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The effect of diet on severity of gastric ulcers in horses
A238 AGA ABSTRACTS
Q G0973 THE COST OF OMEPRAZOLE VERSUS OPEN ANTI-REFLUX SURGERY IN THE LONG-TERM MANAGEMENT OF REFLUX ESOPHAGITIS. HE Myrvold, L Lundell, B Liedman, J Hatlebakk, P Miettinen, E Janatuinen, SA Pedersen, K Thor, K Lewander, P NystriSm, NO St~lhammar and The Nordic GERD Study Group. Depts of Surgery, Trondheim University Hospital, Norway, Sahlgren's Hospital, Gothenburg, Sweden, Haukeland Hospital, Bergen, Norway, University Hospital Kuopio, Finland, Odense Hospital, Denmark, Ersta Hospital, Stockholm, Sweden and Astra H~issle, MSlndal, Sweden. Efforts to control costs in health care have resulted in great interest regarding the costs of surgical and medical treatment of reflux esophagitis. The aim of this study was to assess for the first time the actual costs of these alternatives in a prospective controlled Nordic multicenter clinical trial. Material and methods: Patients with erosive esophagitis were initially treated with omeprazole (OME) to control symptoms and to heal esophagitis and thereafter randomized to maintenance therapy with OME using the dose which was needed to heal esophagitis (n=139 on 20 mg and n=16 on 40 mg) or open fundoplication (n=144, an additional 11 patients refused surgery). In case of relapse patients on maintenance treatment not responding to higher doses of OME (max 60 mg) were offered surgical treatment. Patients randomised to surgery were reoperated and/or given OME if needed. The patients were contacted by phone months 3 and 9, were seen by the doctor every 6 months and endoscopy was done at 12, 36 and 60 months. The total costs after three years were calculated. Protocol driven visits and endoscopies were excluded from the surgery arm. Discontinued patients (n=16 in OME arm, n=12 in surgery arm) were assumed to incur no further costs. Calculations were based on each countries' cost of surgery, including reoperation for late complications, out patient visits, endoscopies, medication, transportation and indirect costs. Indirect costs refer to sick leave for employed patients. Results: The per patient three year cost (USD) of medical treatment and surgery Norway, Finland Sweden Denmark Med Surg Med Surg Med Surg Med Surg Medication 2788 664 3093 670 3287 651 4 2 3 0 706 Operation 445 5461 278 5218 760 9307 359 4388 Visits 469 278 537 301 183 120 480 257 2Dir.med.c.* 3702 6 4 0 3 3 9 0 8 6190 4229 10077 5069 5351 Transport 89 47 83 44 107 57 97 51 Indirect c. 1455 6 0 7 0 1 4 0 0 5843 1098 4582 743 3099 ZTotal 5246 12520 5391 12076 5435 14716 5908 8500 *Differences were significant at the 5% level in all countries except for Finland. No confidence intervals were calculated for indirect costs, and hence, total costs, since these costs refer to employed patients only (n = 93 in OME, n = 74 in the surgery arm.) Conclusions: In Sweden, Denmark and Norway, the direct medical cost during three years is significantly lower for medical treatment than for surgery. In Finland the direct medical costs are approximately equal. In all Nordic countries, the total three year cost of medical treatment for an employed patient is substantially lower than the total cost of surgery. The study was supported by Astra H~issle AB. • G0974 TREATMENT OF HELICOBACTER PYLORI INFECTION IN RHESUS MONKEYS USING A NOVEL ANTIADHESION COMPOUND. J. Mysore, P. Simon, D. Zopf, A. Dubois. Uniformed Services University of the Health Sciences, and Armed Forces Radiobiology Research Institute, Bethesda, MD, Neose Technologies, Inc, Horsham, PA. Treatment of H. pylori infection with antibiotics leads to the emergence of resistant strains, thus requiring the development of novel therapeutic strategies. The goal of the present study was to explore the possibility of interfering with bacterial attachment to superficial epithelial cells. NE0080 is the sodium salt of the oligosaccharide 3'sialyllactose that occurs naturally in human and bovine milk and can inhibit the adhesion of 11. pylori to human cells in vitro. Six male rhesus monkeys that had been 11. pylori positive for over 12 months were selected for the present study. Five of them had been experimentally infected with a mixture of cagA+ vacA+ strains isolated from patients, and the sixth one had become naturally infected with a cagA+ vacA+ strain in the breeding colony. NE0080 (33 mg/kg, t.i.d.) was given for 28 days. Videegastroscopies were performed before and at regular intervals during and after treatment, and 6 gastric biopsies were harvested each from the corpus and antrum (total 12 biopsies) for quantitative cultures and histology (H&E and Genta stains). One animal infected with one of the strains isolated from humans became H. pylori negative at day 30 and it remained negative for the next 6 months. Two other animals became H. pylori-negative at days 14 and 28, respectively, but then were 1-1.pylori-posifive at subsequent times. The three last animals remained colonized. The five animals who were not cured of H. pylori infection were then treated with NE0080 (167mg/kg, t.i.d.) for 56 days. During this treatment, the two animals with temporary clearance again were intermittently negative, but infection subsequently relapsed. They were then treated with NE0080 (167mg/kg) + omeprazole (0.4mg/kg) t.i.d, for 28 days, but no additional benefit was observed. Gastritis decreased in the animal that was cured of H. pylori infection, but did not
GASTROENTEROLOGY Vol. 114, No. 4
change in the other animals. No side effects were observed in any of the animals receiving NE0080 at either dose with or without omeprazole, and body weight, CBC, ALl', and AST did not change significantly. Thus, antiadhesive therapy is safe, it can cure or decrease 1-1.pylori colonization in rhesus monkeys, and the addition of a proton pump inhibitor does not appear to increase cure rate. Research funded by Neose Technologies, Inc, Horsham, PA. G0975
THE EFFECT OF DIET ON SEVERITY OF GASTRIC ULCERS IN HORSES. J.A. Nadeau. F.M. Andrews, A.G. Mathew, R.A. Argenzio, and J.T. Blackford High short chain fatty acid (SCFA) concentrations coupled with a low gastric juice pH have been implicated in causing acid injury and ulceration of the gastroesophageal portion of the stomach of pigs and horses and may be related to reflux esophagitis in man. The effects of two diets, a high carbohydrate high protein diet and a moderate carbohydrate low protein diet, on gastric juice pH, hydrogen ion concentration, SCFA (acetic, butyric, isobutyric, propionic, isovaleric and valeric) concentrations and number and severity of ulcers in the gastroesophageal portion of the stomach were evaluated in six 7-year-old female horses fitted with gastric cannulas. Gastric juice was collected from the stomach immediately after and 1 to 8, 10, 12, and 24 hours after feeding a high carbohydrate high protein diet (Diet 1) or a moderate carbohydrate low protein diet (Diet 2) in a 2 period randomized crossover design. Gastric juice pH and acidity were measured using a standard glass electrode and electrometric titration to endpoint pH 7.0, respectively. SCFA concentrations were measured using gas chromatography. Number and severity of gastric lesions were scored using a standard scoring system. 1 An ANOVA was performed on the data using the mixed procedure in SAS to compare diet and time differences (P < 0.05). Regression analysis using all variables to explain lesion severity was run using the stepwise model selection to determine if multiple variables would improve prediction of gastric lesion scores. Gastric juice pH, acetic, butyric, and valeric acid concentrations were significantly higher and acidity was significantly lower in gastric juice from horses fed diet 1. Gastric lesion severity was higher (P < 0.01) in horses fed diet 2. Gastric lesion number was higher (P=0.14) in horses fed diet 2, but this was not significant. Based on the regression model, horses fed diet 1 that had increased gastric juice valeric, butyric, and propionic acid concentrations and lower gastric juice pH were likely to have more severe lesions. Horses fed diet 2 that had increased gastric juice valeric and butyric acid concentrations were likely to have more severe lesions. A high carbohydrate diet may generate increased SCFA, which at a low pH, may increase number and severity of gastric ulcers. A high carbohydrate high protein diet may generate increased SCFA, but the protein, due to its buffering capacity, may negate the ability of the SCFA to cause acid injury and ulceration in the gastroesophageal portion of the stomach. On the other hand, a moderate carbohydrate low protein diet may produce high SCFA at a low pH, which may predispose to gastroesophageal acid injury and ulceration. [1] Macallister CM, Andrews FM, Deegan E, etal. A scoring system for gastric ulcers. Equine Veterinary Journal. (In Press). G0976
DOPAMINE MAY DIRECTLY INCREASE PROSTAGLANDIN E2 C O N T E N T IN RAT GASTRIC MUCOSA. Yoshi Nagahata, Yasutomo Azumi, Temyuki Akimoto and Hideaki Nomura. First Department of Surgery, Kobe University School of Medicine, Kobe, Japan. We have reported that dopamine (DA) increased gastric mucosal blood flow (GBF) and prostaglandin (PG) E2 content in gastric mucosa. The aim of this study was to see how DA increased PGE2 content in gastric mucosa. Materials and Methods: Wistar strain male rats were used. DA (5 pg/kg/min), fusaric acid (FA, 100 mg/kg), and indomethacin (IDM, 10 mg/kg), were administered, respectively. GBF was measured by the electrolytic hydrogen clearance method. PGE2 content was determined by RIA and norepinephrine (NE) content was measured by HPLC. PGE2 content was also determined after gastric glandular mucosa was incubated for 4 hr in 10 mM phosphatebuffered saline (PBS, pH7.4, 37°C). DA (1.0 pg/ml), NE (1.0 pg/ml), FA (0.1 mg/ml), and IDM (10 pg/mi) were added in PBS before the incubation. PGE2 content after incubation PGE2(lag/g) DA 3.35 ± 0.37* DA + FA 3.33 _+0.39* DA + IDM 3.06 ± 0.32 DA + FA + IDM 3.10 _+0.36 NE 3.37 ± 0.40* NE + IDM 1.63 ± 0.27** FA 2.77 ± 0.34 IDM 1.12 ± 0.13"* control 2.89 ± 0.42 DA, NE; 1.0 ~tg/ml, FA; 0.1 mg/ml, IDM; 10 ~tg/ml, *; p < 0.05, **; p < 0.01 vs control Results: Administration of DA increased GBF and NE and PGE2 content.
Q G0973 THE COST OF OMEPRAZOLE VERSUS OPEN ANTI-REFLUX SURGERY IN THE LONG-TERM MANAGEMENT OF REFLUX ESOPHAGITIS. HE Myrvold, L Lundell, B Liedman, J Hatlebakk, P Miettinen, E Janatuinen, SA Pedersen, K Thor, K Lewander, P NystriSm, NO St~lhammar and The Nordic GERD Study Group. Depts of Surgery, Trondheim University Hospital, Norway, Sahlgren's Hospital, Gothenburg, Sweden, Haukeland Hospital, Bergen, Norway, University Hospital Kuopio, Finland, Odense Hospital, Denmark, Ersta Hospital, Stockholm, Sweden and Astra H~issle, MSlndal, Sweden. Efforts to control costs in health care have resulted in great interest regarding the costs of surgical and medical treatment of reflux esophagitis. The aim of this study was to assess for the first time the actual costs of these alternatives in a prospective controlled Nordic multicenter clinical trial. Material and methods: Patients with erosive esophagitis were initially treated with omeprazole (OME) to control symptoms and to heal esophagitis and thereafter randomized to maintenance therapy with OME using the dose which was needed to heal esophagitis (n=139 on 20 mg and n=16 on 40 mg) or open fundoplication (n=144, an additional 11 patients refused surgery). In case of relapse patients on maintenance treatment not responding to higher doses of OME (max 60 mg) were offered surgical treatment. Patients randomised to surgery were reoperated and/or given OME if needed. The patients were contacted by phone months 3 and 9, were seen by the doctor every 6 months and endoscopy was done at 12, 36 and 60 months. The total costs after three years were calculated. Protocol driven visits and endoscopies were excluded from the surgery arm. Discontinued patients (n=16 in OME arm, n=12 in surgery arm) were assumed to incur no further costs. Calculations were based on each countries' cost of surgery, including reoperation for late complications, out patient visits, endoscopies, medication, transportation and indirect costs. Indirect costs refer to sick leave for employed patients. Results: The per patient three year cost (USD) of medical treatment and surgery Norway, Finland Sweden Denmark Med Surg Med Surg Med Surg Med Surg Medication 2788 664 3093 670 3287 651 4 2 3 0 706 Operation 445 5461 278 5218 760 9307 359 4388 Visits 469 278 537 301 183 120 480 257 2Dir.med.c.* 3702 6 4 0 3 3 9 0 8 6190 4229 10077 5069 5351 Transport 89 47 83 44 107 57 97 51 Indirect c. 1455 6 0 7 0 1 4 0 0 5843 1098 4582 743 3099 ZTotal 5246 12520 5391 12076 5435 14716 5908 8500 *Differences were significant at the 5% level in all countries except for Finland. No confidence intervals were calculated for indirect costs, and hence, total costs, since these costs refer to employed patients only (n = 93 in OME, n = 74 in the surgery arm.) Conclusions: In Sweden, Denmark and Norway, the direct medical cost during three years is significantly lower for medical treatment than for surgery. In Finland the direct medical costs are approximately equal. In all Nordic countries, the total three year cost of medical treatment for an employed patient is substantially lower than the total cost of surgery. The study was supported by Astra H~issle AB. • G0974 TREATMENT OF HELICOBACTER PYLORI INFECTION IN RHESUS MONKEYS USING A NOVEL ANTIADHESION COMPOUND. J. Mysore, P. Simon, D. Zopf, A. Dubois. Uniformed Services University of the Health Sciences, and Armed Forces Radiobiology Research Institute, Bethesda, MD, Neose Technologies, Inc, Horsham, PA. Treatment of H. pylori infection with antibiotics leads to the emergence of resistant strains, thus requiring the development of novel therapeutic strategies. The goal of the present study was to explore the possibility of interfering with bacterial attachment to superficial epithelial cells. NE0080 is the sodium salt of the oligosaccharide 3'sialyllactose that occurs naturally in human and bovine milk and can inhibit the adhesion of 11. pylori to human cells in vitro. Six male rhesus monkeys that had been 11. pylori positive for over 12 months were selected for the present study. Five of them had been experimentally infected with a mixture of cagA+ vacA+ strains isolated from patients, and the sixth one had become naturally infected with a cagA+ vacA+ strain in the breeding colony. NE0080 (33 mg/kg, t.i.d.) was given for 28 days. Videegastroscopies were performed before and at regular intervals during and after treatment, and 6 gastric biopsies were harvested each from the corpus and antrum (total 12 biopsies) for quantitative cultures and histology (H&E and Genta stains). One animal infected with one of the strains isolated from humans became H. pylori negative at day 30 and it remained negative for the next 6 months. Two other animals became H. pylori-negative at days 14 and 28, respectively, but then were 1-1.pylori-posifive at subsequent times. The three last animals remained colonized. The five animals who were not cured of H. pylori infection were then treated with NE0080 (167mg/kg, t.i.d.) for 56 days. During this treatment, the two animals with temporary clearance again were intermittently negative, but infection subsequently relapsed. They were then treated with NE0080 (167mg/kg) + omeprazole (0.4mg/kg) t.i.d, for 28 days, but no additional benefit was observed. Gastritis decreased in the animal that was cured of H. pylori infection, but did not
GASTROENTEROLOGY Vol. 114, No. 4
change in the other animals. No side effects were observed in any of the animals receiving NE0080 at either dose with or without omeprazole, and body weight, CBC, ALl', and AST did not change significantly. Thus, antiadhesive therapy is safe, it can cure or decrease 1-1.pylori colonization in rhesus monkeys, and the addition of a proton pump inhibitor does not appear to increase cure rate. Research funded by Neose Technologies, Inc, Horsham, PA. G0975
THE EFFECT OF DIET ON SEVERITY OF GASTRIC ULCERS IN HORSES. J.A. Nadeau. F.M. Andrews, A.G. Mathew, R.A. Argenzio, and J.T. Blackford High short chain fatty acid (SCFA) concentrations coupled with a low gastric juice pH have been implicated in causing acid injury and ulceration of the gastroesophageal portion of the stomach of pigs and horses and may be related to reflux esophagitis in man. The effects of two diets, a high carbohydrate high protein diet and a moderate carbohydrate low protein diet, on gastric juice pH, hydrogen ion concentration, SCFA (acetic, butyric, isobutyric, propionic, isovaleric and valeric) concentrations and number and severity of ulcers in the gastroesophageal portion of the stomach were evaluated in six 7-year-old female horses fitted with gastric cannulas. Gastric juice was collected from the stomach immediately after and 1 to 8, 10, 12, and 24 hours after feeding a high carbohydrate high protein diet (Diet 1) or a moderate carbohydrate low protein diet (Diet 2) in a 2 period randomized crossover design. Gastric juice pH and acidity were measured using a standard glass electrode and electrometric titration to endpoint pH 7.0, respectively. SCFA concentrations were measured using gas chromatography. Number and severity of gastric lesions were scored using a standard scoring system. 1 An ANOVA was performed on the data using the mixed procedure in SAS to compare diet and time differences (P < 0.05). Regression analysis using all variables to explain lesion severity was run using the stepwise model selection to determine if multiple variables would improve prediction of gastric lesion scores. Gastric juice pH, acetic, butyric, and valeric acid concentrations were significantly higher and acidity was significantly lower in gastric juice from horses fed diet 1. Gastric lesion severity was higher (P < 0.01) in horses fed diet 2. Gastric lesion number was higher (P=0.14) in horses fed diet 2, but this was not significant. Based on the regression model, horses fed diet 1 that had increased gastric juice valeric, butyric, and propionic acid concentrations and lower gastric juice pH were likely to have more severe lesions. Horses fed diet 2 that had increased gastric juice valeric and butyric acid concentrations were likely to have more severe lesions. A high carbohydrate diet may generate increased SCFA, which at a low pH, may increase number and severity of gastric ulcers. A high carbohydrate high protein diet may generate increased SCFA, but the protein, due to its buffering capacity, may negate the ability of the SCFA to cause acid injury and ulceration in the gastroesophageal portion of the stomach. On the other hand, a moderate carbohydrate low protein diet may produce high SCFA at a low pH, which may predispose to gastroesophageal acid injury and ulceration. [1] Macallister CM, Andrews FM, Deegan E, etal. A scoring system for gastric ulcers. Equine Veterinary Journal. (In Press). G0976
DOPAMINE MAY DIRECTLY INCREASE PROSTAGLANDIN E2 C O N T E N T IN RAT GASTRIC MUCOSA. Yoshi Nagahata, Yasutomo Azumi, Temyuki Akimoto and Hideaki Nomura. First Department of Surgery, Kobe University School of Medicine, Kobe, Japan. We have reported that dopamine (DA) increased gastric mucosal blood flow (GBF) and prostaglandin (PG) E2 content in gastric mucosa. The aim of this study was to see how DA increased PGE2 content in gastric mucosa. Materials and Methods: Wistar strain male rats were used. DA (5 pg/kg/min), fusaric acid (FA, 100 mg/kg), and indomethacin (IDM, 10 mg/kg), were administered, respectively. GBF was measured by the electrolytic hydrogen clearance method. PGE2 content was determined by RIA and norepinephrine (NE) content was measured by HPLC. PGE2 content was also determined after gastric glandular mucosa was incubated for 4 hr in 10 mM phosphatebuffered saline (PBS, pH7.4, 37°C). DA (1.0 pg/ml), NE (1.0 pg/ml), FA (0.1 mg/ml), and IDM (10 pg/mi) were added in PBS before the incubation. PGE2 content after incubation PGE2(lag/g) DA 3.35 ± 0.37* DA + FA 3.33 _+0.39* DA + IDM 3.06 ± 0.32 DA + FA + IDM 3.10 _+0.36 NE 3.37 ± 0.40* NE + IDM 1.63 ± 0.27** FA 2.77 ± 0.34 IDM 1.12 ± 0.13"* control 2.89 ± 0.42 DA, NE; 1.0 ~tg/ml, FA; 0.1 mg/ml, IDM; 10 ~tg/ml, *; p < 0.05, **; p < 0.01 vs control Results: Administration of DA increased GBF and NE and PGE2 content.