Antioxidant treatment ameliorates germ cell apoptosis induced by a high-dose ionizing irradiation in rats.

BACKGROUND: Exposure to ionizing radiation results in cytotoxic and genotoxic effects caused mainly by the oxidative damage. In the present study, we investigated the radioprotective effect of novel antioxidant cocktail on germ cell apoptosis and spermatogenesis in rats subjected to whole body radiation (WBIR). METHODS: Adult male rats weighing 250-270 g were divided into four groups, eight rats each. Group 1 served as untreated control, group 2 received an IP single dose of antioxidant cocktail (1 ml). Group 3 was exposed to a WBIR (6 Gy). Group 4 received antioxidant cocktail before WBIR. Rats from each group were killed after 48 h. MDA levels were measured in serum (TBARS assay). Johnsen's criteria and the number of germinal cell layers were used to categorize spermatogenesis. TUNEL assay was used to determine germ cell apoptosis. Statistical analysis was performed using one-way ANOVA test. RESULTS: WBIR resulted in histological testicular damage (decrease in Johnsen's criteria, p < 0.05) that was accompanied by a significant increase in germ cell apoptosis, expressed as the number of apoptotic cells per 100 tubules (AI-1 apoptotic index) and the number of positive tubules per 100 tubules (AI-2 apoptotic index). Treatment with antioxidant cocktail resulted in a significant decrease in germ cell apoptosis (33% decrease in AI-1, p < 0.05 and 34% decrease in AI-2, p < 0.05) that was accompanied by an improved spermatogenesis (increase in Johnsen's criteria, p < 0.05). CONCLUSIONS: In a rat model of WBIR, antioxidant treatment ameliorates oxidative stress-induced testicular damage, decreases germ cell apoptosis and improves spermatogenesis.

The role of intermediate filaments in maintaining integrity and function of intestinal epithelial cells after massive bowel resection in a rat.

PURPOSE: Intermediate filaments (IFs) are a part of the cytoskeleton that extend throughout the cytoplasm of all cells and function in the maintenance of cell-shape by bearing tension and serving as structural components of the nuclear lamina. In normal intestine, IFs provide a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. The purpose of this study was to evaluate the role of IFs during intestinal adaptation in a rat model of short bowel syndrome (SBS). MATERIALS AND METHODS: Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75% bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression (DGE) analysis was used to determine the cytoskeleton-related gene expression profiling. IF-related genes and protein expression were determined using real-time PCR, Western blotting and immunohistochemistry. RESULTS: Massive small bowel resection resulted in a significant increase in enterocyte proliferation and concomitant increase in cell apoptosis. From the total number of 20,000 probes, 16 cytoskeleton-related genes were investigated. Between these genes, only myosin and tubulin levels were upregulated in SBS compared to sham animals. Between IF-related genes, desmin, vimentin and lamin levels were down-regulated and keratin and neurofilament remain unchanged. The levels of TGF-ß, vimentin and desmin gene and protein were down-regulated in resected rats (vs sham animals). CONCLUSIONS: Two weeks following massive bowel resection in rats, the accelerated cell turnover was accompanied by a stimulated microfilaments and microtubules, and by inhibited intermediate filaments. Resistance to cell compression rather that maintenance of cell-shape by bearing tension are responsible for contraction, motility and postmitotic cell separation in a late stage of intestinal adaptation.

Accelerated intestinal epithelial cell turnover after bowel resection in a rat is correlated with inhibited hedgehog signaling cascade.

PURPOSE: The hedgehog (Hh) signaling pathway is one of the key regulators of gastrointestinal tract development. Recent studies point to the role of hedgehog signaling in regulating adult stem cells involved in maintenance and regeneration of intestinal stem cells. The purpose of this study was to evaluate the role of Hh signaling during intestinal adaptation in a rat model of short bowel syndrome (SBS). METHODS: Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75 % bowel resection. Parameters of intestinal adaptation, enterocyte proliferation, and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression analysis was used to determine the Hh signaling gene expression profiling. Hh-related genes and protein expression were determined using Real-Time PCR, Western blotting, and immunohistochemistry. RESULTS: Massive small bowel resection resulted in a significant increase in enterocyte proliferation and concomitant increase in cell apoptosis. From the total number of 20,000 probes, 13 genes related to Hh signaling were investigated. In jejunum, eight genes were down-regulated, three genes up-regulated, and two genes remained unchanged. In ileum, five genes were down-regulated and six genes were unchanged in SBS vs sham animals. SBS rats also demonstrated a significant three- to fourfold decrease in SMO, GIL, and PTCH mRNA, and protein levels (determined by Real-Time PCR and Western blot) compared to control animals. CONCLUSION: Two weeks following massive bowel resection in rats, the accelerated cell turnover was accompanied by an inhibited Hh signaling pathway. Hh signaling may serve as an important mediator of reciprocal interactions between the epithelium and the underlying mesenchymal stroma during intestinal adaptation following massive bowel resection in a rat.

The role of the BMP signaling cascade in regulation of stem cell activity following massive small bowel resection in a rat.

PURPOSE: Bone morphogenetic proteins (BMPs) are a group of growth factors that are implicated in intestinal growth, morphogenesis, differentiation, and homeostasis. The role of the BMP signaling cascade in stimulation of cell proliferation after massive small bowel resection is unknown. The purpose of this study was to evaluate the role of BMP signaling during intestinal adaptation in a rat model of short bowel syndrome (SBS). METHODS: Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75 % bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression analysis was used to determine the BMP signaling gene expression profiling. BMP-related genes and protein expression were determined using real-time PCR, Western blotting and immunohistochemistry. RESULTS: From the total number of 20,000 probes, 8 genes related to BMP signaling were investigated. From these genes, five genes were found to be up-regulated in jejunum (BMP1-10 %, BMP2-twofold increase, BMP3-10 %, BMP2R-12 % and STAT3-28 %) and four genes to be up-regulated in ileum (BMP1-16 %, BMP2-27 %, BMP3-10 %, and STAT3-20 %) in SBS vs sham animals with a relative change in gene expression level of 10 % or more. SBS rats also demonstrated a significant increase in BMP2 and STAT3 mRNA and protein levels (determined by real-time PCR and Western blot) compared to control animals. CONCLUSION: Two weeks following massive bowel resection in rats, the BMP signaling pathway is stimulated. BMP signaling may serve as an important mediator of reciprocal interactions between the epithelium and the underlying mesenchymal stroma during intestinal adaptation following massive bowel resection in a rat.

Fenofibrate reduces intestinal damage and improves intestinal recovery following intestinal ischemia-reperfusion injury in a rat.

PURPOSE: Fenofibrate (FEN) is known as a nuclear receptor activator which regulates many pathophysiological processes, such as oxidative stress, inflammation, and leukocyte endothelium interactions. Recent studies have demonstrated an anti-oxidant, anti-inflammatory, and anti-ischemic role of FEN in the attenuation of ischemia-reperfusion (IR) injury in the kidney, liver, brain, and heart. The purpose of the present study was to examine the effect of FEN on intestinal recovery and enterocyte turnover after intestinal IR injury in rats. METHODS: Male Sprague-Dawley rats were divided into four experimental groups: (1) sham rats underwent laparotomy, (2) sham-FEN rats underwent laparotomy and were treated with intraperitoneal (IP) FEN (20 mg/kg); (3) IR rats underwent occlusion of both the superior mesenteric artery and the portal vein for 30 min followed by 24 h of reperfusion, and (4) IR-FEN rats underwent IR and were treated with IP FEN immediately before abdominal closure. Intestinal structural changes, Park's injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 h following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real-time PCR, Western blot, and immunohistochemistry. RESULTS: Treatment with FEN resulted in a significant decrease in Park's injury score in jejunum (32 %) and ileum (33 %) compared to IR animals. IR-FEN rats also demonstrated a significant increase in mucosal weight in jejunum (23 %) and ileum (22 %), mucosal DNA (38 %) and protein (65 %) in jejunum, villus height in jejunum (17 %) and ileum (21 %), and crypt depth in ileum (14 %) compared to IR animals. IR-FEN rats also experienced significant proliferation rates as well as lower apoptotic indices in jejunum and ileum which was accompanied with higher Bcl-2 levels compared to IR animals. CONCLUSIONS: Treatment with fenofibrate prevents intestinal mucosal damage and stimulates intestinal epithelial cell turnover following intestinal IR in a rat model.

Effect of taurine on intestinal recovery following intestinal ischemia-reperfusion injury in a rat.

PURPOSE: Taurine (TAU) is a sulfur-containing amino acid that is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti-oxidation, and immunomodulation. Several studies have established that treatment with TAU significantly protects cerebral, cardiac and testicular injury from ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of TAU on intestinal recovery and enterocyte turnover after intestinal IR injury in rats. METHODS: Male Sprague-Dawley rats were divided into four experimental groups: (1) Sham rats that underwent laparotomy, (2) Sham-TAU rats that underwent laparotomy and were treated with intraperitoneal (IP) TAU (250 mg/kg); (3) IR-rats that underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 48 h of reperfusion, and (4) IR-TAU rats that underwent IR and were treated with IP TAU (250 mg/kg) immediately before abdominal closure. Intestinal structural changes, Park's injury score, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. The expression of Bax, Bcl-2, p-ERK and caspase-3 in the intestinal mucosa was determined using Western blot and immunohistochemistry. RESULTS: Treatment with TAU resulted in a significant decrease in Park's injury score compared to IR animals. IR-TAU rats also demonstrated a significant increase in mucosal weight in jejunum and ileum, villus height in jejunum and ileum and crypt depth in ileum compared to IR animals. IR-TAU rats also experienced significantly lower apoptotic indices in jejunum and ileum which was accompanied by a higher Bcl-2/Bax ratio compared to IR animals. CONCLUSIONS: Treatment with taurine prevents gut mucosal damage and inhibits intestinal epithelial cell apoptosis following intestinal IR in a rat.

Diagnosis and surgical management of recurrent tracheoesophageal fistulas.

Recurrent tracheoesophageal fistula (TEF) is difficult to diagnose and even more difficult to repair. The key to the diagnosis is an adequate contrast study and bronchoscopy. The key to the repair is complete separation of the esophagus from the trachea, with the placement of viable tissue between the two suture lines. I have presented a personal experience with 38 consecutive repairs of recurrent TEFs. The original series of 26 patients had three recurrences, all of which were re-repaired successfully. My more recent experience with the last 12 patients, who were far more complex, was also successful in ultimately repairing the recurrent TEFs.

Treatment with glutamine is associated with down-regulation of Toll-like receptor-4 and myeloid differentiation factor 88 expression and decrease in intestinal mucosal injury caused by lipopolysaccharide endotoxaemia in a rat.

Recent evidence suggests that lipopolysaccharide (LPS) endotoxaemia in a rat causes significant mucosal injury. Our objective was to determine the effects of glutamine (Gln) on Toll-like receptor 4 (TLR-4), myeloid differentiation factor 88 (Myd88) and tumour necrosis factor (TNF)-alpha receptor-associated factor 6 (TRAF6) expression in intestinal mucosa following LPS endotoxaemia in a rat. For this purpose, male Sprague-Dawley rats were assigned randomly to one of three experimental groups of 10 rats each: (i) control rats underwent intraperitoneal (i.p.) injection of sterile saline once a day; (ii) rats were treated with LPS given i.p. once a day at a dose of 10 mg/kg for 48 h (two doses); and (iii) rats were pretreated with oral Gln given in drinking water (2%) 48 h before and following injection of LPS. Intestinal mucosal parameters, enterocyte proliferation and apoptosis were determined at death. TLR-4 and MyD88 mRNA expression was measured with reverse transcription-polymerase chain reaction (RT-PCR). TLR-4 and MyD88 protein expression were analysed by Western immunoblotting. We observed a statistically significant (P < 0.05) decrease in mucosal weight, mucosal DNA and enterocyte proliferation and a significant increase in enterocyte apoptosis in rat intestine, following LPS administration. These changes were attenuated significantly by dietary Gln. Expression of TLR-4, MyD88 and TRAF6 mRNA in the mucosal ileum was significantly higher in LPS rats versus control rats (P = 0.0006, P = 0.0015, P = 0.03, respectively) as well as TLR-4 and MyD88 protein expression. The administration of Gln reduced significantly the expression of TLR-4, MyD88 and TRAF6 (P = 0.023, P = 0.014, P = 0.035, respectively) mRNA as well as TLR-4 and MyD88 protein expression in ileum compared to LPS animals. We did not find a significant change in the expression of TLR-4, MyD88 or TRAF6 in the jejunum of different groups. We conclude that treatment with Gln was associated with down-regulation of TLR-4, MyD88 and TRAF6 expression and concomitant decrease in intestinal mucosal injury caused by LPS endotoxaemia in a rat.

Effect of elevated intra-abdominal pressure and hyperoxia on portal vein blood flow, hepatocyte proliferation and apoptosis in a rat model.

BACKGROUND/PURPOSE: Indications for a laparoscopic approach for the management of biliary atresia in children are not clearly defined. We have recently shown that persistent intra-abdominal pressure (IAP) significantly decreased portal vein (PV) flow. Ventilation with a high concentration of oxygen after abdomen deflation raises concerns of increased oxidative stress but has also been shown to exert beneficial effects on splanchnic ischemia/reperfusion. The purpose of the present study was to evaluate the effects of IAP and hyperoxia on liver histology, hepatocyte proliferation and apoptosis in a rat model of abdominal compartment syndrome (ACS). METHODS: Male Sprague-Dawley rats were anesthetized with intraperitoneal ketamine and xylasine. After a midline laparotomy, the PV was isolated. Ultrasonic blood flow probes were placed on the vessel for continuous measurement of regional blood flow. Mean arterial blood pressure (MABP) was continuously measured. Two large-caliber percutaneous peripheral intravenous catheters were introduced into the peritoneal cavity for inflation of air and measurement of IAP. Rats were divided into three experimental groups: 1) Sham rats were subjected to IAP of 0 mmHg; 2) ACS rats were subjected to IAP of 6 mmHg for 2 hours and were ventilated with air; and 3) ACS-O (2) rats were subjected to IAP of 6 mmHg for 2 hours and were ventilated with 100 % O (2) during the operation and ventilation was continued for 6 hours after operation. Liver structural changes, hepatocyte proliferation (using BrdU assay) and apoptosis (using Tunel assay) were determined 24 hours following operation. RESULTS: IAP at 6 mmHg caused a twofold decrease in PV flow compared to sham animals. Hyperoxia resulted in a less significant decrease in PV flow compared to air-ventilated animals. Despite a significant decrease in PV blood flow, 24 hours after abdominal deflation only a few animals demonstrated histological signs of liver damage. The small histological changes were accompanied by increased hepatocyte apoptosis and enhanced hepatocyte proliferation in 25 % of animals, suggesting a liver repair response. CONCLUSIONS: Despite a significant decrease in PV blood flow, persistent IAP for 2 hours results in few changes in liver histology, and stimulates hepatocyte proliferation and apoptosis in only a few animals, supporting the presence of a recovering mechanism. Treatment with hyperoxia did not significantly change hepatocyte proliferation and apoptosis.

Familial extra-adrenal pheochromocytoma. A new syndrome.

Pheochromocytomas in the same anatomic site, the right renal hilum, occurred in a family over three successive generations. For two patients in the latter two generations, scintigraphy with iodine 131-tagged metaiodobenzylguanidine (MIBG) showed tumors only in the region of the right renal hilum, thus indicating that they were primary lesions. At surgery, except for lymph node metastases noted microscopically in one patient, tumors were found only near the right renal hilum. The adrenal glands seemed normal on inspection, palpation, and computed tomography. In another family, a mother and son had primary pheochromocytomas arising from the urinary bladder. We suggest that primary extra-adrenal pheochromocytoma is a syndrome in which specific genetic abnormalities determine sites of tumor development.

Incidence and clinical features of patent ductus arteriosus in low-birthweight infants: a prospective analysis of 150 consecutively born infants.

The incidence of persistent patency of the ductus arteriosus beyond the third day of life was prospectively determined in 100 preterm infants with birthweights of 2,000 gm or less and 50 infants with birthweights of 2,001 to 2,500 gm. The overall incidence was 21% and was inversely related to increasing gestational age and birthweight. The data suggest that immaturity is the major determinant of the persistent patency of the ductus arteriosus. Spontaneous delayed closure of the ductus occurred in 79% of patients that survived the immediate neonatal period. There was a high degree of association between the presence of a patent ductus arteriosus (PDA) and respiratory distress syndrome (RDS). Eight infants with severe RDS and PDA developed heart failure and four required surgical ligation of the ductus. None of the infants with birthweights greater than 2,000 gm who had PDA developed heart failure or required surgical ligation of the ductus arteriosus.

Splenic trauma in the pediatric patient: the integrated roles of ultrasound and computed tomography.

Seven children who sustained splenic trauma were scanned by ultrasound and computed tomography (CT) or ultrasound and nuclear liver/spleen scan. All patients were managed conservatively and did not need abdominal surgery. On the initial sonogram, the majority of children had multiple areas of both increased and decreased echogenicity. Hematomas were followed to resolution in five of seven children and were usually multiple and hypoechoic prior to complete disappearance. On contrast-enhanced CT scans, areas of splenic hemorrhage appeared as low attenuation. Our small patient population demonstrates that, following an initial CT scan, sonography is helpful for sequential splenic imaging to show when the appearance of the spleen returns to normal. When correlated with the clinical information, such data are helpful to the clinician in determining when a child who has sustained splenic trauma may resume normal activity.

Surgical treatment of gastroesophageal reflux in children: a combined hospital study of 7467 patients.

OBJECTIVE: To review retrospectively the combined clinical experience with the surgical treatment of persistently symptomatic gastroesophageal reflux (SGER) in childhood from seven large children's surgery centers in the United States. DESIGN: During the past 20 years, 7467 children <18 years of age underwent antireflux operations for SGER at the seven participating hospitals. Fifty-six percent were neurologically normal (NN) and 44% were neurologically impaired (NI). The most frequent diagnostic studies were upper gastrointestinal series (68%), esophageal pH monitoring (54%), gastric emptying study (32%), and esophagoscopy (25%). The age at operation was under 12 months in 40% and 1 to 10 years in 48%. The type of fundoplication was Nissen (64%), Thal (34%), and Toupet (1.5%). A gastric emptying procedure was performed on 11.5% of NN patients and 40% of NI patients. Laparoscopic fundoplication was performed on 2.6% of patients. RESULTS: Good to excellent results were achieved in 95% of NN and 84.6% of NI patients. Major complications occurred in 4.2% of NN and 12.8% of NI patients. The most frequent complications were recurrent reflux attributable to wrap disruption (7.1%), respiratory (4.4%), gas bloat (3.6%), and intestinal obstruction (2.6%). Postoperative death occurred in 0.07% of NN and 0.8% of NI patients. Reoperation was performed in 3.6% of NN and 11.8% of NI patients. The results and complications were similar among the participating hospitals and did not seem related to the type of fundoplication used. CONCLUSION: The excellent results (94% cure) and low morbidity with gastroesophageal fundoplication with or without a gastric emptying procedure from a large combined hospital study indicate that operation should be used early for SGER in NN children and to facilitate enteral feedings and care in NI children.

Liver fibrosis (cardiac cirrhosis) five years after modified Fontan operation for tricuspid atresia.

A 15-year-old girl was found to have severe liver fibrosis on liver biopsy at the time of cholecystectomy, 5 1/2 years following a modified Fontan procedure (right atrial-right ventricular conduit) for tricuspid atresia. Postoperative right atrial pressures were consistently elevated above 13 mm Hg and this, in part, may have been due to progressive mild conduit stenosis. Because of increasing symptoms, the patient underwent successful revision of the conduit at the age of 15 years. It is suggested that sustained systemic venous hypertension caused the striking morphologic changes in the liver and that this serious complication may significantly affect the long-term prognosis of patients surviving the Fontan procedure.

Obstructive jaundice secondary to chronic pancreatitis in children: report of two cases and review of the literature.

Chronic pancreatitis is a rare childhood illness, most often presenting with nausea, vomiting, and recurrent abdominal pain. Obstructive jaundice secondary to biliary stricture is an uncommon manifestation of childhood pancreatitis, with only 11 patients previously described in the surgical literature. We report our experience with two additional children with jaundice secondary to pancreatitis and review the literature on this problem. Laboratory tests are often of little diagnostic value, and a high index of suspicion is essential for correct diagnosis. Endoscopic retrograde cholangiopancreatography is emerging as an extremely useful diagnostic study in these patients. The surgical management of this uncommon pediatric illness remains controversial.

Abdominal aneurysms in childhood: report of a case and review of the literature.

Abdominal aneurysms are rare in children and are usually found in association with congenital cardiac or aortic malformations, connective tissue disorders, trauma, or previous arterial catheter placement. A 4-year-old girl who had a common iliac artery aneurysm, who had no history of arterial catheter placement or trauma, and who had no evidence of Marfan's or Ehlers-Danlos syndrome, arteritis, coarctation of the aorta, or other diseases associated with childhood aneurysms is presented. Resection of the aneurysm and arterial reconstruction were performed without the use of prosthetic material or vein graft. Pathologic examination showed no evidence of inflammation or medial degeneration in any of the layers of the arterial wall. This is the fourth report found in the literature of documented idiopathic abdominal aneurysm in a child. The conditions associated with abdominal aneurysms in childhood are discussed, and the literature is reviewed.

A comparison between operative and nonoperative management of blunt injuries to the liver and spleen in adult and pediatric patients.

Nonoperative management of blunt trauma involving the liver and spleen has been accepted in stable pediatric patients but has been controversial in adult patients. The purpose of this study was to compare nonoperative management of blunt liver and spleen injuries in adult patients with a similar group of adult patients treated operatively and with a group of pediatric patients treated nonoperatively. A 5-year retrospective study was carried out on all hemodynamically stable patients who came to our institution with blunt abdominal trauma. There were 20 adults treated operatively (group I), 25 adults treated nonoperatively (group II), and 34 pediatric patients treated nonoperatively (group III). The mean acute physiology and chronic health evaluation score for group I was 5.1; group II, 3.1; and group III, 7.9. Delayed splenectomy was required in four adult patients in group I and in one patient in group III. There were no deaths. The mean total blood requirement was 6.0 units for group I, 2.8 units for group II, and 1.7 units for group III. The average hospital stay was 19.1 days for group I, 12.6 days for group II, and 9.2 days for group III. These data suggest that the outcome of adult patients whose blunt liver and spleen injuries are managed nonoperatively is comparable with that of pediatric patients treated nonoperatively and is as good as that of adults undergoing early laparotomy.

Etiology and management of respiratory complications after repair of esophageal atresia with tracheoesophageal fistula.

This article reviews the cause and management of respiratory symptoms after repair of esophageal atresia with tracheoesophageal fistula (TEF). Postoperative respiratory symptoms developed in 31 (46%) of 68 patients and included apnea and bradycardia, respiratory arrest, aspiration, and recurrent pneumonia. The respiratory symptoms were initially attributed to gastroesophageal reflux (GER) in 20 patients (64%), tracheomalacia in 4 patients (13%), recurrent TEF in 4 patients (13%), and anastomotic stricture in 3 patients (10%). Three patients with GER and the three patients with a stricture were initially managed nonoperatively. The remaining 25 patients underwent surgical correction of the underlying cause of the respiratory symptoms. Despite aggressive management of this problem, 14 (45%) of these 31 patients had persistent or recurrent respiratory symptoms. Although GER is the most common cause of respiratory complications in patients who have undergone prior TEF repair, other factors are often responsible for these symptoms and should not be overlooked.

The importance of different calorie sources in the intravenous nutrition of infants and children.

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.

Definitive treatment of Hirschsprung's disease in the newborn with a one-stage procedure.

BACKGROUND: The purpose of this study was to review our experience and early follow-up with 15 one-stage pull-through procedures performed at the time of diagnosis in neonates and infants with Hirschsprung's disease. METHODS: Historic chart review of all patients with the new diagnosis of Hirschsprung's disease seen at the C.S. Mott Children's Hospital at the University of Michigan, Ann Arbor, between June 1989 and June 1992 was performed. Progress notes, operative and anesthetic records, pathology reports, and outpatient follow-up notes were used for data collection. RESULTS: Operative technique included a modified endorectal pull-through after determining the presence of ganglion cells by frozen section. No colostomies were performed before or after operation. Three patients had affected family members. All infants were born at term. Operation was performed within 24 hours of diagnosis and as early as 48 hours of age. Twelve patients had standard rectosigmoid disease, two had total colonic disease, and another had long-segment disease. Bowel function returned within 4 days of operation, and feeding was instituted by postoperative day 6 in all patients. All of the patients with rectosigmoid disease are doing well. Patients with long-segment or total colonic disease had more problems but are currently at home and doing well. Morbidity included two postoperative bowel obstructions and three patients with postoperative enterocolitis. CONCLUSIONS: A single definitive operation may be used to treat Hirschsprung's disease diagnosed in the newborn. Long-term follow-up in these patients is required.