April 1995 Motility and Nerve-Gut Interactions A683

• NON-INVASIVE EMG-GU1DED BIOFEEDBACK:EFFECTIVE LONG TERM THERAPY FOR ENCOPRESIS IN CHILDREN

M. S a p s , K. C o x , E. Rich, M.Fitzsimmons ,W. Berquist Depar tment of Pediatrics, California Pacific Medical Center, San

Francisco, CA In order to determine the efficacy of non-intrusive, surface EMG-guided biofeedback for encopresis and constipation in children, we evaluated the outcome of 24 children with a mean (range) follow-up period of 22(8-38) months who we were able to contact from a total of 31 children who had completed the biofeedback program from 1991-1994. Fifteen males with a mean age of 7.7(4-12) years and 9 females with mean age 9.1(5-12)years had been referred for management of constipation and encopresis when stool softening and regular defecatory behavior was unsuccessful and were determined by anorectal manometry to have inability to relax the external anal sphincter with defecatory attempts. They completed up to ten one-hour sessions using surface EMG electrodes both perianally on the abdominal muscles with video-game directed biofeedback programs designed to teach external anal sphincter and abdominal wall muscle contraction and relaxation individually or in coordination to achieve a normal defecatory response. Of these 24 children, 5 (21%) were post-Hirschsprung's repair, 3(13%) were post-imperforate anus repair, 1(4%) had myelomeningocele and the remaining 15 (62%) were functional. At the end of biofeedback therapy 9(37%) were successful (S), 11(46%)were significantly improved(I) , and 4(16%) were unimproved compared to their pre-biofeedback performance for a total of 20(84%) rehabilitated (S+I). At the end of the 22 month average follow up period there were 9(38%) still successful, 8(33%) improved and 7(29%) failures for a total of 17 (71%) remaining rehabilitated. The 7 long term failures occurred in 5 of 15 (33%) children with functional encopresis and 2 of 9 (22%) with non-functional encopresis. We conclude that EMG- guided biofeedback without an internal probe remains effective in the rehabilitation of childhood encopresis as determined by long term outcome analysis.

M E T A B O L I S M OF ARACHIDONIC ACID IN NORMAL AND INFLAMED SMALL INTESTINE, S.K. Sarna, W.B. Campbell, C. Hanke and P. Jouet. Depts. of Surgery and Pharmacology and Toxicology. Medical College of WI, Milwaukee, WI 53226.

Arachidonic acid is a potent inflammatory response mediator. It is co-synthesized with platelet-activating factor and metabolized by three pathways that are cyclooxygenase, lipoxygenase and cytochrome P-450 dependent. Each pathway leads to biologically active metabolites. Several of these metabolites have proinflammatory activities, including vasodilatation, neutrophil activation, chemotaxis, increase in capillary permeability, and leukocyte adherence to endothelium. We investigated the metabolism of arachidonic acid in the normal and inflamed canine small intestine to identify metabolites that may contribute to abnormal motility. We reported previously that ileal inflammation suppresses phasic contractions, including migrating motor complexes, and stimulates giant migrating contractions. An intraluminal catheter was surgically implanted in proximal ileum of 4 dogs. After recovery, ileal inflammation was induced by a series of three ethanol (75 ml, 95%) and acetic acid (50 ml, 20%) infusions on days 1, 2 and 5. The dogs were anesthetized on day 6 to harvest tissue. Full thickness tissue samples were taken from the inflamed ileum and normal jejunum. Each sample was separated into lamina propria and muscularis externa layers by scraping with a glass slide in a Petri dish. Each tissue sample was incubated with 14C-arachidonic acid and the 14C-metabolites isolated with reverse phase HPLC. The major m e t a b o l i t e in the m u s c u l a r i s ex t e rna was 12- hydroxyeicosatetraenoic acid (12-HETE). Inflammation increased the synthesis of 12-HETE greater than 2-fold. Further purification by normal phase HPLC, derivitization and analysis by gas chromatography-mass spectrometry confirmed that the metabolite was 12-HETE. Analysis by chiral phase HPLC indicated that the product was the S isomer. 12(S)- HETE is a lipoxygenase product. The major metabolites in the normal lamina propria were thromboxane B2 and prostaglandins F20 ~ and D 2. Inflammation suppressed the synthesis of these metabolites but increased that of 12-HETE in the lamina propria. We conclude that ileal inflammation in the ethanol/acetic acid model stimulates the synthesis of 12(S)-HETE and suppresses the production of prostaglandins F2a, D2 and thromboxane B2. The increased synthesis of 12-HETE in the muscularis externa suggests that it may have a role in the suppression of phasic contractions or stimulation of giant migrating contractions during inflammation. The cellular source of 12-HETE remains to be identified.

• SMALL INTESTINAL INFLAMMATION STIMULATES ABNORMAL COLONIC MOTOR ACTIVITY. S.K. Sarna. C. Singaram, V.E. Cowles, A. Brandon, R.E. Ryan, and D. Gourleay. Depts of Surg and Physiol, Med Coil of WI, Milw WI 53226 and Dept. of Mad, U of WI, Mad, WI 53793.

Small intestinal inflammation in Crohn's ileitis and in bacterial, viral or parasitic infections causes diarrhea, urgency of defecation and abdominal cramping. We investigated the hypothesis that small intestinal inflammation stimulates abnormal colonic motor activity that contributes to these symptoms. Five dogs were surgically instrumented with 15 strain gauge transducers, 7 on the colon, 1 on the stomach and 7 on the small intestine. After control recordings for 4 days, the dogs were infected with 2 x 104 larvae,/kg of the nematode T. spiralis. Recordings were made for 2 weeks after infection. All dogs developed diarrhea from the 2rid to the 5th day after infection. Colonic motor activity was analyzed in four periods: 1) Control (before infection), 2) Early infection (days 1 & 2), 3) Peak infection (days 3, 4 & 5), 4) Recovery (days 8 & 12). Three additional dogs were similarly infected, but euthanized on day 4 to harvest jejunal, ileal and colonic tissue. Immunocytes were quantitated in the muscularis externa and lamina propria per high power field using immunohis toehemist ry . R e s u l t s : T. spiralis infection produced inflammation in the je junum but not in the i leum or the colon. Polymorphonuclear cells in the muscularis externa and lamina propria of the jejunum increased 54 and 35-fold, myeloperoxidase activity, 50 and 9- fold, B-lymphocytes 5 and 8-fold, and T-lymphocytes 2 and 10-fold, respectively, as compared with the ileum. There was no significant increase in any of the immunocytes in the colon. The number of parasites 622 ± 66/era length, was significantly greater in the jejunum than in the ileum or the colon 0 ± 0, and 0 + 0/cm length, respectively. However, jejunal inflammation significantly increased the frequency of colonic giant migrating contractions (GMCs) from 0.02 + 0.02/h in control to 0.7 + 0.2/h during peak inflammation. 76 + 10% of these GMCs originated in the small intestine and propagated into the colon. The colonic GMCs during peak inflammation propagated 14.4 + 2.6 cm vs 4.8 + 4.8 cm in control. Jejunal inflammation also decreased the frequency of MMCs: control 1.7 ± 0.2/11, early inflammation 1.4 + 0. l/h, peak inflammation 0.4 + 0.1 (p < 0.05), recovery 0.9 + 0.1/tl. Conclusions: 1) Small bowel inflammation alone, without any inflammatory changes in the colon, stimulates abnormal colonic motor activity. 2) The abnormal colonic motor activity may be secondary to the activation of small intestinal immunocytes. 3) The increased frequency of colonic GMCs and their greater distance of propagation would rapidly propel colonic contents to the distal colon, contributing to diarrhea.

• H I G H VISCOUS LUMINAL CONTENT CAUSES DIFFERENT M A N O M E T R I C OUTCOMES BETWEEN METHODOLOGIES. Y.Sasaki and A.Munakata. First Department of Internal Medicine, t-Iirosaki University School of Medicine, t-Iirosaki, Japan. Aim: Contractile activity of the human colon was usually measured by using an opentip perfused tube system (PT) or by a tube mounted strain gauge system (TSG). However, shape of recorded pressure activities, that is, the duration, amplitude and gradient varied with studies. The difference may arise partially from viscosity of luminal contents, where the pressure is transmitted. We compared two methodologies for pressure measurement under material of various viscosities. Methods: The PT with outer diameter of 0.5 mm, length of 90 em and TSG were used for the comparison. They were placed in a sealed flask filled with the material mimicking luminal contents: air, water and flour gel containing 80, 60 and 50 % water. For each material, the PT was perfused with babble-free water by a low compliance perfusion pump at a rate of 0.1, 0.2 and 0.5 ml/min, where gradients of pressure rise obtained by the pore occlusion were I0, 20 and 100 mmHg/sec, respoetively. Ten consecutive trapezoidal pressure variations with the up- and down-gradient of ± 100 mmHg/see, maximal value of 180 mmttg were manually made by air inflation and monitored by another TSG. The pressure values from three devices were recorded in memory of a computer and simultaneously displayed on a monitor at 0.1 see interval. Results: The TSG accurately represented the artificial pressure variation not depending upon the materials where it was immersed. However, at the perfusion rate of 0.1 ml/min, the PT decreased its response property to 20 mmHg/see and underestimated the pressure change in the flour gel containing 60 and 50 % water, where motility index per one pressure variation was 81 -+0.7 and 63 ±0.5 % of that for the TSG, respectively. At the perfusion rate of 0.2 ml/min, the detected pressure overshot that by the TSG in the flour gel containing 50% water. The motility index was found to be 113 ± 0.2 % of that for the TSG.

In flour containing 50% water P~ffl~sion nt©: 0.1 mthr~n 0.2 mVml~

- - , ; PT 100

Conclusion: At the perfusion rate of less than 0,2 ml/min, the PT was largely changed in its dynamic property depending on the viscosity of materials where it was placed. This finding may cause the different shapes of pressure changes recorded in the human colon among studies or subjects. The TSG was a more reliable methodology for measuring colonic pressure than the PT.