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Frederick J Rescorla

Publications and source records attributed to Frederick J Rescorla.

17 recordsLinked to original sources
PubMed2007

Iron chelation acutely stimulates fetal human intestinal cell production of IL-6 and VEGF while decreasing HGF: the roles of p38, ERK, and JNK MAPK signaling.

Bacteria have developed mechanisms to sequester host iron via chelators such as deferoxamine (DFO). Interestingly, DFO has been shown to stimulate acute intestinal epithelial cell inflammatory cytokine production in the absence of bacteria; however, this mechanism has not been elucidated. Intestinal epithelial cell production of IL-6 and TNF-alpha is elevated in various gastrointestinal pathologies, including acute intestinal ischemia. Similarly, VEGF and HGF are essential to intestinal epithelial cell integrity. Therapeutic strategies that decrease IL-6 and TNF-alpha while increasing VEGF and HGF therefore have theoretical appeal. We hypothesized that 1) fetal human intestinal epithelial cells acutely produce increased IL-6, TNF-alpha, VEGF, and HGF during iron chelation and 2) the MAPK pathway mediates these effects. Fetal human intestinal epithelial cells were stimulated by iron chelation (1 mM DFO) with and without p38 MAPK, ERK, or JNK inhibition. Supernatants were harvested after 24 h of incubation, and IL-6, TNF-alpha, VEGF, and HGF levels were quantified by ELISA. Activation of MAPK pathways was confirmed by Western blot analysis. DFO stimulation resulted in a significant increase in epithelial cell IL-6 and VEGF production while yielding a decrease in HGF production (P<0.05). Unexpectedly, TNF-alpha was not detectable. p38 MAPK, ERK, and JNK inhibition significantly decreased IL-6, VEGF, and HGF production (P<0.05). In conclusion, DFO acutely increases fetal human intestinal epithelial cell IL-6 and VEGF expression while causing an unexpected decrease in HGF expression and no detectable TNF-alpha production. Furthermore, chelator-induced intestinal epithelial cell cytokine expression depends on p38, ERK, and JNK MAPK pathways.

Blotting, Western↗
PubMed2006

Proteomic analysis of neuroblastoma subtypes in response to mitogen-activated protein kinase inhibition: profiling multiple targets of cancer kinase signaling.

INTRODUCTION: Survival for high-risk neuroblastoma (NB) remains poor despite aggressive therapy. Novel therapies are vital for improving prognosis. We previously showed differential NB subtype sensitivity to p42/44 mitogen-activated protein kinase (ERK/MAPK) pathway inhibition. In this study, we investigated proteomic changes associated with resistance or sensitivity to MAPK kinase (MEK) inhibition in NB subtypes. MATERIALS AND METHODS: SH-SY5Y (N-type), BE(2)-C (I-type), and SK-N-AS (S-type) were treated with MEK inhibitor U0126 (10 microM) for 1 and 24 h. Proteins were extracted from untreated and treated cells and analyzed for differential expression by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Selected polypeptides were extracted from the gel and identified by liquid chromatography-linked tandem mass spectrometry (LC-MS/MS). RESULTS: We identified 15 proteins that were decreased by 2.5-fold between untreated and 1 h treated cells and subsequently up-regulated 5-fold after 24 h drug treatment. N-type NB (MEK-resistant) showed the least altered proteomic profile whereas the I-type (MEK-sensitive) and S-type NB (MEK-intermediate) generated significant protein changes. The majority of proteins identified were induced by stress. CONCLUSIONS: Protein differences exist between MEK inhibitor-treated NB subtypes. Identified polypeptides all have roles in mediating cellular stress. These data suggest that inhibition of the ERK/MAPK in NB subtypes leads to an intracellular stress response. The most resistant NB cell line to MEK inhibitor treatment generated the least protective protein profile, whereas the intermediate and most sensitive NB cells produced the most stress response. These findings suggest stress related protein expression may be targeted in assessing a response to ERK/MAPK therapeutics.

Butadienes↗
PubMed2006

Effect of corticosteroid therapy on outcomes in biliary atresia after Kasai portoenterostomy.

PURPOSE: This study tests the hypothesis that steroid administration improves the outcome of biliary atresia (BA) by evaluating the efficacy of postoperative steroid use on surgical outcomes in infants with BA. METHODS: Steroid use and outcomes in patients with BA were retrospectively analyzed at a tertiary pediatric hospital. Institutional review board approval was obtained. RESULTS: Kasai portoenterostomy (PE) was performed in 43 patients with BA treated from 1992 to 2004 (16 boys and 27 girls). Twenty-one PE patients received steroids and 22 did not. Portoenterostomy was successful in 24 patients (55.8%) with consistent serum bilirubin less than 2 mg/dL. Sixteen (66%) received postoperative steroids. A normal postoperative bilirubin was achieved at 6 months in 16 (76%) of 21 patients with steroids compared with 8 (37%) of 22 in untreated controls (Fisher's Exact test, P = .01). Of the 43 patients, 19 (44%) required liver transplantation, including 7 (37%) of 19 with steroids vs 12 (63%) of 19 without (P = .2). Twenty-eight infants developed cholangitis (fever with and without changes in hepatic function): 25 after PE and 3 after transplant. Of the 25, 12 (48%) received steroids. Seven died (16%) (range, 7 months to 4 years): 2 while awaiting transplantation (received steroids) and 5 after transplantation (1 received steroids and 4 were untreated). Survival was 86% (18/21) in patients with steroids and 82% (18/22) in those without. Transplant survival (74%) was comparable to previously reported historical controls (82%). CONCLUSIONS: The Kasai PE continues to be the procedure of choice in infants with BA younger than 3 months. A significantly improved clearance of postoperative jaundice and lower serum bilirubin levels were observed in patients receiving steroids. However, steroids had no effect on the incidence of cholangitis, need for liver transplantation, and overall survival. A prospective study with standardized dose and length of steroid administration and longer period of follow-up is necessary to more accurately assess the effectiveness of steroids after PE.

Adrenal Cortex Hormones↗
PubMed2006

Incidence of persistent left superior vena cava in esophageal atresia.

PURPOSE: Esophageal atresia is known to be associated with a variety of additional congenital anomalies in multiple organ systems. Emphasis on cardiovascular anomalies has been focused on aortic arch and intrinsic cardiac malformations. Persistent left superior vena cava (PLSVC) is the most common venous thoracic anomaly in the general population and creates a problem when central venous access is required. This review was undertaken to define the incidence of PLSVC in infants with esophageal atresia and to determine if any subgroup of associated anomalies poses additional risk. METHODS: A retrospective, institutional review board-approved review of all children treated for esophageal atresia from 1993 to 2002 at Riley Hospital for Children was undertaken. Of 118 children, 89 had sufficient data for inclusion. Charts were reviewed for gestational age, weight, type of atresia, echocardiogram, and associated anomalies. Statistical analysis was performed using the Fisher's Exact test. RESULTS: Of 89 children, 8 (9.9%; confidence interval, 4%-17%) had PLSVC compared with the reported incidence of 0.3% in the general population. Presence of additional organ system anomalies did not significantly increase relative risk for PLSVC. CONCLUSION: The incidence of PLSVC is significantly increased in children with esophageal atresia when compared with the general population. This increased incidence of PLSVC is not influenced by the presence of cardiac or other associated anomalies. This finding should be kept in mind when central venous access is required in this patient population.

Abnormalities, Multiple↗
PubMed2006

Long-term outcomes in patients with stage IV neuroblastoma.

AIM OF STUDY: Long-term outcome studies in survivors with stage IV neuroblastoma (NB) are sparse. This review evaluates late complications and long-term outcomes in stage IV NB survivors. METHODS: A retrospective review of stage IV NB survivors was performed to analyze outcomes, including long-term morbidity, recurrence, and survival. MAIN RESULTS: Of 153 patients with stage IV NB, 52 (34%) survived (male-female, 26:26). Age at diagnosis was 29.1 +/- 31.7 months in survivors. Eighteen were 1 year or younger and 34 were older than 1 year compared with 10 nonsurvivors 1 year or younger and 91 older than 1 year (P = .0003, Fisher's Exact test). Primary tumor sites were adrenal (35), retroperitoneal (11), mediastinal (3), pelvic (2), and no primary with tumor metastases identified (1). Ten survivors had favorable and 16 had unfavorable histology compared with 1 favorable and 18 unfavorable in nonsurvivors (P = .01). Four survivors had MYCN amplification (> or = 10 copies) and 2 deletions of 1p and 11q. Sites of metastasis in survivors and nonsurvivors were similar. Treatment in survivors included surgery in 51 (75% [39/51] complete tumor resection [CTR]); chemotherapy, 50; radiation, 17; stem cell transplantation, 20; and bone marrow transplant, 1. In nonsurvivors, 13 (25%) of 53 (P < < .0001) had CTR, 18 stem cell transplantation, and 12 bone marrow transplant. Six patients had tumor recurrence but survived (mean, 9.3 +/- 8.3 years; range, 6 months-24 years). Recurrence was local (1), distant (2), and both (3) and was treated by resection, chemotherapy, and radiation. The mean age of survivors was 12.4 +/- 8.3 years (range, 2-34 years). In all stage IV cases, event-free survival was 30% and overall survival was 34%. Long-term complications occurred in 23 (44%) survivors, including endocrine disturbances (7), orthopedic (5), cataracts (2), adhesive bowel obstruction (2), hypertension (1), bronchiolitis (1), blindness (1), peripheral neuropathy (1), nonfunctioning kidney (1), cholelithiasis (1), and thyroid nodule (1). CONCLUSION: Only 34% of patients with stage IV NB survived despite aggressive multimodal therapy. Age of younger than 1 year, favorable pathology, CTR, and no recurrence were the only statistically significant factors that favored survival. Forty-four percent of survivors experienced late morbidity, and tumor recurred in 6 (11.5%) of 52. Patients should be monitored for tumor recurrence and long-term sequelae. New methods of treatment are required to achieve better outcomes.

Child, Preschool↗
PubMed2006

Malignant adrenal tumors.

Adrenal tumors, apart from neuroblastoma, are relatively rare in infancy and childhood. Most adrenal lesions are benign, and both benign and malignant tumors may be hormonally active thus, making accurate preoperative diagnosis difficult. The two main malignant tumors are adrenocortical carcinoma and pheochromocytoma. In both tumors, it may be difficult to determine benign from malignant and the biologic behavior and degree of invasion may portend a more malignant course. Surgical excision is the primary therapy for both tumors, including excision of metastatic and recurrent tumor. An open procedure should be considered for invasive adrenocortical carcinoma and in pheochromocytomas in which preoperative imaging demonstrates metastatic nodal disease. A laparoscopic approach is preferred for lesions in which preoperative imaging demonstrates a localized lesion. Chemotherapy, although without proven efficacy, is utilized in some children with metastatic or unresectable disease.

Adrenal Gland Neoplasms↗
PubMed2006

Pancreatic disorders in children: relationship of postoperative morbidity and the indication for surgery.

Pancreatic surgery in children is a rare occurrence, and this unfamiliarity can be associated with the assumption of significant morbidity and mortality. The indication for pediatric pancreatic surgery and its relationship to postoperative complications and mortality was evaluated. Patients with pancreatic disease requiring surgical intervention from 1992 to 2004 at a tertiary referral center were retrospectively reviewed. Disorders were divided into 3 categories: 1) pancreatitis, 2) trauma, and 3) tumors. Sixty-two patients (28 males and 34 females), average age was 9.5 years (range, 1 week-18 years), underwent 72 operations. Thirty-seven procedures in 30 category I patients, 18 procedures in 15 category II, and 17 operations in 17 category III. There was only one death. A total of 33.9 per cent of the patients had postoperative complications that included: infection (11%), pseudocyst (6%), diabetes mellitus (5.6%), pancreatic fistula (3%), bowel obstruction (1.3%), extracellular fluid (1.3%), pleural effusion (1.3%), and recurrent abdominal pain (13%) (all in category I patients). There was equivalent morbidity between all 3 groups but unique differences with in the categories. Recurrent abdominal pain characterized category I patients, fistulas were more common in category II, and diabetes mellitus was primarily related to near total excisions in category III. Pancreatic surgery in children is associated with a very low mortality (1.6%) and morbidity equal to that of adult patients. Unique types of morbidities occur with each category of disease state.

Abdominal Pain↗
PubMed2005

Supraumbilical pyloromyotomy: a unique indication for antimicrobial prophylaxis.

BACKGROUND: The umbilical fold incision for infantile hypertrophic pyloric stenosis provides a convenient exposure and cosmetically appealing scar. This study investigates the possible difference in infection rates between traditional and supraumbilical approaches for pyloromyotomy. METHODS: All patients who underwent pyloromyotomy for infantile hypertrophic pyloric stenosis at a tertiary pediatric hospital were reviewed. Baseline wound infection rate was determined through review of patients with right upper quadrant incisions (group 1). A nonrandomized comparison was performed between patients with a supraumbilical approach (group 2) and those undergoing supraumbilical incisions after prophylactic antibiotic administration (group 3). RESULTS: Complete records were reviewed on 384 patients over a 6-year period. Demographics and preoperative factors were similar among groups. The rate of infection in group 1 (n = 258) was 2.3%. With introduction of the supraumbilical approach, there was a statistically significant increase in wound infection rate to 7.0% (chi 2 ; group 1 vs group 2, P < .05). The use of prophylactic antibiotics with a supraumbilical approach reduced this rate of infection back to 2.3% (chi 2 ; group 1 vs group 3, P < 1.0 and group 2 [n = 85] vs group 3 [n = 42], P < .3). CONCLUSIONS: The risk of wound infection by classic pyloromyotomy of 2.3% is significantly increased with an open supraumbilical approach. The use of prophylactic antibiotics reduces this risk of wound infection.

Anti-Infective Agents↗
PubMed2005

Long-term outcomes in total colonic aganglionosis: a 32-year experience.

BACKGROUND/METHODS: A 32-year retrospective review from 1972 to 2004 analyzed complications and long-term outcomes in children with total colonic aganglionosis (TCA) as they relate to the procedure performed. RESULTS: Thirty-six patients (27 boys, 9 girls) had TCA. The level of aganglionosis was distal ileum (26), mid-small bowel (8), midjejunum (1), and entire bowel (1). Enterostomy was performed in 35 of 36. Eight developed short bowel syndrome. Twenty-nine (81%) had a pull-through at 15 +/- 6 months (modified Duhamel 20, Martin long Duhamel 4, and Soave 5). Six had a Kimura patch. Postoperative complications (including enterocolitis) were more common after long Duhamel and Soave procedures. Seven (19%; 2 with Down's syndrome) died (3 early, 4 late) from pulmonary emboli (1), sepsis (1), fluid overload (1), viral illness (1), liver failure (1), arrhythmia (1), and total bowel aganglionosis (1). Mean follow-up was 11 +/- 9 years (range, 6 months-29 years). Twenty-four (83%) of 29 patients exhibited growth by weight of 25% or more, 21 (91%) of 23 older than toddler age had 4 to 6 bowel movements per day, and 17 (81%) of 21 were continent. In 5 of 6, the Kimura patch provided functional benefit with proximal disease. CONCLUSION: Long-term survival was 81%. The highest morbidity occurred with long Duhamel or Soave procedures. The modified Duhamel is our procedure of choice in TCA. Bowel transplantation is an option for TCA with unadapted short bowel syndrome.

Adolescent↗
PubMed2005

Surgical considerations in cystic fibrosis: a 32-year evaluation of outcomes.

BACKGROUND: Information concerning long-term operative outcomes in patients with cystic fibrosis (CF) is relatively sparse in the operative literature. METHODS: A retrospective review of CF patients with operative conditions was performed (1972-2004) at a tertiary children's hospital to analyze outcomes including long-term morbidity and survival. RESULTS: A total of 226 patients with CF presented with an operative diagnosis (113 men, 113 women). A total of 422 operations were performed in 213 patients (94%). The mean age at operation was 4.1 +/- 6.2 years (range, 1 d to 26 y) and 109 were neonates. Fifteen of 42 (36%) babies with simple meconium ileus (MI) were treated nonoperatively with hypertonic enemas, 27 of 42 and all 45 patients with complicated MI required operation, including 15 with jejunoileal atresia (17%). Seventeen of 27 (63%) patients with meconium ileus equivalent had MI as neonates; 7 of 27 (26%) required operation. Eight of 9 (89%) with fibrosing colonopathy required operation. Organ transplantation was required in 21 patients. Follow-up evaluation was possible in 204 of 213 (96%) patients. The duration of follow-up evaluation was 14.9 +/- 8.5 years (range, 2 mo to 35 y). Operative morbidity was 11% at 1 year, 2% at 2 to 4 years, 1% at 5 to 10 years, and less than 1% at more than 10 years. There were 24 deaths (11%); 22 followed CF-related pulmonary complications and included 8 of 16 (50%) children with pneumothorax. CONCLUSIONS: Long-term survival in CF patients has improved significantly (89%), with many surviving into the fourth decade. MI may predispose to late complications including meconium ileus equivalent and fibrosing colonopathy. Pneumothorax in CF patients is an ominous predictor of mortality. Children with CF are living longer and are good candidates for operation, but require long-term follow-up evaluation because of ongoing exocrine dysfunction.

Abdomen↗
PubMed2004

Predictors of successful outcome after cholecystectomy for biliary dyskinesia.

PURPOSE: Laparoscopic cholecystectomy is accepted therapy for children with ill-defined abdominal pain and impaired gallbladder emptying (biliary dyskinesia). Follow-up shows poor clinical response in many of these patients. The purpose of this report is to identify clinical and radiographic predictors of successful outcome after cholecystectomy for biliary dyskinesia. METHODS: The authors retrospectively reviewed records of 51 children after laparoscopic cholecystectomy for biliary dyskinesia (1990 to 2003). Clinical symptoms, radiographic findings, and pathology were evaluated. Subjective clinical improvement is stratified using an established patient satisfaction score. Logistic regression analysis determines statistically independent predictors of successful outcome. RESULTS: Thirty-eight of 51 (75%) patients were available for follow-up. Twenty-seven of 38 (71%) patients reported complete resolution of symptoms. Nausea was the only symptom predictive of successful outcome by univariate analysis (odds ratio, 5.00). A cholecystokinin-stimulated, gallbladder ejection fraction less than 15% also predicts successful outcome (odds ratio, 8.00). Children with an ejection fraction greater than 15% did not have predictable resolution of symptoms. When present with pain and nausea, gallbladder emptying less than 15% has a positive predictive value of 93% and a negative predictive value of 81%. CONCLUSIONS: Together, nausea, pain, and decreased gallbladder emptying (<15%) most reliably predict which children will benefit from cholecystectomy for biliary dyskinesia.

Abdominal Pain↗
PubMed2004

Duodenal atresia and stenosis: long-term follow-up over 30 years.

BACKGROUND: Duodenal atresia and stenosis is a frequent cause of congenital, intestinal obstruction. Current operative techniques and contemporary neonatal critical care result in a 5% morbidity and mortality rate, with late complications not uncommon, but unknown to short-term follow-up. METHODS: A retrospective review of patients with duodenal anomalies was performed from 1972 to 2001 at a tertiary, children's hospital to identify late morbidity and mortality. RESULTS: Duodenal atresia or stenosis was identified in 169 patients. Twenty children required additional abdominal operations after their initial repair with average follow-up of 6 years (range, 1 month to 18 years) including fundoplication (13), operation for complicated peptic ulcer disease (4), and adhesiolysis (4). Sixteen children underwent revision of their initial repair: tapering duodenoplasty or duodenal plication (7), conversion of duodenojejunostomy to duodenoduodenostomy (3), redo duodenojejunostomy (3), redo duodenoduodenostomy (2), and conversion of gastrojejunostomy to duodenoduodenostomy (1). There were 10 late deaths (range, 3 months to 14 years) attributable to complex cardiac malformations (5), central nervous system bleeding (1), pneumonia (1), anastomotic leak (1), and multisystem organ failure (2). CONCLUSIONS: Late complications occur in 12% of patients with congenital duodenal anomalies, and the associated late mortality rate is 6%, which is low but not negligible. Follow-up of these patients into adulthood is recommended to identify and address these late occurrences.

Abnormalities, Multiple↗
PubMed2002

Laparoscopic splenectomy.

The laparoscopic technique for splenectomy has become the preferred method for splenectomy at many institutions over the last 10 years. The advantages of laparoscopic splenectomy include a shortened postoperative hospitalization, improved cosmesis, and less analgesic requirements. It is associated with longer operating times, a steep learning curve, and may be difficult in cases of splenomegaly. A careful search should be made for accessory spleens, and capsular disruption must be avoided. New techniques and smaller instruments have facilitated recent advances in the technical aspects of laparoscopic splenectomy.

Adolescent↗
PubMed2002

Surgical management of duodenal injuries in children.

BACKGROUND: The goal of this study was to review current injury characteristics, severity, intervention, and outcome of duodenal injuries from a single, pediatric trauma facility. METHODS: A retrospective review was performed of duodenal injuries in children less than 16 years of age from 1990 to 2000. RESULTS: Twelve children had duodenal injuries as a result of blunt abdominal trauma. Six injuries were the result of motor vehicle crashes. Nonaccidental trauma (2) and contact injury (4) provided the remaining cases. Diagnosis was achieved by abdominal computed tomography. Severity of duodenal injury included grade I (1), II (8), and III (3). Seven patients had associated visceral or neurologic injuries. Average Injury Severity Score was 18. Duodenal repair was required in 9 of the 10 patients explored. Treatment included observation (3); primary repair, alone, (2) or with proximal decompression (4); and pyloric exclusion with gastrojejunostomy (3). Exclusion techniques had fewer complications (0% vs 57%) and fewer hospital days (19 vs 23). CONCLUSIONS: Blunt abdominal trauma remains the most prevalent mechanism for pediatric duodenal injuries. Patients undergoing pyloric exclusion for severe duodenal trauma had a lesser morbidity and a shorter hospital stay in this small series. Pyloric exclusion remains an alternative for the treatment of severe duodenal injuries in selected children.

Abdominal Injuries↗
PubMed2002

Laparoscopic splenectomy has become the gold standard in children.

Splenectomy is frequently required in children with various hematologic disorders. The reported advantages of laparoscopic splenectomy (LS) include less pain, shorter hospital stay, and improved cosmesis. This report evaluates the outcome of children undergoing LS at a single children's facility. One hundred twelve children underwent LS by the lateral approach between August 1995 and February 2001. Indications for LS were hereditary spherocytosis in 58, idiopathic thrombocytopenic purpura in 21, sickle cell disease in 19, and other conditions in 14. LS alone was completed in 89 children and LS and cholecystectomy (LSC) in 20. Three required conversion to open splenectomy. Accessory spleens were identified in 19. Complications included ileus (four), acute chest syndrome (four), bleeding (two), pneumonia (one), and diaphragm perforation (one). There was no mortality. An accessory spleen was missed in one child with recurrent anemia. Average operative time for LS was 106 minutes and for LSC 135 minutes. Operative time for LS decreased with experience but the difference was not significant. Average length of stay was 1.51 days (range 1-11) and was longer in sickle cell disease (2.47 days) versus hereditary spherocytosis (1.29 days) and idiopathic thrombocytopenic purpura (1.16 days). We conclude that LS is safe and effective in children with hematologic disorders and is associated with minimal morbidity, zero mortality, and a short length of stay.

Adolescent↗