A846 AGA ABSTRACTS

• G3471

TWO-LUMEN TUBING IS REQUIRED FOR ACCURATE BAROSTAT STUDIES. T. Tam, H. Mui 1, S. Jundler 2, G. Tougas, D. Armstrong. Division of Gastroenterology, McMaster Univ, Ham)lton; lMui Scientific, 2G&J Electronics, Toronto Ontario Canada.

Backeround A barostat maintains preset intraballoon pressures to measure gastrointestinal (GI) wall tone or deliver luminal pressure stimuli. The connecting tubing configuration affects barostat function but published guidelines do not specify optimal design. Aim To assess the effect of tubing configuration (1 v. 2 lumina) and diameter on barostat operation. Methods Different tubing configurations connected a barostat (G & J Distender II) to a pump (modified barostat) which generated a series of volume changes (5 inflation/deflation cycles: 30 to 375 ml) in a closed system. The barostat maintained preset pressures of 8, 24 & 48 mm Hg for each combination of tubing configuration, volume change, pump speed (15, 30 ml/s) and barostat motor speed (15, 25, 40 ml/s). In a single lumen configuration (S: 0.8, 2, 3 & 5mm Internal Diameter {ID}), pressure monitoring and volume delivery used the same lumen; with two lumina, pressure monitoring (M: 0.8, 2, 3 & 5ram ID) and volume delivery (V: 2, 3 & 5mm ID) used separate lumina. Pressure was recorded at the barostat (B) and pump (P); differences between preset barostat pressure (PP) and P were calculated giving Absolute Operating Error (AOE={PP-P}) and Percentage OE (%OE={100*[{PP-P}/PP]}). Results %OE are shown for 6 designs (preset pressure: 8mmHg, motor speed: 40 ml/s, length 250 cm).

Single lumen Two lumen tubing (* D < 0.05 v. V5M2) Volume $2 $5 V3M2 V 3 M 3 V 5 M 2 V5M5 30ml -11.8% -12.5% *0.94% -9.0% -3.1% -12.4% 60 ml -13.0 % -10.0 % *0.63 % -8.8 % -1.0 % -12.8 % 100ml -12.9% -12.5% *0.15% -8.2% -1.5% -14.8% 225 ml -15.9 % -12.4 % *0.82 % -7.2 % -1.8 % -12.2 % 375 ml -21.2 % -11.2 % *0.50 % -8.3 % -2.0 % -13.1%

AOE are comparable at preset pressures of 8, 24 and 48 mm Hg resulting m lower %OE at higher pressures; AOE and %OE are lower with two lumen tubing, apart from V5M5. Singl e lumen tubing (0.8 mm ! D) produces very large AOE; the lowest OE occurs when M is smaller than V: %OE is consistently lowest with V3M2 tubing. Summary_ Single lumen tubing at all diameters, underestimates pressures (10.0-21.2%) significantly. Two lumen tubing is accurate only if M < V and is most accurate if M=2 mm and V=3 mm; however, it also underestimates pressures (7.2-14.8%) if M _> V. Conclusion Tubing configuration has a profound effect on barostat- controlled, preset pressures in a distant chamber, corresponding to a GI luminal balloon. A single lumen tubing design is inadequate for barostat studies; it will grossly underestimate visceral pressures and is unsuitable for studies of GI sensorimotor function. Two-lumen tubing should be used with a measuring lumen ID (2 mm) which is less than the volume delivery lumen ID (3 mm), regardless of the capacity of the organ studied. Support: CAG-Astra Fellowship, Canadian MRC, G & J Electronics.

• G3472

FUNCTIONAL EXPRESSION OF NATRIURETIC PEPTIDE CLEARANCE RECEPTOR (NPR-C) IN RABBIT GASTRIC MUSCLE CELLS. B.-0. Teng, K.S. Murthy, J.-G. Jin and G. M. Makhlouf. Departments of Medicine and Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA.

We have previously shown that VIP interacts with the natriuretic peptide clearance receptor (NPR-C) to activate a constitutive nitric oxide synthase (eNOS) expressed in smooth muscle cells. The aim of this study was to characterize the NPR-C by molecular and functional approaches. Muscle ceils were isolated from rabbit stomach and cultured in DMEM-10 for two weeks. RT-PCR using specific primers for NPR-C and NPR-B yielded products of the expected size (541 bp and 228 bp, respectively). No PCR product was obtained using NPR-A specific primers. Cloning and nucleotide sequence analysis of the PCR product obtained with NPR-C specific primers showed close similarity to bovine (90.4%), human (88.0%), and rat (84.3%) nucleotide sequences. Northern analysis using NPR-C cDNA yielded discrete mRNA species. In control studies, RT-PCR using specific primers for endothelial cell (VEGFR and PECAM) and interstitial cell (c-kit) markers showed absence of endothelial and interstitial cells in these muscle cultures. In membranes isolated from dispersed gastric muscle ceils, cANP4-23 (a selective NPR-C ligand), ANP, and VIP stimulated NOS activity (30 -+ 4, 28-*-5 and 59 + 7 pmol [3H]citrulline/mg protein) over and above maximal NOS activity stimulated by optimal Ca a÷ concentrations (100 pM); NOS activity stimulated by Ca 2+ and agonists was abolished by L-NNA. Incubation of the membranes for 1 h with maximal concentrations of Gail or Gala antibody inhibited NOS activity stimulated by cANP4°23, ANP and VII? by 30 -+ 5% to 63 +- 3%; inhibition by a combination of Gail and Gaiz antibodies was additive (82%-84%). Antibodies to a subunits of other G proteins had no effect. Consistent with involvement of Gail and Gai2, cANP4-23 and ANP inhibited forskolin-stimulated cAMP formation by 47% to 58%; the inhibition was abolished by treatment of muscle cells with pertussis toxin.

GASTROENTEROLOGY Vol. 114, No. 4

Conclusion: VIP and ANP interact with the NPR-C expressed in gastric smooth muscle cells; the receptor is coupled via Geql and Goti2 to activation of constitutive NOS and inhibition of adenylyl cyclase.

G3473

GASTROPARESIS AS THE INITIAL PRESENTATION IN MULTIPLE SCLEROSIS. H.Ter, M.Bayek, N.Marcon. The Wellesley Hospital, Toronto, Canada.

Introduction: Gastroparesis is a rare f irst manifestation of multiple sclerosis (Ann. Neurol. 1981; 10: 397-98). Case report: We report a case of a previously well 34 years old white female who had a 3 weeks history of postprandial bloating, nausea and vomiting associated with a 7kg weight loss. Laboratory results involving a complete blood count, chemistry, TSH, cortisol level and sedimentation rate were normal. A head CT scan had been performed at the referring hospital and was reported as normal. Gastroscopy showed no mechanical gastric outlet obstruction. A small bowel follow- through also ruled out more distal obstruction. A solid phase gastric emptying scan showed a markedly prolonged T1/2 of 398 minutes. During the period of admission, she developed numbness over the dermatomes of the divisions I and II of the right trigeminal nerve. She also later noticed mild right-sided facial weakness which became progresively more pronounced over several days. She became dysarthric and developed a scanning speech. Her gait became ataxic. An MRI scan was performed and showed multiple foci of abnormal signal intensity in the left and right middle cerebellar peduncles, pons, medulla, as well as multiple cerebral white matter lesions, changes consistent with multiple sclerosis. Her gastroparetic symptoms were controlled with Cisapride at 20rag PO AC/TID and QHS. High dose methylprednisolone was administered intravenously with resolution of all her symptoms. The patient was discharged home independent in all activities of daily living, on a tapering steroid dose and cisapride. Discussion: Animal studies have shown that gastric motility is influenced by various regions in the brainstem and medulla, specifically the nucleus of the solitary tract, nucleus raphc obscurus and the dorsal motor nucleus of the vagus. This patient had lesions involving the brainstem and medulla which could explain her gastroparetic symptoms. The chronology of her presenting symptoms and the location of her lesions are highly suggestive of gastroparesis being the f irst manifestation of her multiple sclerosis. Multiple sclerosis should be considered in any patient who presents with symptoms of gastroparesis of unknown etiology.

G3474

THE EFFECT OF LANREOTIDE THERAPY ON GALLBLADDER EMtrrYING IN PATIENTS VClTH ACROMEGALY. AV Thillainayagam 1, DRM Lindsell 2, HE Tumer 3, DP JewelP, and JAH Wass 3. Departments of Gastroenterology 1, Radiology 2 and Endocrinology 3, Oxford Radcliffe Hospitals, Oxford, UK.

Background There is an increased prevalence of gallstones in patients with Acromegaly who are treated with the somatostatin analogue octreotide. It has been suggested that use of the recently developed longer-acting somatostatin analogues would be less likely to encourage the development of gallstones in Acromegalics, but there is a paucity of supportive data. We therefore carried out a prospective study of the effects of a longer-acting somatostatin analogue, Lanreotide (30rag by intramuscular injection every 7-10 days), on gallbladder empying characteristics in six patients with Acromegaly (mean duration 8.5 years). Methods Ultrasound scans of the gallbladder were performed at 0800h and, after measuring length (l), height (h) and width (w) of the gallbladder, the fasting volume (FV) of the gallbladder was calculated according to the formula <pi>/6 x lhw. These measurements were repeated 20 and 40min after ingestiOn by the patients of 250ml of a balanced polymeric feed, Ensure, in order to assess the smallest gallbladder volume (residual volume, RV). Repeat scans were performed (midway between Lanreotide injections) after 9 months treatment. Results were compared using Wilcoxon's signed rank test (two-tailed). Results Three of the patients were found to have small (<10mm diameter) gallstone at the start of the study, but were asymptomatic. No patient developed new stones during the study. Before Lanreotide treatment maximal gallbladder emptying (mean [interquartile range]) was 90% [87-93] compared to 58% [44-72] after treatment (p < 0.03). Prior to Lanreotide therapy RV was 3.5ml [2.3-6.3], but rose to 25.5ml [12.4-36] after therapy (p < 0.03), while FV (52ml [24.5-58.5]) remained unchanged by treatment with Lanreotide (80ml [29.5-88.5]). Conclusion These findings: (i) suggest that gallbladder emptying is indeed impaired by Lanreotide therapy, and (ii) militate against the hypothesis that gallstone development may be less common in patients treated with longer- acting somatostatin agonists.