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Intrajejunal capsaicin causes pain in the human jejenum
A760 AGA ABSTRACTS
GASTROENTEROLOGY Vol. 114, No. 4
G3132 FREQUENCY AND DURATION OF SYMPTOMS IN PATIENTS WITH IRRITABLE BOWEL SYNDROME (IBS). B. Hahn, RTP, NC; M. Watson, RTP, NC; D. Gunput, Greenford UK; J. Heuijerjans, Zeist, The Netherlands; S Yan, RTP, NC. Although patients with IBS often describe periods of symptoms alternating with quiescent periods, few studies have prospectively documented symptom patterns. The purpose of this study was to determine the frequency and duration of IBS symptoms over a 12-week period using a daily telephone data entry system. Patients 18 years or older with a diagnosis of IBS based on the Rome criteria were recruited from ambulatory care centers/hospitals and physician offices in the US, UK, and The Netherlands for an observational diary study. A total of 122 patients entered the study; those with diary reports on 70 or more days (N=59) were included in the analysis. As part of a larger survey, patients recorded whether they experienced each of the following symptoms: abdominal pain/discomfort, bloating, altered stool form, altered stool passage, and mucus. The sample was predominantly female (78%), and the average age was 49. The frequency distribution of the proportion of days with at least one symptom is shown below: Percent of reported days 80- I00 60 - 79 40 - 59 20 - 39 0- 19
Percent of total 23.8 18.7 23.8 22.1 11.9
The average proportion of reported days on which subjects experienced individual symptoms was as follows: pain/discomfort 32.8% bloating 28.0%, altered stool form 24.8%, altered stool passage 17.9%, and mucus 6.5%. Symptom patterns were further characterized by examining the number of episodes, which were defined as periods of consecutive days during which one or more symptoms were reported, bounded by at least one day (24 hours) of no symptoms. Patients in our sample experienced between 1 and 24 episodes, with 78% reporting 10-20 episodes over the course of the 12-week study. The median episode duration was 2.4 days; median duration for days without symptoms was 2.5 days. These results suggest that IBS is best characterized as a chronic illness with frequently recurring symptoms. This research was funded by Glaxo Wellcome. G3133 THE DEMOGRAPHY OF IRRITABLE BOWEL SUFFERERS WITH CO-EXISTING DEPRESSION. EM Hallyburton, AM Veitch, MJG Farthing. Digestive Diseases Research Centre, St Bartholomew's & The Royal London School of Medicine & Dentistry, London, UK. Introduction and aims: Irritable bowel syndrome (IBS) and depression commonly co-exist. As part of the recruitment process for a trial investigating the use of an antidepressant in patients with co-existing IBS and depression, a radio advertisement was used to contact subjects with both of these conditions in the community in London. The aim of this study was to characterise the population of respondents to the advertisement who considered themselves to suffer from IBS co-existent with depression Patients and methods: A radio advertisement seeking subjects with IBS and depression was transmitted on a London-wide radio station for 7 days. Respondents who replied by telephone were then sent a brief questionnaire which included the ICD-10 diagnostic criteria for depression. Further questionnaires were sent including ICD-10 criteria, Rome criteria for IBS and demographic profiles. Results: 384 responded to the radio advertisement. 241 (62.7%) responded to the first questionnaire of whom 234 (97%) met the ICD-10 criteria for depression. 34 (14.1%) had mild depression, 134 (55.6%) had moderate depression, and 66 (27.3%) had severe depression. All depressed subjects fulfilled Rome criteria for IBS. To date, 224 (58.3%) have responded to the second questionnaire. 215 (95.9%) met criteria for IBS and 214 (95.5%) were depressed. 60 (26.8%) had mild depression, 120 (53.6%) had moderate depression and 34 (15.2%) had severe depression. All respondents were grouped according to social class, A,B,CI, 42.4% and C2,D,E, 57.6% compared to the demographics of radio station listeners social class A,B,C1, 58.5% and C2,D,E, 41.5%; p<0.0001. Respondents not in full time employment were A,B,C 1 20 (21%) and C2,D,E were 34 (26%); p=0.4. Conclusions: IBS sufferers, with depression, within the community correctly assign their abdominal symptoms to IBS and clearly recognis e their depressive symptoms as judged by ICD-10 criteria. The respondents were predominantly in the lower social classes in contrast to the predominance of upper social classes in the radio station listener population. These findings may have relevance for the management of these conditions in primary care. • G3134 IDENTIFICATION OF TIlE CEREBRAL LOCI PROCESSING HUMAN SWALLOWING FUNCTION: A H20 TMPET ACTIVATION STUDY. S. Hamdy*t, J. C. Rothwell*, D. J. Brooks:[:, tQ. Aziz, "~D. G. Thompson. *MRC Human Movement & Balance Unit, Institute of Neurology, London, tDept of Gastroenterology, Hope Hospital, University of Manchester & :~MRC Cyclotron Unit, Hammersmith Hospital, London, UK. Background: Using transcranial magneto-electric stimulation we have recently demonstrated that the cortico-fugai pathways to human swallowing
musculature can be mapped to motor and premotor cortex (Nature Med. 1996; 2(11):1217-1224). However, little is known about the functional organisation of the cerebral regions active during normal volitional swallowing. Aims: To determine the cerebral loci which process human volitional swallowing function. Methods: Six healthy right handed male volunteers (mean age 41 yrs, age range 35-49 yrs) were studied using O 15 labeled water PET activation imaging. A randomised 12 scan paradigm was performed in each subject during the conditions of: i, rest and ii. water swallows (5ml/bolus, continuous infusion) at frequencies of 0.1, 0.2 and 0.3 Hz, visually cued and monitored using submental EMG. Group and individual parametric covariate analysis was performed (SPM96 TM) assuming linear and nonlinear correlations. Normalised data were then co-registered with standardised MRI templates. Results: Group analysis identified increased cerebral blood flow (CBF) (p<0.005) within: bilateral caudolateral sensorimotor cortex (Brodman Areas (BA) 3, 4 and 6), right anterior insula, right orbito-frontal cortex (BA 11), left mesial frontal cortex (BA 6 and 32), left antero-medial temporal cortex (BA 38), left thalamus, left superio-medial cerebellum, and dorsal and ventral brainstem. Decreased CBF was also observed, notably (p<0.001) within: bilateral posterior parietal cortex (BA 7) and anterior occipital cortex (BA 19), left superior frontal cortex (BA 8), right pre-frontal cortex (BA 9), and right superio-medial temporal cortex (BA 41 and 42). Individual analysis identified asymmetric inter-hemisphere representation within the sensorimotor cortex in 4 of the 6 subjects: 3 lateralising to right hemisphere and 1 to left hemisphere. Conclusions: Volitional swallowing has multiregional cerebral representation, strongest in sensorimotor cortex, cerebellum and brainstem, that each display differing degrees of inter-hemispheric asymmetry. These findings help explain the complex nature of swallowing disorders after focal cerebral injury. • G3135 UTILITY OF SCREENING TESTS IN IRRITABLE BOWEL SYNDROME. L. R. Harem (1), S.C. Sorrells (1), J. P. Harding (1), A. R. Northcutt (1), A. T. Heath (2), G. F. Kapke (3), and A.W. Mangel (1). Departments of Gastroenterology Clinical Research (1) and Clinical Statistics (2), Glaxo Welleome Inc., 5 Moore Drive, Research Triangle Park, NC 27709; Department of Technical Affairs, Covance, Indianapolis, IN 46214 (3). Background: The diagnosis of irritable bowel syndrome (IBS) is based upon fulfillment of a constellation of symptoms defined by either the Manning or Rome Criteria after appropriate exclusion of organic disease. As there are no measurable or pathognomonic entities routinely associated with IBS, it becomes a matter of individual physician discretion to determine which specific tests to order and when the exclusionary studies are complete. In the present study, we evaluated the results of the hydrogen breath test, thyroid stimulating hormone (TSH) levels, ova and parasite determination and structural evaluation of the colon in over 1000 IBS patients. Methods: Data were collected from two large multicenter studies of patients with the diagnosis of IBS. Flexible sigmoidoscopy was performed on all patients under the age of 50, not having a normal exam within the past 2 years. For patients over the age of 50 a flexible sigmoidoscopy and barium enema or colonoscopy were required if a normal exam was not documented within the past 2 years. TSH levels were drawn on all patients who did not have documented normal results within the previous 12 months. Ova and parasite determination was performed on patients not having a normal exam within the past 3 months and all patients were required to have a hydrogen breath test. Results: A structural evaluation of the colon was required in 306 patients, and 7 abnormal results were found. Findings on four of the abnormal studies could have contributed to IBS-like symptoms of abdominal pain and/or change in bowel habits. Six percent (67/1209) and 2% (19/1154) of patients were found to have abnormal TSH levels and ova and parasite positively, respectively. Of the subjects with abnormal TSH levels, 50% were hypothyroid and 50% hyperthyroid. Positive ova and parasite collections were found in 19 patients. The most common species identified on stool culture was Blastocystis h0minis which was cultured from 8 samples. Twenty three percent (256/1122) of patients had an abnormally high hydrogen breath test result. A comparison of abnormal test results showed no gender dependence with abnormalresults observed in 25% of males and 22% of females. CONCLUSION: Based on the combined data from these two multicenter studies with IBS patients, determination of lactose intolerance is advisable at some point during the work-up of IBS patients. Supported by Glaxo Wellcome • G3136 INTRAJEJUNAL CAPSAICIN CAUSES PAIN IN T I l E HUMAN JEJUNUM. J Hammer, HF Hammer, AJ Eherer, W Petritsch, P Holzer, GJ Krejs. Depts. of Medicine, Universities of Graz and Vienna, and Dept of Experimental and Clinical Pharmacology University of Graz, Austria. Introduction: Stimulation of sensory nerves with capsaicin has been shown to cause intestinal secretion in the rat and stimulate motility of human small intestine in vitro. The Aim of the Study: To investigate the effects of sensory nerve stimulation by capsaicin on the human jejunum in vivo. Methods: Intestinal perfusion studies were performed in 12 healthy subjects using a 4-lumen tube with a proximal occlusion balloon and a plasma-like electrolyte
Motility and Nerve-Gut Interactions A761
April 1998 solution. After an initial control period 5 (n=3), 10 (n=8), or 50 (n=l) lag/ml capsaicin was added to the perfusate for a 60-minute test period, followed by a final control period. Absorption rates of water, sodium, potassium, chloride and bicarbonate were determined in a 30-cm segment of jejunum using a non absorbable volume marker. Results: At all 3 concentrations of capsaicin there were no significant changes in water and electrolyte absorption as compared to control periods. Two subjects who received I0 lag/ml developed abdominal cramps at the end of the 60-min test period. The subject receiving 50 pg/ml experienced crampy abdominal pain within 20 minutes and pain persisted until the end of the 60-min test period. Cramps resolved within five minutes after ending the capsaicin perfusion according to protocol. Cramps or abdominal discomfort did not develop during any of the control periods. Summary: In contrast to animal experiments, intrajejunal capsaicin does not cause secretion or alter absorption in the human jejunum in vivo. Capsaicin caused crampy abdominal pain in a concentration and time related manner. This was unexpected because capsaicin fails to evoke reactions indicative of pain in the rat. Conclusion: The present study demonstrates that in healthy volunteers abdominal pain can be elicited by chemical stimulation of the intestinal mucosa. Future studies will have to address whether capsaicin caused pain by directly stimulating nociceptive afferents in the intestinal mucosa or by stimulating excessive contraction or distention of the gut. • G3137 W H O L E GUT SENSITIVITY IN CONSTIPATION PREDOMINANT IRRITABLE BOWEL SYNDROME (CPIBS): 80 PERCENT OF PATIENTS EXHIBIT AN ABNORMALITY. 1RM Hammonds, ILA Houghton, Ipj Whorwell, 2j Morris, ICY Francis, 3j Mills. Depts of 1Medicine and 2Statistics, University Hospital of South Manchester, M20 2LR and 3Glaxo Wellcome, Stockley Park West, Uxbridge, UB11 1BT, U.K. We have recently observed that patients with diarrhoea predominant irritable bowel syndrome (DPIBS) have increased sensitivity to balloon distension throughout the length of the gastrointestinal tract, with the jejunum being the site most likely to exhibit this phenomenon (Gastroenterology 1995;108:A601). The aim of this study was to extend these observations and compare sensory and motility responses to balloon distension of the oesophagus (O), duodenum (D), jejunum (J), ileum (I), colon (C) and rectum (R) in 14 patients with CPIBS (aged 29-64 yrs, all female) with 25 healthy volunteers (aged 20-61 yrs, all female). All patients fulfilled the Rome criteria for CPIBS and had their level of anxiety assessed using the Hospital Anxiety and Depression questionnaire (abnormal scores > 10). Results With the exception of the J [vol to discomfort (ml): IBS 40(20,140) geometric mean (range) v controls 59(40,100); p=0.01], the sensory thresholds in the O [13(5,60) v 15(7.5,45); p=0.38], D [48(10,160) v 64(40,110); p=0.14], I [40 (15,150) v 54(30,110); p=0.09], C [124(50,300) v 154(60,280); p=0.26] and R [118 (40,300) v 165(80,400); p=0.06] were not significantly different between patients and controls. Comparison of individual patient sensory thresholds with the 90% control range, however, did show altered sensitivity (increased or decreased) in at least one site of the gut in 79% of patients. This was reflected by increased sensitivity in 7% of patients in O, 29% in D, 29% in J, 20% in I, 25% in C and 36% in R; and decreased sensitivity in 14% of patients in O, 7% in D, 7% in J, 10% in I, 8% in .C and 14% in R. These differences in sensitivity were not associated with differences in gut compliance between the patient and control groups for the O [compliance (ml/mmHg) at 5ml: IBS 0.41(0.16,1.19) median (range) v controls 0.31(0.14,0.87); p=0.12], D [40ml: 3.42(1.73,9.52) v 2.40(1.08,6.40); p=0.24], J [40ml: 1.89(1.30,33.30) v 2.04(0.80,4.30); p=0.82], 1 [40ml: 1.52(1.10,5.70) v 2.22(0.80,8.90); p=0.66] and C [80ml: 6.11(2.70,12.70) v 5.51(2.40,10.40); p=0.64]; although the compliance of R was greater in the patients compared with controls [80ml: 9.20(5.00,28.60) v 5.19(1.80,14.00); p=0.01]. A correlation analysis of the patients level f sensitivity with their gut compliance revealed no significant relationships [O, p=0.49, p=0.09; D, p=0.57, p=0.08; J, p=0.50, p=0.14; I, p=0.26, p=0.67; C, p=0.47, p=0.20; R p=0.27, p=0.48]. Likewise, although the patients had higher anxiety scores [9(3,16)] than controls [5(1,9); p=0.002], there was no correlation between their sensory threshold and anxiety score [O, r---0.14, p=0.64; D, r=--0.18, p=0.53; J, r=-0.38, p=0.18; I, r=0.09, p=0.82; C, r=0.02, p=0.96; R, r=-0.18, p=0.55]. Conclusions Just as in DPIBS, CPIBS patients are most likely to exhibit a perceptual change in the J. Furthermore, 80% CPIBS patients exhibited some form of sensory abnormality (increased or decreased) at some level in the gastrointestinal tract. These results lend further support to the notion that perCeptual abnormalities contribute to the pathophysiology of IBS. This research was supported in part by a grant from Glaxo Wellcome, U.K. • G3138 DESCENDING PERINEUM SYNDROME: CLINICAL AND LABORATORY FEATURES AND OUTCOME OF PELVIC FLOOR RETRAINING. G. Harewood, B. Coulie, D. Rath, J.H. Pemberton, M. Camilleri. Mayo Foundation, Rochester, MN. The descending perineum syndrome (DPS) is rarely encountered in clinical practice, and may present with either an evacuation disorder or incontinence of stool or urine. Our aim was to retrospectively analyze the Mayo Clinic experience of this disorder over the ten year period from 1987-1997.
Methods: Clinical records were used to abstract demographic features,
associations, risk factors, results on tests of anorectal manometry, scintigraphic rectal emptying with measurement of rectoanal angle at rest and during defecation, and balloon expulsion. A questionnaire was mailed to ascertain which patients underwent pelvic floor retraining at Mayo Clinic or elsewhere, and to evaluate outcome and current symptoms in 1997. Results (mean _+SD): (1) Clinical: There were 38 patients (36F, 2M) with mean age 52 -+ 15 years at presentation. Presenting symptoms werei constipation (92%), sense of incomplete rectal evacuation (84%), excessive straining (92%), digital evacuation (29%) and fecal incontinence (16%). Three patients had combined symptoms of excessive straining to defecate and fecal incontinence. Thirty-three patients underwent anorectal manometry; 24 patients underwent scintigraphic rectal evacuation. (2) Laboratory testing: Anal sphincter resting pressure 75 -+ 35 mmHg; squeeze pressure 138 -+ 45 mmHg; expulsion of a balloon from the rectum required >200g weight added in 21% of patients; scintigraphic evacuation of radiolabeled Veegum resin was 55 -+ 24% (normal >54%); change of rectoanal angle from rest to defecation position was 14.4 -+ 9.6 ° (normal >15°); perineal descent was 4.9 -+ 1.3cm (normal <4cm). Scintigraphic evacuation, rectoanal angle and perineal descent were abnormal in 21%, 50% and 79% of the patients respectively. (3) Associated riskJactors: multiparity with vaginal delivery (58%), hysterectomy and/or cystocele/rectocele repair (70%). (4) Mailed questionnaire: Seventeen patients responded. All clinical and laboratory features were not significantly different in questionnaire responders vs. nonresponders. Ten of 17 patients underwent pelvic floor retraining. At 2-year median follow-up (range 1-6 yr), 67% still experienced constipation or excessive straining. Conclusions: DPS is identifiable by clinical and relatively simple l~iboratory testing, and the most prevalent abnormality was a documented perineal descent >4.0cm. Balloon expulsion is an insensitive screening test (only 21% positive) for DPS. Symptoms persist despite pelvic floor retraining in the majority of patients who responded to a questionnaire, suggesting that current approaches to treatment for this chronic disorder of rectal evacuation are suboptimal. • G3139 IRRITABLE BOWEL SYNDROME: RESPONSES TO GASTRIC DISTENTION. M. Harnish. S. Elsenbruch, W. Orr; Lynn Health Science Institute, Oklahoma City, OK. Irritable bowel syndrome (IBS) is characterized by gastrointestinal (GI) symptoms for which no recognized organic GI etiology can be found. Recent data suggest that the pathophysiology of IBS may involve a shift in the threshold of sensitivity to visceral stimuli. This altered perception may in turn lead to altered responses in GI regulatory systems. The objective of the current study was to investigate the effect of gastric distention on gastric myoelectrical activity in IBS patient s compared to healthy individuals. Methods: Eight IBS patients and seven healthy were studied using electrogastrography (EGG). Prior to a 20 minute baseline recording (Period 1), subjects were asked to complete a visual analog scale (VAS) inquiring about how full their stomach felt. They were then given 100cc volumes of water, followed by another VAS scale. They continued to ingest water until they had reached a subjective rating on the VAS 20% greater than their baseline subjective level. A 30 minute recording period followed (Period 2). Following this recording period, subjects resumed ingesting water until they reached a point on the VAS 50% greater than their baseline subjective level. A 60 minute recording period followed (Period 3). A symptom checklist, consisting of various GI, autonomic, and somatic items, was also completed each time. Dependent variables included the dominant frequency (DF) and dominant power (DP) calculated via the spectral analysis of the EGG data, the volume of water ingested to reach each subjective level, and the number of symptoms experienced. The data were analyzed using a 2x3 ANOVA followed by comparisons using the Tukey HSD. Results: 1) The groups did not differ significantly in the amount of water ingested to reach a particular subjective rating. 2) There was a trend for DP towards a significant interaction between group and period (p<.07). Controls showed an increase in DP following ingestion of water, while the IBS patients failed to exhibit a similar change (See Fig.). The groups' DPs were significantly different following water ingestion (p<.05). 3) Both IBS patients and controls demonstrated a significant decrease in DF following ingestion of the water (p<.01). 4) IBS patients reported significantly more symptoms than controls after the water ingestion (p<.03).
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Conclusions: 1) These results confirm previous findings in our lab that IBS patients fail to modulate gastric myoelectrical activity in response to a variety of stimuli. 2) Taken together, these findings suggest that IBS may involve an alteration in responses to visceral stimuli leading to a failure to demonstrate compensatory responses to gastric distention and meal ingestion.
GASTROENTEROLOGY Vol. 114, No. 4
G3132 FREQUENCY AND DURATION OF SYMPTOMS IN PATIENTS WITH IRRITABLE BOWEL SYNDROME (IBS). B. Hahn, RTP, NC; M. Watson, RTP, NC; D. Gunput, Greenford UK; J. Heuijerjans, Zeist, The Netherlands; S Yan, RTP, NC. Although patients with IBS often describe periods of symptoms alternating with quiescent periods, few studies have prospectively documented symptom patterns. The purpose of this study was to determine the frequency and duration of IBS symptoms over a 12-week period using a daily telephone data entry system. Patients 18 years or older with a diagnosis of IBS based on the Rome criteria were recruited from ambulatory care centers/hospitals and physician offices in the US, UK, and The Netherlands for an observational diary study. A total of 122 patients entered the study; those with diary reports on 70 or more days (N=59) were included in the analysis. As part of a larger survey, patients recorded whether they experienced each of the following symptoms: abdominal pain/discomfort, bloating, altered stool form, altered stool passage, and mucus. The sample was predominantly female (78%), and the average age was 49. The frequency distribution of the proportion of days with at least one symptom is shown below: Percent of reported days 80- I00 60 - 79 40 - 59 20 - 39 0- 19
Percent of total 23.8 18.7 23.8 22.1 11.9
The average proportion of reported days on which subjects experienced individual symptoms was as follows: pain/discomfort 32.8% bloating 28.0%, altered stool form 24.8%, altered stool passage 17.9%, and mucus 6.5%. Symptom patterns were further characterized by examining the number of episodes, which were defined as periods of consecutive days during which one or more symptoms were reported, bounded by at least one day (24 hours) of no symptoms. Patients in our sample experienced between 1 and 24 episodes, with 78% reporting 10-20 episodes over the course of the 12-week study. The median episode duration was 2.4 days; median duration for days without symptoms was 2.5 days. These results suggest that IBS is best characterized as a chronic illness with frequently recurring symptoms. This research was funded by Glaxo Wellcome. G3133 THE DEMOGRAPHY OF IRRITABLE BOWEL SUFFERERS WITH CO-EXISTING DEPRESSION. EM Hallyburton, AM Veitch, MJG Farthing. Digestive Diseases Research Centre, St Bartholomew's & The Royal London School of Medicine & Dentistry, London, UK. Introduction and aims: Irritable bowel syndrome (IBS) and depression commonly co-exist. As part of the recruitment process for a trial investigating the use of an antidepressant in patients with co-existing IBS and depression, a radio advertisement was used to contact subjects with both of these conditions in the community in London. The aim of this study was to characterise the population of respondents to the advertisement who considered themselves to suffer from IBS co-existent with depression Patients and methods: A radio advertisement seeking subjects with IBS and depression was transmitted on a London-wide radio station for 7 days. Respondents who replied by telephone were then sent a brief questionnaire which included the ICD-10 diagnostic criteria for depression. Further questionnaires were sent including ICD-10 criteria, Rome criteria for IBS and demographic profiles. Results: 384 responded to the radio advertisement. 241 (62.7%) responded to the first questionnaire of whom 234 (97%) met the ICD-10 criteria for depression. 34 (14.1%) had mild depression, 134 (55.6%) had moderate depression, and 66 (27.3%) had severe depression. All depressed subjects fulfilled Rome criteria for IBS. To date, 224 (58.3%) have responded to the second questionnaire. 215 (95.9%) met criteria for IBS and 214 (95.5%) were depressed. 60 (26.8%) had mild depression, 120 (53.6%) had moderate depression and 34 (15.2%) had severe depression. All respondents were grouped according to social class, A,B,CI, 42.4% and C2,D,E, 57.6% compared to the demographics of radio station listeners social class A,B,C1, 58.5% and C2,D,E, 41.5%; p<0.0001. Respondents not in full time employment were A,B,C 1 20 (21%) and C2,D,E were 34 (26%); p=0.4. Conclusions: IBS sufferers, with depression, within the community correctly assign their abdominal symptoms to IBS and clearly recognis e their depressive symptoms as judged by ICD-10 criteria. The respondents were predominantly in the lower social classes in contrast to the predominance of upper social classes in the radio station listener population. These findings may have relevance for the management of these conditions in primary care. • G3134 IDENTIFICATION OF TIlE CEREBRAL LOCI PROCESSING HUMAN SWALLOWING FUNCTION: A H20 TMPET ACTIVATION STUDY. S. Hamdy*t, J. C. Rothwell*, D. J. Brooks:[:, tQ. Aziz, "~D. G. Thompson. *MRC Human Movement & Balance Unit, Institute of Neurology, London, tDept of Gastroenterology, Hope Hospital, University of Manchester & :~MRC Cyclotron Unit, Hammersmith Hospital, London, UK. Background: Using transcranial magneto-electric stimulation we have recently demonstrated that the cortico-fugai pathways to human swallowing
musculature can be mapped to motor and premotor cortex (Nature Med. 1996; 2(11):1217-1224). However, little is known about the functional organisation of the cerebral regions active during normal volitional swallowing. Aims: To determine the cerebral loci which process human volitional swallowing function. Methods: Six healthy right handed male volunteers (mean age 41 yrs, age range 35-49 yrs) were studied using O 15 labeled water PET activation imaging. A randomised 12 scan paradigm was performed in each subject during the conditions of: i, rest and ii. water swallows (5ml/bolus, continuous infusion) at frequencies of 0.1, 0.2 and 0.3 Hz, visually cued and monitored using submental EMG. Group and individual parametric covariate analysis was performed (SPM96 TM) assuming linear and nonlinear correlations. Normalised data were then co-registered with standardised MRI templates. Results: Group analysis identified increased cerebral blood flow (CBF) (p<0.005) within: bilateral caudolateral sensorimotor cortex (Brodman Areas (BA) 3, 4 and 6), right anterior insula, right orbito-frontal cortex (BA 11), left mesial frontal cortex (BA 6 and 32), left antero-medial temporal cortex (BA 38), left thalamus, left superio-medial cerebellum, and dorsal and ventral brainstem. Decreased CBF was also observed, notably (p<0.001) within: bilateral posterior parietal cortex (BA 7) and anterior occipital cortex (BA 19), left superior frontal cortex (BA 8), right pre-frontal cortex (BA 9), and right superio-medial temporal cortex (BA 41 and 42). Individual analysis identified asymmetric inter-hemisphere representation within the sensorimotor cortex in 4 of the 6 subjects: 3 lateralising to right hemisphere and 1 to left hemisphere. Conclusions: Volitional swallowing has multiregional cerebral representation, strongest in sensorimotor cortex, cerebellum and brainstem, that each display differing degrees of inter-hemispheric asymmetry. These findings help explain the complex nature of swallowing disorders after focal cerebral injury. • G3135 UTILITY OF SCREENING TESTS IN IRRITABLE BOWEL SYNDROME. L. R. Harem (1), S.C. Sorrells (1), J. P. Harding (1), A. R. Northcutt (1), A. T. Heath (2), G. F. Kapke (3), and A.W. Mangel (1). Departments of Gastroenterology Clinical Research (1) and Clinical Statistics (2), Glaxo Welleome Inc., 5 Moore Drive, Research Triangle Park, NC 27709; Department of Technical Affairs, Covance, Indianapolis, IN 46214 (3). Background: The diagnosis of irritable bowel syndrome (IBS) is based upon fulfillment of a constellation of symptoms defined by either the Manning or Rome Criteria after appropriate exclusion of organic disease. As there are no measurable or pathognomonic entities routinely associated with IBS, it becomes a matter of individual physician discretion to determine which specific tests to order and when the exclusionary studies are complete. In the present study, we evaluated the results of the hydrogen breath test, thyroid stimulating hormone (TSH) levels, ova and parasite determination and structural evaluation of the colon in over 1000 IBS patients. Methods: Data were collected from two large multicenter studies of patients with the diagnosis of IBS. Flexible sigmoidoscopy was performed on all patients under the age of 50, not having a normal exam within the past 2 years. For patients over the age of 50 a flexible sigmoidoscopy and barium enema or colonoscopy were required if a normal exam was not documented within the past 2 years. TSH levels were drawn on all patients who did not have documented normal results within the previous 12 months. Ova and parasite determination was performed on patients not having a normal exam within the past 3 months and all patients were required to have a hydrogen breath test. Results: A structural evaluation of the colon was required in 306 patients, and 7 abnormal results were found. Findings on four of the abnormal studies could have contributed to IBS-like symptoms of abdominal pain and/or change in bowel habits. Six percent (67/1209) and 2% (19/1154) of patients were found to have abnormal TSH levels and ova and parasite positively, respectively. Of the subjects with abnormal TSH levels, 50% were hypothyroid and 50% hyperthyroid. Positive ova and parasite collections were found in 19 patients. The most common species identified on stool culture was Blastocystis h0minis which was cultured from 8 samples. Twenty three percent (256/1122) of patients had an abnormally high hydrogen breath test result. A comparison of abnormal test results showed no gender dependence with abnormalresults observed in 25% of males and 22% of females. CONCLUSION: Based on the combined data from these two multicenter studies with IBS patients, determination of lactose intolerance is advisable at some point during the work-up of IBS patients. Supported by Glaxo Wellcome • G3136 INTRAJEJUNAL CAPSAICIN CAUSES PAIN IN T I l E HUMAN JEJUNUM. J Hammer, HF Hammer, AJ Eherer, W Petritsch, P Holzer, GJ Krejs. Depts. of Medicine, Universities of Graz and Vienna, and Dept of Experimental and Clinical Pharmacology University of Graz, Austria. Introduction: Stimulation of sensory nerves with capsaicin has been shown to cause intestinal secretion in the rat and stimulate motility of human small intestine in vitro. The Aim of the Study: To investigate the effects of sensory nerve stimulation by capsaicin on the human jejunum in vivo. Methods: Intestinal perfusion studies were performed in 12 healthy subjects using a 4-lumen tube with a proximal occlusion balloon and a plasma-like electrolyte
Motility and Nerve-Gut Interactions A761
April 1998 solution. After an initial control period 5 (n=3), 10 (n=8), or 50 (n=l) lag/ml capsaicin was added to the perfusate for a 60-minute test period, followed by a final control period. Absorption rates of water, sodium, potassium, chloride and bicarbonate were determined in a 30-cm segment of jejunum using a non absorbable volume marker. Results: At all 3 concentrations of capsaicin there were no significant changes in water and electrolyte absorption as compared to control periods. Two subjects who received I0 lag/ml developed abdominal cramps at the end of the 60-min test period. The subject receiving 50 pg/ml experienced crampy abdominal pain within 20 minutes and pain persisted until the end of the 60-min test period. Cramps resolved within five minutes after ending the capsaicin perfusion according to protocol. Cramps or abdominal discomfort did not develop during any of the control periods. Summary: In contrast to animal experiments, intrajejunal capsaicin does not cause secretion or alter absorption in the human jejunum in vivo. Capsaicin caused crampy abdominal pain in a concentration and time related manner. This was unexpected because capsaicin fails to evoke reactions indicative of pain in the rat. Conclusion: The present study demonstrates that in healthy volunteers abdominal pain can be elicited by chemical stimulation of the intestinal mucosa. Future studies will have to address whether capsaicin caused pain by directly stimulating nociceptive afferents in the intestinal mucosa or by stimulating excessive contraction or distention of the gut. • G3137 W H O L E GUT SENSITIVITY IN CONSTIPATION PREDOMINANT IRRITABLE BOWEL SYNDROME (CPIBS): 80 PERCENT OF PATIENTS EXHIBIT AN ABNORMALITY. 1RM Hammonds, ILA Houghton, Ipj Whorwell, 2j Morris, ICY Francis, 3j Mills. Depts of 1Medicine and 2Statistics, University Hospital of South Manchester, M20 2LR and 3Glaxo Wellcome, Stockley Park West, Uxbridge, UB11 1BT, U.K. We have recently observed that patients with diarrhoea predominant irritable bowel syndrome (DPIBS) have increased sensitivity to balloon distension throughout the length of the gastrointestinal tract, with the jejunum being the site most likely to exhibit this phenomenon (Gastroenterology 1995;108:A601). The aim of this study was to extend these observations and compare sensory and motility responses to balloon distension of the oesophagus (O), duodenum (D), jejunum (J), ileum (I), colon (C) and rectum (R) in 14 patients with CPIBS (aged 29-64 yrs, all female) with 25 healthy volunteers (aged 20-61 yrs, all female). All patients fulfilled the Rome criteria for CPIBS and had their level of anxiety assessed using the Hospital Anxiety and Depression questionnaire (abnormal scores > 10). Results With the exception of the J [vol to discomfort (ml): IBS 40(20,140) geometric mean (range) v controls 59(40,100); p=0.01], the sensory thresholds in the O [13(5,60) v 15(7.5,45); p=0.38], D [48(10,160) v 64(40,110); p=0.14], I [40 (15,150) v 54(30,110); p=0.09], C [124(50,300) v 154(60,280); p=0.26] and R [118 (40,300) v 165(80,400); p=0.06] were not significantly different between patients and controls. Comparison of individual patient sensory thresholds with the 90% control range, however, did show altered sensitivity (increased or decreased) in at least one site of the gut in 79% of patients. This was reflected by increased sensitivity in 7% of patients in O, 29% in D, 29% in J, 20% in I, 25% in C and 36% in R; and decreased sensitivity in 14% of patients in O, 7% in D, 7% in J, 10% in I, 8% in .C and 14% in R. These differences in sensitivity were not associated with differences in gut compliance between the patient and control groups for the O [compliance (ml/mmHg) at 5ml: IBS 0.41(0.16,1.19) median (range) v controls 0.31(0.14,0.87); p=0.12], D [40ml: 3.42(1.73,9.52) v 2.40(1.08,6.40); p=0.24], J [40ml: 1.89(1.30,33.30) v 2.04(0.80,4.30); p=0.82], 1 [40ml: 1.52(1.10,5.70) v 2.22(0.80,8.90); p=0.66] and C [80ml: 6.11(2.70,12.70) v 5.51(2.40,10.40); p=0.64]; although the compliance of R was greater in the patients compared with controls [80ml: 9.20(5.00,28.60) v 5.19(1.80,14.00); p=0.01]. A correlation analysis of the patients level f sensitivity with their gut compliance revealed no significant relationships [O, p=0.49, p=0.09; D, p=0.57, p=0.08; J, p=0.50, p=0.14; I, p=0.26, p=0.67; C, p=0.47, p=0.20; R p=0.27, p=0.48]. Likewise, although the patients had higher anxiety scores [9(3,16)] than controls [5(1,9); p=0.002], there was no correlation between their sensory threshold and anxiety score [O, r---0.14, p=0.64; D, r=--0.18, p=0.53; J, r=-0.38, p=0.18; I, r=0.09, p=0.82; C, r=0.02, p=0.96; R, r=-0.18, p=0.55]. Conclusions Just as in DPIBS, CPIBS patients are most likely to exhibit a perceptual change in the J. Furthermore, 80% CPIBS patients exhibited some form of sensory abnormality (increased or decreased) at some level in the gastrointestinal tract. These results lend further support to the notion that perCeptual abnormalities contribute to the pathophysiology of IBS. This research was supported in part by a grant from Glaxo Wellcome, U.K. • G3138 DESCENDING PERINEUM SYNDROME: CLINICAL AND LABORATORY FEATURES AND OUTCOME OF PELVIC FLOOR RETRAINING. G. Harewood, B. Coulie, D. Rath, J.H. Pemberton, M. Camilleri. Mayo Foundation, Rochester, MN. The descending perineum syndrome (DPS) is rarely encountered in clinical practice, and may present with either an evacuation disorder or incontinence of stool or urine. Our aim was to retrospectively analyze the Mayo Clinic experience of this disorder over the ten year period from 1987-1997.
Methods: Clinical records were used to abstract demographic features,
associations, risk factors, results on tests of anorectal manometry, scintigraphic rectal emptying with measurement of rectoanal angle at rest and during defecation, and balloon expulsion. A questionnaire was mailed to ascertain which patients underwent pelvic floor retraining at Mayo Clinic or elsewhere, and to evaluate outcome and current symptoms in 1997. Results (mean _+SD): (1) Clinical: There were 38 patients (36F, 2M) with mean age 52 -+ 15 years at presentation. Presenting symptoms werei constipation (92%), sense of incomplete rectal evacuation (84%), excessive straining (92%), digital evacuation (29%) and fecal incontinence (16%). Three patients had combined symptoms of excessive straining to defecate and fecal incontinence. Thirty-three patients underwent anorectal manometry; 24 patients underwent scintigraphic rectal evacuation. (2) Laboratory testing: Anal sphincter resting pressure 75 -+ 35 mmHg; squeeze pressure 138 -+ 45 mmHg; expulsion of a balloon from the rectum required >200g weight added in 21% of patients; scintigraphic evacuation of radiolabeled Veegum resin was 55 -+ 24% (normal >54%); change of rectoanal angle from rest to defecation position was 14.4 -+ 9.6 ° (normal >15°); perineal descent was 4.9 -+ 1.3cm (normal <4cm). Scintigraphic evacuation, rectoanal angle and perineal descent were abnormal in 21%, 50% and 79% of the patients respectively. (3) Associated riskJactors: multiparity with vaginal delivery (58%), hysterectomy and/or cystocele/rectocele repair (70%). (4) Mailed questionnaire: Seventeen patients responded. All clinical and laboratory features were not significantly different in questionnaire responders vs. nonresponders. Ten of 17 patients underwent pelvic floor retraining. At 2-year median follow-up (range 1-6 yr), 67% still experienced constipation or excessive straining. Conclusions: DPS is identifiable by clinical and relatively simple l~iboratory testing, and the most prevalent abnormality was a documented perineal descent >4.0cm. Balloon expulsion is an insensitive screening test (only 21% positive) for DPS. Symptoms persist despite pelvic floor retraining in the majority of patients who responded to a questionnaire, suggesting that current approaches to treatment for this chronic disorder of rectal evacuation are suboptimal. • G3139 IRRITABLE BOWEL SYNDROME: RESPONSES TO GASTRIC DISTENTION. M. Harnish. S. Elsenbruch, W. Orr; Lynn Health Science Institute, Oklahoma City, OK. Irritable bowel syndrome (IBS) is characterized by gastrointestinal (GI) symptoms for which no recognized organic GI etiology can be found. Recent data suggest that the pathophysiology of IBS may involve a shift in the threshold of sensitivity to visceral stimuli. This altered perception may in turn lead to altered responses in GI regulatory systems. The objective of the current study was to investigate the effect of gastric distention on gastric myoelectrical activity in IBS patient s compared to healthy individuals. Methods: Eight IBS patients and seven healthy were studied using electrogastrography (EGG). Prior to a 20 minute baseline recording (Period 1), subjects were asked to complete a visual analog scale (VAS) inquiring about how full their stomach felt. They were then given 100cc volumes of water, followed by another VAS scale. They continued to ingest water until they had reached a subjective rating on the VAS 20% greater than their baseline subjective level. A 30 minute recording period followed (Period 2). Following this recording period, subjects resumed ingesting water until they reached a point on the VAS 50% greater than their baseline subjective level. A 60 minute recording period followed (Period 3). A symptom checklist, consisting of various GI, autonomic, and somatic items, was also completed each time. Dependent variables included the dominant frequency (DF) and dominant power (DP) calculated via the spectral analysis of the EGG data, the volume of water ingested to reach each subjective level, and the number of symptoms experienced. The data were analyzed using a 2x3 ANOVA followed by comparisons using the Tukey HSD. Results: 1) The groups did not differ significantly in the amount of water ingested to reach a particular subjective rating. 2) There was a trend for DP towards a significant interaction between group and period (p<.07). Controls showed an increase in DP following ingestion of water, while the IBS patients failed to exhibit a similar change (See Fig.). The groups' DPs were significantly different following water ingestion (p<.05). 3) Both IBS patients and controls demonstrated a significant decrease in DF following ingestion of the water (p<.01). 4) IBS patients reported significantly more symptoms than controls after the water ingestion (p<.03).
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Conclusions: 1) These results confirm previous findings in our lab that IBS patients fail to modulate gastric myoelectrical activity in response to a variety of stimuli. 2) Taken together, these findings suggest that IBS may involve an alteration in responses to visceral stimuli leading to a failure to demonstrate compensatory responses to gastric distention and meal ingestion.