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The role of autonomic testing in determining the inheritance pattern and pathogenesis of familial achalasia
April 1 9 9 5
INCREASED ACCURACY OF C14-D-XYLOSE BREATH TEST FOR DETECTING SMALL INTESTINAL BACTERIAL OVERGROWTH BY CORRECTION WITH GASTRIC EMPTYING. C-S Chang, G-H Chen, SN Peng, C-K Huang, S-J Wang*, C-H Kao*. Section of Gastoenterology, Department of Internal Medicine, Department of Nuclear Medicine*, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C. To date, there is no general agreement as to which test should be preferred for the diagnosis of small intestinal bactedal overgrowth. The 1-g C14-D-xylose breath test has been proposed to be a very sensitive and specific test for the diagnosis of bactedal overgrowth. However, in patients with severe motor dysfunction, the lack of consistent delivery of C14-D-xylose to the region of bacterial contamination may result in a "negative" result. The aim of this study was to determine if the accuracy of C14-D-xylose breath test for detecting bacterial overgrowth can be increased by correction with the gastdc emptying rate of C14-D-xylose. Methods: Ten culture positive patients and 10 culture negative controls were included in the study. Small intestinal aspirate for bacteriologic culture was obtained endoscopically. Liquid phase gastdc emptying study was performed to assess the amount of C14-D-xylose entered the small intestine. The results of the percentage of expired 14002 at 30 min were corrected with the amount of C14-D-xylose entered the small intestine. Results: There were 6 patients in the culture positive group with 14002 concentration above the normal limit. There were 3 patients, with initially negative results by the uncorrected method, turned to be positive after correction. All these 3 patients had prolonged gastric emptying of C14-D-xylose. When compared with cultures of small intestine aspirates, the sensitivity and specificity of the uncorrected 014D-xylose breath test were 60% and 90% respectively. In contrast, the sensitivity and specificity of the corrected C14-D-xylose breath test improved to be 90% and 100% respectively. Conclusions: Using the gastdc emptying rate of C14-D-xylose as a correcting factor, we found a higher sensitivity and specificity for C14-D-xylose breath test than the conventional method to detect small intestinal bacterial overgrowth.
SPECIFIC QUALITY OF LIFE QUESTIONNAIRE IN IRRITABLE BOWEL SYNDROME. EFFECT OF FEDOTOZINE. O. Chassany. J. Gen~ve, J.L. Abitbol, B. Scherrer, M. Dapoigny, B. Fraitag. Service Mddical d'Accueil, H6pital Lariboisi~re, 75010 Paris; Institut de Recherche Jouveinal, 94260 Fresnes; Service d'Hdpatogastroent~rologie, H6tel Dieu, 63003 Clermont-Ferrand. France. Health related quality of life measure is an important outcome in the evaluation of drug effect in Irritable Bowel Syndrome (IBS). No specific quality of life questionnaire has until now been developed. Aims of this randomized, double blind, placebo-controlled, parallel group trial, were to assess the efficacy of fedotozine (FZ) using a specifically designed for IBS quality of life questionnaire and to confirm coherence of questionnaire answers. The study was carried out by 70 French investigators. After a 10 to 14 days run-in placebo period, only patients with persisting lower abdominal pain were included in the trial. 277 patients (167 women, 100 men; mean age : 42 + 14) were randomized in 2 groups, receiving during 6 weeks, either oral FZ 30 nag t.Ld. (n=144) or placebo (PL) t.i.d. (n = 133). The quality of life measure consisted of a self-administered questionnaire of 59 items (answer : yes/no), that was filled in by patients in the practitioner's waiting room before and after 6 weeks of treatment with FZ or PL. Main outcome criterion was the intensity of lower abdominal pain with intent-to-treat analysis comparing the mean improvement over the last 3 weeks of treatment (ANOVA). A factorial analysis verified if questionnaire answers were consistent to the expected answers, whatever the treatment received. 8 questions negatively asked, resulted in inverse answers and were excluded from further analysis using multiple correspondances. After stratification on age and sex, analysis revealed a significant difference (p = 0,033) of FZ over PL. During treatment, the improvement of abdominal pain was also significantly higher on FZ than on PL (p = 0,038). C o n c l u s i o n . The use of IBS specific quality of life questionnaire confirmed the efficacy of FZ in the symptomatic relief of IBS lower abdominal pain as assessed by patients. This new specific scale is a ~ f i x l tool in the evaluation of drug efficacy during therapeutic trials in IBS. This research was handed by Jouveinal, Fresnes, France.
Motility and Nerve-Gut Interactions
A581
SCINTIGRAPHIC TRANSIT THROUGH THE STOMACH, SMALL BOWEL AND COLON IN PATIENTS WITH CHRONIC DIARRHEA. F. Charles, S.F. Phillips, M. Camilleri, G.M. Thomforde. Gastroenterology Research Unit, Mayo Clinic, Rochester, MN. We have validated previously (Gastroenterology 106:A476, 1994) the clinical utility of a simplified, scintigraphic test for transit abnormalities in patients with a variety of gastrointestinal symptoms. In the present study, we evaluated transit through the stomach, small bowel and colon in 93 consecutive patients with chronic diarrhea (z3 loose stools/d for more than six months). Thirty-three of them were subsequently diagnosed with organic diseases (including 8 with prior gastric surgery) as a cause of diarrhea, and 60 were categorized as irritable bowel syndrome (IBS; 15 with a history of cholecystectomy). METHODS: Following an overnight fast, ]~atients swallowed a methac~-~ate ~ d pH-sensitive capsule containing IIIlnCI3labelled amberlite pellets (1 mm average diameter); two hours later, a 99roTe-labelled (Amberlite pellets) egg-meal was eaten. Scans were taken with a gamma-camera at 0, 2, 4, 6 and 24 hours (H2-24). Gastric emptying and small bowel transit were evaluated by the percent of 99mTc left in the stomach at H2 (N: 54-76%) and H4 (N: 0-40%), and 99rnTc reaching the cecum at H6 (N: 11-70%) respectively. Colonic transit was quantified as the geometric center of 111InC13 counts at H4 (GC4, N< 1.4) and H24 (GC24, N: 1.7-4). RESULTS are expressed as the number of patients with slow (S), normal (N) and fast (F) transit. Stomach Small Bowel Colon S
N
F
S
N
F
S
N
F
Organic diseases (33) 9 12 12 8 13 12 3 17 13 Functional (60) IBS(45) 4 19 22 6 37 2 8 28 9 Cholecystectomy (15) 1 12 2 3 12 0 1 8 6 SUMMARY AND CONCLUSIONS: Rapid gastric emptying was common in patients with IBS, but not when cholecystectomy had been performed (p<0.02 by Fisher's exact test). Of 12 with organic disease and rapid gastric emptying, 8 had previously undergone gastric surgery. Thus, there appears to be a subgroup of IBS patients, without prior cholecystectomy, in whom rapid gastric emptying may contribute to the pathophysiology of chronic diarrhea.
THE ROLE OF AUTONOMIC TESTING IN DETERMINIG THE INHERITANCE PATTERN AND PATHOGENESIS OF FAMILIAL ACHALASIA. G Chelimsky, TC Chelimsky, JT Boyle. Depts. of Peds and Neurology, Case Western Reserve and University Hospitals of Cleveland, OH. Recent descriptions of diffuse autonomic dysfunction in patients with achalasia have called into question the traditional view of an underlying neuropathy restricted to the smooth muscle of the esophagus: We performed comprehensive autonomic testing in a family in which 2 children manifested classical clinical, radiological and manometric signs of achalasia. They later developed physical signs of a combined central and peripheral neurologic disorder. The other family members had no complaints. A i m s : To defme: (1) the extent of autonomic dysfunction in this family; (2) if autonomic testing localized the nervous system lesion associated with achalasia; (3) the mode of inheritance of this lesion. Methods: We performed autonomic resting that included: variation of heart rate associated with deep breathing (DB), changes in heart rate and blood pressure during Valsalva maneuver (VM) and tilt table test (TTr), sweat pattern by thermoregulatory sweat test (TST), quantitative sweat output pattern by axon reflex sweat test (QSART), and tear output following pilocarpine (PT). The parasympathetic system was evaluated by DB, VM and PT. The sympathetic system was evaluated by VM, TIT, QSART and TST. An abnormal QSART indicates peripheral autonomic dysfunction. TST defines central, peripheral or mixed autonomic disorder. Results: The table summarizes results of autonomic testing in this family. Positive results (+) indicate an abnormal testing based on description in methods section. F-~y Member Mother Father Son Daughter Daughter
Age A ~ (Yrs) -lasia 44 44 17 + 14 + 11
Location Central Peripheral + +
+ + + +
B r ~ P~a~ymp SLmE+ + +
+ + + +
Conclusions: 1) Comprehensive autonomic testing revealed that this family has a diffuse autonomic disorder dominantly inherited from the father. 2) The asymptomatic affected family members manifest a peripheral autonomic neuropathy only. 3) The distinguishing feature of the patients with achalasia is evidence of a central autonomic disorder.
INCREASED ACCURACY OF C14-D-XYLOSE BREATH TEST FOR DETECTING SMALL INTESTINAL BACTERIAL OVERGROWTH BY CORRECTION WITH GASTRIC EMPTYING. C-S Chang, G-H Chen, SN Peng, C-K Huang, S-J Wang*, C-H Kao*. Section of Gastoenterology, Department of Internal Medicine, Department of Nuclear Medicine*, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C. To date, there is no general agreement as to which test should be preferred for the diagnosis of small intestinal bactedal overgrowth. The 1-g C14-D-xylose breath test has been proposed to be a very sensitive and specific test for the diagnosis of bactedal overgrowth. However, in patients with severe motor dysfunction, the lack of consistent delivery of C14-D-xylose to the region of bacterial contamination may result in a "negative" result. The aim of this study was to determine if the accuracy of C14-D-xylose breath test for detecting bacterial overgrowth can be increased by correction with the gastdc emptying rate of C14-D-xylose. Methods: Ten culture positive patients and 10 culture negative controls were included in the study. Small intestinal aspirate for bacteriologic culture was obtained endoscopically. Liquid phase gastdc emptying study was performed to assess the amount of C14-D-xylose entered the small intestine. The results of the percentage of expired 14002 at 30 min were corrected with the amount of C14-D-xylose entered the small intestine. Results: There were 6 patients in the culture positive group with 14002 concentration above the normal limit. There were 3 patients, with initially negative results by the uncorrected method, turned to be positive after correction. All these 3 patients had prolonged gastric emptying of C14-D-xylose. When compared with cultures of small intestine aspirates, the sensitivity and specificity of the uncorrected 014D-xylose breath test were 60% and 90% respectively. In contrast, the sensitivity and specificity of the corrected C14-D-xylose breath test improved to be 90% and 100% respectively. Conclusions: Using the gastdc emptying rate of C14-D-xylose as a correcting factor, we found a higher sensitivity and specificity for C14-D-xylose breath test than the conventional method to detect small intestinal bacterial overgrowth.
SPECIFIC QUALITY OF LIFE QUESTIONNAIRE IN IRRITABLE BOWEL SYNDROME. EFFECT OF FEDOTOZINE. O. Chassany. J. Gen~ve, J.L. Abitbol, B. Scherrer, M. Dapoigny, B. Fraitag. Service Mddical d'Accueil, H6pital Lariboisi~re, 75010 Paris; Institut de Recherche Jouveinal, 94260 Fresnes; Service d'Hdpatogastroent~rologie, H6tel Dieu, 63003 Clermont-Ferrand. France. Health related quality of life measure is an important outcome in the evaluation of drug effect in Irritable Bowel Syndrome (IBS). No specific quality of life questionnaire has until now been developed. Aims of this randomized, double blind, placebo-controlled, parallel group trial, were to assess the efficacy of fedotozine (FZ) using a specifically designed for IBS quality of life questionnaire and to confirm coherence of questionnaire answers. The study was carried out by 70 French investigators. After a 10 to 14 days run-in placebo period, only patients with persisting lower abdominal pain were included in the trial. 277 patients (167 women, 100 men; mean age : 42 + 14) were randomized in 2 groups, receiving during 6 weeks, either oral FZ 30 nag t.Ld. (n=144) or placebo (PL) t.i.d. (n = 133). The quality of life measure consisted of a self-administered questionnaire of 59 items (answer : yes/no), that was filled in by patients in the practitioner's waiting room before and after 6 weeks of treatment with FZ or PL. Main outcome criterion was the intensity of lower abdominal pain with intent-to-treat analysis comparing the mean improvement over the last 3 weeks of treatment (ANOVA). A factorial analysis verified if questionnaire answers were consistent to the expected answers, whatever the treatment received. 8 questions negatively asked, resulted in inverse answers and were excluded from further analysis using multiple correspondances. After stratification on age and sex, analysis revealed a significant difference (p = 0,033) of FZ over PL. During treatment, the improvement of abdominal pain was also significantly higher on FZ than on PL (p = 0,038). C o n c l u s i o n . The use of IBS specific quality of life questionnaire confirmed the efficacy of FZ in the symptomatic relief of IBS lower abdominal pain as assessed by patients. This new specific scale is a ~ f i x l tool in the evaluation of drug efficacy during therapeutic trials in IBS. This research was handed by Jouveinal, Fresnes, France.
Motility and Nerve-Gut Interactions
A581
SCINTIGRAPHIC TRANSIT THROUGH THE STOMACH, SMALL BOWEL AND COLON IN PATIENTS WITH CHRONIC DIARRHEA. F. Charles, S.F. Phillips, M. Camilleri, G.M. Thomforde. Gastroenterology Research Unit, Mayo Clinic, Rochester, MN. We have validated previously (Gastroenterology 106:A476, 1994) the clinical utility of a simplified, scintigraphic test for transit abnormalities in patients with a variety of gastrointestinal symptoms. In the present study, we evaluated transit through the stomach, small bowel and colon in 93 consecutive patients with chronic diarrhea (z3 loose stools/d for more than six months). Thirty-three of them were subsequently diagnosed with organic diseases (including 8 with prior gastric surgery) as a cause of diarrhea, and 60 were categorized as irritable bowel syndrome (IBS; 15 with a history of cholecystectomy). METHODS: Following an overnight fast, ]~atients swallowed a methac~-~ate ~ d pH-sensitive capsule containing IIIlnCI3labelled amberlite pellets (1 mm average diameter); two hours later, a 99roTe-labelled (Amberlite pellets) egg-meal was eaten. Scans were taken with a gamma-camera at 0, 2, 4, 6 and 24 hours (H2-24). Gastric emptying and small bowel transit were evaluated by the percent of 99mTc left in the stomach at H2 (N: 54-76%) and H4 (N: 0-40%), and 99rnTc reaching the cecum at H6 (N: 11-70%) respectively. Colonic transit was quantified as the geometric center of 111InC13 counts at H4 (GC4, N< 1.4) and H24 (GC24, N: 1.7-4). RESULTS are expressed as the number of patients with slow (S), normal (N) and fast (F) transit. Stomach Small Bowel Colon S
N
F
S
N
F
S
N
F
Organic diseases (33) 9 12 12 8 13 12 3 17 13 Functional (60) IBS(45) 4 19 22 6 37 2 8 28 9 Cholecystectomy (15) 1 12 2 3 12 0 1 8 6 SUMMARY AND CONCLUSIONS: Rapid gastric emptying was common in patients with IBS, but not when cholecystectomy had been performed (p<0.02 by Fisher's exact test). Of 12 with organic disease and rapid gastric emptying, 8 had previously undergone gastric surgery. Thus, there appears to be a subgroup of IBS patients, without prior cholecystectomy, in whom rapid gastric emptying may contribute to the pathophysiology of chronic diarrhea.
THE ROLE OF AUTONOMIC TESTING IN DETERMINIG THE INHERITANCE PATTERN AND PATHOGENESIS OF FAMILIAL ACHALASIA. G Chelimsky, TC Chelimsky, JT Boyle. Depts. of Peds and Neurology, Case Western Reserve and University Hospitals of Cleveland, OH. Recent descriptions of diffuse autonomic dysfunction in patients with achalasia have called into question the traditional view of an underlying neuropathy restricted to the smooth muscle of the esophagus: We performed comprehensive autonomic testing in a family in which 2 children manifested classical clinical, radiological and manometric signs of achalasia. They later developed physical signs of a combined central and peripheral neurologic disorder. The other family members had no complaints. A i m s : To defme: (1) the extent of autonomic dysfunction in this family; (2) if autonomic testing localized the nervous system lesion associated with achalasia; (3) the mode of inheritance of this lesion. Methods: We performed autonomic resting that included: variation of heart rate associated with deep breathing (DB), changes in heart rate and blood pressure during Valsalva maneuver (VM) and tilt table test (TTr), sweat pattern by thermoregulatory sweat test (TST), quantitative sweat output pattern by axon reflex sweat test (QSART), and tear output following pilocarpine (PT). The parasympathetic system was evaluated by DB, VM and PT. The sympathetic system was evaluated by VM, TIT, QSART and TST. An abnormal QSART indicates peripheral autonomic dysfunction. TST defines central, peripheral or mixed autonomic disorder. Results: The table summarizes results of autonomic testing in this family. Positive results (+) indicate an abnormal testing based on description in methods section. F-~y Member Mother Father Son Daughter Daughter
Age A ~ (Yrs) -lasia 44 44 17 + 14 + 11
Location Central Peripheral + +
+ + + +
B r ~ P~a~ymp SLmE+ + +
+ + + +
Conclusions: 1) Comprehensive autonomic testing revealed that this family has a diffuse autonomic disorder dominantly inherited from the father. 2) The asymptomatic affected family members manifest a peripheral autonomic neuropathy only. 3) The distinguishing feature of the patients with achalasia is evidence of a central autonomic disorder.