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Biomedical subjects

B W Warner

Publications and source records attributed to B W Warner.

At least 55 records · Page 3Linked to original sources

Intestinal adaptation is enhanced by epidermal growth factor independent of increased ileal epidermal growth factor receptor expression.

BACKGROUND/PURPOSE: Intestinal adaptation after massive small bowel resection (SBR) is augmented by epidermal growth factor (EGF) via an unknown mechanism. We recently have observed that EGF increases the expression of EGF receptor mRNA and protein content in the remnant ileum after SBR. The purpose of this study was to determine whether the magnitude of EGF-induced receptor expression correlates with intestinal adaptation. METHODS: A 50% proximal SBR or sham operation (bowel transection with reanastomosis) was performed on male ICR mice. Animals from each group were then selected randomly to receive either human recombinant EGF (150 microg/kg/d) or saline by twice daily intraperitoneal injections. The remnant ileum was harvested at 1 week, and parameters of adaptation measured as changes in protein content. Ileal EGF receptor mRNA was quantitated using a ribonuclease protection assay. Changes in the expression ileal EGF receptor protein were determined by Western blot after immunoprecipitation. Comparisons of mean values between groups was performed using analysis of variance (ANOVA) and a P value of less than .05 was considered significant. Values are presented as mean +/- SEM. RESULTS: EGF was mitogenic to the ileum after sham operation as monitored by increases in ileal protein content (2.21 +/- 0.002 mg/cm Sham v 2.97 +/- 0.25 mg/cm Sham +/- EGF; P < .05). After SBR, adaptation resulted in increased ileal protein content (4.45 +/- 0.27 mg/cm), which was substantially boosted by EGF (5.98 +/- 0.39 mg/cm; P < .05). No differences were detected in ileal EGF receptor mRNA or protein expression between Sham or SBR groups that did not receive EGF. However, EGF significantly enhanced the expression of ileal EGF receptor mRNA to an equal extent after both sham and SBR (approximately threefold). The magnitude of this increase in EGF receptor protein (four- to sixfold) was similar in both EGF groups as shown by Western blotting. CONCLUSIONS: Changes in ileal EGF receptor expression are not mandatory for adaptation to occur. EGF upregulates the expression of mRNA and protein for its own intestinal receptor in vivo. Because EGF-induced receptor expression was comparable after both SBR and Sham operation, the beneficial effect of EGF during adaptation is likely caused by other factors in addition to increased receptor expression.

Adaptation, Physiological↗

A multicenter trial of 6-aminocaproic acid (Amicar) in the prevention of bleeding in infants on ECMO.

BACKGROUND/PURPOSE: Intracranial hemorrhage (ICH), is a major source of morbidity and the leading cause of death in neonates treated with extracorporeal membrane oxygenation (ECMO). Anecdotal reports have suggested that epsilon-aminocaproic acid (EACA) can decrease the risk of ICH. The purpose of this study was to evaluate, in a multiinstitutional, prospective, randomized, blinded fashion, the effect of EACA on the incidence of hemorrhagic complications in neonates receiving ECMO. METHODS: All neonates (except congenital diaphragmatic hernia) who met criteria for ECMO at three institutions were eligible for enrollment. EACA (100 mg/kg) or placebo was given at the time of cannulation followed by 25 mg/kg/h for 72 hours. Bleeding complications, transfusion requirements, and thrombotic complications were recorded. Post-ECMO imaging included head ultrasound scan computed tomography (CT) scan, and duplex ultrasound scan of the inferior vena cava and renal vessels. RESULTS: Twenty-nine neonates were enrolled (EACA, 13 and placebo, 16). Five (17.2%) patients had a significant (grade 3 or larger) ICH. There was no statistical difference in the incidence of significant ICH in patients who received EACA (23%) versus placebo (12.5%). Septic patients accounted for all of the ICH in the EACA group. Thrombotic complications (aortic thrombus and SVC syndrome) developed in two patients from the placebo group. There was no difference in thrombotic circuit complications between groups. CONCLUSIONS: Our results suggest that the use of EACA in neonates receiving ECMO is safe but may not decrease the overall incidence of hemorrhagic complications.

Aminocaproic Acid↗

Ovarian cysts in the pediatric population.

With the widespread availability and use of pelvic sonography, the rate at which ovarian cysts are detected in the pediatric population has increased, and such cysts are an important problem encountered in pediatric surgical practice. Rational management should take into account key factors such as symptoms, patient age, menarchal status, cysts size, and character, as well as associated medical conditions. The purpose of this review is to discuss the incidence and pathophysiology of ovarian cysts in children. A management strategy is presented based on the above-mentioned key factors.

Adolescent↗

Adaptation after small bowel resection is attenuated by sialoadenectomy: the role for endogenous epidermal growth factor.

BACKGROUND: Epidermal growth factor (EGF) is likely involved during adaptation after small bowel resection (SBR) because some studies have shown enhanced adaptation by EGF administration. Because the major source of endogenous EGF in mice is the submandibular glands, we sought to determine the effect of submandibular gland excision (SAL) and luminal or systemic EGF replacement on adaptation after SBR. METHODS: A 50% proximal SBR or Sham-SBR (bowel transection and reanastomosis) was performed on male C57BL/6 mice after either SAL or gland mobilization only. Additional mice underwent both SBR and SAL and then received daily EGF or saline solution by intraperitoneal or orogastric administration. At 1 week, adaptation was characterized in the ileum as changes in villus height, DNA, and protein content. RESULTS: SAL significantly attenuated the increase in ileal villus height, total protein, and DNA content after SBR. Both systemic and oral EGF reversed these findings equally and significantly augmented all parameters of intestinal adaptation after SAL. CONCLUSIONS: Submandibular EGF is important for the adaptive response to massive SBR. As both luminal and systemic EGF equally reversed the findings following SAL and SBR, the specific site of action for endogenous EGF during adaptation is either the luminal or basolateral surface of the enterocyte.

Adaptation, Physiological↗

Epidermal growth factor receptor expression following small bowel resection.

BACKGROUND: Adaptation following massive small bowel resection (SBR) is an important compensatory response. While epidermal growth factor (EGF) has been shown to augment this response, the mechanism and role of EGF and its intestinal receptor (EGF-R) during adaptation are not known. The purpose of this study was to determine the effect of massive SBR and adaptation on intestinal expression of EGF-R. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent either a 75% mid-SBR with primary reanastomosis or sham operation (bowel transection with reanastomosis). Ileal mucosa was harvested from animals of each group at 6 and 12 hr, 1, 3, and 5 days, and 1, 2, and 4 weeks after operation. Expression of EGF-R protein was studied by Western blotting. Expression of EGF-R mRNA was determined by quantitative reverse-transcriptase polymerase chain reactions normalized to beta-actin. RESULTS: When compared with sham, SBR resulted in a modest (32%) increase in the expression of EGF-R mRNA at 1 week (P < 0.003). A twofold greater expression of EGF-R protein corresponded to this time point. While not statistically significant, expression of EGF-R mRNA was slightly greater after SBR at every other time point measured. CONCLUSION: Following massive SBR, expression of both EGF-R mRNA and protein is slightly increased in the ileum with a more pronounced increase in protein. These findings, which have not previously been reported, suggest that changes in EGF-R signaling may not play a major role during the initiation and or progression of intestinal adaptation following massive SBR.

Animals↗

A defective EGF-receptor in waved-2 mice attenuates intestinal adaptation.

While the pathophysiology of intestinal adaptation following small bowel resection (SBR) is not well understood, there is evidence to suggest an important role for epidermal growth factor (EGF) in this process. In waved-2 mice, a naturally occurring mutation results in reduced EGF receptor protein tyrosine kinase activity. We tested the hypothesis that an intact EGF receptor is essential for adaptation by subjecting this strain of mice to SBR. A 50% proximal SBR or sham operation (bowel transection with reanastomosis only) was performed in waved-2, heterozygous, and wildtype mice. After 3 days, adaptation was characterized in the remnant ileum as changes in DNA and protein content per unit length. Villus height and crypt depth were measured, and crypt cell proliferation rates were determined by the percentage of crypt cells taking up 5-bromodeoxyuridine. Following sham surgery, all mice regained their preoperative weight by the third postoperative day. After SBR, all mice gained weight while the waved-2 mice did not. Ileal DNA and protein significantly increased after SBR in wild-type and heterozygous mice while these parameters were unchanged in the waved-2 mice. Villus height and crypt cell proliferation increased in response to SBR in all groups; however, the changes were less pronounced in the waved-2 mice. Adaptation after SBR is impaired in waved-2 mice. Signal transduction by the EGF receptor is a critical component of this response. These data endorse a crucial role for EGF and its receptor in the pathogenesis of intestinal adaptation.

Adaptation, Physiological↗

Extracorporeal life support for the treatment of viral pneumonia: collective experience from the ELSO registry. Extracorporeal Life Support Organization.

UNLABELLED: Viral pneumonia is the most common indication for pediatric extracorporeal life support (ECLS). Despite this fact, no previous studies have directly stratified patient outcome according to viral etiology. METHODS: Using the Extracorporeal Life Support Organization (ELSO) registry database, the authors reviewed the national experience of patients undergoing ECLS with culture or serologically demonstrated viral pneumonia and compared outcome parameters according to viral etiology. RESULTS: Patients differed with respect to age and weight according to the viral type. Patients with respiratory syncytial virus (RSV, median age 3 months), herpes simplex virus (HSV, 0.13 months), cytomegalovirus (CMV, 2.5 months), and adenovirus (0.6 months) were younger than those with other viruses (5.5 months). The patient groups did not significantly differ with respect to pre-ECLS Pao2 mean airway pressure (MAP), oxygenation index (OI), mode, or duration of ECLS. The overall survival of patients with viral pneumonia was 57%, although patients with RSV or CMV were found to have a 67% survival. Patients infected with HSV and adenovirus had a significantly lower survival rate (31% and 25%, respectively) when compared with those with RSV. In addition RSV pneumonia was associated with fewer cardiovascular complications than several of the other viral types. When comparison was made between survivors and nonsurvivors, a higher last pre-ECLS MAP and increased incidence of elevated creatinine and renal failure requiring dialysis were noted among nonsurvivors. CONCLUSION: ECLS remains an important modality in the treatment of neonatal and pediatric patients with respiratory failure secondary to viral pneumonia. The survival rate of these patients varies according to the type of viral infection.

Adenovirus Infections, Human↗

Liver hemorrhage during laparotomy in patients with necrotizing enterocolitis.

UNLABELLED: Major liver hemorrhage (LH) without obvious iatrogenic injury was recently observed in several patients during operation for necrotizing enterocolitis (NEC). The purpose of this study was to determine the incidence and risk factors associated with the development of LH in patients with NEC. METHODS: The hospital charts of patients with NEC who underwent surgical exploration during a 5-year period (1989-1994) were reviewed. The patients in whom LH developed without obvious significant iatrogenic liver injury were compared with those who did not have LH. RESULTS: Eight of the 68 patients reviewed had LH. The survival rate for those with LH was 13%, compared with 88% for those without LH (P < .001). The patients with LH had a younger gestational age (28 +/- 3 weeks v 32 +/- 5 weeks) and a lower birth weight (1,262 +/- 489 g v 1,649 +/- 666 g); however, the differences were not significant. The patients with LH had significantly lower preoperative mean arterial blood pressure (35 +/- 1 mm Hg v 46 +/- 3 mm Hg; P < .001) and required greater fluid intake (272 +/- 28 mL/kg/d v 186 +/- 9 mL/kg/d; P < .01) for the 24 hours preceding surgery. CONCLUSION: LH is as an important and lethal complication associated with laparotomy in very small infants with NEC. The presence of hypotension and the administration of large amounts of volume in the preoperative period appear to be risk factors. Earlier surgical intervention and restoration of blood pressure using inotropic agents, once a particular level of fluid administration has been achieved, my be preventive.

Birth Weight↗

Pulmonary hemorrhage: a novel complication after extracorporeal life support.

Pulmonary hemorrhage (PH) occurs infrequently as a complication in neonates with respiratory failure. Major PH has been observed at the authors' institution in several neonates after "successful" completion of extracorporeal life support (ECLS) therapy. The authors sought to determine the incidence of PH and the risk factors associated with this unique and newly described morbidity after ECLS. The hospital records of all patients who had PH after ECLS were reviewed. The control patients were the first three infants who underwent ECLS just before each PH case. PH was defined as the occurrence of bloody tracheal secretions associated with a deterioration in pulmonary status. Demographics, ventilator/ECLS parameters, fluid management, coagulation, and laboratory studies were evaluated in the pre-ECLS, during ECLS, and in the post-ECLS period. From 1985 to 1993, 13 (6%) of 214 neonates suffered major PH, at a mean time of 43.2 +/- 9.2 hours after the ECLS course. The overall mortality rate for children with PH was 38%, compared with 5% among the control patients. In the pre-ECLS phase, patients with PH required more fluid (153.6 +/- 20.2 mL/kg/d v 106.8 +/- 10.2 mL/kg/d) and were acidemic for a longer period (2.3 +/- 1.2 hours v 0.6 +/- 0.2 hours; pH < 7.25). No differences were noted in AaDo2 or oxygenation index criteria. During ECLS, inotropes were required more often (23% v 0%; P < .01) because hypotension was more common (77% v 33%; P < .05). Activated clotting times (ACT) and heparin requirements were equivalent for the two groups. After ECLS the patients with PH required longer ventilatory assistance (184.9 +/- 48.2 hours v 83.4 +/- 16.7 hours) and supplemental oxygen (24.3 +/- 3.0 days v 17.2 +/- 1.9 days). No coagulation abnormalities were identified at the time of PH. Higher SGPT (185.4 +/- 146.4 U/L v 22.6 +/- 3.5 U/L; P < .05) and BUN (69.3 +/- 7.5 mg/dL v 47.2 +/- 5.9 mg/dL; P < .05) also were noted for the patients with PH. PH represents an important and novel morbidity in neonates after ECLS. Prolonged acidosis, a high fluid requirement before ECLS, the need for blood pressure support during ECLS, and evidence of renal and/or hepatic dysfunction serve to identify patients who have a high risk for the development of this complication.

Acidosis↗

Wilms tumor.

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Child↗

A randomized, prospective trial of standard Hickman compared with Groshong central venous catheters in pediatric oncology patients.

BACKGROUND: Safe and reliable central venous access is critical in the management of children with cancer. A recently described valved catheter (Groshong) requires less frequent flushing to preserve catheter patency, theoretically reducing daily care costs for the catheter as well as lessening the risk of mechanical or infectious complications. This study compared standard Hickman to Groshong catheters in a group of pediatric oncology patients. STUDY DESIGN: From December 1992 to May 5, 1994, 20 consecutive pediatric oncology patients were randomized by medical record number to receive either a standard dual lumen Hickman (7F) or Groshong (9.5F) catheter. All patients were prospectively followed on a weekly basis and a log was maintained regarding complications and cost of maintenance of the catheter until it was removed. RESULTS: Ten patients received Groshong catheters and ten received Hickman catheters. Total catheter days for each group were similar (Hickman, 2,599 compared with Groshong, 2,389 days). Five Groshong catheters required removal because of mechanical complications and several required daily flushes because of blood backing up into the catheter lumen. When taking into account the cost of associated complications, no differences were noted in daily cost for maintenance between the two catheters. CONCLUSIONS: When considering the cost of complications, Groshong catheters were no less expensive to maintain compared with standard Hickman catheters. Furthermore, Groshong catheters malfunctioned more frequently and required a greater number of urokinase instillations for withdrawal occlusion. The use of the Groshong catheter in pediatric oncology patients cannot be supported by the present study.

Catheterization, Central Venous↗

Intestinal adaptation following massive small bowel resection in the mouse.

BACKGROUND: Transgenic mice represent powerful tools for studying the role of genes and their expression under multiple conditions, and they may provide a unique model for studies of intestinal adaptation after massive small bowel resection (SBR). This study characterized a successful model for SBR and intestinal adaptation in the mouse. STUDY DESIGN: Sham operation (bowel transection with reanastomosis) or SBR was performed on male C57BL/6 mice. A solid or liquid diet, various sizes of monofilament suture for the anastomosis, and resection of 50 or 75 percent of the proximal small intestine were studied. In other studies, intestinal adaptation was characterized as changes in intestinal wet weight, DNA, protein, villus height, crypt depth, and crypt cell proliferation rates at 12 hours, 24 hours, three days, and one, two, and four weeks after 50 percent SBR. RESULTS: Survival was significantly improved with a liquid diet (8 percent compared with 88 percent; p < .001) and modestly improved by using the smallest suture for anastomosis (60 percent for 7-0 compared with 88 percent for 9-0; p = not significant). Mice did not tolerate more than 50 percent SBR (16 percent survival rate for 75 percent SBR compared with 85 percent survival rate for 50 percent SBR; p < .01). Small bowel resection augmented ileal wet weight, DNA and protein content, villus height, crypt depth, and crypt-cell proliferation rates. CONCLUSIONS: Provision of a liquid diet, using a small suture for anastomosis, and resection of no more than 50 percent of the proximal small intestine are important for survival. This model will permit researchers using transgenic mice to better understand critical genes during intestinal adaptation after SBR.

Adaptation, Biological↗

Induction of gastroduodenal prolapse by antral heterotopic pancreas.

Ectopic pancreas is the most common congenital anomaly in the gastric antrum. In some patients, there is a distinct tendency for this lesion to produce intermittent crampy abdominal pain by provoking gastroduodenal prolapse. This condition should be considered after a more distal prolapse from intussusception is excluded. An upper gastrointestinal series performed during an episode of symptoms may be diagnostic of this entity.

Choristoma↗

The use of extracorporeal life support in pediatric burn patients with respiratory failure.

Respiratory failure is the most common cause of death after thermal injury and may be caused by inhalation injury, acute respiratory distress syndrome (ARDS) or pneumonia. ARDS is usually associated with sepsis; however, it may also occur during burn shock, especially in patients that have a delayed or inadequate fluid resuscitation. During the past 24 months, five pediatric burn patients underwent extracorporeal life support (ECLS) for respiratory failure unresponsive to optimal medical management. The mean age of the patients was 26 months (range, 8.5 to 48 months), with a mean burn size of 46% TBSA (> 95% third degree). The etiology of the respiratory failure included severe bronchospasm in a 22-month-old former premature infant with bronchopulmonary dysplasia; three patients with ARDS; and one patient with a severe inhalation injury. All five patients required greater than 56 cm H2O peak pressures and 100% FIO2 at the time of beginning ECLS. The oxygenation index (OI) ranged from 45 to 180. Three (60%) of the patients survived. In the three patients who ultimately survived, significant improvements in pulmonary and hemodynamic parameters occurred within 96 hours of ECLS. The two patients who died showed no improvement and were removed from ECLS at 10 and 11 days; both expired within hours. The patients who expired developed significant hemodynamic instability, coagulopathy, and hemorrhage from their burn wounds. The extent and degree of burn injury did not seem to alter the outcome. Indications for considering ECLS in the pediatric burn patient are unmanageable, life threatening pulmonary insufficiency in patients that undergo a relative short course of pre-ECLS ventilator support.(ABSTRACT TRUNCATED AT 250 WORDS)

Burns↗

Urinary nitrite and nitrate concentrations in patients with idiopathic persistent pulmonary hypertension of the newborn and effect of extracorporeal membrane oxygenation.

Persistent pulmonary hypertension of the newborn (PPHN) often requires extracorporeal membrane oxygenation (ECMO), during which time pulmonary vascular resistance gradually declines. Nitric oxide (NO) is a recently recognized pulmonary vasodilator, but its role in PPHN is unknown. We tested the hypothesis that the concentrations of the urinary metabolites of NO, i.e. nitrite and nitrate, are reduced in patients with PPHN and increase during ECMO as the PPHN resolves. Eight newborn infants with PPHN on ECMO were studied. Daily urinary concentrations of nitrite/nitrate were measured. We found that mean urinary concentrations of nitrite/nitrate were lower in patients with PPHN than in 47 controls without pulmonary disease (p < 0.005). Urinary nitrite/nitrate concentration showed an initial increase after initiation of ECMO. However, a decrease to concentrations still lower than controls occurred on the day before decannulation. We conclude that intrinsic NO production is significantly lower in patients with PPHN than in controls but increases with oxygenation. We speculate that decreased urinary NO metabolite concentrations imply a role for NO deficiency in the pathogenesis of PPHN.

Extracorporeal Membrane Oxygenation↗

Traumatic delivery: a risk factor for bleeding during ECMO?

Traumatic delivery is associated with orthopedic, nervous, and soft tissue injuries. Anticoagulation for extracorporeal membrane oxygenation (ECMO) support may predispose to hemorrhage from these birth injuries. A case of delayed hemoperitoneum secondary to hepatic laceration after delivery and ECMO, not previously reported, is detailed herein.

Birth Injuries↗