Biomedical subjects

M Z Schwartz

Publications and source records attributed to M Z Schwartz.

At least 19 recordsLinked to original sources

PubMed2001

Novel effect of leptin on small intestine adaptation.

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.

Adaptation, Physiological↗

PubMed2001

GLP-2alpha accelerates recovery of mucosal absorptive function after intestinal ischemia/reperfusion.

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.

Analysis of Variance↗

PubMed2001

Pharmacotherapy and growth factors in the treatment of short bowel syndrome.

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.

Child, Preschool↗

PubMed2000

Growth-factor enhancement of compromised gut function following massive small-bowel resection.

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.

Animals↗

PubMed2000

Glucagonlike peptide-2 analogue enhances intestinal mucosal mass after ischemia and reperfusion.

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.

Animals↗

PubMed2000

Interleukin-11 enhances small intestine absorptive function and mucosal mass after intestinal adaptation.

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.

Adaptation, Physiological↗

PubMed2000

Glucagonlike peptide-2 analogue enhances intestinal mucosal mass and absorptive function after ischemia-reperfusion injury.

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.

Animals↗

PubMed2000

Treatment of inflammatory bowel disease in a rodent model with the intestinal growth factor glucagon-like peptide-2.

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.

Animals↗

PubMed1999

Glucagonlike peptide-2 enhances small intestinal absorptive function and mucosal mass in vivo.

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.

Animals↗

PubMed1999

Cost-effective imaging approach to the nonbilious vomiting infant.

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%.

Algorithms↗

PubMed1998

Effect of laminin on the nuclear localization of nucleolin in rat intestinal epithelial IEC-6 cells.

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.

Animals↗

PubMed1998

Hepatocyte growth factor up-regulates SGLT1 and GLUT5 gene expression after massive small bowel resection.

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.

Animals↗

PubMed1998

Enhancement of intestinal adaptation by hepatocyte growth factor.

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.

Adaptation, Physiological↗

PubMed1998

Enteral glutamine does not enhance the effects of hepatocyte growth factor in short bowel syndrome.

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.

Adaptation, Physiological↗

PubMed1997

Influence of luminal hepatocyte growth factor on small intestine mucosa in vivo.

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.

Animals↗

PubMed1997

Congenital malformations of the lung and mediastinum--a quarter century of experience from a single institution.

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.

Adolescent↗

PubMed1997

Renal autotransplantation for renovascular hypertension caused by midaortic syndrome.

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.

Adolescent↗

PubMed1997

Hepatocyte growth factor enhances intestinal mucosal cell function and mass in vivo.

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.

Animals↗