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E12 embryonic mouse intestines show appropriate spatiotemporal developmental patterns in a serumless, chemically-defined in vitro organ culture system
GASTROENTEROLOGY Vol. 114, No. 4
AS76 AGA ABSTRACTS
G3590 NUTRITION SUPPORT IN ACUTE PANCREATITIS: USE OF PREDICTIVE CRITERIA AND EXPERIENCE WITH ENTERAL NUTRITION. DR Duerksen. S Wong, C Stoller. Dept of Medicine, University of Manitoba. Winnipeg, Manitoba, Canada. Background and Methods: The severity of acute pancreatitis may be estimated by use of Ranson and Glasgow criteria(C). Many patients with severe and complicated acute pancreatitis require nutrition support. It has been suggested that patients with severe or complicated pancreatitis, as determined by the above criteria, receive early nutrition support. Many centers advocate parenteral nutrition rather than enteral feeding in order to "rest" the pancreas. At our institution, it is common practice to institute enteral feeding in patients with pancreatitis who have a functional GI tract. The purpose of this study was to review the nutrition support of all patients requiring hospitalization with acute pancreatitis for > I0 days to determine i) the usefulness of Ranson and Glasgow criteria to predict need for invasive nutrition support, and ii) the safety and effectiveness of enteral (jejunal/gastric) nutrition. Re.suits: Over a 6 year period 125 patients were hospitalized for > 10 days with acute pancreatitis. Patients were divided into three groups (gp) according to nutrition support: 1) no nutrition support 2) TPN 3) Enteral (EN) _+TPN. All of the patient in gp 1 began oral intake < 10 days after admission and did not require invasive nutrition support. Results are expressed as mean _+SEM. N -> 3 Ranson C _>3 Glasgow C
No Nutrition 75 24 39
TPN 22 11 13
EN 28 11 15
The negative predictive value of Ranson C and Glasgow C ->3 determining the need for nutrition support was 65 % and 62 % respectively. Enteral nutrition (NJ(n=17); J(n=8); NG(n=3)) was successful in 75 % of patients for 19 ± 2.8 days. These patients were classified as having severe pancreatitis (Ranson C 2.54 ± 0.24; Glasgow C 3.0--!-0.25). Pseudocysts were present in 65 % of patients. The mean volume of formula provided was 1665 -+ 123 ml and achieved 5.5 ± 0.9 days after EN initiation. PN was also provided to 64 % of these patients during their 64.3 ± 10 day hospital stay. Reasons for failure of enteral support included nausea and emesis (n=5) and tube dislodgment (n=l). One patient who was also fed orally demonstrated a worsening of pancreatitis. Conclusions: Ranson and Glasgow C (>3) do not reliably predict the need for nutritional support in patients with acute pancreatitis. Jejunal feeding was tolerated in patients with severe and complicated pancreatitis. No major complications were observed in patients being enterally fed. Enteral nutrition should be considered in patients with severe acute pancreatitis. • G3591 El2 EMBRYONIC MOUSE INTESTINES SHOW APPROPRIATE SPATIOTEMPORAL DEVELOPMENTAL PATTERNS IN A SERUMLESS, CHEMICALLY-DEFINED I N VITRO ORGAN CULTURE SYSTEM. G_.Duh, D. Thomas, D. Warburton Los Angeles, CA. Introduction: Autocrine/paracrine signaling mechanisms play vital roles in
intestinal development. The purpose of this study was to develop an in vitro model of intestinal development using organ culture of embryonic mouse intestine in a serumless, chemically-defined medium. This model has the advantage in that the effects of specific regulatory factors on intestinal development can be studied in situ with cells in their natural local cellular environment. M e t h o d s : Intact El2 guts from stomach to proximal colon were dissected from Swiss-Webster mouse embryos and divided into approximately the foregut and mid/hindgut, with the associated mesentery and/or pancreas either left intact or removed mechanically. Organ cultures were performed using Fitton-Jackson modification BGJb medium with added ascorbic acid and penicillin/streptomycin, 5% CO2 and 95% air at 37°C. The cultures were grown for 6 days, with medium changes every 2 days. Histologic preparations of the cultured tissues are used for evaluation and morphometric studies. Results: Tissues remain viable and show visible increases in size and wall thickness after 6 days of culture. Periodic contractile activity could be seen after day 5, indicative of smooth muscle development. Histologically, mesodermal structures are well-organized with a distinct outer muscularis layer and lamina propria. The epithelium, while undifferentiated at El2, develops into sheets of simple columnar epithelium with numerous villus-like protuberances which are more prominent in the proximal small bowel. Villiform structures are not seen in the developing colon, which is often distinguishable from the small bowel by the presence of large, alcian bluepositive cells which appear to be goblet cells. These features are comparable to those of embryonic mouse intestines at E15.5 days of development. The epithelium develops poorly if the attached connective tissue is mechanically separated and/or if excessive tissue trauma occurs. The pancreas, which attaches to the foregut, develops well-defined acinar structures, and branching morphogenesis can be seen in histologic sections. Summary: 1. El2 embryonic mouse intestines cultured in a chemicallydefined medium show slower, but appropriate spatio-temporal developmental patterns compared to embryonic mouse intestines in vivo, and can be used as a
model to study the effects of specific regulatory factors on embryonic development. 2. Close association with mesenchymal tissue appears to be essential for intestinal epithelial development in this organ culture model. 3. E-12 embryonic mouse pancreas, which is attached to the foregut, shows visible developmental changes after 6 days of organ culture. Supported by Childrens Hospital Los Angeles - Research Institute. G3592
CAN A MIXED FIBRE SOURCE ENTERAL FEED OVERCOME THE ABNORMAL COLONIC RESPONSE TO NASOGASTRIC TUBE FEEDING? +H.Duncan, +S.Cole, *C. Green, +T.Bowling, +D.Silk. +Department of Gastroenterology and Nutrition, Central Middlesex Hospital NHS Trust, London. *Nutricia Research, The Netherlands. Introduction: Up to 25% of patients receiving continuous enteral feeding (CEF) develop diarrhoea, the pathogenesis of which remains unclear. Our previous studies show that CEF related diarrhoea is likely to be due to an abnormal colonic response to tube feeding. Bolus feeding of a fibre free enteral diet, designed to mimic normal feeding patterns also causes diarrhoea in healthy subjects. Using single fibre source diets in patients can also cause diarrhoea. Aim: The aim of the present study was to determine whether the abnormal colonic response to feeding with a fibre free enteral diet could be overcome by bolus administration of a novel mixed fibre (soluble and insoluble) source feed containing fibre amounts similar to a normal fibre intake. M e t h o d s : Intraluminal pressure recordings in the unprepared descending and sigmoid colon were studied in 6 healthy subjects using an established technique on 2 separate occasions in random order. Continuous recordings were made for 8 hours; 3 hours before and 5 hours after the start of an intragastric tube fed bolus infusion of either a polymeric enteral diet (Group 1) or the new mixed fibre diet (Group 2). Subjects were fed 250ml over 15 minutes 2 hourly for 2 instillations (16.7kcal/min, 105mgN/min). The pressure records were analysed in 30 minute epochs for the study segment (sum of 4 channels) activity index (AI = area under the curve: mmHg.min) by fully automated computer analysis. Results: All 6 of group I and 5 of 6 subjects in group 2 developed diarrhoea. In Group 1, there was a significant fall in postfed AI (mean (SEM) AI --- 2505 (72), p < 0.05, paired t-test) compared to prefed AI (AI = 2957 (227)). In Group 2, there was no significant difference in prefed (AI = 2553 (232)) and postfed (AI = 2558 (151)) activity index. However, in Group 2, there was a significant fall in the AI in the first hour after feeding (AI = 1773 (208), p = 0.01), with later recovery to levels above fasting (AI = 3116 (178), p = 0.03). The suppression of colonic motility is likely to be a causative factor in enteral tube feeding related diarrhoea. However, the later recovery to levels above fasting in the fibre supplemented group suggests that a mixed fibre source may exert a delayed but protective effect on colonic motor function. Research funded by Nutricia Corporate Research, Holland & The Sir Jules Thorn Charitable Trust. @ G3593
DOES A NASOGASTRIC TUBE ADVERSELY AFFECT DISTAL COLONIC MOTILITY AND CONTRIBUTE TO PATHOGENESIS OF ENTERAL FEEDING-RELATED DIARRHEA? H. Duncan. S. Cole, T. Bowling, D. Silk. Dept. Gastroenterology and Nutrition, Central Middlesex Hospital NHS Trust, U.K. Enteral tube feeding related diarrhoea is common. Continuous nasogastric tube (NGT) feeding causes abnormal suppression of colonic motility and diarrhoea. Bolus NGT feeding of 250ml of enteral diet causes diarrhoea associated with suppression of distal colonic motility, but when a bolus of an identical enteral diet is drunk, diarrhoea does not develop. The aim of this study was to investigate if the presence of a NGT was a contributing factor in adversely affecting distal colonic motility and resulting development of diarrhoea. Intraluminal pressure recordings in the unprepared distal colon were studied in three groups of six healthy volunteers using an established water perfusion technique. Continuous recordings were made for 3 h before and 5 h following administration of a polymeric diet. Subjects in Group 1 drank 250ml of a standard 1 kcal/ml polymeric enteral feed over 15 min 2-hourly for two instillations (16.7 kcal/min, 105 mgN/min); Group 2 subjects were bolus fed an identical feed via NGT, and subjects in Group 3 drank the feed with a NGT in-situ. Pressure records were analysed in 30 min epochs for the study segment (sum of four channels) activity index (AI area under the curve: mmHg/min) by fully automated computer analysis. No subject in group 1 developed diarrhoea, with no significant difference in AI before (AI-3376 (se 209) mmHg/min) or after drinking the feed (AI-3363 (se 210), p=0.48). All six subjects in Group 2 developed diarrhoea, associated with a significant fall in AI with tube feeding (fasting AI-2957 (se 227), fed AI-2505 (se 72), p<0.05). No subject in Group 3 developed diarrhoea, with no significant difference in AI before (AI-3368 (se 122) mmHg/min) or after drinking the feed (AI-3161 (se 128), p=0.14). Drinking boluses of a polymeric enteral diet does not suppress colonic motor activity even with a NGT in-situ. However bolus feeding via a NGT suppresses colonic motility with development of diarrhoea. These results suggest that neither the enteral diet nor the presence of a NGT in-situ, cause abnormal suppression of distal
AS76 AGA ABSTRACTS
G3590 NUTRITION SUPPORT IN ACUTE PANCREATITIS: USE OF PREDICTIVE CRITERIA AND EXPERIENCE WITH ENTERAL NUTRITION. DR Duerksen. S Wong, C Stoller. Dept of Medicine, University of Manitoba. Winnipeg, Manitoba, Canada. Background and Methods: The severity of acute pancreatitis may be estimated by use of Ranson and Glasgow criteria(C). Many patients with severe and complicated acute pancreatitis require nutrition support. It has been suggested that patients with severe or complicated pancreatitis, as determined by the above criteria, receive early nutrition support. Many centers advocate parenteral nutrition rather than enteral feeding in order to "rest" the pancreas. At our institution, it is common practice to institute enteral feeding in patients with pancreatitis who have a functional GI tract. The purpose of this study was to review the nutrition support of all patients requiring hospitalization with acute pancreatitis for > I0 days to determine i) the usefulness of Ranson and Glasgow criteria to predict need for invasive nutrition support, and ii) the safety and effectiveness of enteral (jejunal/gastric) nutrition. Re.suits: Over a 6 year period 125 patients were hospitalized for > 10 days with acute pancreatitis. Patients were divided into three groups (gp) according to nutrition support: 1) no nutrition support 2) TPN 3) Enteral (EN) _+TPN. All of the patient in gp 1 began oral intake < 10 days after admission and did not require invasive nutrition support. Results are expressed as mean _+SEM. N -> 3 Ranson C _>3 Glasgow C
No Nutrition 75 24 39
TPN 22 11 13
EN 28 11 15
The negative predictive value of Ranson C and Glasgow C ->3 determining the need for nutrition support was 65 % and 62 % respectively. Enteral nutrition (NJ(n=17); J(n=8); NG(n=3)) was successful in 75 % of patients for 19 ± 2.8 days. These patients were classified as having severe pancreatitis (Ranson C 2.54 ± 0.24; Glasgow C 3.0--!-0.25). Pseudocysts were present in 65 % of patients. The mean volume of formula provided was 1665 -+ 123 ml and achieved 5.5 ± 0.9 days after EN initiation. PN was also provided to 64 % of these patients during their 64.3 ± 10 day hospital stay. Reasons for failure of enteral support included nausea and emesis (n=5) and tube dislodgment (n=l). One patient who was also fed orally demonstrated a worsening of pancreatitis. Conclusions: Ranson and Glasgow C (>3) do not reliably predict the need for nutritional support in patients with acute pancreatitis. Jejunal feeding was tolerated in patients with severe and complicated pancreatitis. No major complications were observed in patients being enterally fed. Enteral nutrition should be considered in patients with severe acute pancreatitis. • G3591 El2 EMBRYONIC MOUSE INTESTINES SHOW APPROPRIATE SPATIOTEMPORAL DEVELOPMENTAL PATTERNS IN A SERUMLESS, CHEMICALLY-DEFINED I N VITRO ORGAN CULTURE SYSTEM. G_.Duh, D. Thomas, D. Warburton Los Angeles, CA. Introduction: Autocrine/paracrine signaling mechanisms play vital roles in
intestinal development. The purpose of this study was to develop an in vitro model of intestinal development using organ culture of embryonic mouse intestine in a serumless, chemically-defined medium. This model has the advantage in that the effects of specific regulatory factors on intestinal development can be studied in situ with cells in their natural local cellular environment. M e t h o d s : Intact El2 guts from stomach to proximal colon were dissected from Swiss-Webster mouse embryos and divided into approximately the foregut and mid/hindgut, with the associated mesentery and/or pancreas either left intact or removed mechanically. Organ cultures were performed using Fitton-Jackson modification BGJb medium with added ascorbic acid and penicillin/streptomycin, 5% CO2 and 95% air at 37°C. The cultures were grown for 6 days, with medium changes every 2 days. Histologic preparations of the cultured tissues are used for evaluation and morphometric studies. Results: Tissues remain viable and show visible increases in size and wall thickness after 6 days of culture. Periodic contractile activity could be seen after day 5, indicative of smooth muscle development. Histologically, mesodermal structures are well-organized with a distinct outer muscularis layer and lamina propria. The epithelium, while undifferentiated at El2, develops into sheets of simple columnar epithelium with numerous villus-like protuberances which are more prominent in the proximal small bowel. Villiform structures are not seen in the developing colon, which is often distinguishable from the small bowel by the presence of large, alcian bluepositive cells which appear to be goblet cells. These features are comparable to those of embryonic mouse intestines at E15.5 days of development. The epithelium develops poorly if the attached connective tissue is mechanically separated and/or if excessive tissue trauma occurs. The pancreas, which attaches to the foregut, develops well-defined acinar structures, and branching morphogenesis can be seen in histologic sections. Summary: 1. El2 embryonic mouse intestines cultured in a chemicallydefined medium show slower, but appropriate spatio-temporal developmental patterns compared to embryonic mouse intestines in vivo, and can be used as a
model to study the effects of specific regulatory factors on embryonic development. 2. Close association with mesenchymal tissue appears to be essential for intestinal epithelial development in this organ culture model. 3. E-12 embryonic mouse pancreas, which is attached to the foregut, shows visible developmental changes after 6 days of organ culture. Supported by Childrens Hospital Los Angeles - Research Institute. G3592
CAN A MIXED FIBRE SOURCE ENTERAL FEED OVERCOME THE ABNORMAL COLONIC RESPONSE TO NASOGASTRIC TUBE FEEDING? +H.Duncan, +S.Cole, *C. Green, +T.Bowling, +D.Silk. +Department of Gastroenterology and Nutrition, Central Middlesex Hospital NHS Trust, London. *Nutricia Research, The Netherlands. Introduction: Up to 25% of patients receiving continuous enteral feeding (CEF) develop diarrhoea, the pathogenesis of which remains unclear. Our previous studies show that CEF related diarrhoea is likely to be due to an abnormal colonic response to tube feeding. Bolus feeding of a fibre free enteral diet, designed to mimic normal feeding patterns also causes diarrhoea in healthy subjects. Using single fibre source diets in patients can also cause diarrhoea. Aim: The aim of the present study was to determine whether the abnormal colonic response to feeding with a fibre free enteral diet could be overcome by bolus administration of a novel mixed fibre (soluble and insoluble) source feed containing fibre amounts similar to a normal fibre intake. M e t h o d s : Intraluminal pressure recordings in the unprepared descending and sigmoid colon were studied in 6 healthy subjects using an established technique on 2 separate occasions in random order. Continuous recordings were made for 8 hours; 3 hours before and 5 hours after the start of an intragastric tube fed bolus infusion of either a polymeric enteral diet (Group 1) or the new mixed fibre diet (Group 2). Subjects were fed 250ml over 15 minutes 2 hourly for 2 instillations (16.7kcal/min, 105mgN/min). The pressure records were analysed in 30 minute epochs for the study segment (sum of 4 channels) activity index (AI = area under the curve: mmHg.min) by fully automated computer analysis. Results: All 6 of group I and 5 of 6 subjects in group 2 developed diarrhoea. In Group 1, there was a significant fall in postfed AI (mean (SEM) AI --- 2505 (72), p < 0.05, paired t-test) compared to prefed AI (AI = 2957 (227)). In Group 2, there was no significant difference in prefed (AI = 2553 (232)) and postfed (AI = 2558 (151)) activity index. However, in Group 2, there was a significant fall in the AI in the first hour after feeding (AI = 1773 (208), p = 0.01), with later recovery to levels above fasting (AI = 3116 (178), p = 0.03). The suppression of colonic motility is likely to be a causative factor in enteral tube feeding related diarrhoea. However, the later recovery to levels above fasting in the fibre supplemented group suggests that a mixed fibre source may exert a delayed but protective effect on colonic motor function. Research funded by Nutricia Corporate Research, Holland & The Sir Jules Thorn Charitable Trust. @ G3593
DOES A NASOGASTRIC TUBE ADVERSELY AFFECT DISTAL COLONIC MOTILITY AND CONTRIBUTE TO PATHOGENESIS OF ENTERAL FEEDING-RELATED DIARRHEA? H. Duncan. S. Cole, T. Bowling, D. Silk. Dept. Gastroenterology and Nutrition, Central Middlesex Hospital NHS Trust, U.K. Enteral tube feeding related diarrhoea is common. Continuous nasogastric tube (NGT) feeding causes abnormal suppression of colonic motility and diarrhoea. Bolus NGT feeding of 250ml of enteral diet causes diarrhoea associated with suppression of distal colonic motility, but when a bolus of an identical enteral diet is drunk, diarrhoea does not develop. The aim of this study was to investigate if the presence of a NGT was a contributing factor in adversely affecting distal colonic motility and resulting development of diarrhoea. Intraluminal pressure recordings in the unprepared distal colon were studied in three groups of six healthy volunteers using an established water perfusion technique. Continuous recordings were made for 3 h before and 5 h following administration of a polymeric diet. Subjects in Group 1 drank 250ml of a standard 1 kcal/ml polymeric enteral feed over 15 min 2-hourly for two instillations (16.7 kcal/min, 105 mgN/min); Group 2 subjects were bolus fed an identical feed via NGT, and subjects in Group 3 drank the feed with a NGT in-situ. Pressure records were analysed in 30 min epochs for the study segment (sum of four channels) activity index (AI area under the curve: mmHg/min) by fully automated computer analysis. No subject in group 1 developed diarrhoea, with no significant difference in AI before (AI-3376 (se 209) mmHg/min) or after drinking the feed (AI-3363 (se 210), p=0.48). All six subjects in Group 2 developed diarrhoea, associated with a significant fall in AI with tube feeding (fasting AI-2957 (se 227), fed AI-2505 (se 72), p<0.05). No subject in Group 3 developed diarrhoea, with no significant difference in AI before (AI-3368 (se 122) mmHg/min) or after drinking the feed (AI-3161 (se 128), p=0.14). Drinking boluses of a polymeric enteral diet does not suppress colonic motor activity even with a NGT in-situ. However bolus feeding via a NGT suppresses colonic motility with development of diarrhoea. These results suggest that neither the enteral diet nor the presence of a NGT in-situ, cause abnormal suppression of distal