Biomedical subjects

T F Tracy

Publications and source records attributed to T F Tracy.

At least 19 recordsLinked to original sources

PubMed2000

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.

Animals↗

PubMed2000

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.

Adult↗

PubMed1999

Intra-uterine growth restriction differentially regulates perinatal brain and skeletal muscle glucose transporters.

Employing Western blot analysis, we investigated the effect of maternal uterine artery ligation causing uteroplacental insufficiency with asymmetrical intrauterine growth restriction (IUGR) upon fetal (22d) and postnatal (1d, 7d, 14d and 21d) brain (Glut 1 and Glut 3) and skeletal muscle (Glut 1 and Glut 4) glucose transporter protein concentrations. IUGR was associated with a approximately 42% decline in fetal plasma glucose (p<0.05) and a approximately 25% decrease in fetal body weights (p<0.05) with no change in brain weights when compared to the sham operated controls (SHAM). In addition, IUGR caused a approximately 45% increase in fetal brain Glut 1 (55 kDa) with no change in Glut 3 (50 kDa) protein concentrations. This fetal brain Glut 1 change persisted, though marginal, through postnatal suckling stages of development (1d-21d), with no concomitant change in brain Glut 3 levels at day 1. In contrast, in the absence of a change in fetal skeletal muscle Glut 1 levels (48 kDa), a 70% increase was observed in the 1d IUGR with no concomitant change in either fetal or postnatal Glut 4 levels (45 kDa). The change in skeletal muscle Glut 1 levels normalized by d7 of age. We conclude that IUGR with hypoglycemia led to a compensatory increase in brain and skeletal muscle Glut 1 concentrations with a change in the brain preceding that of the skeletal muscle. Since Glut 1 is the isoform of proliferating cells, fetal brain weight changes were not as pronounced as the decline in somatic weight. The increase in Glut 1 may be protective against glucose deprivation in proliferating fetal brain cells and postnatal skeletal myocytes which exhibit 'catch-up growth', thereby preserving the specialized function mediated by Glut 3 and Glut 4 towards maintaining the intracellular glucose milieu.

Aging↗

PubMed1999

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.

Adolescent↗

PubMed1999

The impact of intraoperative culture on treatment and outcome in children with perforated appendicitis.

BACKGROUND: Most protocols for the operative treatment of perforated appendicitis use a routine culture. Although isolated studies suggest that routine culture may not be necessary, these recommendations generally are not based on objective outcome data. METHODS: The authors reviewed the records of 308 children who underwent operative treatment for perforated appendicitis between 1988 and 1998 to determine if information gained from routine culture changes the management or improves outcome. Inclusion criteria included either gross or microscopic evidence of appendiceal perforation. RESULTS: Mean patient age was 7.5 years, 51% were boys, and there was no mortality. The majority of children (96%) underwent culture that was positive for either aerobes (21%), anaerobes (19%), or both (57%). Antibiotics were changed in only 16% of the patients in response to culture results. The use of empiric antibiotics, as compared with modified antibiotics, was associated with a lower incidence of infectious complication, shorter fever duration, and decreased length of hospitalization. We also investigated the relationship between culture isolates and antibiotic regimens with regard to outcome. The utilization of antibiotics suitable for the respective culture isolate or organism sensitivity was associated with an increased incidence of infectious complication and longer duration of both fever and length of hospitalization. Finally, the initial culture correlated poorly with subsequent intraabdominal culture (positive predictive value, 11%). CONCLUSION: These outcome data strongly suggest that the practice of obtaining routine cultures can be abandoned, and empiric broad spectrum antibiotic coverage directed at likely organisms is completely adequate for treatment of perforated appendicitis in children.

Adolescent↗

PubMed1999

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.

Accidents, Home↗

PubMed1998

Perforated appendicitis in children: risk factors for the development of complications.

BACKGROUND: Many aspects of the management of perforated appendicitis in children remain controversial. The objective of this study was to define risk factors associated with the development of postoperative complications in children undergoing treatment for perforated appendicitis. METHODS: We reviewed all children (age < 16 years) who were treated for perforated appendicitis at Cardinal Glennon Children's Hospital between 1988 and 1997. Inclusion criteria included either gross or microscopic evidence of appendiceal perforation. RESULTS: Of 285 children with perforated appendicitis, 279 underwent immediate operative treatment. Mean patient age was 7.7 years and there were no deaths. Major postoperative complications included intra-abdominal abscess (n = 17), ileus (n = 7), mechanical intestinal obstruction (n = 6), and wound infection (n = 4). All children who had a postoperative abscess had more than 5 days of symptoms before operation. Within this subgroup, drain placement was associated with not only decreased postoperative abscess formation and but also shorter duration of fever and length of hospitalization. The incidence of mechanical obstruction or ileus was not increased and the rate of wound infection was actually lower after drainage. CONCLUSIONS: Drain placement appears to be helpful in children with late diagnosis but is of little benefit when the duration of symptoms is less than 5 days. Thus it is likely that drains are most useful in patients with well-established and localized abscess cavities.

Abdominal Abscess↗

PubMed1998

Cholestatic liver injury increases circulating TNF-alpha and IL-6 and mortality after Escherichia coli endotoxemia.

We employed a bile duct ligation (BDL) model of cholestatic liver injury to test the hypothesis that this form of preexisting hepatic dysfunction alters the kinetics of circulating TNF-alpha and IL-6 after Escherichia coli endotoxemia, thereby augmenting mortality and lung injury by a TNF-alpha:leukotriene (LT) axis of inflammation. Male rats were catheterized 13 d after BDL or sham surgery and studied while awake 18 to 24 h later. Cholestasis after BDL was confirmed by baseline serum bilirubin (BDL = 7.34 +/- 0.72 mg/dl, mean +/- SEM, n = 17 versus Sham = 0.25 +/- 0.07, n = 20; p < 0.005) and histopathology. Sham and BDL animals received E. coli lipopolysaccharide serotype O55:B5 (LPS, 5 mg/kg i.v.) or 0.9% NaCl (NS) ending at t = 0 and were monitored over 24 h for vital signs and hemodynamics. In parallel studies, lipoxygenase inhibition was performed using diethylcarbamazine or the 5-lipoxygenase activating-protein inhibitor MK-886. Blood was collected at baseline and at t = 1.5, 3.5, and 24 h for formed elements and for serum endotoxin, TNF-alpha, IL-6, bilirubin, and alanine aminotransferase (ALT). Organs were evaluated at 24 h for histopathology, including neutrophil (PMN) densities and wet/dry weight (W/D) ratios. Cholestasis reduced survival after otherwise nonlethal endotoxemia, with seven of 11 BDL + LPS rats dying within 24 h versus no deaths in BDL + NS (n = 6), Sham + LPS (n = 14), or Sham + NS (n = 6) animals (p < 0.01). Despite equivalent serum endotoxin between groups, circulating TNF-alpha was 8-fold higher in BDL + LPS than in Sham + LPS rats at 1.5 and 3.5 h (p < 0.001), whereas serum TNF-alpha did not differ between BDL + NS and Sham + NS rats. IL-6 likewise was increased differentially by 1.5 h in BDL + LPS animals (11.98 +/- 2.42 ng/ml) versus Sham + LPS rats (3.05 +/- 0.58 ng/ml, p < 0.05). Hypothermia, bradycardic hypotension, and leukopenia were most severe and prolonged in BDL + LPS rats, which also had significantly higher ALT values, W/D ratios, and organ PMN counts. LT inhibition failed to reduce BDL-related differences in serum cytokines or survival after endotoxemia. Thus, cholestasis augments inflammatory responses to gram-negative endotoxemia, sensitizing the host to enhanced fluid flux in multiple organs and to mortality by a LT-independent mechanism.

Alanine Transaminase↗

PubMed1998

Gadolinium chloride suppresses hepatic oval cell proliferation in rats with biliary obstruction.

Liver injury due to bile duct ligation (BDL) is histologically characterized by cholestasis, bile ductular proliferation, hepatocellular damage, portal fibrosis, and ultimately biliary cirrhosis. Stem cells within the liver may act as progenitor cells for small epithelial cells termed oval cells that can differentiate into bile duct cells or hepatocytes, whereas myofibroblasts are the principal source of collagen production in fibrosis. The aims of this study were to determine 1) whether BDL induces oval cell proliferation and 2) whether blockade of Kupffer cells affects oval cell proliferation, bile duct proliferation, and myofibroblast transformation in experimental biliary obstruction. Male Sprague-Dawley rats were divided into two groups to receive either a single dose of gadolinium chloride (a selective Kupffer cell blocking agent) or vehicle. One day later, the gadolinium- and vehicle-treated groups were further subdivided to receive either BDL or sham operation. The rats were sacrificed on day 7 postoperatively. Serum was collected for measurement of aspartate aminotransferase, gamma-glutamyl transpeptidase, and bilirubin levels. Liver tissue was taken for evaluation of fibrosis, bile ductular cells, oval cells, and myofibroblasts. BDL resulted in elevated aspartate aminotransferase, gamma-glutamyl transpeptidase, and bilirubin in serum, and gadolinium pretreatment did not modify these effects. BDL induced marked oval cell proliferation, which was completely prevented by gadolinium pretreatment. Gadolinium did not affect the induction of bile duct expansion or myofibroblasts after BDL. We conclude that experimental biliary obstruction induces oval cell proliferation, which can be prevented by gadolinium pretreatment. This suggests that bile ductular proliferation and myofibroblast transformation are not mediated by Kupffer cells and that ductular proliferation can proceed in the absence of oval cells. Alternatively, gadolinium may directly affect oval cell proliferation after BDL.

Animals↗

PubMed1997

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.

Adolescent↗

PubMed1997

NF-kappaB activation and modulation in hepatic macrophages during cholestatic injury.

Cholestatic liver injury induces an inflammatory response that follows the activation of hepatic macrophages. Constitutive activation of the transcription factor, NF-kappaB, was found in these macrophages over the course of hepatic injury. Since NF-kappaB activation has been shown to have a key role in the inflammatory process, the modulatory effects of the antioxidant, alpha-tocopherol succinate, and the glucocorticoid, dexamethasone, on NF-kappaB activation were examined in this study. Male Sprague Dawley rats underwent 2-7 days of common bile duct division and ligation (CBDL) or sham laparotomy. Hepatic macrophages were isolated by collagenase Pronase perfusion and purified by centrifugal elutriation. Activation was determined by electrophoretic mobility shift assay and ELISA. We determined that NF-kappaB activation in injured hepatic macrophages could only be inhibited by dexamethasone. Dexamethasone-mediated inhibition of NF-kappaB activation required the synthesis of a regulatory protein since cycloheximide-treated cells were resistant to its effects. Furthermore, dexamethasone-treated hepatic macrophages showed elevated steady-state levels of IkappaB-alpha mRNA, suggesting the role of IkappaB-alpha as a potential regulatory mediator. Consistent with constitutive transcriptional activation we showed constitutive secretion of TNF-alpha from injured hepatic macrophages which could be inhibited by dexamethasone. These data show for the first time, in a biologically significant model of hepatic injury, constitutive activation of the key inflammatory transcription factor NF-kappaB and cytokine TNF-alpha. These results support an approach focused on the NF-kappaB/IkappaB-alpha pathway as a critical target for therapeutic intervention during hepatic injury, and the consideration of possible steroid-based therapies.

Analysis of Variance↗

PubMed1996

Cholestatic liver injury down-regulates hepatic glutathione synthesis.

Hepatocellular injury caused by cholestasis may be caused in part by oxidant stress. The purpose of this study was to establish how acute cholestasis might alter hepatic glutathione homeostasis and to determine whether injured hepatocytes are capable of reverting to normal glutathione homeostatic mechanisms. Acute cholestasis was achieved by surgical ligation of the common bile duct in rats. Bile duct ligation induced a 3.7-fold increase in hepatic glutathione content over 4 days. This increase was not due to increased hepatic activity of gamma-glutamylcysteine synthetase (GCS); on the contrary, whole-liver GCS activity was substantially diminished in the bile duct-ligated liver to 34 and 11% of normal after 4 and 7 days, respectively. To determine if hepatocytes removed from the cholestatic environment maintained these changes in glutathione homeostasis, hepatocytes were isolated from bile ductligated livers and established in primary culture. In cells isolated after 4 days of bile duct ligation, the elevated hepatocyte glutathione content decreased and the low GCS activity increased over 2 days in culture. More importantly, the ability of postcholestatic hepatocytes to substantially increase their glutathione synthetic capacity by increasing GCS activity in response to stress was preserved. This compensatory increase was due primarily to new protein synthesis. Together, these observations suggest that acute cholestasis impairs the ability of the liver to synthesize glutathione by down-regulating the key regulatory enzyme for its synthesis in response to acutely elevated glutathione levels and that the impaired glutathione synthetic capacity is corrected after cells are removed from the cholestatic environment.

Animals↗

PubMed1996

Critical analysis of the operative treatment of Hirschsprung's disease.

OBJECTIVE: To critically analyze complications and long-term results of the operative treatment of Hirschsprung's disease. DESIGN: Medical records of patients with Hirschsprung's disease were reviewed retrospectively. Follow-up was obtained using a standardized telephone questionnaire. SETTING: Major pediatric referral center. PATIENTS: Eighty-two infants and children (68 boys, 14 girls) were treated for Hirschsprung's disease during a 20-year period (1975 to 1994). The age at diagnosis was younger than 30 days in 47 neonates (57%), 30 days to 1 year in 22 infants (27%), and older than 1 year in 13 children (16%). Aganglionosis was limited to the rectosigmoid region in 66 patients (81%). Fifty-five Soave (endorectal) and 27 Duhamel (retrorectal) primary pull-through operations were performed. MAIN OUTCOME MEASURES: Postoperative complications, reoperations, hospitalization, and current bowel habits. RESULTS: Eighteen children (67%) undergoing the Duhamel operation recovered uneventfully compared with 33 children (60%) undergoing the Soave operation. The complications following the Duhamel operation included enterocolitis in five cases (19%), rectal achalasia in four cases (15%), and persistent rectal septum in two cases (7%). Additional operations, which included myomectomy, rectal septum division, diverting enterostomy, and sphincterotomy, were required in seven patients (26%). Only one patient required more than one reoperation. In contrast, complications following the Soave operation included enterocolitis in 15 cases (27%), rectal stenosis in 12 (22%), anastomotic leak in four (7%), late perirectal fistula in three (5%), rectal prolapse in one (2%), and recurrent severe constipation in one (2%). Sixteen patients (29%) required additional operations, including diverting enterostomy, myomectomy, redo pull-through, sphincterotomy, fistulectomy, and revision of rectal prolapse. In this group nearly two reoperative procedures per patient were required. Telephone follow-up (mean, 89.3 months) after pull-through operations in 61 patients (74%) showed a mean of 2.8 stools per day, with 13 patients (21%) requiring daily medications. CONCLUSIONS: The most common operations (Soave and Duhamel) for Hirschsprung's disease result in an uneventful recovery in only 60% to 67% of patients. Although both Soave and Duhamel pull-through operations have nearly identical reoperation rates (26% vs 29%), complications after Soave pull-through operations often require multiple, more extensive procedures. Short-term total continence rates for both procedures are less than 50%, however, 100% became continent by 15 years after the pull-through procedure. Further refinement in operative technique and close follow-up are warranted.

Anastomosis, Surgical↗

PubMed1996

The inflammatory response in pediatric biliary disease: macrophage phenotype and distribution.

PURPOSE: Extrahepatic biliary obstruction in infants and children leads to ductal hyperplasia and portal fibrosis. Inflammatory mediators responsible for increased cellular proliferation and matrix deposition are hypothesized to result from the intrahepatic recruitment and activation of lymphocytes and macrophages (M phi). The authors previously showed components of this mechanism in studies that demonstrated increased adhesion molecule expression in biliary atresia, as well as evidence of altered hepatic M phi function during the course of experimental cholestatic liver injury. Therefore they sought determine the expression of macrophage receptor markers CD68 and CD14 in pediatric biliary disease. METHODS: Sixteen liver specimens were snap-frozen and cryosectioned onto polylysine-coated slides. Sections were stained with murine monoclonal antibodies to CD68 (resident M phi) and CD14 (monocyte-M phi lipopolysaccharide [LPS] receptor) glycoproteins. The sections were analyzed using a semiquantitative scale of proliferation and were position-graded from 0 to 3 (maximal). RESULTS: Blinded analysis showed that marked proliferation of CD68-positive cells occurred in five of the six patients with biliary atresia (BA) and in one patient who had severe cholestasis. Normal perisinusoidal liver M phi were found in specimens from patients with hepatitis (2), choledochal cyst (1), and congenital hepatic fibrosis (1). Similarly, expression of CD14 periportal M phi was found only in patients with BA or cholestasis (1.9 +/- 0.3 [mean +/- SEM]) and was absent in other diseases. Strong sinusoidal expression of CD14 was evident in all patients who had extrahepatic biliary obstruction. An early biopsy specimen from a premature infant with BA did not show cholestasis, fibrosis, CD68 Mø proliferation, or CD14 expression; however, another biopsy specimen, obtained further in the course of jaundice showed the progressive development of all features. CONCLUSION: These findings suggest proliferation of resident M phi in association with cholestasis. The presence of the LPS receptor on periportal cells during cholestatic liver injury points to a potential source of cytokines responsible for the inflammatory reaction of biliary atresia.

Antigens, CD↗

PubMed1996

Delayed rupture of the abdominal aorta in a child after a suspected handlebar injury.

Blunt abdominal trauma resulting in a laceration of the abdominal aorta is extremely rare. Only one previous example of this injury has been reported in a child. We present the clinical course and surgical management of blunt disruption of the infrarenal aorta in a 13-year-old boy with a subsequent delayed rupture of a third aortic laceration. This is the youngest patient to die from this type of injury after blunt abdominal trauma.

Abdominal Injuries↗

PubMed1996

Alterations in tumor necrosis factor-alpha expression by hepatic macrophages following acute cholestatic liver injury.

The liver is unique for its large resident macrophage (HM phi) population as a potential source of immunoregulatory cytokines. The present study was designed to determine HM phi function in a rat model of cholestasis (CBDL). Northern blot analysis of TNF-alpha mRNA showed a profound difference in the dose response to bacterial lipopolysaccharide (LPS) between sham and CBDL HM phi. Sham HM phi demonstrated an 8-fold difference in induction of TNF-alpha mRNA versus CBDL HM phi. TNF-alpha secretion, determined by enzyme-linked immunosorbent assay, was significantly higher from LPS-activated sham HM phi versus the same cells activated with Gram-positive bacterial peptidoglycan while CBDL HM phi were more responsive to peptidoglycan than to LPS. These results demonstrate stimulus- and response-specific functional alterations in the HM phi population during acute cholestatic injury. We speculate that these functional alterations are phenotypically induced in acute liver injury resulting in responses that are not characteristic of normal HM phi.

Acute Disease↗

PubMed1996

Lipopolysaccharide and tumor necrosis factor-alpha synergy potentiate serum-dependent responses of rat macrophages.

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are major mediators of sepsis and multiple organ failure. Serum-mediated macrophage activation requires lipopolysaccharide (LPS) and its serum binding protein, lipopolysaccharide binding protein as a ligand for the receptor CD14. This study was designed to determine whether cytokines participate in regulation of serum-mediated LPS activation. Rat macrophages were stimulated with LPS with and-without TNF-alpha or IL-1 beta and activation was determined by detection of TNF-alpha by specific enzyme-linked immunosorbent assay or TNF-alpha mRNA by Northern blot analysis. The addition of TNF-alpha but not IL-1 beta, in the presence of serum, leads to potentiation of macrophage activation after LPS stimulation. This effect could be specifically inhibited by neutralization of LPS with polymyxin B or an antibody against TNF-alpha. This study shows that LPS and TNF-alpha synergize to potentiate serum-mediated macrophage activation. These results demonstrate another element of the control mechanism of cytokine secretion following macrophage activation in sepsis.

Animals↗

PubMed1996

Molecular and cellular control points in pediatric liver injury and repair.

Several exciting areas of cellular and molecular biology of the liver have led to a better understanding of the mechanisms of pediatric liver injury and repair. Soon these advances will lead to treatment options for specialized areas of pediatric hepatology. Most of the current goals of surgical therapy lead to either successful hepatic resection for tumors or biliary decompression for atresia. We have come to accept the unfortunate fact that ongoing chronic liver disease ultimately leads to replacement by transplantation. The purpose of this article is to demonstrate areas of recent basic science advancement, directly related to pediatric liver disease, that may provide opportunities and new strategies to obviate the progression from early injury to end-stage liver disease or to augment repair of the injured liver.

Biliary Atresia↗