Antimurine antibody formation following OKT3 therapy.

OKT3 is an IgG2a murine monoclonal antibody directed against the CD3 antigen receptor of human T lymphocytes. A major concern with OKT3 treatment in solid organ transplant recipients is the development of antimouse antibody, which may preclude retreatment with this agent. We have administered OKT3 on 215 occasions (150 renal, 34 hepatic, 26 cardiac, 5 pancreatic) in 179 patients between April 1982 and December 1988. The mean duration of treatment was 10.5 days (range, 2-22 days). Antimouse antibody data were analyzed on the most recent 133 treatment courses where the antibody status was available pretreatment. Determination of antimouse antibody production was elicited by ELISA technology at days 0, 7, 14, and 28 of OKT3 treatment. Patients were categorized according to the antibody response as follows: (a) absence of antibody; (b) low titer (1:100); or (c) high titer (greater than or equal to 1:1000). Our earlier experience has demonstrated that retreatment with OKT3 is successful in groups a and b. The development of antimurine antibodies was analyzed with regard to the following parameters: (1) The duration of OKT3 treatment; (2) treatment type (prophylactic, primary, or secondary); (3) primary treatment or retreatment; (4) concomitant immunosuppressive regimen (double or triple therapy); (5) dosage of concomitant immunosuppressive drugs; and (6) transplant organ type. The following results were obtained. (1) Duration of treatment had no effect on antibody production (11.0 days in antibody negative and 10.0 days in antibody positive). (2) There was no difference in antibody formation rates for the first treatment of OKT3 when it was used as prophylaxis (26%), primary (19%), or secondary (27%) therapy. (3) Antibody formation rate with first treatment was 29%; with retreatment, patients who were antibody negative following first treatment became positive in 28% of cases, and retreated patients who were low titer positive following first treatment converted to high titer in 57% of cases. (4) Antibody formation was higher in patients receiving double immunosuppressive therapy (36%) than in those receiving triple immunosuppressive therapy (21%) during OKT3 treatment. (5) Concomitant immunosuppression was lower in the antibody-positive group during OKT3 therapy: steroids, 61 mg/day vs. 52 mg/day; azathioprine, 89 mg/day vs. 66 mg/day; CsA, 317 mg/day vs. 186 mg/day. (6) Antibody formation rates were lower in non-renal transplants following first treatment with OKT3 (liver 17%, heart 17%, kidney 28%); this reflects the higher doses of concomitant immunosuppressive therapy used in nonrenal transplants.(ABSTRACT TRUNCATED AT 400 WORDS)

Continuous hemodiafiltration in children.

Continuous arteriovenous hemofiltration is a form of renal replacement therapy whereby small molecular weight solutes and water are removed from the blood via convection, alleviating fluid overload and, to a degree, azotemia. It has been used in many adults and several children. However, in patients with multisystem organ dysfunction and acute renal failure, continuous arteriovenous hemofiltration alone may not be sufficient for control of azotemia; intermittent hemodialysis or peritoneal dialysis may be undesirable in such unstable patients. Recently, the technique of continuous arteriovenous hemodiafiltration has been used in many severely ill adults. We have used continuous arteriovenous hemodiafiltration in four patients at Children's Hospital Medical Center. Patient 1 suffered perinatal asphyxia and oliguria while on extracorporeal membrane oxygenation. Patients 2 and 4 both had Burkitt lymphoma and tumor lysis syndrome. Patient 3 had septic shock several months after a bone marrow transplant. All had acute renal failure and contraindications to hemodialysis or peritoneal dialysis. A blood pump was used in three of the four patients, while spontaneous arterial flow was adequate in one. Continuous arteriovenous hemodiafiltration was performed for varying lengths of time, from 11 hours to 7 days. No patient had worsening of cardiovascular status or required increased pressor support during continuous arteriovenous hemodiafiltration. The two survivors (patients 2 and 4) eventually recovered normal renal function. Continuous arteriovenous hemodiafiltration is a safe and effective means of renal replacement therapy in the critically ill child. It may be ideal for control of the metabolic and electrolyte abnormalities of the tumor lysis syndrome.

Rapid improvement in the renal tubular dysfunction associated with tyrosinemia following hepatic replacement.

The postoperative management of patients with hereditary tyrosinemia type I (McKusick 27670) following liver transplantation is often complicated by the renal tubular dysfunction associated with this disease. To characterize better the temporal course of the improvement in renal excretory activity following hepatic replacement, renal tubular function and metabolite excretion were studied in a 4-year-old girl with hereditary tyrosinemia during the immediate post-transplantation course. Tubular reabsorption of bicarbonate and phosphate were normal 5 days following transplantation, in contrast to glucosuria, hyperaminoaciduria, and tyrosyluria, which persisted for approximately 3 weeks. After hepatic replacement, serum amino acid concentrations returned to normal and succinylacetone was no longer detected in the urine. This is the third tyrosinemia patient reported to achieve complete resolution of urinary abnormalities following transplantation, and the only patient in whom renal tubular function was formally assessed within the first postoperative week.

Causes and management of portal hypertension in the pediatric population.

Therapeutic options for children with portal hypertension now include a broad range of pharmacologic, endoscopic, and surgical procedures. Thoughtful application of all of these options can improve quality of life by decreasing the complications of portal hypertension and can decrease mortality by preventing the consequences of variceal hemorrhage. The development of portal hypertensive gastropathy following palliative procedures such as endoscopic sclerotherapy and band ligation may limit their long-term success in children. The excellent results now obtained with selective portosystemic shunts and liver transplantation assure that definitive surgical treatments will continue to be important components in the treatment of children with portal hypertensive complications or progressive liver disease. Evolving procedures, such as TIPS, represent excellent short-term life-preserving techniques to stabilize critically ill patients while awaiting liver transplantation. Their role in the future, long-term management of children is yet to be defined.

Blunt liver injury in childhood: evolution of therapy and current perspective.

One hundred eighty-eight consecutive children with serious blunt abdominal or multisystem trauma were evaluated between August 1981 and July 1985. Of the 188 patients, 53 (28%) were found to have hepatic parenchymal injuries and are the basis of this report. Four of the 53 (8%) underwent emergency laparotomy for exsanguinating hemorrhage; two patients died, both of hepatic vein lacerations, and two are alive and well after right hepatic lobectomy. Forty-nine (92%) of the children with liver injuries did not require operation for hemorrhage. Four of these 49 patients developed serious complications; hemobilia occurred in one patient and bile peritonitis occurred in three. The one case of hemobilia was resolved without surgery. One child underwent a delayed operative biliary tract reconstruction that was successful. The other two children required a combination of debridement and drainage procedures. Fifty-one of the 53 children (96%) are currently alive without morbidity related to their liver injuries. Both children who died had multiple trauma including central nervous system injuries and had exsanguinating hemorrhage that required emergency laparotomy at initial evaluation. There were no children with "late" hemorrhage and none who developed septic complications. Nonoperative management of most childhood blunt abdominal trauma is possible. Widespread use of abdominal computerized tomography scanning has made this approach practical. This large series of consecutive liver injuries from a large pediatric trauma center illustrates the advantages and the risks of a selective but primarily nonoperative approach to liver trauma in children.

Liver transplantation in Ohio.

BACKGROUND: Since its inception in 1984, the Ohio Solid Organ Transplantation Consortium has tracked liver transplantation outcomes for its five member institutions. Presented herein is a 12-year summary of this data analyzed to determine whether, with increasing experience, outcomes have improved in a cost-effective manner. METHODS: Between July 1984 and June 1996, 1,063 liver transplants were performed in Ohio in 943 patients (772 adults and 171 children), of which 943 were primary and 120 were retransplants (13%). Outcome comparisons were made for three eras: 1984-1988, 1988-1992, and 1992-1996. RESULTS: The percentage of urgent (United Network for Organ Sharing status 1 and 2) transplants has decreased (62% to 41%), whereas that of homebound patients has increased (38% to 59%). Average time on the waiting list has increased from 39 to 165 days, and the average length of stay has decreased from 44 to 27 days. Patient survival at 1-year increased in each era (64%, 80%, and 82%, respectively). Although actual hospital charges have remained relatively constant, they have decreased substantially when compared in 1985 dollars as corrected for inflation. CONCLUSIONS: Patients undergoing liver transplantation in Ohio are now listed earlier in the course of their disease and wait longer for their transplant, but enjoy a better chance of survival, have a shorter hospital stay, and a relatively less expensive operation. These data indicate that with increased experience, the Ohio Solid Organ Transplantation Consortium liver transplantation teams perform liver transplantation in a more cost-effective manner.

Congenital diaphragmatic hernia survival and use of extracorporeal life support at selected level III nurseries with multimodality support.

BACKGROUND: Congenital diaphragmatic hernia (CDH) has been cited to have a mortality rate of 50%. There have been multiple studies at individual institutions demonstrating potential benefits from various strategies including extracorporeal life support (ECLS), delayed repair, and lower levels of ventilator support. There has been no multicenter survey of institutions offering these modalities to describe the current use of ECLS and survival of these infants. In addition, the relationship between the number of patients with CDH managed at an individual institution and outcome has not been evaluated. METHODS: We queried 16 level III neonatal intensive care centers on the use of ECLS and survival of infants with CDH who were treated during 2 consecutive years (1993 to 1995). Data are presented as mean +/- SEM, median, and range. RESULTS: Data were collected on 411 patients. Of these, 71% +/- 8% were outborn and 8% +/- 3% were considered nonviable. Overall survival of CDH infants was 69% +/- 4% (range, 39% to 95%). The survival rate of infants on ECLS was 55% +/- 4%, whereas survival of infants not requiring ECLS was significantly increased at 81% +/- 5% (p = 0.005). The mean rate of ECLS use was 46% +/- 2%. There was no correlation between the number of cases per year at an individual institution and overall survival, ECLS survival, or ECLS use (r = 0.341, 0.305, and 0.287, respectively). There was also no correlation between case volume at an individual institution and ECLS survival (r = 0.271). CONCLUSIONS: The current survival rate and rate of ECLS use in infants with CDH at level III neonatal intensive care units in the United States are 69% +/- 4% and 46% +/- 2%, respectively. There is no correlation between the yearly individual center experience with managing CDH and rate of ECLS use or outcome.

Thoracoscopy for intrathoracic tumors.

The technique of thoracoscopy has been performed on 49 occasions in 45 patients for the diagnosis or staging of intrathoracic tumors. The patients ranged from 8 months to 68 years old. Eight procedures were performed for pleural disease, 16 for mediastinal masses, 22 for parenchymal lesions, and 3 for intrathoracic staging. Seventeen patients had had previous invasive procedures performed without a pathological diagnosis being established. In 28 thoracoscopy procedures, a positive diagnosis for malignancy was obtained; in 6 instances, areas of unsuspected tumor involvement were identified. A correct diagnosis was obtained by thoracoscopy in 45 procedures for a 92% overall accuracy rate. There was no clinically significant morbidity in this series and no procedure-related mortality. Thoracoscopy, performed under stellate ganglion block and regional anesthesia, has proved to be a very attractive method of diagnosing intrathoracic neoplasia with very low morbidity.

Multisystem trauma.

Several unique features of childhood anatomy and physiology mandate an approach to evaluation and treatment of multiply injured children that differs from that applied to adults. Details of this approach have been presented, with particular emphasis, on early, aggressive multimodal imaging, nonoperative management of splenic, hepatic, renal, and duodenal injuries, and specific aids in early precise definition of extent of injury (contrast-enhanced CT, serum levels of hepatic enzymes, and diagnostic peritoneal lavage). The outcome of this approach preserves maximum function and minimizes morbidity when performed in an institution having the requisite supportive resources.

Thoracic surgical problems in infancy and childhood.

Thoracic surgical problems in infants and children range from congenital anomalies to acquired inflammatory problems. This article reviews the most common parenchymal, pleural, and mediastinal problems encountered in infants and children and presents recommendations for prompt and accurate diagnosis and therapy.

Obstructive airway disease in infants and children.

Airway obstruction in infants and children can produce rapidly progressive life-threatening emergencies. An understanding of the common symptom complexes associated with regional obstructive abnormalities allows rapid evaluation and appropriate therapy. This article discusses the most common types of obstructive congenital and acquired airway anomalies, describes their symptomatology, and reviews the available diagnostic and treatment options.

Liver transplantation in children.

Children with end-stage liver disease now have a greater chance of survival through treatment with hepatic transplantation. This article reviews the pediatric liver transplantation process, including selection and evaluation of candidates, operative procedures, postoperative complications, and long-term survival.

A simple technique to redirect malpositioned Silastic central venous catheters.

A simple and noninvasive method to redirect malpositioned Silastic central venous catheters is described. A syringe is connected to the catheter hub, and burst injections of saline cause the tip of the catheter to flip into the correct intravascular position. The present technique has been applied to more than 30 pediatric patients with excellent results. A detailed description of the technique and case examples are presented.

Achalasia mimicking peptic esophageal stricture.

Peptic stricture of the esophagus and achalasia both cause dysphagia. They are not always readily distinguished by history. The usual workup with upper gastrointestinal x ray and endoscopy may also fail to differentiate the two disorders. Two cases are presented wherein antireflux procedures were mistakenly performed when achalasia was present rather than peptic stricture. Dysphagia was unrelieved and extensive further procedures were required. In a third patient referred for a peptic stricture, manometry revealed the correct diagnosis and heller myotomy provided relief. It is recommended that manometry be performed as a part of the preoperative workup in patients in whom there is any element of dysphagia.

Endoscopic balloon dilation of outlet stenosis after gastric bypass.

Eighteen of 22 patients with stenotic gastrojejunostomies following gastric bypass surgery were successfully corrected by endoscopically placing a guidewire through the narrowed outlet and then passing a dilating balloon catheter over the wire. No complications occurred. All procedures were done without general anesthesia, and 64 per cent were done without hospitalization. This procedure can spare patients prolonged hospitalization for nasogastric decompression or reoperation, the two standard approaches to this problem. Successful use of this technique to dilate obstructed gastric partitions and distal esophageal strictures suggests that it may be considered for any gastrointestinal stenosis within reach of the endoscope.

New methods for assessing liver function in infants and children.

Assessment of liver function in infants and children has traditionally relied on static indices of hepatic structure, cellular integrity, or function and are often based on the release of substances from damaged tissues. There has been a rapid development of dynamic tests based on the measurement of substances metabolized or cleared from blood by the liver. These tests, which have been touted to offer a more precise quantitative estimation of hepatic functional capacity, include the measurement of serum bile acids and the hepatic metabolism of xenobiotic compounds such as caffeine and lidocaine. Serum bile acid measurements appear to be reliable indicators of enterohepatic circulation and may be useful in screening for liver disease. It has been observed that caffeine metabolism is decreased in patients with various forms of liver disease in correlating with disease status. Caffeine has the advantage of being well tolerated when administered orally; the saliva level parallels the serum concentration, making a non-invasive test feasible. Lidocaine is metabolized by oxidative de-ethylation to monoethylglycinexylide (MEGX); analysis of MEGX by common laboratory instrumentation makes rapid evaluation of liver function possible. The MEGX values correlated were with pretransplant liver disease assessment. These tests are currently being evaluated at other centers and, if the initial studies are repeated, they offer the hope for reliable dynamic tests of hepatic function.

Childhood tracheobronchial mucoepidermoid carcinoma: a case report and review of the literature.

Mucoepidermoid carcinoma of the lung presenting in childhood is an uncommon neoplasm. Symptoms of progressive bronchial obstruction proceed the recognition of this lesion. The well-confined local growth and minimal metastatic potential of childhood mucoepidermoid carcinoma make local resection with maximum conservation of pulmonary parenchyma the recommended operative treatment. Adequate surgical resection precludes the need for further radiation therapy or chemotherapy. This report details the presentation and treatment of a child with this rare tumor and reviews the present literature experience with childhood mucoepidermoid carcinoma.

Cardiac arrest in the ECMO candidate.

Extracorporeal membrane oxygenation (ECMO) improves survival in appropriately selected full-term neonates with severe respiratory failure. The clinical course and outcome of infants placed on ECMO after sustaining a cardiac arrest is not known. This study reviews the characteristics and outcome of 10 neonates, identified by retrospective review, placed on ECMO at Children's Hospital Medical Center (CHMC), Cincinnati, OH, after sustaining a cardiac arrest. Long-term survival in this group was 60%, significantly less than the 87% overall ECMO survival in infants at CHMC (P less than .01). Survivors and nonsurvivors in the cardiac arrest group were similar with regard to gestational age, birth weight, Apgar scores, and arterial PO2 prior to cannulation. Nonsurvivors had an ECMO course complicated by progressive multisystem organ failure. Head computed tomography obtained at the time of discharge demonstrated right-sided brain lesions in three of six survivors. Despite these radiographic findings, early clinical follow-up suggests adequate growth and development with no individuals demonstrating a severe neurological deficit. Thus, ECMO can play a role in the resuscitation of neonatal ECMO candidates sustaining cardiac arrest prior to or at the time of cannulation. Early clinical follow-up suggests adequate preservation of neurological function in this extremely high-risk group.

Thoracoscopy for intrathoracic neoplasia in children.

The technique of thoracoscopy allows a unique opportunity to examine the entire hemithorax. Between July 1975 and April 1981 we performed over 150 thoracoscopic procedures for evaluation of intrathoracic pathology at the University of Florida. Twenty-five of these procedures, performed in 23 patients, were undertaken for the diagnosis or staging of intrathoracic tumors in patients whose ages ranged from 8 mo to 18 yr. Forty-eight percent were for parenchymal tumors, 44% for mediastinal masses, and 8% for pleural disease. Twelve of these patients had at least 1 invasive procedure performed prior to thoracoscopy without a diagnosis being established. In 17 procedures a positive tissue diagnosis of malignancy was obtained, and in 6 of these cases areas of previously unsuspected intrathoracic tumor involvement were identified by thoracoscopy. In 3 patients simultaneous thoracoscopy-guided transdiaphragmatic needle biopsy of the liver was performed with a positive tumor diagnosis being achieved in 1. The clinical course of the patients following the 8 procedures in which neoplasia was not encountered confirmed the diagnosis of benign disease in all but 1. A single patient with an enlarged mediastinal lymph node had a falsely negative thoracoscopy biopsy and was subsequently diagnosed as having recurrent Hodgkin's disease. The overall diagnostic accuracy in these patients was, therefore, 92%. Complications in these patients have been minimal, and there was not mortality due to the thoracoscopic procedure. These clinical results would suggest an important role for thoracoscopy in the evaluation of intrathoracic neoplasia in children.

Catheter-induced urinary bladder rupture presenting with pneumoperitoneum.

Neonatal bladder injury is rare and usually associated with umbilical artery catherization. Patients may present with apparent renal failure, abdominal distension, and respiratory distress. Treatment involves operative closure of the perforation and bladder drainage. A case of Foley catheter-induced bladder rupture in a premature infant, not previously reported in the literature, is detailed.