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Autonomic functioning during sleep distinguishes IBS patient subgroups
AJG – September, Suppl., 2001
symptoms are bouts of chronic abdominal pain. The overall prevalence of acute intermittent porphyria is less than 10 per 100,000. In contrast, functional bowel disorders are a much more common cause of chronic abdominal pain-like symptoms. The purpose of this study was to evaluate the usefulness of 24 hr. urine porphyrin collection in diagnosing chronic abdominal pain as compared to the Rome II diagnostic criteria for functional bowel disorders. Methods: Medical records and laboratory studies were reviewed for all patients who had urine porphyrins ordered at Mayo Clinic Scottsdale for the period Jan 1988 –June 2000. Demographic data, chief complaint, and indication for ordering urine porphyrins were reviewed. Patients were also evaluated for the presence of non-GI neurologic symptoms of porphyria and symptoms of a functional bowel disorder. Results: 103 patients had urine porphyrins ordered during the study period. Two patients were excluded for inadequate information, with 101 remaining in the study sample. 51 (50%) of these patients had chronic abdominal pain as the chief complaint and indication for ordering urine porphyrins. None of these patients had a positive urine study suggestive of acute intermittent porphyria. 42 of these 51 patients (82%) met the Rome II criteria for a functional bowel disorder, most commonly irritable bowel syndrome (45%), functional abdominal pain (29%), functional abdominal bloating (4%) and functional dyspepsia (4%). In contrast, only 9 (18%) of the patients who had porphyrins ordered for non-GI complaints (rash, urine changes, etc) met the diagnostic criteria for a functional bowel disorder (p ⬍ 0.000001). Only 14 (27%) of the patients with chronic abdominal pain had any neurologic symptoms compared to 24 of 50 patients (48%) not diagnosed with chronic abdominal pain (p ⬍ 0.03). Conclusions: Absent a neurologic symptom, testing urine porphyrins for chronic abdominal pain is not a useful diagnostic undertaking. In patients with chronic abdominal pain, functional bowel disorders are a much more likely diagnosis with a higher pretest probability. Our data suggests that the use of the Rome II criteria is a more valuable tool for the diagnosis of chronic abdominal pain as opposed to urine porphyrin collection.
Abstracts
S321
1018 Cloning of two prokineticin cDNAs: recombinant proteins potently contract gastrointestinal smooth muscle Qun-Yong Zhou*, Clayton M. Bullock, Michelle Y. Cheng and Frederick J. Elhert. 1Department of Pharmcology, University of California, Irvine, CA. Purpose: to identify novel regulators of gastrointestinal motility. Methods: Two novel human cDNAs have been cloned based on their sequence similarity to a frog secretion protein and a non-toxic protein of mamba snake venom. These human cDNAs encode two secreted proteins of 86 and 81 amino acids. Recombinant proteins with authentic N-terminal sequences have been produced in E coli and refolded into functional proteins by careful control of protein aggregation. Results: Northern blot hybridization has revealed that these cDNAs are expressed in gastrointestinal tract, particularly the stomach. Mass spectrometry has confirmed the formation of five pairs of disulfide bonds. Refolded recombinant proteins potently contract gastrointestinal smooth muscle with EC50 values in the subnanomolar range. The recombinant proteins had no effect on the contractility of vascular and respiratory smooth muscle. To reflect their potent and specific effects on gastrointestinal smooth muscle cells, we have named these recombinant proteins prokineticins. Mutagenesis studies have further revealed the importance of disulfide bonds and conserved N-terminus for the bioactivity of prokineticins. Ligand binding studies with iodinated prokineticin 1 revealed the presence of a high affinity site in ileal smooth muscle. The displacement of specific prokineticin binding by GTP␥S suggests that prokineticin receptor may belong to the family of G protein-coupled receptor. Conclusions: Our results indicate that we have identified novel endogenous protein regulators of gastrointestinal motility. The availability of recombinant prokineticins should provide novel therapeutic agents for disorders involved impaired gastrointestinal motility.
1019 1017 Autonomic functioning during sleep distinguishes IBS patient subgroups William C Orr1*, Jennifer J Thompson1 and Sigrid Elsenbruch2. 1Lynn Health Science Institute, Oklahoma City, Oklahoma, United States; and 2 Dept. of Medical Psychology, University of Essen, Essen, Germany. Purpose: Previous studies in our laboratory have demonstrated autonomic functioning during sleep to be a unique indicator of abnormal physiology in patients with IBS. Our previous work has shown that sympathovagal balance during REM sleep is enhanced in IBS patients and this appears to be secondary to a substantial withdrawal of vagal tone. The purpose of this study was to investigate whether autonomic measures discriminate patients with diarrhea (D) versus constipation (C) predominant IBS. Methods: Patients with IBS-D (N ⫽ 10) IBS-C (N ⫽ 15) and controls (N ⫽ 21) were studied for one night in the sleep laboratory utilizing complete polysomnography. Autonomic functioning was assessed via spectral analysis of beat to beat variability in heart rate. Specific high frequency (HF) and low frequency (LF) bands in the spectrum have been shown to be associated respectively with vagal and sympathetic input to the heart. The LF/HF ratio is used as a measure of sympathovagal balance. Results: The results indicated that the LF/HF ratio was significantly greater during stage 2 and REM sleep (p ⬍ .05) in the IBS-D group only. Significant differences were not noted in the waking state. Although not statistically significant (p ⫽ .08), vagal tone was diminished in IBS-D patients during stage 2 and REM sleep compared to the IBS-D and controls. Conclusions: 1. Autonomic functioning during sleep distinguishes patients with diarrhea predominant IBS. 2. Sympatho-vagal balance is enhanced in IBS-D patients primarily due to substantial vagal withdrawal during stage 2 and REM sleep.
High fibre supplementation in patients with irritable bowel syndrome (IBS). Comparison between diet and partially hydrolysed guar-gum (PHGG) fibre treatment in a multicenter randomised open trial Maurizio Zilli, Giancario Parisi*, MariaPaola Miani, Enrico Bottona, Maurizio Carrara, Giorgio Verdianelli, Giuseppe Battaglia, Alessandra Faedo, Serena Desideri, Claudio Marzolino, Angelo Tonon, Gioacchino Leandro and Mario Ermani. 1Associazione Interdisciplinare per gli Studi in Gastroenterologia ed Epatologia, (AISGE), Abano Terme (PD), Italy. Purpose: To evaluate the improvement of IBS symptoms in outpatients using high fibre diet or taking PHGG fibre. Methods: 188 (49 males and 139 females,40,3 ⫾ 14,6 yrs-old) consecutive outpatients with IBS were included in a multicenter randomised open trial. They were assigned to high fibre diet (A; n ⫽ 94) or PHGG fibre group (B; n ⫽ 94). At 4 weeks, those patients who did not improve symptomatology were crossed over and assigned to the alternative group (A-to-B, n ⫽ 46 and B-to-A, n ⫽ 10; p ⬍ 0,001). At baseline, 4, 8 and 12 weeks two IBS core symptoms (bowel habit and abdominal pain) were assessed and patients were invited to express their feeling about the overall improvement of the treatment. Results: At baseline all patients had mild to severe abdominal pain and altered bowel habit. Table 1 shows the persistence of abdominal pain, alterd bowel habit and patients subjective evaluation of improvement in the diet group (both diet only and A-to-B) and PHGG group(both PHGG only and B-to-A). Conclusions: The main findings of our study were that a high fibre supplementation in general(both diet and PHGG fibre) improved IBS core symptoms (abdominal pain and altered bowel habit) and patients treated with PHGG fibre self-reported significantly higher improvement. Given poor compliance with fibre supplementation diet is often reported by clinicians in IBS patients, the use of PHGG fibre seems to be as effective as diet and to induce better compliance in patients.
symptoms are bouts of chronic abdominal pain. The overall prevalence of acute intermittent porphyria is less than 10 per 100,000. In contrast, functional bowel disorders are a much more common cause of chronic abdominal pain-like symptoms. The purpose of this study was to evaluate the usefulness of 24 hr. urine porphyrin collection in diagnosing chronic abdominal pain as compared to the Rome II diagnostic criteria for functional bowel disorders. Methods: Medical records and laboratory studies were reviewed for all patients who had urine porphyrins ordered at Mayo Clinic Scottsdale for the period Jan 1988 –June 2000. Demographic data, chief complaint, and indication for ordering urine porphyrins were reviewed. Patients were also evaluated for the presence of non-GI neurologic symptoms of porphyria and symptoms of a functional bowel disorder. Results: 103 patients had urine porphyrins ordered during the study period. Two patients were excluded for inadequate information, with 101 remaining in the study sample. 51 (50%) of these patients had chronic abdominal pain as the chief complaint and indication for ordering urine porphyrins. None of these patients had a positive urine study suggestive of acute intermittent porphyria. 42 of these 51 patients (82%) met the Rome II criteria for a functional bowel disorder, most commonly irritable bowel syndrome (45%), functional abdominal pain (29%), functional abdominal bloating (4%) and functional dyspepsia (4%). In contrast, only 9 (18%) of the patients who had porphyrins ordered for non-GI complaints (rash, urine changes, etc) met the diagnostic criteria for a functional bowel disorder (p ⬍ 0.000001). Only 14 (27%) of the patients with chronic abdominal pain had any neurologic symptoms compared to 24 of 50 patients (48%) not diagnosed with chronic abdominal pain (p ⬍ 0.03). Conclusions: Absent a neurologic symptom, testing urine porphyrins for chronic abdominal pain is not a useful diagnostic undertaking. In patients with chronic abdominal pain, functional bowel disorders are a much more likely diagnosis with a higher pretest probability. Our data suggests that the use of the Rome II criteria is a more valuable tool for the diagnosis of chronic abdominal pain as opposed to urine porphyrin collection.
Abstracts
S321
1018 Cloning of two prokineticin cDNAs: recombinant proteins potently contract gastrointestinal smooth muscle Qun-Yong Zhou*, Clayton M. Bullock, Michelle Y. Cheng and Frederick J. Elhert. 1Department of Pharmcology, University of California, Irvine, CA. Purpose: to identify novel regulators of gastrointestinal motility. Methods: Two novel human cDNAs have been cloned based on their sequence similarity to a frog secretion protein and a non-toxic protein of mamba snake venom. These human cDNAs encode two secreted proteins of 86 and 81 amino acids. Recombinant proteins with authentic N-terminal sequences have been produced in E coli and refolded into functional proteins by careful control of protein aggregation. Results: Northern blot hybridization has revealed that these cDNAs are expressed in gastrointestinal tract, particularly the stomach. Mass spectrometry has confirmed the formation of five pairs of disulfide bonds. Refolded recombinant proteins potently contract gastrointestinal smooth muscle with EC50 values in the subnanomolar range. The recombinant proteins had no effect on the contractility of vascular and respiratory smooth muscle. To reflect their potent and specific effects on gastrointestinal smooth muscle cells, we have named these recombinant proteins prokineticins. Mutagenesis studies have further revealed the importance of disulfide bonds and conserved N-terminus for the bioactivity of prokineticins. Ligand binding studies with iodinated prokineticin 1 revealed the presence of a high affinity site in ileal smooth muscle. The displacement of specific prokineticin binding by GTP␥S suggests that prokineticin receptor may belong to the family of G protein-coupled receptor. Conclusions: Our results indicate that we have identified novel endogenous protein regulators of gastrointestinal motility. The availability of recombinant prokineticins should provide novel therapeutic agents for disorders involved impaired gastrointestinal motility.
1019 1017 Autonomic functioning during sleep distinguishes IBS patient subgroups William C Orr1*, Jennifer J Thompson1 and Sigrid Elsenbruch2. 1Lynn Health Science Institute, Oklahoma City, Oklahoma, United States; and 2 Dept. of Medical Psychology, University of Essen, Essen, Germany. Purpose: Previous studies in our laboratory have demonstrated autonomic functioning during sleep to be a unique indicator of abnormal physiology in patients with IBS. Our previous work has shown that sympathovagal balance during REM sleep is enhanced in IBS patients and this appears to be secondary to a substantial withdrawal of vagal tone. The purpose of this study was to investigate whether autonomic measures discriminate patients with diarrhea (D) versus constipation (C) predominant IBS. Methods: Patients with IBS-D (N ⫽ 10) IBS-C (N ⫽ 15) and controls (N ⫽ 21) were studied for one night in the sleep laboratory utilizing complete polysomnography. Autonomic functioning was assessed via spectral analysis of beat to beat variability in heart rate. Specific high frequency (HF) and low frequency (LF) bands in the spectrum have been shown to be associated respectively with vagal and sympathetic input to the heart. The LF/HF ratio is used as a measure of sympathovagal balance. Results: The results indicated that the LF/HF ratio was significantly greater during stage 2 and REM sleep (p ⬍ .05) in the IBS-D group only. Significant differences were not noted in the waking state. Although not statistically significant (p ⫽ .08), vagal tone was diminished in IBS-D patients during stage 2 and REM sleep compared to the IBS-D and controls. Conclusions: 1. Autonomic functioning during sleep distinguishes patients with diarrhea predominant IBS. 2. Sympatho-vagal balance is enhanced in IBS-D patients primarily due to substantial vagal withdrawal during stage 2 and REM sleep.
High fibre supplementation in patients with irritable bowel syndrome (IBS). Comparison between diet and partially hydrolysed guar-gum (PHGG) fibre treatment in a multicenter randomised open trial Maurizio Zilli, Giancario Parisi*, MariaPaola Miani, Enrico Bottona, Maurizio Carrara, Giorgio Verdianelli, Giuseppe Battaglia, Alessandra Faedo, Serena Desideri, Claudio Marzolino, Angelo Tonon, Gioacchino Leandro and Mario Ermani. 1Associazione Interdisciplinare per gli Studi in Gastroenterologia ed Epatologia, (AISGE), Abano Terme (PD), Italy. Purpose: To evaluate the improvement of IBS symptoms in outpatients using high fibre diet or taking PHGG fibre. Methods: 188 (49 males and 139 females,40,3 ⫾ 14,6 yrs-old) consecutive outpatients with IBS were included in a multicenter randomised open trial. They were assigned to high fibre diet (A; n ⫽ 94) or PHGG fibre group (B; n ⫽ 94). At 4 weeks, those patients who did not improve symptomatology were crossed over and assigned to the alternative group (A-to-B, n ⫽ 46 and B-to-A, n ⫽ 10; p ⬍ 0,001). At baseline, 4, 8 and 12 weeks two IBS core symptoms (bowel habit and abdominal pain) were assessed and patients were invited to express their feeling about the overall improvement of the treatment. Results: At baseline all patients had mild to severe abdominal pain and altered bowel habit. Table 1 shows the persistence of abdominal pain, alterd bowel habit and patients subjective evaluation of improvement in the diet group (both diet only and A-to-B) and PHGG group(both PHGG only and B-to-A). Conclusions: The main findings of our study were that a high fibre supplementation in general(both diet and PHGG fibre) improved IBS core symptoms (abdominal pain and altered bowel habit) and patients treated with PHGG fibre self-reported significantly higher improvement. Given poor compliance with fibre supplementation diet is often reported by clinicians in IBS patients, the use of PHGG fibre seems to be as effective as diet and to induce better compliance in patients.