IKOMA, A

NAKADA, K

REYNOLDS, JC

STARZL, TE

SUZUKI, T

TODO, S

Ikoma, A

Nakada, K

Suzuki, T

Reynolds, JC

Todo, S

Starzl, TE

Name not available

Effect of FK 506 on gastrointestinal tract: Comparison with erythromycin

D-Scholarship@Pitt

.... April 1993 ASSESSMENT OF COLONIC TRANSIT IN 24 HOURS. R Hutchinson, A Notghi *, L K Harding*, & D Kunar. Department of Surgery, The Queen Elizabeth Hospital, Birmingham, & *Department of Physics & Nuclear Medicine, IUIley Road Hospital, Birmingham, UNITED KIN:;OOM. CUrrent scintigraphic methods of meuuring colonic transit involve upto 60 hours of data acquisition. To determine if canparable information can be obtained in shorter, mre convenient studies, the da ta available at 24 hours was canpared With the colonic transit results from 6O-hour studies. Colonic transit was measured in 70 subjects. Indiun-III was delivered by enteric-coated capsules Wich break dowr, in the teI1llinal lleun releasing boluses of radio-isotope into the lleocaecal region. Gamna camera images were acquired for upto 60 hours. The colon was divided into 5 regions of interest (ROI IS) and segmental colonic transit was calculated for each subject. Using segmental colonic transit data from whole studies, subjects were classified as follows:- 1) normal, 2) rapid colonic transit, 3) generalised colonic delay, 4) right-sided colonic delay, and 5) left-sided colonic delay. The distribution of SCintigraphic activity throughout the colon at 24 hours was also used to classify subjects. How this method of assessing colonic transit canpares With the whole 6O-hour study is shown below:-1) Normal 2) Rapid 3) Gen. delay 4) R. delay 5) L. delay All subjects No. of subjects 6O-hour study 24-hour study 19 16 13 12 11 6 26 25 1 1 70 60 Agreement 84% 92:t: 55% 96% 100% 86% Categorisation of subjects using data available at 24 hours correlates well with the eventual categorisation of Mlbjects using data from conventional 6O-hour studies. We canclwie that information on colonic transit may be obtained in shorter, more convenient 24-hour studiea. • ANTRODUODENAL MANOMETRY AND INTESTINAL PAmOLOGY CORRELATE IN CONGENITAL CHRONIC NTESTINAL PSEUDO·OBSTRUCTION (eIP) PE Hyman. C DiLorenzo. A Hoon. S Krishnamurthy .,P Dean '+,MD Schuffler" Harbor-UCLA Medical Ctr. Torrance. Pacific Medical Ctr, Seattle. and Univ of Tennessee-Baptist Memorial Hosp, Memphis' + CIP is a clinical diagnosis applied to a heterogeneous group of nerve and muscle disorders. Nineteen patients with congenital CIP (7 male, 18 TPN dependent) had both antroduodenal manometry and full thickness small bowel biopsies. evaluated by H&E and Smith's silver stains of the myenteric plexus. Ages at manometry ranged from 2 mo to 19 y (median I y). Ages at biopsy ranged from 7 mo to 17 y (median 2.5 y). Biopsies showed neuropathy in 15. myopathy in 3,and no diagnostic abnormality in I. lO that a pathological diagnosis was made in 18 of 19 (95%). Manometry differentiated between neuropathy (normal amplitude, disorganized contractions) and myopathy (persistently low amplitude organIZed contractions) in 15 of 19 (79%). but 4 studies with persistently low amplitude disorganized contractions were judged Indeterminate. All 15 diagnostic manometries agreed with pathology. Those with aganglionosis or severe hypoganglionosis (n = 3) had IIOrma! amplitude, totally disorganized contractions. In those with IIIOderate hypoganglionosis (n =7) nonpropagating clusters of normal lII\plitude contractions were the predominant feature and MMCs ~ Ibsent, a typical pattern for preterm infants. Two with lllaturational arrest and I with neuronal dysplasia had dilated dUOdenums and persistently low amplitude uncoordinated COntractions. The final 2 patients with neuropathy had MMCs, but ~ abnormal nerve plexi were limited to sites distal to the ligament lrettz. All 3 patients with myopathy had MMCs and persistently ~ amplitude contractions. One patient with a non-diagnostic biopsy - ... low amplitude uncoordinated contractions remains a diagnostic PnIIlIem. We conclude that abnormalities of antroduodenal ~ correlated with morphologic disease in congenital CIP, ~~ be used to distinguish between myopathy and neuropathy. ;:.",~mental changes in preterm infant motility may provide a - for lOme neuropathic forms of CIP. Motility and Nerve-Gut Interactions A525 • GASTRIC AND SMALL INTESTINAL MOTILITY IN HUMANS FOLLOWING SMALL BOWEL TRANSPLANTATION ISBTI. WR Hutson. PE Putnam. S Todo. K Abu·Elmagd. JR Reynolds andH Furukawa. Departments of Medicine and Transplantstion Surgery. University of Pittsburgh School of Medicine. Pittsburgh. PA. SBT in humans is an uncommonly performed procedure and little is known about the effects on gastrointestinal motility and transit. The purpose of this study was to characterize motility of the stomach and small intestine in the post SBT patient and to correlate radionuclide gastric emptying IGEI with these findings. Methods: Gastric and small bowel motility studies were performed in 6 patients 14 males. 3 females: mean age 21 yrs.:range 8·33 yr •. 1 who had undergone either SBT alone. combined small bowellli"er transplantstion. or multi"isceral transplanta· tion after a mean of 9.5 months Irange 2·29 mos.l. Prior to transplanta· tion. all patients had short gut syndrome. and f> had TPN related liver disease. All patients were able to eat solid food or tolerate enteral nutri· tion at the time of the study. Motility was measured usmg either a mul· tilumen perfusion catheter or a solid state catheter with multiple transducers. A 4' •. 5 hour fasting period was obtsined followed by in· gestion of either 150 grams of Ensure lRI or a 511 kcal solid meal and 1·2 hours of postprandial recording. GE of solids and liquids was measured in 3 patients using meals contsining 99mTc'SC labeled eggs and 99mTc·SC labeled Gatorade. Results: Fastin" period: Antral motility \I as abnormal in all patients exhibited by d""reased amplitude or frequency of contrar· tions. Propagated MMC activity be"an in the stomach in 1 patient on 3 different occasions. Two patients exhibited MMC activity beginning in the intestine. Of those. one patient had 4 MMe·s. 2 of which were propa· gated and 2 simultsneous and the other had both simultaneous and retr{)o grade MMC activity. Both propagated and non propagated burst activity was present crossing native bowel to transplanted bowel. Bands of quiescence alternating with bands of aeth'itv were common. Onlv those patients who had undergone multivisceral transplantstion had propaga. tion of MMC' activity. Fed pattern: No patient had normal postprandial activity in either the stomach or small bowel. Solid GE was normal in 2 patients and prolonged in one of the 3 tested: liquid GE was prolonged in 1 patient and normal in 2 patients. Conclusions: 11 Both gastric and small bowel motility following SBT are abnormal. 21 Transmission of contrac· tion waves from native intestine to transplanted intestine occurs. al· though it is not always coordinated. 31 Multivisceral transplantation appears to increase the likelihood of propagated MMC activity as opposed to small bowel or small bowel/liver transplantstion. 41 GE does not corre· late with gastric or small bowel activit}' and it is unclear why this is so .~--------I • EFFECT OF FK 506 ON GASTROINTESTINAL TRACT: COMPAR· ISON Willi ERYTHROMYCIN. A. Ikoma, K. Nakada. T. Suzuki, J.C. Reynolds. S. Todo, T.E. Starzl. Dept. of Surgery and Internal Medicine, Univen;ity of Pittsburgh, School of Medicine, Pittsburgh, PA. Macrolides have potent effects on gastrointestinal motility and are used as prokinetic agents. Macrolides. however, like erythromycin (EM) and the novel macrolide immunosuppressant FK-506 (FK) may also cause nausea vomiting and abdominal pain after intravenous administration. AIM: To test the hypothesis that the emesis induced by FK results from similar motility effects as the structurally related macrolide antibiotic, EM. Methods: The effect of FK on emesis and GI motility was compared with the effect of EM in 5 healthy conscious dogs. Eight strain gage transducers were fixed on the GI tract from the antrum to the colon. After a 2-week recovery period, FK (0.1 mg/kg) or EM (3mg/kg) was injected inD'avenously in bolus during phase I of MMC, 30 min after cessation of phase III of the duodenum in the fasting state. Ondansetron (OND) (0.15mg/kg). an antiemetic which antagonizes 5-HT3 receptor in the chemoreceptor trigger zone and peripherally or aD'opine sulfate (0.1 mg/kg) was given intravenously 30 min or \0 min respectively prior to injection of FK or EM. Clinical findings and motility were monitored for 3 houn;. Each experiment was repeated twice. Results: Retching or vomiting occurred in 80% of FK experiments and 70% of EM experiments. FK caused small amplitude phasic contractions along the entire GI tract that staned 4.7± 0.4 min after injection and continued for 4.8±1.8 min at the proximal jejunum while EM induced strong upper GI conD'actions that staned 0.6±O.1 min after injection and lasted for 51.9±17.9 min at the proximal jejunum. FK induced 6 retrograde peristaltic contractions (RPCs) in 60% of experiments while EM induced 16 RPCs in 70% of experiments. FK induced 21 giant migrating contractions (GMCs) in 100% of experiments while EM induced only 3 GMCs in 20% of experiments. Emesis after FK or EM tended to be decreased by both atropine and OND. Atropine significantly reduced the amplitude and duration of contractions induced by both FK and EM (p<O.05). In contrast, OND reduced the amplitude of contractions induced by FK (p< 0.05) but had no effect on EM. Conclusion: l.Two macrolides FK and EM have potent effects on GI motility and vomiting in the dog. 2. The effects of FK are abolished by both OND and atropine while those of erythromycin are abolished by atropine. Despite similarity in structure, the motility effects of FK and EM differs in both character and mechanism. I \ \ 

EFFECT OF FK-506 ON GASTROINTESTINAL-TRACT - COMPARISON WITH ERYTHROMYCIN

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EFFECT OF FK-506 ON GASTROINTESTINAL-TRACT - COMPARISON WITH ERYTHROMYCIN

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