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smonths (3-41mo)]. ADM results were categorized as antral hypomotility (AH), small intestinalneuropathy (SBN), both AH and SBN present (BP) or normal (NL). The manometric responseto erythromycin (ERY) and octreotide(O) was also reviewed. ADM results in clinical respond-ers (CR)(>50% symptom improvement), were compared with clinical non-responders (CNR).Patient Characteristics: 22/31 (71%) patients had diabetic (DM) and 9/31 (29%) had idio-pathic (ID) gastroparesis. Mean four hour gastric retention by nuclear scintigraphy was 44%(16-100%). Mean duration of symptoms prior to implantation was 5.9 years (1-16 years).Primary symptom was nausea/vomiting in 94% and abdominal pain in 6%. Mean HemoglobinA1c among diabetics was 8.2 (5-11.1). Baseline characteristics between CR and CNR werestatistically equivalent (p>0.05). Results: Overall, 71% were CR (16DM/ 6I) and 29% wereCNR (6DM/3I). Gastric emptying normalized in 38% of CR and 71% of CNR (p=0.25).ADM showed AH in (38.7%) (8DM, 4I), SBN in (9.7%) (2DM, 1I), BP in 29.0% (6DM,3I), and NL in 22.6% (7DM, 0I). AH was identified in 59% patients with DM and 88%patients with ID (p = 0.10). SBN was identified in 36% patients with DM and 49% patientswith ID (p=0.49). Following insertion of the GES, a clinical response occurred in 67%AH,73%SBN, 63% BP, and 71% NL. There was no difference in the clinical response in patientswith different manometric patterns (p>0.05). A CR occurred in 16/24 (67%) patients whoresponded to ERY and 6/7 (86%) without antral contractions after ERY (p>0.05). A CRoccurred in16/25 (64%) patients who responded to O and 8/8 (100%) patients withoutintestinal response to O (p=0.05). Conclusions: 1) Manometric abnormalities demonstratedby ADM in patients with medically refractory DM and ID gastroparesis are common (77.4%)but not universally present. 2) AH is the most frequently identified abnormality (68%)with concomitant SBN often present (43%). 3) Contrary to our prediction, a manometricabnormality did not predict a negative clinical response to GES. In fact, patients with SBNand no response to O had a better response to GES.
T1355
Effect of Azithromycin On Antroduodenal Pressure Profiles of Patients withGastrointestinal DysmotilityPayam Chini, Baharak Moshiree, Wei Hou, Phillip P. Toskes
Background: Only a paucity of prokinetic agents exists for the treatment of gastroparesisand small bowel dysmotility. Azithromycin (AZI) is a semi-synthetic macrolide which issimilar to Erythromycin (EES)-a prokinetic used commonly for treatment of gastroparesis-but does not interact with the cytochrome P-450 pathway of hepatic metabolism and maytherefore be preferable in patients on other concominant medications. Our prior resultsshowed significant differences with respect to motility index and duration of antral activitybetween AZI and EES. (Am J Gastroenterology 2005; 100: S-326) Aim: The purpose of thisstudy was to compare the effect of AZI and EES on small bowel activity. Method: Weevaluated a consecutive series of 34 patients [10 M, 24 F, mean age 42 ± 15 yrs] referredto our Clinical Motility Lab for evaluation of chronic abdominal pain or suspected gastrointes-tinal dysmotility undergoing 24 hour antroduodenal manometry. Pressure profiles wererecorded in the baseline period, fed state after a standardized meal, and postprandial afteradministration of EES (250 mg IV), AZI (250 mg IV) and Octreotide (OCT, 50 mcg SC) indifferent intervals. Only the antegrade activity fronts (AF's), with normal propagation velocity< 11cm/min, and amplitudes on average of 10-40 mm Hg lasting at least 5 minutes in theduodenum were included. The characteristics of the migratory motor complexes (MMC's)at baseline, postprandial AF's and phase III-like contractions after administration of EES,AZI, and OCT were also studied separately for comparison. The data was analyzed using arepeated measures analysis of variance (ANOVA) with the SAS software for comparison ofeach of the medications. Results: Comparison of EES and AZI shows that AZI induced moreAFs in the duodenum during antroduodenal manometry (p=0.014). OCT induced moreAF's in the small bowel than both EES (p=0.001) and AZI (p=0.001). There was no statisticallysignificant differences between EES and AZI when further subgrouping patients into thosewith abnormal gastric emptying scintigraphy -GES- (p=0.061), normal GES (p=0.979), andabnormal small bowel activity based on manometry findings (p=0.089). Conclusions: AZIinduces AF's in the duodenum more frequently than EES although OCT induces duodenalcontractions more than both. The disadvantages of OCT include inhibition of gastric motility,inferiority in terms of route of drug administration, and side effect profile (Gut 1994;35:1064-1069). Our findings suggest azithromycin effectively stimulates both antral andsmall bowel activity and thus may improve not only gastric but also small bowel transit inpatients with dysmotility.
T1356
Acoustic Stress Attenuates Gastric Migrating Motor Complex, WithoutAffecting Motilin Release, Via Inhibiting Sympatho-Vagal Balance in ConsciousDogsHitoshi Nakajima, Hiroshi Taniguchi, Kenji Imai, Hajime Ariga, Kirk A. Ludwig,Christopher R. Mantyh, Theodore N. Pappas, Toku Takahashi
Background: Migrating motor complex (MMC) is well characterized by the appearance ofgastrointestinal contractions in the interdigestive state. The occurrence of gastric phase IIIis regulated by the cyclic increase of plasma motilin in dogs and humans. Impaired gastricMMC (G-MMC) has been shown in subset of functional dyspepsia (FD) patients (Am JGastroenterol. 92: 481, 1997). Stress is involved in the pathogenesis of FD and caninestudies show that acoustic stress inhibits G-MMC (Eur J Pharmacol. 131: 123, 1986). Westudied whether acoustic stress affects motilin release and autonomic nerves functions inconscious dogs. Methods:In five hound dogs, strain gauze force transducers were chronicallyimplanted on the gastric body, antrum, duodenum, proximal jejunum, and distal jejunum.Twenty min after finishing gastric phase III, dogs were forced to hear an intense music (80-90 dB) through earpieces for 90 min. To evaluate the autonomic nerves function in aconscious state, we utilized heart rate variability (HRV) analysis. HRV data were derivedfrom the ECG signal by measuring the beat-to-beat intervals of the cardiac cycle. The highfrequency (HF; 0.15-0.4 Hz) and low frequency (LF; 0.04-0.15 Hz) band of the HRV powerspectrum were used as a marker of vagal and sympathetic activity, respectively. The powerin LF/HF ratio was used as an indicator of sympatho-vagal balance. To study whetheracoustic stress affects plasma motilin release, plasma motilin levels were measured by a
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radioimmunoassay. Results: The occurrence of G-MMC was significantly inhibited duringacoustic stress, while intestinal MMC (I-MMC) was not inhibited. Duration of G-MMC cyclewas significantly prolonged following acoustic stress from 96±15 min to 115±32 min (n=5, P<0.01). Heart rate and LF component were increased, while HF component was attenuatedduring acoustic stress. As a result, acoustic stress significantly increased LF/HF ratio. Gastricphase III contractions, but not intestinal phase III contractions, were almost completelyabolished during the acoustic stress. In contrast, elevated motilin release was still observedduring the acoustic stress. Conclusion: In spite of impaired G-MMC, I-MMC and motilinrelease remained intact during acoustic stress. HRV analysis showed the reduced activity ofparasympathetic nerves and increased activity of sympathetic nerves during acoustic stress.Acoustic stress attenuates the sensitivity and/or response to motilin, resulting in impairedG-MMC. It is conceivable that stress may interfere with the occurrence of gastric phase IIIin humans, especially FD patients.
T1357
Predictive Model for the Cutaneous EGG Based On Internal and ExternalGastric Muscle Probes In VivoThomas L. Abell, Elizabeth Rickman, William Johnson, Robert Schmieg, J. R. Salameh,Saleem Islam, Steve Bigler, Charu Subramony
Introduction: The Origin of the cutaneous EGG remains controversial. The ability to recordboth mucosal and serosal EGG—by endoscopy and laparoscopy/otomy—offers a methodof comparison of the origins of the cutaneous EGG. We hypothesized that the cutaneousEGG is a mixture of signals from the internal and external layers which in-vivro probescould help determine. Patients: 16 patients (14 f, 2 m, mean age 30 years, with diagnosis:Diabetes 3, Idiopathic 13) were studied with mucosal EGG and serosal EGG, at the timeof temporary and permanent GES placement. These were compared with the cutaneousEGG on the same patients. All EGGs were recorded in resting/fasting conditions and analyzedby signal averaging for average frequency and amplitude. Methods: The mucosal and serosalEGG data were obtained from electrodes placed either endoscopically through the mucosainto the inner muscle layer or surgically through the serosa into the outer muscle layer atthe time of placement of temporary or permanent electrical stimulation devices. CutaneousEGG data was obtained by attaching electrodes to the skin in a standardized manner. Allof the data was then compared by linear regression to predict the cutaneous EGG signal.Results: The mucosal frequency (F), amplitude(A) and F/A Ratio (FAR) were all used asindependent variables. (See table). The most significant finding occurred with the MucosalF/A Ratio which accounted for 49% of the variablility of the cutaneous EGG. Conclusions:The model of cutaneous EGG formulation using mucosal and serosal probes offers a methodo-logy for studying the origin of the cutaneous EGG. Future studies, correlating mucosal andserosal signals with Cajal cell structure of patients are already in progess, and may offeradditional insights into the cutaneous EGG.Correlation of Cutaneous EGG results with Mucosal and Serosal EGG results
T1358
Rapid Gastric Emptying Is Associated with Impaired Gastric Accommodationand Nausea in Patients with Chronic Upper Gastrointestinal SymptomsRobert M. Taylor, Linda Anh B. Nguyen, William J. Snape
Background: Chronic upper GI symptoms have been attributed to multiple pathophysiologicabnormalities among which include H. pylori, visceral hypersensitivity, impaired gastricaccommodation (dV), and gastroparesis. Delgado-Aros et al. (Gastro 2004) have alsodescribed a subset of dyspepsia patients who have rapid gastric emptying associated withsmaller postprandial gastric volumes. Aims: 1) Assess whether rapid 2 hour gastric emptying(GE) is associated with pathophysiologic abnormalities as measured by the barostat. 2)Determine if there are upper GI symptoms that correlate with rapid GE. Patients/Methods:112 patients (age 42.4 + 1.4; F=79, M=33) with chronic upper GI symptoms >6 months(nausea, vomiting, early satiety and/or epigastric pain) were evaluated with a standardizedsolid GE study by nuclear scintigraphy and gastric barostat. GE was expressed as percentretention at 2 and 4 hours. Gastric sensation, compliance, and dV were measured with thebarostat balloon placed in the fundus endoscopically under fluoroscopic guidance. ImpaireddV is defined as the postprandial change in volume <64mL. Gastric compliance was measuredwith the barostat using isobaric distensions. Sensation was measure by stepwise volumedistentions. The dominant symptom was identified for each patient (nausea, vomiting, nauseaand vomiting, or pain). Patients were subdivided according to 2 hour GE: rapid = 0-9%(N=20), mildly rapid = 10-39% (N=70), normal = 40-60% (N=16), delayed >60% (N=6).Physiologic parameters were compared using an unpaired t-test. Results expressed as mean+ SEM. Results: 106/112 (94.6%) patients had a 2 hour GE <60%. 56 (50%) patients hadimpaired dV. Patients with rapid GE had impaired dV compared to those with normal (23.3+ 26.5 mL vs. 100.3 + 24.3 mL, p=0.04) or delayed GE (23.3 + 26.5 mL vs 138.8+ 48.8mL, p<0.05). There were no differences in sensory threshold or compliance between thegroups (p>0.05). Predominant nausea was more prevalent in patients with rapid GE comparedto those with normal GE (30% vs. 0%, p=0.02. Vomiting or pain were not different betweengroups. Conclusion: Rapid GE is associated with impaired dV and nausea when comparedto patients with normal or delayed GE at 2 hours. This likely represents a subgroup ofpatients with dumping syndrome in the absence of prior gastric surgery. This finding issimilar to the results of a study by Delgado-Aros et al, which utilized GE at 1 hour and SPECT.