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Biomedical subjects

Daniel H Teitelbaum

Publications and source records attributed to Daniel H Teitelbaum.

At least 19 recordsLinked to original sources

Intestinal epithelial cell proliferation is dependent on the site of massive small bowel resection.

Early intestinal adaptation after massive small bowel resection (SBR) is driven by increased epithelial cell (EC) proliferation. There is a clear clinical difference in the post-operative course of patients after the loss of proximal (P) compared to distal (D) small bowel. This study examined the effects of the site of SBR on post-resectional intestinal adaptation, and investigated the potential mechanisms involved. C57BL/6J mice (n = 7/group) underwent: (1) 60% P-SBR, (2) 60% D-SBR, (3) 60% mid (M)-SBR and (4) SHAM-operation (transection/reanastomosis). Mice were sacrificed at 7 days after surgery and ECs and adjacent mucosal lymphocytes (IELs) isolated. Adaptation was assessed in both jejunum and ileum by quantification of villus height, crypt depth, villus cell size, crypt cell size (microns), goblet cell number, and EC proliferation (%BrdU incorporation). Proliferation signalling pathways including keratinocyte growth factor (KGF)/KGFR(1), IL-7/IL-7R, and epidermal growth factor receptor (EGFR) were measured by RT-PCR. Expression of IL-7 was further analysed by immunofluorescence. Data were analyzed using ANOVA. All three SBR models led to significant increases in villus height, crypt depth, goblet cell numbers and EC proliferation rate when compared to respective SHAM groups. The strongest morphometric changes were found for jejunal segments after M-SBR and for ileal segments after P-SBR. Furthermore, morphometric analysis showed that at 1-week post-resection a tremendous increase in EC numbers occurred in jejunal villi (cell hyperplasia), whereas a significant increase in EC size predominated in ileal villi (cell hypertrophy). mRNA expression of KGF, KGFR(1), IL-7R, and EGFR showed a significant increase only after D-SBR, whereas IL-7 increased significantly after SBR in all investigated models, and this was confirmed by immunofluorescence studies. Early intestinal adaptation shows distinct differences depending on the site of SBR, and is predominately driven by cell hyperplasia in jejunal villi and cell hypertrophy in ileal villi. However, the exact mechanisms, which guide these signalling pathways are still unclear.

Adaptation, Physiological↗

Are the long-term results of the transanal pull-through equal to those of the transabdominal pull-through? A comparison of the 2 approaches for Hirschsprung disease.

PURPOSE: The transanal endorectal pull-through (TERPT) is becoming the most popular procedure in the treatment of Hirschsprung disease (HD), but overstretching of the anal sphincters remains a critical issue that may impact the continence. This study examined the long-term outcome of TERPT versus conventional transabdominal (ABD) pull-through for HD. METHODS: Records of 41 patients more than 3 years old who underwent a pull-through for HD (TERPT, n = 20; ABD, n = 21) were reviewed, and their families were thoroughly interviewed and scored via a 15-item post-pull-through long-term outcome questionnaire. Patients were operated on between the years 1995 and 2003. During this time, our group transitioned from the ABD to the TERPT technique. Total scoring ranged from 0 to 40: 0 to 10, excellent; 11 to 20 good; 21 to 30 fair; 31 to 40 poor. A 2-tailed Student t test, analysis of covariance, as well as logistic and linear regression were used to analyze the collected data with confidence interval higher than 95%. RESULTS: Overall scores were similar. However, continence score was significantly better in the ABD group, and the stool pattern score was better in the TERPT group. A significant difference in age at interview between the 2 groups was noted; we therefore reanalyzed the data controlling for age, and this showed that age did not significantly affect the long-term scoring outcome between groups. CONCLUSION: Our long-term study showed significantly better (2-fold) results regarding the continence score for the abdominal approach compared with the transanal pull-through. The stool pattern and enterocolitis scores were somewhat better for the TERPT group. These findings raise an important issue about the current surgical management of HD; however, more cases will need to be studied before a definitive conclusion can be drawn.

Child↗

Intestinal epithelial cell-derived interleukin-7: A mechanism for the alteration of intraepithelial lymphocytes in a mouse model of total parenteral nutrition.

Total parenteral nutrition (TPN), with the absence of enteral nutrition, results in profound changes to both intestinal epithelial cells (EC) as well as the adjacent intraepithelial lymphocyte (IEL) population. Intestinal EC are a rich source of IL-7, a critical factor to support the maintenance of several lymphoid tissues, and TPN results in marked EC changes. On this basis, we hypothesized that TPN would diminish EC-derived IL-7 expression and that this would contribute to the observed changes in the IEL population. Mice received enteral food and intravenous crystalloid solution (control group) or TPN. TPN administration significantly decreased EC-derived IL-7 expression, along with significant changes in IEL phenotype; decreased IEL proliferation; and resulted in a marked decrease in IEL numbers. To better determine the relevance of TPN-related changes in IL-7, TPN mice supplemented with exogenous IL-7 or mice allowed ad libitum feeding and treated with exogenous administration of anti-IL-7 receptor (IL-7R) antibody were also studied. Exogenous IL-7 administration in TPN mice significantly attenuated TPN-associated IEL changes, whereas blocking IL-7R in normal mice resulted in several similar changes in IEL to those observed with TPN. These findings suggest that a decrease in EC-derived IL-7 expression may be a contributing mechanism to account for the observed TPN-associated IEL changes.

Animals↗

Influence of the site of small bowel resection on intestinal epithelial cell apoptosis.

Massive small bowel resection (SBR) results in a significant increase in intestinal epithelial cell (EC) proliferation as well as apoptosis. Because the site of SBR (proximal (P) vs. distal (D)) affects the degree of intestinal adaptation, we hypothesized that different rates of EC apoptosis would also be found between P-SBR and D-SBR models. Wild-type C57BL/6J mice underwent: (1) 60% P-SBR, (2) 60% D-SBR, or (3) SHAM-operation (transaction-reanastomosis) at the mid-gut point. Mice were sacrificed after 7 days. EC apoptosis was measured by TUNEL staining. EC-related apoptotic gene expression including intrinsic and extrinsic pathways was measured with reverse transcriptase-polymerase chain reaction. Bcl-2 and bax protein expression were analyzed by Western immunoblotting. Both models of SBR led to significant increases in villus height and crypt depth; however, the morphologic adaptation was significantly higher after P-SBR compared to D-SBR (P<0.01). Both models of SBR led to significant increases in enterocyte apoptotic rates compared to respective sham levels; however, apoptotic rates were 2.5-fold higher in ileal compared to jejunal segments (P<0.01). P-SBR led to significant increases in bax (pro-apoptotic) and Fas expression, whereas D-SBR resulted in a significant increase in TNF-alpha expression (P<0.01). EC apoptosis seems to be an important component of intestinal adaptation. The significant difference in EC apoptotic rates between proximal and distal intestinal segments appeared to be due to utilization of different mechanisms of action.

Adaptation, Physiological↗

Enterogenesis in a clinically feasible model of mechanical small-bowel lengthening.

BACKGROUND: Recent work indicates that mechanical force induces small-bowel growth, although methods reported do not have direct clinical application. We report a clinically feasible technique of enterogenesis and describe intestinal function in this model. METHODS: Using a pig model (n = 11), we stretched isolated small intestinal segments mechanically for 7 days in vivo with an intraluminal device. Control segments were not stretched. Morphology, histology, and epithelial proliferation were assessed. Absorption and epithelial barrier function were examined in an Ussing chamber. RESULTS: Stretch segments were significantly longer than Control segments and had nearly 2-fold greater surface area (P < .001). Mucosal thickness was much greater in Stretch than Control segments (772 +/- 134 vs. 647 +/- 75 microm, P = .02). Although villus height was reduced in Stretch and Control segments (353 +/- 76 vs. 324 +/- 76 microm, P = .6) versus native jejunum (522 +/- 87, P < .0005), crypt depth was increased dramatically in Stretch (450 +/- 95 microm) versus Control segments (341 +/- 64, P = .005). This observation was accompanied by a 2-fold increase in cellular proliferation (26.3 +/- 3.8 vs 12.1 +/- 6.6 % bromodeoxyuridine+, P < .05). Barrier function was intact ([3H]-mannitol permeation, 0.16 +/- 0.08%, vs native jejunum, 0.17 +/- 0.08%, P = .81). Glucose-mediated sodium transport was similar in Stretch versus native jejunum segments (60.0 +/- 23.5 vs 82.3 +/- 47.3 microA/cm2, P = .31), as was carbachol-induced chloride transport (82.4 +/- 72.2 vs 57.2 +/- 33.4 microA/cm2, P = .54) and alanine absorption (16.46 +/- 12.94 vs 23.53 +/- 21.31 microA/cm2, P = .53). CONCLUSIONS: Mechanical stretching induces small intestinal growth, while maintaining function. Epithelial architecture does change, such that a decrease in villus height is offset by a marked increase in crypt depth and a 2-fold increase in epithelial proliferation. Epithelial barrier and absorptive functions remain intact. The device described may have direct clinical applicability.

Animals↗

Comparison of Karydakis versus midline excision for treatment of pilonidal sinus disease.

Pilonidal sinus disease is associated with a high rate of recurrence and complications. The Karydakis (KAR) method, whereby an asymmetric subcutaneous flap obliterates the anal crease, has been shown to be effective in adults. The goal of this study is to assess the efficacy of the KAR procedure in the operative treatment of children with pilonidal sinus disease compared to those treated via a midline excision (ME). Sixty-eight cases of pediatric pilonidal sinus excision were reviewed over the past 10 years. Data abstracted included surgical approach, complication rate and recurrence rate. Student's t-test or the Chi square test was used for statistical analysis, with P < 0.05 being considered significant. An ME was performed in 44 patients; the KAR method was used in 24 patients. Mean age at diagnosis was 14.4 +/- 4.2 years for the ME group compared to 15.7 +/- 4.3 years for the KAR patients (P = 0.18). Mean operative time was significantly longer with the KAR method (58.7 +/- 25.6 min) compared to 46.3 +/- 18.6 for the primary ME (P = 0.04). Despite the increased operative dissection, there was no difference (P = 0.42) in early post-operative complication rates between groups (25% in the KAR group compared to 34.8% in the ME group). Initial drainage of an abscess had no significant effect upon the recurrence/complication rate in either group. Recurrence rate alone was lower in patients operated on via the KAR approach 0% versus 11.0% using the ME (P = 0.153). Recurrence and complication rates were lower for those patients with a pilonidal sinus treated by the KAR method compared to the ME, but the results did not reach significance. In conclusion, this study does show a potential benefit for children treated with the KAR method for pilonidal sinus. This study mimics the data obtained in adult patients and suggests that a larger study is likely to achieve significance.

Adolescent↗

Interleukin-7 administration alters intestinal intraepithelial lymphocyte phenotype and function in vivo.

BACKGROUND: Interleukin-7 (IL-7) plays a crucial role in controlling T-cell development and homeostasis. IL-7 knock out and IL-7 receptor knock out mice show distinct declines in absolute numbers of the intestinal intraepithelial lymphocytes (IEL). Therefore, we hypothesized that exogenous administration of IL-7 would alter IEL phenotype and function. METHODS: Adult C57BL/6J mice were treated with IL-7 or saline. Mice were euthanized at day 7. Cytokine and keratinocyte growth factor (KGF) expressions were measured with RT-PCR. IEL phenotype was studied with flow cytometry. Finally, to address the association of endogenous epithelial cell (EC)-derived IL-7 and IEL, confocal microscopy was used to observe co-localization of IL-7 to IEL subpopulations. RESULTS: IL-7 administration significantly increased IEL numbers. CD8alphabeta+ IEL increased 3.2-fold, CD8+CD44+ IEL increased 1.3-fold, and alphabeta-T-cell receptor (TCR)+ IEL increased 1.3-fold. IL-7 administration also significantly changed both alphabeta-TCR+ IEL- and gammadelta-TCR+ IEL-derived cytokine expressions. Interestingly, IL-7 administration also led to a significant increase in KGF expression. Confocal microscopy showed a high level of co-localization between the alphabeta-TCR+ IEL and EC-derived IL-7. gammadelta-TCR+ IEL showed a lower level, but still significant, co-localization. CONCLUSION: IL-7 administration significantly affected IEL phenotype and function. The observed co-localization suggests that there is a close IEL-EC cross-communication mediated by EC-derived IL-7 expression.

Animals↗

Impact of work-hour restrictions on residents' operative volume on a subspecialty surgical service.

BACKGROUND: Whether the 80 hours per week limit on surgical residents' work hours has reduced the number or variety of cases performed by residents is unknown. STUDY DESIGN: We quantified residents' operative experience, by case category, on a pediatric surgical service. The number of senior and junior residents' cases were compared between residents from the year before (n = 47) and after (n = 44) the 80-hour limit. Residents also completed a questionnaire about their operative and educational experience. As an additional dimension of the educational experience, resident participation in clinic was assessed. Student's t-test was used. RESULTS: Total number of cases performed either by senior (before, 1.58 +/- 0.42 versus after, 1.84 +/- 0.82 cases/day) or junior (before, 0.70 +/- 0.21 versus after, 0.71 +/- 0.15) residents has not changed (p = NS). Senior residents' vascular access and endoscopy rate increased; other categories remained stable. Residents' perception of their experience was unchanged. But residents' participation in outpatient clinic was significantly decreased (before, 66.0% +/- 14.7% versus after, 17.0% +/- 19.9% of clinics covered, p < 0.005). CONCLUSIONS: The 80-hour limit has had minimal impact on residents' operative experience, in case number and variety, and residents' perceptions of their educational experience. Residents' reduction in duty hours may have been achieved at the expense of outpatient clinic experiences.

Adult↗

Laparoscopic vs open surgical approach for intussusception requiring operative intervention.

PURPOSE: Laparoscopy has recently been used to treat intussusception that cannot be reduced radiologically. The effectiveness and practical nature of this approach has been questioned. METHODS: This study retrospectively analyzed the authors' experience with this laparoscopic approach and compared this to the conventional open laparotomy procedure. RESULTS: Sixteen patients were treated via laparoscopy, with 2 of these requiring conversions to an open procedure (12.5%). Twenty-five patients underwent an open reduction. Operative time was not significantly different (P = .698) between the laparoscopic (49.56 +/- 26.40 minutes) and open groups (45.00 +/- 24.74). Length of stay, however, was significantly reduced (P = .005) in the laparoscopic group (3.00 +/- 1.31 days) compared to the open group (4.52 +/- 1.98). Total hospital charges were lower in the laparoscopic group ($8171 +/- 2595) compared to the open group ($11,672 +/- 5466); this difference was not significant (P = .088). There were no significant differences in intra- or postoperative complication rates (P = .637) between the 2 approaches. CONCLUSIONS: Although there remains a group who will require a conversion to an open procedure, the laparoscopic approach should be considered a safe and effective option for all children who do not respond to a radiological reduction.

Child↗

Stretta as the initial antireflux procedure in children.

BACKGROUND: The Stretta procedure is an endoluminal antireflux procedure using radio frequency to induce collagen tissue contraction, remodeling, and modulation of lower esophageal sphincter physiology in an effort to treat gastroesophageal reflux disease (GERD). Although Stretta has been widely reported in the adult GERD literature as a viable initial surgical option, similar use in children has not been reported. The authors present the first report of Stretta as the initial antireflux procedure in children with GERD, evaluating indications, safety, and efficacy. METHOD: The charts of 8 children (aged 11-16 years) who received Stretta between January 2003 and September 2003 were retrospectively reviewed under an Institutional Review Board protocol. All patients had documented GERD preoperatively. Three children required concomitant feeding tube placement (percutaneous gastrostomy tube, group A). Five children with isolated severe GERD refractory to aggressive medical therapy received Stretta only (group B). RESULTS: Stretta was successfully completed in all 8 children. In group A, 1 child developed a postoperative aspiration, which was successfully treated. All 3 children had resolution of their GERD symptoms (ie, feeding intolerance, emesis) and were able to tolerate full enteral nutrition post-Stretta. In group B, 3 of 5 children are currently off medications and asymptomatic on short-term follow-up (6-15 months). Of the remaining 2, 1 experienced symptomatic relief immediately postprocedure, but symptoms recurred off medications. Stretta was deemed unsuccessful in the remaining patient, and Nissen fundoplication was subsequently performed without difficulty. CONCLUSIONS: Stretta can be safely and successfully used as the initial antireflux procedure for children with GERD. Concomitant Stretta with PEG is an attractive option in children with preexisting GERD who require long-term feeding access. Longer follow-up and a larger patient population are needed to better confirm the safety and efficacy of Stretta presented in this report.

Adolescent↗

Total colonic Hirschsprung's disease: a 28-year experience.

PURPOSE: The aim of this study was to review outcomes after surgical treatment of total colonic Hirschsprung's disease (TCH). METHODS: Twenty-five records of patients with TCH treated between 1974 and 2002 were reviewed. Follow-up data were collected using a standardized questionnaire. Objective functional outcome was assessed using a scoring system. RESULTS: Twenty patients had aganglionosis of the colon and distal ileum, 5 of whom had a more extensive condition. One of these 5 patients underwent an endorectal pull-through (ERPT), 1 underwent intestinal transplantation, and 3 died. Four of the remaining 20 patients underwent a primary ERPT, 16 received a stoma as neonates followed by ERPT in 12, and a Martin-Duhamel procedure or Swenson's operation in 3 (median age, 10.5 months); 1 remains with an ostomy. Postoperative complications included enterocolitis (55%), anal stricture (25%), and perineal excoriation (20%). Mean follow-up were 17.5 years (+/-11.1 years). Eighty-nine percent were free of recurrent enterocolitis. Frequency of bowel movements is 1 to 5 per day in 82% of the patients, 18% have 6 or more bowel movements per day. Occasional soiling is noted in 40% (one third of those requiring nighttime diapers). Overall functional outcome was good in 83%. Those patients with the longest follow-up periods had the best stooling scores (P = .04). CONCLUSIONS: Surgical treatment of TCH is associated with a number of complications including recurrent enterocolitis and anal strictures. Long-term outcome is quite favorable.

Anastomosis, Surgical↗

Failure of cholecystokinin-octapeptide to prevent TPN-associated gallstone disease.

PURPOSE: Gallstone formation is a common problem in neonates on prolonged courses of total parenteral nutrition (TPN). The authors hypothesized that the use of cholecystokinin-octapeptide (CCK), given at the time of TPN administration, would prevent gallstone formation in a high-risk group of patients with TPN. METHODS: A prospective, randomized, blinded, controlled trial of neonates who were on a prolonged course of TPN for prematurity (25 infants), necrotizing enterocolitis (NEC, 8 infants), or abdominal surgery (5 infants) were selected randomly to receive CCK vs placebo. Patients remained on the study until taking more than 50% of energy enterally. Children were recalled between 2 and 4 years after completing TPN for ultrasonographic examination of their hepatobiliary tree. RESULTS: Neonates (38 studied) required a mean (+/-SD) of 33 +/- 16 days of TPN. Cholelithiasis was detected in 4 (10%) infants. Cholecystokinin-octapeptide was not effective in preventing the formation of gallstones (3 stones in infants receiving CCK, P = .51). Diagnosis (P = .56), birth weight (P = .54), gestational age (P = .18), and duration of TPN (P = .53) did not correlate with gallstone formation. To address the management of these stones, all 4 were placed on a prolonged course of ursodeoxycholic acid (mean duration, 11.6 +/- 5.4 months). Two additional infants (not in the original study) with TPN-associated gallstone disease were also given a trial of ursodeoxycholic acid. Serial ultrasounds were performed every 6 months. No patient achieved any degree of stone dissolution. One patient underwent cholecystectomy for symptomatology. CONCLUSIONS: Total parenteral nutrition-associated gallstones were detected in 10% of children, and most are nonsymptomatic. Cholecystokinin-octapeptide prophylaxis was not effective in preventing TPN-associated gallstones. In addition, the use of ursodeoxycholic acid did not dissolve gallstones, once identified. Future methods will be needed to address the prevention and treatment of these stones.

Cholagogues and Choleretics↗

The effect of phenol on ingrown toenail excision in children.

PURPOSE: Ingrown toenails in children are a common problem with a high recurrence rate. The objective of this retrospective data review was to compare simple excision of the nail matrix with excision plus phenol (EPP) application in the treatment of ingrown toenails. METHODS: The charts of 69 children who underwent surgical treatment of one or more ingrown toenails from 1994 to 2000 were reviewed. The primary procedure was noted (excision alone [EA] vs EPP) and dates of recurrences and reoperations were recorded. Parents were then surveyed by phone regarding complications, cosmetic outcome, and overall satisfaction with the procedure. Five scale categories, ranging from "strongly agree" to "strongly disagree", were used, with responses of "strongly agree" and "agree" considered as a good outcome. Either Student's t test or the chi2 test (P < .05 considered significant) was used for analysis. RESULTS: Thirty-one patients (45%) were in the EPP group whereas the remaining 38 had EA. Mean length of follow-up was 4.3 years for the EA group and 2.1 years for the EPP group. There was no difference in age at operation or length of follow-up between the 2 groups. Boys were predominant in both groups. The survey response rate was 50/69 (73%). The recurrence rate of ingrown toenails in the EA group was 42% vs 4% in the EPP group (P = .003). There were no significant differences in parental response with regard to operative experience (P = .31) and the cosmetic result (P = .13), with most of the respondents (78%) indicating a good outcome for both questions. CONCLUSIONS: The addition of phenol to the surgical excision of ingrown toenail significantly reduced the incidence of recurrence, with similar patient satisfaction and an equivalent cosmetic result.

Adolescent↗

Lack of enteral nutrition--effects on the intestinal immune system.

BACKGROUND: Total parenteral nutrition (TPN) results in a loss of mucosal immune function by alterations in both phenotype and function of intraepithelial lymphocytes (IEL). We hypothesized that the observed changes with TPN administration are caused by the lack of enteral feeding, and not to the TPN solution itself. METHODS: Mice received oral feeding (Control), TPN alone (TPN), or TPN plus oral feeding (TPN+Food). Mice were killed after 7 days, and bacteriological cultures from spleen, liver, and mesenteric lymph nodes obtained, with bacterial translocation (BT) being defined as a positive culture. IEL phenotype was analyzed by flow cytometry. IEL messenger RNA (mRNA) cytokine expression used reverse transcriptase polymerase chain reaction (RT-PCR). Apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining. RESULTS: BT significantly (P < 0.05, with analysis of variance [ANOVA]) increased in the TPN group (53%) compared with Control (9%) and TPN+Food (14%) groups. TPN also resulted in a significant (P < 0.01) increase in epithelial cell apoptosis: TPN 7.6 +/- 1.1% versus Control 2.9 +/- 1.1% and TPN+Food 2.1 +/- 0.3% (mean +/- SD). Height of the villus-crypt complex was significantly decreased in TPN mice (315 +/- 16 microm) compared with Control (431 +/- 27 microm) and TPN+Food (421 +/- 26 microm) groups. IEL phenotypes significantly changed with TPN administration: CD4+ CD8- as well as CD4+ CD8+ subpopulations were reduced compared with Control or TPN+Food mice; as were the CD8alphabeta+ thymus-dependent, and CD8+ CD44+ mature IEL. IEL cytokine mRNA expression was also significantly altered with TPN: IL-2 and IL-10 expression declined, and IL-4 IL-6, interferon gamma (IFN-gamma), transforming growth factor beta-1 (TGF-beta1), and tumor necrosis factor-alpha (TNF-alpha) were increased, when compared with Control or TPN+Food mice. CONCLUSIONS: This study demonstrates that the major factor responsible for TPN-induced BT and IEL-changes is the lack of enteral feeding and not the administration of the TPN solution itself.

Animals↗

Pediatric short bowel syndrome: redefining predictors of success.

OBJECTIVE: To determine predictors of survival and of weaning off parenteral nutrition (PN) in pediatric short bowel syndrome (SBS) patients. SUMMARY BACKGROUND DATA: Pediatric SBS carries extensive morbidity and high mortality, but factors believed to predict survival or weaning from PN have been based on limited studies. This study reviews outcomes of a large number of SBS infants and identifies predictors of success. METHODS: Multivariate Cox proportional hazards analysis was conducted on 80 pediatric SBS patients. Primary outcome was survival; secondary outcome was ability to wean off PN. Nonsignificant covariates were eliminated. P < 0.05 was considered significant. RESULTS: Over a mean of 5.1 years of follow-up, survival was 58 of 80 (72.5%) and 51 weaned off PN (63.8%). Cholestasis (conjugated bilirubin > or =2.5 mg/dL) was the strongest predictor of mortality (relative risk [RR] 22.7, P = 0.005). Although absolute small bowel length was only slightly predictive, percentage of normal bowel length (for a given infant's gestational age) was strongly predictive of mortality (if <10% of normal length, RR of death was 5.7, P = 0.003) and of weaning PN (if > or =10% of normal, RR of weaning PN was 11.8, P = 0.001). Presence of the ileocecal valve (ICV) also strongly predicted weaning PN (RR 3.9, P < 0.0005); however, ICV was not predictive of survival. CONCLUSIONS: Cholestasis and age-adjusted small bowel length are the major predictors of mortality in pediatric SBS. Age-adjusted small bowel length and ICV are the major predictors of weaning from PN. These data permit better prediction of outcomes of pediatric SBS, which may help to direct future management of these challenging patients.

Child Nutritional Physiological Phenomena↗

Use of cholecystokinin-octapeptide for the prevention of parenteral nutrition-associated cholestasis.

OBJECTIVE: To determine whether cholecystokinin-octapeptide (CCK-OP) would prevent or ameliorate parenteral nutrition-associated cholestasis (PNAC) among high-risk neonates treated with total parenteral nutrition. STUDY DESIGN: This was a multicenter, double-blind, randomized, controlled trial conducted between 1996 and 2001. PATIENTS: Neonates at risk for the development of PNAC included very low birth weight neonates and those with major surgical conditions involving the gastrointestinal tract. SETTING: Tertiary care hospitals. INTERVENTION: Patients were randomized to receive CCK-OP (0.04 mug/kg per dose, twice daily) or placebo. Eligible infants were all <30 days of age. Patients were enrolled within 2 weeks after birth or within 7 days after surgery. OUTCOME MEASURES: The primary outcome measure was conjugated bilirubin (CB) levels, which were measured weekly. Secondary outcome measures included incidence of sepsis, times to achieve 50% and 100% of energy intake through the enteral route, number of ICU and hospital days, mortality rate, and incidences of biliary sludge and cholelithiasis. RESULTS: A total of 243 neonates were enrolled in the study. CCK-OP administration did not significantly affect CB levels (1.76 +/- 3.14 and 1.93 +/- 3.31 mg/dL for CCK-OP and placebo groups, respectively; mean +/- SD). Secondary outcome measures also were not significantly affected by the study drug. CONCLUSIONS: Use of CCK-OP failed to reduce significantly the incidence of PNAC or levels of CB. CCK-OP had no effect on other secondary measures and should not be recommended for the prevention of PNAC.

Bilirubin↗