Changes in liver function tests in patients with inflammatory bowel disease on enteral nutrition

Morphologic and functional hepatic changes occur in inflammatory bowel disease (IBD). Patients with this disease often require the administration of artificial nutritional support. Liver function tests (LFT) derangement is a widely recognized side-effect of total parenteral nutrition (TPN). Therefore, the use of this modality of nutritional support may be an additional factor to cause hepatic damage in IBD patients. However whether or not the same occurs in patients receiving total enteral nutrition (TEN) is not well-established. The aim of the present study was to evaluate the effect of TEN upon LFT in patients with moderate to severe acute attacks of IBD, by means of a prospective, controlled, and nonrandomized design. Forty-nine patients were included; 29 (11 patients with ulcerative colitis and 18 with Crohn's disease) received TEN, and 20 (11 with ulcerative colitis and 9 with Crohn's disease) did not. Both groups were homogeneous regarding age, sex, disease activity index, nutritional status, and length of the study (24.8 +/- 1.3 vs 23.9 +/- 16.8 days). In all cases, weekly measurements of serum alkaline phosphatase, GOT, and GPT were performed. There were no significant differences in LFT at the beginning of the study between groups. The percentage of patients showing derangement of some LFT during the study did not differ between both groups: six of 29 (20.6%) in TEN group vs three of 20 (15%) in control group. Six out of the nine patients (in both groups) who developed LFT derangement had one or more causes, other than TEN for explaining hepatic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glutamine-enriched total parenteral nutrition in patients with inflammatory bowel disease

BACKGROUND: Studies in animal models of inflammatory bowel disease (IBD) suggest that supplementation of total parenteral nutrition with glutamine (gln), a conditionally essential amino acid in catabolic conditions, increases gln plasma concentrations, reduces intestinal damage, improves nitrogen balance and may improve the course of the disease. However, human data supporting this assumption are missing. METHODS: A total of 24 consecutive patients with an acute exacerbation of IBD (19 Crohn's disease; five ulcerative colitis) and scheduled for total parenteral nutrition (TPN) (>7 days) were randomised. Parallel to a standardised anti-inflammatory therapy, the patients received either a TPN with 1.5 g/kg body weight of a standard amino acid or an isonitrogenic, isocaloric TPN with 1.2 g/kg body weight of a standard amino acid and 0.3 g/kg L-alanine-L-glutamine. Primary end points were gln plasma concentrations and intestinal permeability assessed by urinary lactulose and D-xylose ratio. RESULTS: Gln plasma levels did not differ significantly in either group throughout the study. Intestinal permeability did not change within 7 days either with or without gln supplementation (Delta-lactulose/xylose ratio: 0.01+/-0.05 (gln+) vs 0.02+/-0.1 (gln-)). The observed changes in inflammatory and nutritional parameters, and also disease activity, length of TPN and hospital stay, were independent of glutamine substitution. Five (41%) patients in the gln+ group and three (25%) patients in the gln- group needed surgical intervention. CONCLUSION: Although limited by the sample size, these results do not support the hypothesis that glutamine substitution has an obvious biochemical or clinical benefit in patients with active IBD scheduled for total parenteral nutrition.     

Impact of enteral and parenteral nutrition on hepatic and muscle glucose metabolism

Liver and muscle metabolism were assessed in dogs adapted to long-term total parenteral (TPN) and enteral (TEN) nutrition. Studies were done in 13 conscious long-term catheterized dogs in which sampling (artery, portal and hepatic vein, and iliac vein), infusion catheters (inferior vena cava, duodenum), and transonic flow probes (hepatic artery, portal vein, and iliac artery) were implanted. Fourteen days after surgery dogs were grouped to receive TPN or TEN. After 5 days of TPN/TEN, substrate balances across the liver and limb were assessed. The liver was a marked net consumer of glucose in both groups (23.6 +/- 3.3 vs 22.6 +/- 2.8 micromol x kg(-1) x min(-1), TPN vs TEN) despite near normoglycemia (6.5 +/- 0.3 vs 6.7 +/- 0.2 mmol/L). Arterial insulin levels were higher during TEN (96 +/- 6 vs 144 +/- 30 pmol/L; p < .05). The majority (79 +/- 13 vs 76% +/- 7%) of the glucose taken up by the liver was released as lactate. Despite higher insulin levels during TEN the nonsplanchnic tissues consumed a lessor quantity of glucose (25.9 +/- 3.3 vs 16.1 +/- 3.9 micro x mol x kg(-1) x min(-1)). In summary, the liver undergoes a profound adaptation to TPN and TEN making it a major site of glucose uptake and conversion to lactate irrespective of the route of nutrient delivery. However, the insulin requirements are higher with TEN possibly secondary to impaired peripheral glucose removal.     

Liver test alterations with total parenteral nutrition and nutritional status.

Liver test abnormalities are a well-recognized complication in the parenterally fed population. Numerous etiologies for the development of elevated liver tests have been suggested. However, the etiology and clinical significance remain unclear. The aim of this retrospective study was to determine the extent of liver-associated test (LAT) abnormalities in patients receiving total parenteral nutrition (TPN) and to investigate whether the composition of TPN solutions and the magnitude of malnutrition could be used to predict subsequent LAT abnormalities. Medical records of 78 adult patients who received TPN for at least 2 weeks were reviewed. All subjects had normal LAT results before TPN, were not receiving hepatotoxic drugs, and had no underlying liver disease. Aspartate aminotransferase peaked transiently during week 2 and returned to normal during week 4. Alkaline phosphatase and total bilirubin peaked during weeks 4 and 3, respectively. The average nonprotein kilocalorie distribution was approximately 80% dextrose and 20% lipid. Caloric intake ranged from 7% to 23% above estimated needs. The mean nutritional status score was 22 +/- 15, with a possible range of 0 to 75 (0 indicates no malnutrition). The composition of TPN solutions was not significantly associated with the changes in the three LATs during any week of the 4-week study. The nutritional status score was significantly associated (p less than .05) with the change in alkaline phosphatase during week 1. This study confirms that LAT abnormalities occur during TPN, but the composition of the solution has no significant ability to predict subsequent LAT abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence,outcome and associated factors of deranged liver function tests in patients on home parenteral nutrition

INTRODUCTION: The prevalence of deranged liver function tests (LFT) in patients on long-term home parenteral nutrition (HPN) is poorly documented. The aim of our study was to document the prevalence of this complication and possible associated factors. METHOD: Retrospective analysis of case notes of 107 patients on HPN was performed. Deranged LFT was defined as any biochemical parameter of LFT that is 1.5 times above the reference range. RESULTS:There were 39 males and the median age was 51 (range 20-73) years old. Median duration of HPN was 40 (range 6-252) months. Underlying diagnoses were Crohn's disease (40%), ischaemic bowel disease in 28.1% (arterial or venous), post-surgical intestinal adhesion and fistula (16.9%) and others (21.7%). The mean energy intake from HPN was 1003+/-544(SD) kcal/day with 845+/-474 kcal/day from glucose, 157+/-127 kcal/day from fat and mean nitrogen intake was 6.2+/-3.6 g/day. Raised alkaline phosphatase (mean 197+/-143(SD)U/L) was the most common abnormality (40 patients). Two patients had hyperbilirubinaemia; one patient had hereditary spherocytosis and in the other patient, the cause could be attributed to HPN with bilirubin of 54 micromol/l. Fifty-one patients (47.7%) had deranged LFT as judged from raised parameters on LFT. Abnormality in LFT was transient in nine patients. For the other 42 patients (39%), abnormalities in LFT remained stable for median duration of follow-up of 18.5 (range 3-180) months. No patients developed decompensated liver disease. On univariate analysis, length of small bowel of less than 100 cm, a higher total caloric intake from HPN (mean 1117+/-486 kcal against 907+/-576 kcal, P<0.05), and higher daily caloric intake from HPN in relation to calculated daily energy requirement (70+/-32% against 57+/-36%) were noted to be significantly associated with deranged LFT. However, on multivariate analysis, length of small bowel of less than 100 cm was the only significant variable for deranged LFT. CONCLUSION: Our finding showed the prevalence of deranged LFT to be 39% and raised alkaline phosphatase was the most common abnormality. Length of small bowel of less than 100 cm was found to be a significant independent variable for deranged LFT and the reason for this observation could be due to higher parenteral caloric intake. In our experience, LFT abnormalities are associated with a good prognosis as none of the patients developed decompensated liver disease.     

Serum concentration of cobalamines during total parenteral nutrition in Crohn's disease

The vitamin B12 status was assessed by measuring the fasting serum (S-) concentration of cobalamines in a consecutive series of 12 patients with Crohn's disease (CD) given total parenteral nutrition (TPN)--nil per os--for between 21 and 97 days (mean, 49 days). At introduction of TPN the S-cobalamine concentration was less than 300 pmol/liter in four patients (group I) and more than 300 pmol/liter in eight (group II). Each day during TPN fat- and water-soluble vitamins, including 2 micrograms of cyanocobalamin, were given. In group I there was a small increase in the S-cobalamine level during the first 2 to 4 weeks of TPN, whereas in group II the values approached the middle of the reference range (190-680 pmol/liter) after 6 to 8 weeks of TPN. It would thus appear that the vitamin regimen studied, including 2 micrograms of cyanocobalamin per 24 hr, is able to maintain the S-cobalamine concentration within the reference range during 6 to 8 weeks of TPN in CD patients with no evidence of vitamin B12 deficiency, and to prevent the development of vitamin B12 deficiency during 2 to 4 weeks of TPN in CD patients with a S-cobalamine level initially below 300 pmol/liter.     

Liver function tests in patients receiving parenteral nutrition

A 5-year prospective study was performed to monitor liver function tests (LFTs) in patients receiving total parenteral nutrition (TPN). A gradual and progressive rise was seen in the plasma concentration of bilirubin, aspartate transaminase, and alkaline phosphatase. The rate of rise was not increased in patients with LFT abnormalities before the start of TPN. Half of the patients had an episode of sepsis during TPN, but overall abnormal LFTs did not appear more common in these patients than in those without obvious sepsis. Patients with malignant disease, those requiring long-term TPN, and those requiring a nonstandard TPN regimen were more likely to develop raised LFTs.     

Effects of glutamine-enriched total parenteral nutrition on acute pancreatitis

AIM: This study was performed to determine the effects of glutamine enriched total parenteral nutrition (TPN) on the patients with acute pancreatitis (AP). METHOD: Forty patients with AP, who had Ranson's score between 2 and 4 received either standard TPN (control group) or TPN with glutamine (treatment group). The patients in the treatment group received TPN containing 0.3 g/kg/days glutamine. At the end of the study, patients were evaluated for nutritional and inflammatory parameters, length of TPN and length of hospital stay. RESULTS: The length of TPN applications were 10.5+/-3.6 days and 11.6+/-2.5 days, and the length of hospital stays were 14.2+/-4.4 and 16.4+/-3.9 days for the treatment and control groups (NS), and the complication rates in the treatment and control groups were 10 and 40%, respectively (P<0.05). The transferrin level increased by 11.7% in the group that received glutamine-enriched TPN (P<0.05), whereas the transferrin level decreased by 12.1% in the control group (NS). At the end of the study, slight but not significant changes were determined in both groups in fasting blood sugar, albumin, blood urea nitrogen (BUN), creatinine, total cholesterol concentrations, aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) activities, leukocytes, CD(4), CD(8), serum Zn, Ca and P levels compare to the baseline levels (NS). Significant decreases were determined in serum lipase, amylase activities and C-reactive protein (CRP) levels in both groups (P<0.05). CONCLUSIONS: The results of this study have shown that glutamine supplementation to TPN have beneficial effects on the prevention of complications in patients with AP.     

老年机械通气病人肠内肠外营养支持的比较

目的:观察老年机械通气病人肠内肠外营养支持的效果.方法:将60例老年机械通气病人随机分为全肠内营养(TEN)组和全肠外营养(TPN)组,每组30例,在摄入同等热量和氮量的条件下进行比较.结果:TEN组血清清蛋白、血红蛋白、氮平衡方面明显优于TPN组(P＜0.05).机械通气时间和临床费用低于TPN组(P＜0.05).两组并发症的发生率无显著性差异(P＞0.05).结论:老年机械通气病人肠内营养较肠外营养能更好的提供营养,缩短机械通气时间,而且费用低.     

Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial

BACKGROUND: Previous studies have shown that plasma free choline concentrations are significantly decreased in many long-term home total parenteral nutrition (TPN) patients. Furthermore, low choline status has been associated with both hepatic morphologic and hepatic aminotransferase abnormalities. A preliminary pilot study suggested choline-supplemented TPN may be useful in reversal of these hepatic abnormalities. METHODS: Fifteen patients (10 M, 5 F) who had required TPN for > or =80% of their nutritional needs were randomized to receive their usual TPN (n = 8), or TPN to which 2 g choline chloride had been added (n = 7) for 24 weeks. Baseline demographic data were similar between groups. Patients had CT scans of the liver and spleen, and blood for plasma free and phospholipid-bound choline, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma glutamyl transferase (GGT), bilirubin, serum lipids, complete blood count (CBC), and chemistry profile obtained at baseline, and weeks 2, 4, 6, 12, 16, 20, 24, and 34. CT scans were analyzed for Hounsfield unit (HU) densities. RESULTS: There were no significant differences in any measured parameters after 2 weeks. However, at 4 weeks, a significant difference in liver HU between groups was observed (13.3+/-5.0 HU [choline] vs 5.8+/-5.2 HU [placebo], p = .04). This significant trend continued through week 24. Recurrent hepatic steatosis and decreased HU were observed at week 34, 10 weeks after choline supplementation had been discontinued. A significant increase in the liver-spleen differential HU was also observed in the choline group (10.6+/-6.2 HU [choline] vs 1.3+/-3.3 HU [placebo], p = .01). Serum ALT decreased significantly (p = .01 to .05) in the choline group vs placebo at weeks 6,12, 20, and 24. Serum AST was significantly decreased in the choline group by week 24 (p = .02). The serum alkaline phosphatase was significantly reduced in the choline group at weeks 2, 12, 20, 24, and 34 (p = .02 to 0.07). Total bilirubin was normal in these patients and remained unchanged during the study. Serum GGT tended to decrease more in the choline group, but the greater decrease was not statistically significant. CONCLUSIONS: Choline deficiency is a significant contributor to the development of TPN-associated liver disease. The data suggest choline is a required nutrient for long-term home TPN patients.     

Abnormal liver function in malnourished patients receiving total parenteral nutrition: a prospective randomized study

A prospective study was performed in clinically malnourished patients in which liver function was tested during a 4-week period of total parenteral nutrition (TPN). The purpose was to determine if concomitant intravenous lipid administration would reduce liver function abnormalities noted to occur frequently in patients receiving TPN. Twenty-five patients were randomly assigned to receive either daily infusions of 200 cc of a 20% lipid emulsion with TPN or TPN without lipid for the first week. In the subsequent 3 weeks all patients received daily intravenous lipid. The early lipid treatment group received 0.7 g lipid/kg BW/day and approximately 280 mg of choline/day from the lecithin emulsifier throughout the entire study period. Liver function tests were performed twice in the first week, then weekly thereafter. There were significant (p less than 0.05) elevations in liver function tests in the early lipid treatment group (for aspartate aminotransferase in weeks 1, 2, and 3, and lactic acid dehydrogenase in weeks 2 and 3). Alkaline phosphatase activity was elevated at weeks 2, 3, and 4 for the lipid-treatment group and at week 1 for the lipid-restricted group. The two groups had a similar elevation in gamma-glutamyltransferase activity. Analysis of covariance demonstrated that the overall duration of TPN, and not the presence or absence of intravenous lipid, was significantly related to the elevations in both alkaline phosphatase and gamma-glutamyltransferase (GGT) levels. In contrast, the early intravenous administration of lipid was significantly related to the increase in aspartate aminotransferase levels. The peak increase in AST was noted at day 7 in the lipid-administration group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Liver composition and histology in growing infant miniature pigs given different total parenteral nutrition fuel mixes

Although young infants are at greater risk for total parenteral nutrition (TPN)-related liver disease than adults, previous studies on the effect of the TPN energy source on the development of hepatic steatosis have been carried out in adult rats and adult humans. We studied the effect of a glucose and a glucose/fat TPN energy regimen on hepatic chemical composition and the development of steatosis in newborn miniature pigs. Twenty miniature pigs were randomized at 10 days of age to receive a TPN regimen which utilized either glucose (group A) or glucose/fat (group B) as the non-nitrogen energy source. After 8 days, blood was drawn for insulin, glucagon, SGPT, albumin, and bilirubin determinations. Samples of liver were obtained at 9 days. Plasma insulin levels were significantly higher and glucagon levels lower in group A piglets than in those in group B. Normal values were obtained for SGPT, albumin, and bilirubin, and no differences were found between groups. Chemical analysis of the livers revealed no differences between groups in the concentrations of glycogen, fat, protein, DNA, and RNA. Group A animals had significantly higher concentrations of water than group B (group A: 0.75 +/- 0.01 liter/kg; group B: 0.74 +/- 0.01; p less than 0.03). A significant correlation was found in group B between the plasma insulin/glucagon ratio and the hepatic glycogen concentration (r = 0.73, p less than 0.05). Group A animals had fat vacuoles in centrilobular hepatocytes, in contrast with group B animals who had visible fat only in Kupffer cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abnormal liver function in malnourished patients receiving total parenteral nutrition: a prospective randomized study.

A prospective study was performed in clinically malnourished patients in which liver function was tested during a 4-week period of total parenteral nutrition (TPN). The purpose was to determine if concomitant intravenous lipid administration would reduce liver function abnormalities noted to occur frequently in patients receiving TPN. Twenty-five patients were randomly assigned to receive either daily infusions of 200 cc of a 20% lipid emulsion with TPN or TPN without lipid for the first week. In the subsequent 3 weeks all patients received daily intravenous lipid. The early lipid treatment group received 0.7 g lipid/kg BW/day and approximately 280 mg of choline/day from the lecithin emulsifier throughout the entire study period. Liver function tests were performed twice in the first week, then weekly thereafter. There were significant (p less than 0.05) elevations in liver function tests in the early lipid treatment group (for aspartate aminotransferase in weeks 1, 2, and 3, and lactic acid dehydrogenase in weeks 2 and 3). Alkaline phosphatase activity was elevated at weeks 2, 3, and 4 for the lipid-treatment group and at week 1 for the lipid-restricted group. The two groups had a similar elevation in gamma-glutamyltransferase activity. Analysis of covariance demonstrated that the overall duration of TPN, and not the presence or absence of intravenous lipid, was significantly related to the elevations in both alkaline phosphatase and gamma-glutamyltransferase (GGT) levels. In contrast, the early intravenous administration of lipid was significantly related to the increase in aspartate aminotransferase levels. The peak increase in AST was noted at day 7 in the lipid-administration group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Small-area variations and sociodemographic correlates for the incidence of Crohn's disease and ulcerative colitis

The objectives of this study were to describe variations in the incidence of inflammatory bowel disease (IBD) within the Canadian province of Manitoba and to analyze sociodemographic factors associated with these variations. The authors used the Manitoba Health insurance databases to measure incidence rates of Crohn's disease and ulcerative colitis for each of 52 postal areas in Manitoba, in 1987-1996. The sociodemographic characteristics of the postal areas were based on data from the 1996 Canadian census. The overall incidence rates of Crohn's disease and ulcerative colitis were identical-15.6 per 100,000. Both diseases showed substantial geographic variation, with incidence rates differing significantly from the provincial average in 15 postal areas for Crohn's disease and in 13 postal areas for ulcerative colitis. There was a significant geographic correlation in the incidence of Crohn's disease and ulcerative colitis (r = 0.49, p < 0.001). The incidence of IBD was higher in urban areas (incidence rate ratio (IRR) = 1.21, 95% confidence interval (CI): 1.00, 1.45). Aboriginal Canadians had significantly lower rates of both Crohn's disease (IRR = 0.11, 95% CI: 0.05, 0.22) and ulcerative colitis (IRR = 0.57, 95% CI: 0.42, 0.79). A higher incidence of IBD was ecologically associated with a higher average family income, a lower proportion of immigrant and Aboriginal Canadian populations, and a smaller average family size.     

An evaluation of total parenteral nutrition in the management of steroid-dependent and steroid-resistant patients with Crohn's disease

This study is an evaluation of short- and long-term benefits of total parenteral nutrition (TPN) in 20 patients with active Crohn's disease but without fistulae. TPN was done during 42 (14-80) days (median-range) after failure of medical therapy including patients with steroid-resistant (11 SR) or steroid-dependent (9 SD) active Crohn's disease. Efficacy of short-term TPN was demonstrated by nutritional repair and achievement of clinical remission in all but one patients. Follow-up was 28 (8-78) months in the 19 patients (10 SR, 9 SD) discharged improved after the end of TPN. At 1 yr, the cumulative recurrence rate was 26% (5/19). During the follow-up, three patients (2 SR, 1 SD) remained symptom-free, 13 (6 SR, 7 SD) had a partial remission defined as relapse controlled by medication, and only three patients (2 SR, 1 SD) had a relapse uncontrolled by medical therapy leading to surgery. Therefore in our selected population without fistula or abscess, after failure of medical therapy TPN was obviously an effective therapy which avoided surgery. Furthermore follow-up indicated that SD and SR were only transient events in the course of Crohn's disease patients.     

消化道肿瘤-T-术后早期肠内营养疗效研究

目的评价消化道肿瘤手术后早期肠内营养的安全性,比较手术后短期应用要素制剂爱伦多的肠内营养与标准肠外营养支持的疗效。 方法62例消化道恶性肿瘤手术患者,随机分为对照组、肠外营养组和肠内营养组。手术后第一天开始等热卡、等氮量的肠外或肠内营养支持一周。检测体重、机体测量指标、血浆各内脏蛋白浓度及氮平衡等营养指标,外周血T细胞亚群、NK细胞和NK细胞活性等免疫指标及血清氨基酸谱。 结果三组病人术后体重下降分别为4．26±1．03ks、2．04±0．65ke和2．12±o．72kg,对照组与肠外营养组、肠内营养组之间差异有显著性(P<0．05),后两组之间无差异。术后各内脏蛋白浓度均低于术前,对照组降低最明显,与肠外或肠内营养组之间差异有显著性(P<0．05),而后两组之间无差异。三组病人平均氮平衡为—8．6±3．12g／d,—4．22±2．02g／d及—3．88±2．35g／d,对照组与肠外或肠内营养组之间差异有显著性(P<0．05),而后两组之间无差异。手术后各组病人外周血T细胞亚群、NK细胞和NK细胞活性均不同程度下降,但三组之间差异无显著性意义。三组病人血清谷氨酰胺水平明显下降,术后1周对照组和肠外营养组血清谷氨酰胺水平仍处于低水平,而肠内营养组却有一定程度恢复。 结论消化道肿瘤手术后早期肠内营养支持是安全、有效的方法,短期肠内营养和肠外营养支持的临床效果基本相同。     

Taurine supplementation in infants receiving long-term total parenteral nutrition

Twenty-one children and 23 adults receiving long-term total parenteral nutrition (TPN) for 27 +/- 23 (SD) months were investigated to determine if they were taurine-deficient because the TPN solutions were taurine-free. The fasting plasma taurine level was reduced in the children to 26 + 13 mumol/liter vs the control 57 +/- 16 mumol/liter (P greater than 0.001). The plasma taurine level was significantly reduced in those adults who absorbed less than 25% of their nutritional needs from their diet. Electroretinograms were abnormal in each of eight children who were examined; isolated cone and rod implicit times were both significantly delayed. Electroretinograms were not abnormal in those adults with low plasma taurine levels. Taurine was added to the TPN solutions of four children, and the plasma taurine level became normal in each of them. Electroretinograms of three of these children became normal. One year after discontinuing intervenous taurine supplementation, the plasma taurine level became abnormal in two of three children. These observations indicate that children, and possibly adults, receiving long-term TPN have a nutritional requirement for taurine.     

Immediate enteral nutrition following multisystem trauma: a decade perspective.

Metabolic support is an integral component of surgical critical care. Although prompt restoration of oxygen availability is clearly essential, the timing, composition, and route of nutritional support may also be decisive factors. The ensuing discussion will focus on: (a) timing of substrate delivery and (b) route of administration based on our clinical investigation over the past decade. The acutely injured patient was selected as a model of ICU hypermetabolism because of relative homogeneity with respect to age, comorbid factors, and stress level. Our first study hypothesis was that early nutritional support would improve outcome in the severely injured, but previously well-nourished patient. During an 18-month period, all patients undergoing laparotomy with a abdominal trauma index (ATI) greater than 15 were randomized to a control or total enteral nutrition (TEN) group. The control patients were given total parenteral nutrition (TPN) after POD 5, whereas the TEN cohort had a needle catheter jejunostomy (NCJ) inserted at laparotomy and received an elemental diet within 12 hours. The control (n = 31) and TEN (n = 32) groups were otherwise comparable with respect to risk stratification. The TEN patients, of course, shared improved nitrogen balance (p less than 0.001), but also had significantly (p less than 0.025) less septic morbidity. Nine (29%) of the controls developed major infections, contrasted to three (9%) of the TEN patients. Acknowledging the benefit of early nutrition, the next issue we addressed was the optimal route of substrate delivery; i.e., TEN vs TPN. The hypothesis was that TEN, compared to TPN, would reduce the injury stress response as reflected by the prioritization of hepatic protein synthesis. TEN given via NCJ and a nutritionally matched TPN solution were administered during the same postoperative period. Indeed, the TEN patients (n = 23) had significantly (p less than 0.05) higher constitutive proteins and lower acute-phase proteins, whereas the TPN patients manifested the opposite protein profile as measured by crossed immunoelectrophoresis. In view of these findings, we continued the study to ascertain clinical impact. Ultimately, 75 patients were randomized, providing groups with equivalent risk factors. Eleven (37%) of the TPN patients developed septic complications compared to five (17%) of the TEN group, and the incidence of major infection was six (20%) following TPN vs one (3%) with TEN. Thus, immediate TEN provided an additional clinical benefit compared to early TPN in these high-risk surgical patients.     

Serum bone marker measurements in bone metabolism disorders associated with inflammatory bowel diseases

Patients with inflammatory bowel disease (IBD) have decreased bone mineral density (BMD), which is usually much more remarkable in patients with Crohn's disease (CD) than those with ulcerative colitis (UC). The aim of the present study was to investigate the usefulness of serum beta-Crosslaps (bCL) and osteocalcin (OC) determinations to assess bone metabolism in patients with IBD. Forty-nine patients with IBD (23 UC, 26 CD) and 46 healthy controls were studied. Serum bCL and OC were measured by Elecsys immunoassay. Compared to controls (0.275 +/- 0.14 ng/ml) the mean bCL concentration was significantly higher in the CD (mean = 0.489 +/- 0.25 ng/ml; p < 0.001) and UC groups (mean = 0.439 +/- 0.3 ng/ml; p < 0.01). The mean OC concentration was significantly higher in the CD group (28.52 +/- 14.75 ng/ml) than in controls (21.42 +/- 7.43 ng/ml) but OC level was not significantly increased in the UC group (24.89 +/- 15.08 ng/ml). There was no significant difference in bCL or OC concentrations between the CD and UC groups. These results indicate that the accelerated bone resorption is not associated with increased bone formation in patients with IBD. These two marker of the bone metabolism could be a good laboratory parameter of bone pathology in patients with IBD, especially in CD.     

A population-based ecologic study of inflammatory bowel disease: searching for etiologic clues

The authors' objective in this study was to determine geographic variations in the incidence of inflammatory bowel disease (IBD), specifically Crohn's disease and ulcerative colitis, in the Canadian province of Manitoba and its association with the sociodemographic, geographic, and disease-related characteristics of the study population. Using the University of Manitoba IBD Epidemiology Database, the authors applied spatial and ecologic techniques to visualize, explore, and model the incidence of Crohn's disease and ulcerative colitis for the period 1990-2001. The study demonstrated marked, statistically significant geographic variability in rates of both Crohn's disease and ulcerative colitis associated with the characteristics of the study population. Incidences of Crohn's disease and ulcerative colitis were observed to be highest among non-Aboriginal persons, persons of high socioeconomic status, persons with the lowest rates of enteric infection, and persons with the highest rates of multiple sclerosis. The observation of an inverse association between IBD incidence and rates of reportable enteric infection at the population level is consistent with the "hygiene hypothesis," which suggests that early exposure to enteric agents affords protection against eventual development of IBD. The positive association between IBD incidence rates and multiple sclerosis suggests that these two chronic, immunologically mediated diseases may have a common environmental etiology. This study underscores the importance of environment in IBD causation.