-4.808 AGA ABSTRACTS

• G3320 EXPANDABLE METAL STENTS IN ACHALASIA: IS THERE A ROLE? S Mukherjee, M Sipple, DS Kaplan, SUNY Health Science Center and Crouse Hospital, Syracuse, NY.

Objectives: Achalasia is treated with pneumatic dilatation or myotomy and botulinum toxin (botox) injections are occasionally used. We describe our experience with expandable metal stents (EMS) in 6 patients with achalasia or pseudoachalasia who failed medical therapy and were not surgical candidates. Methods: From July 1995 to November 1997 7 EMS were placed in 6 patients (A-F). Patient A was 30 years old but the average age of the rest was 81 years. There were 4 males and 2 females. Barium swallows were done in all 6 patients and esophageal manometry in 3. Manometric records were not available (and manometry not repeated) in patients D-F who each had achalasia for at least 10 years. 4 patients had achalasia and 2 had pseudoachalasia. Successive botox injections were done in 4 patients (A,B,C,E) and pneumatic dilatation in 1 (B). Patient F only agreed to periodic Maloney dilatations or a metal stent. Pneumatic dilatation was considered high risk in 5 patients and none were surgical candidates. 3 different metal stents were used - Wilson Cook 8 cm 2 stent (A), Schneider II stent (B,C) and older Schneider I stent (D-F). Results: Immediate success was achieved in 4 patients (66%) with 0% procedure mortality (they were maintained on a supraglottic diet). The Wilson Cook stent slipped into the stomach upon deployment and was removed immediately. 2 patients were symptom-free for 6 months but required repeat endoscopy for recurrent dysphagia - food bolus removed endoscopically in patient D and a second metal stent placed in patient F as the original stent had migrated proximally above the GE junction 1 month mortality approached 33% (both patients died of myocardial infarction). Conclusion: We believe EMS provide symptomatic relief in selected patients with achalasia or pseudoachalasia who have short life expectancies, failed medical treatment or are poor surgical candidates in our small series the Schneider I metal stent was most beneficial.

• G3321 GASTROINTESTINAL (GI) SYMPTOMS AFTER TRANSPLANTATION (TX), K. Mullins, M. DeMeo, A. Keshavarzian, T. Murphy, S. Fisher, E. Garrity, M. Mullen, R. Lewis, M. Bakhos,. Dept. of Med. and Surg., Loyola Univ. Med Center, Maywood, I1.

Aims: We observed an increased frequency of nausea, vomiting and abdominal distention in lung tx pts. These problems often resulted in prolonged hospitalization, increased risk of aspiration, and failure to realize nutritional goals. The etiology of these symptoms was unclear but thought secondary to vagal injury or the immunosuppressive therapy. The aim of our study was to identify the prevalence and severity of GI complaints in this population in comparison to pts receiving heart and renal tx as well as CABG. Methods: A retrospective evaluation of 252 pts was performed assessing GI symptoms six months to one year after surgery. 75 lung tx pts, 68 heart tx pts, 59 renal tx pts and 50 CABG pts, were sent questionnaires concerning GI symptoms When appropriate, symptoms were qualified in terms of frequency and severity. A symptom index was also calculated which determined overall presence of symptoms, weighted for frequency and severity. The differences among the groups were calculated using Chi-Square. Results: Comparisons were made between three groups: lung tx pts, tx controls, and CABG pts. Nausea was more prevalent in lung tx pts (63%) compared to tx controls (35%) and CABG pts (10%)(p < .001). The frequency of this symptom was also greater in the lung tx group with 21% experiencing daily nausea compared to 7% of the tx control and 4% of CABG pts. Additionally, abdominal distention was significantly different among the groups with 43% of lung tx pts experiencing symptoms as compared to 31% of tx controls and 24% of CABG patients (p<.002). More lung tx pts complained of limitations to food intake (34%) after surgery compared to tx controls (16%) and CABG pts (6%)(p<.029). However, 49% of lung tx pts stated that they ate more after surgery than prior to their operation, as compared to 30% of tx control pts and 10% of CABG pts (p<.001). Overall, lung tx pts had more symptoms (88%) than tx controls (72%) and CABG pts (70%) (p<.016) as well as a greater symptom index compared to the other groups (p<.0001). There was no difference between pts suffering from odynophagia, dysphagia, or GERD in the three groups. Additionally, there was no difference in the three groups regarding stool frequency, consistency, appetite or overall feeling of well being. Conclusion: Lung transplant patients have an increased prevalence of nausea and abdominal distention compared to renal/heart transplant patients and CABG patients. Nausea also occurred more frequently in the lung tx group compared to the other groups. Overall, lung transplants had more symptoms and a greater symptom index than the transplant control group and CABG patients. Lung transplant patients revealed an overall increase in po intake but a decrease in the amount of intake per meal. The increased prevalence and frequency of these symptoms remained in the lung transplant population even after adjustment for age, sex and length of postoperative follow up by multivariate analysis.

GASTROENTEROLOGY Vol. 114, No. 4

• G3322

AUTONOMIC AND NEUROENDOCRINE RESPONSES TO RECTO- SIGMOID STIMULATION. J. Munakata, E.A. Mayer, L. Chang, M. Schmulson, M. Liu, G. Tougas, M. Kamath, B. Naliboff. UCLA/CURE Neuroenteilc Disease Program; Depts. of Medicine and Psychiatry, UCLA School of Medicine, Los Angeles, CA, McMaster Univ., Hamilton, ONT and WLA-VA Medical Center, Los Angeles, CA.

Background: Visceral afferent stimulation results in activation of HPA axis and autonomic nervous systems, involving the central release of CRF. Repetitive noxious sigmoid stimulation results in the development of rectal hyperalgesia in patients with irritable bowel syndrome (IBS) but not in normals (N) (Gastroenterology 112:55;1997). This sensitization response is more pronounced in IBS females compared to IBS males. Aims: To evaluate the effect of repetitive noxious sigmoid stimulation on vagal and neuroendocrine responses to recto-sigmoid distension in 1) IBS vs. N and 2) males vs. females. Methods: 26 ROME+ IBS patients (16M, 10F, mean age: 37) and ll N (6M, 5F, mean age: 34) were studied during rest, during rectal distension (baseline and post-sigmoid stimulation) and during sigmoid stimulation. Heart rate and beat-to-beat variability (HRV;vagal) were recorded continuously (500 samples/sec). Cardiopulmonary vagal tone (sympathetic/ vagal ratio) was determined from the amount of EKG interbeat variability associated with respiration (respiratory sinus arrythmia) and computed using a spectral analysis technique. Cortisol, epinephrine and ACTH levels were determined from assays of blood samples obtained before and after sigmoid stimulation. Results: 1) A significant interaction between group (IBS and N) and condition (rectal and sigmoid stimulation) was observed for vagal tone (p<0.05). While rectal distension resulted in an increase in vagal tone for IBS patients before and after sigmoid stimulation, a decrease in vagal tone was observed for N. Conversely, sigmoid stimulation resulted in a decrease in vagal tone for IBS but an increase for N. Compared to N, 1BS patients showed lower cortisol levels before (22 + 5 vs. 10-+ 2, p<0.05) and after sigmoid conditioning (23 -+ 4 vs. 9 -+ 1, p<0.05), respectively. 2) Cortisol levels were similar in males and females at baseline. However, following sigmoid stimulation cortisol levels increased in males but decreased in females. Conclusions: Compared to N, IBS show an increased vagal response to rectal distension, decreased vagal response to sigmoid distension and lowered cortisol levels. These findings suggest an alteration in central control mechanisms involved in autonomic and neuroendocrine responses to visceral stimuli. Supported by NIH grant DK 48351 (EAM)

• G3323 THE NATRIURETIC PEPTIDE CLEARANCE RECEPTOR (NPR-C) IS COUPLED VIA INHIBITORY G PROTEINS TO ACTIVATION OF PLC-I3 AND INHIBITION OF ADENYLYL CYCLASE IN TENIA COLI. K.S. Murthy, J.-G Jin, B.-Q. Teng, J.R. Gilder and G.M. Makhlouf. Depts. of Medicine and Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA.

We have previously shown that ANP and the selective NPR-C agonist, cANP4-23, induce relaxation of gastric muscle by activating a constitutive nitric oxide synthase (NOS) coupled to pertussis toxinsensitive G proteins (Gil and Gi2). The absence of NOS activity in guinea pig tenia coli suggests that NPR-C may mediate a different, NOS-independent response in tenia. NPR-C possesses a truncated cytoplasmic domain devoid of guanylyl cyclase activity that can couple to G proteins. RT-PCR and Northern analysis demonstrated expression of the NPR-C in cultured guinea pig tenia coli muscle cells. RT-PCR using specific primers for endothelial, neuronal and inducible NOS, showed absence of expression of eNOS, nNOS or iNOS, corroborating the evidence from functional studies demonstrating absence of NOS activity. cANP4-23 caused contraction of dispersed tenia coli muscle cells (25.7 + 0.8 /am decrease in cell length). The contraction was abolished by the phosphofipase C-I3 (PLC-13) inhibitor, U73122 (10 /aM), or by 60-rain treatment with PTx (400 ng/ml). Contraction was not affected by nifedipine (1 /aM) or the PLA 2 inhibitor, DEDA (10 /aM) which normally block contraction in longitudinal muscle. The pattern implied that contraction in tenia was mediated by IP3-dependent Ca 2+ release resulting from activation of a PLC-[3 isoform via a PTx-sensitive G protein. Consistent with activation of an inhibitory G protein, cANP4-23 inhibited forskolin-stimulated cAMP formation (forskolin: 16.3-+ 1.9 pmol/106 cells; forskolin plus cANP4-23: 2.3 + 1.3). The inhibition was completely reversed by pretreatment of the cells with PTx. ANP and VIP interact, respectively, with NPR-A and VIP 2 receptors mediating relaxation, as well as with NPR-C; when relaxant effects were blocked with cA- and/or cG-kinase inhibitors both agonists induced contraction. Conclusion: In tenia coli, NPR-C is coupled to activation of PLC-[3 and inhibition of adenylyl cyclase. Activation of NPR-C results in PTx-sensitive Ca 2+ release and contraction, and inhibition of cAMP.

• G3324

THE CLINICAL UTILITY OF SYMPTOMS ASSESSMENT IN PATIENTS WITH FUNCTIONAL DYSPEPSIA. E.R. Muth 1, K.L. Koch 2, S.A. Bingaman 2, R.M. Stern3, Naval Aei'ospace Medical Research Laboratory 1, Pensacola, FL; Departments of Medicine 2 and Psychology 3, The Pennsylvania State University, University Park and Hershey, PA.

Patients with functional dyspepsia are often sub-grouped according to their symptoms (Talley, et al, 1991). These sub-groups tend to lack