- Email: [email protected]
A multinational comparison of racecadotril and loperamide in the treatment of acute watery diarrhea in adults
Apri12000
AGAA377
shown in the table. Except one (myalgia) there were no serious side effects. 7 pts are still on low dose (3-6 mg) treatment (1-11 months). 2 of these pts showed clinical relapse after withdrawl of budesonide. 5 pts are still in remission 3-6 months after the end of therapy. Histological reevaluation showed complete remission in one pt and improvement with reduction of the Iymphcytic mucosal infiltration in another. Conclusion: Oral budesonide seems to be an promising alternative treatment of collagenous and microscopic colitis. In addition to clinical benefit this topic steroid with a high first pass metabolism rarely shows systemic side effects. Pre- and posttreatment stool analysis Frequency/d
S·weight (g/24 h)
S·fat (g/24h)
S-water(%)
5(2-8) 1.5 (0-2)
510 (300-810) 240 (125-385)
119(6.8-174) 5.9 (2.7-8.5)
88 (815 - 92.8) 81.5 (70.5-84.3)
ing and diarrhea. Results: Study subjects reported that the technology caused minimal inconvenience. Correlation coefficients were calculated between lactose intake and the three symptoms. This calculation was conducted for several time lags between diet and symptoms. Correlations between lactose ingestion and gas production in a typical LI patient (positive hydrogen breath test) and a symptomatic control (negative hydrogen breath test) are shown. The LI subject showed a higher average correlation with (P < 0.13), thus enabling this technology to distinguish LI from non-specific GI symptoms. Conclusions: We have established the only interactive software to date which has enabled the differentiation of individuals who have specific food intolerances (e.g. LI) from controls. It is hypothesized that this technology will enable us to identify other dietary intolerances as may be seen in disorders such as GERD.
1997 pre
post
1995 MECHANISM OF DIARRHEA IN MICROSCOPIC COLITIS. Marijana B. Nedeljkovic Protic, Dusanka Necic, Svetlana Milutinovic Djuric, Njegica Jojic, Petar Svorcan, Branka Dapcevic, Obren Popovic, Yugoslav Railway Health Ctr, Belgrade, Yugoslavia; Med Centar Zvezdara, Belgrade, Yugoslavia; Med Ctr Zvezdara, Belgrade, Yugoslavia. INTRODUCTION: Microscopic colitides(MC) are newly recognized forms of colitis. Chronic watery diarrhea and colicky abdominal pains are basic clinical symptoms in patients with these forms of colitis. Endoscopical and X rays examinations of gastrointestinal tract are normal. Microscopical changes of colonic biopsy specimens are major cryterium for diagnosis of Me. PURPOSE: Purpose of this study was to search for the pathophysiological mechanism of diarrhea based on data of fecal osmotic gap, fecal electrolytes, as well as to classify them according to the specific types of diarrhea. MATERIALS AND METHODS: 37 patients were included in our study. Control group was composed of 18 healthy persons. There were 30 patients with complete conditions for diagnosis of MC [23 with lymphocytic colitis(LC) and 7 with colagenous colitis (CC)]. We were not able to confirm diarrhea in 7 patients with histological diagnoses of MC. All tested patients collected stool for three days (72 h). Concentration of sodium and potassium were determined by flame photometry and concentration of chloride by the titration method of Scribner. Fecal osmotic gap was calculated from the difference of measured osmolality of fecal fluid and double sum of the sodium and potassium concentration. For the statistical analysis we used analysis of variance, Fischer test and LSD test. DISCUSSION: Sodium concentration of the fecal fluid in our patients with LC and CC was highly increased. Potassium concentration in patients with LC was significantly less than among healthy people. The mean values of chloride concentrations in patients with CC were significantly higher compared to the control group. Our patients have had a great loss of electrolytes (Na+, K+, Cl) trough stool. These results were expected for sodium and chloride. Great potassium loss by stool appear because of its correlation with daily stool weight. This fact may explain uncommon sever hypokalemia in some patients with MC. LC and CC are characterized by secretory diarrhea. On the basis of values of Fecal Osmotic Gap, 86,7% of our patients have had a secretory diarrhea. Only 4 patients (13,3%) have had an osmotic diarrhea. CONCLUSION: On the basis of our results we may conclude that diarrhea in microscopic colitides (LC,CC) belongs to the secretory type of diarrhea. The major pathophysiological mechanism in patients with LC may be explained by the decrease of active sodium absorption. Decreased ClIHC0 3 exchange rate and increased electrogenic chloride secretion are coexistent pathways in genesis of diarrhea in colagenous colitis.
1996 DIET/SYMPTOM PATTERN MATCHING: A NOVEL DIAGNOS· TIC TOOL FOR LACTOSE INTOLERANCE. Elizabeth A. Noyszewski, Jonathan H. Kaufman, Linda B. Hurd, James D. Lewis, Gary R. Lichtenstein, Univ of Pennsylvania, Philadelphia, PA. Introduction: Lactose inlactose intolerant - _. 'control tolerance (LI) is currently diagnosed by the hydrogen breath test or the blood glucose test. Both tests require a fast, and involve substantial lactose e J 4 5 ... 6 ingestion which can cause " time lag (hI'S) patient discomfort. Most people with LI have individual threshold levels over which lactose ingestion produces symptoms. We hypothesize that an individual s intolerance to a range of lactose intake can be measured by historical diet/symptom pattern matching. A technology that employs this method may enable individuals with LI to increase dairy intake without gastrointestinal distress. Methods: We developed novel software for a handheld computer that enables individuals to record food intake and gastrointestinal symptoms as they occur. Subjects recorded diet and symptom events for 7 days. The information was transferred to a central database and converted to lactose ingestion time courses, and time courses of typical symptoms associated with LI: flatulence, abdominal pain/cramp-
1-
I:K . -.--.~n2 P2 ....
I
A MULTINATIONAL COMPARISON OF RACECADOTRIL AND LOPERAMIDE IN THE TREATMENT OF ACUTE WATERY DI· ARRHEA IN ADULTS. David Prado, for the Adult Racecadotril Study Group, Hosp Nuestra Senora del Pilar, Guatemala, Guatemala. Racecadotril (acetorphan) is an orally active, potent inhibitor of enkephalinase, which exerts an antisecretory antidiarrheal effect without increasing intestinal transit time. The aim of this study was to compare the antidiarrheal efficacy, safety, and tolerability of racecadotril with those of loperamide, assessing their effects on the resolution of the signs and symptoms of diarrhea, in patients in developing countries who had acute watery diarrhea of less than three days' duration. 945 outpatients from 14 countries and 21 centers were randomized to receive racecadotril (1OOmg) or loperamide (2mg) three times daily. The primary efficacy criterion was duration of diarrhea; secondary efficacy criteria were overall clinical response, occurrence and duration of abdominal pain and distension, and occurrence of associated signs and symptoms. Occurrence of constipation and adverse events were the main safety assessments. Diarrhea resolved rapidly after both racecadotril and loperamide (47.2 and 46 hours, respectively), and 93% of patients on racecadotril and 96% on loperarnide achieved clinical success. Racecadotril produced a significantly greater reduction in abdominal pain and distension than loperamide (p=0.012 and 0.034, respectively). The duration of abdominal distension was significantly shorter with racecadotril (6.2 v 23.2 hours; p=O.OOOl), and constipation was also significantly less frequent with racecadotril (18% v 29%; p=O.OOl). Fewer patients on racecadotril experienced treatment-related adverse events (9% v 18%). This large-scale study confirms that racecadotril resolves the symptoms of acute diarrhea rapidly and effectively. Moreover, racecadotril produced more rapid resolution of abdominal symptoms and less constipation than loperamide.
1998 DIAGNOSIS OF GRAFT VERSUS HOST DISEASE BY COLOR DOPPLER IMAGING; A PROGNOSTIC VIEW. Dagmar G. Schreiber-Dietrich, Stefan A. Klein, Hans Martin, Hans Seifert, Dieter Hoelzer, Christoph F. Dietrich, Univ Hosp Frankfurt, Frankfurt, Germany. Introduction: Involvement of the gastrointestinal tract in patients with acute graft versus host disease (aGvHD) is often severe. To define prognostic factors of clinical outcome abdominal ultrasonography was applied. High resolution ultrasonography (HRU) is sensitive in detecting bowel wall thickening. Color Doppler imaging (CDI) may differentiate between inflammatory and ischemic bowel segments. Methods: 16 consecutive patients with histologically proven acute skin-GvHD (10 m, 6 f, mean age 49 ± 12 years) or clinical signs of gastrointestinal GvHD were examined by HRU and CDI (Siemens Elegra; bowel wall thickness, flow pattern in the superior mesenteric artery (SMA) and in the bowel wall). Results: 14 of the examined aGvHD-patients showed thickened bowel wall segments in the ileocecal region (> 3 mm). 4 of these 14 patients presented no diarrhea. In 11/14 patients increased blood flow in the bowel wall was found. In contrast, 3/14 patients showed ischemic bowel wall lesions with high resistance flow pattern in the SMA. These 3 patients did not respond to immunosuppressive therapy and died within a period of 2 weeks, whereas II patients with hyperdynamic changes could be successfully treated by enforced immunosuppression. Conclusion: Ultrasonography may detect thickened bowel wall segments in asymptomatic and symptomatic patients with aGvHD. Determination of the splanchnic blood flow dynamics is helpful in identifying patients with poor prognosis.
AGAA377
shown in the table. Except one (myalgia) there were no serious side effects. 7 pts are still on low dose (3-6 mg) treatment (1-11 months). 2 of these pts showed clinical relapse after withdrawl of budesonide. 5 pts are still in remission 3-6 months after the end of therapy. Histological reevaluation showed complete remission in one pt and improvement with reduction of the Iymphcytic mucosal infiltration in another. Conclusion: Oral budesonide seems to be an promising alternative treatment of collagenous and microscopic colitis. In addition to clinical benefit this topic steroid with a high first pass metabolism rarely shows systemic side effects. Pre- and posttreatment stool analysis Frequency/d
S·weight (g/24 h)
S·fat (g/24h)
S-water(%)
5(2-8) 1.5 (0-2)
510 (300-810) 240 (125-385)
119(6.8-174) 5.9 (2.7-8.5)
88 (815 - 92.8) 81.5 (70.5-84.3)
ing and diarrhea. Results: Study subjects reported that the technology caused minimal inconvenience. Correlation coefficients were calculated between lactose intake and the three symptoms. This calculation was conducted for several time lags between diet and symptoms. Correlations between lactose ingestion and gas production in a typical LI patient (positive hydrogen breath test) and a symptomatic control (negative hydrogen breath test) are shown. The LI subject showed a higher average correlation with (P < 0.13), thus enabling this technology to distinguish LI from non-specific GI symptoms. Conclusions: We have established the only interactive software to date which has enabled the differentiation of individuals who have specific food intolerances (e.g. LI) from controls. It is hypothesized that this technology will enable us to identify other dietary intolerances as may be seen in disorders such as GERD.
1997 pre
post
1995 MECHANISM OF DIARRHEA IN MICROSCOPIC COLITIS. Marijana B. Nedeljkovic Protic, Dusanka Necic, Svetlana Milutinovic Djuric, Njegica Jojic, Petar Svorcan, Branka Dapcevic, Obren Popovic, Yugoslav Railway Health Ctr, Belgrade, Yugoslavia; Med Centar Zvezdara, Belgrade, Yugoslavia; Med Ctr Zvezdara, Belgrade, Yugoslavia. INTRODUCTION: Microscopic colitides(MC) are newly recognized forms of colitis. Chronic watery diarrhea and colicky abdominal pains are basic clinical symptoms in patients with these forms of colitis. Endoscopical and X rays examinations of gastrointestinal tract are normal. Microscopical changes of colonic biopsy specimens are major cryterium for diagnosis of Me. PURPOSE: Purpose of this study was to search for the pathophysiological mechanism of diarrhea based on data of fecal osmotic gap, fecal electrolytes, as well as to classify them according to the specific types of diarrhea. MATERIALS AND METHODS: 37 patients were included in our study. Control group was composed of 18 healthy persons. There were 30 patients with complete conditions for diagnosis of MC [23 with lymphocytic colitis(LC) and 7 with colagenous colitis (CC)]. We were not able to confirm diarrhea in 7 patients with histological diagnoses of MC. All tested patients collected stool for three days (72 h). Concentration of sodium and potassium were determined by flame photometry and concentration of chloride by the titration method of Scribner. Fecal osmotic gap was calculated from the difference of measured osmolality of fecal fluid and double sum of the sodium and potassium concentration. For the statistical analysis we used analysis of variance, Fischer test and LSD test. DISCUSSION: Sodium concentration of the fecal fluid in our patients with LC and CC was highly increased. Potassium concentration in patients with LC was significantly less than among healthy people. The mean values of chloride concentrations in patients with CC were significantly higher compared to the control group. Our patients have had a great loss of electrolytes (Na+, K+, Cl) trough stool. These results were expected for sodium and chloride. Great potassium loss by stool appear because of its correlation with daily stool weight. This fact may explain uncommon sever hypokalemia in some patients with MC. LC and CC are characterized by secretory diarrhea. On the basis of values of Fecal Osmotic Gap, 86,7% of our patients have had a secretory diarrhea. Only 4 patients (13,3%) have had an osmotic diarrhea. CONCLUSION: On the basis of our results we may conclude that diarrhea in microscopic colitides (LC,CC) belongs to the secretory type of diarrhea. The major pathophysiological mechanism in patients with LC may be explained by the decrease of active sodium absorption. Decreased ClIHC0 3 exchange rate and increased electrogenic chloride secretion are coexistent pathways in genesis of diarrhea in colagenous colitis.
1996 DIET/SYMPTOM PATTERN MATCHING: A NOVEL DIAGNOS· TIC TOOL FOR LACTOSE INTOLERANCE. Elizabeth A. Noyszewski, Jonathan H. Kaufman, Linda B. Hurd, James D. Lewis, Gary R. Lichtenstein, Univ of Pennsylvania, Philadelphia, PA. Introduction: Lactose inlactose intolerant - _. 'control tolerance (LI) is currently diagnosed by the hydrogen breath test or the blood glucose test. Both tests require a fast, and involve substantial lactose e J 4 5 ... 6 ingestion which can cause " time lag (hI'S) patient discomfort. Most people with LI have individual threshold levels over which lactose ingestion produces symptoms. We hypothesize that an individual s intolerance to a range of lactose intake can be measured by historical diet/symptom pattern matching. A technology that employs this method may enable individuals with LI to increase dairy intake without gastrointestinal distress. Methods: We developed novel software for a handheld computer that enables individuals to record food intake and gastrointestinal symptoms as they occur. Subjects recorded diet and symptom events for 7 days. The information was transferred to a central database and converted to lactose ingestion time courses, and time courses of typical symptoms associated with LI: flatulence, abdominal pain/cramp-
1-
I:K . -.--.~n2 P2 ....
I
A MULTINATIONAL COMPARISON OF RACECADOTRIL AND LOPERAMIDE IN THE TREATMENT OF ACUTE WATERY DI· ARRHEA IN ADULTS. David Prado, for the Adult Racecadotril Study Group, Hosp Nuestra Senora del Pilar, Guatemala, Guatemala. Racecadotril (acetorphan) is an orally active, potent inhibitor of enkephalinase, which exerts an antisecretory antidiarrheal effect without increasing intestinal transit time. The aim of this study was to compare the antidiarrheal efficacy, safety, and tolerability of racecadotril with those of loperamide, assessing their effects on the resolution of the signs and symptoms of diarrhea, in patients in developing countries who had acute watery diarrhea of less than three days' duration. 945 outpatients from 14 countries and 21 centers were randomized to receive racecadotril (1OOmg) or loperamide (2mg) three times daily. The primary efficacy criterion was duration of diarrhea; secondary efficacy criteria were overall clinical response, occurrence and duration of abdominal pain and distension, and occurrence of associated signs and symptoms. Occurrence of constipation and adverse events were the main safety assessments. Diarrhea resolved rapidly after both racecadotril and loperamide (47.2 and 46 hours, respectively), and 93% of patients on racecadotril and 96% on loperarnide achieved clinical success. Racecadotril produced a significantly greater reduction in abdominal pain and distension than loperamide (p=0.012 and 0.034, respectively). The duration of abdominal distension was significantly shorter with racecadotril (6.2 v 23.2 hours; p=O.OOOl), and constipation was also significantly less frequent with racecadotril (18% v 29%; p=O.OOl). Fewer patients on racecadotril experienced treatment-related adverse events (9% v 18%). This large-scale study confirms that racecadotril resolves the symptoms of acute diarrhea rapidly and effectively. Moreover, racecadotril produced more rapid resolution of abdominal symptoms and less constipation than loperamide.
1998 DIAGNOSIS OF GRAFT VERSUS HOST DISEASE BY COLOR DOPPLER IMAGING; A PROGNOSTIC VIEW. Dagmar G. Schreiber-Dietrich, Stefan A. Klein, Hans Martin, Hans Seifert, Dieter Hoelzer, Christoph F. Dietrich, Univ Hosp Frankfurt, Frankfurt, Germany. Introduction: Involvement of the gastrointestinal tract in patients with acute graft versus host disease (aGvHD) is often severe. To define prognostic factors of clinical outcome abdominal ultrasonography was applied. High resolution ultrasonography (HRU) is sensitive in detecting bowel wall thickening. Color Doppler imaging (CDI) may differentiate between inflammatory and ischemic bowel segments. Methods: 16 consecutive patients with histologically proven acute skin-GvHD (10 m, 6 f, mean age 49 ± 12 years) or clinical signs of gastrointestinal GvHD were examined by HRU and CDI (Siemens Elegra; bowel wall thickness, flow pattern in the superior mesenteric artery (SMA) and in the bowel wall). Results: 14 of the examined aGvHD-patients showed thickened bowel wall segments in the ileocecal region (> 3 mm). 4 of these 14 patients presented no diarrhea. In 11/14 patients increased blood flow in the bowel wall was found. In contrast, 3/14 patients showed ischemic bowel wall lesions with high resistance flow pattern in the SMA. These 3 patients did not respond to immunosuppressive therapy and died within a period of 2 weeks, whereas II patients with hyperdynamic changes could be successfully treated by enforced immunosuppression. Conclusion: Ultrasonography may detect thickened bowel wall segments in asymptomatic and symptomatic patients with aGvHD. Determination of the splanchnic blood flow dynamics is helpful in identifying patients with poor prognosis.