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Browse Health

Credentials

Education ?

Medical School Score Rankings
University of Minnesota, Twin Cities (1970)
  •  
Top 25%

Awards & Distinctions ?

Awards  
One of America's Leading Experts on:
Obesity
Short Bowel Syndrome
Castle Connolly America's Top Doctors® (2004 - 2008, 2010 - 2015)
Associations
American Board of Surgery

Affiliations ?

Dr. Schwartz is affiliated with 21 hospitals.

Hospital Affiliations

Score

Rankings

  • St. Luke's Hospital/Bethlehem *
    801 Ostrum St, Bethlehem, PA 18015
    •  
    Top 25%
  • Bryn Mawr Rehabilitation Hospital
    414 Paoli Pike, Malvern, PA 19355
    •  
    Top 25%
  • Thomas Jefferson University Hospital
    111 S 11th St, Philadelphia, PA 19107
    •  
    Top 25%
  • Main Line Hospital - Bryn Mawr
    130 S Bryn Mawr Ave, Bryn Mawr, PA 19010
    •  
    Top 25%
  • Saint Christopher's Hospital for Children *
    Pediatric Surgery
    3601 A St, Philadelphia, PA 19134
    •  
    Top 50%
  • St. Luke's Miners Memorial Hospital
    360 W Ruddle St, Coaldale, PA 18218
    •  
  • Abington Memorial Hospital
    1200 Old York Rd, Abington, PA 19001
    •  
  • St Luke's Quakertown Hospital
    300 S 11th St, Quakertown, PA 18951
    •  
  • Mercy Fitzgerald Hospital
    1400 Lansdowne Ave, Darby, PA 19023
    •  
  • Warren Hospital
    185 Roseberry St, Phillipsburg, NJ 08865
    •  
  • St Lukes Hospital
  • Saint Luke's Hospital - Allentown Campus
    1736 W Hamilton St, Allentown, PA 18104
  • St. Christopher's Pediatric Associates
  • Bryn Mawr Hospital
  • Children`s Hospital
  • Children's Hospital
  • St Lukes Health Network
  • St. Christopher's Hospital for Children Specialty Care at St. Luke's
  • Dupont Hosp For Children, Wilmington, De
  • M L Hospital, Inc Bryn Mawr
  • A I Dupont Hospital For Children
  • * This information was reported to Vitals by the doctor or doctor's office.

    Publications & Research

    Dr. Schwartz has contributed to 112 publications.
    Title The Effect of Hepatocyte Growth Factor on Gene Transcription During Intestinal Adaptation.
    Date August 2011
    Journal Journal of Pediatric Surgery
    Excerpt

    Previously, we investigated the physiologic effects of hepatocyte growth factor (HGF) on intestinal adaptation using a massive small bowel resection (MSBR) rat model. To correlate these altered physiologic changes with gene alterations, we used microarray technology at 7, 14, and 21 days after MSBR.

    Title Dose Variation of Hepatocyte Growth Factor and Its Effects on an Animal Model of Tpn-induced Liver Injury.
    Date October 2010
    Journal The Journal of Surgical Research
    Excerpt

    Total parenteral nutrition (TPN) induced liver failure is the leading indication for transplantation in children. Our previous research demonstrated the benefit of a specific intravenous dose of hepatocyte growth factor (HGF) in the amelioration of TPN-induced liver injury. This study was designed to ascertain the optimum concentration of HGF in an animal model of TPN-induced liver injury.

    Title A Comparison of Laparoscopic and Open Nissen Fundoplication and Gastrostomy Placement in the Neonatal Intensive Care Unit Population.
    Date April 2010
    Journal Journal of Pediatric Surgery
    Excerpt

    The aim of this study was to compare outcomes after laparoscopic and open techniques for Nissen fundoplication and gastrostomy placement in the neonatal intensive care unit (NICU) population.

    Title Growth Factor Modulation of Hepatic Inflammation: a Novel Approach to the Management of Total Parenteral Nutrition-associated Liver Disease.
    Date March 2010
    Journal Journal of Pediatric Surgery
    Excerpt

    Dependence on total parenteral nutrition in intestinal failure or short bowel syndrome patients can lead to many complications. The most significant complication is progressive liver injury leading to liver failure. This study assesses the potential of hepatocyte growth factor (HGF) in modulating the hepatic response in a rat cholestatic liver injury model.

    Title Terminal Ileal Atresia, Total Colonic Aganglionosis, and Thrombophilia.
    Date December 2009
    Journal Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
    Excerpt

    Inherited thrombophilia, a predisposition for a hypercoagulable state, has been associated with cases of intestinal atresia. In this communication, we report a case of terminal ileal atresia and total colonic aganglionosis (Hirschsprung's disease), a rarely documented association, in a neonate who seemed to have a hypercoagulable state. The case stresses the need for recognition of this sequence of events in order to achieve optimal management.

    Title Growth Factor Manipulation of Intestinal Angiogenesis: a Possible New Paradigm in the Management of Inflammatory Bowel Disease.
    Date September 2009
    Journal The Journal of Surgical Research
    Excerpt

    Using the transgenic HLA-B27 rat model of inflammatory bowel disease (IBD), we have previously demonstrated hepatocyte growth factor's (HGF) potential to ameliorate diarrhea and decrease bowel injury. This study was designed to assess the effect of HGF on the neovascularization and inflammation in IBD.

    Title Modulation of the Inflammatory Response and Apoptosis Using Epidermal Growth Factor and Hepatocyte Growth Factor in a Liver Injury Model: a Potential Approach to the Management and Treatment of Cholestatic Liver Disease.
    Date March 2009
    Journal Journal of Pediatric Surgery
    Excerpt

    The major side effect of total parenteral nutrition is liver injury leading to liver failure. This study was designed to assess specific growth factors in modulating the hepatic response in an ANIT-induced liver-injury model.

    Title A Rare Cause of Vaginal Bleeding in a 7-month-old Female Infant.
    Date May 2008
    Journal Journal of Pediatric Surgery
    Excerpt

    Ovarian sex cord stromal tumor (OSCST), sclerosing type, is an extremely rare ovarian tumor. Sex hormone production by OSCST can result in isosexual or heterosexual precocious puberty in younger patients. We present a case of a 7-month-old female infant found to have a sclerosing-type OSCST that presented with vaginal bleeding and very prominent vellus hair at the mons pubis. This represents the youngest patient reported in the literature with this subset of OSCST.

    Title Hepatocyte Growth Factor Increases Glucagon Immunoreactivity in Jejunal Cells During Intestinal Adaptation.
    Date August 2006
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND: The administration of hepatocyte growth factor (HGF) during intestinal adaptation is known to enhance intestinal adaptation. Glucagon has also been implicated as a potential mediator of intestinal adaptation. Previous studies have shown that HGF and glucagon synergistically increase the proliferation of hepatocytes. HGF has also been shown to be preferentially expressed within the glucagon-positive cells of the pancreas, possibly indicating a paracrine or endocrine effect of HGF on glucagon. This study was designed to determine if HGF stimulation in the small intestine during intestinal adaptation influenced mucosal glucagon expression. METHODS: Adult male Sprague-Dawley rats were randomized to either a 70% massive small bowel resection group (MSBR) or an HGF-treated MSBR group (MSBR-HGF). Seven days after surgery, HGF was administered intravenously at 150 mug/kg per day for 14 days. At day 21, the ileal and jejunal mucosa was harvested. The RAE 230A GeneChip (Affymetrix, Santa Clara, Calif) and MAS5 software were used to determine alterations in gene expression in the small intestine mucosa. Immunofluorescent staining of the ileal and jejunal mucosa using an antiglucagon antibody was performed and evaluated qualitatively. RESULTS: The MSBR-HGF group had significantly greater protein and DNA content (P < .05) than the MSBR group. Glucagon gene expression in the MSBR-HGF group was decreased compared with the MSBR group, and immunohistostaining for glucagon in the ileum revealed no difference in intensity between the 2 groups. However, the jejunal MSBR-HGF group demonstrated significantly greater glucagon immunoreactivity than the jejunal MSBR group. CONCLUSION: Our data suggest that the HGF-induced increase in glucagon availability is disassociated from glucagon gene up-regulation. Thus, HGF may not only enhance intestinal adaptation directly, but also indirectly by increasing the "local" availability of other growth factors in the absence of their gene up-regulation.

    Title Proteasome Gene Upregulation: a Possible Mechanism for Intestinal Adaptation.
    Date February 2006
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: The mechanisms that control intestinal adaptation remain unknown. To better understand the adaptive process, microarray technology was used to analyze gene expression in a rat model of intestinal adaptation. METHODS: Adult male Sprague-Dawley rats underwent either a massive small bowel resection (70%) with anastomosis or a sham operation with small bowel transection and reanastomosis. After 21 days, ileal mucosa RNA was extracted. Individual RNA samples (n = 5 per group) were labeled and hybridized to 10 separate RAE 230A rat GeneChips. The signal values were calculated and the 2 groups were compared using a t test with the multiple testing correction of Benjamini and Hochberg (false discovery rate of 10%). Probe sets were analyzed for overrepresented physiologic pathways using Expression Analysis Systematic Explorer (EASE). RESULTS: Of the 15,866 probe sets on the RAE 230A GeneChip, 5437 probe sets were unexpressed and excluded. Of the remaining 10,429 probe sets, several overrepresented pathways (EASE score <0.01 after Bonferroni correction) were identified. Further analysis revealed that 13 probe sets related to proteasome degradation (an enzyme complex implicated in the regulation of cell proliferation) were significantly upregulated in the intestinal adaptation group compared to the sham group. CONCLUSIONS: Proteasomes may play a critical role in regulating the proliferation of intestinal mucosa during intestinal adaptation.

    Title Hepatocyte Growth Factor Treatment Ameliorates Diarrhea and Bowel Inflammation in a Rat Model of Inflammatory Bowel Disease.
    Date June 2004
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Transfection of the HLA-B27 gene into normal Fischer rats induces phenotypic changes similar to inflammatory bowel disease (IBD). This study investigated the benefits of 2 doses of hepatocyte growth factor (HGF) on the manifestations of IBD in this rat model. METHODS: Fischer rats and HLA-B27 rats were divided into 4 groups: Fischer rats treated with saline, HLA-B27 rats treated with saline, HGF at 150 microg/kg/d, and HGF at 300 microg/kg/d. HGF or saline was infused for 14 days via an osmotic pump attached to a catheter in the internal jugular vein. After treatment, rats were evaluated for diarrhea and reduction in gross and microscopic bowel inflammation. Statistics were determined using analysis of variance (ANOVA). A P value < or =.05 was considered significant. RESULTS: Administration of HGF at 150 microg/kg/d decreased diarrhea by 40%, gross inflammation by 41%, and microscopic inflammation by 72% (P < or =.05). At 300 microg/kg/d HGF decreased diarrhea by 46%, gross inflammation by 45%, and microscopic inflammation by 54% (P < or =.05). CONCLUSIONS: HGF administration reduces the clinical manifestations of IBD in this rat model. Similar effects were seen at both doses of HGF administration, implying that there is a plateau above which further increases in HGF levels provides no added benefit. HGF administration may be clinically useful in the management of IBD.

    Title Glucagonlike Peptide-2 Analogue: a Possible New Approach in the Management of Inflammatory Bowel Disease.
    Date June 2004
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Glucagonlike peptide-2alpha (GLP-2alpha) has been shown to be a growth factor for the small intestine. This study investigated the benefits of intravenous and intraluminal administration of GLP-2alpha using a rat model of inflammatory bowel disease (IBD). METHODS: Normal Fisher rats and HLA-B27 (IBD) rats were treated for 14 days as follows: Fisher, intravenous saline (n = 6); HLA-B27, intravenous saline (n = 6); HLA-B27, intravenous GLP-2alpha (50 microg/kg/d; n = 5); Fisher, intraluminal saline (n = 5); HLA-B27, intraluminal saline (n = 5); or intraluminal GLP-2alpha (50 microg/kg/d; n = 5). Rats were evaluated for frequency of diarrhea, and the bowel was analyzed for gross and microscopic lesions. Statistical evaluations were determined using analysis of variance (ANOVA). A P value of.05 was significant. RESULTS: Intravenous GLP-2alpha decreased diarrhea and the number of bowel lesions (P <.05). Microscopic inflammation was reduced by 24% but was not statistically significant. Intraluminal GLP-2alpha decreased the number of small intestine lesions (P <.05) and the microscopic inflammation (P <.05) but did not significantly reduce diarrhea or the overall number of bowel lesions. CONCLUSIONS: GLP-2alpha ameliorates the signs of IBD in HLA-B27 rats. Intravenous GLP-2alpha reduces diarrhea more effectively than intraluminal administration, and both routes are equally effective in ameliorating inflammation. GLP-2alpha potentially provides a new modality for the treatment of IBD.

    Title Hepatocyte Growth Factor Ameliorates Inflammatory Bowel Disease in a Rat Model.
    Date May 2004
    Journal Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract
    Excerpt

    This study was designed to investigate the benefits of administration of hepatocyte growth factor in a rat model of inflammatory bowel disease. Transfection of the HLA-B27 gene into Fisher rats induces a phenotype similar to inflammatory bowel disease. Fisher rats and HLA-B27 rats were divided into six groups: (1) Fisher, intravenous saline; (2) HLA-B27, intravenous saline; (3) HLA-B27, intravenous hepatocyte growth factor; (4) Fisher, luminal saline; (5) HLA-B27, luminal saline; and (6) HLA-B27, luminal hepatocyte growth factor. Rats received a 14-day infusion through an osmotic pump attached to a catheter positioned in either the jugular vein or the terminal ileum. Rats were evaluated for stool character, and gross and microscopic bowel inflammation. Statistics were analyzed using analysis of variance or the Kruskal-Wallis nonparametric test. A value of P<0.05 was significant. Compared to untreated HLA-B27 rats, intravenous administration of hepatocyte growth factor decreased diarrhea by 41% and microscopic inflammation by 54% (P<0.05). Luminal hepatocyte growth factor exposure decreased total bowel lesions by 53% and microscopic inflammation by 40% compared to untreated HLA-B27 rats (P<0.05), but it did not have an effect on diarrhea. Administration of hepatocyte growth factor ameliorates many of the features of bowel disease in this rat model and theoretically could have therapeutic applications in the management of inflammatory bowel disease in humans.

    Title A Possible Mechanism for Prevention of Intestinal Programmed Cell Death After Ischemia-reperfusion Injury by Hepatocyte Growth Factor Pretreatment.
    Date February 2003
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Intestinal ischemia-reperfusion (IR) injury produces necrosis and apoptosis resulting in tissue loss. The authors have observed previously that pretreatment with hepatocyte growth factor (HGF) attenuates enterocyte apoptosis after IR. This study investigated the effects of HGF on tissue levels of caspase-8, an apoptosis initiator, and caspase-3, an apoptosis effector, in intestinal mucosa after IR. METHODS: Thirty rats underwent placement of jugular venous catheters connected to osmotic pumps; 15 rats received vehicle, and 15 rats received HGF (150 microg/kg/d). After a 48-hour infusion, 5 rats from each group underwent either 35 minutes of superior mesenteric artery occlusion alone, or ischemia followed by 2 or 6 hours of reperfusion. Mucosal protein was analyzed for caspase-8 and caspase-3 activity. DNA fragmentation was used to measure the presence of apoptosis. Statistical significance was determined using analysis of variance. RESULTS: After 6 hours of reperfusion, caspase-3 activity was increased significantly in control animals (P <.05). In HGF-pretreated animals, caspase-8 and caspase-3 activities were significantly reduced at 6 hours compared with control animals (P <.05). CONCLUSION: By preventing the activation of enterocyte caspase enzymes, and, thus, reducing apoptosis, HGF may enhance preservation of the intestine after IR injury.

    Title Il-11 Pretreatment Reduces Cell Death After Intestinal Ischemia-reperfusion.
    Date January 2003
    Journal The Journal of Surgical Research
    Excerpt

    BACKGROUND: Intestinal ischemia-reperfusion (IR) injury results in enterocyte necrosis and apoptosis. This study was designed to evaluate the potential protective effects of interleukin-11 (IL-11) pretreatment on intestinal mucosa following IR injury. MATERIALS AND METHODS: Sham (n = 7) and control animals (n = 7) received 48 h of intravenous saline while treatment animals (n = 7) received IL-11 (750 microg/kg/day). Sham animals then underwent laparotomy alone, while control and treatment animals underwent 35 min of mesenteric artery occlusion and 120 min of reperfusion. Midjejunum samples were obtained and serum was drawn. Fluorometric assays were performed for hexosaminidase A (HEX A) and beta-glucuronidase (GLUC), markers of enterocyte necrosis. Apoptosis was quantified by TUNEL and confirmed by DNA fragmentation. Transcription of Bcl-2, an antiapoptotic regulator, was assessed by multiplex RT-PCR. Statistical analysis was performed using ANOVA and expressed as means +/- SEM. RESULTS: In pretreated animals, HEX A and GLUC activities after IR were reduced from 570 +/- 54 to 426 +/- 47 nmol/ml/h (P < 0.05) and from 183 +/- 29 to 125 +/- 7 nmol/ml/h (P < 0.01), respectively. Pretreated animals had a reduced number of apoptotic cells per 10 crypts (79 +/- 11) compared with untreated rats (255 +/- 17) after IR injury (P < 0.01). Mucosal DNA from pretreated rats qualitatively showed less fragmentation on electrophoresis. Relative Bcl-2 band intensity was higher in pretreated animals (1.04 +/- 0.09) compared with controls (0.78 +/- 0.07) (P < 0.05). CONCLUSIONS: IL-11 pretreatment reduced crypt cell apoptosis after IR injury, possibly by upregulating Bcl-2. Treated animals also demonstrated attenuation in the release of certain lysosomal enzymes. These data indicate that following IR injury, IL-11 improves enterocyte survival by reducing necrosis and apoptosis.

    Title Transfection of the Sodium/glucose Cotransporter into Colon Mucosa: a Novel Treatment for Short Bowel Syndrome.
    Date August 2002
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Short bowel syndrome results from small intestine loss but frequently is associated with survival of the colon. This study was designed to determine if colonic mucosa could be induced to absorb galactose by tranfection of the sodium glucose cotransporter, SGLT-1 into a colonic segment. METHODS: Using 10 rats, a 7-cm segment of colon was infused for 1 hour with a solution containing 50 microg/mL of a plasmid with or without an SGLT-1 insert. An 80% small bowel resection was performed, and the segment was interposed into the small bowel. On the third day [14C] galactose absorption was measured. Mucosal RNA was extracted, and relative band intensities were measured using primers for SGLT-1. Statistical analysis was performed using the Student's t test and expressed as mean +/- SEM. RESULTS: Rats transfected with the SGLT-1 plasmid showed a significant increase (194%) in galactose absorption compared with controls. Transfected animals also showed high levels of of SGLT-1 transcription when compared with controls (792% increase). CONCLUSIONS: These data show that in vivo exposure of colon mucosa to a plasmid containing SGLT-1 allows transfer of that gene into enterocytes. Expression of SGLT-1 can create an absorptive segment that may in part alleviate the malabsorption associated with short bowel syndrome.

    Title Hepatocyte Growth Factor Pretreatment Reduces Apoptosis and Mucosal Damage After Intestinal Ischemia-reperfusion.
    Date August 2002
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Ischemia-reperfusion (IR) injury to the intestine can result in mucosal damage and cellular death. This study was designed to evaluate the protective effects of pretreatment with hepatocyte growth factor (HGF) on intestine after moderate IR injury. METHODS: Control animals (n = 7) received 48 hours of intravenous saline, and treatment animals (n = 7) received HGF (150 microg/kg/d). After 35 minutes of mesenteric artery occlusion and 120 minutes of reperfusion, serum and jejunal mucosa samples were obtained. Fluorometric assays were performed for hexosaminidase A (HEX A) and beta-glucuronidase (GLUC), enzyme markers of enterocyte necrosis. Apoptosis was quantified by the TUNEL method. Transcription of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) was assessed by multiplex reverse transcription polymerase chain reaction (RT-PCR) Statistical analysis was performed using the Student's t test. RESULTS: After HGF pretreatment, HEX A and GLUC activities were reduced from 543 +/- 28 to 343 +/- 35 nmole/h/mL (P <.01) and 183 +/- 29 to 119 +/- 22 nmole/h/mL (P <.01), respectively. Pretreated animals had a reduced number of apoptotic cells per 10 crypts (33 +/- 11) compared with untreated rats (225 +/- 24) after IR injury (P <.01). Mean IFN-gamma band intensity was lower in HGF-pretreated animals (0.05 +/- 0.02) compared with controls (0.31 +/- 0.09; P <.05). CONCLUSIONS: Pretreatment with HGF reduces the severe crypt apoptosis and cellular necrosis after IR injury to the intestine. These data suggest that HGF may be beneficial in attenuating IR damage and thus may have significant clinical application.

    Title Leptin: a New Growth Factor for the Small Intestine.
    Date April 2002
    Journal Journal of Pediatric Surgery
    Excerpt

    PURPOSE: This study was designed to evaluate the potential growth factor effects of systemic administration of leptin on mucosal mass and absorptive function in normal rat intestine. METHODS: Twenty male Sprague-Dawley rats underwent placement of a jugular venous catheter connected to a subcutaneous osmotic pump designed to deliver its contents at a constant rate. The rats were divided into 4 groups (n = 5 per group) based on the contents of the osmotic pump: group 1, 0.1% bovine serum albumin; group 2, leptin, 6.25 microgram/kg/d; Group 3, leptin, 18.75 microgram/kg/d; Group 4, leptin, 43.75 microgram/kg/d. After a 14-day infusion, [(14)C] galactose and [(14)C] glycine absorption were determined using a closed, recirculation technique. DNA content was determined from mucosal biopsies. Total RNA was extracted from mucosal samples, reverse transcribed, and amplified via polymerase chain reaction for the following primer pairs: sodium/glucose cotransporter (SGLT-1), fructose transporter (GLUT-5), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, internal standard). Statistical analysis was performed by analysis of variance and expressed as mean plus minus SEM. RESULTS: Systemic administration of increasing doses of leptin enhanced DNA content when compared with the appropriate control (group 2, 1.06 plus minus 0.04 [P <.05]; group 3, 1.1 plus minus 0.05 [P <.01]; and group 4, 1.07 plus minus 0.06 [P <.05]. Leptin enhanced mucosal absorptive function (galactose: group 2, 2.31 plus minus 0.15 [P <.01]; group 3, 2.71 plus minus 0.06 [P <.01]; group 4, 2.19 plus minus 0.28 [P <.05]; glycine: group 2, 2.34 plus minus 0.31 [P <.05]; group 3, 3.32 plus minus 0.14 [P <.01]; group 4, 3.1 plus minus 0.27 [P <.01]) in the normal intestine when compared with the appropriate control animals. Also, leptin enhanced the gene expression of the carbohydrate transporters when compared with the appropriate control rats. CONCLUSIONS: These data show that systemic leptin administration enhances mucosal mass and absorptive function in normal rat intestine. Thus, leptin appears to be a growth factor for normal small intestine and may play a role in patients who acquire intestinal dysfunction.

    Title Interleukin-11 Enhances Intestinal Absorptive Function After Ischemia-reperfusion Injury.
    Date April 2002
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Interleukin-11 (IL-11) is a multifunctional cytokine that has been shown to improve small bowel adaptation and enhance cellular recovery after bowel ischemia. This study was designed to examine the effects of systemic IL-11 on small bowel absorptive function in a rat model of intestinal ischemia and reperfusion (IR) injury. METHODS: Sprague-Dawley rats underwent placement of a venous catheter connected to an osmotic pump, which delivered its contents over 3 days. Rats were divided into 3 groups: sham operation/systemic saline; 30-minute superior mesenteric artery occlusion/systemic saline; superior mesenteric artery occlusion/systemic IL-11, 750 microgram/kg/d. After the infusion, (14)C-galactose or (14)C-glycine absorption was measured using an in vivo, recirculation technique. Statistical significance was determined using analysis of variance. RESULTS: In control rats, 30 minutes of IR decreased absorption of galactose from 2.62 to 2.02 micromoles/cm(2) (P <.01), and glycine from 2.79 to 1.72 micromoles/cm(2) (P <.01). Rats treated with systemic IL-11 showed improved absorption of galactose of 2.39 micromoles/cm(2) (P <.05), and glycine at 2.21 micromoles/cm(2) (P <.05). Mucosal DNA content was reduced significantly from 7.37 to 5.61 microgram DNA/mg by IR (P <.01). IL-11 treatment did not significantly alter DNA content during this period. CONCLUSIONS: These data show that 30 minutes of intestinal IR significantly decreases intestinal absorptive function in this animal model. When compared with untreated control animals, administration of systemic IL-11 significantly increased the absorption of carbohydrate and amino acid in rats recovering from mesenteric IR.

    Title Glucagonlike Peptide-2 Analogue Enhances Intestinal Mucosal Mass and Absorptive Function After Ischemia-reperfusion Injury.
    Date January 2002
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: This study was designed to explore the efficacy of a synthetic analogue of glucagonlike peptide-2 (GLP-2a) in enhancing mucosal mass and absorptive function in a rat model of intestinal ischemia-reperfusion (I-R) injury. METHODS: Each of 20 Sprague-Dawley rats underwent placement of a jugular venous catheter connected to a subcutaneous osmotic pump designed to deliver its contents over 3 days. Rats were divided into 4 groups (n = 5 per group): (1) normal intestine/saline infusion; (2) 30-minute superior mesenteric artery occlusion/saline infusion, (3) normal intestine/ GLP-2alpha infusion, and (4) 30-minute superior mesenteric artery occlusion/GLP-2alpha infusion. Subsequently, mean mucosal 14C-galactose and 14C-glycine absorption and DNA content were determined for each group. RESULTS: In saline-treated rats, 30 minutes of mesenteric ischemia decreased mean mucosal galactose absorption by 29% (P < .05), glycine absorption by 22% (P = .12), and DNA content by 28% (P < .01) when compared with rats with uninjured intestine. In rats subjected to 30 minutes of intestinal ischemia, GLP-2alpha significantly improved galactose absorption by 46% (P < .05), glycine absorption by 84% (P < .01), and DNA content by 63% (P < .01) when compared with saline-treated control rats. In rats with mesenteric I-R injury treated with GLP-2a, galactose absorption was returned to normal. Glycine absorption and DNA content were increased significantly by 44% (P < .01) and 18% (P < .05), respectively, beyond the baseline for normal intestine. CONCLUSIONS: Thirty minutes of intestinal ischemia followed by immediate reperfusion significantly decreased mucosal mass and absorptive function, validating this rat model of I-R injury. After mesenteric I-R, GLP-2a significantly increased mucosal DNA content and absorption of 14C-galactose and 14C-glycine when compared with untreated control rats. After I-R injury, GLP-2a restored mucosal mass and absorptive function to normal or above-normal levels.

    Title Glp-2alpha Accelerates Recovery of Mucosal Absorptive Function After Intestinal Ischemia/reperfusion.
    Date September 2001
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: The authors' previous laboratory results have shown that rats treated for 3 days with intravenous GLP-2alpha, a synthetic protease-resistant form of glucagonlike peptide-2, showed increased mucosal mass and absorptive function when compared with saline-treated controls after intestinal ischemia/reperfusion (I/R). This study was designed to explore the temporal relationship between injury that occurs secondary to intestinal I/R and recovery of mucosal absorptive function with and without GLP-2alpha treatment. METHODS: Each of 18 male Sprague-Dawley rats (300 to 333 g) was subjected to superior mesenteric artery occlusion for 30 minutes, during which time a jugular venous catheter was placed and connected to a subcutaneous infusion pump. Rats were divided into 4 groups based on the type and duration of infusion as follows: group 1, systemic saline at 1 microL/h for 24 hours (n = 5); group 2, systemic GLP-2alpha at 100 microg/kg/d for 24 hours (n = 5); group 3, systemic saline at 1 microL/h for 72 hours (n = 4); and group 4, systemic GLP-2alpha at 100 microg/kg/d for 72 hours (n = 4). Immediately after the infusions, (14)C-galactose and (14)C-glycine absorption was measured using an in vivo, closed-recirculation technique and expressed as micromoles per square centimeter intestine +/- SEM. Statistical analysis was performed using analysis of variance. RESULTS: Twenty-four hours after intestinal I/R injury, there was a decrease in substrate absorption but no significant difference between the saline and GLP-2alpha-treated groups (galactose absorption, 1.13 +/- 0.09 in group 1 v 1.35 +/- 0.11 in group 2, P =.15; glycine absorption, 1.18 +/- 0.13 in group 1 v 1.34 +/- 0.15 in group 2, P =.36). However, after the 72-hour infusion, absorption of galactose and glycine was significantly increased in the rats receiving GLP-2alpha as compared with the saline-infused control group (galactose absorption, 1.24 +/- 0.13 in group 3 v 1.88 +/- 0.10 in group 4, P <.01; glycine absorption, 1.64 +/- 0.07 in group 3 v 2.05 +/- 0.08 in group 4, P <.05). Compared with previously determined levels of absorption in normal, uninjured rat intestine (1.50 +/- 0.12 micromol/cm(2) for galactose and 1.85 +/- 0.17 micromol/cm(2) for glycine), after I/R a 72-hour infusion of GLP-2alpha increased galactose absorption 26% (P <.05) and glycine absorption 11% (P =.29) beyond baseline. CONCLUSIONS: When initiated at the time of intestinal I/R, a continuous infusion of GLP-2alpha accelerated recovery of mucosal absorptive function in rats. Remarkably, carbohydrate absorption at 72 hours was increased to a level significantly greater than that in normal, uninjured rat intestine. J Pediatr Surg 36:570-572.

    Title Pharmacotherapy and Growth Factors in the Treatment of Short Bowel Syndrome.
    Date June 2001
    Journal Seminars in Pediatric Surgery
    Excerpt

    A review of the pharmacologic substances and growth factors that have been studied experimentally and administered clinically for the management of short bowel syndrome is presented. The medical management of short bowel syndrome is multifaceted. In the acute phase, efforts focus on fluid and electrolyte management and the reduction of gastric acid output. As enteral feeding is initiated, antimotility and antisecretory agents may be effective in reducing gastrointestinal losses. Additional modalities of management, including nutrients and growth factors, may be directed at maximizing absorptive function beyond that which occurs with intestinal adaptation. Continued research aimed at further elucidating the process of intestinal adaptation may allow us to use the various peptides and hormones that act as growth factors for the bowel mucosa. Knowledge gained from these studies combined with gene therapy techniques will result in the permanent enhancement of intestinal function beyond the normal adaptation process, eliminate the dependence on total parenteral nutrition, and avoid the need for intestine transplantation.

    Title Novel Effect of Leptin on Small Intestine Adaptation.
    Date June 2001
    Journal The Journal of Surgical Research
    Excerpt

    BACKGROUND: Leptin is a 16-kDa peptide produced by adipocytes that plays an important role in the regulation of body fat and satiety. We have previously shown that leptin is a growth factor for normal rat small intestine. This study was designed to examine the effect of systemic leptin administration on small bowel absorptive function after massive small bowel resection (MSBR). MATERIALS and METHODS: Twenty-one adult male Sprague-Dawley rats underwent an 80% small bowel resection and end-to-end jejunoileal anastomosis. Seven days following resection, all rats had placement of a jugular venous catheter connected to a subcutaneously placed osmotic minipump and were divided into three groups based on the content of each minipump: Group 1 (n = 7) 0.1% bovine serum albumin; Group 2 (n = 7) leptin 2 microg/kg/day; and Group 3 (n = 7) leptin 4 microg/kg/day. Following a 14-day infusion period, [(14)C]galactose absorption was measured using a closed-recirculation technique. Mucosal DNA content was determined for all groups using a standard DNA purification kit. Mucosal RNA was extracted and RT-PCR was performed using the following primers: sodium/glucose cotransporter (SGLT-1), fructose transporter (GLUT-5), and glyceraldehyde-3-phosphate dehydrogenase, an internal standard. PCR products were separated on a 4% agarose gel and relative band intensities were measured. Statistical analysis was performed using ANOVA and expressed as means +/- SEM. RESULTS: Group 2 showed a 44% increase in galactose absorption (P < 0.01) and a 14% increase in GLUT-5 band intensity (P < 0.05), but no change in DNA content or SGLT band intensity. CONCLUSIONS: This study demonstrates for the first time that leptin enhances small intestine carbohydrate absorption beyond the normal adaptive response following MSBR. Leptin may be clinically useful in patients with inadequate intestinal function.

    Title Treatment of Inflammatory Bowel Disease in a Rodent Model with the Intestinal Growth Factor Glucagon-like Peptide-2.
    Date October 2000
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Microinjection of a Fisher (F344) rat zygote with human HLA-B27 and beta2-microglobulin genes induces spontaneous chronic gastrointestinal (GI) inflammation similar to lesions seen in patients with inflammatory bowel disease (IBD). This study was designed to evaluate the potential therapeutic benefit of GLP-2, an intestinal growth factor, in this transgenic rat model of IBD. METHODS: Five F344 (control) and 10 HLA-B27 (on a F344 background) rats at 25 weeks of age were used. Rats were divided into the following 3 groups: group 1, F344 rats, no treatment (n = 5); group 2, HLA-B27, no treatment (n = 5); and group 3, HLA-B27, treated with a 14-day systemic infusion (via the jugular vein) of GLP-2 at 50 microg/kg/d (n = 5). After infusion, all rats underwent laparotomy, and the intestine from the ligament of Treitz to the rectum was harvested. Total mucosal damage (percent surface area) was measured using image analysis software (Sigmascan 2.0). Microscopic analysis was performed by a blinded reviewer and scored as follows: 0, no inflammation; 1, mild inflammation; 2, moderate inflammation; and 3, severe inflammation. Colonic mucosal total RNA was assayed for tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), internal standard, mRNA by reverse transcriptase polymerase chain reaction. Statistical analysis was performed using analysis of variance (ANOVA) and expressed as mean +/- SEM. RESULTS: Normal F344 rats did not show evidence of gross or histological lesions in the small or large intestine. GLP-2 reduced total mucosal damage from 9.0% +/- 0.7% in group 2 to 0.9% +/- 0.5% in group 3 (P < .01). The histological lesion score was reduced from 7.0 +/- 0.6 in group 2 to 4.4 +/- 0.8 in group 3 (P < .01). Furthermore, GLP-2 reduced the mean band intensity (MBI) of TNF-alpha (0.4 +/- 0.04 in group 2 to 0 in group 3, P < .01) and IFN-gamma (0.3 +/- 0.02 in group 2 to 0 in group 3, P < .01). CONCLUSIONS: These data show for the first time that GLP-2 significantly reduces gross (90% decrease) and histological (40% decrease) lesions in this rat model of IBD. This is further supported by a significant decrease in gene expression of the inflammatory mediators TNF-alpha (100% decrease) and IFN-gamma (100% decrease). These data suggest a potential therapeutic role for GLP-2 in IBD.

    Title Growth-factor Enhancement of Compromised Gut Function Following Massive Small-bowel Resection.
    Date June 2000
    Journal Pediatric Surgery International
    Excerpt

    Our laboratory has shown that epidermal growth factor (EGF) and hepatocyte growth factor (HGF) can improve the function of normal rat small intestine. This study was designed to evaluate the role of these growth factors on the residual small intestine following massive (80%) small bowel resection. Our data demonstrate that EGF and HGF can enhance intestinal substrate absorption and mucosal mass beyond that which occurs with intestinal adaptation. These growth factors may be beneficial in the management of children with short bowel syndrome.

    Title Glucagonlike Peptide-2 Analogue Enhances Intestinal Mucosal Mass After Ischemia and Reperfusion.
    Date March 2000
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Glucagonlike peptide-2 (GLP-2), a product of the posttranslational processing of proglucagon, has been shown to enhance mucosal mass and function in both normal intestine and in the residual intestine after massive small bowel resection. This study was designed to determine if a synthetic, protease-resistant analogue of GLP-2 (GLP-2alpha) can enhance mucosal mass in small intestine after ischemia and reperfusion (I/R) injury. METHODS: Ten young adult male Sprague-Dawley rats underwent laparotomy and superior mesenteric artery occlusion for a period of 40 minutes. During this period of ischemia, each rat underwent placement of a jugular venous catheter that was connected to a subcutaneously placed osmotic pump designed to deliver its contents over 3 days. The rats were divided into 2 groups based on the contents of the pumps: group 1, saline at 1 microL/h (n = 6) and group 2, GLP-2alpha at 100 microg/kg/d (n = 4). Three days after insertion of the pumps the small intestine was harvested from the surviving rats for determination of mucosal DNA and protein content. Statistical analysis was performed using unpaired Student's t test. RESULTS: After I/R injury to the small intestine, a 3-day systemic infusion of GLP-2alpha significantly increased mucosal DNA content 41% (P<.05) and mucosal protein content 60% (P<.05) when compared with saline-treated controls. In addition, infusion of GLP-2alpha reduced mortality from 50% to 25%. CONCLUSIONS: These data show for the first time that GLP-2alpha enhances mucosal mass following I/R injury to the small intestine. GLP-2alpha may be of benefit to patients with intestinal ischemia syndromes such as necrotizing enterocolitis and midgut volvulus.

    Title Interleukin-11 Enhances Small Intestine Absorptive Function and Mucosal Mass After Intestinal Adaptation.
    Date March 2000
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Interleukin-11 (IL-11) recently has been shown to enhance mucosal mass after massive small bowel resection (MSBR). However, enhanced mucosal mass may not correlate with increased substrate absorption. This study was designed to examine the effect of systemic administration of increasing doses of IL-11 on small intestine absorptive function and mucosal mass after MSBR. METHODS: Twenty-five Sprague-Dawley rats underwent an 80% small bowel resection and end-to-end jejunoileal anastomosis. Seven days after resection, all rats had placement of a jugular venous catheter connected to a subcutaneously placed osmotic pump. The rats were divided into 5 groups based on the content of the pump: group 1 (control, n = 5) received 0.1% bovine serum albumin (BSA) and groups 2 through 5 (n = 5 each) received IL-11 at 250, 500, 750, and 1,000 microg/kg/d, respectively. After a 14-day infusion period, [14C] galactose and [14C] glycine absorption was measured using an in vivo closed-recirculation technique. Mucosal DNA content also was determined for each group. Statistical analysis was performed by analysis of variance and expressed as mean +/-SEM. RESULTS: IL-11 administered at 250 microg/kg/d, a dose used in previous studies, did not significantly affect substrate absorption. However, compared with the control group, administration of higher doses of IL-11 produced a significant increase in substrate absorption and mucosal mass. The dose of IL-11 producing the overall optimal response based on the parameters measured (galactose absorption, 72% increase over control; glycine absorption, 112% increase over control; and DNA content, 98% increase over control) was 750 microg/kg/d. CONCLUSIONS: In addition to an increase in mucosal mass, these data show for the first time that IL-11 enhances absorptive function beyond the normal adaptive response after MSBR. Furthermore, the maximum effect of IL-11 on absorptive function was shown at 750 microg/kg/d, which is 3 times the dose used in previously reported studies. This study suggests that IL-11 may be useful clinically in patients with inadequate intestinal function.

    Title Cost-effective Imaging Approach to the Nonbilious Vomiting Infant.
    Date July 1999
    Journal Pediatrics
    Excerpt

    OBJECTIVE: To develop a cost- and time-effective algorithm for differentiating hypertrophic pyloric stenosis (HPS) from other medical causes of emesis in infants referred from community-based pediatricians and family practitioners to the imaging department of a tertiary children's care facility. METHODS: Eighty-nine vomiting infants (22 females, 67 males) between the ages of 11 and 120 days (mean, 43.5 days) had received nothing by mouth for at least 1 hour before the study. Each child was assessed for duration of vomiting, status of body weight, time and volume of last ingestion, and time of last emesis. A #8 French (Sherwood Medical, St Louis, MO) nasogastric feeding tube was placed in the child's stomach. The contents were aspirated and measured to determine likelihood of HPS. An aspirated volume >/=5 mL implicated gastric outlet obstruction, and ultrasonography (US) was performed. If this study was positive for HPS, the patient was referred for surgery. If US was negative, an upper gastrointestinal series (UGI) was performed. An aspirated stomach contents volume <5 mL suggested a medical cause for the emesis, and UGI was performed. Pediatric surgeons with no knowledge of the volume results palpated the abdomens of 73 of 89 infants (82%). RESULTS: Twenty-three of 89 patients (25%) had HPS. The aspirate criteria for HPS had a sensitivity of 91%, a specificity of 88%, and an accuracy of 89%. Of the false-positive studies (total = 8), six were related to recent significant ingestion (within 2 hours of the study), and two were attributable to antral dysmotility. The surgeons palpated the mass in 10 of 19 patients (53%). Sensitivity and specificity were 53% and 93%, respectively. Only 6 of 89 infants (7%) required both US and UGI to determine the etiology of the nonbilious vomiting. By performing the UGI in 66 patients, it was also found that 14% had slow gastric emptying and 79% had gastroesophageal reflux. Eighty-one percent of the gastroesophageal reflux was significant. CONCLUSION: The volumetric method of determining the proper imaging study is cost- and time-effective in the evaluation of the nonbilious vomiting infant for pyloric stenosis. If US was performed initially in all patients referred for imaging, two studies would have been performed in 68 of 89 patients (76%) to define the etiology of the emesis. Because we used the volumetric method, 62 fewer imaging studies were performed, representing a savings of $4464 and 30 hours of physician time. If children are given nothing by mouth for 3 to 4 hours before gastric aspiration, the specificity of the volumetric method improves to 94%, and the accuracy improves to 96%.

    Title Glucagonlike Peptide-2 Enhances Small Intestinal Absorptive Function and Mucosal Mass in Vivo.
    Date April 1999
    Journal Journal of Pediatric Surgery
    Excerpt

    PURPOSE: Glucagonlike peptide-2 (GLP-2) is a 33-amino acid peptide that appears to be highly tissue specific for the intestine. This study was designed to examine the effect of systemically administered GLP-2 on intestinal absorptive function and mucosal mass, and determine the in vivo dose-response curves for this new peptide. METHODS: Twenty-five young adult male Sprague-Dawley rats had placement of jugular venous catheters connected to subcutaneously placed osmotic minipumps. The rats were divided into five groups based on the contents in the osmotic pump: group 1 (control, n = 5) normal saline and groups 2, 3, 4, and 5 (n = 5 each) were given GLP-2 at 5, 50, 250, and 500 microg/kg/d, respectively. After a 14-day infusion, [C14] galactose and [C14] glycine absorption were measured in a 10-cm segment of midsmall intestine using an in vivo closed-recirculation technique. Mucosal DNA content and protein content of the same small bowel segment were also determined for each group. Statistical analysis was performed by analysis of variance (ANOVA). RESULTS: GLP-2 significantly increased galactose absorption at a dose of 50 (P<.01), 250 (P<.01), and 500 (P<.05) microg/kg/d and glycine absorption at a dose of 50, 250, and 500 microg/kg/d (P<.01). GLP-2 also significantly increased mucosal DNA content at a dose of 50 (P<.01) and 250 (P<.05) microg/kg/d and protein content at a dose of 50 and 250 microg/kg/d (P<.01). CONCLUSIONS: These data demonstrate that GLP-2 can enhance normal rat small intestine mucosal mass and absorption in vivo with the maximum effect seen at 50 microg/kg/d.

    Title Enteral Glutamine Does Not Enhance the Effects of Hepatocyte Growth Factor in Short Bowel Syndrome.
    Date February 1999
    Journal Journal of Pediatric Surgery
    Excerpt

    PURPOSE: This study was designed to determine if luminally administered glutamine alone functions as a growth factor or is synergistic with hepatocyte growth factor (HGF) after massive small bowel resection (MSBR). METHODS: Twenty Sprague-Dawley rats underwent an 80% small bowel resection and jejunostomy tube placement. Seven days later the rats were divided into four groups: group 1, control, no further treatment (n = 5); group 2 received glutamine (4% of total food intake per day) via an orogastric tube (n = 5); group 3 received intraluminal HGF via a jejunostomy tube at 75 microg/kg/d (n = 5); and group 4 received glutamine and HGF at the same doses, respectively. After a 14-day HGF infusion, glutamine feeding, or both combined, [C14] glycine absorption (micromol/L/cm2 intestine) and mucosal DNA and protein content (microg/mg mucosa) were measured in the remaining small bowel. RESULTS: Glutamine alone had no effect on substrate absorption and protein or DNA content. HGF increased galactose absorption (106% increase over control, P<.01), glycine absorption (95% increase over control, P<.05), protein content (44% increase over control, P<.01), and DNA content (32% increase over control, P<.01). The combination of glutamine and HGF did not prove to be synergistic. CONCLUSIONS: These data demonstrate that in this short bowel model, glutamine alone did not enhance intestinal function. Furthermore, glutamine is not synergistic with HGF. This study suggests that glutamine alone may not be useful clinically in patients with inadequate intestinal function.

    Title Effect of Laminin on the Nuclear Localization of Nucleolin in Rat Intestinal Epithelial Iec-6 Cells.
    Date June 1998
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Laminin is a major component of extracellular matrix. The mechanism of action of laminin on cell proliferation, differentiation, and migration is not fully understood. In this study, we investigated the role of extracellular matrix, especially laminin, on the cellular localization of the nuclear protein, nucleolin, and on cell proliferation. Immunofluorescent and western blot analysis indicated that nucleolin was translocated most efficiently to the nucleus in the small intestinal rat epithelial cell line (IEC-6) when cultured on laminin-coated plates. Specifically, nucleolin was observed predominantly in cytoplasm in the cells cultured without laminin. In contrast, nuclear localization was observed in the cells cultured on laminin. This effect of laminin on nucleolin translocation was time-dependent. Laminin was also observed to stimulate proliferation of IEC-6 cells in serum free medium. Our results suggest that laminin alters the distribution of nucleolin which may be an early signal for cell proliferation.

    Title Enhancement of Intestinal Adaptation by Hepatocyte Growth Factor.
    Date April 1998
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Hepatocyte growth factor (HGF) was originally shown to enhance hepatocyte DNA synthesis. Recently, the expression of HGF and its receptor (c-met) were observed in the intestinal tract. In a previous study, we demonstrated that HGF can increase normal rat intestinal epithelial mass and function in vivo. This study was designed to determine if HGF, given either systemically or luminally, can enhance intestinal epithelial mass and function beyond the normal adaptive response after massive small bowel resection. METHODS: Twenty young adult male Sprague-Dawley rats underwent an 80% small bowel resection. Seven days after resection, systemic infusion (via the jugular vein) or luminal perfusion (via the jejunum) were performed using subcutaneously placed osmotic minipumps. The rats were divided into four groups: group 1, systemic saline, (control, n=5); group 2, systemic HGF at 150 microg/kg/d (n=5); group 3, luminal saline, (control, n=5); and group 4, luminal HGF at 75 microg/kg/d (n=5). After a 14-day infusion, [C14] galactose and [C14] glycine absorption (micromol/cm2 intestine), mucosal DNA content (microg/mg mucosa) and protein content (microg/mg mucosa) were measured in the remaining small intestine of each rat. RESULTS: Systemic infusion of HGF increased galactose absorption 68% (P<.05), glycine absorption 57% (P<.05), DNA content 17% (P<.01), and protein content 57% (P<.01), when compared with the appropriate control. Luminal perfusion of HGF also increased galactose absorption 114% (P<.01), glycine absorption 126% (P<.01), DNA content 32% (P<.01), and protein content 45% (P<.01), when compared with the appropriate control. CONCLUSIONS: These data demonstrate for the first time that HGF can significantly enhance intestinal epithelial cell function and mucosal mass beyond the normal adaptive response. Luminal administration appeared to produce a greater response when compared with systemic administration but was significant only for galactose absorption (P<.05). HGF may be clinically useful in patients with short bowel syndrome.

    Title Hepatocyte Growth Factor Up-regulates Sglt1 and Glut5 Gene Expression After Massive Small Bowel Resection.
    Date March 1998
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Hepatocyte growth factor (HGF), originally known to stimulate hepatocyte DNA synthesis, also has been shown to stimulate growth of intestinal epithelial cells in vitro. The authors recently demonstrated that HGF can dramatically increase substrate absorption beyond the normal adaptive response after massive small bowel resection in the rat. However, the mechanism for this enhanced substrate absorption is unknown. This study was designed to determine if up-regulation of gene expression by HGF of the Na+/glucose cotransporter SGLT1 and the facilitative glucose transporter GLUT5 is a possible mechanism of action. METHODS: Young adult Sprague-Dawley rats underwent an 80% small bowel resection and jejunostomy tube placement. Seven days later, an osmotic minipump was connected to the subcutaneously placed jejunostomy tube. The rats were divided into two groups based on the contents in the minipumps: group 1, saline (control, n = 5); and group 2, HGF at 75 microg/kg/d (n = 5). After a 14-day infusion, biopsy specimens of the small bowel mucosa were obtained. After total RNA extraction, Northern blot analysis was performed with SGLT1 and GLUT5 cDNA probes. Auto radiographs were quantitated by image analysis. RESULTS: SGLT1 mRNA levels were significantly up-regulated in the HGF-treated animals (121% increase, P<.01) when compared with the control. Up-regulation of GLUT5 mRNA levels was also seen in the HGF-treated animals (96% increase, P < .01). CONCLUSIONS: These data, demonstrating that HGF upregulates intestine epithelial glucose transporter gene expression after massive small bowel resection, may elucidate a mechanism of action for the enhanced carbohydrate absorption after HGF administration. This growth factor may be useful for patients with short bowel syndrome.

    Title Growth Factor Enhancement of Intestinal Function: Dramatic Response but Lack of Synergism.
    Date January 1998
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: The authors have shown that gastrin and epidermal growth factor (EGF) exert a trophic effect on intestinal epithelial cells. Because these peptides may have different mechanisms by which they stimulate these cells, this study was designed to determine the effect of gastrin and EGF on the intestinal epithelial cell and to evaluate their potential synergistic effect. METHODS: Twenty young adult male Sprague-Dawley rats underwent placement of jugular venous catheters that were connected to subcutaneously placed osmotic minipumps. The rats were divided into four groups based on the content of the osmotic pump: Group 1, saline (control, n = 5); Group 2, EGF at 150 microg/kg/d (n = 5); Group 3, gastrin at 13.5 nmol/kg/d (n = 5); and Group 4, EGF at 150 microg/kg/d plus gastrin at 13.5 nmol/kg/d (n = 5). After a 14-day intravenous infusion, [C14] galactose and [C14] glycine absorption (pmol/cm2 intestine), mucosal DNA content (microg/mg mucosa), and protein content (microg/mg mucosa) were measured in the small intestine of each rat. RESULTS: The galactose absorption, glycine absorption, DNA content, and protein content were significantly increased by EGF (69%, 28%, 64%, and 55%, respectively) and gastrin (72%, 60%, 93%, and 48%, respectively) when compared with control. Combining EGF and gastrin also significantly increased these parameters (61%, 44%, 96%, and 70%, respectively) when compared with control. However, these data demonstrate no further enhancement than the effect of each peptide alone. CONCLUSION: EGF and gastrin individually may be useful for patients who have inadequate intestinal function, but when combined did not exert a synergistic benefit.

    Title A Comparison of the Effect of Growth Factors on Intestinal Function and Structure in Short Bowel Syndrome.
    Date January 1998
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: Epidermal growth factor (EGF) and Insulin like growth factor-1 (IGF-1) increase substrate absorption beyond the normal adaptive response after massive small bowel resection in the rat. However, the mechanism for this response is unknown. This study was designed to evaluate the ultrastructural features of the rat small intestine epithelium after exposure to EGF and IGF-1 and correlate any changes with a possible hypothesis regarding the mechanism for the increased absorption. METHODS: Male Sprague-Dawley rats underwent an 80% small bowel resection and jejunostomy tube placement. Seven days later an osmotic pump placed subcutaneously and containing the test substance was connected to the jejunostomy tube. The rats were assigned to one of three groups: group 1 received normal saline (control, n = 5); group 2 received EGF at 150 microg/kg/d (n = 5); and group 3 received IGF-1 at 20 mg/kg/d (n = 5). After a 14-day infusion, a portion of mid-small bowel was resected for light and electron microscopic evaluation from each of the animals. The following features were compared between the groups: villous length, crypt length, villous-crypt ratio, villi per millimeter mucosa, goblet cell distribution, eosinophilic infiltrates, number and distribution of organelles, length of microvilli, and completeness of microvillous surface. RESULTS: Ultrastructurally, the bowel epithelium was well preserved in all animals. There were no objective ultrastructural differences between the controls and growth factor-exposed animals. The mean villous-crypt ratio, mean number of villi per millimeter of mucosa (cross section), and mean microvillous height were not significantly different among the groups. However, there was a subjective increase in the number of lysosomes in the enterocytes exposed to EGF and IGF-1. CONCLUSIONS: Administration of EGF and IGF-1 after massive small bowel resection does not appear to significantly alter the small intestine epithelial ultrastructure when compared with the control group. The increase in lysosomes in some of the enterocytes of the animals exposed to growth factors may be important because this finding was not seen in any of the control electron photomicrographs. Studies to evaluate enterocyte gene and protein expression are necessary to determine the mechanism of EGF and IGF-1 enhancement of substrate absorption beyond intestinal adaptation.

    Title Unusual Peptide-secreting Tumors in Adolescents and Children.
    Date October 1997
    Journal Seminars in Pediatric Surgery
    Excerpt

    Endocrine tumors of the pancreas and intestine are uncommon but challenging lesions. Those tumors that arise in the pancreas are typically derived from one of the various cell types of the islet of Langerhans and secrete the peptide associated with the cell type. In general, the primary tumors are small, relatively slow growing, and many are benign. However, certain tumors are malignant, more aggressive, and metastasize early, such as gastrinomas, glucagonomas, and VIPomas. Many of these tumors can be multicentric, and some may arise in the duodenum of small intestines. Tumors that arise more often in the intestine are carcinoids and VIPomas. The endocrine effects of many of these tumors such as VIPomas or gastrinomas can be life-threatening. A markedly elevated level of a specific peptide will generally be sufficient to establish the diagnosis. Often, the greatest challenge is localizing the tumor(s). The only opportunity for cure is complete surgical excision. Palliation can be accompanied through tumor reduction, surgically of with antineoplastic agents (eg, doxorubicin and 5-fluorouracil). Palliation from symptoms also can be accomplished by blockade of the peptide's secretion of effects. The prognosis is variable and depends on cell type, resectability, and presence of metastases.

    Title Hepatocyte Growth Factor Enhances Intestinal Mucosal Cell Function and Mass in Vivo.
    Date September 1997
    Journal Journal of Pediatric Surgery
    Excerpt

    Hepatocyte growth factor (HGF), originally known to stimulate hepatocyte DNA synthesis, recently has been shown to enhance growth of intestinal epithelial cells in vitro. However, there have been no studies on the effect of HGF on the function of intestinal epithelial cells in vivo. This study was designed to examine the effect of systemically administrated HGF on intestinal epithelial cell mass and function. Twenty young adult male Sprague-Dawley rats underwent placement of jugular venous catheters connected to subcutaneously placed osmotic minipumps. The rats were divided into four groups based on the contents in the osmotic pump: Group 1 (control, n = 5), normal saline; Group 2 (n = 5), HGF 75 microg/kg/d; Group 3 (n = 5), HGF 150 microg/kg/d; and Group 4 (n = 5), HGF 300 microg/kg/d. After a 14 day infusion, [C14] galactose and [C14] glycine absorption were measured in a 10-cm segment of mid small intestine using an in vivo closed-recirculation technique. Mucosal DNA content and protein content of the same small bowel segment were determined for each group. With all three doses, HGF significantly increased DNA content (P < .01) and protein content (P < .05). HGF also significantly increased galactose absorption (P < .01) with all three doses. Glycine absorption was increased with a dose of 75 (P < .05) and 150 microg/kg/d (P < .01), but not at a dose of 300 microg/kg/d. These data demonstrate that HGF can increase intestinal epithelial cell mass and function in vivo. HGF may be clinically useful in patients with short bowel syndrome.

    Title Influence of Luminal Hepatocyte Growth Factor on Small Intestine Mucosa in Vivo.
    Date September 1997
    Journal The Journal of Surgical Research
    Excerpt

    In 1984, a growth factor was identified that stimulated hepatocyte DNA synthesis. This growth factor, referred to as hepatocyte growth factor (HGF), has been shown to enhance growth of intestinal epithelial cells in vitro. Recently, we reported that HGF can increase absorption and intestinal mass when given systemically in an in vivo model. This study was designed to examine if luminally administrated HGF can stimulate intestinal epithelial cell mass and function. Twenty-five young adult Sprague-Dawley rats had catheters inserted into the small intestine and connected to subcutaneously placed osmotic minipumps. The rats were divided into five groups (n = 5 for each group) based on the contents in the osmotic pump: group 1 received normal saline (control); groups 2, 3, 4, and 5 received HGF in increasing doses of 30, 75, 150, and 300 microg/kg/day, respectively. Following a 14-day infusion, [14C]galactose and [14C]glycine absorption was measured in 10-cm segments of mid-small intestine using an in vivo closed-recirculation technique. Mucosal DNA content and protein content of the same small bowel segment were determined for each group. HGF significantly increased galactose absorption at doses of 75 (P < 0.01) and 150 (P < 0.05) microg/kg/day and glycine absorption at doses of 30 (P < 0.05) and 75 (P < 0.01) microg/kg/day. HGF significantly increased DNA content (P < 0.01) at each dose and protein content when given at 30 (P < 0.01) and 75 (P < 0.01) microg/kg/ day. These data demonstrate that luminal administration of HGF can increase intestinal epithelial cell mass and function in vivo. HGF may be clinically useful in patients with inadequate intestinal function.

    Title Acute Abdomen. Laboratory Evaluation and Imaging.
    Date July 1997
    Journal Seminars in Pediatric Surgery
    Excerpt

    The child with an acute abdomen requires a thorough history and physical examination followed by a focused laboratory and imaging evaluation. The laboratory evaluation is more beneficial in determining management than in establishing diagnosis. Ultrasonography has become increasingly useful in the evaluation of the child with acute abdominal pain.

    Title Renal Autotransplantation for Renovascular Hypertension Caused by Midaortic Syndrome.
    Date May 1997
    Journal Journal of Pediatric Surgery
    Excerpt

    Midaortic syndrome (MAS) is a well-recognized but rare cause of renovascular hypertension (RVH). Several techniques have been described to treat RVH caused by MAS. The authors recently treated two children with MAS and RVH. In both patients the right kidney had two renal arteries. A 13-year-old boy presented with severe headaches, pain in his lower extremities with exertion, and marked hypertension (blood pressure, 170/110). An aortogram demonstrated 70% narrowing of his abdominal aorta from the suprarenal region to 5 cm above the iliac bifurcation. There was significant stenosis of the celiac axis, superior mesenteric artery, and left renal artery. The right kidney had two renal arteries, and the upper pole artery was stenotic at its origin. A 10-year-old girl, known to have hypertension for several years had an aortogram that demonstrated 70% narrowing of the abdominal aorta from the suprarenal region to 3 cm above the iliac bifurcation. There was involvement of the left renal artery at its orifice. She also had two renal arteries to the right kidney with the right upper pole artery being stenotic at its origin and in the mid-portion of the vessel. Aortic reconstruction was accomplished with a polytetrafluoroehtylene (PTFE) bypass graft in each case. The first case also involved patch angioplasty of the celiac axis. In both cases, the right kidney was autotransplanted. It was removed intraoperatively, cold perfused, and the two renal arteries reconstructed followed by transplantation to the right iliac vessels. In both cases the left renal artery was reimplanted into the PTFE graft. Both patients had uncomplicated postoperative courses. The 13-year-old boy had evidence of renal ischemia in a portion of the lower pole of the autotransplanted kidney by DTPA scan. He has mild hypertension controlled with antihypertensive medication. The 10-year-old girl has a normal DTPA scan and is normotensive. MAS is a rare and challenging congenital vascular anomaly that causes RVH. In the presence of double renal arteries the technique of autotransplantation with cold perfusion and "bench" vascular reconstruction reduces the warm ischemia time and should produce satisfactory results.

    Title Congenital Malformations of the Lung and Mediastinum--a Quarter Century of Experience from a Single Institution.
    Date April 1997
    Journal Journal of Pediatric Surgery
    Excerpt

    Congenital malformations of the lung are rare and vary widely in their presentation and severity. The authors reviewed 25 years of experience with specific reference to diagnosis, treatment, and outcome. From July 1970 to June 1995, 70 patients were diagnosed with congenital malformations of the lung, which included sequestration (n = 20), foregut anomalies (n = 20), congenital lobar emphysema (CLE; n = 10), congenital cystic adenomatoid malformation (CCAM; n = 5), benign lung cysts (n = 6), lung aplasia/ hypoplasia (n = 4), and other miscellaneous disorders (n = 5). All patients with pulmonary hypoplasia presented at birth. With the exception of one patient, infants with CCAM and CLE presented before 5 months of age. All other patients presented from birth to 16 years of age. A prenatal diagnosis was accurate in two patients. Although prompt surgical management is the rule, the exceptions were children with bilateral lung involvement. Corrective surgery was delayed in some patients in whom extended respiratory support was required or in whom the delay led to an increase in pulmonary reserve. Extracorporeal membrane oxygenation (ECMO) was used in two patients pre- and postoperatively to manage persistent pulmonary hypertension. This review, representing the largest series of congenital lung lesions, showed that (1) prenatal diagnosis is useful but generally does not change the outcome; (2) computerized tomography (CT) is the optimum postnatal diagnostic imaging modality if chest radiography is not definitive; (3) ECMO can be an adjunct in treating associated pulmonary hypertension; (4) pulmonary resection (lobectomy) is the surgical procedure of choice for most lesions; (5) expected survival is good; and (6) pulmonary hypertension is the most common cause of mortality.

    Title What's New in Pediatric Surgery.
    Date March 1997
    Journal Journal of the American College of Surgeons
    Title Ultrasonography As an Adjunct in the Diagnosis of Acute Appendicitis: a 4-year Experience.
    Date June 1996
    Journal Journal of Pediatric Surgery
    Excerpt

    This study was designed to evaluate the sensitivity and specificity of abdominal ultrasonography as a diagnostic modality in a large series of children who presented with possible appendicitis. From August 1990 to July 1994, 452 children (203 boys, 249 girls) with an average age of 11 years (range, 1 to 20 years) underwent graded compression ultrasonography of the right lower quadrant of the abdomen for the evaluation of possible appendicitis. In the first 18 months of the study all patients with the possible diagnosis of appendicitis (group I; 180 patients) had abdominal ultrasonography after members of the surgical team evaluated and documented their findings in the medical record. In the second study period (30 months), abdominal ultrasonography was recommended only when the clinical diagnosis of acute appendicitis was equivocal (group II; 272 patients). Abdominal ultrasonography was performed using the graded compression technique with a 5.0-MHz linear array transducer. A positive ultrasound study for appendicitis was defined as the presence of an enlarged noncompressible appendix with an outer wall to outer wall diameter of greater than 6 mm, the presence of a complex mass, or the presence of an appendicolith. The sonographic data were correlated with surgical and pathological findings. Appendicitis was confirmed in 112 of the 452 cases. In 17 of these, the appendix was perforated. In the overall group of 452 children, abdominal ultrasonography had a sensitivity of 90%, specificity of 96%, and accuracy of 95%. There was no significant morbidity in the 11 patients with a false-negative study result. All 11 patients had an uncomplicated appendectomy. There were 11 false-positive results; 10 of these patients had a negative laparotomy result (negative laparatomy rate, 8.9%). For the two groups, the sensitivity and specificity of ultrasonography in the diagnosis of appendicitis were equivalent (group 1: 88% sensitivity, 96% specificity; group 2: 92% sensitivity, 97% specificity). On the basis of the high sensitivity and specificity rates, ultrasonography of the appendix can be a useful adjunct to standard examination in the diagnosis of acute appendicitis.

    Title Update on the Analysis of the Need for Pediatric Surgeons in the United States.
    Date June 1995
    Journal Journal of Pediatric Surgery
    Excerpt

    Accurate estimations of pediatric surgical manpower needs are necessary if this specialty is to avoid the consequences of under- or oversupply, and reasonable decisions must be made relative to the number of training programs needed. METHODS: Fifteen, 10, and 5 years ago, pediatric surgeons (PSs) in 62 standard metropolitan statistical areas (SMSAs) having a population of at least 200,000 were asked to estimate the number of PSs needed in their localities. A computer program analogous to the SOSSUS program was designed to project the number of PSs that would result from various numbers of trainee graduates per year. The program has been updated for comparison. Known input data included the present number and age of PSs, age range of trainees, current US population projections to the year 2025, and the average retirement age. RESULTS: These PSs estimated that 88 additional PSs are needed in the next 10 years. Currently, 26 programs in the United States graduate an average of 24 trainees per year, and six programs in Canada graduate six trainees per year. The previous projection indicated that 20 trainees per year would result in 525 PSs in 1993, and the actual number is 559; so the figures indicate that 27 or 28 PSs are entering practice each year. The apparent increase in numbers is related to entry of Canadian trainees primarily, and a few others, into practice. The current computer projection indicates that 20 graduate trainees per year would result in an absolute increase of 0.55% per year, and 25 per year would result in an increase of 1.43% per year, to 2020, while the increases in the US population would be 1.02% per year for all ages and 0.52% for 0 to 15 year olds. If all programs currently being considered for approval are certified, as many as 36 trainees per year--or 7 times the rate of the 0-15-year population increase--will result. CONCLUSION: Although an average of 20 graduates per year entering practice would keep pace with the pediatric population, 25 to 27 graduates per year--or 3.5 to 4 times the rate of the 0- to 15-year population increase--can be accommodated now into the current system of delivery of pediatric surgical care on the basis of estimated need. Many more graduates than this would create an excess of surgeons before long.

    Title Splenic Injury in Children After Blunt Trauma: Blood Transfusion Requirements and Length of Hospitalization for Laparotomy Versus Observation.
    Date August 1994
    Journal Journal of Pediatric Surgery
    Excerpt

    Nonoperative management (observation) of blunt injury to the spleen under the appropriate conditions has been shown to be successful and safe. However, concern has been raised that this approach may lead to longer hospitalizations and more frequent and greater volumes of blood transfusion and, therefore, increased risk of blood-borne infection when compared with laparotomy for blunt splenic injury. At the University of California, Davis Medical Center, two separate management teams provide trauma care to patients under 16 years of age, one of which is more oriented to nonoperative care. This provided the opportunity for a retrospective review in which length of hospitalization and blood transfusion requirements were compared for patients undergoing laparotomy and those being observed. From July 1988 to January 1992, 36 patients under the age of 16 were evaluated after blunt trauma and found to have an injury to the spleen. Eleven children were managed nonoperatively. The mechanisms of injury were similar in the operative and nonoperative groups. The average age and hematocrit for the operative and nonoperative groups (respectively) were 9.1 years, 30.6 g%, and 6.9 years, 34.4 g%. Comparing the operative and laparotomy groups, the length of hospital stay (9.9 v 8.4 days) and intensive care unit stay (5.1 v 4.3 days) were similar. The average blood transfusion volumes for the observed group was 0.5 U compared with 5.3 U for the laparotomy group. A subgroup of patients (n = 9) who were stable but underwent abdominal exploration received an average of 1.4 U.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Maintenance of the Placental Circulation to Evaluate and Treat an Infant with Massive Head and Neck Hemangioma.
    Date June 1993
    Journal Journal of Pediatric Surgery
    Excerpt

    A maternal ultrasound was obtained because of polyhydramnios at approximately 30 weeks gestation. The study identified a fetus with a large, solid mass involving the neck and left face. Because of the concern for airway obstruction, we sought an alternative to normal delivery or routine cesarean section. At 35.5 weeks gestation the mother underwent deep halothane anesthesia followed by cesarean section. Initially, only the head and neck of the fetus were delivered and a large hemangioma was noted to involve the anterior and left neck and all of the left face to the left eye. While maintaining placental and umbilical cord circulation, the infant was successfully nasotracheally intubated. The umbilical cord was divided and the delivery completed. At 1 week of age the infant underwent partial excision of that portion of the hemangioma overlying the trachea and the left external carotid artery was ligated. The infant was successfully extubated 12 days later. In the first 4 months of life she had three episodes of platelet trapping requiring high-dose systemic steroid therapy. Beginning at 8 months of age she was begun on intralesional injections of a 50/50 solution of triamcinolone and betamethasone with a marked reduction in the size of the lesion. Preservation of the placental circulation during delivery resulted in the avoidance of a potential hypoxic or fatal event. Intermittent intralesional steroid injections appear to have played a role in the marked reduction in the size of this large subcutaneous head and neck hemangioma.

    Title Radiological Case of the Month. Congenital Pyloric Atresia in Down Syndrome.
    Date March 1993
    Journal American Journal of Diseases of Children (1960)
    Title Fetal Tracheal Intubation with Intact Uteroplacental Circulation.
    Date February 1993
    Journal Anesthesia and Analgesia
    Title Successful Transplantation of Newborn Rat Intestine As a Free Graft.
    Date July 1992
    Journal Transplantation Proceedings
    Title Outpatient Inguinal Herniorrhaphy in Premature Infants: is It Safe?
    Date May 1992
    Journal Journal of Pediatric Surgery
    Excerpt

    Because postoperative apnea and bradycardia in premature infants following inguinal herniorrhaphy remains a concern, outpatient repair has not been recommended. We have been performing outpatient inguinal herniorrhaphy in premature infants and the present study reviews our experience. Between 1985 and 1990, 1,294 outpatient inguinal herniorrhaphies were performed. Of this group 124 patients (9.6%) were identified as being premature (less than or equal to 36 weeks gestational age). Average ages were: gestational age 32.7 weeks (range, 24 to 36 weeks); postnatal age 12.6 weeks (range, 3 to 24 weeks); and postconceptional age (gestational plus postnatal) 45.3 weeks (range, 34 to 59 weeks). Twenty-two infants previously required ventilatory support, 11 patients had apnea/bradycardia, and 9 patients developed bronchopulmonary dysplasia. General anesthesia (usually nitrous oxide and fluothane) was used in all patients and 75% underwent endotracheal intubation. The average operating room time was 40 minutes (range, 20 to 115 minutes) and the average recovery room time was 94 minutes (range, 30 to 240 minutes). There were no perioperative deaths. One patient became apneic immediately after extubation in the operating room. No further episodes were noted after 4 hours of observation. Another patient following discharge had a brief apneic episode at home while on an apnea monitor, which was relieved with gentle stimulation. Both patients had no further sequelae. Bradycardia to 80 beats/min was noted in two patients, and resolved spontaneously in the recovery room. Laryngospasm after extubation in the operating room occurred in two patients, one of whom required brief reintubation and the other resolved spontaneously. Two patients required postoperative ventilation: one was extubated in the recovery room and the other was hospitalized for 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Absence of Malignant Hyperthermia Contractures in Becker-duchenne Dystrophy at Age 2.
    Date February 1992
    Journal Muscle & Nerve
    Excerpt

    Two 2-year-old males underwent muscle biopsy that established the histopathologic diagnosis of Becker dystrophy in one, and Duchenne dystrophy in the other. Concomitant contracture testing with caffeine or halothane was normal for malignant hyperthermia (MH). The results suggest that acute hypermetabolism or acute rhabdomyolysis during anesthesia, in patients with these disorders, is related to the X-linked myopathy and its associated muscle deterioration, rather than to the autosomal dominant MH.

    Title Nuclear Magnetic Resonance As a Noninvasive Method of Diagnosing Intestinal Ischemia: Technique and Preliminary Results.
    Date October 1991
    Journal Journal of Pediatric Surgery
    Excerpt

    Despite the long-standing effort to identify a noninvasive method of diagnosing intestinal ischemia, no reliable biochemical or radiographic technique has evolved. We explored the use of phosphorus nuclear magnetic resonance (PNMR) as a method of detecting surgically induced intestinal ischemia. Using Lewis strain rats (250 to 300 g), small intestine ischemia was produced by ligation in succession from the ligament of Treitz to the ileocecal valve 1 of 2 (group I), 2 of 3 (group II), 3 of 4 (group III), and 4 of 5 (group IV) mesenteric terminal vessels. A sham-operated group was used as a control. Following the surgical procedure, the abdomen was closed and the rat positioned under the PNMR apparatus. Using phosphorus spectroscopy, data were analyzed using a computer program and plotted on a graph indicating relative peaks for the phosphate-based compounds. As a means of comparing groups, we devised an inorganic phosphate to phosphocreatine ratio ("ischemia index"), a qualitative measurement indicating trends used to evaluate ischemia. At the completion of the PNMR study, the abdomen was reopened and proximal, mid, and distal small intestine segments were harvested for histological evaluation using a previously established grading system for intestinal ischemia. Preoperatively, immediately postoperatively, and approximately 2 hours postoperatively, blood samples were obtained for hexosaminidase levels. With increasing vascular ligation, there was an upward trend in both the histological appearance of ischemia and the PNMR ischemia index indicative of increasing tissue ischemia. A similar trend was identified when the histological ischemia grade was directly correlated with the PNMR ischemia index. Hexosaminidase levels did not correlate with ischemia in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Agenesis of the Extrahepatic Bile Ducts: Report of Five Cases.
    Date September 1990
    Journal Journal of Pediatric Surgery
    Excerpt

    Five patients were encountered in whom agenesis either of the proximal extrahepatic biliary ducts (four patients) or total absence of the extrahepatic bile ducts and gall bladder (one patient) were evaluated. Jaundice was diagnosed from at birth to 3 weeks of age (average, 1.2 weeks of age) in these five patients. The patients' ages ranged from 2 to 8 weeks at the time of surgical exploration. Findings at surgery showed either absence of the entire extrahepatic biliary ducts or proximal bile duct remnants, no evidence of an inflammatory process, and no fibrous mass present at the portahepatis. Liver biopsy specimens showed histological evidence of cholestasis, minimal bile duct proliferation and fibrosis, and nearly complete absence of inflammation. In three patients in whom a portocholecystostomy was performed, no bile flow was obtained. Two patients underwent surgical exploration and liver biopsy only. One patient died as a result of severe congenital heart disease at 3 months of age. Four patients have undergone successful hepatic transplantation. These patients are now 10 months to 6 years of age. In our review of the literature, we were unable to find any reports of bile duct agenesis despite the fact that it appears to be a known phenomenon. We conclude that patients with biliary agenesis have early onset of jaundice when compared with patients with biliary atresia, absence of inflammation at the portahepatis at the time of surgical exploration, as well as on biopsy of the liver. Portoenterostomy or portocholecystostomy are likely to fail. We believe that liver transplantation is the treatment of choice for this rare entity.

    Title Abdominal Masses in the Newborn.
    Date March 1990
    Journal Pediatrics in Review / American Academy of Pediatrics
    Title Papillomatous Transformation of the Gallbladder in Metachromatic Leukodystrophy.
    Date February 1990
    Journal Pediatric Pathology / Affiliated with the International Paediatric Pathology Association
    Excerpt

    Papillomatous transformation of the gallbladder was found in a patient with metachromatic leukodystrophy who presented with an abdominal mass. Cholecystectomy was performed, and involvement of the gallbladder was confirmed by metachromatic stains and electron microscopy.

    Title Primary Repair Without Routine Gastrostomy is the Treatment of Choice for Neonates with Esophageal Atresia and Tracheoesophageal Fistula.
    Date November 1989
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Excerpt

    Gastrostomy and staged repair are techniques frequently recommended for the management of esophageal atresia with distal tracheoesophageal fistula (EA-TEF), especially for those infants at high risk. We describe 42 consecutive patients with EA-TEF treated during the past 8 years. Staged repair and preliminary gastrostomy were not routinely employed. Fifteen infants were considered to be at high risk (Waterston class C). Surgical treatment via an extrapleural approach consisted of fistula division and primary single-layer end-to-end esophageal anastomosis. Four patients required proximal esophageal circular myotomy. Four patients early in the series received a gastrostomy at or before definitive repair for various life-threatening indications. One patient had fistula division only and died before esophageal anastomosis was possible. Two neonates died before repair and another died after repair. The deaths in this series of patients were unrelated to EA-TEF. One patient developed a clinically significant anastomotic leak. Four patients required multiple dilatations for anastomotic stricture. Fundoplication was necessary in 3 patients with symptomatic gastroesophageal reflux. Our data demonstrate that excellent overall survival (90%) with low morbidity (15%) can be achieved using primary repair without preliminary gastrostomy in most neonates with EA-TEF. We believe that mortality in high-risk patients with EA-TEF is due to associated life-threatening anomalies.

    Title Complications of Prematurity That May Require Surgical Intervention.
    Date September 1988
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Excerpt

    Many complications related to prematurity may require surgical intervention. Between July 1981 and July 1987, treatment of patent ductus arteriosus (PDA) (228 patients), necrotizing enterocolitis (NEC) (49 patients), and complications of high-pressure ventilation (eight patients) was reviewed. A PDA was ligated in 136 patients, with one death and one complication. Ninety-two patients had treatment with indomethacin, with 35 failures. A PDA was associated with NEC in 37 of the 49 patients, with a 73% mortality when they occurred within 72 hours of each other. Two patients died following pulmonary resection for lung cysts. The two patients with pneumoperitoneum and pneumopericardium were successfully treated with tube drainage. A PDA ligation was successful, with low mortality and morbidity. Treatment with indomethacin was unsuccessful in 38% of patients. There is a high mortality when NEC and PDA occur within 72 hours of each other.

    Title Association of Closure of Patent Ductus Arteriosus and Development of Necrotizing Enterocolitis.
    Date July 1988
    Journal Journal of Pediatric Surgery
    Excerpt

    Over a 5-year period ending in June 1986, 234 neonates with evidence of a significant patent ductus arteriosus (PDA) underwent ductal manipulation. Thirty-four infants (15%) developed evidence of necrotizing enterocolitis (NEC). When NEC and treatment of PDA were within 72 hours of each other, there was a 71% mortality rate. When NEC and PDA ligation were greater than 72 hours apart, there were no deaths. Development of NEC prior to ductal closure was associated with a mortality of 57%, as opposed to no mortality when the development of NEC occurred after ductal closure. Our data suggest that infants who develop NEC before PDA ligation incur a high mortality.

    Title Small Intestine Transplantation: a Logical Solution for Short Bowel Syndrome?
    Date May 1988
    Journal Journal of Pediatric Surgery
    Excerpt

    The purpose of this study is to determine whether small intestine transplantation could be considered as an alternative treatment in infants and children with short bowel syndrome. The potential nutritional consequence of orthotopic small intestine transplantation was evaluated in a rat model. Young Lewis strain rats (weighing 250 to 275 g) were used. Lewis rats with resection of 90% of the small intestine were studied as short bowel group (group I, n = 5). In the transplant group rats, 90% of the original small intestine was transplanted orthotopically using microvascular techniques (group II, n = 5). During the study period of 8 weeks, group II gained weight at rates equal to that of normal age matched rats (+30% of the preoperative weight), whereas rats with short bowel (group I) lost 10% of their weight. Two weeks following transplantation, serum albumin levels were maintained in the normal range in group II. However, group I rats showed decreased albumin levels. Serum cholesterol levels showed no significant difference between the two groups. Maltose absorption was evaluated as a functional test of small intestinal graft absorption (1.0 mg/g body weight of maltose was orally administered, and serum glucose levels were measured). The glucose level at 45 minutes was significantly blunted in group I in comparison with group II. The data from this study suggested that small intestine transplantation can produce adequate nutritional support to sustain growth and development in this rat model. It would be anticipated that small intestine transplantation in patients with short bowel syndrome would also benefit nutritionally.

    Title Management of Patent Ductus Arteriosus: a Comparison of Operative V Pharmacologic Treatment.
    Date April 1988
    Journal Journal of Pediatric Surgery
    Excerpt

    Over a 5-year period ending June 1986, 183 premature infants with evidence of a hemodynamically significant patent ductus arteriosus (PDA) associated with cardiopulmonary compromise underwent pharmacologic and/or surgical ductal manipulation. One hundred seven infants underwent surgical ligation and 76 initially received indomethacin. The average birth weight was 10% less and 1 week less for the surgically treated v the indomethacin-treated infants. Among the infants undergoing ligation, there were no failures of therapy and one surgically related complication. Among the infants receiving indomethacin, 42% failed to improve, and 84% of these infants required surgical intervention. Those infants who failed indomethacin therapy in general weighed less, had a shorter gestation and required prolonged ventilatory support. In no instance was death directly attributable to either therapeutic modality. Our data suggest that surgical ligation of hemodynamically significant PDA yields a more predictable result with low morbidity and no mortality. We believe it is the preferred treatment for premature infants less than 800 g.

    Title Influence of Epidermal Growth Factor on Intestinal Function in the Rat: Comparison of Systemic Infusion Versus Luminal Perfusion.
    Date March 1988
    Journal American Journal of Surgery
    Excerpt

    Epidermal growth factor may be a trophic substance for the small intestine. Previous studies had not evaluated intestinal absorption after long-term continuous administration of epidermal growth factor or compared luminal perfusion with systemic infusion. Epidermal growth factor (150 micrograms/kg/day) was continuously infused either systemically or luminally for 14 days into young adult Fisher strain rats. Luminal studies were performed by creating 10 cm Thiry-Vella loops. At the conclusion of the 14 day infusions, mucosal DNA concentration and absorption of carbon-14 galactose and carbon-14 glycine were determined. The increase in DNA concentration after systemic or luminal infusion of epidermal growth factor was not statistically significant. However, galactose absorption increased 1.9-fold (p less than 0.05) after systemic epidermal growth factor infusion and glycine absorption increased 4.4-fold (p less than 0.01). Luminal epidermal growth factor perfusion increased galactose absorption 2.4-fold (p less than 0.05) and glycine absorption 4.1-fold (p less than 0.01). Thus, both systemic and luminal administration of epidermal growth factor can significantly increase substrate absorption. Additional studies on the physiologic implications and clinical usefulness of these data are warranted.

    Title Fetal Intestinal Transplants in Syngeneic Rats: a Developmental Model of Intestinal Immunity.
    Date June 1987
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    We conducted a longitudinal study of the development of lymphoid tissue in fetal small intestine transplanted to a subcutaneous site in adult syngeneic Fischer strain rats. Fetal jejunoileal segments obtained between 18 and 21 days of gestation were transplanted to a dorsal subcutaneous site on syngeneic adult rats. Three weeks later, intestinal segments greater than 2.5 cm in length were found in 70% of recipients. Each week for 6 wk post-transplantation, a full-thickness biopsy was obtained for histologic and immunohistologic examination. At the time of transplantation, fetal rat intestine did not display Peyer's patches, intraepithelial lymphocytes, lymphoid follicles, or IgA-containing plasma cells. These lymphoid structures reached adult levels by 4 wk after transplantation, and the sequence of development of the lymphoid structures in the transplants appeared to match the postnatal development of normal small intestine. After immunizing the in situ intestine or the transplanted fetal intestine with cholera toxin, the number of cells producing specific antibodies to the immunogen increased significantly in intestinal transplants and in situ intestine. In contrast, few if any cells synthesizing antibodies to cholera toxin developed in the transplants after i.p. immunization. This study suggests that fetal intestinal transplants behave as part of the mucosal immune system. This model may provide useful approaches to studying the development of mucosal immunity.

    Title A Possible Serum Marker for Rejection After Small Intestine Transplantation.
    Date February 1987
    Journal American Journal of Surgery
    Excerpt

    Frequent histologic evaluation of mucosal biopsies remains the most reliable method of monitoring and diagnosing rejection after small intestine transplantation, but lengthy processing time can result in delay in diagnosis. Unfortunately, a serum marker for monitoring small intestine transplantation rejection has not been identified. Hexosaminidase, a lysosomal acid hydrolase, has been shown to increase in serum in association with intestinal ischemia, a finding also associated with acute rejection after small intestine transplantation. We measured N-acetyl hexosaminidase levels after transplantation in three groups of five rats each as follows: Group I, Lewis strain small intestine to Lewis recipients; Group II, Wistar small intestine to Lewis recipients; and Group III, Wistar small intestine to Lewis recipients treated with 25 mg/kg per day of cyclosporine. Serum N-acetyl hexosaminidase levels and mucosal biopsies were obtained on days 0, 2, 4, 6, 8, 10, 12, 14, and 21. Rats in Groups I and III survived without gross evidence of rejection. Three rats in Group II died between 8 and 10 days, and serum N-acetyl hexosaminidase levels increased 24 to 48 hours before death. In the remaining Group II rats, the N-acetyl hexosaminidase levels were significantly higher on days 10, 12, and 14 after transplantation (p less than 0.05). In two of five rats, the histologic changes of rejection occurred later than the increase in N-acetyl hexosaminidase levels. Because measurement of N-acetyl hexosaminidase levels is a rapid and simple serum assay, it may be useful for monitoring rejection after small intestine transplantation.

    Title The Influence of Gastrin on Gastrointestinal Function.
    Date February 1987
    Journal Journal of Pediatric Surgery
    Excerpt

    To improve intestinal function in children with short bowel syndrome, our laboratory has focused on identifying substances, which may enhance the function of small intestine epithelium. Previous studies have demonstrated that gastrin appeared to exert a trophic effect on the gastrointestinal tract. We chose to evaluate the influence of chronic, systemic, and luminal administration of gastrin-17 on substrate absorption in both fetal and mature rat small intestine. Transplanted fetal small intestine, mature small intestine in situ, and isolated mature small intestine segments were the surgical preparations used. Saline (control) or gastrin-17 (13.5 nmol/kg/d) was administered continuously for 14 days either systemically or luminally using osmotic pumps. The response to the saline or gastrin-17 infusions was determined by measuring absorption of radiolabeled substrates (14-C-galactose and 14-C-glycine). Following transplantation of fetal small intestine to a syngeneic host, galactose absorption rose 250% (P less than .01) and glycine absorption rose 130% (P less than .05) when compared with controls (N = 10). The response of mature jejunum and ileum following systemic gastrin infusion was a mild to moderate rise in galactose and glycine absorption, although statistical significance was not achieved. However, following luminal gastrin infusion into mature small intestine segments, there was a 4.54 fold rise in galactose absorption (P less than .01) and a 4.79 fold rise in glycine absorption (P less than .01) when compared with controls. These data suggest that gastrin can enhance substrate absorption in rat fetal and mature small intestine and that luminal perfusion appears to induce the greatest response.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Enhancement of Small Intestine Absorption by Intraluminal Gastrin.
    Date September 1986
    Journal The Journal of Surgical Research
    Excerpt

    Several studies have suggested that gastrointestinal peptides can produce trophic changes in the small intestine epithelium. In a previous study utilizing a rat fetal intestine transplant model, we reported that chronic, continuous, systemic administration of gastrin-17 increased carbohydrate absorption 2.5-fold and protein absorption 1.3-fold. The present study was designed to evaluate the effect of chronic luminal perfusion of gastrin on substrate absorption in rat mature small intestine. A 10-cm segment of mid small intestine was isolated with both ends brought out as abdominal wall stomas (creating a Thiry-Vella loop) and bowel continuity was established by end-to-end anastomosis. After a 1-week recovery, the tips of two catheters were positioned at approximately 3 and 6 cm from the proximal end of the isolated small intestine segment. A 14-day continuous luminal perfusion was accomplished by connecting the other ends of the catheters to subcutaneously placed osmotic pumps filled to deliver saline (control; N = 10) or gastrin-17 (13.5 nM/kg/day; N = 7). At the completion of the luminal perfusion, intestinal absorption was determined with labeled substrates [14C]galactose and [14C]glycine) using a closed, recirculation technique. Absorption (microM/cm2 small intestine) of galactose in the control animals was 1.44 +/- 0.18 and for the gastrin infused rats, it was 6.56 +/- 0.46. Glycine absorption was 1.63 +/- 0.31 for the control group and 7.83 +/- 0.62 for the gastrin infused group. Thus, in this rat model, intraluminal gastrin infusion was capable of increasing carbohydrate (galactose) absorption 456% (P less than 0.01) and protein (glycine) absorption 480% (P less than 0.01). These data represent the first demonstration that intraluminal gastrin can influence small intestine mucosal function by enhancing substrate absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Surgical Management of the Infant with Mesenchymal Hamartoma of the Chest Wall.
    Date July 1986
    Journal Journal of Pediatric Surgery
    Excerpt

    Mesenchymal hamartoma of the chest wall is a rare lesion that presents as a chest wall mass. Four infants are reported, three of whom underwent extensive chest wall resection.

    Title "balanced" Thoracic Drainage is the Method of Choice to Control Intrathoracic Pressure Following Repair of Diaphragmatic Hernia.
    Date November 1985
    Journal Journal of Pediatric Surgery
    Excerpt

    Respiratory failure from pulmonary hypoplasia continues to be the major cause of death in newborn infants with diaphragmatic hernia. Recent investigations have suggested that postnatally induced pulmonary injury can result from excessive positive or negative intrathoracic pressure and contribute to the respiratory deterioration. Therefore, the method of thoracic drainage on the side of the diaphragmatic hernia is critical in controlling and maintaining normal intrathoracic pressure in both intrathoracic spaces. No chest tube or an ipsilateral chest tube connected to water seal, can result in either excessive negative or positive intrathoracic pressure and, therefore, both methods should be avoided. Recently, we employed a "balanced" intrathoracic drainage system which maintains the ipsilateral intrathoracic pressure within the normal physiologic range of +2 to -8 cm H2O regardless of the degree of pulmonary hypoplasia, presence of an ipsilateral pulmonary air leak, straining by the infant, or mechanical ventilation. This system is simple, requires no suction apparatus, and is easily assembled with equipment readily available within the hospital. This technique has been utilized in 18 newborn infants with diaphragmatic hernia and pulmonary hypoplasia. There have been no complications which specifically could be related to the balanced drainage system.

    Title An Alternate Method for Intraoperative Cholangiography in Infants with Severe Obstructive Jaundice.
    Date November 1985
    Journal Journal of Pediatric Surgery
    Excerpt

    Differentiation between biliary atresia, biliary hypoplasia and severe neonatal hepatitis continues to require direct visualization of the biliary ducts. This is usually accomplished by operative cholangiography using radiographic contrast material. Recently, we have employed an alternate technique of operative cholangiography using methylene blue. This method identifies patent biliary ducts by direct visualization. Methylene blue cholangiography (MBC) has been used in 16 infants with severe obstructive jaundice. In contrast to the radiopaque cholangiogram, MBC more accurately demonstrated biliary hypoplasia in two patients. In addition to the better resolution obtained by MBC, it can be performed in considerably less time than that usually required for x-ray cholangiography.

    Title Short Bowel Syndrome in Infants and Children.
    Date October 1985
    Journal Pediatric Clinics of North America
    Excerpt

    This article defines short bowel syndrome and reviews the pathophysiology, medical management, and surgical manipulations proposed to improve intestinal absorption. Emphasis is also placed on possible future methods of management.

    Title Can Gastrointestinal Hormones Enhance Intestinal Absorption?
    Date October 1985
    Journal Surgery
    Excerpt

    Recent studies have suggested that certain gastrointestinal peptides exert a trophic effect on the small intestine. We chose to evaluate the effect of glucagon and cholecystokinin-octapeptide (CCK-OP) on absorption of substrates in both developing and mature small intestine. Developing small intestine was evaluated in a rat fetal intestine transplant model, and mature rat small intestine was studied in in situ but isolated 10 cm segments of jejunum and ileum. Glucagon, 10 micrograms/kg/day, and CCK-OP, 45 micrograms/kg/day, were delivered continuously for 14 days through a subcutaneous osmotic pump. Intestinal absorption was determined with labeled substrates (14C-galactose and 14C-glycine) by a recirculation perfusion technique. Absorption results were expressed as percentage increase over control. The fetal intestine response to glucagon infusion was a 13% rise in galactose absorption and a 27% rise in glycine absorption. After CCK-OP infusion, fetal galactose absorption was 11% and glycine absorption rose 17%. Mature jejunal galactose absorption rose 53% and glycine absorption rose 55% after glucagon infusion. The ileal response to glucagon was a 271% rise in galactose absorption (p less than 0.05) and a 21% increase in glycine absorption. Infusion of CCK-OP decreased jejunal galactose absorption 3% but increased glycine absorption 41%. The ileal response was a 224% increase in galactose absorption (p less than 0.05) and a 19% increase in glycine absorption. Our data suggest that chronic administration of glucagon and CCK-OP can increase substrate absorption in developing and mature rat small intestine. Perhaps manipulation of the gastrointestinal hormone environment may result in increased absorption in man.

    Title Postoperative Small Bowel Intussusception.
    Date October 1985
    Journal The Western Journal of Medicine
    Title Enhancement of Small Intestine Function by Gastrin.
    Date August 1985
    Journal The Journal of Surgical Research
    Excerpt

    Frequently, congenital or acquired small intestine (SI) abnormalities in infants lead to inadequate absorption. Gastrin has been suggested as a trophic hormone for SI epithelial cells. We chose to evaluate the effect of gastrin on the function and maturation of developing SI using a rat fetal intestine transplant model. Jejunoileal segments (7-8 cm) obtained from 19 to 20 days gestation fetal rats were implanted subcutaneously in syngeneic adult rats. Two weeks following transplantation the control group (N = 10) was continuously infused with saline and the study group (N = 9) was continuously infused with gastrin-17 (13.5 nM/kg/day) for 14 days. Following the infusion, intestinal maturation and function were evaluated by mucosal DNA concentration, disaccharidase activity, and absorption of [14C]galactose and [14C]glycine. Absorption (microM/cm2 SI) by the control and study groups for galactose was 1.10 +/- 0.18 vs 2.73 +/- 0.25, and for glycine was 1.68 +/- 0.23 vs 2.22 +/- 0.26, respectively. DNA concentration (microgram/mg SI) of the control and study groups was 410 +/- 43 vs 1031 +/- 158, respectively. Lactase and sucrase activity were similar in both groups. Although maltase (microM substrate hydrolyzed/min/g SI) was 13.5 +/- 2.7 for the gastrin group vs 7.9 +/- .9 for the control group, statistical significance was not achieved. Thus, gastrin produced a statistically significant increase in DNA concentration (cell mass) (P less than 0.01). More importantly, to our knowledge, this is the first demonstration that exogenously administered gastrin can increase absorption of carbohydrate (galactose; P less than 0.01) and protein (glycine; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Growth and Function of Transplanted Fetal Rat Intestine: Effect of Cyclosporine.
    Date May 1985
    Journal Surgery
    Excerpt

    After transplantation of fetal rat small intestine in rat strains with major genetic differences, the effectiveness of cyclosporine (CyA) as an immunosuppressive agent and its effect on intestinal function were evaluated. Substrate absorption, disaccharidase activity, DNA concentration, and histologic appearance were measured and compared with those of fetal intestine transplanted in syngeneic animals. Sixteen of 20 grafts survived in the control (syngeneic) group and 14 of 20 grafts survived in the nonsyngeneic group when treated with CyA (25 mg/kg/day). None of the 10 nonsyngeneic grafts survived when no CyA was administered. Absorption of 14C-galactose in the syngeneic transplants was 0.70 +/- 0.70 mumol/cm2 intestine compared with 1.03 +/- 0.16 mumol/cm2 intestine in the nonsyngeneic transplants treated with CyA. Absorption of 14C-glycine in the respective groups was 1.63 +/- 0.22 mumol/cm2 intestine (syngeneic group) and 1.75 +/- 0.20 mumol/cm2 intestine (nonsyngeneic group treated with CyA). DNA concentration was 410 +/- 43 micrograms/mg intestine mucosa (syngeneic group) and 477 +/- 27 micrograms/mg intestine mucosa (nonsyngeneic group). There was a significant decrease in maltase and sucrase activity in the group treated with CyA but lactase activity was comparable in both groups. Evidence of mild to moderate cellular rejection was seen in only 25% of the nonsyngeneic grafts treated with CyA. When this rat fetal intestine transplant model is used, CyA appears to be an effective immunosuppressive agent and does not significantly impair growth and development of the intestine.

    Title Stimulation of Bile Output by Gastrointestinal Hormones Following Portoenterostomy for Biliary Atresia.
    Date November 1984
    Journal Journal of Pediatric Surgery
    Excerpt

    For biliary atresia portoenterostomy with externally draining conduit provides a model for quantitation of hepatic excretory function and for assessment of the physiologic response of the intrahepatic biliary system to gastrointestinal hormones in a human hepatopathologic condition. Four patients with biliary atresia were serially evaluated from 2 weeks to 43 months following total bile diverting portoenterostomy. A fifth patient with no bile flow provided a control for these studies. The pattern of Rose Bengal excretion for three patients with a satisfactory clinical course was different from that of a fourth patient with highly variable flow and persistent cholestasis. Marked volume and bicarbonate concentration increases in bile were noted 30 to 45 minutes after secretin infusion but only in the four patients with bile flow. The volume response to glucagon was more diffuse. Bilirubin and bile acid concentrations decreased in the stimulated bile flow periods and hourly outputs of these cholephils were not increased above basal. During two intervals of low bile output, secretin markedly increased bile flow in the patient with persistent cholestasis establishing the patency of the hepatoenteric anastomosis (functional obstruction) in contrast to the lack of secretin response in the control (structural obstruction).

    Title Systemic-pulmonary Shunting and Hemoptysis in a Benign Intrathoracic Teratoma.
    Date March 1984
    Journal Pediatric Radiology
    Excerpt

    Hemoptysis as a presenting symptom in benign intrathoracic teratoma is rare, but we have documented one such case and discuss the various possibilities of why such a problem should arise. The bleeding was secondary to systemic-pulmonary artery shunting, caused at least in part by extensive pleural adhesions. The exact cause of the adhesions was not determined but possibilities include previous infection or trauma. The tumor was successfully removed surgically.

    Title Staged Reduction Using a Silastic Sac is the Treatment of Choice for Large Congenital Abdominal Wall Defects.
    Date March 1984
    Journal Journal of Pediatric Surgery
    Excerpt

    Although the survival for infants with abdominal wall defects (AWD) has dramatically improved, agreement on the optimum surgical approach has not been reached. From October 1970 through March 1983, 31 neonates with gastroschisis and 14 neonates with omphalocele were treated. Reduction of the herniated viscera with primary fascial and skin closure was performed in 30% of the gastroschisis patients and 64% of the omphalocele patients. The remaining infants were managed by staged reduction of the herniated viscera using a Silastic sac. Overall, 27 of 45 patients (60%) were treated by staged reduction. Our procedure for staged reduction includes application of a Silastic sac as soon as the infant is stable. The herniated contents are reduced as rapidly as possible so that the prosthetic sacs can be removed within seven days. Abdominal wall stretching, "milking" of the intestinal contents into the stomach for decompression and a gastrostomy tube are avoided. The duration of hospitalization was not influenced by the method of abdominal wall closure in the gastroschisis infants. However, the hospitalization was approximately 10 days longer for those omphalocele patients managed by staged reduction. Complications which occurred in these patients include: respiratory distress (1); wound infection after removal of the Silastic sac (2); intestinal fistula (1); intestinal resection (3); intraabdominal sepsis (1); and incisional hernia (3). There was one death in the omphalocele group and three deaths in the gastroschisis group. Therefore, the overall survival for the 45 patients with AWD was 91%. Staged reduction of the herniated abdominal contents can be a safe, uncomplicated method of obtaining abdominal wall closure in neonates with AWD.

    Title An Improved Technique for Circular Myotomy in Long-gap Esophageal Atresia.
    Date March 1984
    Journal Journal of Pediatric Surgery
    Excerpt

    Circular myotomy has allowed the surgeon to establish esophageal continuity in early infancy in patients with long-gap esophageal atresia. This report describes the use of a #5 Fogarty balloon catheter, passed by the surgeon into the proximal esophagus to facilitate the myotomy. The catheter is passed through a pursestring suture placed at the tip of the proximal esophagus. The balloon is inflated to fill but not distend the lumen. The myotomy is performed approximately two cm proximal to the esophageal end and; upon its completion, it will provide 1 to 1.5 cm of additional length. The advantages of the surgeon placing the catheter into the esophagus include: complete control of the balloon size and position, and the ability to use the catheter to manipulate the proximal esophagus atraumatically.

    Title Management of Congenital Arteriovenous Malformations.
    Date December 1983
    Journal Surgery
    Excerpt

    Twenty-five patients with congenital arteriovenous malformations (AVMs) involving the head, neck, trunk, or extremities were treated over a 10-year period. In patients with more extensive lesions, selective angiography was essential to delineate the extent of the AVM and its vascular anatomy. AVMs that produced congestive heart failure, hemorrhage, pain, or cosmetic embarrassment were excised if possible. Intra-arterial embolization is useful in the reduction of vascularity before operation or as the primary treatment for unresectable lesions. Incomplete excision or embolization of the AVM often results in a recurrence. However, nonsymptomatic lesions may be observed, and extremity varicosities can be treated by external compression.

    Title Hexosaminidase: a Marker for Intestinal Gangrene in Necrotizing Enterocolitis.
    Date November 1983
    Journal Journal of Pediatric Surgery
    Excerpt

    Detection of intestinal ischemia, prior to necrosis, is a major clinical problem. The lysosomal acid hydrolase, hexosaminidase (HEX), is known to be elevated in intestinal infarction. To determine if this enzyme could differentiate between partial intestinal ischemia and full-thickness intestinal gangrene, the following rat study was designed. Partial segmental intestinal ischemia was created by ligating alternate vascular bundles over a short (6 vessel) segment of the small-bowel mesentery, and complete segmental intestinal vascular occlusion was achieved by ligating the blood supply to the ileocecal segment. Preoperative serum HEX values were obtained from 15 animals. The rats were separated into one sham-operated and two intestinal ischemia groups. At four hours after surgery HEX values were determined. Total HEX activity was significantly elevated four hours after insult in both partial and complete intestinal ischemia, (P less than 0.005 and P less than 0.001 respectively). Total HEX activity was greater in complete intestinal ischemia than in partial ischemia, (P less than 0.05). Three neonates with intestinal perforation, secondary to necrotizing enterocolitis, were evaluated. The mean preoperative HEX activity was 1421 nmol/hr/mL serum and the mean post-resection HEX activity was 808 nmol/hr/mL serum. These data suggest that serum HEX activity may be a good marker for intestinal gangrene in neonates with necrotizing enterocolitis.

    Title Subclavian-artery-to-innominate-vein Fistula Presenting with Congestive Failure in a Newborn Infant.
    Date September 1983
    Journal Pediatric Cardiology
    Excerpt

    Congestive heart failure associated with intrathoracic arterio-venous fistula has not, to our knowledge, been reported previously in a newborn infant. A 2 X 4 mm arterio-venous fistula between the subclavian artery and innominate vein presented on the first day of life with heart failure and required surgical intervention. The uncommon location of the fistula produced potentially misleading radiologic findings. When the infant was 2 days old the fistula and a 12 mm diameter persistent ductus arteriosus were ligated; following this, heart failure regressed.

    Title Management of Perforated Appendicitis in Children. The Controversy Continues.
    Date April 1983
    Journal Annals of Surgery
    Excerpt

    A specific treatment plan for management of perforated appendix in children, initiated at the Children's Hospitals in Boston, and later utilized at the Child Health Center in Galveston, has been applied to 143 patients by many surgical housestaff and faculty. The protocol consists of appendectomy, routine use of systemic gentamicin, ampicillin and clindamycin, antibiotic peritoneal irrigation, and transperitoneal drainage through the incision. The average age of the children in this series was 9.1 years (range 14 months to 21 years). The average length of hospitalization was 12.1 days. The use of this protocol resulted in only 11 patients (7.7%) developing significant complications. Complications related to infection occurred in only six of the eleven patients (4.2%). There were no deaths. This protocol of intensive primary therapy can significantly decrease the sequelae from perforated appendicitis in children.

    Title A Prospective Evaluation of Intestinal Stenosis Following Necrotizing Enterocolitis.
    Date April 1983
    Journal Journal of Pediatric Surgery
    Excerpt

    In a retrospective study, we noted a 25% incidence of colonic stenosis following medical management of necrotizing enterocolitis (NEC). From March, 1980 to March, 1982, we performed routine contrast enemas to prospectively identify the incidence of colonic stenosis following medical management for NEC. Three to four weeks following recovery from the acute phase of NEC 28 infants were prospectively evaluated by contrast enema for post-NEC stenosis. Ten of the 28 infants had one or more sites of colonic stenosis (36%). Four infants were symptomatic when the contrast enema was performed and underwent colonic resection. Three of the six asymptomatic infants developed symptoms requiring surgery within 33 days following hospital discharge. Therefore, seven of the ten infants with post-NEC stenosis required segmental colectomy. Three patients with colonic stenosis have remained asymptomatic and are being followed on an outpatient basis. The weight gain in these three infants has been steady and has paralleled a normal growth curve. The data from this study demonstrate that: (1) the incidence of post-NEC colonic stenosis is 36%; (2) patients with colonic stenosis initially may not have symptoms but may become symptomatic after hospital discharge; (3) the sites of stenosis frequently are located in the left colon; and (4) normal weight gain can occur despite the presence of colonic stenosis. Because of the above findings, we recommend routine contrast enemas in all patients with NEC who have had successful medical management.

    Title Combined Esophageal and Duodenal Atresia: Sonographic Findings.
    Date February 1983
    Journal Ajr. American Journal of Roentgenology
    Title Elective Splenectomy in Children: Indications and Operative Approach.
    Date December 1982
    Journal Texas Medicine
    Title Management of Morbid Obesity by Jejunoileal Bypass.
    Date July 1982
    Journal World Journal of Surgery
    Title Partial Ileal Bypass for Hypercholesterolaemia.
    Date March 1982
    Journal Lancet
    Title Positive Results of Jejunoileal Bypass Surgery: Emphasis on Lipids with Comparison to Gastric Bypass.
    Date February 1982
    Journal International Journal of Obesity
    Excerpt

    The positive results of jejunoileal bypass are briefly reviewed: significant weight reduction, lowering of blood pressure, mitigation of diabetes, improved physical functions, amelioration of osteoarthritis and thrombophlebitis, and improved self-esteem and socialization. A major benefit of jejunoileal bypass is the marked and permanent plasma cholesterol and triglyceride reductions. At one year plasma cholesterol is reduced 42 percent, with plasma triglyceride lowered 35 percent. In a comparable series of gastric bypass patients one year after operation, the plasma triglyceride lowering was identical at 35 percent; however, the plasma cholesterol reduction was only 14 percent. Although we currently perform mostly gastric bypasses as the primary metabolic operation for morbid obesity, we believe the jejunoileal bypass should not be discarded from the armamentarium of the surgeon committed to the treatment of this malignant disease.

    Title Antibiotic-associated Colitis.
    Date November 1981
    Journal American Journal of Diseases of Children (1960)
    Title Tracheal Compression As a Cause of Apnea Following Repair of Tracheoesophageal Fistula: Treatment by Aortopexy.
    Date April 1981
    Journal Journal of Pediatric Surgery
    Excerpt

    Tracheal compression is one of the many causes of apnea following repair of esophageal atresia with tracheoesophageal fistula. Since May, 1977 we have treated eight patients with "dying spells" usually occurring during and following a feeding. These episodes were characterized by cyanosis and bradycardia, which progressed to apnea. Tracheal compression was documented to be the etiology of the apnea spells. Other possible causes such as aspiration from gastroesophageal reflux, recurrent tracheoesophageal fistula and esophageal stricture were eliminated. Eight infants underwent aortopexy that was successful in terminating the apneic episodes in seven patients with an average follow-up of 20 mo. One patient continued to have symptoms from a previously undiagnosed vascular ring which was successfully divided one month following aortopexy. After being asymptomatic for 1 mo this infant died from a cardiorespiratory arrest at home. An autopsy did not reveal the cause. Intermittant tracheal obstruction leading to apneic spells is a life-threatening entity following tracheosophageal fistula repair, which can be corrected by aortopexy.

    Title Intestinal Stenosis Following Successful Medical Management of Necrotizing Enterocolitis.
    Date April 1981
    Journal Journal of Pediatric Surgery
    Excerpt

    In the past decade, increased clinical awareness and better medical and surgical management of necrotizing enterocolitis (NEC) has resulted in improved survival. With an increase in the number of infants surviving the acute stages of NEC the sequelae, including intestinal stenosis, have become more apparent. In the past 5.5 yr, 62 patients with NEC have been treated at our institution. Of the 28 survivors of medical management for NEC seven patients developed intestinal stenosis. An average of 23 days elapsed between the recovery from NEC and the diagnosis of colonic stenosis. Only three patients manifested symptoms of intestinal obstruction. Two patients had blood in their stools and two patients were asymptomatic. Five infants were managed by primary or staged resection of the intestinal stenosis. The remaining two patients were treated nonoperatively. Our data suggests a high incidence of intestinal stenosis (25%) following medical management of NEC. There is a marked preference for the stenosis to occur on the left side of the colon. Colon stenoses can exist without symptoms and radiographically proven areas of stenosis can resolve. We recommend that all infants following medical management of NEC have a barium enema prior to hospital discharge. In selected cases asymptomatic patients with colonic stenosis may not require operative intervention.

    Title Childhood Obesity.
    Date April 1980
    Journal The Surgical Clinics of North America
    Title Glycerin Toxicity in an Infant Following Enteric Administration.
    Date January 1979
    Journal Journal of Pediatric Surgery
    Title Plication of the Diaphragm for Symptomatic Phrenic Nerve Paralysis.
    Date September 1978
    Journal Journal of Pediatric Surgery
    Excerpt

    Paralysis of the diaphragm in infants may produce severe respiratory difficulty because of the paradoxic motion of the affected diaphragm and shift of a mobile mediastinum to the contralateral side. Six infants with diaphragmatic paralysis and severe respiratory distress underwent plication of the diaphragm by a simple technique. Five of the six infants had significant improvement in respiratory effort and were ultimately weaned from ventilatory support. One patient with bilateral paralysis had only minimal improvement. Diaphragmatic function returned in two patients after plication. Plication of the diaphragm is a safe and useful procedure to improve ventilation in infants with a paralyzed diaphragm. Since this technique does not prevent return of diaphragmatic function, it should be employed prior to the development of sequelae of prolonged assisted ventilation and sooner if the phrenic nerve is permanently injured.

    Title Huge Splenic Cyst in a Newborn: Comparison with 10 Cases in Later Childhood and Adolescence.
    Date November 1977
    Journal Ajr. American Journal of Roentgenology
    Excerpt

    Radiographic, sonographic, and histologic findings in a case of a huge splenic cyst in a newborn are presented. The patient had the characteristic findings, particularly the visceral displacement, associated with splenic cysts in a series of 10 older children and adolescents. The occurrence in a newborn of a large splenic cyst histologically similar to those found in older children supports the hypothesis that they are developmental rather than traumatically acquired.

    Title Significance of Pneumatosis Cystoides Intestinalis After Jejunoileal Bypass.
    Date March 1977
    Journal American Journal of Surgery
    Excerpt

    In 148 radiographs taken two weeks to twenty-seven months postoperatively in a series of 402 jejunoileal bypass patients at the University of Minnesota, twenty-four patients demonstrated roentgen evidence for pneumatosis intestinalis on twenty-eight separate episodes. This primarily involved the right colon. Clinical signs and symptoms were reviewed in association with the roentgen findings. Symptoms of nausea, vomiting, fever, and abdominal stress were noted but were not universal. Six patients had no significant change in abdominal complaints at the time the pneumatosis was seen and seven patients had similar clinical findings without roentgen evidence for pneumatosis. Thus, the radiographic findings of pneumatosis intestinalis do not represent a specific sign for bypass enteritis.

    Title Hepatic Lesions of Central Pericellular Fibrosis in Morbid Obesity, and After Jejunoileal Bypass.
    Date November 1976
    Journal American Journal of Clinical Pathology
    Excerpt

    Histologic findings in liver biopsy specimens obtained from 88 patients before and one and two years after end-to-end jejunoileal bypass are compared. In addition to the expected fatty changes, mild changes of centrilobular, pericellular fibrosis were present in the initial biopsies in 8.6%; a year later they had become apparent in 46%. Portal-central bridging developed in 6.8%, and early micronodular cirrhosis in 3.4%--always in those with central pericellular fibrosis. Electron-microscopic study of pre-bypass liver biopsies from eight addtional patients showed collagen and electron-dense material resembling basement membranes within the spaces of Disse in seven, although only four had light-microscopic evidence of minimal central pericellular fibrosis. The existence of these light- and electron- microscopic changes before jejunoileal bypass suggests that there is a lesion in morbid obesity that may be exacerbated during the first year after operation.

    Title Treatment of Heterozygous Type Ii Hyperlipidemia by Partial Ileal Bypass in a Pediatric Population.
    Date October 1976
    Journal Journal of Pediatric Surgery
    Excerpt

    Nine patients underwent partial ileal bypass as management for heterozygous type II hyperlipidemia. The average age of this group was 12.5 yr. Follow-up has ranged from 1 to 6 yr. The growth and development of these children proceeded normally. The overall average serum cholesterol reduction was 33% when compared to the preoperative but postdietary control value. Side effects of the procedure include transient diarrhea and inability to absorb vitamin B12, requiring periodic parenteral administration. Partial ileal bypass has been shown to be an effective and obligatory method of treatment of hypercholesterolemia in children.

    Title Fasting and Stimulated Serum Gastrin Levels in Humans Following Jejuno-ileal Bypass.
    Date August 1976
    Journal The Journal of Surgical Research
    Title The Effect of Portacaval Shunt on Plasma Lipids and Tissue Cholesterol Synthesis in the Dog.
    Date August 1976
    Journal Surgery
    Excerpt

    Portacaval shunt (PCS) has been proposed as a therapy for hyperlipidemia; however, its lipid-lowering mechanism is unknown. In this study PCS was performed on ten mongrel dogs to measure its effect on plasma lipids and on the cholesterol synthesizing ability of the liver and intestines, the major indodenous cholesterol synthesizing tissues. Plasma was analyzed for total cholesterol (CHOL), triglycerides (TG), and the CHOL content of three plasma lipoprotein fractions. Jejunal, ileal, and hepatic cholesterol synthetic rates were determined by 14C-acetate incorporation to CHOL in tissue slices obtained at operation before PCS and 44 +/- 4.1 (S.D.) days after PCS. Plasma CHOL decreased by 18 +/- 7 (S.E.), 34 +/- 8 (S.E.), and 57 +/- 14 (S.E.) mg. per 100 ml. by 4, 6, and 16 weeks after PCS, respectively. TG decreased by 13 +/- 5 (S.E.), 27 +/- 5 (S.E.), and 30 +/- 9 (S.E.) mg. per 100 ml. at corresponding time intervals. Paired Student's test analysis of CHOL and TG changes are significant at the p less than 0.05 level. CHOL content of the three plasma lipoprotein fractions decreased correspondingly. Intestinal tissue CHOL synthesis rates changed only slightly. Hepatic synthetic rates increased by 30 to 40%; however, no synthetic rate changes were statistically significant at the p less than 0.05 level. PCS is associated with decreased in plasma CHOL [42% (see article)] AND TG [53% (see article)] in dogs up to 16 weeks following operation. Statistically significant changes in endogenous CHOL synthesis were not demonstrated by this study. The mechanism by which PCS affects plasma lipids in the dog is unknown as yet.

    Title Intestinal Bypass Procedures. Partial Ileal Bypass for Hyperlipidemai and Jejunoileal Bypass for Obesity.
    Date July 1975
    Journal Current Problems in Surgery
    Title Letter: Hepatic Fat After Intestinal Bypass.
    Date May 1974
    Journal The New England Journal of Medicine
    Title Surgical Treatment of Obesity.
    Date April 1974
    Journal Advances in Surgery
    Title Preoperative Preparation, Operative Technique, and Postoperative Care of Patients Undergoing Jejunoileal Bypass for Massive Exogenous Obesity.
    Date May 1973
    Journal The Journal of Surgical Research
    Title Cholesterol Dynamics Following Partial Ileal Bypass Versus Following Partial Ileal Excision in the Rabbit.
    Date June 1972
    Journal Surgery
    Title Liver Function and Morphology Following Distal Ileal Excision in the Rabbit.
    Date January 1972
    Journal Surgical Forum
    Title Cholesterol Synthesis and Turnover Rates Following Ileal Bypass and Ileal Excision in the Rabbit.
    Date November 1971
    Journal Surgical Forum
    Title Cholesterol Excretion Following Chronic Ileal Bypass.
    Date March 1970
    Journal Surgery
    Title Cholesterol Excretion in the Chronically Bypassed Ileum.
    Date May 1969
    Journal Surgical Forum
    Title The Effect of Oral and Intravenous D-ribose on Plasma Insulin Levels in Unanesthetized Dogs.
    Date August 1968
    Journal Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (new York, N.y.)
    Title Acute Abdomen.
    Date
    Journal Adolescent Medicine (philadelphia, Pa.)
    Excerpt

    Abdominal pain is a common complaint in adolescents, and its evaluation is challenging. This article provides a method of evaluating the adolescent with acute abdominal pain, reviews the more common causes that may lead to surgical intervention, and provides algorithms for determining a specific diagnosis and mode of treatment.

    Title Study of an Ovarian Sclerosing Stromal Tumor Presenting As Vaginal Bleeding in a 7-month-old.
    Date
    Journal Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
    Excerpt

    This communication describes the histological, immunohistochemical, ultrastructural, and cytogenetic study of an ovarian sclerosing stromal tumor resected from a 7-month-old girl who presented with vaginal bleeding. The tumor is very rare, its pathogenesis is not clear, and its hormonal activity has been subject to debate. In addition, it has been rarely seen in children and never in infants, with the youngest patient reported being 10 years of age. Histological study of the tumor showed a process of multinodular asynchronous growth followed by gradual loss of cells, hyalinization, and eventual transformation into corpora albicantia-like structures, thus indicating that the process may be more akin to an ovarian nodular follicular hyperplasia than to a classical neoplasm. The study also documented an elevated proliferative MIB-1 index in the process, which had not been investigated in earlier reports, and illustrated the immunohistochemical reactivity of some of its stromal cells to progesterone receptors.

    Title Early Experience with Single Incision Thoracoscopic Surgery in the Pediatric Population.
    Date
    Journal Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
    Excerpt

    Abstract Introduction: Single incision pediatric endosurgery is gaining popularity in children. We have recently applied the single incision approach for thoracoscopic procedures. We report our initial experience with single incision thoracoscopic surgery in the pediatric population. Methods: A retrospective chart review of the first 10 single incision thoracoscopic operations done at our institution was conducted. The patients' mean age and weight and the median operative time, postoperative length of stay, and time until discontinuation of chest tubes were determined. Results: The 10 procedures were performed in eight patients (two patients each had bilateral procedures). The procedures performed included wedge resection and mechanical pleurodesis for spontaneous pneumothorax (n = 7), wedge biopsies for lymphoma (n = 1) and chronic granulomatous disease (n = 1), and resection of an apical extrapulmonary neuroblastoma (n = 1). All of the procedures were completed without intraoperative complication or significant blood loss. In each case, multiple trocars and/or unsheathed instruments were passed through a single small incision, which was subsequently used for the chest tube(s). The mean patient age was 13.5 years (range 3-18 years). The mean weight was 47 kilograms (range 16-63 kg). The median operative time was 64 minutes (range 50-201 minutes). The median postoperative length of stay was 7 days (range 3-19 days). The median time until chest tube removal was 3 days (range 2-15 days). The mean follow up was 7 months (range 3-12 months). One patient developed a recurrent pneumothorax and persistent air leak after having undergone a wedge resection and pleurodesis for a spontaneous pneumothorax and required a reoperation. Conclusion: Single incision thoracoscopic surgery is a feasible alternative to the traditional multiple incision approach in the pediatric population. The in-line positioning of the camera and instruments often proves to be an advantage rather than a hindrance.

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