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D L Sigalet

Publications and source records attributed to D L Sigalet.

At least 19 recordsLinked to original sources
PubMed2006

Glucagon-like peptide-2 induces a specific pattern of adaptation in remnant jejunum.

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine hormone which is uniquely trophic for the intestine; a physiological role in regulating nutrient absorptive capacity is becoming apparent. GLP-2, independent of enteral feeding, stimulates a classical pattern of intestinal adaptation in terminal ileum following resection. Herein we investigate the effects of GLP-2 on the jejunal remant using a rat model of short bowel syndrome (SBS). Juvenile 250- to 275-g SD rats underwent 80% distal small bowel resection, leaving 20 cm of proximal jejunum and venous catheterization. Animals were maintained with total parenteral nutrition (TPN) or TPN+10 microg/kg/hr GLP-2 (n=8 per group). After 7 days, intestinal permeability was assessed by urinary recovery of gavaged carbohydrate probes. Animals were euthanized, and the intestines taken for analysis of morphology, crypt cell proliferation, apoptosis, and expression of SGLT-1 and GLUT-5 transport proteins. GLP-2 treatment reduced intestinal permeability and increased in vivo glucose absorption, small intestinal weight, surface area, villus height, crypt depth, and microvillus height. Intestinal mucosal DNA and protein content per unit length of the small bowel were increased (P < 0.05 for all comparisons). However, in contrast to previous studies examining GLP-2's effects on remnant ileum, the jejunal crypt apoptotic index was increased in GLP-2-treated animals, with no increase in SGLT-1 or GLUT 5 expression. These results show that exogenous GLP-2 treatment of animals with jejunal remnant reduces intestinal permeability, increases glucose absorption, and stimulates morphological features of intestinal adaptation including increased micovillus height and surface area. However, the pattern of changes seen is different from that in remnant ileum. This suggests that GLP-2's effects are specific to different regions of the bowel. Nonetheless, remnant jejunum is responsive to GLP-2 in the absence of enteral nutrition. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2 in modulating nutrient absorptive capacity.

Adaptation, Physiological↗
PubMed2004

Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome.

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine peptide that is released in response to luminal nutrients and has unique trophic actions in the gastrointestinal tract. These features suggest GLP-2 may be important in controlling intestinal adaptation. We examined the relationship over time of GLP-2 production and adaptation to intestinal resection, the effects of resection-induced malabsorption on GLP-2 production, and the correlation of endogenous serum GLP-2 levels with adaptation as measured by crypt-cell proliferation (CCP). We initially examined the effect of nutrient malabsorption, induced by a 90% resection of the proximal intestine studied on day 4, on the time course and levels of GLP-2 release. Secondly, the degree of malabsorption was varied by performing intestinal transection or 50, 75, or 90% resection of proximal small intestine. Finally, the relationship of GLP-2 levels over time with adaptation to a 90% resection was examined by determining GLP-2 levels on days 7, 14, and 28, and correlating this with intestinal adaptation, as assessed by morphology and CCP rate. A 90% resection significantly increased basal and postprandial GLP-2 levels, with a net increase in nutrient-stimulated exposure over 90 min; GLP-2 exposure (integrated levels vs. time) increased 12.7-fold in resected animals (P < 0.001). Basal and postprandial GLP-2 levels significantly correlated with the magnitude of intestinal resection (r(2) = 0.71; P < 0.001), CCP (r(2) = 0.48; P < 0.005), and nutrient malabsorption (protein, P < 0.001; fat, P < 0.005). The increase in CCP was maintained to 28 days after small bowel resection and was associated with an ongoing elevation in GLP-2 release. These findings suggest that GLP-2 is important in initiating and maintaining the small intestinal adaptive response to resection.

Adaptation, Physiological↗
PubMed2002

Epidermal growth factor improves nutritional outcome in a rat model of short bowel syndrome.

BACKGROUND/PURPOSE: This study investigates the effect of epidermal growth factor (EGF) on nutrient absorption in a rat model of short bowel syndrome (SBS). METHODS: Male juvenile rats underwent either transection (Sham) or ileocecal resection leaving a 20-cm jejunal remnant. Animals underwent follow-up for 10 days, and resected animals were treated with placebo or recombinant human EGF (1-53). Animals were pair fed; in vivo nutrient absorption, intestinal permeability, morphology, and total intestinal DNA and protein content were measured. RESULTS: Resected EGF-treated animals lost significantly less weight than those in the placebo group (-4.2 +/- 3 v -13.7 +/- 6.9%), absorbed significantly more 3-0 methylglucose (76.8 +/- 6.6 v 64.9 +/- 10.1%), and had reduced permeability (lactulose/mannitol ratio, 0.35 +/- 0.19 v 0.60 +/- 0.20; P <.05 for all comparisons). CONCLUSIONS: These findings show that treatment of short bowel syndrome animals with EGF reduced weight loss and improved carbohydrate absorption and intestinal permeability. These findings suggest that enteral EGF may be a useful therapy for short bowel syndrome; further studies are indicated.

Absorption↗
PubMed2002

Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant.

BACKGROUND/PURPOSE: Neutropenic enterocolitis (typhlitis) is a common consideration after bone marrow transplantation. This study reviews the authors' experience with abdominal pain and typhlitis in an active pediatric bone marrow transplant program. METHODS: The Pediatric Bone Marrow Transplant Program Database was reviewed for patients presenting with abdominal pain or typhlitis. RESULTS: From 1993 to 2000 a total of 142 transplants have been performed. Of these, 97 patients had abdominal pain, and 5 had radiologically proven typhlitis. Nonspecific abdominal pain developed on the 12 +/- 11th day posttransplant, whereas patients in whom typhlitis developed were diagnosed on day 15.5 +/- 7. All patients were treated with prophylactic antibiotics consisting of acyclovir, fluconazole, and septra. With the onset of abdominal pain, 73 of 97 patients were placed on therapeutic antibiotics; patients identified with typhlitis had amphotericin plus GCSF added. No clinical features differentiated abdominal pain patients from typhlitis. Oral feeding and time of discharge was similar in both groups. Surgical intervention was not required, and no patients died with typhlitis. CONCLUSIONS: Abdominal pain is a common symptom after bone marrow transplant; however, typhlitis is relatively rare, and surgical intervention was not required in this series. Broad-spectrum (including fungal) antibiotic therapy appears to be an effective treatment for typhlitis in this patient population.

Abdominal Pain↗
PubMed2001

Portal venous decompression with H-type mesocaval shunt using autologous vein graft: a North American experience.

BACKGROUND/PURPOSE: Portal hypertension in children often is caused by prehepatic venous obstruction or intrahepatic fibrosis without cirrhosis. This situation is uniquely amenable to shunting; this report details the experience of 3 North American centers with an H-type mesocaval shunt using autologous vein, which has been widely used in European centers. METHODS: Retrospective chart review was conducted of records from 1980 through 1999 at 3 North American institutions. Charts were reviewed for etiology of portal hypertension, diagnostic workup, preoperative management, operative results and complications, postoperative shunt patency, patient well-being, and eventual need for liver transplantation. RESULTS: Twenty patients were identified with prehepatic causes of venous obstruction undergoing shunt therapy. Eleven had portal venous thrombosis or cavernous transformation. Of these, 3 had umbilical catheters placed in the neonatal period. Five children had American-Indian cirrhosis, 1 had congenital hepatic fibrosis, and 3 had hepatic fibrosis associated with polycystic kidney disease. Patients presented at a median age of 3.7 years and underwent follow-up for an average of 4.3 years after surgery. These patients had an average of 3.6 bleeding episodes, (with 3.9 attempts at sclerotherapy) and received 3 units of blood preoperatively. Average age at operation was 8 years, average weight was 30 kg, and perioperative blood requirement was 200 mL. In general, patients did well postoperatively; 2 patients required reoperation for lymphatic leaks, and there was 1 death caused by a leaking G-tube, unrelated to shunt functioning. Two patients had transient encephalopathy postoperatively, and 1 patient had severe pancreatitis. All shunts remain patent, with good function and no further bleeding. CONCLUSIONS: These results are encouraging, and we would suggest that the H-type mesocaval shunt utilizing autologous vein be considered for wider use in pediatric patients with prehepatic cause of portal hypertension. An algorithm for the work-up of pediatric patients with variceal bleeding is presented, with the recommendation that shunt surgery be considered early in patients with a prehepatic or fibrotic causes of portal hypertension.

Algorithms↗
PubMed2001

In vivo measurement of intestinal absorption using 3-0 methylglucose in short bowel syndrome.

PURPOSE: The management of patients with short bowel syndrome is complicated by the paucity of methods to assess in vivo the absorptive capacity of the remaining bowel. The purpose of this experiment was to assess the feasibility of using urinary recovery of 3-0 methylglucose (3-0 MG) as a quantitative measure of carbohydrate absorptive capacity, comparing it with in vivo absorption and in vitro glucose transport studies. METHODS: Male Sprague Dawley rats underwent either a 90% proximal small bowel resection or sham resection (n = 8 in each group). Animals were pair fed, weighed, and followed up for 14 days. A 3-day balance study was done, measuring feed intake and fecal output for percentages of fat and energy absorption. Animals were gavaged with 3-0 MG/Mannitol solution, and 4-hour urinary recovery of sugars was assessed using high-performance liquid chromatography (HPLC). On different days these studies were repeated with increasing amounts of added normal glucose (1 mol/L, 1.25 mol/L, and 1.5 mol/L) in the gavage solution given to compete for 3-0 MG transport, and thus increase the "sensitivity" of the test. Animals were then killed, and sections of intestine taken for in vitro assessment of glucose transport using radiolabeled 3-0 MG in Ussing chambers. RESULTS: Total energy, carbohydrate, and fat absorption all were reduced significantly in the resected animals, as was 3-0 MG urinary recovery (62.9 +/- 10.5%) in controls versus (35.8 +/- 17.5%) in resected animals (P <.05). 3-0 MG urinary recovery correlated well with dietary carbohydrate absorption (r = 0.74), and with Ussing chamber measures of glucose flux (r = 0.97). Adding exogenous glucose to the test solution to "compete" for 3-0 MG transport sites did not improve sensitivity. CONCLUSIONS: These results show that 3-0 MG is useful in measuring nutrient absorption capacity in rats after massive small bowel resection. Further studies to validate these methods in human patients with short bowel syndrome are suggested.

3-O-Methylglucose↗
PubMed2001

Short bowel syndrome in infants and children: an overview.

Short bowel syndrome is a spectrum of malnutrition resulting from inadequate bowel length. In infant and pediatric patients, the most common causes are necrotizing enterocolitis, abdominal wall defects, jejunal ileal atresia, and mid gut volvulus. There appear to be regional variations in etiology. Since the publication of Wilmore's classic monograph in 1972, there have been significant improvements in monitoring and nutritional support. In the modern era, survival rate ranges from 80% to 94%, and the presence or absence the ileal cecal valve appears to not impact on mortality rate, but does significantly affect the length of time on total parenteral nutrition TPN. The most common morbidities remain sepsis, both central line related and bacterial overgrowth, and TPN cholestasis. Long-term recovery of these children often is remarkably normal, but there is a 10% to 15% incidence of neurologic and developmental defects. The clinical and ethical considerations around the care of infants with 20 to 40 cm of residual bowel remains controversial, as does the place of intestinal transplantation, especially in patients developing gut failure in infancy. Perioperative surgical decision making plays a critical role in the long-term outcome of these patients. This chapter presents an overview of the current status of care and outcome in this difficult population; these topics are further expanded in subsequent chapters.

Child↗
PubMed2001

ALX-0600 (NPS Allelix Corp).

NPS Allelix (formerly Allelix Biopharmaceuticals) is developing the glucagon-like peptide 2 (GLP-2) analog ALX-0600 for the potential treatment of gastrointestinal diseases, including short bowel disease. GLP stimulates the growth of the lining of the small intestine, thus increasing the absorptive area of the intestine [214370], [315107]. ALX-0600 also has potential for mucositis associated with cancer chemotherapy and inflammatory bowel disease [331459]. During the third quarter of 1999, a pilot phase II trial began for short bowel syndrome (SBS) [331459]. ALX-0600 began pivotal phase II trials in 2000 following the completion of the pilot trial which was designed to measure the safety, tolerability, and any other drug-related improvements in nutrient absorption and physical changes in the gut of a small number of patients with SBS. Allelix hopes to bring this drug to the market by 2001 [341519]. Allelix filed an application to the FDA for Orphan Drug designation in the third quarter of 1999 [331459]; in August, the designation was approved [377524]. As of November 1998, Allelix was in discussions with a potential marketing partner for worldwide development and marketing [305000]. In August 1998, the USPTO issued a notice of allowance to Allelix for its basic patent containing claims covering the composition and medical uses of ALX-0600 and related GI drug candidate compounds [2946571.

Amino Acid Sequence↗
PubMed2000

Hormonal therapy for short bowel syndrome.

PURPOSE: Treatment of short bowel syndrome (SBS) can be difficult; this study examines the effect of parental administration of different peptide hormones in a rat model of SBS. METHODS: Juvenile male Lewis rats (220 to 240 g) underwent resection of the proximal 90% of small bowel and were assigned randomly to treatment groups: growth hormone (GH), insulinlike growth factor-1 (IGF-1), glucagonlike peptide-2 (GLP-2; given as ALX-0600, a potent protease resistant analogue of the human GLP-2), control-resected (Con-R), or control-transected (Con-T). Drugs were delivered by continuous subcutaneous infusion via Alzet mini-pumps: controls received equivalent volumes of drug vehicle. Animals were pair-fed (23 g chow per day) and followed up for 14 days monitoring weight gain. Animals were killed and active transport, hormone profiles, and intestinal morphology were assessed. RESULTS: Hormonal treatments significantly increased weight gain in all groups (GH, 9.9+/-4.9; IGF-1, 6.0+/-9.6; and GLP-2, 0.8+/-2.7 v. -6.2+/-4.7 in untreated resected animals [weight as percentile initial weight]). This was associated with a significant alteration in intestinal morphology in the IGF-1-treated animals, and an increase in glucose transport rates in all hormonally treated animals when compared with untreated control resected animals. CONCLUSIONS: These results show that IGF-1, GH, and GLP-2 all improve short-term weight gain after massive bowel resection in a rat model. The effects seen on weight gain may be caused by improved dietary nutrient absorption from an increase in the intestinal surface area or increase in transporting activity or alterations in the metabolic efficiency of the animal. These findings suggest further studies of these therapies as treatment for short-bowel syndrome are indicated.

Animals↗
PubMed2000

Impact of FK506 and steroids on adaptation after intestinal resection or segmental transplantation.

Segmental small intestinal transplantation (SIT) using living related donors (LRD) is being evaluated as a therapy, clinically. Advantages of this technique include an increase in the donor pool, optimization of the timing of transplants, and potential immunologic benefits. However, the ability of a short segment of intestine to function after transplantation has not been investigated in large animal models. This study evaluates the impact of immunosuppression on the adaptive process and the ability of a transplanted segment of intestine to adapt. A pig model of segmental SIT was used. Animals were resected, leaving 150 cm of distal ileum (n = 5), resected and treated with FK506 (n = 4), or steroids (n = 4), or with FK506 + steroids (n = 7), or transplanted using a similar segment of ileum and treated with FK506 + steroid immunosuppression (n = 9). Animals undergoing resection, or resection plus steroid treatment, did well, gaining weight post-operatively (37% and 15% of preoperative weight, respectively). However, animals undergoing resection and treated with FK506 or FK506 + steroids did poorly, losing weight (-14% and -22% of preoperative weight, respectively) and showing significant impairment of intestinal adaptation, morphologically and functionally. Furthermore, FK506-treated animals developed inflammatory changes in the intestinal mucosa, mimicking rejection. Segmental SIT animals had a high rate of rejection (66%) and showed a similar impairment in adaptation. Hence, segmental SIT is a stringent physiological test of intestinal adaptation. FK506 appears to impair gut function after resection, either directly, or by interfering with the adaptive process. In this model of segmental SIT, FK506 and steroids at the doses tested did not provide adequate immunosuppression to prevent rejection and the graft did not function adequately to allow growth. Further studies are required to evaluate the mechanisms underlying these findings, and to determine if similar effects occur in humans.

Adaptation, Physiological↗
PubMed2000

Differential sugar absorption as a marker for adaptation in short bowel syndrome.

PURPOSE: There are no reliable monitoring methods for following up with patients with short bowel syndrome (SBS). This study examines the use of inert sugar markers (mannitol and lactulose) as indicators of the surface area increases occurring with adaptation. METHODS: Juvenile male rats underwent either transection with intestinal reanastomosis or resection with removal of the proximal 90% of the small bowel, leaving 10 cm of terminal ileum (n = 8 in each group). Animals were studied in vivo, measuring absorption of mannitol and lactulose on day 7, 14, and 28 and killed with the representative histological samples taken on day 7, 14, and 28. RESULTS: Resected animals showed significant increases in intestinal length (initial bowel length 10 cm, final length 17.8 +/- 1.4 cm, while transected showed no significant changes (101 +/- 2 cm): resection also increased intestinal circumference (initial circumference 0.5 cm +/- 0.1 cm, final circumference 1.1 cm +/- 0.2 cm in resected animals, while transected animals remained unchanged). Resected animals also showed significant increases in villus height (0.7 +/- 0.06 mm initially, 0.9 +/- 0.09 mm at day 28), and but a decrease in villus density (116 +/- 20 villi/mm2 initially, 78 +/- 20 villi/mm2 at day 28), again controls showed no changes. This resulted in a significant increase in intestinal surface area in resected animals over the study; surface area initially calculated at 640 +/- 80 cm2 increasing to 1,440 +/- 360 cm2, while controls showed no significant change in surface area. There was also an increase in mannitol absorption, which went from 1.8 +/- 0.6% on day 7 to 2.56 +/- 0.6% on day 28 in resected animals, while permeability actually decreased over time. (All data mean +/- SD, with P<.05 by Student's t test). Mannitol absorption correlated well with intestinal surface area (R2 = 0.82). CONCLUSION: These results suggest that inert sugar markers, such as lactulose and mannitol, may be useful in following adaptation in patients who have short bowel syndrome.

Absorption↗
PubMed2000

Leiomyoma of the esophagus associated with bronchial obstruction owing to inflammatory pseudotumor in a child.

Although relatively common in adults, leiomyoma of the esophagus is a rare disorder in children. A single case report describes the coexistence of both esophageal and bronchial leiomyoma in a child. The authors describe the diagnostic and treatment challenges encountered in a 2-year-old boy with coexisting inflammatory pseudotumor and esophageal leiomyoma presenting as massive atelectasis.

Airway Obstruction↗
PubMed1999

Effect of combined immunosuppressive drug therapy on small intestinal nutrient transport in the rat.

OBJECTIVE: Prevention of rejection and preservation of graft function remain as obstacles to clinical small intestinal transplantation (SIT). This study evaluated the effects of combined immunosuppressive agents (FK506, Rapamycin, and Mycophenolate Mofetil) on intestinal function and animal well being. METHODS: Screening for additive toxicity was done in experiment one (D1, n = 10); doses were: FK506 0.3 mg/kg/d, Rapamycin 2 mg/kg/d, and Mycophenolate Mofetil 20 mg/kg/d, orally once daily. Control animals (C1, n = 10) received equivalent vehicle. In the second phase of the experiment, the effect of an additional parenteral treatment phase was investigated, with drug treated animals (D2, n = 6) received FK506 0.3 mg/kg, Rapamycin 1 mg/kg, and Mycophenolate Mofetil 10 mg/kg sq q12h for 1 week followed by FK506 3 mg/kg, Rapamycin 1 mg/kg, and Mycophenolate Mofetil 10 mg/kg p.o. q12h for 4 weeks. Control animals (C2, n = 6) received equivalent vehicle. Parameters followed were weight gain, nutrient absorption, drug levels and nutrient transport in vitro. RESULTS: Controls grew normally, while weight gain was significantly reduced in drug treated animals: This was paralleled by a reduction in dietary fat absorption. Drug levels were low to therapeutic for all drugs in both experiments; FK506 appeared to affect Rapamycin and Mycophenolate Mofetil metabolism, increasing levels of both as FK506 doses increased. Nutrient transport was either not effected (D1) or increased (D2). CONCLUSIONS: We conclude that low dose combination immunosuppressive therapy inhibits weight gain, without affecting absorption of dietary energy, or adversely affecting glucose transport. We postulate a systemic metabolic cause, which requires additional investigation at the cellular level; additional studies are also required to determine if the additive immunosuppression outweigh the side effects for SIT.

3-O-Methylglucose↗
PubMed1999

Lymphatic absorption of glucose and fatty acids as determined by direct measurement.

BACKGROUND/PURPOSE: Treatment of chylous leaks using enteral feeds supplemented with medium chain triglycerides (MCT) is used widely but often ineffective. Few studies have examined the conventional dogma that MCTs and simple sugars are absorbed directly via the portal system. This study tests the hypothesis that significant absorption of MCTs and simple sugars occurs via the lymphatics. METHODS: A stable, awake rat model with cannulation of the mesenteric lymph duct, portal and jugular veins, and duodenum was used. Venous catheters were infused with saline at 2.5 mL/hr, while the duodenal tube was infused with emulsified fatty acids at 3 mL/hr (0.3% palmitic acid [C16:0] + 0.35% of test nutrient: either Lauric acid [C12:0; n = 5] octanoic acid [C8:0; n = 6] or 3-0-methylglucose, [n = 5].) After 4 hours of stabilization, the animals were given a differentially radiolabeled pulse of palmitic acid plus test nutrient and the subsequent appearance in lymphatic, portal, and jugular systems was measured. Total lymphatic appearance was measured directly; appearance in the portal and jugular systems was measured using the area under the curve method. RESULTS: Results are expressed as mean +/- SD. Palmitic acid: lymphatic absorption (LA), 49.2+/-7.4%; portal venous absorption (PA), 19.8+/-15%; total absorption (TA), 69+/-12.4%. Lauric acid: LA, 32.9+/-6.7%; PA, 7.5+/-2.9%; TA, 40.4+/- 6.3%. Octanoic acid: LA, 5.6+/-2.1%; PA, 27.3+/-6.5%; TA, 32.9+/-4.8%. 3-0 methylglucose: LA, 8.6+/-2.2%; PA 69+/-39%; TA, 76.6+/-39.5. Total lymphatic flow: palmitic plus lauric group, 14+/-2 mL; palmitic plus octanoic, 12.5+/-4.4 mL; palmitic plus 3-0 methylglucose, 12.8+/-2.9 mL. (Total volume measure over 4 hours after giving the radiolabeled pulse.) CONCLUSIONS: The portal venous uptake of the medium chain fatty acid (MCFA), octanoic acid, was not significantly greater than the uptake of the long-chain palmitic acid, but the absorption of lauric acid was less. There are different absorption patterns between different medium-chain fatty acids; however, lymphatic absorption of MCFAs and simple sugars does occur. Total measured absorption of MCFAs is less than that of long-chain fatty acids or sugars. Further work is required to demonstrate the utility of MCT supplementation on nutritional status and lymphatic flow rates in chylous leak syndromes, and to examine the factors that control the results of absorption of fatty acids of varying chain lengths, both in normal and pathological states.

Absorption↗
PubMed1999

Survival of patients with esophageal atresia: influence of birth weight, cardiac anomaly, and late respiratory complications.

PURPOSE: The aim of this study was to determine the influence of various prognostic factors on the outcome of esophageal atresia patients. METHODS: The authors reviewed 240 charts of patients admitted with esophageal atresia or tracheoesophageal fistula (EA-TEF) in a single institution. A logistic regression model was used with survival as the dependent variable and era of repair, birth weight, and cardiac anomaly as independent variables. RESULTS: Era was statistically significant (P = .011); 87% (117 of 134) of patients survived in the era from 1980 through 1997 compared with 78% (83 of 106) from 1960 through 1979. Cardiac anomaly (CHD) was a significant risk factor (P = .001); 88% (176 of 199) survived without cardiac anomaly, whereas only 59% (24 of 41) survived with cardiac disease. Eighty-four percent (185 of 219) of infants with a birth weight (BW) of more than 1,500 g survived, compared with 71% (15 of 21) of infants with a birth weight of less than 1,500 g. This was not statistically significant (P = .59). Early hospital deaths were primarily cardiac and chromosomal (61%). Late deaths were primarily respiratory (59%; two-tailed Fisher's Exact test, P = .004). CONCLUSIONS: (1) Survival of patients with esophageal atresia has significantly improved in the recent years. (2) Low birth weight (<1,500 g) does not seem to affect survival. (3) Associated cardiac and chromosomal anomalies are significant causes of death, particularly for early demise. (4) Late death from respiratory disease (tracheomalacia, reactive airway disease, reflux, and aspiration) warrants attention, and a close follow-up of postoperative patients is suggested.

Abnormalities, Multiple↗
PubMed1998

Mechanisms underlying intestinal adaptation after massive intestinal resection in the rat.

BACKGROUND/PURPOSE: The regulatory events that control the adaptive response after massive intestinal resection are poorly understood. An improved understanding could lead to improved clinical therapies. This study tests the hypothesis that massive intestinal resection increases nutrient transport by upregulation of mRNA for the sodium glucose cotransporter (SGLT1). METHOD: Male Lewis rats (225 to 250 g) were studied. Control animals (Con, n = 6) underwent ileal transection 15 cm proximal to the cecum; resected animals (Res, n = 8) underwent resection of all bowel proximal to the terminal 15 cm of ileum. Animals were followed up for 14 days, pair fed, and weighed daily. At the time of death the terminal ileum was studied quantifying SGLT1 mRNA using reverse transcriptase-polymerase chain reaction (RT-PCR) normalized to B-actin, in vitro glucose transport in Ussing Chambers, and histology. RESULTS: All animals survived; animals that were transected regained preoperative weight by day 10, and underwent resection by day 14. Significant adaptation occurred with increases in villus height, (control jejunum 934 +/- 79; control ileum, 811 +/- 64 v resected ileum, 949 +/- 83 [P < .05]). Nutrient flux (J mucosal --> serosa; Jms) was increased in resected ileum (3-0 Methyl-D-Glucose flux: 0.71 +/- 0.2 v 0.56 +/- 0.04 in Con ileum [P < .05; units, micromol/cm2/hr of 3-0 Methyl-D-Glucose]). This was paralleled by an increase in expression of the SGLT1 gene in resected ileum, 104 +/- 14, versus Con ileum, 74 +/- 9 (P < .05; values normalized versus expression of B-actin). CONCLUSION: SGLT1 expression may be useful as a marker of the adaptive process after massive resection and potentially may be used as an endpoint of therapy after resection clinically.

Adaptation, Physiological↗