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An α2-adrenoreceptor agonist disrupts canine jejunal myoelectric activity
April 1 9 9 5
BACTERIOTHERAPY FOR CHRONIC CONSTIPATIONA LONG TERM FOLLOW-UP. P Andrews, TJ Borody, NP Shortis, S Thompson. Centre for Digestive Diseases, Sydney 2046, AUSTRALIA. We have previously postulated that constipation results from infection of bowel flora by uncharacterised bacterial species which inhibit motility by secretion of their toxins. If true, constipation could be manipulated b y antibioticsI and bowel flora change. 2 Here, we examined the long term effects of bowel flora change in patients with severe chronic constipation (CC) (defaecation fewer than 3 times per week for more than 12 months). Aim: To study the long term effects of bowel flora replacement in patients with CC. Methods: Consecutive patients (n=45) with CC were entered into the trial. A liquid culture comprising 20 Cultured, non-pathogenic enteric anaerobes/aerobes, including Bacteroides, E. coli and Lactobacillu$ species, were m a d e up to 300cc. Pre-treatment, patients underwent 3 day antibiotic course (neomycin sulfate, metronidazole, nystatin and bismuth subcitrate) and bowel lavage (PEG) while on a low fibre diet. On the 4th day bacterial cultures were infused via colonoscope into the caecum (under CO 2 cover), followed the next day b y a 2nd infusion via enema. Patient follow up was carried out at 9-19 months (x = 14.2 _+2.86) after procedure. Results: 40/45 patients (89%) obtained gratifying relief in defecation ease, bloating and abdominal pain immediately after the procedure. At follow up 18/30 (60%) of those contacted continued to have normalised defaecation without laxative use. Conclusions: I. Manipulation of colonic microflora may provide long term relief of CC. 2. Colonic microflora abnormality m a y be an important cause of CC. Refs: I. Borody TJ, et al. Gastroenterology 1989; 96: A52. 2. Andrews P, et al. Gastroenterology 1994; 106: A590.
• B O T U L I N U M T O X I N F O R A C H A L A S I A : A PLACEBO C O N T R O L L E D T R I A L W I T H F O L L O W - U P OF SIX M O N T H S . V . A n n e s e , F . P e r r i G.Napolitano,M.Basciani,P.Simone,A.Andriulli,G.Vantrappen, CSS Hospital, San G i o v a n n i Rotondo, Italy.
R e c e n t l y i n t r a s p h i n c t e r i c i n j e c t i o n of B o t u l i n u m toxin (Botx) was shown to be e f f e c t i v e in the short t e r m t r e a t m e n t of achalasia. We p e r f o r m e d a doubleblind, p l a c e b o - c o n t r o l l e d s t u d y on the results of B o t x in i0 c o n s e c u t i v e s y m p t o m a t i c a c h a l a s i a p a t i e n ts. Patients w e r e r a n d o m i z e d to treatment w i t h either 100U of Botx (25 U/ml) or normal saline, injected e n d o s c o p i c a l l y at 8 d i f f e r e n t sites of the LES (0.5 ml each). P a t i e n t s w e r e e v a l u a t e d at 1,3 and 6 months f o l l o w i n g t h e r a p y b y s y m p t o m scores, manometry and r a d i o n u c l i d e emptying. Patients who failed to r e s p o n d to i n j e c t i o n t h e r a p y at 1 m o n t h followup u n d e r w e n t p n e u m a t i c dilatation. Patients who had d e v e l o p p e d s y m p t o m s at 3 months follow-up were t r e a ted by a second B o t x injection. Results None of the 5 patients treated with placebo showed changes in symptoms score or objective tests. All underwent p n e u m a t i c dilatation. F o u r of the 5 patients treated w i t h Botx r e q u i r e d a second i n j e c t i o n at the 3 months f o l l o w - u p visit. S y m p t o m score, LES basal p r e s sure and e s o p h a g e a l r e t e n t i o n s i g n i f i c a n t l y improved after B o t x i n j e c t i o n and p n e u m a t i c dilatation c o m p a r e d to b a s e l i n e and p l a c e b o (p<.02). No significant d i f f e r e n c e was found b e t w e e n Botx and pneumatic d i l a t a t i o n at the 6 months follow-up visit. (M±SD) LES (mmHg) S y m p t o m score 10'Retention Basal 34±8 3.4±0.6 74±24 P l a c e b o i mo 35±9 3.2±0.4 67±28 Botx i mo 27±10 0.4±0.5 53±23 Botx 6 mo 25±9 0.5±0.3 49±25 Dilat 6 mo 16±6 0.4±0.4 28±31 C o n c l u s i o n B o t u l i n u m toxin injections are able to r e l i e v e the symptoms to the same degree as pneumatic d i l a t a t i o n . L E S p r e s s u r e and esophageal e m p t y i n g showed less improvement. The clinical benefit wanes over time but is r e s t o r e d after further injections.
Motility and Nerve-Gut Interactions
A563
AN ot2-ADRENORECEPTOR AGONIST DISRUPTS CANINE JEJUNAL MYOELECTRIC ACTIVITY. L.A. Anestidou, C.F. Burrows. Dept of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL Xylazine HCI, an a2-adrenoreceptor agonist with predictable sedative and analgesic properties, is extensively used in canine anesthetic protocols. AIM: In this study, we examined the effects of xylazine HCI administration on jejunal myoelectric activity in four adult hound dogs chronically implanted with bipolar silver wire electrodes. METHODS: After an 18 hour fast, a bolus dose of 0.5 mg/kg iv of either 0.9% NaC1 (control) or 2% xylazine HC1 (treatment) was administered as follows: a) fasted state: 10 rain. after the beginning of intermittent spike activity (phase II) of the MMC and b)fed state: 20 rain. after the introduction (by feeding commercial meat based diet) of the postprandial pattern. RESULTS: 0.5 mg/kg iv of xylazine HCI caused an immediate inhibition of phase II spike activity for 126.02 rain. _+ 12.98 (SE of least square mean), (p < 0.05).This period of phase I-like activity was longer than the control phase I and caused significant prolongation of MMC duration (from 122.75 rain. _+ 11.14to 253.14 rain. + 11.14). Despite the presence of a similarly significant 82.81 rain. _+ 1,92 postprandial spike activity inhibition immediately after xy!azine administration, fed pattern duration was not significantly prolonged. Both phase II and postprandial spike activity returned at pretreatment values upon termination of the xylazine-induced phase l-like period. CONCLUSIONS: Administration of xylazine HCI in dogs a) inhibits jejunal phase II and fed spike activity to induce a finite, dose-dependent phase I-like period and b) prolongs jejunal MMC duration.
• EFFECT OF GLP-I ON ANTROPYLORIC MOTILITIY; TRANSPYLORIC FLOW AND GASTRIC EMPTYING OF NON-NUTRIENT LIQUIDS IN CONSCIOUS DOGS. M. Anvari, C.A. Paterson, E.E. Daniel, T.J. McDonald*. Departments of Surgery and Physiology, McMaster University, Hamilton, and *Dept. of Medicine, University of Western Ontario, London, Canada. The role of GLP-I in the regulation of gastric emptying is poorly understood. We studied the effect of GLP-I, on antropyloric motility, gastric emptying and transpyloric flow in 5 conscious clogs equipped with chronic gastric and duodenal cannula. Antropyloroduodenal motility was measured with a seven-lumen sleeve/sidehole catheter during concurrent measurements of transpyloric flow and gastric emptying for 30 rain after instillation of 500 ml of saline into the stomach. Recordings were started 15 minutes after i- start of intravenous infusion of 0.9 M Saline at 5.5 ml/min (Control), ii- 10 ml intravenous bolus of GLP-1 (20pmol/kg) followed by GLP-1 infusion (2.4 pmol/kg/min) at a rate of 5.5 ml/minute. Each dog underwent 3 studies under each test condition. Infusion of GLP-1 was associated with retardation of gastric emptying (22_+6%) in the 30 min period, in comparison to the controls (89_+3%). During saline infusion most of the liquid meal emptied in the first 10 minutes (table). During this period, there was a significant drop in the number and volume of flow pulses during GLP-I infusion in comparison to the control. This change in transpyloric flow was associated with inhibition of antropyloric pressure waves (APWs) and stimulation of isolated pyloric pressure waves (IPPWs) and increase in basal pyloric tone induced by intravenous GLP-I infusion (table). values in first 10 min Control GLP-1 % emptying 76.8+4.2 7.6+2.5 * No. flow pulses 20.2+2.0 1.3+0.8 * flow pulse volume 18.0+3.0 1.2_+0.6 * APW/min 2.4_+0.3 0.8_+0.3 * IPPW/min 0.1-+0.05 1.3_+0.3 * pyloric tone 1.9-+0.3 7.4_+1.3 * (mean _+SE, * p
BACTERIOTHERAPY FOR CHRONIC CONSTIPATIONA LONG TERM FOLLOW-UP. P Andrews, TJ Borody, NP Shortis, S Thompson. Centre for Digestive Diseases, Sydney 2046, AUSTRALIA. We have previously postulated that constipation results from infection of bowel flora by uncharacterised bacterial species which inhibit motility by secretion of their toxins. If true, constipation could be manipulated b y antibioticsI and bowel flora change. 2 Here, we examined the long term effects of bowel flora change in patients with severe chronic constipation (CC) (defaecation fewer than 3 times per week for more than 12 months). Aim: To study the long term effects of bowel flora replacement in patients with CC. Methods: Consecutive patients (n=45) with CC were entered into the trial. A liquid culture comprising 20 Cultured, non-pathogenic enteric anaerobes/aerobes, including Bacteroides, E. coli and Lactobacillu$ species, were m a d e up to 300cc. Pre-treatment, patients underwent 3 day antibiotic course (neomycin sulfate, metronidazole, nystatin and bismuth subcitrate) and bowel lavage (PEG) while on a low fibre diet. On the 4th day bacterial cultures were infused via colonoscope into the caecum (under CO 2 cover), followed the next day b y a 2nd infusion via enema. Patient follow up was carried out at 9-19 months (x = 14.2 _+2.86) after procedure. Results: 40/45 patients (89%) obtained gratifying relief in defecation ease, bloating and abdominal pain immediately after the procedure. At follow up 18/30 (60%) of those contacted continued to have normalised defaecation without laxative use. Conclusions: I. Manipulation of colonic microflora may provide long term relief of CC. 2. Colonic microflora abnormality m a y be an important cause of CC. Refs: I. Borody TJ, et al. Gastroenterology 1989; 96: A52. 2. Andrews P, et al. Gastroenterology 1994; 106: A590.
• B O T U L I N U M T O X I N F O R A C H A L A S I A : A PLACEBO C O N T R O L L E D T R I A L W I T H F O L L O W - U P OF SIX M O N T H S . V . A n n e s e , F . P e r r i G.Napolitano,M.Basciani,P.Simone,A.Andriulli,G.Vantrappen, CSS Hospital, San G i o v a n n i Rotondo, Italy.
R e c e n t l y i n t r a s p h i n c t e r i c i n j e c t i o n of B o t u l i n u m toxin (Botx) was shown to be e f f e c t i v e in the short t e r m t r e a t m e n t of achalasia. We p e r f o r m e d a doubleblind, p l a c e b o - c o n t r o l l e d s t u d y on the results of B o t x in i0 c o n s e c u t i v e s y m p t o m a t i c a c h a l a s i a p a t i e n ts. Patients w e r e r a n d o m i z e d to treatment w i t h either 100U of Botx (25 U/ml) or normal saline, injected e n d o s c o p i c a l l y at 8 d i f f e r e n t sites of the LES (0.5 ml each). P a t i e n t s w e r e e v a l u a t e d at 1,3 and 6 months f o l l o w i n g t h e r a p y b y s y m p t o m scores, manometry and r a d i o n u c l i d e emptying. Patients who failed to r e s p o n d to i n j e c t i o n t h e r a p y at 1 m o n t h followup u n d e r w e n t p n e u m a t i c dilatation. Patients who had d e v e l o p p e d s y m p t o m s at 3 months follow-up were t r e a ted by a second B o t x injection. Results None of the 5 patients treated with placebo showed changes in symptoms score or objective tests. All underwent p n e u m a t i c dilatation. F o u r of the 5 patients treated w i t h Botx r e q u i r e d a second i n j e c t i o n at the 3 months f o l l o w - u p visit. S y m p t o m score, LES basal p r e s sure and e s o p h a g e a l r e t e n t i o n s i g n i f i c a n t l y improved after B o t x i n j e c t i o n and p n e u m a t i c dilatation c o m p a r e d to b a s e l i n e and p l a c e b o (p<.02). No significant d i f f e r e n c e was found b e t w e e n Botx and pneumatic d i l a t a t i o n at the 6 months follow-up visit. (M±SD) LES (mmHg) S y m p t o m score 10'Retention Basal 34±8 3.4±0.6 74±24 P l a c e b o i mo 35±9 3.2±0.4 67±28 Botx i mo 27±10 0.4±0.5 53±23 Botx 6 mo 25±9 0.5±0.3 49±25 Dilat 6 mo 16±6 0.4±0.4 28±31 C o n c l u s i o n B o t u l i n u m toxin injections are able to r e l i e v e the symptoms to the same degree as pneumatic d i l a t a t i o n . L E S p r e s s u r e and esophageal e m p t y i n g showed less improvement. The clinical benefit wanes over time but is r e s t o r e d after further injections.
Motility and Nerve-Gut Interactions
A563
AN ot2-ADRENORECEPTOR AGONIST DISRUPTS CANINE JEJUNAL MYOELECTRIC ACTIVITY. L.A. Anestidou, C.F. Burrows. Dept of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL Xylazine HCI, an a2-adrenoreceptor agonist with predictable sedative and analgesic properties, is extensively used in canine anesthetic protocols. AIM: In this study, we examined the effects of xylazine HCI administration on jejunal myoelectric activity in four adult hound dogs chronically implanted with bipolar silver wire electrodes. METHODS: After an 18 hour fast, a bolus dose of 0.5 mg/kg iv of either 0.9% NaC1 (control) or 2% xylazine HC1 (treatment) was administered as follows: a) fasted state: 10 rain. after the beginning of intermittent spike activity (phase II) of the MMC and b)fed state: 20 rain. after the introduction (by feeding commercial meat based diet) of the postprandial pattern. RESULTS: 0.5 mg/kg iv of xylazine HCI caused an immediate inhibition of phase II spike activity for 126.02 rain. _+ 12.98 (SE of least square mean), (p < 0.05).This period of phase I-like activity was longer than the control phase I and caused significant prolongation of MMC duration (from 122.75 rain. _+ 11.14to 253.14 rain. + 11.14). Despite the presence of a similarly significant 82.81 rain. _+ 1,92 postprandial spike activity inhibition immediately after xy!azine administration, fed pattern duration was not significantly prolonged. Both phase II and postprandial spike activity returned at pretreatment values upon termination of the xylazine-induced phase l-like period. CONCLUSIONS: Administration of xylazine HCI in dogs a) inhibits jejunal phase II and fed spike activity to induce a finite, dose-dependent phase I-like period and b) prolongs jejunal MMC duration.
• EFFECT OF GLP-I ON ANTROPYLORIC MOTILITIY; TRANSPYLORIC FLOW AND GASTRIC EMPTYING OF NON-NUTRIENT LIQUIDS IN CONSCIOUS DOGS. M. Anvari, C.A. Paterson, E.E. Daniel, T.J. McDonald*. Departments of Surgery and Physiology, McMaster University, Hamilton, and *Dept. of Medicine, University of Western Ontario, London, Canada. The role of GLP-I in the regulation of gastric emptying is poorly understood. We studied the effect of GLP-I, on antropyloric motility, gastric emptying and transpyloric flow in 5 conscious clogs equipped with chronic gastric and duodenal cannula. Antropyloroduodenal motility was measured with a seven-lumen sleeve/sidehole catheter during concurrent measurements of transpyloric flow and gastric emptying for 30 rain after instillation of 500 ml of saline into the stomach. Recordings were started 15 minutes after i- start of intravenous infusion of 0.9 M Saline at 5.5 ml/min (Control), ii- 10 ml intravenous bolus of GLP-1 (20pmol/kg) followed by GLP-1 infusion (2.4 pmol/kg/min) at a rate of 5.5 ml/minute. Each dog underwent 3 studies under each test condition. Infusion of GLP-1 was associated with retardation of gastric emptying (22_+6%) in the 30 min period, in comparison to the controls (89_+3%). During saline infusion most of the liquid meal emptied in the first 10 minutes (table). During this period, there was a significant drop in the number and volume of flow pulses during GLP-I infusion in comparison to the control. This change in transpyloric flow was associated with inhibition of antropyloric pressure waves (APWs) and stimulation of isolated pyloric pressure waves (IPPWs) and increase in basal pyloric tone induced by intravenous GLP-I infusion (table). values in first 10 min Control GLP-1 % emptying 76.8+4.2 7.6+2.5 * No. flow pulses 20.2+2.0 1.3+0.8 * flow pulse volume 18.0+3.0 1.2_+0.6 * APW/min 2.4_+0.3 0.8_+0.3 * IPPW/min 0.1-+0.05 1.3_+0.3 * pyloric tone 1.9-+0.3 7.4_+1.3 * (mean _+SE, * p