomiting syndrome is increasingly recognized in adults. However, the lack of awareness of CVS in adults has led to small numbers of diagnosed patients and a paucity of published data on the causes, diagnosis and management of CVS in adults. This article is a state-of-knowledge overview on CVS in adults and is intended to provide a framework for management and further investigations into CVS in adults.

Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects.

BACKGROUND: Gastric emptying scintigraphy (GES) using a radio-labelled meal is used to measure gastric emptying. A nondigestible capsule, SmartPill, records luminal pH, temperature, and pressure during gastrointestinal transit providing a measure of gastric emptying time (GET). AIMS: To compare gastric emptying time and GES by assessing their correlation, and to compare GET and GES for discriminating healthy subjects from gastroparetics. METHODS: Eighty-seven healthy subjects and 61 gastroparetics enrolled with simultaneous SmartPill and GES. Fasted subjects were ingested capsule and [(99m)Tc]-SC radio-labelled meal. Images were obtained every 30 min for 6 h. Gastric emptying time and percentage of meal remaining at 2/4 h were determined for each subject. The sensitivity/specificity and receiver operating characteristic analysis of each measure were determined for each subject. RESULTS: Correlation between GET and GES-4 h was 0.73 and GES-2 h was 0.63. The diagnostic accuracy from the receiver operating characteristic curve between gastroparetics and healthy subjects was GET = 0.83, GES-4 h = 0.82 and GES-2 h = 0.79. The 300-min cut-off time for GET gives sensitivity of 0.65 and specificity of 0.87 for diagnosis of gastroparesis. The corresponding sensitivity/specificity for 2 and 4 h standard GES measures were 0.34/0.93 and 0.44/0.93, respectively. CONCLUSION: SmartPill GET correlates with GES and discriminates between healthy and gastroparetic subjects offering a nonradioactive, standardized, ambulatory alternative to scintigraphy.

Treatment of gastroparesis: a multidisciplinary clinical review.

This clinical review on the treatment of patients with gastroparesis is a consensus document developed by the American Motility Society Task Force on Gastroparesis. It is a multidisciplinary effort with input from gastroenterologists and other specialists who are involved in the care of patients with gastroparesis. To provide practical guidelines for treatment, this document covers results of published research studies in the literature and areas developed by consensus agreement where clinical research trials remain lacking in the field of gastroparesis.