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Background/purpose: Children who require a liver transplant at an early age risk chronic allograft rejection (CAR) and other causes of allograft loss. Multiple retransplants may be required for long-term patient survival. The authors evaluate this approach based on our results and technical difficulties., Methods: Charts of 7 children who received 3 or more liver transplants from 1989 to the present were reviewed retrospectively., Results: A total of 151 children required liver transplantation at our institution since 1989. Of these, 4 boys and 3 girls (mean age, 6.2 years; range, 3 to 14 years) have received 3 or more allografts. The etiology of liver failure for the penultimate allograft was CAR (n = 6) and hepatic artery thrombosis (HAT; n = 1). Five cases required modification of portal vein or hepatic artery anastomoses. Two patients with vena caval strictures required supradiaphragmatic vena caval reconstruction. The original Roux-en-Y limb was adequate for biliary reconstruction in all cases. Five children currently are alive (survival rate, 71%) with good graft function having had a mean follow-up of 23 months (range, 2 to 48 mos.)., Conclusions: The operative procedure for the multiple hepatic transplant child is challenging. The transplant team must be prepared for intraoperative issues such as extended organ ischemia time during hepatectomy, extensive blood loss, and potential need for creative organ revascularization techniques. Overall, multiple retransplant results are good and justify the use of multiple allografts.

We report a case of a teratoid Wilms tumor arising within a supernumerary ectopic ureteropelvic structure in a 7-year-old boy. The tumor was near the right kidney but was completely separate from it. On the contralateral side, the child had a duplication of the ureteral system. Pathologic examination revealed the mass to be completely enveloped by a fibromuscular sac lined by urothelium. The tumor had a botryoid, polypoid architecture and, in addition to areas of classic Wilms tumor, had extensive squamous, mucinous, and columnar elements. Teratoid Wilms tumors are rare and, to the best of our knowledge, have not previously been described as arising either in anomalous urinary structures or at 7 years of age.

Purpose: The aim of this review was to determine the incidence of gastrointestinal perforation after pediatric liver transplantation and to identify risk factors and clinical indicators that may lead to an earlier diagnosis., Methods: A retrospective chart review of all children who presented with gastrointestinal perforation after liver transplantation at our institution between January 1, 1987 and August 1, 1996 was performed., Results: One hundred fifty-seven orthotopic liver transplants were performed in 128 children. Fifty-eight reexplorations, excluding those for retransplantation, were performed in 38 children. Ten perforations occurred in six children (incidence, 6.4%). Two children required multiple reexplorations because of several episodes of perforation. The sites of perforation were duodenum (n=1), jejunum (n=8), and ileum (n=1). A single-layer closure was used to repair five perforations, two-layer closures in four, and resection with primary anastomosis in another. The type of repair did not affect the occurrence of subsequent perforations. All the children were less than 18 months old. Four children had undergone prior laparotomy. All children had choledochoenteric anastomoses, but only one had a perforation associated with it. One child sustained bowel injury during the dissection for the liver transplant, but none of the perforations occurred at this site. Bowel function had returned before perforation in five children. Five children were receiving systemic antibiotics at the time of their perforation, and none had been dosed with pulse steroids for rejection. All of the children had significant changes in their temperature. Acute leukopenia developed in one child. A leukocytosis developed in the rest of the children. Abdominal radiographs demonstrated pneumoperitoneum in only one child. All children had positive culture findings from their abdominal drains. Cytomegalovirus developed in one child. Although the diagnosis of gastrointestinal perforation after pediatric liver transplant remains difficult, positive drain culture findings and significant alterations in temperature and leukocyte counts suggest its presence. Pneumoperitoneum is rarely present., Conclusion: A high index of suspicion and timely laparotomy, especially in children less than 2 years of age, may be the only way to rapidly diagnose and treat this potentially devastating complication of liver transplant.

Purpose: Fibrosing colonopathy is a newly described entity seen in children with cystic fibrosis. The radiological hallmarks are foreshortening of the right colon with varying degrees of stricture formation. High-dose enzyme therapy has been implicated as the cause of this process. The purpose of this study is to review the author's experience with evaluation and treatment of these patients., Methods: There are currently 380 patients being treated at our CF center. Fifty-five of these patients have been treated with high-dose enzyme therapy (> 5,000 units of lipase/kg). The medical records of these patients, who are at risk for developing fibrosing colonopathy, were reviewed for the presence of recurrent abdominal complaints, and the work-up and treatment of these symptoms., Results: Chronic complaints of abdominal pain, distension, change in bowel habits, or failure to thrive were present in 24 of the 55 patients treated with high-dose enzymes. So far, 18 of these 24 patients have been evaluated by contrast enema. Thirteen of eighteen have been found to have fibrosing colonopathy characterized by foreshortening and strictures of the colon. Additional findings included focal strictures of the right colon (7 of 13), long segment strictures (5 of 13), and total colonic involvement (1 of 13). Nine patients with the most severe symptoms have undergone colon resection, including five segmental right colectomies, three extended colectomies (ileo-sigmoid anastomosis), and one subtotal colectomy with end-ileostomy. Pathological evaluation has shown submucosal fibrosis, destruction of the muscularis mucosa, and eosinophilia. No postoperative complications or deaths occurred. All nine postoperative patients have noted marked symptomatic improvement. Contrast enema follow-up results are available for six patients, and have documented no recurrent strictures to date. Three of four nonoperative patients have less severe symptoms and are currently being treated conservatively. The other family has refused surgery and the patient is being treated symptomatically., Conclusion: High-dose lipase replacement has been implicated as the etiology for FC and was present in all of our patients. Our cystic fibrosis center now routinely limits lipase to 2,500 U/kg per dose. We recommend the use of the contrast enemas to evaluate at-risk patients who have chronic abdominal complaints or who present with recurrent bowel obstruction. Colon resection should be performed in those with clinically and radiographically significant strictures with the expectation of a good outcome.

We report a case of pleomorphic liposarcoma arising in the root of the mesentery of an adolescent girl. Pleomorphic liposarcoma is an extremely rare tumor in the pediatric age group, and few well-documented cases are found in the literature. To the best of our knowledge, none have been described in the abdomen. The histologic and ultra-structural features of this tumor are described, and the literature concerning pediatric pleomorphic liposarcoma is reviewed.

Liver transplantation became a very successful therapy when cyclosporin A was introduced as an immunosuppressive agent. In an effort to evaluate the contribution of difficult or uncontrolled allograft rejection to mortality, the authors determined the most important factors that limited survival after liver transplantation. Eighty-two children received a total of 94 liver transplants from January 1987 to the present. Patients' records were reviewed for complications that contributed to morbidity and mortality and to assess which complications were preventable. Twelve patients died (15%), nine within 6 weeks of liver transplantation. The chief contributing cause of death was hepatic artery thrombosis (one patient), brain death after liver transplantation for fulminant hepatic failure (two patients), primary allograft nonfunction or dysfunction (two patients), allograft rejection (three patients), or other problems (four patients). Overall, hepatic artery thrombosis occurred in 3.1%, allograft rejection in 57%, fulminant hepatic failure in 7%, and donor organ dysfunction in 7%. Allograft rejection contributed directly to the cause of death in three children (4%). The authors conclude that few deaths after pediatric liver transplantation are caused by failure of immunosuppression. A high survival rate can be achieved after transplantation by eliminating the correctable complications that most frequently occur in the early postoperative period.

Mast cells are tissue-resident immune cells that are capable of signaling many different cell types in vascularized tissue including epithelia and smooth muscle. We have developed an in vitro coculture system in which secretion of serotonin by a mucosal mast cell line (RBL-2H3) can be studied at a single cell level by measuring Ca2+ transients in fura-2 loaded mast cells and serotonin-sensitive A7r5 smooth muscle cells using fluorescence video microscopy and digital image processing. A7r5 cells elevate intracellular Ca2+ via 5HT2 receptors in response to bath-applied serotonin with an ED50 for serotonin of 550nM. Crosslinking IgE receptors with antigen caused Ca2+ transients in the mucosal mast cells. Ca2+ responses in the smooth muscle were detected approximately 30-240 sec after the initiation of the mast cell Ca2+ responses. Smooth muscle Ca2+ responses were dependent on preloading mast cells with serotonin and were blocked by the 5HT2 antagonist ketanserin. The timing and magnitude of the smooth muscle responses indicated that secretion from mast cells can lead to local concentrations of serotonin in the range of 300 nM within 1 min of antigen stimulation. This coculture technique has allowed the first direct demonstration of serotonin-mediated signaling between immune cells and vascular elements.

The ultimate prognosis for patients with short bowel syndrome (SBS) has become progressively more favorable over the past decade. Advances in long-term total parenteral nutrition (TPN) have allowed this group of patients to meet nutritional needs while the process of intestinal adaptation occurs. Unfortunately, a subgroup of patients with SBS have hepatic failure (HF), most often secondary to TPN-induced cholestasis. Combined small bowel and liver transplantation (LT) offers a sound anatomic solution for cases of HF with SGS, but it remains experimental at this time. We propose that an isolated LT is a viable alternative mode of therapy for the patient with HF and SBS. The following characteristics were reviewed for five patients with SBS and HF who underwent LT: age at transplantation, weight, liver function, survival, intestinal length, volume of feeding before surgery, and current feeding tolerance and liver function. Four boys and one girl, aged 5.5 to 15 months (average, 11.9), had LT. The total bilirubin level at the time of transplantation was 14.4 to 37 mg/dL (average, 24.7). The patients weighed between 3.8 and 12 kg (average, 8.0), and feeding tolerance ranged from no enteric to complete enteric feeding (average, < 33% of calories by enteric feeding). Bowel loss was attributed to necrotizing enterocolitis in two cases, volvulus in two, and birth hypoxia in one. Bowel length ranged from 60 to 120 cm (average, 88.6). Four children (80%) survived LT, and the average follow-up period was 9.3 months. Three (75%) are home; one is on combined hyperalimentation and enteral feeding, and two are on full enteric feeding. One remains in a chronic care facility, on combined enteral and intravenous feeding. The average daily enteral feeding now comprises more than 70% of caloric requirements. The total bilirubin level is .6 to .8 mg/dL (average, .71). Isolated LT for HF in the patient with SBS effectively restores liver function, allowing time for further intestinal adaptation.

The histogenesis of the undifferentiated (embryonal) sarcoma of the liver has been much debated. Originally, some investigators suggested that the tumor could originate from a mesenchymal hamartoma. Others doubted this hypothesis. The demonstration of alpha-1-antitrypsin in some tumors and of cytokeratins in others gave rise to new theories suggesting that the tumor was either a fibrous histiocytoma or a sarcomatoid hepatocellular carcinoma. As a new development in this search for the genesis of the undifferentiated (embryonal) sarcoma of the liver, this report describes a case that seems to substantiate, for the first time, the original hypothesis histogenetically linking the undifferentiated (embryonal) sarcoma and the mesenchymal hamartoma. The case is that of a 12-yr-old girl who developed an undifferentiated (embryonal) sarcoma of the liver in conjunction with a mesenchymal hamartoma. Furthermore, in places, the tumor exhibited striking epithelial differentiation as well as immunoreactivity for cytokeratins, alpha-1-antitrypsin and vimentin. Immunoreactivity for alpha-fetoprotein was limited to the areas of epithelial differentiation.

Children who survive liver transplantation (LT) suffer the adverse effects of life-long immunosuppression. In an attempt to minimize these effects, we have instituted a program of tapering immunosuppression, resulting in chronic monotherapy for children after LT. Seventy-three children ages 4 months to 19 years received LT between January 1987 and December 1992. Patient survival was 85% (62/73), with graft survival of 73%, at one year. Triple therapy with prednisone, cyclosporine, and azathioprine begun at transplant was tapered as follows: 1-2 mg/kg prednisone at discharge was reduced by .2 mg/kg every 2 months until a .2 mg/kg total was reached. Alternate-day steroids (.2 mg/kg) were begun at 1 year and discontinued at 1.5 years. AZA (1 mg/kg) was begun posttransplant and discontinued after any serious viral illness or by 1 year. Currently 37 survivors are > 18 months post-LT and were considered candidates for monotherapy. Monotherapy was attempted in 28 (76%), and 25 of these remain on monotherapy an average of 2 years later. All have normal liver function. After monotherapy and alternate-day steroids were achieved, 66% of children < 5th percentile for height at the time of transplant improved to greater than the 5th percentile. There were 3 (11%) patients who rejected while on monotherapy an average of 1.15 years after it was started. These patients had the following predisposing factors that decreased cyclosporine levels and led to rejection: common bile duct stricture, chronic and intermittent antibiotic administration for urinary tract infection, and noncompliance. In the 9 potential candidates not tapered to monotherapy, 6 have had recurrent acute or chronic rejection; 2 of these now receive FK506. We conclude that the majority of stable pediatric LT recipients may be safely tapered to chronic cyclosporine monotherapy. Increased growth is a major benefit of decreased steroid dosing in these children. Cyclosporine absorption and adequate levels are crucial for success of this approach.

A simple technique for determining the correct catheter length in percutaneous tunnelled catheters in infants and young children has been devised that virtually guarantees accurate catheter tip placement. Sixty-six patients, aged newborn to 5 years (mean, 1.6 years) have successfully undergone this technique. It is safe, simple, precise, quick, and cost effective. It requires only a hemostat, a suture, and the supplies provided in the prepackaged catheter kit. This technique should be used whenever a percutaneous technique for accessing the vein is used and fluoroscopy is available.

The vasoactive factors thrombin, bradykinin (BK), and ATP are released in response to tissue damage and inflammation and act on endothelium to modulate vascular perfusion. We have investigated the second messenger response of endothelium activated by these agonists and, in particular, the mechanism of desensitization to BK. Fura-2 fluorescence ratio imaging of calf pulmonary artery endothelial cells (CPAE) revealed 5- to 10-fold increases on intracellular Ca (Cai) in response to these agents. Maximal doses caused Cai to increase from 52 to 248 nM (thrombin), 556 nM (BK), and 643 nM (ATP). Agonists elicited a rapid (within 30 s) increase of Cai due to release of Ca from intracellular stores followed by a secondary elevation of Cai dependent on entry of external Ca. The temporal characteristics of the Cai responses to all agonists were heterogeneous from cell to cell, and, interestingly, repeated stimulation gave identical signature responses from individual cells, although the amplitude of the Cai response decreased to thrombin and especially bradykinin but not for ATP. This decrease was agonist specific because ATP elicited large increases of Cai after thrombin or BK desensitization. Maximal desensitization was obtained with BK applied for 5-10 min followed by a rest of < 10 min before restimulation. Although desensitization primarily reduced the elevation of Cai due to the release of the internal store, entry of extracellular Ca was also reduced. Cells responded heterogeneously to desensitization in that those with prominent extracellular Ca entry responded most strongly upon a second stimulation with BK. Because desensitized cells still responded to ATP with an increase of Cai, the desensitization was controlled at a step prior to the activation of phospholipase C. Desensitization occurred by a reduction of BK receptor number; a 10-min BK pretreatment reduced [3H]BK binding to receptors by 70% (from 14,600 receptors/cell, Km = 5 nM, to 5,300). As surface receptor numbers decreased, internalized receptors increased as assayed by an acetic acid wash. The time course of the receptor internalization was similar to the decrease in Cai response to BK. We conclude that the vasoactive agonists thrombin, BK, and ATP increase the second messenger Cai in endothelial cells and that a desensitized Cai response occurs with BK, but not with ATP, due to downregulation and endocytosis of the BK receptor.

A 8.6-kg, 10-month-old boy with idiopathic cavernous transformation of the portal vein developed variceal hemorrhage refractory to nonoperative management. A distal splenorenal shunt was performed while the bleeding was controlled with balloon tamponade. Hemorrhage was successfully controlled with no recurrent bleeding and the shunt remains patent at 1 year of follow-up.

Abstracts accepted for presentation at a pediatric surgical meeting usually result in publication. This study attempts to evaluate the relationship of abstracts to the finished, published manuscript. Thirty-three papers published in the Journal of Pediatric Surgery over a 2-year period were randomly selected and compared with their original program abstracts. Only 10 of 33 (30%) had the same title and authors as their abstract. Nine manuscripts underwent revisions of their title and two had different first authors. Nine (27%) had one more author, two had 2 more authors, and 3 had one less author. Only 11 of 33 (33%) had the same data in the paper and in the abstract. Fifteen (45%) had numbers that were mathematically inconsistent with their abstracts. (Range was from 75% fewer cases to 210% more patients.) Ten papers had smaller numbers of patients or experiments while nine had larger numbers than their respective abstracts. Of the seven experimental papers, four had smaller numbers than their original abstract. The conclusions stated in the papers were similar to the program abstracts in 23 of 33 comparisons. In the remaining ten, the conclusions were not only different but rather routinely weaker than in the abstract. In no instance were the data or conclusions stronger. Two papers bore little relationship to their abstract. These facts suggest a need for change in the current evaluation process wherein a highly competitive abstract leads to a presentation, which leads to publication. At the very least, the need is shown for authors to evaluate data completely before submitting an abstract, so that the program committee actually reads the true data.(ABSTRACT TRUNCATED AT 250 WORDS)

A study of 21 consecutive autopsy specimens of infants less than one year of age and weighing less than 6 kilograms was performed to determine the topographic anatomy and regional relationships of the central venous anatomy. This anatomy was compared with 14 additional autopsies performed upon older children. There was no significant difference in diameter between the internal jugular and subclavian venous system, on either the right or left side. In the infant, the right and left subclavian veins entered the central system at an acute angle. The left innominate vein joined the right innominate vein at a right angle. These angulations become less acute after one year of age. This adult configuration may account for the relative ease of central venous cannulation through the percutaneous subclavian approach in the older patient. In contrast, the external and internal jugular veins entered centrally in almost a straight line even in the infant. The findings of this study suggest that the internal and external jugular veins should be considered as safe and reliable portals for percutaneous entry into the central venous system in infants. In the infant less than one year of age, the difficult patient (for example, those with thrombocytopenia or severe pulmonary failure) or when the surgeon is less familiar with the infraclavicular approach, the veins of the neck may, in fact, be the site of choice. Additionally, we believe that a surgeon should not hesitate to switch to the internal or external jugular site after unsuccessful attempts at percutaneous entry into the subclavian vein.

Ninety-four patients underwent rectal biopsy with a suction capsule during a two year period. This painless procedure was performed in seventy-one patients for diagnosis of aganglionosis (Hirschsprung's disease). In nine patients, no ganglion cells were encountered, and subsequent surgery confirmed the diagnosis of Hirschsprung's disease in each of these patients. In twenty-three patients, biopsies were taken to search for neuronal storage disease. Six specimens contained abnormal material in the cytoplasm of the ganglion cells.

Twenty pediatric patients with a mean age of 9.2 years exhibited 21 injuries to arteries of an extremity and underwent operation. Included were 12 iatrogenic injuries and nine non-iatrogenic penetrating injuries. Femoral, brachial, popliteal, radial, axillary, iliac, and tibial arteries were sites of vascular trauma. Long-term follow-up, averaging 36 months, was possible in 14 patients. Postoperative scanograms, digital impedance plethysmographic studies, and bone age roentgenograms were routinely obtained. Limb length disparities greater than 5 mm, extremity blood pressure differentials greater than 10 mm Hg, and bone age retardation were encountered. Proper treatment of pediatric patients with acute arterial injuries of an extremity requires early operative intervention and continuous postoperative follow-up during years of active growth. If chronic arterial insufficiency ensues, arteriographic studies should be obtained and arterial reconstruction undertaken.

The infusion of live E. coli in the puppy produces a severe and usually lethal model of pediatric septic shock with characteristic reduction in cardiac output and blood pressure. Hemodynamic abnormalities are partially reversed with fluid resuscitation alone, and large volumes, supplemented with albumin well within tolerated fluid loads, produce the most pronounced corrections of these derrangements. Certain metabolic changes appear to be unique to the young animal and their correction is less successful regardless of resuscitation regimen. These findings suggest that the initial fluid management of the bacteremic pediatric patient should include Ringer's lactate and 5% albumin at approximately 105% of patient's blood volume. Further resuscitation fluid, as well as the role of steroids and antibiotics, remain work currently being carried out in our laboratory.

Thymic cysts are considered uncommon lesions in the differential diagnosis of pediatric neck masses. They have been described as asymptomatic and of little clinical consequence. Recent reports have stressed the possibility of respiratory compromise associated with these lesions. We reviewed our experience with cervical thymic cysts with emphasis on respiratory problems. Ten pediatric patients underwent surgery and were found to have cervical thymic cysts. Ages ranged from newborn to 14 years. There were four boys and six girls. Two were found to have the thymic cysts at time of neck exploration for Grave's disease and hyperparathyroidism. Of the remaining eight patients, all had mobile cystic masses, located anterior to but extending beneath the lower third of the sternocleidomastoid muscle. The size of the mass ranged from 3.0 to 8.5 cm. Preoperative diagnosis included cystic hygroma/branchial cleft cyst (five), lymphoma (one), teratoma (one), and thymic cyst (one). All had a history of rapidly developing neck mass. Seven of the eight gave a history of upper respiratory tract infection (URI) prior to the development of the mass. Five had imaging studies that showed tracheal compression. Three of these required airway management in the early postoperative period. All were excised through a neck incision, with two requiring sternal extension. Histology showed cholesterol crystals, Hassall's corpuscles, and giant cell reaction diagnosis of thymic cysts. There has been no recurrence and no permanent respiratory sequela in the ten patients. Cervical thymic cysts are benign lesions that may be more common than literature suggests.(ABSTRACT TRUNCATED AT 250 WORDS)

Thermodilution cardiac output determinations were compared with dye-dilution measurements in normovolemic and hypovolemic puppies. Good correlation was achieved with small volumes of cold and warm saline. Injectate volumes and significant caval displacement of the injectate port did not significantly affect thermodilution output measurements. This study demonstrates that thermodilution is a reliable and practical method of cardiac output determination in small subjects and suggests that this technique may be useful in the clinical management of neonates and small infants.

Over the past decade, nonoperative management of most pediatric blunt abdominal trauma has emerged as accepted practice. It is possible that treatment of associated hollow visceral disruption might be missed or delayed because of this nonoperative approach. In a review of all cases of intestinal perforation from blunt trauma seen over the past 6 years, we found 12 cases of intestinal disruption in more than 600 cases of significant blunt trauma. Child abuse caused eight cases and four were motor vehicle related (MVR). Seven of eight battered children had a delay of more than 48 hours from injury to hospital presentation. Three of four MVR patients had an 18-hour delay from injury to operation. Ten of 12 patients survived. The two children who succumbed were both battered and were moribund and unstable when first seen and failed to respond to aggressive stabilization and surgery. Serial physical examinations, contrast radiographic studies, and peritoneal lavage were the most helpful diagnostic modalities. There were no significant complications and no patient required more than one operation (except for ostomy closure). All surviving patients are well at followup and seven of ten have been followed for more than 3 years; two are not yet 1 year from surgery and one is lost to followup. Several principles have emerged from this review: 1) motor vehicle trauma and child abuse are the major etiologic factors in childhood blunt trauma; 2) accurate and rapid diagnosis of intestinal perforation in children is difficult; 3) recovery in the presence of stable vital signs can be expected, even with the long delays; and 4) abused children must be carefully evaluated for abdominal trauma.

Transillumination (TI) is a safe and reliable technique for evaluating masses or the presence of free air in the thorax or abdomen. TI can also be of help in the accurate placement of catheters or needles in the chest, abdomen, bladder, or vessels. Its use in several hundred cases has been documented by this report.

The association of gastroesophageal reflux and its sequelae in the infant with cystic fibrosis has gone virtually unnoticed. Eight of 40 newly diagnosed infants with cystic fibrosis seen over a 24 month period had significant gastroesophageal reflux, characterized by vomiting (7 infants), recurrent pneumonia (7 infants), and failure to thrive (4 infants). Gastroesophageal reflux was demonstrated by a combination of barium swallow, scintiscan, manometry, and esophagoscopy. Three infants had rapid and permanent alleviation of symptoms after standard medical therapy; in five infants, therapy failed and they required a Nissen fundoplication. Three infants required postoperative ventilatory support for 1, 2, and 5 days. No tracheostomies were required. Postoperative hospital stay averaged 12 days (range 5 to 30 days). There were no complications or perioperative deaths. All children had complete relief of their preoperative symptoms. The group that required surgery presented earlier (mean 7 weeks of age) to the cystic fibrosis center than either the medically treated group (mean 5 months of age) or the group free of gastroesophageal reflux symptoms (5 1/2 months of age). Also, postoperative hospitalization time markedly decreased from 50 percent of 577 combined patient days preoperatively to 4 percent of 1,639 days postoperatively; this 4 percent then paralleled what was seen in the group without gastroesophageal reflux (3 percent of 19,966 combined patient days) and the group controlled medically (5 percent of 1,897 days). The pulmonary manifestations of cystic fibrosis are extremely variable, and evaluation of the effect that any intervention has on the natural history of the disease is difficult. Nonetheless, we believe that even this small series suggests that gastroesophageal reflux and its complications can significantly alter the courses of some children with cystic fibrosis. Gastroesophageal reflux should be managed as aggressively as it is in any child with reflux, and a successful and safe reduction of symptoms can be expected with intensive management.

Total proctocolectomy for benign disease can be done entirely from within the abdominal incision, thus, avoiding the extra time and inconvenience of operating with the patient in the lithotomy position. This procedure is quick and simple, and the visibility is excellent even in a narrow adult male pelvis, and the lithotomy position is completely eliminated. Results in six patients have been gratifying.

Glucocorticoid hormones induced a stringent dependence on serum for the in vitro proliferation of Fu5 rat hepatoma cells by suppressing the growth rate and final quiescent cell density. Treatment of dexamethasone-suppressed quiescent Fu5 with serum plus insulin caused a rapid reinitiation of cellular proliferation and DNA synthesis that peaked at 16 h. RNA dot blot analysis of this time course showed that the transcript levels for the proto-oncogenes c-fos, c-myc, and c-rasKi peaked at 0.5, 2, and 4 h, respectively, while expression of c-rasHa and ornithine decarboxylase transcripts rose steadily during 16 h. Microspectrofluorimetric measurements of cytosolic calcium (Ca2+i) with fura-2 showed that insulin and serum, alone or in combination, elicited no changes in Ca2+i over a 50-min time course, although ATP, which is not a mitogen, induced large increases in Ca2+i. Cytosolic pH, pHi, was also measured using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Insulin and serum, alone or in combination, did not cause pHi to increase in either 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) (pHi 7.17)- or HCO3/CO2 (pHi 7.19)- buffered media. Acid-loading of cells with NH4Cl indicated that both quiescent and proliferating Fu5 cells have equally active, amiloride-sensitive Na/H exchangers. Therefore, induction of DNA synthesis and proto-oncogene expression occurs in Fu5 epithelial tumor cells in the absence of any short term increases of pHi or Ca2+i.

We have described an infant in whom migration of a transected umbilical artery catheter resulted in sudden vascular ischemia of an extremity. Early operative retrieval was successful, but long-term effects of this complication were encountered. We have outlined an approach to the initial management of the complication. In addition, this case demonstrates the need for careful follow-up for identification and treatment of the long-term sequelae in the involved extremity.

Regulation of intracellular pH (pHi) was studied in Fu5, a rat hepatoma cell line that maintains a variety of differentiated functions. Microspectrofluorimetry of the pH-sensitive dye 2',7'-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF) was used to measure pHi in 10-15 cells growing on cover glasses that were mounted in a flow-through chamber on the stage of a microscope. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solutions, pHi was 7.14, and intrinsic buffer capacity was inversely related to pHi. Amiloride (0.1 mM) caused pHi to decrease by 0.33 pH units in 4 min. Recovery from an acid load (using either NH4 prepulse technique or Na-free solutions) was completely blocked by amiloride. In HCO3-CO2-buffered solutions, pHi was 7.15, and buffer capacity was relatively insensitive to pHi between pHi of 6.6 and 7.2. Amiloride caused pHi to decrease by only 0.09 units. Recovery from an acid load was Na dependent, occurred in Cl-free solutions, and was totally blocked by the combination of amiloride plus 0.5 mM dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (H2DIDS); recovery occurred when either amiloride or H2DIDS was removed. Removal of external Cl caused a rapid, H2DIDS-blockable alkalinization that was faster in HCO3-CO2 than in HEPES. The apparent Km for Clout for relaxation of Cl-free alkalinization was 4.5 mM. Rate of HCO3 transport during Cl-free treatment increased at alkaline resting pHi. It is concluded that Fu5 cells have two Na-dependent base-loading mechanisms and an acid-loading Cl-HCO3 exchanger. In solutions containing HCO3-CO2, the Na-H exchanger accounts for approximately 40% of recovery from an acid load, and a Na-HCO3 cotransporter accounts for the remainder. Recovery from an alkaline load appears to occur through the activity of the Cl-HCO3 exchanger.

Regulation of intracellular pH, pHi, was studied using microspectrofluorimetry of the pH-sensitive, fluorescent dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein in the rat intestinal crypt cell line, IEC-6. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solutions with pHi 7.25, treatment with a pulse of NH4Cl caused cells to acidify and then recover to control level. Because recovery was Na dependent, blocked by 1 mM amiloride, and unaffected by the presence and absence of Cl, it was likely because of a Na+-H+ exchanger. Cells were also acid loaded by changing from HEPES to HCO3-CO2-buffered solutions. pHi again recovered, but 1 mM amiloride reduced the rate of H+ efflux by only 47%. This HCO3-dependent, amiloride-insensitive H efflux required Na+ but not Cl- and was completely blocked by 200 microM [H2] 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). We conclude that a Na+-HCO3- cotransporter was operative. Cl-free solutions caused pHi to increase from 7.19 to 7.41; this effect required the presence of exogenous HCO3-CO2 but not Na and was blocked by 200 microM [H2]DIDS. A Cl- -HCO3- exchanger is the most likely explanation for these data. All the pHi regulatory mechanisms are operative in NaCl-HCO3-CO2-buffered solutions. The Na+-H+ and Na+-HCO3- mechanisms are acid extruders, whereas the Cl- -HCO3- exchanger is an acid loader. These transporters may be important for generating HCO3 secretion by intestinal crypt cells.

Since shock secondary to hemorrhage is not infrequently encountered in the pediatric patient, a puppy model was devised to help measure and monitor cardiovascular and metabolic changes that occur before and after resuscitation from hypovolemic shock (mean arterial pressure of 50 mm Hg for 1 hr). Three resuscitation protocols were compared: whole blood (replacement:shed) 1:1, 5% albumin in Ringer's lactate 1:1; and Ringer's lactate 3:1. All dogs survived the experiment and responded similarly during the shock period. Thermal dilution cardiac output rose in all groups after resuscitation; however, in the Ringer's lactate and 5% albumin groups, cardiac output was statistically greater than that observed in the blood group. In all groups, pH and blood pressure approached but did not return completely to baseline levels after resuscitation. In addition, early resuscitation demonstrated a further decrease pH ("hidden acidosis") before it began to return toward normal as resuscitation progressed. This study suggests that the infusion of large volumes of Ringer's lactate or 5% albumin in Ringer's lactate are equally efficacious in the treatment of hemorrhage. However, 5% albumin seems to be preferable because it allows infusion of a smaller quantity of electrolyte solution with equivalent physiologic benefits.

During the past 4 yr, 60 patients with Hirschsprung's disease have been treated at our institution. Twenty-eight patients within this group have undergone a modified endorectal pull-through procedure. There are 18 males and 10 females in the series. There are 5 children with total colonic involvement, 3 patients with aganglionosis to the mid-transverse colon, and one child with Hirschsprung's disease extending to the distal jejunum. The associated anomalies have consisted of four cases of Down's syndrome, one of whom also has transposition of the great vessels. There has been no operative-related mortality or late mortality in our series. Two major complications (anastomotic leak following a colostomy closure and incorrect pathological diagnosis of aganglionic level) and five minor complications have occurred. The average follow-up period is 31.3 mo. The functional results postoperatively have been excellent. The 18 patients over the age of 3 yr are completely toilet-trained. The remaining patients are too young to be toilet-trained, but are continent in the sense that they do not soil between bowel movements. Because of the satisfying functional results in this series, we have now expanded our indications for this procedure to patients requiring total colectomy for ulcerative colitis and familial polyposis. During the past 2 yr, 8 patients with ulcerative colitis have undergone the endorectal pull-through together with a total colectomy.

The ideal wound-support material would reinforce a wound early in the healing process when intrinsic wound strength is the weakest, yet disappear over time, preventing many of the untoward late effects seen with currently utilized nonabsorbable materials. This study was designed to evaluate the effectiveness of a newly designed absorbable material, polyglycolic acid mesh (Dexon), as a buttress for abdominal wounds closed under moderate tension. Young male rats (n = 211) were divided into three experimental groups. Animals in groups 1 (n = 96) and 2 (n = 95) had a 1.2 cm2 midline abdominal wall defect created and closely primarily. Animals in group 2 had a 2 X 5 cm piece of polyglycolic acid mesh sutured to the anterior abdominal wall overlying the closed abdominal defect. Animals in group 3 (n = 20) were unoperated controls. The animals in groups 1 and 2 were killed 1, 2, 3, 4, and 5 weeks after surgery. The entire anterior abdominal wall was removed and placed upon a bursting strength testing device. Bursting strength determinations of the supported and unsupported abdominal closures revealed that the strength of the wounds reinforced with polyglycolic acid mesh was significantly greater than unsupported wounds at 1, 2, and 3 weeks after surgery. Wounds supported with mesh had bursting strengths similar to unoperated abdomens by the first postoperative week. This study demonstrates that abdominal wall defects in rats closed primarily develop increased wound strength when the closure is supported by absorbable polyglycolic acid mesh. The use of an absorbable material may alleviate potential late complications associated with implantation of nonabsorbable materials. The clinical application of such a material remains to be determined.

Angiography is often essential in the evaluation of patients with suspected vascular injuries. However, arterial cannulation has a significant inherent complication rate, especially in small patients. Therefore, a less invasive method of evaluating children with such injuries is desirable. We report nine children (age range, 9 months to 16 years; median, 7 years) in whom intravenous digital subtraction angiography (IV-DSA) was used to evaluate suspected vascular injuries. IV-DSA showed a false aneurysm in two children, one managed by ligation alone and the other by resection with primary anastomosis. One child was found to have an arteriovenous fistula, which was treated by ligation. An iliac occlusion, following an arteriogram to evaluate a liver tumor, was documented by IV-DSA and successfully managed with aggressive anticoagulant therapy. Demonstration of a normal vascular tree avoided exploration in four children. A planned skin flap was abandoned in a child who suffered an electrical injury when IV-DSA showed lack of adequate vascular supply. In all nine cases, the IV-DSA obviated the need for intraarterial angiography. In addition to avoiding arterial cannulation, IV-DSA required significantly less radiation and less time to perform than conventional arteriography. Motion artifact, vessel overlap, and some loss of minute detail are some of its potential shortcomings. IV-DSA is an effective method of screening children with suspected vascular injuries. In addition, our experience has shown that IV-DSA can be the definitive diagnostic procedure, although intraarterial angiography may be necessary in selected cases.

A child born without scalp, or dura to cover the brain (aplasia cutis congenita) was successfully treated by a multidiscipline team. A coexisting rupture omphalocele forced a change in treatment from the currently recommended regimen of mandatory early scalp closure. Homograft skin was used to protect the brain during the time the omphalocele was treated and skin flaps were delayed. Fluoroscein dye was utilized to determine flap viability and predicted ischemia until after a third delaying procedure was performed. The successful outcome suggests that the present philosophy of early surgical closure being essential for survival in infants with large cranial defects can be altered and, in fact, permanent full-thickness flaps may be designed, tested for viability, and delayed while homograft skin protects the infant's brain from infection and thrombosis.

Seventy children and adolescents hospitalized for Crohn's disease at the University of Michigan Medical Center between 1966 and 1976 are reviewed. Thirty-three of these children were managed medically and 37 underwent a total of 60 operative procedures. There were 33 bowel resections, 7 appendectomies, 4 abscess drainages, 3 bowel bypasses, and 13 miscellaneous operative procedures. The total operative mortality was 1.7%, and there were 10 complications, all of which were successfully managed. Among the 26 children undergoing bowel resections, 22 were below the third percentile for weight preoperatively. Nearly two-thirds of these gained weight to the 35th percentile following resection. The remainder of the children had a variety of growth and symptomatic responses to surgery. Resection aimed at complete removal of diseased bowel can be expected to yield substantial weight gain in children with Crohn's disease.

A premature baby with gastroschisis, ileal atresia and secondary short gut syndrome was sustained with the use of peripheral hyperalimentation consisting of 2 per cent Amigen, 12 per cent glucose and 10 per cent Intralipid at an average rate of 140 to 160 milliliters per kilogram per day or 100 to 111 kilocalories per kilogram per day. The weight of the child increased during the first four months to approximately 14 grams per day, with body length increasing by about 6 millimeters per week. Six reliable measurements of the total body water of the child during the four month period were obtained using deuterium oxide dilution followed by double vacuum distillation and falling drop analysis in a constant temperature chamber. Measurements obtained showed a gradual decrease of total body water from 77.13 per cent of body weight to 60.50 per cent during the study period, with values consistently on the lower end of the spectrum of known normal controls, even during periods of increased growth rates of as much as 35 grams per day. These data on total body water, coupled with the observed gains in body weight and length, support tissue accretion rather than fluid retention as the mechanism of weight gain in long term, high volume peripheral hyperalimentation.

An 18-month-old boy ingested approximately 18 g FeSO4, equivalent to 336 mg/kg elemental Fe. He rapidly developed severe gastroenteric symptoms, obtundation, and transient hypotension. The serum iron level two hours after ingestion was 6,798 micrograms/dL. He was treated with deferoxamine intravenously, enterally, and as a lavage solution. His hospital course was notable for lack of severe neurologic, hepatic, metabolic, or cardiovascular complications acutely with apparent complete recovery, although he returned six weeks after ingestion with intestinal obstruction due to a jejunal stricture.

Since the first attempted repair in 1935, a total of 365 infants have undergone treatment for esophageal atresia with or without tracheoesophageal fistula. To evaluate the improvement in our results, we have divided our patients into four, approximately equal, time periods. The overall late survival has indeed improved during each of the four decades from between 36% and 53% to 68% in the last ten years. During this past decade, the group A risk infants (35 patients) had a 3% mortality, the group B (20 patients) had a 5% mortality, but the group C babies (22 patients) had a 41% mortality due to associated anomalies or severe prematurity. Anastomotic leaks and recurrent fistulas were each encountered in approximately 5% of the cases in all decades. Postoperative stricture has been encountered in 20% of the entire series and no esophageal replacements have been required.

The intravenous infusion of amino acid and carbohydrate solutions is a well-established technique for nutritional support of the pediatric surgical patient. By using peripheral veins for total parenteral nutrition (TPN), weight gain can be achieved and the complications of central venous catheters avoided. Over a 2-year period, 45 patients from 1 day to 16 years of age received peripheral TPN in which fat provided a major portion of the daily calories. Treatment periods ranged from 5 to 74 days. Each patient received 125 cc/kg/day, with 30% of the calories derived from a fat emulsion and the remainder from a 12% glucose-2% amino acid solution. All 29 patients under 1 year of age gained weight, averaging 18 gm/day. These infants received an average of 98.8 calories/kg/day, with 31 calories provided by fat. In this group, the mean nonprotein calorie to nitrogen ratio (CNR) was 285 calories/gm, ranging from 239 to 343. Fat calorie and carbohydrate CNRs were determined and no correlation to weight gain could be found for either calorie source. The few complications related to this technique included three episodes of phlebitis, two small skin sloughs, two subcutaneous abscesses, and two episodes of jaundice. Normal weight gain can be achieved in infants after operation by employing peripherally infused, intravenous fat as a major calorie source. Furthermore, regardless of calorie source, a CNR of 285 calories/gm allows normal growth and weight gain in these critically ill neonates.

During the last four years, 25 patients have been operated upon using a technical modification of the endorectal procedure for the treatment of Hirschsprung's disease. There have been no major complications, and the ease with which the lower anastomosis was carried out has been quite remarkable. This opinion has been substantiated by surgeons who previously used other techniques for the lower anastomosis and have now adopted this modification.

The efficacy of corticosteroid therapy in the treatment of shock remains controversial. In order to evaluate this question, the following controlled experimental study was undertaken. There were 44 puppies (2-6 kg) used to examine the effects of methylprednisolone (30 mg/kg) in both hemorrhagic and live Escherichia coli septic shock. In order to isolate the effects of steroid treatment, no volume or antibiotic therapy was given. Arterial, venous, and pulmonary artery catheterization allowed continuous hemodynamic and metabolic monitoring. One control group received steroid treatment and was not subjected to shock. Septic shock was achieved by a rapid bolus infusion of 10(9) live E. coli organisms. Hemorrhagic shock was produced by bleeding the puppy an average of 43% of his blood volume. Four septic and four hemorrhagic shock groups received either no treatment, steroids at the time of shock, or steroids 30 min before or after shock. Cardiac outputs of less than 50% of control values and significant lactic acidosis were documented in all of the shock animals. The septic groups showed more profound alterations in these parameters and a decreased overall survival. No statistically significant differences could be found, however, in the hemodynamic, metabolic or survival figures among the different septic shock groups, or among the various hemorrhagic shock animals. The anticipated preservation of cardiac output and decrease in leakage of lysosomal acid phosphatase were not seen with any treatment schedule. The theoretical benefits of corticosteroid treatment in shock could not be documented in these two models of severe septic and hemorrhagic shock in puppies.