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W L Hasler,
L A Wilson,
H P Parkman,
K L Koch,
T L Abell,
L Nguyen,
P J Pasricha,
W J Snape,
R W McCallum,
I Sarosiek,
G Farrugia,
J Calles,
L Lee,
J Tonascia,
A Unalp-Arida,
F Hamilton
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ABSTRACT: 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.
Neurogastroenterology and Motility 02/2013; · 3.41 Impact Factor
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M Grover,
C E Bernard,
P J Pasricha,
M S Lurken,
M S Faussone-Pellegrini,
T C Smyrk,
H P Parkman,
T L Abell,
W J Snape, W L Hasler,
R W McCallum,
L Nguyen,
K L Koch,
J Calles,
L Lee,
J Tonascia,
A Ünalp-Arida,
F A Hamilton,
G Farrugia
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ABSTRACT: 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.
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.
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.
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.
Neurogastroenterology and Motility 02/2012; 24(6):531-9, e249. · 3.41 Impact Factor
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ABSTRACT: 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.
Neurogastroenterology and Motility 01/2011; 23(1):8-23. · 3.41 Impact Factor
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M. Camilleri,
N. K. Thorne,
Y. Ringel, W. L. Hasler,
B. Kuo,
T. Esfandyari,
A. Gupta,
S. M. Scott,
R. W. Mccallum,
H. P. Parkman,
E. Soffer,
G. E. Wilding,
J. R. Semler,
S. S.c. Rao
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ABSTRACT: 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 ∼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 ∼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.
Neurogastroenterology and Motility 07/2010; 22(8):874 - e233. · 3.41 Impact Factor
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M Camilleri,
N K Thorne,
Y Ringel, W L Hasler,
B Kuo,
T Esfandyari,
A Gupta,
S M Scott,
R W McCallum,
H P Parkman,
E Soffer,
G E Wilding,
J R Semler,
S S C Rao
[show abstract]
[hide abstract]
ABSTRACT: Colon transit (CT) measurements are used in the management of significant constipation. The radiopaque marker (ROM) method provides limited information.
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
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.
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.
Neurogastroenterology and Motility 05/2010; 22(8):874-82, e233. · 3.41 Impact Factor
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L Kloetzer,
W D Chey,
R W McCallum,
K L Koch,
J M Wo,
M Sitrin,
L A Katz,
J M Lackner,
H P Parkman,
G E Wilding,
J R Semler, W L Hasler,
B Kuo
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ABSTRACT: 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.
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.
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.
The WMC is able to differentiate between healthy and gastroparetic subjects based on gastric and small bowel motility profiles.
Neurogastroenterology and Motility 05/2010; 22(5):527-33, e117. · 3.41 Impact Factor
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I Sarosiek,
K H Selover,
L A Katz,
J R Semler,
G E Wilding,
J M Lackner,
M D Sitrin,
B Kuo,
W D Chey, W L Hasler,
K L Koch,
H P Parkman,
J Sarosiek,
R W McCallum
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ABSTRACT: Wireless pH and pressure motility capsule (wireless motility capsule) technology provides a method to assess regional gastrointestinal transit times.
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).
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.
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).
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.
Alimentary Pharmacology & Therapeutics 10/2009; 31(2):313-22. · 3.77 Impact Factor
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W L Hasler
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ABSTRACT: 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.
Neurogastroenterology and Motility 04/2009; 21(3):229-43. · 3.41 Impact Factor
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ABSTRACT: 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.
Neurogastroenterology and Motility 03/2009; 21(5):492-9, e1-2. · 3.41 Impact Factor
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ABSTRACT: 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.
Neurogastroenterology and Motility 01/2009; 20(12):1269-82. · 3.41 Impact Factor
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T L Abell,
K A Adams,
R G Boles,
A Bousvaros,
S K F Chong,
D R Fleisher, W L Hasler,
P E Hyman,
R M Issenman,
B U K Li,
S L Linder,
E A Mayer,
R W McCallum,
K Olden,
H P Parkman,
C D Rudolph,
Y Taché,
S Tarbell,
N Vakil
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ABSTRACT: 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.
Neurogastroenterology and Motility 05/2008; 20(4):269-84. · 3.41 Impact Factor
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B Kuo,
R W McCallum,
K L Koch,
M D Sitrin,
J M Wo,
W D Chey, W L Hasler,
J M Lackner,
L A Katz,
J R Semler,
G E Wilding,
H P Parkman
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ABSTRACT: 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).
To compare gastric emptying time and GES by assessing their correlation, and to compare GET and GES for discriminating healthy subjects from gastroparetics.
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.
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.
SmartPill GET correlates with GES and discriminates between healthy and gastroparetic subjects offering a nonradioactive, standardized, ambulatory alternative to scintigraphy.
Alimentary Pharmacology & Therapeutics 02/2008; 27(2):186-96. · 3.77 Impact Factor
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T L Abell,
R K Bernstein,
T Cutts,
G Farrugia,
J Forster, W L Hasler,
R W McCallum,
K W Olden,
H P Parkman,
C R Parrish,
P J Pasricha,
C M Prather,
E E Soffer,
R Twillman,
A I Vinik
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ABSTRACT: 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.
Neurogastroenterology and Motility 05/2006; 18(4):263-83. · 3.41 Impact Factor
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ABSTRACT: Frequency and amplitude characteristics of normal and dysrhythmic slow waves in different gastric regions are poorly characterized. Using endoscopic mucosal mapping, we quantified slow wave frequency and power at predetermined sites under control conditions and with glucagon. Twelve healthy volunteers underwent gastroscopy with midazolam. Bipolar recording electrodes were directed to 12, 7, and 2 cm proximal to the pylorus along the greater and lesser curvatures. Dominant frequencies at all sites were 2.96 +/- 0.07 cycles min(-1) (cpm). Powers of the dominant frequency were 59 +/- 7% lower 12 cm vs 2 cm from the pylorus (P < 0.01), but were similar along the greater and lesser curvatures. Glucagon (0.3 mg IV) decreased dominant frequencies (1.40 +/- 0.10 cpm, P < 0.01) and elicited power reductions which varied by region (36 +/- 37% at 12 cm vs 79 +/- 20% at 2 cm, P < 0.01). Comparing dominant frequencies from mucosal recordings and electrogastrography revealed minimal slow wave uncoupling. In conclusion, endoscopic mucosal mapping demonstrates slow wave power gradients from the proximal to distal stomach under normal conditions. Glucagon evokes bradygastria with minimal uncoupling and elicits inhibitory effects on slow wave power which are more potent in the distal antrum. This method provides insight into the mechanisms of action of gastric slow wave dysrhythmic stimuli.
Neurogastroenterology and Motility 11/2004; 16(5):557-65. · 3.41 Impact Factor
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ABSTRACT: The objective of this document is to present the consensus opinion of the American Motility Society Clinical GI Motility Testing Task Force on the performance and clinical utility of electrogastrography (EGG). EGG is a non-invasive means of recording human gastric myoelectrical activity or slow waves from cutaneous leads placed over the stomach. In healthy volunteers, EGG tracings exhibit sinusoidal waveforms with a predominant frequency of 3 cycles per minute (cpm). Clinical studies have shown good correlation of these cutaneous recordings with those acquired from serosally implanted electrodes. The amplitude of the EGG waveform increases with ingestion of caloric or non-caloric meals. Some patients with nausea, vomiting, or other dyspeptic symptoms exhibit EGG rhythm disturbances or blunting of meal-evoked EGG signal amplitude increases. These abnormalities correlate to some degree with delayed gastric emptying of solids. In selected patients, EGG may be complementary to gastric emptying testing. To date, no therapies have convincingly demonstrated in controlled studies that correcting abnormalities detected by EGG improves upper gastrointestinal symptoms. Proposed clinical indications for performance of EGG in patients with unexplained nausea, vomiting and dyspeptic symptoms must be validated by prospective controlled investigations.
Neurogastroenterology and Motility 05/2003; 15(2):89-102. · 3.41 Impact Factor
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ABSTRACT: To systematically review research on the prevalence of abdominal and pelvic surgery in patients with irritable bowel syndrome.
Computer searches of MEDLINE, EMBASE and Current Contents were performed independently by both investigators to identify appropriate studies. Primary study selection criteria included: (i) population-based samples of adult irritable bowel syndrome patients; (ii) the use of appropriate symptom-based criteria to identify irritable bowel syndrome patients; and (iii) comparison of the prevalence of abdominal and pelvic surgery in irritable bowel syndrome patients vs. control populations. Secondary analysis was performed on published studies of referral populations and case series.
Two population-based studies met the primary study selection criteria and revealed an increased prevalence of surgery in irritable bowel syndrome patients vs. controls for cholecystectomy (4.6% vs. 2.4%, respectively; odds ratio, 1.9; 95% confidence interval, 1.2-3.2) and hysterectomy (18% vs. 12%, respectively; odds ratio, 1.6; 95% confidence interval, 1.1-2.2). Secondary analysis revealed an increased prevalence of appendectomy and other abdominal and pelvic surgery in irritable bowel syndrome patients.
Irritable bowel syndrome is associated with a disproportionately high prevalence of abdominal and pelvic surgery, but most studies exhibit sub-optimal study design and do not define the factors causing the increased prevalence of surgery in these patients.
Alimentary Pharmacology & Therapeutics 05/2003; 17(8):997-1005. · 3.77 Impact Factor
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ABSTRACT: Animal studies demonstrate that nizatidine, an H2-receptor inhibitor, may enhance colonic activity independent of its effect on acid secretion. The effect of nizatidine on human colonic motility is unknown. We evaluated the potential prokinetic property of nizatidine in 12 healthy subjects (10 men and 2 women, age 21-46 years). Each subject received either nizatidine (600 mg), famotidine (80 mg, a H2-receptor inhibitor used as a control), or a placebo, on separate days in randomized order at least 3 days apart. Following an overnight fast, a three-lumen catheter fitted with a stimulus balloon and two barostat bags was placed in the descending colon. The gastrocolonic response was tested by antral balloon inflation and the colonic peristaltic reflex was evaluated by colonic distension. Changes in colonic motility were assessed by volume changes in the barostat bags. Antral distension evoked volume-dependent increases in colonic motility, maximal at a 300-ml inflation, as demonstrated by a reduced bag volume. Nizatidine enhanced colonic motility in response to antral distension at 200 and 300 ml, compared with famotidine and placebo. Colonic distension evoked volume-dependent increases in colonic motility proximal to the stimulus balloon. Compared with famotidine and placebo, nizatidine enhanced the ascending and descending contractile limbs of the peristaltic reflex but did not affect relaxation distal to the balloon. In conclusion, nizatidine enhanced the gastrocolonic response and the colonic peristaltic reflex in healthy subjects. Further research on the prokinetic action of nizatidine in the colon may lead to novel treatments for idiopathic constipation.
Journal of Pharmacology and Experimental Therapeutics 11/2001; 299(1):159-63. · 3.83 Impact Factor
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Gastroenterology 02/2001; 120(1):263-86. · 11.68 Impact Factor
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ABSTRACT: Distal gastric distension may contribute to meal-related dyspeptic symptoms. This study's aims were to determine the effects of distinct nutrient classes on symptoms induced by distal gastric distension and their dependence on 5-hydroxytryptamine(3) (5-HT3) receptors. Nine healthy subjects rated pain, nausea, and bloating induced by isobaric distal gastric distensions (6-24 mmHg) during duodenal lipid, carbohydrate, protein, or saline perfusion after treatment with placebo or the 5-HT3 receptor antagonist granisetron (10 microg/kg iv). Distensions produced greater pain, nausea, and bloating with lipid at 1.5 kcal/min compared with saline (P < or = 0.02), primarily because of greater distal gastric volumes at each distending pressure. In contrast, carbohydrate and protein had no significant effect. At 3 kcal/min, lipid increased symptoms through a volume-independent as well as a volume-dependent effect. Granisetron did not affect symptom perception or gastric pressure-volume relationships. In conclusion, isobaric distal gastric distension produces more intense symptoms during duodenal lipid compared with saline perfusion. Symptom perception during distal gastric distension is unaffected by 5-HT3 receptor antagonism.
AJP Gastrointestinal and Liver Physiology 02/2001; 280(2):G201-8. · 3.43 Impact Factor
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ABSTRACT: The pathophysiology of functional dyspepsia may involve abnormal processing of visceral stimuli at the level of the central nervous system. There is accumulating evidence that visceral and somatic pain processing in the brain share common neuronal substrates. However, the cerebral loci that process sensory information from the stomach are unknown. The aim of this study was to localize the human brain regions that are activated by gastric distention.
Brain (15)O-water positron emission tomography was performed in 15 right-handed healthy volunteers during baseline and distal gastric distentions to 10 mm Hg, 20 mm Hg, threshold pain, and moderate pain. Pain, nausea, and bloating were rated during baseline and distentions (0-5 scale). Statistical subtraction analysis of brain images was performed between distentions and baseline.
Symptoms increased with distending stimulus intensity (maximum pain, 2.1 +/- 0.4; nausea, 2.2 +/- 0.4; bloating, 3.7 +/- 0.2). Paralleling increases in distention stimulus and symptoms, progressive increases in activation (P < or = 0.05), were observed in the thalami, insula bilaterally, anterior cingulate cortex, caudate nuclei, brain stem periaqueductal gray matter, cerebellum, and occipital cortex.
Symptomatic gastric distention activates structures implicated in somatic pain processing, supporting the notion of a common cerebral pain network.
Gastroenterology 02/2001; 120(2):369-76. · 11.68 Impact Factor
