�������˳���Ӫ����Ҫ�����ٴ��о�

目的　研究适当提高肠内营养能量与蛋白质的供给对重度营养不良的肠瘘病人营养状况、能量代谢和脏器功能的影响。方法　选择 2 0 0 1年 5月至 2 0 0 2年 3月的肠瘘病人 2 0例 ,随机分为两组 ,两组病人均给予百普素。对照组病人总热量按 1 5×静息能量消耗 (REE)供给 ,研究组病人按 2 0×REE供给。观察在 15d内两组病人的营养状况、能量代谢和脏器功能的变化。结果　在 15d的营养支持后研究组病人体重增加了 2 0kg ,而对照组病人仅增加 1 3kg。进行营养支持后两组病人的REE无明显变化 ,但呼吸商 (RQ)逐渐增高 ,在第 5、10、15天有显著变化 (P <0 0 1) ,在第 15天 ,研究组RQ达到 0 91,显著高于对照组 (P <0 0 5 )。两组病人在底物氧化率方面差异无显著性意义。在第 10和 15天血清前白蛋白、转铁蛋白、纤维连接蛋白、白蛋白浓度较营养支持前有显著增加 ,且研究组均显著高于对照组。两组病人血糖、血脂和肝肾功能均无明显改变。结论　适量提高肠瘘病人肠内营养的热量和蛋白质供给量可迅速地改善重度营养不良肠瘘病人的营养状态 ,且不会引起代谢紊乱和脏器功能损害。     

Partially hydrolyzed guar gum alleviates small intestinal mucosal damage after massive small bowel resection along with changes in the intestinal microbiota

PurposeShort bowel syndrome is associated with intestinal mucosal inflammation and microbial dysbiosis, leading to intractable complications. Partially hydrolyzed guar gum (PHGG) has trophic and anti-inflammatory effects on the intestine. We investigated whether PHGG ameliorates small intestinal mucosal damage and alters the intestinal microbiota using a rat small bowel resection (SBR) model.MethodsSprague Dawley rats were divided into sham operation (Sham), Sham/PHGG, SBR, and SBR/PHGG groups. On day 21, all rats were euthanized. To assess small intestinal mucosal damage, the degeneration rate was morphometrically evaluated and immunohistochemically examined using anti-CD45 antibodies. Analyses of fecal microbiota using 16S rRNA and short-chain fatty acid production were also performed.ResultsThe mucosal degeneration rate was significantly higher in the SBR group than in the Sham or SBR/PHGG groups. The number of CD45-positive cells was significantly higher in the SBR group than in the Sham, Sham/PHGG, or SBR/PHGG groups. The relative abundance of family Lachnospiraceae was significantly higher in the SBR/PHGG group than in the SBR group.ConclusionsPHGG administration alleviated small intestinal mucosal damage which could be associated with modulation of the intestinal microbiota.     

Morphological and functional changes in the colon after massive small bowel resection

Purpose

Anecdotal evidence suggests that the colon plays an important role after small bowel resection (SBR). However, colonic changes have not previously been studied. The aim of this study was to characterize morphological and functional changes within the colon after SBR and elucidate the influence of diet complexity on adaptation.

Method

In study 1, 4-week-old piglets underwent a 75% SBR or sham operation and were studied at 2, 4, and 6 weeks postoperation to allow analysis of early and late adaptation responses. Piglets received a polymeric infant formula (PIF).In study 2, SBR piglets received an elemental diet and were studied at 6 weeks postoperation and compared with SBR + PIF piglets from study 1. For both studies, immunohistochemistry was used to quantitate intestinal cell types. Changes in functional proteins were measured by Western blot, enteroendocrine/peptide YY (PYY), enterocyte/liver fatty acid binding protein (L-FABP), and goblet cells/trefoil factor 3 (TFF3).

Results

In study 1, early and late adaptation-related changes were observed after SBR. Early adaptation included increased numbers of enterocytes (P = .0001), whereas late adaptation included increased proliferative cell numbers (P = .02). Enteroendocrine, goblet, and apoptotic cells numbers were significantly elevated in the resected group at all time-points studied (P < .05). Functional changes included increased levels of L-FABP (P = .04) and PYY (P = .03). There was no change in TFF3 expression.In study 2, feeding with an elemental diet resulted in suboptimal adaptation as evidenced by reduced rate of weight gain and significant reductions in total cell numbers (P = .0001), proliferative (P = .0001) and apoptotic cells (P = .04), enteroendocrine cells (P = .001), and PYY expression (P .004).

Conclusion

These findings indicate that significant morphological and functional changes occur in the colon after massive SBR and that these occur as early and late adaptation responses. Elemental diet was associated with suboptimal adaptation suggesting an effect of diet complexity on colonic adaptation.     

Effect of sex and sex hormones on structural intestinal adaptation after massive small bowel resection in rats

Purpose

The gonadal steroids play a major role in the regulation of many functions. The purpose of the current study was to evaluate the effect of sex and sex hormones on intestinal adaptation in a rat model of short bowel syndrome (SBS).

Methods

In the first experiment, male and female Sprague-Dawley rats underwent bowel transection and re-anastomosis (sham group) or 75% small bowel resection and anastomosis (SBS group). Relative changes in parameters of intestinal adaptation (overall bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth) were measured on day 15 and were compared with respect to sex. In the second experiment, male rats were divided into 4 experimental groups: SBS rats, SBS castrated rats, SBS castrated rats treated with testosterone, and SBS castrated rats treated with estradiol. Parameters of intestinal adaptation were compared with respect to hormonal treatment. Statistical significance was determined by Student's t test and analysis of variance with P < .05 considered significant.

Results

Sex had minimal effects on intestinal adaptation. Both male and female rats showed a comparable increase in all parameters of intestinal adaptation. In the second experiment, castration led to significant decrease in bowel and mucosal weight, mucosal DNA and protein in both jejunum and ileum compared with SBS animals. Castrated rats also had lower jejunal villus height and crypt depth compared with SBS animals. Testosterone attenuated this negative effect of castration on bowel regrowth. Rats treated with testosterone showed a significant increase in bowel and mucosal weight, mucosal protein in both jejunum and ileum, mucosal DNA, villus height, and crypt depth in jejunum compared with castrated nontreated animals. Treatment with estradiol after resection and castration had minimal effect on bowel regrowth.

Conclusions

Bowel regrowth after massive small bowel resection is not sex-related. Depletion of androgens by castration inhibited intestinal adaptation. Testosterone has shown a strong stimulating effect on bowel regrowth.     

大鼠广泛肠切除后小肠组织miR-125a和Mcl-1的表达及意义

目的：探讨广泛肠切除后miR-125a和抗凋亡蛋白（Mcl-1）在肠上皮细胞中表达的变化及其在短肠综合征剩余肠管适应性变化过程中的意义。方法选取8周龄的SD雄性大鼠54只,分为实验组（18只,进行70％的大范围小肠切除,距回盲部近端15 cm和Treitz韧带远端10 cm处分别切断小肠,然后行空回肠端端吻合）、肠切除对照组（18只,在距回盲部近端15 cm处切断肠管然后再吻合）和手术对照组（18只,仅行开关腹手术）。术后1周在距吻合口远端1 cm处取材,采用免疫组织化学方法和实时荧光定量 PCR检测各组大鼠小肠组织中 Mcl-1和 miR-125a 表达。结果实验组大鼠肠组织中Mcl-1阳性表达率为18．8％（3／16）,明显低于手术对照组（76．5％,13／17）和肠切除对照组（83．3％,15／18）（均P＜0．01）;miR-125a相对表达量为1.92,明显高于肠切除对照组（1.01）和手术对照组（1.05）（均P＜0．01）。结论 miR-125a和Mcl-1在广泛肠切除诱导的肠道适应过程中发挥重要作用,二者之间通过一定的机制相互调节。     

Effect of probiotics on intestinal regrowth and bacterial translocation after massive small bowel resection in a rat

Background/Purpose

Because of their ability to inhibit intestinal bacterial overgrowth, probiotics (PROs) have been advocated for the treatment of patients with short bowel syndrome (SBS). This study was conducted to determine the effect of PROs on bacterial translocation and intestinal regrowth after massive small bowel resection in a rat.

Methods

Male Sprague-Dawley rats were divided into 3 experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent 75% small bowel resection, and SBS-PRO rats underwent bowel resection and were treated with a PRO given in drinking water from day 4 through 14. Intestinal structural changes (bowel circumference, overall bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, enterocyte proliferation and enterocyte apoptosis) and bacterial translocation (BT) to mesenteric lymph nodes, liver, portal blood, and peripheral blood were determined on day 15 after operation.

Results

Sham rats exhibited a 20% BT to the mesenteric lymph nodes (level I), liver (level II), and blood (level III). Short bowel syndrome rats demonstrated a 100% BT to lymph nodes (level I) and liver (level II) and 40% translocation to peripheral blood (level III). Treatment with PROs resulted in a significant decrease in BT to all 3 target organs and decreased enterocyte apoptosis compared with SBS-untreated animals. Short bowel syndrome rats showed a significant increase (vs sham) in jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth. Short bowel syndrome rats also had a greater proliferation index and apoptotic index in both jejunum and ileum compared with sham animals. SBS-PRO rats showed a significant increase (vs SBS rats) in crypt depth in ileum and a mild decrease in apoptotic index in jejunum and ileum, compared with SBS-untreated animals.

Conclusions

In a rat model of SBS, PROs decrease BT through mechanisms which maybe dependent on intestinal mucosal integrity.     

Epidermal growth factor receptor signaling regulates goblet cell production after small bowel resection

Background/Purpose

Intestinal adaptation is a compensatory response to massive small bowel loss in which there are increased numbers of absorptive enterocytes. However, the generation of secretory epithelial cell subtypes in this process has not been investigated. The purpose of this study was to examine the adaptive changes of several small intestinal cell lineage changes in response to massive small bowel resection (SBR).

Methods

A 75% SBR or sham operation was performed on male Sprague-Dawley rats. On postoperative day 7, the remnant ileum was harvested and immunohistochemical staining for goblet, Paneth, and enteroendocrine cells was performed. Cell subtypes were evaluated as cells per micrometer of villus/crypt length and compared among operations.

Results

A significant increase in goblet cell density occurred after SBR. Intestinal resection did not alter the number of Paneth and enteroendocrine cells. In additional experiments, inhibition of epidermal growth factor receptor signaling was associated with a diminished goblet cell density.

Conclusions

The adaptive response of the intestine to massive bowel loss results in an expansion of the goblet cell population in addition to greater numbers of absorptive enterocytes. Although the mechanism and purpose for selective expansion of these stem cell-derived lineages are not presently known, epidermal growth factor receptor signaling appears to be a common pathway.     

Preventing enterocyte apoptosis after massive small bowel resection does not enhance adaptation of the intestinal mucosa

Background

After massive small bowel resection (SBR), increased rates of enterocyte apoptosis are observed in the remnant bowel via a mechanism requiring bax gene expression. This study tested the hypothesis that adaptive mucosal growth could be enhanced by the novel strategy of preventing postresection enterocyte apoptosis.

Methods

Male bax-null and corresponding wild-type (WT) mice underwent a 50% proximal SBR or sham operation (bowel transaction with reanastomosis alone). Mice were killed after a full adaptation interval of 1 month. Adaptation was measured in the remnant ileum as alterations in villus height, crypt depth, and wet weight. Rates of enterocyte proliferation were derived by immunostaining of crypt enterocytes for Ki-67 and apoptosis by the presence of apoptosis bodies.

Results

The expected increase in enterocyte apoptosis after SBR occurred in the WT mice but was unchanged in the bax-null mice. Despite the prevention of postresection apoptosis in the bax-null mice, all parameters of adaptation and proliferation increased equally after SBR in both groups of mice.

Conclusions

Bax deficiency prevents the increase in enterocyte apoptosis that occurs after massive SBR throughout the entire adaptation period. Attenuation of postresection enterocyte apoptosis does not augment mucosal adaptation to massive intestinal loss.     

精氨酸促进短肠综合征肠道代偿及其机制的初步研究

目的研究肠内营养中添加精氨酸对广泛肠切除术后大鼠肠道代偿的影响。方法将30只SD大鼠随机分为Con组（假手术）、SB组（短肠对照）和SB—Arg组（短肠加用精氨酸）,各组大鼠于术后第2。14天分别给予等氮、等热量的肠内营养支持．其中SB-Arg组肠内营养中添加L-精氨酸（300mg·kg^-1·d^-1）。比较术后各组体质量、脂肪吸收率、血浆总游离脂肪酸及必需脂肪酸水平、小肠代偿指标、肠黏膜细胞增殖和凋亡的差异。结果SB组术后早期营养支持2周后,其体质量较Con组低,各项肠道代偿指标均明显升高（P〈0．05）。SB-Arg组大鼠脂肪吸收率[（84．9±3．2）％]、血浆游离脂肪酸水平[（650．0±86．5）mg／L]、回肠黏膜质量[（18．0±3．5）mg·cm^-1·100g^-1]、回肠DNA含量[（29．6±3．3）μg·cm^-1·100g^-1]、小肠蛋白质含量[空肠（65．5＋7．3）μg·cm^-1·100g^-1和回肠（39．2±2．3）μg·cm^-1·100g^-1]和小肠增殖指数（空肠31±4,回肠32±2）均高于SB组的[（81．3±3．9）％、（289．5±76．9）mg／L、（13．5±3．0）mg·cm^-1·100g^-1（26．0＋2．6）μg·cm^-1·100g^-1（59．8±6．2）μg·cm^-1·100g^-1、（35．4±2．3）μg·cm^-1·100g^-1、（22±3）及（25±3）,均P〈0．05];小肠超微结构亦观察到SB-Arg组大鼠小肠绒毛高度、隐窝深度及黏膜厚度均大于SB组大鼠（P〈0．05）。结论肠内营养中添加适量精氨酸能促进短肠综合征大鼠肠道结构及功能的代偿．其机制可能为促进肠黏膜细胞增殖、抑制其凋亡。     

Establishing norms for intestinal length in children

Background

Existing data on pediatric intestinal length (IL) are limited because most studies report postmortem values. Using prospective data, appropriate norms for IL were developed.

Method

The IL measurements, using a silk suture on the antimesenteric border, were prospectively made on patients between 24 weeks of gestational age and 5 years of age undergoing laparotomy. Patients with gastrointestinal malformations or those above or below 2 SDs for growth parameters were excluded. A curve fitting process was applied to determine the best model for IL (small bowel and colon separately) from among postconception age, weight, and height at surgery.

Results

One hundred eight patients participated in this study. Highly predictive (R² > 0.8) models for IL were determined for all predictor variables (postconception age, weight, and height) examined suggesting that all of these variables are excellent predictors determinants of IL. Although all models had statistically similar properties, the model using height had the best performance across the full range of the variable.

Conclusion

Although age, weight, nor height was definitely superior for the prediction of IL, we propose that until external validations of our models occur, height at surgery be used for the prediction of expected small intestinal and colon length in infants.     

能量估测公式评估短肠综合征患者静息能量消耗的研究

目的 研究目前常用的4种能量消耗估测公式在评估短肠综合征患者静息能量消耗(REE)时的准确性以及静息能量消耗与人体成分指标的相关性.方法 以2001年1月至2010年10月收治的短肠综合征患者为研究对象.全部病例41例,其中男性30例,女性11例;年龄18～60岁,平均(37±16)岁;平均身高(164.3 ±9.0)cm;平均体质量(47.0±9.3)kg;平均残余小肠(52±45)cm.所有患者均需要行长期肠外或肠内加肠外营养支持治疗.采用间接能量代谢检测仪检测患者REE,同时使用目前常用的4种REE估测公式(HB、SR、FAO、LIU)对患者进行REE估测,并评价两者间差异.利用人体成分分析仪对患者进行身体成分分析.结果 全部患者实测REE的平均值为(1218 ±293)Kcal,与4种计算公式估测REE值均有相关性,相关系数分别为:HB(r=0.588,P<0.01),SR(r=0.591,P<0.01),FAO(r=0.411,P<0.01),LIU(r=0.585,P<0.01).实测REE和4种估测REE进行配对t检验的结果 显示,在总样本中,实测REE值与HB、SR和FAO公式估测值的差异无统计学意义(均P<0.05),但比LIU公式估测值高出14.17%(P<0.01).实测REE与体质量、无脂体质量、体细胞总体有显著相关性,相关系数分别为0.548、0.641和0.581.结论 评估短肠综合征患者REE时应首选间接能量代谢检测仪,在没有条件使用该检测仪而需利用估测公式评估时,应尽量避免使用LIU公式,而应选择SR公式进行评估.短肠综合征患者的REE与体质量、无脂体质量、体细胞总体均有相关性,其中无脂体质量的相关性最高.

Abstract：

Objectives To determine the accuracy of resting energy expenditure (REE) calculated by using the Harris-Benedict(HB) equation, Food and Agriculture Organization/World Health Organization/ United Nations University (FAO/WHO/UNU) equations (FAO equations) , Shizgal-Rosa (SR) equation and the LIU equation in patients with short bowel syndrome(SBS). In addition, to explore the relationship between measured REE and body weight, fat free mass, body cell mass, fat mass and fat mass percent. Methods Fourty-one SBS patients including 30 male and 11 female, aged from 18 to 60 years admitted between January 2001 and October 2010 were enrolled in this study. All patients required long-term parenteral or enteral plus parenteral nutrition support Their mean age and mean stature were (37 ± 16) years and (164. 3 ± 9. 0) cm, and the average body weight and residual small intestine was (47.4 ± 9. 3) kg and (52 ±45) cm. Measured REEs and calculated REEs of SBS patients were estimated respectively by indirect calorimetry and REE equations, and then defined the difference of them. And body mass were metered by body composition analyzer. Results A significant correlation was found between measured REEs (1218 ± 293) Kcal and calculated REEs from the HB equation (r = 0. 588, P < 0.01), the SR equations (r = 0.591,P<0.01), the FAO equations (r=0.411 ,P<0.01) and the LIU equation (r=0.585,P<0.01).In the total sample, the paired t test between measured REEs and REEs derived from the HB equation,SR equation and FAO equation showed no significant difference (P > 0. 05). However, measured REEs were significantly higher than REEs calculated using the LIU equations by 14. 17% (P <0. 01). There was also a significant correlation between measured REEs and body weight, fat free mass and body cell mass (r = 0. 548,0. 641 and 0. 581). Conclusions Indirect calorimetry is preferred when an accurate REE estimate of SBS patients is necessary. However, if this machine is not available, SR equation is recommended to use and LIU equation must be avoided. Fat free mass may be more useful than body weight in REE calculation.     

The extent of intestinal failure-associated liver disease in patients referred for intestinal rehabilitation is associated with increased mortality: an analysis of the Pediatric Intestinal Failure Consortium database

Background

The advent of regional multidisciplinary intestinal rehabilitation programs has been associated with improved survival in pediatric intestinal failure. Yet, the optimal timing of referral for intestinal rehabilitation remains unknown. We hypothesized that the degree of intestinal failure-associated liver disease (IFALD) at initiation of intestinal rehabilitation would be associated with overall outcome.

The effect of intravenous lipid emulsions and mucosal adaptation following massive bowel resection

Aims and objectives

Fish oil (FO) lipid emulsion and a new lipid emulsion (SMOF) are important treatments for intestinal failure-associated liver disease. We evaluated the efficacy of FO and SMOF lipid emulsion on intestinal mucosal adaptation using a total parenteral nutrition (TPN)-supported rat model of short bowel syndrome.

Preservation of extracorporeal tissue in closing gastroschisis augments intestinal length

Background

Prenatal closure of the umbilical ring in gastroschisis may result in an amorphous, nonviable appearing extracorporeal tissue that is resected during the repair. However, it is unclear whether such remnant intestine is truly nonviable.

Methods and Results

We examined the outcomes of patients when this tissue is preserved. We identified 8 patients who presented with a closing gastroschisis and a mass of tissue connected by a vascular pedicle. Four patients underwent abdominal exploration with resection of the mass and gastroschisis closure. Histologic examination revealed normal intestinal wall architecture. All patients in this group developed short bowel syndrome, requiring long-term parenteral nutrition. Conversely, 4 patients underwent abdominal exploration with internalization of the remnant tissue, a maneuver referred to as “parking,” along with either silo placement, or primary closure of the gastroschisis. At re-exploration, 3 of 4 patients were found to have viable intestine, and bowel continuity was reestablished. The mean parenteral nutrition requirement for this group was significantly shorter than the resected group.

Conclusion

In this series, we show that this amorphous tissue, when preserved, may exhibit normal intestinal architecture and absorptive function. Therefore, such remnant tissue should be preserved as it may significantly increase bowel length and minimize parenteral nutrition requirement.     

Reversal of intestinal failure-associated liver disease in infants and children on parenteral nutrition: experience with 93 patients at a referral center for intestinal rehabilitation

Purpose

Intestinal failure (IF)-associated liver disease (IFALD) complicates the treatment of children with IF receiving parenteral nutrition (PN). We hypothesized that prevention or resolution of IFALD was possible in most children and that this would result in improved outcomes.

Methods

We reviewed prospectively gathered data on all children referred to the intestinal rehabilitation and transplantation center at our institution. Total bilirubin level (TB) was used as the marker for IFALD. Patients were grouped based on TB at referral and at subsequent inpatient stays and outpatient visits. Standard treatment consisted of cycling of PN, limiting lipid infusion, enteral stimulation, use of ursodeoxycholic acid, and surgical intervention when necessary. Outcomes such as mortality, dependence on PN, and need for transplantation were assessed. Statistical analyses were performed using Fisher's exact, Mann-Whitney U, and Wilcoxon signed rank tests.

Results

Ninety-three patients with intestinal failure and on PN were treated at our center from 2003 to 2009. Median age at referral was 5 months (0.5-264 months). Prematurity was a complicating factor in 63 patients and necrotizing enterocolitis was the most common diagnosis. Eighty-two children had short bowel syndrome, whereas the remaining 11 had extensive motility disorders. 97% of children required significant alteration of their PN administration. At referral, 76 of 93 children had TB 2.0 mg/dL or higher, and 17 had TB below 2.0 mg/dL. TB normalized in 57 of 76 children with elevated TB at referral, and TB remained elevated in 19. Normalization of TB was associated with a mortality of 5.2%, and transplantation was needed in 5.2%. Conversely, when TB remained elevated, mortality was 58% (P = .0002 vs TB normalized), and transplantation occurred in 58% owing to failure of surgical and medical rehabilitation.

Conclusions

Most children referred for treatment of IF have IFALD. A dedicated IF rehabilitation program can reverse IFALD in many children, and this is associated with improved outcome.     

Outcomes of intestinal failure—a comparison between children with short bowel and dysmotile intestine

Background

We investigated whether mortality, intestinal adaptation, and liver function differ between intestinal failure (IF) patients with either short bowel (SB) or bowel dysmotility (DM).

Patients and methods

Twenty-six consecutive patients with SB (n = 20) or DM (n = 6) treated between 2000 and 2007 were retrospectively assessed. Intestinal failure was defined as less than 25% of age-adjusted small intestinal length or dependence on parenteral nutrition (PN) more than 6 months.

Results

Median age-adjusted small intestinal length (17% vs 45%) and gestational age (35 vs 40 weeks) were (P < .05) shorter, whereas proportion of the remaining colon (86% vs 0%) was (P < .05) higher in the SB group relative to the DM group. Overall survival was 92%. Median peak serum bilirubin (80 vs 25 μmol/L) and rate of cholestasis (11/20 vs 0/6) were higher (P < .05) in the SB group. Short bowel rather than DM as an etiology of IF predicted weaning off PN (RR, 39.3; 95% confidence interval [CI], 1.43-526; P < .01) and development of cholestasis (risk ration [RR], 18.3; 95% CI, 0.658-127; P < .05). Three SB children developed liver failure and two died, whereas neither of these occurred in the DM group.

Conclusions

Children with SB are more likely to wean off PN but more prone to cholestatic liver disease than those with DM as an etiology of IF.