Open and laparoscopic appendectomy are equally safe and acceptable in children.

BACKGROUND: The aim of this study was to evaluate prospectively whether laparoscopic (LA) and open appendectomy (OA) are equally safe and feasible in the treatment of pediatric appendicitis. METHODS: A total of 517 children with acute appendicitis were randomly assigned to undergo LA or OA appendectomy, based on the schedule of the attending surgeon on call. Patient age, sex, postoperative diagnosis, operating time, level of training of surgical resident, length of postoperative hospitalization, and minor and major postoperative complications were recorded. Chi-square analysis and the Student t-test were used for statistical analysis. RESULTS: In all, 376 OA and 141 LA were performed. The two groups were comparable in terms of patient demographics and the incidence of perforated appendicitis. The operative time was also similar (47.3 +/- 19.7 vs 49.9 +/- 12.9 min). The overall incidence of minor or major complications was 11.2% in the OA group and 9.9% in the LA group. CONCLUSION: Pediatric patients with appendicitis can safely be offered laparoscopic appendectomy without incurring a greater risk for complications. Nevertheless, a higher (but not significantly higher) abscess rate was found in patients with perforated appendicitis who underwent laparoscopy.

Clinical features of a human Rac2 mutation: a complex neutrophil dysfunction disease.

The case of an infant with multiple, rapidly progressive, soft-tissue infections is presented. Despite features suggesting a neutrophil disorder, results of screening tests of phagocyte function were normal. A novel, multifaceted leukocyte disorder-distinguished by defects in shape change, chemotaxis, ingestion, degranulation, superoxide anion production, and bactericidal activity-was established secondary to a defect in Rac2.

Macrophage phenotype during cholestatic injury and repair: the persistent inflammatory response.

BACKGROUND/PURPOSE: Biliary decompression for congenital or acquired obstruction (eg, biliary atresia) does not uniformly lead to liver repair, restore function, or prevent cholangitis. The authors hypothesize that failed repair is caused by altered macrophage (Mo) phenotypes central to an ongoing inflammatory and fibrogenic response. METHODS: In adult rats, biliary obstruction was performed by suspension of the common bile duct for 5 or 7 days. Decompression followed release of the loop until death during the course of liver repair. To determine Mo phenotype in the presence or absence of resident macrophages, animals were either administered gadolinium chloride or saline before injury and repair. At death, hepatic Mo were isolated, stained with MAC-1 (CD11b/CD 18) and OX-3 (MHC class II), and quantified with flow cytometry. Liver sections were immunostained for ED-1 and ED2; positive Mo were counted per square millimeter of tissue. RESULTS: Obstruction led to bile duct proliferation, fibrosis, and inflammation. Decompression relieved jaundice and ductal hyperplasia. After injury, hepatic Mo showed an 80% phenotypic conversion to MAC-1 and OX-3-positive cells. Cells isolated from livers at 9 days of repair persisted with 60% MAC-1 and 77% OX-3 expression. Gadolinium reduced Kupffer cells at all stages of repair. Recruited Mo in treated animals increased 4-fold greater than controls. CONCLUSIONS: Kupffer cells appear to limit the recruitment and persistence of a systemic macrophage phenotype in liver injury and repair. Cell surface markers for systemic macrophages appear after injury and persist during repair, despite adequate biliary decompression. After biliary decompression, this macrophage phenotype accounts for inflammatory complications such as cholangitis and ongoing fibrosis.

The role of preoperative chemotherapy in the treatment of infantile fibrosarcoma.

Infantile fibrosarcoma (IFS) is a rare tumor most often affecting the extremities of infants and young children. Unlike its adult counterpart, IFS has a low potential for metastatic spread, and surgical extirpation alone has therefore resulted in an excellent prognosis. The amputation rate, however, exceeds 50%. The dramatic response in 2 recent cases to preoperative chemotherapy, given in an attempt to avoid amputation, prompted this report and a review of the literature.

Kupffer cell inactivation delays repair in a rat model of reversible biliary obstruction.

BACKGROUND: During cholestatic liver injury, Kupffer cells (KC) and activated macrophages modulate cell proliferation and subsequent matrix deposition. The role of KC in the restoration of cell architecture and matrix metabolism during repair following chronic cholestatic liver injury is unknown. MATERIALS AND METHODS: To determine the effect of KC inactivation, adult male Sprague-Dawley rats underwent bile duct suspension (BDS) for 5 days followed by reversal of the obstruction. Saline (control) and gadolinium chloride (10 mg/kg) were administered 1 day prior to BDS and 1 day prior to reversal, to inactivate KC during both injury and repair. Serum bilirubin and quantitative cell morphometry were compared to verify the reversibility of the model. Collagen content of the liver was measured in trichrome-stained paraffin sections using NIH imaging software. RESULTS: Reversibility of the obstruction was verified by normalization of direct serum bilirubin, which peaked at 8.42 +/- 0.76 mg/dL following 5 days of BDS and returned to sham-operated levels 2 days after reversal, 0.36 +/- 0.15 mg/dL. Hematoxylin and eosin (H&E)-stained paraffin-embedded liver sections from gadolinium-treated animals at 4 and 7 days after reversal exhibited persistent bile duct proliferation, matrix deposition, and inflammation. Gadolinium-treated animals had altered collagen metabolism compared to saline controls. Whereas the collagen content in the saline group slowly returned to sham-operated levels over time, the treatment group demonstrated progressive accumulation of collagen during repair which was statistically significant at 7 days following reversal (8.79%/mm(2) +/- 2.17 in gadolinium group vs 2. 33%/mm(2) +/- 0.34 in saline group, P = 0.0003). CONCLUSIONS: These results demonstrate that inactivation of resident hepatic macrophages during liver repair impairs collagen metabolism, inhibits the resolution of fibrosis, and allows the persistence of inflammatory cell infiltrates in the portal areas. This is the first evidence of profibrogenic responses in the absence of an intact KC compartment during repair after cholestatic injury.

The unpredictable character of congenital cystic lung lesions.

BACKGROUND: The spectrum of congenital cystic disease of the lung ranges from hydrops and neonatal respiratory distress to asymptomatic lesions. Surgical management is dictated by the presence of symptoms, recurrent infection, and the potential risk of malignant transformation. METHODS: Since 1995, all consecutive patients with congenital cystic lung lesions underwent follow-up for symptoms, treatment, and correlation of presumptive with pathological diagnosis. RESULTS: Twelve cystic lung lesions were identified. Seven were diagnosed with mediastinal shift in utero; in 6 of 7, the shift subsequently resolved. Overall, 6 of 7 lesions that were followed up serially decreased in size. Two patients were symptomatic in utero; 1 underwent thoracoamniotic shunting, 1 pleurocentesis for impending hydrops. Postnatally, these 2, and 2 other newborns required urgent surgery. Five of 8 asymptomatic patients had elective resection by 16 months, and 4 await operation. In 6 of the 9 surgical cases (67%), there was a discrepancy between preoperative and pathological diagnosis. There were 4 hybrid congenital cystic adenomatoid malformation (CCAM)/sequestrations. CONCLUSIONS: At least 6 of 7 congenital cystic lung lesions decreased in size regardless of gestational age or presence of mediastinal shift. Antenatal intervention is therefore rarely indicated. Hybrid morphology may necessitate resection of stable, asymptomatic lesions to prevent the theoretical concern for associated malignancies as well as other complications of CCAM.

Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation.

A 5-week-old male infant presented with severe bacterial infections and poor wound healing, suggesting a neutrophil defect. Neutrophils from this patient exhibited decreased chemotaxis, polarization, azurophilic granule secretion, and superoxide anion (O(2)(-)) production but had normal expression and up-regulation of CD11b. Rac2, which constitutes >96% of the Rac in neutrophils, is a member of the Rho family of GTPases that regulates the actin cytoskeleton and O(2)(-) production. Western blot analysis of lysates from patient neutrophils demonstrated decreased levels of Rac2 protein. Addition of recombinant Rac to extracts of the patient neutrophils reconstituted O(2)(-) production in an in vitro assay system. Molecular analysis identified a point mutation in one allele of the Rac2 gene resulting in the substitution of Asp57 by an Asn (Rac2(D57N)). Asp57 is invariant in all defined GTP-binding proteins. Rac2(D57N) binds GDP but not GTP and inhibits oxidase activation and O(2)(-) production in vitro. These data represent the description of an inhibitory mutation in a member of the Rho family of GTPases associated with a human immunodeficiency syndrome.

Cost-effectiveness of laparoscopy in children.

BACKGROUND: Laparoscopy may offer fast recovery and improved cosmesis, but its cost has been perceived as excessive. OBJECTIVE: To analyze the total hospital costs of laparoscopy vs open surgery. DESIGN: Retrospective cost-effectiveness analysis evaluating all cases performed in a 36-month period (September 1995 to August 1998). Cases were evaluated for operative time, itemized cost of supplies, and length of hospitalization. SETTING: Operations performed by pediatric surgeons in a tertiary care children's hospital. PATIENTS: Consecutive children undergoing laparoscopic or open appendectomies, cholecystectomies, fundoplications, and splenectomies. Patients were not randomized to laparoscopy, or open surgery. INTERVENTIONS: Laparoscopic procedures performed with a core set of reusable equipment and a limited number of disposable instruments. MAIN OUTCOME MEASURES: Cost surplus of laparoscopy was evaluated, and compared with savings associated with decreased hospital stay, to obtain cost-effectiveness of laparoscopy per procedure. RESULTS: There were 26 laparoscopic and 359 open appendectomies; 33 laparoscopic and 3 open cholecystectomies; 16 laparoscopic and 18 open fundoplications; and 16 laparoscopic and 7 open splenectomies. Excess operating costs per procedure were $442.00 for appendectomy, $634.60 for fundoplication, $847.50 for cholecystectomy, and $1551.30 for splenectomy. Hospital stay was decreased for all laparoscopies, resulting in an overall savings per laparoscopic procedure of $2369.90 for appendectomy, $5390.90 for fundoplication, $1161.00 for cholecystectomy, and $858.90 for splenectomy. CONCLUSIONS: Laparoscopy is cost-effective, particularly for fundoplication, appendectomy, and cholecystectomy. Detailing the costs of supplies, operating time, and length of stay allows interinstitutional comparison and critical cost-analysis of laparoscopy. With a more selective use of reusable instruments and further shortening of operative time, the global savings of laparoscopy may increase.

Rollover injuries in residential driveways: age-related patterns of injury.

BACKGROUND: The major objective of the present study was to determine the severity of nonfatal injuries sustained by children (<16 years old) when a motor vehicle rolls over them. We also sought to determine whether younger children (<24 months old) demonstrated different patterns of injury and/or a worse outcome, compared with older children (>24 months old). METHODS: We reviewed the medical records of 3971 consecutive admissions to a single trauma service at an urban children's hospital between March 1990 and October 1994. During this time period, 26 (0.7%) children presented with rollover injuries incurred by motor vehicles in residential driveways. Outcome was measured by length of both intensive care unit admission and hospitalization. RESULTS: Two children died shortly after admission and were excluded from the remainder of the study. Younger children (<24 months old) had significantly higher injury severity scores and lower pediatric trauma scale scores. Both the duration in the intensive care unit and the length of hospitalization were significantly longer in younger children, compared with children >24 months old. One explanation for these observations was that younger children had a significantly higher incidence of both head and neck and extremity injury but a similar incidence and severity of chest and abdominal trauma, compared with older children. Injuries requiring operative intervention were rare. CONCLUSION: Younger patients sustaining rollover injuries in the residential driveway have a worse outcome, in part, because of the head and neck or extremity injures that they incur. The majority of rollover injuries can be managed conservatively. pediatric trauma, driveway, pedestrian events, rollover injuries, injury severity score, pediatric trauma scale.

Transmucosal passage of bacteria across rat intestinal epithelium in the Ussing chamber: effect of nutritional factors and bacterial virulence.

Transmucosal passage of bacteria across the intestine, the essential and prerequisite step for bacterial translocation, cannot be effectively studied using in vivo models of translocation. We have adapted the Ussing chamber into a fresh, sterile organ culture system that can facilitate the study of bacterial-epithelial interactions. Intestinal membranes were mounted in the Ussing chamber and perfused with a solution rich in putative mucosal micronutrients. The transmembrane potential difference was constantly monitored as a marker of intestinal integrity. Transmucosal passage of various bacteria across the normal intestinal epithelium was quantitated, and the mucosal membrane was examined by light and transmission electron microscopy. The addition of potassium cyanide to the mucosal perfusate resulted in an irreversible loss of potential difference. Oxygen deprivation also led to a precipitous drop in potential difference, but it was reversible with prompt reoxygenation. In contrast, intestinal membranes perfused with a solution consisting of Dulbecco's modified Eagle's medium + 20 mM glutamine maintained their potential difference for a sustained period (>180 min). Both the viability and structural integrity of the ileal intestinal membrane were maintained in culture ex vivo using this perfusate. Qualitative differences were observed in the mechanism of transmucosal passage of mild to moderately virulent bacteria such as Escherichia coli C-25 and Proteus mirabilis M-13, which pass through the intestinal epithelium without causing overt damage to the mucosa, and more virulent organisms such as Salmonella typhimurium, which cause extensive mucosal damage by light and transmission electron microscopy. The Ussing system should provide a useful model of intact organ culture for the study of the mechanisms of bacterial translocation and the pathogenesis of enteric infections.

Operative management of asphyxiating thoracic dystrophy after pectus repair.

Pectus excavatum repair usually results in unchanged or improved pulmonary function. However, a small subset of patients will experience severely impaired pulmonary function after pectus repair caused by restrictive lung disease, and no adequate surgical approach has been described for this condition. A procedure is described that is a variation of an operation for Jeune's thoracic dystrophy, that resulted in marked respiratory improvement in this setting. A 14-year-old boy had undergone standard pectus excavatum repair at age 4, from which he recovered uneventfully. Beginning at age 10 to 12 years progressive restrictive pulmonary disease, recurrent pneumonia, and cor pulmonale developed, which resulted in almost constant shortness of breath and the need for continuous nasal positive pressure support. Pulmonary function test results were markedly abnormal and worsening. He underwent an operative procedure consisting of sternal split that was wedged open permanently with rib struts, opening of pleura bilaterally, and six rib resections bilaterally. His postoperative recovery was satisfactory, and his pulmonary functions have shown steady improvement. He is now completely off oxygen and pressure support, has improved exercise tolerance, and has returned to school. Severe restrictive lung disease after pectus repair can be successfully managed with aggressive operative procedures. Patients should have close follow-up after pectus repair for the development of this potentially debilitating disorder to allow earlier repair.

Blunt intestinal injury in children. Diagnostic and therapeutic considerations.

OBJECTIVES: To identify computed tomographic (CT) findings in children who have experienced blunt trauma and who have known intestinal injuries and to correlate these findings with the findings of the initial physical examination. DESIGN: A retrospective review of children (aged < 18 years) known to have an intestinal injury as a consequence of blunt trauma. SETTING: A university-affiliated children's hospital with a level 1 pediatric trauma center. PATIENTS: Children younger than 18 years who were admitted for examination of injuries or for management of complications related to intestinal injuries. INTERVENTIONS: Clinical and radiographic evaluation and laparotomy for intestinal injuries other than duodenal hematoma. MAIN OUTCOME MEASURES: The identification and correlation of relevant findings during the physical examination, on the CT scan, and during surgery. The assessment of intervals from injury to diagnosis and intervention and the description of associated injuries. RESULTS: Twenty-two patients sustained intestinal injuries as a result of blunt trauma. Most (15) of the patients were passengers injured in motor vehicle crashes; 14 of these patients were wearing seat belts. Focal blows to the abdomen from bicycle handlebars, hockey sticks, or falls onto blunt objects were implicated in the remaining patients. For 19 of the 22 patients, the initial physical examination was conducted at Cardinal Glennon Children's Hospital, St Louis, Mo, and 18 of the 19 patients underwent a concurrent CT evaluation. Peritonitis was found in 5 of these 18 patients. Tenderness on physical examination was noted in 9 of the 18 patients (tenderness was not noted in 3 patients, and 1 patient had unreliable examination findings due to a cervical spinal cord injury). Computed tomographic findings of pneumoperitoneum and extravasation of enteral contrast material were uncommon but diagnostic (in 5 patients). Free fluid in the pelvis in the absence of a solid organ injury, bowel wall thickening, and fluid-filled loops of bowel were more frequently useful signs of possible intestinal injury (in 9 of the 18 patients) and led to earlier exploration when used in conjunction with physical examination as an indication for surgery. Most injuries were treated with segmental resection or suture repair, but enterostomies were required in 2 patients. Complications (i.e., the need for enterostomy and fascial dehiscence) were seen as a result of late or missed diagnosis, which could occur as late as 4 to 6 weeks after injury as intestinal obstruction due to stricture. CONCLUSIONS: The initial physical examination findings and CT evaluation can independently identify the presence of intestinal injury in approximately 25% of cases. In the remainder of cases, the awareness of the more subtle findings of bowel injury on a CT scan can complement the physical examination findings and potentially lead to a more timely intervention for bowel injury.

Video-assisted thoracic surgical repair of a foramen of Bochdalek hernia.

A case report of a congenital posterolateral diaphragmatic hernia in an adolescent is presented and a technique for thoracoscopic repair of Bochdalek hernia is described. Postoperative discomfort was minimal and the hospital stay was less than 24 hours. Video-assisted thoracic surgery may be the technique of choice for repair of certain congenital diaphragmatic hernias when identified after infancy.

Effect of secretory IgA on transepithelial passage of bacteria across the intact ileum in vitro.

BACKGROUND: Bacterial translocation is a process believed to result in nosocomial infections. Secretory IgA (sIgA) may have a role in the prevention of translocation by its ability to bind and aggregate bacteria, a function termed "immune exclusion." The present study was done to determine the effect of specific binding of sIgA to bacteria on the movement of these organisms across the intact epithelial membrane. STUDY DESIGN: Bacterial translocation across intact intestinal segments of rats were assessed in vitro using the Ussing model. Secretory IgA (0.25 mg per mL) from pooled human colostrum was added to the perfused segments of ileum in the Ussing system. Subsequently, the membranes were exposed to 5 x 10(9) cfu per mL Escherichia coli on their mucosal side. A second experiment tested the effect of human IgG when perfused with E. coli using the same preparation. All experiments had paired matched rats in a control group without immunoglobulin. The ability of sIgA and IgG to bind to E. coli was studied by an in vitro assay, as well as by transmission electron microscopy and immunofluorescence of random IgA/E. coli experiments. Measurements obtained in all experimental and control groups were the incidence and amount of bacterial passage and the potential difference generated by the intestinal segments (an index of viability). RESULTS: There were no differences in potential difference between control and experimental groups in either of the two experiments. Secretory IgA bound E. coli and completely prevented passage of E. coli as compared with rats in the control group. IgG bound E. coli; however, the incidence of passage was equal to that of rats in the control group. However, the presence of IgG resulted in a significantly reduced number of bacteria that passed when compared with controls (p < 0.05). Electron microscopic studies revealed intact surface morphology and immunofluorescence revealed aggregates of IgA and E. coli on the mucosal, but not submucosal, surface of the ileal membranes. CONCLUSIONS: This study provides direct evidence of immune exclusion by sIgA. When bound to bacteria, it prevents passage across a morphologically intact segment of viable intestinal tissue.

Necrotizing enterocolitis in the extremely low birth weight infant.

Improved neonatal management has resulted in an enlarging population of extremely low birth weight (ELBW) infants. These infants have a high incidence of necrotizing enterocolitis (NEC) and a high mortality rate. The authors compared two groups of NEC patients: ELBW infants (< 1,000 g and/or < or = 28 weeks' gestation) and "standard" premature infants (29 to 36 weeks' gestation). NEC was classified according to the extent of bowel involvement: (1) focal, (2) diffuse, or (3) pan involvement (pan necrosis). Clinical laboratory, radiological, pathological, and bacteriologic findings, management, and mortality were analyzed. There were no significant differences between the groups with respect to gender, race, delivery mode, or incidence of prenatal or perinatal problems. The most common presenting signs in both groups were abdominal distension, vomiting, and feeding intolerance. The onset of signs and the time of first feedings were significantly later in the ELBW group. Pneumatosis was the most frequent initial radiological finding (60% of the ELBW group, 75% of the premature group). Portal vein air (PVA) was present in 29% of the ELBW and premature infants. Seventy-one percent of ELBW infants with PVA had pan involvement, versus 40% of premature infants (P < .05). There were significant differences in the peritoneal cultures between the groups. The premature group had significantly more Escherichia coli (54% v 23%). The ELBW group had a wider variety of microorganisms (eg, Clostridium sp, Pseudomonas sp, and yeast). Survival was significantly higher for the premature group (84% v 55%). The mortality rate was 93% when pan involvement was present in the ELBW group.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of intestinal mucus in transepithelial passage of bacteria across the intact ileum in vitro.

BACKGROUND: Although gastrointestinal mucus is one of a number of putative host defense mechanisms that protect the gut barrier against microbial translocation, little experimental data are available to show its role in this process. The present study sought to determine the role of mucus depletion on the transepithelial passage of bacteria across viable segments of rat ileum mounted in Ussing chambers in vitro. METHODS: Intestinal mucus was depleted in 12 rats after injection with pilocarpine (160 mg/kg intraperitoneally) 45 minutes before intestinal harvest. The mucosal surfaces of the perfused gut segments mounted in the Ussing chamber were exposed to 5 x 10(9) CFU/ml Escherichia coli C-25. Viability was monitored by continuous measurements of the potential difference generated by the membranes. The electrical characteristics were unaltered by pilocarpine pretreatment or exposure to bacteria. RESULTS: Bacterial passage occurred in 100% of pilocarpine membranes as compared with 33.3% in controls (p < 0.05). Pilocarpine-treated membranes resulted in 19.9 +/- 7.5 mg of retrievable mucus as compared with 28.8 +/- 7.2 mg in controls (p < 0.05). Light and transmission electron microscopy revealed an intact epithelial surface in all membranes. There was a marked decrease in mucus on the surface of pilocarpine-treated membranes. CONCLUSIONS: Intestinal mucus secretion is a critical factor in the barrier function of the gut, and its depletion results in a dramatic increase in bacterial passage across the intact rat ileum.

Adaptation in short-bowel syndrome: reassessing old limits.

The improving survival of patients with severe short-bowel syndrome along with the advent of successful intestinal transplantation have accentuated the need to answer two questions. (1) Is there an intestinal length below which adaptation to full enteral nutrition can not be expected to occur? (2) How much time is necessary to complete intestinal adaptation? We reviewed the outcome of 21 infants with less than 50 cm of small intestine to answer these questions. Patients were divided into three groups based on intestinal length, regardless of ileocecal valve status: group I, < 10 cm (n = 3); group II, 10 to 30 cm (n = 11); and group III, 30 to 50 cm (n = 7). Data were collected to assess survival, incidence of adaptation, time to adaptation, and causes of mortality. Infants in group I did not achieve intestinal adaptation to full enteral nutrition. One survived and 2 died, one from varicella pneumonia and the other after intestinal transplantation. Eight of the 11 (73%) patients in group II survived and 5 of 8 (63%) survivors achieved full intestinal adaptation after a mean interval of 320 days (range, 148 to 506 days) on parenteral nutrition. Six of the seven patients (86%) in group III survived and all survivors (100%) achieved complete enteral adaptation after an average of 376 days (range, 58 to 727 days). The overall survival was 71% (15/21), but survival in patients with > 10 cm was 78%.(ABSTRACT TRUNCATED AT 250 WORDS)

Mucosal glutamine utilization after small-bowel transplantation: an electrophysiologic study.

A short course of FK 506 after small bowel transplantation averts rejection in the rat and achieves indefinite survival of the recipient whose nutritional status is dependent on the function of the intestinal graft. Ex vivo electrophysiologic studies using the Ussing Cell were conducted to delineate functional competence of the graft by evaluating mucosal ion transport and glutamine utilization. Orthotopic small-bowel transplantation was performed in Lewis (LEW) rats as recipients of either Brown-Norway (BN) allografts or LEW syngeneic grafts. Allograft recipients received FK 506 either as a short course (2 mg/kg on Day 0-4 after transplantation) or continuously (2 mg/kg Day 0-4, then 0.5 mg/kg weekly). Ileal mucosa was harvested from small bowel grafts 9 and 60 days after transplantation and mounted in the Ussing Cell containing Hanks' balanced salt solution with/without L-glutamine (20 mM). Transmembrane potential difference (PD), which represents mucosal active ion transport, and mucosal resistance, an index of membrane integrity, were recorded. Nine days after transplantation, mucosal PD was the same in the ileum from syngeneic grafts, allografts treated with FK 506 and normal LEW and BN rats, and the addition of glutamine increased PD equally in all groups. In comparison, PD was markedly decreased in allografts undergoing rejection, and the glutamine response was blunted. Sixty days after transplantation, mucosal PD was reduced in allografts treated with a short course of FK 506, but normal in allografts receiving continuous immunosuppression with FK 506 and in syngeneic grafts. A decrease of mucosal resistance was not a feature of rejection nor a sequel of limited FK 506 therapy. Our data indicate that allograft rejection results in a significant decrease in mucosal PD and a poor response to glutamine. Control of rejection by FK 506 preserves normal electrophysiologic responses of the allograft mucosa.

Unique characteristics of the neonatal intestinal mucosal barrier.

The purpose of this study was to compare the newborn and weanling intestinal mucosa to determine differences in: (1) the electrophysiologic characteristics of the mucosal barrier; (2) the effects of glutamine supplementation on these physiological characteristics; and (3) transmucosal bacterial passage. The Ussing chamber was used to study ileal mucosa from newborn (1 to 4 days old) and weanling (21 days old) piglets. After the seromuscularis was stripped off the bowel wall, the mucosa was mounted in the chamber and perfused with Hanks Balanced Salt Solution (HBSS) or HBSS + 20 mmol/L of glutamine. Following initial stabilization, potential difference (PD) and resistance (R) were measured at 30-minute intervals for 2 hours. Transmucosal bacterial passage was measured by quantitative cultures of the mucosal and serosal reservoirs obtained 2 hours after adding 10(8) E coli C-25 to the mucosal reservoir. Six groups of membranes were studied: (1) newborn and HBSS; (2) weanling and HBSS; (3) newborn and HBSS + glutamine; (4) weanling and HBSS + glutamine; (5) newborn - HBSS + glutamine + E coli; and (6) weanling - HBSS + glutamine + E coli. Newborn ileal mucosa had significantly lower PD and R compared with weanling at all time points. Glutamine led to a significant increase in PD in both newborn and weanling. Newborn mucosa had a significantly increased incidence of transmucosal bacterial passage (4/7) compared with weanling (0/10). These findings suggest that: (1) newborn mucosal barrier has uniquely different electrophysiologic characteristics; (2) glutamine improves the metabolic activity as measured by PD in both newborn and weanling; and (3) the newborn mucosal barrier allows increased transmucosal passage of bacteria.