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Investigation of the effects of melatonin treatment on streptozotocin (STZ)-induced diabetic rat ileum in vitro
Munich), and for Campylobacter jejuni (complement fixation test, Virion, Wuerzburg), Salmonella Typhi and S. Paratyphi A-C and Shigelfa sonnei and Sh. tlexneri (Gruber-Widal, Dade Behring, Marburg). Results: Serum was available from 45 consecutive patients (34 female, 1 ] male, median age 60 years). The median time period between onset of diarrhea and diagnosis of collagenous colitis was 10 months. Positive serum titres for Yersinia IgG and IgA were found in 33 (73.4%) and 37 (82.3%) of patients, another 6 (13.3%) and 4 (8.9%) patients had borderline titres, respectively. Two patients were also positive for Yersinia lgM (4.4%), and one was borderline (2.2%). In contrast, all 45 sera tested negative for Campylobacter, Salmonella and Shigella. Conclusions: Our study suggests a high prevalence of serum IgG and IgA antibodies against Yersinia species in patients with collagenous colitis. This finding may suggest a potential role of infection with Yersinia species in the etiology of this chronic disease.
patients. Methods: We performed a retrospective chart review to identify all patients treated for CDAD during hospitalization from January 2000 to September 2001. Eight variables were studied: age, sex, albumin, ICU location at/prior to diagnosis, diabetes, current hemodialysis, prior place of residence (home, nursing home, etc.). CD had to be documented by a positive CD-toxin assay in all cases. Failure of metronidazole was defined as persistence of symptoms of CDAD after 5 days of uninterrupted therapy including unresolved diarrhea, abdominal pain or fever. A response to metronidazole was defined as improvement in all symptoms at = < 5 days of therapy including reduction of diarrhea to < 2 bowel movements per day. Charts were excluded in cases of poor documentation and patient intolerance of metronidazole side-effects. Results: 119 CDAD cases were identified and 99 patients met inclusion criteria. Sixty one responded to metronidazole therapy and 38 failed treatment. Age, gender, presence of diabetes, hemodialysis, and place of residence did not predict failure of metronidazole. However, albumin < 2.5g/1 and ICU location at/prior to diagnosis did predict failure: odds ratio 11.7 (%95 CI: 4.0-31.6) and 4.1 (%95 CI: 1.3-12.2) respectively. The area under the ROC was 0.80 for predicting metronidazole failure when considering these 2 variables. No patient died from CDAD. Conclusions: Albumin level < 2.5g/1 and prior hospitalization in the ICU were predictors of failure of metronidazole therapy for CDAD Those patients with a low albumin or admitted recently to the ICU may benefit from oral vancomycin therapy at outset.
S1053 Is Toxigenic Clostridinm difficile Frequently Present in the Human Gut Flora? Masahiro lizuka, Shiho Konno, Kenji Sasaki, Akiko Sato, Yasuo Horie, Sumio Watanabe [Background] Clostridium difficile (C. difficile) is a major cause of nosocomial diarrhea. It is generally believed that administration of broad spectrum of antibiotics disrupts the pattern of the normal gut flora and enables colomsation with C. difficile. However, we have sometimes experienced C. difficile-associated diarrhea in non-hospitalized patients during antibiotics therapy, and have wondered if there is a possibility that in some cases administration of antibiotics disrupts the pattern of the normal gut flora and enables proliferation of C. difficile that was previously present in the host gut flora. To answer this question, we attempted to clarify whether healthy human adults have toxigenic C. difficile in the gut flora by RT-PCR using glass powder that can eliminate PCR inhihitors in feces and increase PCR sensitivity. [Methods] (1)Fecal samples were collected with informed consent from 10 healthy human adult volunteers (mean age: 35.3 years old). They had not received any antibiotics in the past 6 months and had not admitted in the hospitals in the past few years. (2)mRNA was extracted from fecal samples with the glass powder (BIt 101, CA) that can eliminate PCR inhibitors. After reverse transcription, converted DNA was amplified by hemi-nested PCR with the primers to toxin B gene of C. difficile. PCR products were digested with Hind Ill to confirm whether the amplified DNA fragments were derived from toxin B gene. RT-PCR was also performed with the same samples after culture for 24 hours. [Results[ (1)Sensitivity: We could detect toxin B gene in as small as 100 atto gram of C. difficfle DNA. (2) Toxin B gene was detected in 5 of 10 (50%) fecal samples, and furthermore, it was detected in all fecal samples after the culture. [Conclusion] Our results suggest that toxigenic C. difficile might be present in the gut flora of healthy human adults more frequently than previously suspected and support the hypothesis that in some cases antibiotics disrupt the normal gut flora and enable proliferation of C. difficile that was previously present in the host gut flora.
$1056 Investigation of the Effects of Melatonin Treatment on Streptozotocin (STZ)Induced Diabetic Rat Ileum in Vitro Kubra Paskaloglu, Goksel Sener, Gul Dulger Diabetes Mellitus is a contributing cause of gastrointestinal dysfunction which is associated with increased reactive oxygen species (ROS). This study was designed to determine the possible protective effect of melatonin (Mel) and/or insulin (Ins) treatment on the functional and biochemical changes caused by hyperglycemia induced oxidative damage in the ileum of STZ diabetic rats. Wistar albino rats of both sexes were subjected to streptozotocin (STZ, 65 mg/kg ip) to induce diabetes. Mel (10 mg/kg ip) and/or Ins (6U/kg sc) were administered for 8 weeks. Control rats received 0.1 M citrate buffer. After decapitation, the ileal tissues were either placed in organ baths or stored for the measurement of tissue levels of malondialdehyde (MDA) as an index of lipid peroxidation and glutathione (GSH) levels. The alterations in the responsiveness of the smooth muscles of ileum in diabetes were investigated. Carbachol (Cch 10-8- 10-3 M) induced contractile responses in the ileum were reduced in the diabetic group. Contractile responses that were significantly attenuated in untreated diabetic rats were restored by treatment with Mel and Ins in combination, whereas Mel or Ins alone have provided limited protection against diabetes induced damage. Glutathiotae (GSH) and malondialdehyde (MDA) levels of ileum were measured. GSH levels which significantly decreased in diabetes were elevated to control levels in the group treated with Mel and Ins combination, and the Mel group whereas, treatment with insulin alone provided only a limited protection. The increase in MDA levels observed after diabetes were also prevemed by treatment with the Mel and Ins combination or the Mel group. In conclusion, diabetic state enhances the generation of free radicals, and that both Mel treatment and glycaemic control by Ins can reduce this oxidative stress. Thus our results suggested that supplementing diabetic patients with adjuvant therapy of Mel may have some benefit for controlling diabetic complications.
$1054 Accelerated Bowel Transit and Overweight Shown in Idiopathic Bile Acid Malabsoyption Riadh Sadik, Hasse Abrahamsson, Kjell-Ame Ung, Per-Ove Stotzer The role of gastrointestinal transit and body weight in idiopathic bile acid malabsorption (IBAM) is unclear. We have recently observed faster small bowel transit and a tendency for faster colonic transit in healthy women with overweight compared to healthy women with normal weight. The aim of this prospective study was to study gastrointestinal transit and body mass index (BMI) in patients with IBAM. Methods: Patients with chronic diarrhoea were prospectively included for transit measurements. All patients went through gastroscopy and colonoscopy with biopsies, faecal cultivation, SeHCAT test and calculation of BMI and routine laboratory tests. Forty-four patients (15 men) had IBAM. A newly developed radiological procedure was used to measure colonic transit, segmental colonic transit and small bowel transit on the same day (Sadik et al. Scand J Gastroenterology 2003). The results were compared to results obtained in 83 healthy subjects. Results: Colonic transit in women with 18AM was 0.9 (0.3-1.7) days vs. 1.5(1.0-3.7) days (median and percemile l0 and 90) in healthy women, p<0.0001. In men with IBAM colonic transit was 0.8 (0.11.0) days, in healthy men 1.3 (0.8-1.9) days, p
$1057 Results of Lactose Digestion Test show that the Intestinal Lactose Digestive Capacity can remain high despite Mucosal Damage and low LA in SBB Harma Koetse, Rod Vonk, Gieneke Gonera-De ]ong, Marion Priebe, Jean-Michel Antoine, Frans Stellaard, Pieter Sauer Background: Lactase activity (LA) in a small intestinal bowel biopsy (SBB) specimen is frequently used as the indicator for hypolactasia, but its relation with the physiological intestinal Lactose digestive capacity has not been established. We compared LA with the results of a new quantitative lactose digestion test, using ~3C-lactose as substrate and 2Hglucose as reference. Method: The results of our new Lactose Digestion Test in 18 children aged 0.8 - 18 yr (mean 3.9, SD 2.4) suspected of small bowel mucosal injury were compared to those of the lactose H2 breath test, the histological changes and the LA in their SBB specimens. The Lactose Digestion Index (LDI) represents the percentage of the consumed lactose substrate dose, which has been digested. Results: In 5/6 patients with a normal histology a normal LA was shown, in 1/6 the LA was low. In all 6 the LD[ was ~- 45% and the H2 breath test result was normal. In 3 of 5 patients with minor histological changes LA and LDI were both normal, with a normal H2 test. One patient with medium histological changes had a low LA with a normal LDI and a normal H2 result. In 6 patients with severe mucosal damage LA was low in 5/6, but 3/5 demonstrated a normal LDI while the H2 test was normal in 3/6. One patiem with severe mucosal damage showed a normal LA with a negative H2 breath test and a low LDI. Interpretation: LDI shows that the total lactose digestive capacity in patients with small imestinal mucosal damage can remain adequate, despite low Lactase Activity in a SBB. Extrapolation of results of single or only a few SBB specimens to the overall lactose digestive intestinal function has therefore to be considered with caution, especially with respect to dietary advises.
$1055 Predicting Failure of Metronidazole Therapy in Patients with Clostridiam dif]idle-Associated Diarrhea Girish Anand, Angel A. Fernandez, Barbara M. Sorondo, Frank K. Friedenberg
S1058
Background: Clostridium difficile (CD) is responsible for 15%-20% of cases of antibiotic associated diarrhea. Mild CD-associated diarrhea (CDAD) resolves with conservative therapy in 15%-23% of patients within 48 hours. In more severe disease, metronidazole is the drug of choice for treatment. Oral vancomycin is the second line agent for the treatment of CDAD. It is given to all patients who fail metronidazole (no improvement in symptoms after 5 days) or have intolerable side-effects. Factors that could identify patients who are likely to fail metronidazole treatment would be clinically useful and could change the current stepped approach to treatment. Objectives: The purpose of our study was to identify factors that predict metroindazole failure for the initial treatment of CDAD in a large cohort of bospitalized
Diarrhoea and the Long Term Traveller - a Longitudinal Study in International Aid Volunteers 1992-1998 Anna C. Casbum-Jones, Caroline Sahin, Susanna Maybin, Jane Zuckerman INTRODUCTION: Travellers' diarrhoea is the commonest related travel illness, affecting 20-50% of adults travelling to the developing world. Gastrointestinal illness in the shortterm traveller, especkafly to the tropics, has been well studied. However, little attention has been paid to the long-term traveller. Voluntary Service Overseas (VSO) volunteers were
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AGA Abstracts
patients. Methods: We performed a retrospective chart review to identify all patients treated for CDAD during hospitalization from January 2000 to September 2001. Eight variables were studied: age, sex, albumin, ICU location at/prior to diagnosis, diabetes, current hemodialysis, prior place of residence (home, nursing home, etc.). CD had to be documented by a positive CD-toxin assay in all cases. Failure of metronidazole was defined as persistence of symptoms of CDAD after 5 days of uninterrupted therapy including unresolved diarrhea, abdominal pain or fever. A response to metronidazole was defined as improvement in all symptoms at = < 5 days of therapy including reduction of diarrhea to < 2 bowel movements per day. Charts were excluded in cases of poor documentation and patient intolerance of metronidazole side-effects. Results: 119 CDAD cases were identified and 99 patients met inclusion criteria. Sixty one responded to metronidazole therapy and 38 failed treatment. Age, gender, presence of diabetes, hemodialysis, and place of residence did not predict failure of metronidazole. However, albumin < 2.5g/1 and ICU location at/prior to diagnosis did predict failure: odds ratio 11.7 (%95 CI: 4.0-31.6) and 4.1 (%95 CI: 1.3-12.2) respectively. The area under the ROC was 0.80 for predicting metronidazole failure when considering these 2 variables. No patient died from CDAD. Conclusions: Albumin level < 2.5g/1 and prior hospitalization in the ICU were predictors of failure of metronidazole therapy for CDAD Those patients with a low albumin or admitted recently to the ICU may benefit from oral vancomycin therapy at outset.
S1053 Is Toxigenic Clostridinm difficile Frequently Present in the Human Gut Flora? Masahiro lizuka, Shiho Konno, Kenji Sasaki, Akiko Sato, Yasuo Horie, Sumio Watanabe [Background] Clostridium difficile (C. difficile) is a major cause of nosocomial diarrhea. It is generally believed that administration of broad spectrum of antibiotics disrupts the pattern of the normal gut flora and enables colomsation with C. difficile. However, we have sometimes experienced C. difficile-associated diarrhea in non-hospitalized patients during antibiotics therapy, and have wondered if there is a possibility that in some cases administration of antibiotics disrupts the pattern of the normal gut flora and enables proliferation of C. difficile that was previously present in the host gut flora. To answer this question, we attempted to clarify whether healthy human adults have toxigenic C. difficile in the gut flora by RT-PCR using glass powder that can eliminate PCR inhihitors in feces and increase PCR sensitivity. [Methods] (1)Fecal samples were collected with informed consent from 10 healthy human adult volunteers (mean age: 35.3 years old). They had not received any antibiotics in the past 6 months and had not admitted in the hospitals in the past few years. (2)mRNA was extracted from fecal samples with the glass powder (BIt 101, CA) that can eliminate PCR inhibitors. After reverse transcription, converted DNA was amplified by hemi-nested PCR with the primers to toxin B gene of C. difficile. PCR products were digested with Hind Ill to confirm whether the amplified DNA fragments were derived from toxin B gene. RT-PCR was also performed with the same samples after culture for 24 hours. [Results[ (1)Sensitivity: We could detect toxin B gene in as small as 100 atto gram of C. difficfle DNA. (2) Toxin B gene was detected in 5 of 10 (50%) fecal samples, and furthermore, it was detected in all fecal samples after the culture. [Conclusion] Our results suggest that toxigenic C. difficile might be present in the gut flora of healthy human adults more frequently than previously suspected and support the hypothesis that in some cases antibiotics disrupt the normal gut flora and enable proliferation of C. difficile that was previously present in the host gut flora.
$1056 Investigation of the Effects of Melatonin Treatment on Streptozotocin (STZ)Induced Diabetic Rat Ileum in Vitro Kubra Paskaloglu, Goksel Sener, Gul Dulger Diabetes Mellitus is a contributing cause of gastrointestinal dysfunction which is associated with increased reactive oxygen species (ROS). This study was designed to determine the possible protective effect of melatonin (Mel) and/or insulin (Ins) treatment on the functional and biochemical changes caused by hyperglycemia induced oxidative damage in the ileum of STZ diabetic rats. Wistar albino rats of both sexes were subjected to streptozotocin (STZ, 65 mg/kg ip) to induce diabetes. Mel (10 mg/kg ip) and/or Ins (6U/kg sc) were administered for 8 weeks. Control rats received 0.1 M citrate buffer. After decapitation, the ileal tissues were either placed in organ baths or stored for the measurement of tissue levels of malondialdehyde (MDA) as an index of lipid peroxidation and glutathione (GSH) levels. The alterations in the responsiveness of the smooth muscles of ileum in diabetes were investigated. Carbachol (Cch 10-8- 10-3 M) induced contractile responses in the ileum were reduced in the diabetic group. Contractile responses that were significantly attenuated in untreated diabetic rats were restored by treatment with Mel and Ins in combination, whereas Mel or Ins alone have provided limited protection against diabetes induced damage. Glutathiotae (GSH) and malondialdehyde (MDA) levels of ileum were measured. GSH levels which significantly decreased in diabetes were elevated to control levels in the group treated with Mel and Ins combination, and the Mel group whereas, treatment with insulin alone provided only a limited protection. The increase in MDA levels observed after diabetes were also prevemed by treatment with the Mel and Ins combination or the Mel group. In conclusion, diabetic state enhances the generation of free radicals, and that both Mel treatment and glycaemic control by Ins can reduce this oxidative stress. Thus our results suggested that supplementing diabetic patients with adjuvant therapy of Mel may have some benefit for controlling diabetic complications.
$1054 Accelerated Bowel Transit and Overweight Shown in Idiopathic Bile Acid Malabsoyption Riadh Sadik, Hasse Abrahamsson, Kjell-Ame Ung, Per-Ove Stotzer The role of gastrointestinal transit and body weight in idiopathic bile acid malabsorption (IBAM) is unclear. We have recently observed faster small bowel transit and a tendency for faster colonic transit in healthy women with overweight compared to healthy women with normal weight. The aim of this prospective study was to study gastrointestinal transit and body mass index (BMI) in patients with IBAM. Methods: Patients with chronic diarrhoea were prospectively included for transit measurements. All patients went through gastroscopy and colonoscopy with biopsies, faecal cultivation, SeHCAT test and calculation of BMI and routine laboratory tests. Forty-four patients (15 men) had IBAM. A newly developed radiological procedure was used to measure colonic transit, segmental colonic transit and small bowel transit on the same day (Sadik et al. Scand J Gastroenterology 2003). The results were compared to results obtained in 83 healthy subjects. Results: Colonic transit in women with 18AM was 0.9 (0.3-1.7) days vs. 1.5(1.0-3.7) days (median and percemile l0 and 90) in healthy women, p<0.0001. In men with IBAM colonic transit was 0.8 (0.11.0) days, in healthy men 1.3 (0.8-1.9) days, p
$1057 Results of Lactose Digestion Test show that the Intestinal Lactose Digestive Capacity can remain high despite Mucosal Damage and low LA in SBB Harma Koetse, Rod Vonk, Gieneke Gonera-De ]ong, Marion Priebe, Jean-Michel Antoine, Frans Stellaard, Pieter Sauer Background: Lactase activity (LA) in a small intestinal bowel biopsy (SBB) specimen is frequently used as the indicator for hypolactasia, but its relation with the physiological intestinal Lactose digestive capacity has not been established. We compared LA with the results of a new quantitative lactose digestion test, using ~3C-lactose as substrate and 2Hglucose as reference. Method: The results of our new Lactose Digestion Test in 18 children aged 0.8 - 18 yr (mean 3.9, SD 2.4) suspected of small bowel mucosal injury were compared to those of the lactose H2 breath test, the histological changes and the LA in their SBB specimens. The Lactose Digestion Index (LDI) represents the percentage of the consumed lactose substrate dose, which has been digested. Results: In 5/6 patients with a normal histology a normal LA was shown, in 1/6 the LA was low. In all 6 the LD[ was ~- 45% and the H2 breath test result was normal. In 3 of 5 patients with minor histological changes LA and LDI were both normal, with a normal H2 test. One patient with medium histological changes had a low LA with a normal LDI and a normal H2 result. In 6 patients with severe mucosal damage LA was low in 5/6, but 3/5 demonstrated a normal LDI while the H2 test was normal in 3/6. One patiem with severe mucosal damage showed a normal LA with a negative H2 breath test and a low LDI. Interpretation: LDI shows that the total lactose digestive capacity in patients with small imestinal mucosal damage can remain adequate, despite low Lactase Activity in a SBB. Extrapolation of results of single or only a few SBB specimens to the overall lactose digestive intestinal function has therefore to be considered with caution, especially with respect to dietary advises.
$1055 Predicting Failure of Metronidazole Therapy in Patients with Clostridiam dif]idle-Associated Diarrhea Girish Anand, Angel A. Fernandez, Barbara M. Sorondo, Frank K. Friedenberg
S1058
Background: Clostridium difficile (CD) is responsible for 15%-20% of cases of antibiotic associated diarrhea. Mild CD-associated diarrhea (CDAD) resolves with conservative therapy in 15%-23% of patients within 48 hours. In more severe disease, metronidazole is the drug of choice for treatment. Oral vancomycin is the second line agent for the treatment of CDAD. It is given to all patients who fail metronidazole (no improvement in symptoms after 5 days) or have intolerable side-effects. Factors that could identify patients who are likely to fail metronidazole treatment would be clinically useful and could change the current stepped approach to treatment. Objectives: The purpose of our study was to identify factors that predict metroindazole failure for the initial treatment of CDAD in a large cohort of bospitalized
Diarrhoea and the Long Term Traveller - a Longitudinal Study in International Aid Volunteers 1992-1998 Anna C. Casbum-Jones, Caroline Sahin, Susanna Maybin, Jane Zuckerman INTRODUCTION: Travellers' diarrhoea is the commonest related travel illness, affecting 20-50% of adults travelling to the developing world. Gastrointestinal illness in the shortterm traveller, especkafly to the tropics, has been well studied. However, little attention has been paid to the long-term traveller. Voluntary Service Overseas (VSO) volunteers were
A-145
AGA Abstracts