GASTROENTEROLOGY
1991;101:1289-1297
Colonic Motility and Transit in Health and Ulcerative Colitis S. NARASIMHA KATHY
AKASHI,
ISMAEL
MENA,
REDDY, JAVIER
GABRIELE
BAZZOCCHI,
and WILLIAM
J. SNAPE,
Preprandial and postprandial colonic motility and transit (scintigraphy), with respect to the splenic flexure, were studied in 10 patients with ulcerative colitis and in 9 healthy subjects. The healthy subjects had a postprandial increase in intraluminal pressure that was significantly (P < 0.03) greater in the descending colon than in other regions of the colon. In ulcerative colitis, the pressure was decreased in all regions compared with healthy subjects, with no significant pressure gradient among different regions. In normal subjects, transit was quiescent during fasting; eating stimulated both antegrade and retrograde transit. In ulcerative colitis, transit was variable before as well as after the meal. Both healthy subjects and patients with ulcerative colitis had more rapid emptying from the splenic flexure into the sigmoid than into the transverse colon. More frequent, low-amplitude, postprandial propagating contractions occurred in ulcerative colitis (P < 0.05) than in healthy subjects. Propagating contractions were always antegrade and caused a rapid movement of the tracer into tbe sigmoid. In conclusion, ulcerative colitis is characterized by (a) decreased contractility, (b) increased low-amplitude propagating contractions, and (c) variable transit. These disturbances may accentuate the diarrhea in ulcerative colitis.
he diarrhea in ulcerative colitis is associated with increased secretion caused by mucosal inflammation. However, changes in contractility may also contribute to increased stool frequency (a] by means of decreased segmental contractions that lead to lower impedance to luminal transit or (b) by means of increased aborad propagating contractions that lead to antegrade propulsion of intraluminal contents. Some studies have suggested that the diarrhea in ulcerative colitis is caused by rectosigmoid inflamma-
GEORGE
CHAN, YANNI,
Jr.
Departments of Medicine and Nuclear Medicine and Inflammatory Harbor-UCLA Medical Center, Torrance, California
T
SIMON
VILLANUEVA-MEYER,
Bowel Disease Center.
tion and irritability rather than by rapid transit (1,2). However, colonic contractility is decreased in patients with active inflammation (3,4). Connell (5) hypothesized that segmenting contractions impede the forward movement of colonic contents. Thus, a decrease in segmental contractions in ulcerative colitis would exacerbate the diarrhea. In healthy subjects, eating results in increased nonpropagating colonic contractions in all segments of the colon (6,7). This gastrocolonic response is diminished in patients with ulcerative colitis (8). Reduced postprandial colonic contractile activity in patients with active ulcerative colitis or functional diarrhea (4,8) may be secondary to a defect in either myogenic function or neural control (8). In vitro studies suggest a defect in the smooth muscle at the biochemical level that results in decreased force development in the colonic muscle of patients with ulcerative colitis (9). We have recently developed techniques to measure the transit of intraluminal contents simultaneously with colonic pressure (10,ll). In this study we applied these techniques (a) to elucidate the underlying motility pattern that leads to decreased colonic motility and increased frequency of stools, (b) to understand the nature of colonic transit, and (c) to correlate transit with motility in ulcerative colitis. Materials
and Methods
Subjects Nine healthy subjects who had no previous gastrointestinal symptoms served as controls. The group in-
Abbreviations used in this paper: MI, motility index; DTPA, diethylenl triaminepentaacetic acid. 0 1991 by tbe American Gastroenterological Association 0016-5085/91/$3.00
1290 REDDYET AL.
GASTROENTEROLOGYVol.1O1.No.5
eluded eight men and one woman ranging in age from 21 to 56 years. Normal subjects had been defined as those with more than three stools per week or less than three stools per day. Ten patients referred to the Inflammatory Bowel Disease Center, Harbor-UCLA Medical Center, with moderate or mild left-sided ulcerative colitis were studied. The patients consisted of six men and four women ranging in age from 27 to 54 years. Patients with severe ulcerative colitis were not recruited for the study, because such patients are unable to eat. Patients with mild colitis (three men and one woman) had one to three stools per day, with or without blood in the stools. Patients with moderate ulcerative colitis (three men and three women) had more than five stools per day, often with blood (12). The extent of clinical involvement and degree of inflammation of the colon were characterized by endoscopy and biopsy (13). Informed, written consent was obtained from each subject, and the study was approved by the Harbor-UCLA Human Subjects Committee Methods All patients consumed a clear liquid diet for 24 hours and fasted 12 hours before the study. The colon was prepared by having the subjects drink 1 gal (3.785L) of a balanced electrolyte solution (Colyte; Reed and Carnrick, Piscataway, NJ) the day before to facilitate the placement of the pressure catheter into the colon and to minimize the effect of colonic contents on recorded signals. A polyvinyl open-tipped catheter, with eight pressure ports spaced 15 cm apart, (ID, 0.8 mm; OD, 1 mm) was used to record intraluminal pressure and to instill the radionuclide marker, technetium Tc 99m. The catheter was introduced into the transverse colon over a guide-wire by means of a flexible colonoscope; no sedation was used.
I I
I
-45
I
-30
1
-15
The subjects were placed in a supine position under a gamma camera (Pho/Gamma HP: Nuclear Chicago, Chicago, IL), and the position of the catheter was confirmed on the persistence oscilloscope of the gamma camera by instilling 2 mL normal saline containing 1 mCi of g9mTc-diethylenetriaminepentaacetic acid (DTPA) into each port and withdrawing it. Once in position, the catheter was securely taped to the subject’s thigh. A 5-mCi dose of 99mTc-DTPA was instilled into the splenic flexure as the bolus. The tracer movement was measured as scintigraphic images acquired every 1 minute and recorded as 64 x 64 matrices of 256 grey levels on a dedicated computer (Sopha Medical Computer, Baltimore, MD). The pressure ports were continuously perfused with distilled water at 6.5 mL/min using a low-compliance capillary system (Arndorfer Medical Specialities; Greendale, WI). The pressure transducers (Model P231A; Stratham Instruments, Oxnard, CA) were connected to Beckman couplers (Model 9853A; Sensormedics, Anaheim, CA) in pressure mode on a Beckman dynograph (Sensormedics). The procedure has been described previously (10,ll). Data Acquisition Intraluminal pressure was measured from the transverse, splenic flexure, distal, and sigmoid colons. Basal activity was recorded for 60 minutes. The subject then consumed a 1000-kcal meal consisting of a white bread roast beef sandwich with mayonnaise and milk shake in less than 10 minutes, and the measurements were continued for an additional 128 minutes. Scintigraphic acquisition was continued during the entire duration of the manometric recording. The intraluminal pressure signals were acquired on a Hewlett Packard FM tape recorder [Model 3968; Hewlett-
1
I
1
I
I
1
0
15
30
45
60
75
TIME (MINUTES)
Figure 1. Effect of eating on colonic motility. There is a significant increase in postprandial MI in the descending and transverse colon in normal subjects [A-A) for the first 30 minutes after eating. The increase in motility in patients with moderate ulcerative colitis (O-O) is less than that in normal subjects. AUC, area under the curve.
November 1991
COLONIC MOTILITY AND TRANSIT IN ULCERATIVE COLITIS
Packard, San Diego, CA) via the Beckman dynograph or directly on a Compaq-386/20 personal computer system specifically developed for gut motility research [reference 14 and unpublished copyrighted computer work by S. N. Reddy). Contractile activity was digitally acquired on the personal computer at five samples per second after filtering the signal with a low-pass cutoff frequency of 2.0 Hz. The signals were then subjected to preprocessing (a) to compensate for gain changes performed during recording to avoid saturation of signals (b) to remove any temporal trends, and (c) to remove movement artifacts that were easily identified visually (14). The scintigraphic images were acquired on the gamma camera computer and were later transferred to the personal computer for further study (I 5).
1291
‘TRANSVERSE COLON A
\L
SPLEN IC FLEXURE
Data Analysis The pressure signals were analyzed for motility index (MI) as the average area under the curve per every 5 minutes. The baseline was defined as the minimum value for each 5 minutes of signal (11). From these data, MI for 15 minutes was calculated. The nature of gastrocolonic response was studied from l-minute MI, because the gastrocoionic response is well defined after the meal as a gradual increase and decrease in contractility (6). The times of occurrence and the amplitudes of propagating contractions before and after the meal were calculated on the computer. Propagation was defined as a contraction that propagated over at least three ports. Thus, because of the 15-cm distance between ports, the “global” propagation from one segment to the other was studied. Pressure gradients, i.e., the pressure differences, between splenic flexure and transverse colon and between splenic flexure and distal colon, were obtained on the computer and correlated visually with the tracer images (15). The transit images were analyzed for time activity in transverse and descending colons by defining an area of interest and summing the intensity levels in the area for each minute (11). The time activity curve, thus, provides a quantification of the amount of tracer, as a function of time, in the defined area. The transit times (t,,,) for emptying from the splenic flexure into the transverse and sigmoid colons were calculated on the gamma camera computer. The t,,, was calculated from the time for the tracer to reach maximum in the defined area after meal (10). The images were also displayed as a function of time by displaying them as a sequence of side by side on the personal computer for visual evaluation of (a) spread vs. time, i.e., to see into which colonic segment the tracer spread with time and to see retrograde or antegrade movement as seen from frame to frame; (b) ultimate movement defined as the segment of the colon into which the tracer moves over the duration of the study, e.g., sigmoid; (c) movement related to propagating contractions; i.e., sudden shifts in intensity of the tracer corresponding to a propagating contraction; and (d) to-and-fro movements defined as successive orad and aborad movements of the tracer (15). The images were also printed in seven gray levels. The tracer movements in relation to contractions were evaluated visually proximal and distal to the splenic flexure. The
DESCENDING COLON
SiGNOlD HEPATIC
B
FLEXURE
JL_r---,.2--J’.-
10mmHg[ 30
] set
COLON
TRANSVERSE
--AAJL-
DESCENDING
COLON ---yd
SIGMOID
i”?
COLON ._/--
Figure 2. Pressure signals. The nature of postprandial contractions in (A) normal subjects and (B) patients with ulcerative colitis is shown by the occurrence of mass contractions in healthy subjects and low-amplitude propagating contractions in ulcerative colitis, respectively.
1292
REDDY ET AL.
GASTROENTEROLOGY
Results
images were reproduced in black and white of varying gray levels, as per the intensity of the trace. All results were analyzed by a statistician unaware of the patient population and were subjected to statistical evaluation by nonparametric tests. The Wilcoxon signed-rank test was used to compare the differences between variables. The results were considered significant if P < 0.05. The values were expressed as means ? SEM.
time
Vol. 101. No. 5
Pressure Signals
All healthy subjects and patients with ulcerative colitis showed colonic pressure signals that were characterized by both tonic and phasic contractions. The phasic contractions were segmental, non-
(MN)
B
II/ IN II
2
2 ti
I
SPLENICFU%lJRE
2 ii 0 : .e x
I
-MNC
E
I
III
I/III
111
I
C.
b ‘Z P ‘5 0 b 2 a
SlCMOloc.
-30
1..1”1.‘,..,“1---1”1”1 -15 0 15
45
30 time
(MN)
60
75
90
105
Figure 3. Propagating contractions. The number and anatomic site of propagating contractions are shown for (A) 10 patients with ulcerative colitis and (B) 9 healthy subjects. There are more aborad propagating contractions before and after meal in patients with ulcerative colitis than in healthy subjects. Because of limited time scale here, some propagating contractions can be seen overlapped.
November
1991
COLONIC MOTILITY
propagating contractions as well as propagating contractions. Nonpropagating contractions. Eating increased nonpropagating contractions in both normal and ulcerative colitis subjects. However, the healthy subjects showed well-defined gastrocolonic response, whereas in ulcerative colitis the postprandial contractility was decreased in amplitude, with no clear-cut gastrocoionic response. Motility index. The MIS for the different regions of the colon in healthy subjects and in patients with ulcerative colitis are shown in Figure 1. In normal subjects, the postprandial MI increased in the transverse (67.0 k 1.8 mm Hg/15 min), descending (78.7 k 4.2 mm Hg/l5 min), and sigmoid (66.0 -+ 1.6 mm Hg/15 min) colons; the pressure in the descending colon was significantly greater than in the other regions of the colon (P < 0.03). This pressure gradient caused intraluminal contents to move proximally and distally from the splenic flexure, as discussed below. In ulcerative colitis, the postprandial MI was decreased in all regions of the colon compared with the healthy subjects but, still, was increased compared with preprandial MI. The pressure was significantly (P < 0.05) decreased in the descending colon (12.6 -C 0.3 mm Hg/l5 min) compared with healthy
AND TRANSIT
IN ULCERATIVE
COLITIS
1293
subjects. The largest increase in postprandial intraluminal pressure occurred in the sigmoid colon (38.0 2 12.0 mm H&5 min). There was no consistent pressure gradient among the different segments of the colon in ulcerative colitis. Propagating contractions. Eating stimulated propagating contractions in both healthy subjects and in patients with ulcerative colitis. Figure 2A shows a propagating mass contraction that occurred 30 minutes after meal in a healthy subject. These contractions propagated from the transverse colon to the descending colon, usually without passing into the rectum. There were one or two such contractions in the healthy subjects after a meal. In patients with colitis, the postprandial propagating contractions were decreased in amplitude compared with normal subjects (see Figure 2B). The amplitudes of the propagating contractions were significantly (P < 0.005) decreased in ulcerative colitis (14.2 ~fr2.3 mm Hg) in comparison with healthy subjects (23.4 L 1.4 mm Hg). Contractions propagated aborally in both normal subjects and patients with ulcerative colitis, with no orad propagation. As shown in Figure 3, the frequency of postprandial propagating contractions was significantly greater (P < 0.05) in ulcerative colitis (4.5 IT0.5/60 min) than in normal subjects (0.9 k 0.3/
30 Min Figure 4. Normal colonic scintigraphs. There is no movement of the tracer during fasting in healthy subjects, as can be seen from the frame taken 5 minutes before meal. The tracer has moved into both transverse and distal colons after the meal was eaten, shown here 30 minutes postprandially. Black represents the highest intensity level of the tracer; white represents no tracer.
GASTROENTEROLOGY Vol.101. No.5
1294 REDDYETAL.
60 min). The increased frequency of contractions was observed in patients with moderate disease activity rather than in patients with mild colitis. Scin tigraphy
As shown in Figure 4, there was little movement of the intraluminal tracer in healthy subjects during fasting. In eight of the nine healthy subjects, the tracer moved into both the descending and transverse colons only after the meal (Figure 4). In the other healthy subject, the movement was antegrade only into the descending colon. In patients with ulcerative colitis, the tracer movement from the splenic flexure was irregular both before and after the meal. In five patients, there was a significant aborad movement of the intraluminal contents during fasting. After the meal, the tracer (a) moved retrograde into the transverse colon and antegrade into the descending colon in two patients, (b) moved antegrade only into the sigmoid colon in four patients, and (c) remained in the splenic flexure in four patients. The antegrade movement of the tracer
in a patient with ulcerative colitis, both before and after the meal, is shown in Figure 5. The time-activity curves in normal subjects showed major antegrade and retrograde movements after eating the meal. The movement was greater into the descending than into the transverse colon (Figure 6A). On the other hand, the time-activity curves of patients with ulcerative colitis showed variability as discussed above. In the case of the patient whose scintigraphs are shown in Figure 5, there was no retrograde movement and the antegrade movement occurred both before and after the meal (Figure 64 into the transverse colon. Figure 7 shows the to-and-fro movements of the tracer that occurred between the splenic flexure and the sigmoid. This can be seen to result in a corresponding zigzag pattern in the time-activity curve (Figure 6B).
In ulcerative colitis, the t,,2 for emptying from the splenic flexure was shorter, hence more rapid, to the sigmoid colon (11.82 1.7minutes) than to the transverse colon (15.6k 4.9 minutes). Both of these times were longer, hence less rapid, than in healthy subjects
to 102 minutes after Figure 5. Sequence of colonic scintigraphs in ulcerative colitis starting from the time of instillation (top leftframe) instillation (bottom right frame) in increments of 3 minutes. The first frame shows the approximate locations of transverse (T), descending (D), and sigmoid (S) colons as well as the rectum (R); the tracer itself is located in the splenic flexure. M denotes meal (60 minutes after tracer instillation), and the numbers in frames refer to time in minutes after tracer instillation. The tracer has moved antegrade only in this patient: such movement occurred even before the meal. The effect of segmenting contractions and the tracer movement as a function of time can be seen in the various frames.
November
COLONIC
1991
120.
oar
MOTILITY
IN ULCERATIVE
COLITIS
1295
Normal
Time
Figure 6. Tie-activity
AND TRANSIT
in
Min
Meal
curves.
A. A healthy subject shows more tracer movement after the meal than before meal: the movement is more into the descending (Desc) colon than into the transverse (Tran) colon.
B. In the patient with ulcerative colitis, there is only antegrade movement into the sigmoid both before and after the meal, with no movement at all into the transverse colon. The zigzag pattern of the curve correlates with the to-and-fro movement of the tracer as shown in Figure 7.
I
B
* .oo
(7.6t 1.3 minutes into the transverse colon 5.4 -+0.6 minutes into the sigmoid colon).
Scintigraphy
2s. 00
and
and Pressure Signals
Propagating contractions (Figure 2) caused coincidental, rapid movement of intraluminal contents at a rate of 2.5 f 0.5 cm/s from the transverse colon to the rectum. Retrograde transit caused by orad propa-
79. M
so. 00
Time
in
I
1
I lM.00
Min
gating contraction never occurred in either the healthy subjects or the patients with ulcerative colitis. Although the propagating contractions in ulcerative colitis were low in magnitude, they caused a moving pressure gradient resulting in forward transit. On the other hand, segmental pressure differences pushed the contents retrograde. Figure 7 shows the movement of the tracer from the splenic flexure to the sigmoid caused by such to-and-fro movements.
1296
REDDY ET AL.
GASTROENTEROLOGY
Vol. 101. No. 5
Figure 7. To-and-fro movement. Propagating contractions and changes in pressure in a patient with ulcerative colitis are reflected as to-and-fro movement of the tracer with gradual, segmental movement of the tracer from the splenic flexure to the sigmoid colon (see also Figures 5 and 6B). Frame increment is 2 minutes. Black represents the highest intensity levels of the tracer; white represents no tracer.
I 15
Discussion No previous studies have correlated changes in postprandial colonic motility with transit in patients with ulcerative colitis. The simultaneous study of motility signals and scintigraphic images allows correlation of the motor pattern with the movement of intraluminal contents. The present study shows several disturbances in colonic motility that are associated with a variable pattern of transit in mild and moderate ulcerative colitis. Two types of intraluminal pressure occur in the colon: segmenting contractions and propagating contractions. Segmental changes in pressure are associated with a slow but gradual retrograde and antegrade transit of the luminal contents that depend on the pressure gradient between the neighboring segments (10,ll). Intraluminal contents move from the region of higher pressure to the lower one. Therefore, higher intraluminal pressures at the splenic flexure, compared with those in the transverse and sigmoid colons, result in both antegrade and retrograde movements of colonic contents (15). Retrograde transit into the transverse colon suggests that it acts as a mixing and storage area (10,11,16). Aborad propagating contractions were associated with rapid movement of intraluminal contents, because the amplitudes of such propagating contractions were greater than those of segmenting contractions. In healthy subjects, eating stimulates increased nonpropagating contractions in the colon; such contractions are greater in the descending colon and the splenic flexure than in other regions. However, there is no continuous high pressure in the descending colon that allows for the movement of the contents. The present study confirms previous reports that postprandial intraluminal pressure increases less in patients with ulcerative colitis than in healthy subjects (2,~). We have reported previously that the number of propagating contractions are decreased significantly in patients with constipation (11) and increased significantly in patients with functional
diarrhea (17). These data suggest that propagating contractions are associated with eventual evacuation. Postprandial propagating contractions appeared more frequently but with lower peak amplitudes in patients with ulcerative colitis than in normal subjects. There are no data on the origin of the colonic propagating contractions. However, it is possible that they are initiated in the colonic myenteric plexus (18). The increase in propagating contractions in patients with ulcerative colitis, similar to patients with funcsuggests that propagating contractional diarrhea (16), tions have some pathogenetic significance in the production of diarrhea. The variable pattern of transit in patients with ulcerative colitis provides further evidence for the significance of the propagating contractions in bringing about different patterns of transit. In patients with ulcerative colitis, the occurrence of multiple to-and-fro movements of the intraluminal contents may decrease the contact time for the contents with the mucosal wall. The decrease in mixing within the transverse colon and the decrease in the contact with the mucosa may exacerbate the secretory diarrhea. The tliz reflects the time for the net movement of the tracer to reach the sigmoid but is not an indication of the speed of the total movement of the intraluminal contents into the rectum. The increased to-and-fro movements observed in ulcerative colitis may decrease t1,2by pushing the intraluminal contents back into the splenic flexure, without, however, affecting the overall transit time into the rectum. In conclusion, because reduced colonic motility is associated with diarrhea and increased motility with constipation (5,19), the decreased contractility, coupled with variable transit, shown in the present study may accentuate the symptoms of diarrhea in ulcerative colitis. Therefore, restoration of normal motility patterns in ulcerative colitis may provide symptomatic relief.
November
1991
COLONIC
References CD. Studies 1. Rao SSC. Read NW, Brown C, Bruce C, Holdsworth on the mechanism of bowel disturbance in ulcerative colitis. Gastroenterology 1987;93:938-944. JP, Geffry Y, Heckersweiler PH. 2. Denis Ph, Colin P, Galmiche Lefrancois R. Pasquis P. Loss of rectal distensibility in active colitis. Gastroenterology 1979;77:45-48. MD. The motility of 3. Kerns F Jr, Almy TP. Abbot IX, Bogodonoff the distal colon in non-specific ulcerative colitis. Gastroenterology 1951;19:492-503. 4. Spriggs EA, Code CF, Bargen JA, Curtis RK, Hightower BA Jr. Motility of the pelvic colon and rectum of normal persons and patients with ulcerative colitis. Gastroenterology 1951;19:480491. 5. Connell 6.
7. 8.
9.
10.
11.
12.
13.
AM. The motility of the pelvic colon. Part 2. Paradoxical motility in diarrhea and constipation. Gut 1962;3:342-348. Snape WJ Jr. Mararazzo SA, Cohen S. Effect of eating and gastrointestinal hormones on human colonic myoelectric and motor activity. Gastroenterology 1987;75:373-378. Tansy MF. Kendall FM. Experimental and clinical aspects of gastrocolonic reflexes. Am J Dig Dis 1973;18:521-531, Snape WJ Jr, Mararazzo SA. Cohen S. Abnormal gastrocolonic response in patients with ulcerative colitis. Gut 1981;21:392396. Snape WJ Jr, Williams R, Mayer EA, Root D. Disturbance in colonic contraction in colonic muscle removed from patients with ulcerative colitis (abstr). Gastroenterology 1987;92:1648. Moreno-Osset M, Bazzocchi G, Lo S, Trobley B. Ristow E, Reddy SN, V-Meyer J. Fain JW, Jing J, Mena I. Snape WJ Jr. Association between postprandial changes in colonic intraluminal pressure and transit. Gastroenterology 1989;96:1265-1273. Bazzocchi G, Ellis J. V-Meyer J, Jing J, Reddy SN, Mena I, Snape WJ Jr. Postprandial colonic transit and motor activity in chronic constipation. Gastroenterology 1990:98:686-693. Helzer JE, Stilling A, Chammas S, Norland CC, Alpers DH. A controlled study of the association between ulcerative colitis and psychiatric diagnosis. Dig Dis Sci 1982;27:512-518, Pera A, Bellando B, Caldera D, Ponti M, Astegiano M, Barletti C. David E. Arrigioni A, Rota G. Verne G. Colonoscopy in
MOTILITY
inflammatory
AND TRANSIT
bowel
disease.
IN ULCERATIVE
Gastroenterology
COLITIS
1297
1987:92:181-
185. SN. Biomedical signal processing on the personal 14. Reddy computer. Proc Annu Conf IEEE Eng Med Biol Sot 1987:12191221. 15. Reddy
SN. Di Lorenzo C. Yanni G, Bazzocchi G. V-Meyer J. Mena I. Hyman PE, Snape WJ Jr. A unified approach to the study of colonic scintigraphy and intraluminal pressure (abstr). Gastroenterology 1990;98:A383.
16. Bazzocchi
G. Snape WJ Jr, Reddy SN, Lanfranchi GA. Relationship between colonic motility and transit in functional diarrhea. Procedures of the 12th International Symposium on Gastrointestinal Motility, Gmunden, Austria, September 1989. 17. Bazzocchi G, Ellis J, V-Meyer J. Reddy SN, Mena I, Snape WJ Jr. Effect of eating on colonic motility and transit in patients with functional diarrhea: simultaneous scintigraphic and manometric evaluation. Gastroenterology 1991;101:1298-1306. 18. Narducci F, Bassotti G. Daniotti S. Soldato P, Pelli M. Morelli A. Identification of muscarinic receptor subtypes mediating colonic
response to eating. Dig Dis Sci 1985;30:124-128. SL, Misiewicz JJ, Kiley N. Effect of eating on motility of the pelvic colon in constipation and diarrhea. Gut 1972:13:805811.
19. Waller
Received March 13, 1990. Accepted June 14,199l. Address requests for reprints to: S. Narasimha Reddy, Eng., 1124 W. Carson Street, Cl Trailer. Harbor-IJCLA Center. Torrance, California 90502. The results of this study were presented Gastroenterological Association meeting
Ph.D., P. Medical
in part at the American in Washington, D.C., in
May 1989. Supported in part by the Inflammatory Bowel Disease Center and in part by UCLA-Harbor Collegium Research Award to S. Narasimha Reddy. The authors thank Dr. Paul E. Hyman for critical comments that enhanced the manuscript and Jenny Jing for help with statistical analysis.
1991;101:1289-1297
Colonic Motility and Transit in Health and Ulcerative Colitis S. NARASIMHA KATHY
AKASHI,
ISMAEL
MENA,
REDDY, JAVIER
GABRIELE
BAZZOCCHI,
and WILLIAM
J. SNAPE,
Preprandial and postprandial colonic motility and transit (scintigraphy), with respect to the splenic flexure, were studied in 10 patients with ulcerative colitis and in 9 healthy subjects. The healthy subjects had a postprandial increase in intraluminal pressure that was significantly (P < 0.03) greater in the descending colon than in other regions of the colon. In ulcerative colitis, the pressure was decreased in all regions compared with healthy subjects, with no significant pressure gradient among different regions. In normal subjects, transit was quiescent during fasting; eating stimulated both antegrade and retrograde transit. In ulcerative colitis, transit was variable before as well as after the meal. Both healthy subjects and patients with ulcerative colitis had more rapid emptying from the splenic flexure into the sigmoid than into the transverse colon. More frequent, low-amplitude, postprandial propagating contractions occurred in ulcerative colitis (P < 0.05) than in healthy subjects. Propagating contractions were always antegrade and caused a rapid movement of the tracer into tbe sigmoid. In conclusion, ulcerative colitis is characterized by (a) decreased contractility, (b) increased low-amplitude propagating contractions, and (c) variable transit. These disturbances may accentuate the diarrhea in ulcerative colitis.
he diarrhea in ulcerative colitis is associated with increased secretion caused by mucosal inflammation. However, changes in contractility may also contribute to increased stool frequency (a] by means of decreased segmental contractions that lead to lower impedance to luminal transit or (b) by means of increased aborad propagating contractions that lead to antegrade propulsion of intraluminal contents. Some studies have suggested that the diarrhea in ulcerative colitis is caused by rectosigmoid inflamma-
GEORGE
CHAN, YANNI,
Jr.
Departments of Medicine and Nuclear Medicine and Inflammatory Harbor-UCLA Medical Center, Torrance, California
T
SIMON
VILLANUEVA-MEYER,
Bowel Disease Center.
tion and irritability rather than by rapid transit (1,2). However, colonic contractility is decreased in patients with active inflammation (3,4). Connell (5) hypothesized that segmenting contractions impede the forward movement of colonic contents. Thus, a decrease in segmental contractions in ulcerative colitis would exacerbate the diarrhea. In healthy subjects, eating results in increased nonpropagating colonic contractions in all segments of the colon (6,7). This gastrocolonic response is diminished in patients with ulcerative colitis (8). Reduced postprandial colonic contractile activity in patients with active ulcerative colitis or functional diarrhea (4,8) may be secondary to a defect in either myogenic function or neural control (8). In vitro studies suggest a defect in the smooth muscle at the biochemical level that results in decreased force development in the colonic muscle of patients with ulcerative colitis (9). We have recently developed techniques to measure the transit of intraluminal contents simultaneously with colonic pressure (10,ll). In this study we applied these techniques (a) to elucidate the underlying motility pattern that leads to decreased colonic motility and increased frequency of stools, (b) to understand the nature of colonic transit, and (c) to correlate transit with motility in ulcerative colitis. Materials
and Methods
Subjects Nine healthy subjects who had no previous gastrointestinal symptoms served as controls. The group in-
Abbreviations used in this paper: MI, motility index; DTPA, diethylenl triaminepentaacetic acid. 0 1991 by tbe American Gastroenterological Association 0016-5085/91/$3.00
1290 REDDYET AL.
GASTROENTEROLOGYVol.1O1.No.5
eluded eight men and one woman ranging in age from 21 to 56 years. Normal subjects had been defined as those with more than three stools per week or less than three stools per day. Ten patients referred to the Inflammatory Bowel Disease Center, Harbor-UCLA Medical Center, with moderate or mild left-sided ulcerative colitis were studied. The patients consisted of six men and four women ranging in age from 27 to 54 years. Patients with severe ulcerative colitis were not recruited for the study, because such patients are unable to eat. Patients with mild colitis (three men and one woman) had one to three stools per day, with or without blood in the stools. Patients with moderate ulcerative colitis (three men and three women) had more than five stools per day, often with blood (12). The extent of clinical involvement and degree of inflammation of the colon were characterized by endoscopy and biopsy (13). Informed, written consent was obtained from each subject, and the study was approved by the Harbor-UCLA Human Subjects Committee Methods All patients consumed a clear liquid diet for 24 hours and fasted 12 hours before the study. The colon was prepared by having the subjects drink 1 gal (3.785L) of a balanced electrolyte solution (Colyte; Reed and Carnrick, Piscataway, NJ) the day before to facilitate the placement of the pressure catheter into the colon and to minimize the effect of colonic contents on recorded signals. A polyvinyl open-tipped catheter, with eight pressure ports spaced 15 cm apart, (ID, 0.8 mm; OD, 1 mm) was used to record intraluminal pressure and to instill the radionuclide marker, technetium Tc 99m. The catheter was introduced into the transverse colon over a guide-wire by means of a flexible colonoscope; no sedation was used.
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-15
The subjects were placed in a supine position under a gamma camera (Pho/Gamma HP: Nuclear Chicago, Chicago, IL), and the position of the catheter was confirmed on the persistence oscilloscope of the gamma camera by instilling 2 mL normal saline containing 1 mCi of g9mTc-diethylenetriaminepentaacetic acid (DTPA) into each port and withdrawing it. Once in position, the catheter was securely taped to the subject’s thigh. A 5-mCi dose of 99mTc-DTPA was instilled into the splenic flexure as the bolus. The tracer movement was measured as scintigraphic images acquired every 1 minute and recorded as 64 x 64 matrices of 256 grey levels on a dedicated computer (Sopha Medical Computer, Baltimore, MD). The pressure ports were continuously perfused with distilled water at 6.5 mL/min using a low-compliance capillary system (Arndorfer Medical Specialities; Greendale, WI). The pressure transducers (Model P231A; Stratham Instruments, Oxnard, CA) were connected to Beckman couplers (Model 9853A; Sensormedics, Anaheim, CA) in pressure mode on a Beckman dynograph (Sensormedics). The procedure has been described previously (10,ll). Data Acquisition Intraluminal pressure was measured from the transverse, splenic flexure, distal, and sigmoid colons. Basal activity was recorded for 60 minutes. The subject then consumed a 1000-kcal meal consisting of a white bread roast beef sandwich with mayonnaise and milk shake in less than 10 minutes, and the measurements were continued for an additional 128 minutes. Scintigraphic acquisition was continued during the entire duration of the manometric recording. The intraluminal pressure signals were acquired on a Hewlett Packard FM tape recorder [Model 3968; Hewlett-
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0
15
30
45
60
75
TIME (MINUTES)
Figure 1. Effect of eating on colonic motility. There is a significant increase in postprandial MI in the descending and transverse colon in normal subjects [A-A) for the first 30 minutes after eating. The increase in motility in patients with moderate ulcerative colitis (O-O) is less than that in normal subjects. AUC, area under the curve.
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COLONIC MOTILITY AND TRANSIT IN ULCERATIVE COLITIS
Packard, San Diego, CA) via the Beckman dynograph or directly on a Compaq-386/20 personal computer system specifically developed for gut motility research [reference 14 and unpublished copyrighted computer work by S. N. Reddy). Contractile activity was digitally acquired on the personal computer at five samples per second after filtering the signal with a low-pass cutoff frequency of 2.0 Hz. The signals were then subjected to preprocessing (a) to compensate for gain changes performed during recording to avoid saturation of signals (b) to remove any temporal trends, and (c) to remove movement artifacts that were easily identified visually (14). The scintigraphic images were acquired on the gamma camera computer and were later transferred to the personal computer for further study (I 5).
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‘TRANSVERSE COLON A
\L
SPLEN IC FLEXURE
Data Analysis The pressure signals were analyzed for motility index (MI) as the average area under the curve per every 5 minutes. The baseline was defined as the minimum value for each 5 minutes of signal (11). From these data, MI for 15 minutes was calculated. The nature of gastrocolonic response was studied from l-minute MI, because the gastrocoionic response is well defined after the meal as a gradual increase and decrease in contractility (6). The times of occurrence and the amplitudes of propagating contractions before and after the meal were calculated on the computer. Propagation was defined as a contraction that propagated over at least three ports. Thus, because of the 15-cm distance between ports, the “global” propagation from one segment to the other was studied. Pressure gradients, i.e., the pressure differences, between splenic flexure and transverse colon and between splenic flexure and distal colon, were obtained on the computer and correlated visually with the tracer images (15). The transit images were analyzed for time activity in transverse and descending colons by defining an area of interest and summing the intensity levels in the area for each minute (11). The time activity curve, thus, provides a quantification of the amount of tracer, as a function of time, in the defined area. The transit times (t,,,) for emptying from the splenic flexure into the transverse and sigmoid colons were calculated on the gamma camera computer. The t,,, was calculated from the time for the tracer to reach maximum in the defined area after meal (10). The images were also displayed as a function of time by displaying them as a sequence of side by side on the personal computer for visual evaluation of (a) spread vs. time, i.e., to see into which colonic segment the tracer spread with time and to see retrograde or antegrade movement as seen from frame to frame; (b) ultimate movement defined as the segment of the colon into which the tracer moves over the duration of the study, e.g., sigmoid; (c) movement related to propagating contractions; i.e., sudden shifts in intensity of the tracer corresponding to a propagating contraction; and (d) to-and-fro movements defined as successive orad and aborad movements of the tracer (15). The images were also printed in seven gray levels. The tracer movements in relation to contractions were evaluated visually proximal and distal to the splenic flexure. The
DESCENDING COLON
SiGNOlD HEPATIC
B
FLEXURE
JL_r---,.2--J’.-
10mmHg[ 30
] set
COLON
TRANSVERSE
--AAJL-
DESCENDING
COLON ---yd
SIGMOID
i”?
COLON ._/--
Figure 2. Pressure signals. The nature of postprandial contractions in (A) normal subjects and (B) patients with ulcerative colitis is shown by the occurrence of mass contractions in healthy subjects and low-amplitude propagating contractions in ulcerative colitis, respectively.
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GASTROENTEROLOGY
Results
images were reproduced in black and white of varying gray levels, as per the intensity of the trace. All results were analyzed by a statistician unaware of the patient population and were subjected to statistical evaluation by nonparametric tests. The Wilcoxon signed-rank test was used to compare the differences between variables. The results were considered significant if P < 0.05. The values were expressed as means ? SEM.
time
Vol. 101. No. 5
Pressure Signals
All healthy subjects and patients with ulcerative colitis showed colonic pressure signals that were characterized by both tonic and phasic contractions. The phasic contractions were segmental, non-
(MN)
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SPLENICFU%lJRE
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-MNC
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b ‘Z P ‘5 0 b 2 a
SlCMOloc.
-30
1..1”1.‘,..,“1---1”1”1 -15 0 15
45
30 time
(MN)
60
75
90
105
Figure 3. Propagating contractions. The number and anatomic site of propagating contractions are shown for (A) 10 patients with ulcerative colitis and (B) 9 healthy subjects. There are more aborad propagating contractions before and after meal in patients with ulcerative colitis than in healthy subjects. Because of limited time scale here, some propagating contractions can be seen overlapped.
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1991
COLONIC MOTILITY
propagating contractions as well as propagating contractions. Nonpropagating contractions. Eating increased nonpropagating contractions in both normal and ulcerative colitis subjects. However, the healthy subjects showed well-defined gastrocolonic response, whereas in ulcerative colitis the postprandial contractility was decreased in amplitude, with no clear-cut gastrocoionic response. Motility index. The MIS for the different regions of the colon in healthy subjects and in patients with ulcerative colitis are shown in Figure 1. In normal subjects, the postprandial MI increased in the transverse (67.0 k 1.8 mm Hg/15 min), descending (78.7 k 4.2 mm Hg/l5 min), and sigmoid (66.0 -+ 1.6 mm Hg/15 min) colons; the pressure in the descending colon was significantly greater than in the other regions of the colon (P < 0.03). This pressure gradient caused intraluminal contents to move proximally and distally from the splenic flexure, as discussed below. In ulcerative colitis, the postprandial MI was decreased in all regions of the colon compared with the healthy subjects but, still, was increased compared with preprandial MI. The pressure was significantly (P < 0.05) decreased in the descending colon (12.6 -C 0.3 mm Hg/l5 min) compared with healthy
AND TRANSIT
IN ULCERATIVE
COLITIS
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subjects. The largest increase in postprandial intraluminal pressure occurred in the sigmoid colon (38.0 2 12.0 mm H&5 min). There was no consistent pressure gradient among the different segments of the colon in ulcerative colitis. Propagating contractions. Eating stimulated propagating contractions in both healthy subjects and in patients with ulcerative colitis. Figure 2A shows a propagating mass contraction that occurred 30 minutes after meal in a healthy subject. These contractions propagated from the transverse colon to the descending colon, usually without passing into the rectum. There were one or two such contractions in the healthy subjects after a meal. In patients with colitis, the postprandial propagating contractions were decreased in amplitude compared with normal subjects (see Figure 2B). The amplitudes of the propagating contractions were significantly (P < 0.005) decreased in ulcerative colitis (14.2 ~fr2.3 mm Hg) in comparison with healthy subjects (23.4 L 1.4 mm Hg). Contractions propagated aborally in both normal subjects and patients with ulcerative colitis, with no orad propagation. As shown in Figure 3, the frequency of postprandial propagating contractions was significantly greater (P < 0.05) in ulcerative colitis (4.5 IT0.5/60 min) than in normal subjects (0.9 k 0.3/
30 Min Figure 4. Normal colonic scintigraphs. There is no movement of the tracer during fasting in healthy subjects, as can be seen from the frame taken 5 minutes before meal. The tracer has moved into both transverse and distal colons after the meal was eaten, shown here 30 minutes postprandially. Black represents the highest intensity level of the tracer; white represents no tracer.
GASTROENTEROLOGY Vol.101. No.5
1294 REDDYETAL.
60 min). The increased frequency of contractions was observed in patients with moderate disease activity rather than in patients with mild colitis. Scin tigraphy
As shown in Figure 4, there was little movement of the intraluminal tracer in healthy subjects during fasting. In eight of the nine healthy subjects, the tracer moved into both the descending and transverse colons only after the meal (Figure 4). In the other healthy subject, the movement was antegrade only into the descending colon. In patients with ulcerative colitis, the tracer movement from the splenic flexure was irregular both before and after the meal. In five patients, there was a significant aborad movement of the intraluminal contents during fasting. After the meal, the tracer (a) moved retrograde into the transverse colon and antegrade into the descending colon in two patients, (b) moved antegrade only into the sigmoid colon in four patients, and (c) remained in the splenic flexure in four patients. The antegrade movement of the tracer
in a patient with ulcerative colitis, both before and after the meal, is shown in Figure 5. The time-activity curves in normal subjects showed major antegrade and retrograde movements after eating the meal. The movement was greater into the descending than into the transverse colon (Figure 6A). On the other hand, the time-activity curves of patients with ulcerative colitis showed variability as discussed above. In the case of the patient whose scintigraphs are shown in Figure 5, there was no retrograde movement and the antegrade movement occurred both before and after the meal (Figure 64 into the transverse colon. Figure 7 shows the to-and-fro movements of the tracer that occurred between the splenic flexure and the sigmoid. This can be seen to result in a corresponding zigzag pattern in the time-activity curve (Figure 6B).
In ulcerative colitis, the t,,2 for emptying from the splenic flexure was shorter, hence more rapid, to the sigmoid colon (11.82 1.7minutes) than to the transverse colon (15.6k 4.9 minutes). Both of these times were longer, hence less rapid, than in healthy subjects
to 102 minutes after Figure 5. Sequence of colonic scintigraphs in ulcerative colitis starting from the time of instillation (top leftframe) instillation (bottom right frame) in increments of 3 minutes. The first frame shows the approximate locations of transverse (T), descending (D), and sigmoid (S) colons as well as the rectum (R); the tracer itself is located in the splenic flexure. M denotes meal (60 minutes after tracer instillation), and the numbers in frames refer to time in minutes after tracer instillation. The tracer has moved antegrade only in this patient: such movement occurred even before the meal. The effect of segmenting contractions and the tracer movement as a function of time can be seen in the various frames.
November
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120.
oar
MOTILITY
IN ULCERATIVE
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Normal
Time
Figure 6. Tie-activity
AND TRANSIT
in
Min
Meal
curves.
A. A healthy subject shows more tracer movement after the meal than before meal: the movement is more into the descending (Desc) colon than into the transverse (Tran) colon.
B. In the patient with ulcerative colitis, there is only antegrade movement into the sigmoid both before and after the meal, with no movement at all into the transverse colon. The zigzag pattern of the curve correlates with the to-and-fro movement of the tracer as shown in Figure 7.
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B
* .oo
(7.6t 1.3 minutes into the transverse colon 5.4 -+0.6 minutes into the sigmoid colon).
Scintigraphy
2s. 00
and
and Pressure Signals
Propagating contractions (Figure 2) caused coincidental, rapid movement of intraluminal contents at a rate of 2.5 f 0.5 cm/s from the transverse colon to the rectum. Retrograde transit caused by orad propa-
79. M
so. 00
Time
in
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Min
gating contraction never occurred in either the healthy subjects or the patients with ulcerative colitis. Although the propagating contractions in ulcerative colitis were low in magnitude, they caused a moving pressure gradient resulting in forward transit. On the other hand, segmental pressure differences pushed the contents retrograde. Figure 7 shows the movement of the tracer from the splenic flexure to the sigmoid caused by such to-and-fro movements.
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GASTROENTEROLOGY
Vol. 101. No. 5
Figure 7. To-and-fro movement. Propagating contractions and changes in pressure in a patient with ulcerative colitis are reflected as to-and-fro movement of the tracer with gradual, segmental movement of the tracer from the splenic flexure to the sigmoid colon (see also Figures 5 and 6B). Frame increment is 2 minutes. Black represents the highest intensity levels of the tracer; white represents no tracer.
I 15
Discussion No previous studies have correlated changes in postprandial colonic motility with transit in patients with ulcerative colitis. The simultaneous study of motility signals and scintigraphic images allows correlation of the motor pattern with the movement of intraluminal contents. The present study shows several disturbances in colonic motility that are associated with a variable pattern of transit in mild and moderate ulcerative colitis. Two types of intraluminal pressure occur in the colon: segmenting contractions and propagating contractions. Segmental changes in pressure are associated with a slow but gradual retrograde and antegrade transit of the luminal contents that depend on the pressure gradient between the neighboring segments (10,ll). Intraluminal contents move from the region of higher pressure to the lower one. Therefore, higher intraluminal pressures at the splenic flexure, compared with those in the transverse and sigmoid colons, result in both antegrade and retrograde movements of colonic contents (15). Retrograde transit into the transverse colon suggests that it acts as a mixing and storage area (10,11,16). Aborad propagating contractions were associated with rapid movement of intraluminal contents, because the amplitudes of such propagating contractions were greater than those of segmenting contractions. In healthy subjects, eating stimulates increased nonpropagating contractions in the colon; such contractions are greater in the descending colon and the splenic flexure than in other regions. However, there is no continuous high pressure in the descending colon that allows for the movement of the contents. The present study confirms previous reports that postprandial intraluminal pressure increases less in patients with ulcerative colitis than in healthy subjects (2,~). We have reported previously that the number of propagating contractions are decreased significantly in patients with constipation (11) and increased significantly in patients with functional
diarrhea (17). These data suggest that propagating contractions are associated with eventual evacuation. Postprandial propagating contractions appeared more frequently but with lower peak amplitudes in patients with ulcerative colitis than in normal subjects. There are no data on the origin of the colonic propagating contractions. However, it is possible that they are initiated in the colonic myenteric plexus (18). The increase in propagating contractions in patients with ulcerative colitis, similar to patients with funcsuggests that propagating contractional diarrhea (16), tions have some pathogenetic significance in the production of diarrhea. The variable pattern of transit in patients with ulcerative colitis provides further evidence for the significance of the propagating contractions in bringing about different patterns of transit. In patients with ulcerative colitis, the occurrence of multiple to-and-fro movements of the intraluminal contents may decrease the contact time for the contents with the mucosal wall. The decrease in mixing within the transverse colon and the decrease in the contact with the mucosa may exacerbate the secretory diarrhea. The tliz reflects the time for the net movement of the tracer to reach the sigmoid but is not an indication of the speed of the total movement of the intraluminal contents into the rectum. The increased to-and-fro movements observed in ulcerative colitis may decrease t1,2by pushing the intraluminal contents back into the splenic flexure, without, however, affecting the overall transit time into the rectum. In conclusion, because reduced colonic motility is associated with diarrhea and increased motility with constipation (5,19), the decreased contractility, coupled with variable transit, shown in the present study may accentuate the symptoms of diarrhea in ulcerative colitis. Therefore, restoration of normal motility patterns in ulcerative colitis may provide symptomatic relief.
November
1991
COLONIC
References CD. Studies 1. Rao SSC. Read NW, Brown C, Bruce C, Holdsworth on the mechanism of bowel disturbance in ulcerative colitis. Gastroenterology 1987;93:938-944. JP, Geffry Y, Heckersweiler PH. 2. Denis Ph, Colin P, Galmiche Lefrancois R. Pasquis P. Loss of rectal distensibility in active colitis. Gastroenterology 1979;77:45-48. MD. The motility of 3. Kerns F Jr, Almy TP. Abbot IX, Bogodonoff the distal colon in non-specific ulcerative colitis. Gastroenterology 1951;19:492-503. 4. Spriggs EA, Code CF, Bargen JA, Curtis RK, Hightower BA Jr. Motility of the pelvic colon and rectum of normal persons and patients with ulcerative colitis. Gastroenterology 1951;19:480491. 5. Connell 6.
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AM. The motility of the pelvic colon. Part 2. Paradoxical motility in diarrhea and constipation. Gut 1962;3:342-348. Snape WJ Jr. Mararazzo SA, Cohen S. Effect of eating and gastrointestinal hormones on human colonic myoelectric and motor activity. Gastroenterology 1987;75:373-378. Tansy MF. Kendall FM. Experimental and clinical aspects of gastrocolonic reflexes. Am J Dig Dis 1973;18:521-531, Snape WJ Jr, Mararazzo SA. Cohen S. Abnormal gastrocolonic response in patients with ulcerative colitis. Gut 1981;21:392396. Snape WJ Jr, Williams R, Mayer EA, Root D. Disturbance in colonic contraction in colonic muscle removed from patients with ulcerative colitis (abstr). Gastroenterology 1987;92:1648. Moreno-Osset M, Bazzocchi G, Lo S, Trobley B. Ristow E, Reddy SN, V-Meyer J. Fain JW, Jing J, Mena I. Snape WJ Jr. Association between postprandial changes in colonic intraluminal pressure and transit. Gastroenterology 1989;96:1265-1273. Bazzocchi G, Ellis J. V-Meyer J, Jing J, Reddy SN, Mena I, Snape WJ Jr. Postprandial colonic transit and motor activity in chronic constipation. Gastroenterology 1990:98:686-693. Helzer JE, Stilling A, Chammas S, Norland CC, Alpers DH. A controlled study of the association between ulcerative colitis and psychiatric diagnosis. Dig Dis Sci 1982;27:512-518, Pera A, Bellando B, Caldera D, Ponti M, Astegiano M, Barletti C. David E. Arrigioni A, Rota G. Verne G. Colonoscopy in
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inflammatory
AND TRANSIT
bowel
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185. SN. Biomedical signal processing on the personal 14. Reddy computer. Proc Annu Conf IEEE Eng Med Biol Sot 1987:12191221. 15. Reddy
SN. Di Lorenzo C. Yanni G, Bazzocchi G. V-Meyer J. Mena I. Hyman PE, Snape WJ Jr. A unified approach to the study of colonic scintigraphy and intraluminal pressure (abstr). Gastroenterology 1990;98:A383.
16. Bazzocchi
G. Snape WJ Jr, Reddy SN, Lanfranchi GA. Relationship between colonic motility and transit in functional diarrhea. Procedures of the 12th International Symposium on Gastrointestinal Motility, Gmunden, Austria, September 1989. 17. Bazzocchi G, Ellis J, V-Meyer J. Reddy SN, Mena I, Snape WJ Jr. Effect of eating on colonic motility and transit in patients with functional diarrhea: simultaneous scintigraphic and manometric evaluation. Gastroenterology 1991;101:1298-1306. 18. Narducci F, Bassotti G. Daniotti S. Soldato P, Pelli M. Morelli A. Identification of muscarinic receptor subtypes mediating colonic
response to eating. Dig Dis Sci 1985;30:124-128. SL, Misiewicz JJ, Kiley N. Effect of eating on motility of the pelvic colon in constipation and diarrhea. Gut 1972:13:805811.
19. Waller
Received March 13, 1990. Accepted June 14,199l. Address requests for reprints to: S. Narasimha Reddy, Eng., 1124 W. Carson Street, Cl Trailer. Harbor-IJCLA Center. Torrance, California 90502. The results of this study were presented Gastroenterological Association meeting
Ph.D., P. Medical
in part at the American in Washington, D.C., in
May 1989. Supported in part by the Inflammatory Bowel Disease Center and in part by UCLA-Harbor Collegium Research Award to S. Narasimha Reddy. The authors thank Dr. Paul E. Hyman for critical comments that enhanced the manuscript and Jenny Jing for help with statistical analysis.
