Interdigestive Motor Activity in Patients with Systemic Sclerosis

Transcription

1 GASTROENTEROLOGY 1982;83: Interdigestive Motor Activity in Patients with Systemic Sclerosis W. D. W. REES, R. J. LEIGH, N. D. CHRISTOFIDES, S. R. BLOOM, and 1. A. TURNBERG Departments of Medicine, Hope Hospital, University of Manchester School of Medicine, Salford and Hammersmith Hospital, DuCane Road, London, England Fasting antral, duodenal, and jejunal motor activity and plasma motilin and pancreatic polypeptide were studied in 15 patients with systemic sclerosis, 6 with and 9 without clinical evidence of small bowel involvement, and 8 healthy control subjects. Normal interdigestive motor activity was present in control subjects and patients without intestinal involvement. However, cyclic motor activity was absent in 3 of the patients with intestinal disease and the motility index per interdigestive cycle (or per 6-h recording period in those without cyclic activity) was significantly less in the antrum (181 ± 103 mm 2 compared with 760 ± 86 and 1116 ± 96 mm 2 for patients without involvement and healthy control subjects, respectively), duodenum (153 ± 101 mm 2 compared with 1425 ± 186 and 1055 ± 241 mm 2 ), and jejunum (268 ± 131 mm 2 compared with 1166 ± 97 and 1105 ± 128 mm 2 ). Metoclopramide and bethanechol significantly increased motor activity at the three sites in all subjects but the magnitude of the metoclopramide response was less in patients with intestinal involvement. Fasting concentrations of motilin and pancreatic polypeptide exhibited cyclic variation with peak values occurring during phase 3 of the interdigestive cycle. Plasma motilin during each phase of motor activity was significantly higher in patients with scleroderma, with or without intestinal involvement, than in control subjects. The abnormal motor activity demonstrated Received December 7, Accepted April 14, Address requests for reprints to: Dr. W.D.W. Rees, Department of Medicine, Hope Hospital, University of Manchester School of Medicine, Eccles Old Road, Salford M6 8HD, United Kingdom. This work was presented in part at the British Society of Gastroenterology Meeting, September Dr. Rees is a Wellcome Senior Research Fellow. The authors are grateful to Professor Malcolm Jayson and the University Department of Rheumatology, Hope Hospital, for introducing us to most of these patients; to the Department of Medical Illustration for providing the figures; and to Mrs. Rostron for typing the manuscript by the American Gastroenterological Association /82/ $02.50 here indicates a possible mechanism by which intestinal stasis and bacterial overgrowth could occur and by which clinical disturbances of intestinal transit might arise. Gastrointestinal involvement commonly occurs in patients with systemic sclerosis (1-12) and it has been suggested that the disturbances in intestinal function are secondary to collagenous replacement of the muscularis propria (13,14). Esophageal motor activity is abnormal in about 70% of patients and the abnormal motor patterns there have been well defined (12,15). There is evidence that the initial involvement produces a defect in neurotransmitter release, while in advanced stages of the disease the motor abnormalities are caused by smooth muscle atrophy (8). Radiologic evidence of gastric or intestinal "sclerosis", or both, occurs in 40% of cases (1,3,4,7), but in contrast to the esophagus, there is very little information available about the pattern of gastric and small bowel motor activity in these patients. The present study was designed to examine the fasting pattern of motor activity in the upper gastrointestinal tract of scleroderma patients, with and without clinical evidence of intestinal involvement, and to investigate the relationship between motor activity and plasma concentrations of motilin and pancreatic polypeptide. Methods The studies were performed on 8 healthy volunteers aged yr (mean ± SE = 37 ± 6 yr) and 15 patients with systemic sclerosis, 9 without evidence of gastrointestinal disease, aged yr (46 ± 6 yr), and 6 with evidence of small bowel scleroderma, aged yr (58 ± 4 yr). All 15 patients had a history of Raynaud's phenomenon and evidence of cutaneous involvement with scleroderma [sclerosis (15), sclerodactyly (15), and digital pitting scars (13)]. Twelve patients, 6 with and 6 without

2 576 REES ET AL. GASTROENTEROLOGY Vol. 83, No. 3 intestinal involvement, had typical changes of scleroderma on histologic examination of forearm skin biopsies (atrophy of dermal appendages and collagen deposition). In 2 patients with gut involvement, biopsy specimens obtained at laparotomy revealed histologic changes of scleroderma in the jejunum and ileum. All 6 patients with intestinal involvement had radiologic evidence of esophageal and small intestine sclerosis [hypomotility (6), dilated loops of small intestine (6), and "hidebound" appearance (4)] and 4 had evidence of steatorrhea and bacterial overgrowth at the time of the motility study. Informed written consent was obtained and the studies had been approved by the Salford Area Ethical Committee. Procedure Intraluminal pressure in the gastric antrum, midduodenum, and proximal jejunum was measured by means of three perfused tubes (internal diameter 1 mm) cemented in series to a Mallinckrodt polyvinyl tube, size 12 (Mallinckrodt Inc., Science Products Division, St. Louis, Mo.). The perfusion ports were located 1, 22, and 30 cm from the distal end of the polyvinyl tube. Each tube was perfused at 0.1 mllmin with 0.15 M sodillm chloride using a Sage pump model 355, (Sage Instruments Div, Orion Research Inc., Cambridge, Mass.); and changes in pressure were measured by external stain gauge transducers (Stratham model P230b, Grass Instrument Co.. Quincy. Mass.)' connected to a direct current pen recorder Grass polygraph, model 7 (Grass Instrument Co.). Compliance was assessed by applying fixed pressures of 50 and 100 mmhg to each tube and measuring the amplitude and frequency responses. A sealed mercury unit was attached to the tip of the polyvinyl tube in order to facilitate its positioning in the proximal jejunum. Experimental Design After a 12-h fast, the composite tube was positioned fluroscopically until the mercury unit was 5 cm distal to the ligament of Treitz. A second polyvinyl tube (Mallinckrodt ventrol tube. size 12) was then positioned with its tip in the gastric antrum. The subjects adopted a semi reclining posture and the stomach and duodenum was kept empty by continuous aspiration (-10 mmhg) of the two ventrol tubes. Motor activity in the antrum, duodenum. and jejunum was continuously recorded while respiration was monitored by means of a belt pneumograph. Fasting motor activity was recorded for 6 h. after which the subjects were given 10 mg of metoclopramide intravenously (over 5 min) during early phase 1 of the inter digestive cycle. The motor response was examined over 45 min. After the appearance of motor quiescence (phase 1). each subject then received subcutaneous bethanechol (2.5 mg) and the response was assessed during a further 45-min period. An intravenous cannula was positioned in an antecubital vein and blood samples (5 ml) were collected at 15-min intervals throughout the study and placed in chilled. heparinized tubes containing trasylol (2000 IU); the plasma being subsequently stored at - 20 C. The time of each blood sample was marked on the motor recording. Analysis and Calculations Blood samples. Motilin was measured with an N terminal reacting porcine antiserum (16) which detected both large and small molecular forms of motilin in plasma (17) and showed no cross-reactivity with other hormones. Changes in 3 pmolll of motilin in plasma could be detected with 95% confidence. Pancreatic polypeptide was measured with an antiserum raised against bovine pancreatic polypeptide (18) and the assay detected changes in concentrations of 8 pmolll with 95% confidence. Motility recordings. Each recording was scanned to determine whether or not a cyclic pattern of motor activity was present. The following indices were measured: (a) Number of complete interdigestive cycles per study period. (b) Total duration of each interdigestive cycle measured from the transition of phase 3 to phase 1 in consecutive cycles. (c) Duration of each phase of motor activity. Phase 1 was defined as a period of motor quiescence, phase 2 as a period of intermittent contractions, and phase 3 as the period of intense motor activity when the bowel was contracting at its maximum frequency. (d) Motility index per inter digestive cycle. The area occupied by contractions during phase 2 and 3 of each interdigestive cycle was measured. In subjects without cyclic activity the area occupied by contractions occurring throughout the 6-h recording period was measured. (e) Motor response to metoclopramide and bethanechol. The area occupied by contractile activity was measured for a 3D-min period following drug administration. Since these drugs were given at the onset of phase 1. the motor response was compared with a similar period in the preceding interdigestive cycles. Results Clinical details of the scleroderma patients are shown in Table 1. The age and male-to-female ratio of healthy subjects and patients with scleroderma not involving the small bowel were similar. Patients with intestinal scleroderma were significantly older than those without (58 ± 4 yr compared with 46 ± 6 yr, P < 0.05). It was possible, however, to match 5 subjects from each group for age and sex distribution when comparing the motility index per interdigestive cycle. The duration of the disease was significantly longer in patients with intestinal involvement (14 ± 3 yr compared with 5 ± 1 yr, p < 0.001).

3 September 1982 INTERDIGESTIVE MOTOR ACTIVITY IN SCLERODERMA 577 Table 1. Clinical Details of Patients With Scleroderma and Healthy Subjects Scleroderma with GI Healthy Sclero- involvesubjects derma ment Number of subjects Age (yr) Mean ± SE 37 ± 6 46 ± 6 58 ± 4 a Range Male-to-female ratio 3:5 2:7 2:4 Duration of disease (yr) 5 ± 1 14 ± 3 b Organs involved S9 S 6 E2 L 1 E6 SI6 L 1 a p < 0.05 compared with health and scleroderma without involvement. b p < compared with scleroderma without involvement. S, skin; E, esophagus; L, lung; SI, small intestine. Fasting Motor Activity A cyclic pattern of motor activity (19) was present in the upper gastrointestinal tract of all healthy subjects and scleroderma patients without intestinal disease. In healthy control subjects, a mean of 2.5 ± 0.3 interdigestive cycles were observed over a 5.4 ± 0.2 h recording period, while in the scleroderma group, 2.9 ± 0.4 cycles occurred during 5.3 ± 0.2 h. However cyclic activity was only present in 3 of the 6 patients with intestinal scleroderma. In 1 of the 3 subjects, cycles were more frequent than usually observed at 7 cycles per 5.4 h. The mean frequency in this group of 6 patients (2.3 ± 1.2 cycles per 5.4 ± 0.3 hj, although little different from the other two groups, conceals the considerable variability observed. As previously described (19), cyclic activity consists of three distinct phases: phase 1, a period of motor quiescence; phase 2, characterized by intermittent contractions; and phase 3, a burst of intense contractions that terminates in phase 1. The mean duration of these phases for the three groups of subjects is shown in Figure 1. The pattern of interdigestive motor activity appeared very similar in healthy subjects and scleroderma patients without intestinal involvement. In the 3 patients with intestinal sclerosis who exhibited cyclic activity, the duration of phases 1 and 2 appeared shorter but the differences were not statistically significant. In order to compare the motor activity per interdigestive cycle in healthy subjects and the two groups of scleroderma patients, 5 subjects from each group were matched so that the age of each subject was within 5 yr of that of a matched subject in the other DURATION OF INTERDIGESTIVE MOTOR ACTIVITY IN HEALTH AND SCLERODERMA; WITH AND WITHOUT G.I. INVOLVEMENT C S n=8 n=9 SC; n = 3 (6) M ± S.E. o Phase 1 m Phase 2 Phase 3 Figure 1. Characteristics of inter digestive motor activity in 8 healthy subjects (C), and 15 sclerodermll' patients, 9 without small intestinal involvement(s) cand 6 with involvement (SG). Values represent mean ± standard error; open bars, phase 1 duration; stippled bars, phase 2 duration; shaded bars, phase 3 duration. two groups (Figure 2). The sex distribution in these subjects was identical in the three groups. A motility index (mm 2 ) was calculated from the amplitude and duration of the contractions which occurred during phases 2 and 3. In two of the patients with small bowel involvement, no contractions were observed during a 6-h period and in these the motility index Motility index per interdigestive cycle (mm') Controls O... ~... ~ Scleroderma Scleroderma +GI AD J M±SEn=5 A: Antrum D: Duodenum J : Jejunum * p < 0.02 ** p < 0.01 *** p < Figure 2. Motility index per interdigestive cycle in 5 agematched healthy controls: scleroqerma without intestinal involvement and scleroderma with intestinal involvement. Values represent mean ± standard error; stippled bars, antrum; open bars, duodenum; shaded bars, jejunum.

4 578 REES ET AL. GASTROENTEROLOGY Vol. 83, No. 3 per cycle was regarded as zero. It may be seen from Figure 2 that the mean motility index was similar at all three sites (antrum, duodenum, and jejunum) in healthy subjects and scleroderma patients with intestinal involvement. However, in the group with small bowel disease, antral (p < 0.02), duodenal (p < 0.01), and jejunal (p < 0.005) motor activity per cycle were significantly less than in control subjects or patients without intestinal sclerosis Motility index per 30 mins. imm') Controls Scleroderma Scleroderma + GI M ± SE A: Antrum D: Duodenum J : Jejunum Response to Metoclopramide and Bethanechol Intravenous metoclopramide (10 mg) significantly increased antral, duodenal, and jejunal motor activity in the three groups of subjects (p < 0.05 to P < 0.005) but the magnitude of the response in those patients with intestinal scleroderma was less than in healthy subjects and patients without small bowel involvement although the difference was not statistically significant (Figure 3). The interval from administration of metoclopramide to the onset of motor contractions was similar in healthy subjects (10 ± 1 min) and patients with scleroderma with (9 ± 2 min) or without intestinal disease (7 ± 2 min). Although bethanechol (2.5 mg) produced a significant increase (p < 0.05) in antral, duodenal, and jejunal motor activity in each of the three groups, the magnitude of the response was less than that to Motility per 30 mins. (mml) Controls Scleroderma Scleroderma +GI M±SE A: Antrum D: Duodenum J: Jejunum A D J A D J n=4 n=9 n=6 m Basal motor activity o Post bethanechol motor activity Figure 4. Motor response to bethanechol in 4 healthy subjects and 15 scleroderma patients. Values represent the mean motility index per 30 min for antrum, duodenum, and jejunum. Stippled bars, basal motor activity (phase 1 and early phase 2); open bars, postbethanechol activity. metoclopramide and was similar in patients and healthy subjects (Figure 4). The interval from the administration to the onset of the contractile response was 13 ± 4 min in healthy subjects, 15 ± 3 min in patients with scleroderma but without intestinal involvement, and 14 ± 3 min in patients with small bowel disease. Although these intervals are longer than those for metoclopramide, the differences did not achieve statistical significance. A D J n=8 A D J n=9 n=6 [II Basal motor activity o Post metoclopramide motor activity Figure 3. Motor response to metoclopramide in 8 healthy subjects and 15 scleroderma patients. Values represent the mean motility index per 30 min for antrum, duodenum, and jejunum. Stippled bars, basal motor activity (phase 1 and early phase 2); open bars, postmetoclopramide motor activity. Plasma Motilin and Pancreatic Polypeptide Plasma motilin during phase 3 of the interdigestive cycle was significantly higher (p < 0.05) than during phases 1 and 2 in the three groups of subjects (Figure 5). However, the motilin concentrations during each interdigestive phase were higher in patients with scleroderma (with and without intestinal involvement) than healthy control subjects (p < 0.05 to P < 0.005). Patients with intestinal involvement had higher plasma motilin values than those without, but the differences were not statistically significant (Figure 5). Pancreatic polypeptide concentrations were also significantly higher during phase 3 of the interdigestive cycle than phases 1 and 2 (Table 2, p < 0.05) in all three groups of subjects. Although pancreatic polypeptide appeared higher in scleroderma pa-

5 ;.:::.:::.:.:::.:.'.:1:::: September 1982 INTERDIGESTIVE MOTOR ACTIVITY IN SCLERODERMA 579 Plasma motilin pmol/l Controls : ~ I T,.I ::l ::.:...:::I :::i :... I Scleroderma Scleroderma +GI ::.l:... I * : : : ~ It ~ I l : ~ 1 ; 3, j,-. 2 ~ " ' 1 ~ 2 3 _ o I i l3- l ~ 2 n=8 n=8 n=3 1 I Phases of 2 interdigestive 3 motor activity p < 0.05 Figure 5. Plasma motilin in 8 healthy subjects and 11 scleroderma patients. Values represent mean ± standard error; stippled bars, motilin levels during phase 1 of interdigestive motor activity; open bars, motilin during phase 2; shaded bars, motilin during phase 3. tients with intestinal disease, the differences were not statistically significant probably because only a small number (3) of patients with intestinal involvement were studied (Table 2). Neither metoclopramide nor bethanechol modified the plasma concentrations of motilin and pancreatic polypeptide in healthy subjects or scleroderma patients. Discussion This study revealed that fasting motor activity in the antrum, duodenum, and proximal jejunum is abnormal in scleroderma patients who have clinical and radiological evidence of small bowel involvement. In 3 of these patients, a cyclic pattern of motor activity was not observed, very infrequent contractions occurring during the 6-h recordings. Measurement of the motility index per interdigestive cycle Table 2. Plasma Pancreatic Polypeptide during the Phases of Interdigestive Motor Activity Plasma pancreatic polypeptide (pm) Phase 1 Phase 2 Phase 3 Healthy subjects (n = 8) 22 ± ± 8 41 ± 18 0 Scleroderma without GI 23 ± 6 27 ± 7 49 ± 12 0 involvement (n = 8) Scleroderma with GI 131 ± ± ± involvement (n = 3) o p < 0.05 compared with phases 1 and 2. (or per recording period in those without cyclic activity) demonstrated the very marked reduction in contractile activity in the 6 patients with intestinal sclerosis. In contrast, the 9 patients without clinical evidence of small bowel involvement had normal inter digestive motor activity. Both metoclopramide and bethanechol stimulated motor activity when administered during phase 1 of the interdigestive cycle in healthy subjects and patients with scleroderma, with and without small bowel disease. It is likely that these abnormalities are due to smooth muscle atrophy with collagenous replacement of.the muscularis propria (8,13,14). In a study of duodenal myoelectric activity in scleroderma, DiMarino et al. (20) showed that all patients had an abnormal response to duodenal distention but only those with severe small bowel involvement failed to respond to secretin and pentagastrin stimulation. These authors suggested that local neurogenic reflexes in the gut may be abnormal in all patients with systemic sclerosis but those with severe intestinal involvement have an additional defect in the smooth muscle response to exogenous stimulation. It is conceivable that the abnormal fasting motor activity observed in our group of scleroderma patients with intestinal disease was due to a similar defect in the smooth muscle response to factors which normally regulate interdigestive motor activity. Their 6 patients with intestinal involvement had a mean age of 54.7 ± 5.1 yr and a 10.1 ± 5.3 yr duration of scleroderma, whereas the 7 without were aged 46.9 ± 3.3 yr and had a 3.1 ± 1. 3 yr history of scleroderma. It is of interest that these figures are very similar to those in our current study (Table 1) and suggest that manifestations of intestinal involvement develop as the duration of the disease, and hence the age of the patients, increases. Although the control of fasting motor activity remains poorly understood, it has been suggested that the generation of antroduodenal phase 3 activity may be caused by release of motilin from the proximal small bowel (21,22) and studies have reported some correlation between the peaks of plasma motilin and the onset of phase 3 in the human antrum or duodenum (23,24). In the present study we observed a similar correlation, and in healthy subjects and both groups of scleroderma patients, plasma motilin was significantly higher during phase 3 activity than phase 1 or phase 2 activity. However, in scleroderma patients, with and without intestinal involvement, plasma motilin was significantly higher than in healthy subjects during each phase of motor activity. This elevated motilin could be caused by either increased secretion or decreased metabolism of the hormone, but we are unable to distinguish between these possibilities on currently available evidence. It

6 580 REES ET AL. GASTROENTEROLOGY Vol. 83, No. 3 is conceivable that local motilin release is regulated by neurogenic mechanisms in the stomach and duodenum (25-27) and that these local reflexes are abnormal in all patients with systemic sclerosis. Plasma pancreatic polypeptide concentrations also correlated with antroduodenal motor activity, peak values occurring with phase 3 activity in all subjects (28,29). In patients with intestinal sclerosis, pancreatic polypeptide concentrations were higher than in the other subjects, although not significantly so and this observation may be explained by the older age of these patients (30). The role of interdigestive motor activity is uncertain but it has been held responsible for clearing the fasting bowel of retained material-the intestinal "housekeeper" of Code (31). If it has this role, then the defects in motor activity in scleroderma patients described here could well lead to intestinal stasis and potential bacterial overgrowth, a common complication of this disease. References 1. Hoskins LC, Norris HT, Gottlieb LS, et al. Functional and morphological alterations of the gastrointestinal tract in progressive systemic sclerosis (scleroderma). Am J Med 1962; 33: Heinz ER, Steinberg AJ, Sackner MA. Roentgenographic and pathologic aspects of intestinal scleroderma. Ann Intern Med 1963;59: Treacy WL, Baggenstoss AH, Slocumb CH, et al. Scleroderma of the oesophagus: a correlation of histologic and physiologic findings. Ann Intern Med 1963;59: Atkinson M, Sunmerling MD. Oesophageal changes in systemic sclerosis. Gut 1966;7: Saladin TA, French AB, Zarafonetis CJD, et al. Oesophageal motor abnormalities in scleroderma and related diseases. Am J Dig Dis 1966;11: Greenberger NJ, Dobbins WO III, Ruppert RD, et al. Intestinal atony in progressive systemic sclerosis (scleroderma). Am J Med 1968;45: Bluestone R, MacMahon M, Dawson JM. Systemic sclerosis and small bowel involvement. Gut 1969;10: Cohen S, Fisher R, Lipshutz W, et al. The pathogenesis of oesophageal dysfunction in scleroderma and Raynaud's disease. J Clin Invest 1972;51: Boyd JA, Patrick SI, Reeves RJ. Roentgen changes observed in generalised scleroderma. Report of 63 cases. Arch Intern Med 1954;94: Hale CH, Schatzki R. Roentgenological appearance of gastrointestinal tract in scleroderma. Am J Roentgenol Radium Ther Nucl Med 1944;51: Harper RA, Jackson DC. Progressive systemic sclerosis. Br J Radiol 1965;38: Cohen S. Motor disorders of the oesophagus. N Engl J Med 1969;301: Morson BC, Dawson, 1M. The colon in systemic sclerosis. In: Gastrointestinal pathology. Oxford: Blackwell Scientific Publications, 1972: Schuffler MD, Beagle RG. Progressive systemic sclerosis of the gastrointestinal tract and hereditary hollow visceral myopathy: two distinguishable disorders of intestinal smooth muscle. Gastroenterology 1979;77: Masi AT. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee, Arthritis Rheumatism 1980;23: Bloom SR, Mitznegg P, Bryant MG. Measurement of human plasma motilin. Scand J Gastroenterol1978;11 (Suppl 39): Christofides ND, Bryant MG, Ghatei MA, et al. Molecular forms of motilin in the mammalian and human gut and human plasma. Gastroenterology 1979;80: Bjornsson OG, Adrian TE, Dawson J, et al. Effects of gastrointestinal hormones on fasting gall bladder storage patterns in man. Eur J Clin Invest 1979;9: Vantrappen G, Janssens J, Hellemans J, et al. The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J Clin Invest 1977;59: DiMarino AJ, Carlson G, Myers A, et al. Duodenal myoelectric activity in scleroderma. Abnormal response to mechanical and hormonal stimuli. N Engl J Med 1963;289: Itoh Z, Takeuchi S, Aizawa I, et al. Changes in plasma motilin concentration and gastrointestinal contractile activity in conscious dogs. Dig Dis Sci 1978;23: Lee KY, Chey WY, Tai H, et al. Radioimmunoassay of motilin. Validation and studies on the relationship between plasma motilin and interdigestive myoelectric activity of the duodenum of dog. Dig Dis Sci 1978;23: Vantrappen G, Janssen J, Peeters T, et al. Intraduodenal ph, motilin and interdigestive migrating motor complexes in man. Scand J Gastroenterol1978;13 (Suppl 49): Rees WDW, Malagelada JR, Miller LJ, Go VLW. Human interdigestive and postprandial gastrointestinal motor and hormone patterns. Dig Dis Sci 1982;27: Chey WY, Lee KY, Tai HH. Endogenous plasma motilin concentration and interdigestive myoelectric activity of the canine duodenum. In: Gut hormones. Bloom SR, ed. Edinburgh, London, New York: Churchill Livingstone Press, 1978: Lee KY, Chang TM, Chey WY. Effect of electrical stimulation of the vagus on plasma motilin concentration in dog. Life Sci 1981;29: You CH, Chey wy, Lee KY. Studies on plasma motilin concentration and interdigestive motility of the duodenum in humans. Gastroenterology 1980;79: Lux G, Femppel J, Lederer P, et al. Pancreatic polypeptide, motilin and somatostatin levels during interdigestive motility in man (abstr). Gastroenterology 1980;78: Janssens J, Hellemans J, Adrian TE, et a1. Pancreatic polypeptide is not involved in the regulation of the migrating motor complex in man. Regul Pepts 1982;3: Schwartz TW, Stenquist B, Olke L, et a1. Synchronous oscillation in the basal secretion of pancreatic polypeptide and gastric acid. Gastroenterology 1979;76: Code CF, Schlegel JR. The gastrointestinal interdigestive housekeeper: motor correlates of the interdigestive myoelectric complex of the dog. In: Daniel EE, ed. Proceedings of the 4th International Symposium on Gastrointestinal Motility. Vancouver, British Columbia: Mitchell Press, 1973;531-3.