Longitudinal assessment of lung area measurements by two-dimensional ultrasound in fetuses with isolated left-sided congenital diaphragmatic hernia.

OBJECTIVE: To evaluate lung growth in healthy fetuses and those with congenital diaphragmatic hernia (CDH) using two-dimensional (2D) ultrasound. METHODS: Fetal right lung measurements obtained by 2D ultrasound between 19 and 37 weeks' gestation were evaluated longitudinally in 66 healthy fetuses and 52 fetuses with isolated left-sided CDH. Right lung areas were determined by the 'tracing' and 'longest-diameters' methods and, subsequently, lung area-to-head circumference ratios (LHRs) were calculated. Functions fitted to these size parameters with respect to gestational age were evaluated for three sets of group-wise comparisons: (1) healthy vs CDH fetuses; (2) different degrees of severity of CDH; and (3) CDH fetuses that survived vs those that died by 6 months postpartum. RESULTS: There was a significantly slower increase in right lung areas and LHRs with advancing gestational age in CDH fetuses than in healthy individuals (P < 0.05). Compared to those with milder forms of CDH, lung areas and LHRs of fetuses with more severe forms displayed a smaller increase (P < 0.05) and LHRs of fetuses with severe CDH did not increase during pregnancy (P > 0.05). Individuals who died postpartum did not show any increase in LHR (P > 0.05) throughout gestation. CONCLUSIONS: The right lung area and LHR, calculated using either the longest-diameters or tracing method, display reduced growth rates during gestation in cases of isolated left-sided CDH as compared with healthy fetuses. The growth curve characteristics of fetal lung areas and LHRs may be useful for predicting neonatal mortality.

Early fetoscopic tracheal occlusion for extremely severe pulmonary hypoplasia in isolated congenital diaphragmatic hernia: preliminary results.

OBJECTIVE: To evaluate the effect of early fetoscopic tracheal occlusion (FETO) (22-24 weeks' gestation) on pulmonary response and neonatal survival in cases of extremely severe isolated congenital diaphragmatic hernia (CDH). METHODS: This was a multicenter study involving fetuses with extremely severe CDH (lung-to-head ratio < 0.70, liver herniation into the thoracic cavity and no other detectable anomalies). Between August 2010 and December 2011, eight fetuses underwent early FETO. Data were compared with nine fetuses that underwent standard FETO and 10 without fetoscopic procedure from January 2006 to July 2010. FETO was performed under maternal epidural anesthesia, supplemented with fetal intramuscular anesthesia. Fetal lung size and vascularity were evaluated by ultrasound before and every 2 weeks after FETO. Postnatal therapy was equivalent for both treated fetuses and controls. Primary outcome was infant survival to 180 days and secondary outcome was fetal pulmonary response. RESULTS: Maternal and fetal demographic characteristics and obstetric complications were similar in the three groups (P > 0.05). Infant survival rate was significantly higher in the early FETO group (62.5%) compared with the standard group (11.1%) and with controls (0%) (P < 0.01). Early FETO resulted in a significant improvement in fetal lung size and pulmonary vascularity when compared with standard FETO (P < 0.01). CONCLUSIONS: Early FETO may improve infant survival by further increases of lung size and pulmonary vascularity in cases with extremely severe pulmonary hypoplasia in isolated CDH. This study supports formal testing of the hypothesis with a randomized controlled trial.

Mechanical bowel preparation for esophagocoloplasty in children: is it really necessary?

Esophagocoloplasty is a commonly performed procedure for esophageal replacement in children. Traditionally, mechanical bowel preparation (MBP) is performed before this operation. However, this practice has been questioned, initially in adults and now in children. The aim of this study was to evaluate the influence of MBP on esophagocoloplasty in a series of children. Data collected from 164 patients who underwent esophagocoloplasty in the Pediatric Surgery Division, University of São Paulo Medical School, from February 1978 to July 2011 were reviewed for postoperative complications. In 134 patients, at least one kind of MBP was performed before the surgery (PREP group). MBP was omitted in 30 patients (NO-PREP group). There was no statistical difference between the groups in the rates of evisceration, colocolic, or cologastric anastomotic dehiscence and death. However, in the NO-PREP group, the incidence of cervical leakage (6.6%) was significantly decreased in comparison with the classical PREP group (25.3%) (P= 0.03). The results of this study suggest that the omission of MBP has a positive impact on the incidence of postoperative complications in esophagocoloplasty.

Prediction and probability of neonatal outcome in isolated congenital diaphragmatic hernia using multiple ultrasound parameters.

OBJECTIVES: To evaluate the accuracy and probabilities of different fetal ultrasound parameters to predict neonatal outcome in isolated congenital diaphragmatic hernia (CDH). METHODS: Between January 2004 and December 2010, we evaluated prospectively 108 fetuses with isolated CDH (82 left-sided and 26 right-sided). The following parameters were evaluated: gestational age at diagnosis, side of the diaphragmatic defect, presence of polyhydramnios, presence of liver herniated into the fetal thorax (liver-up), lung-to-head ratio (LHR) and observed/expected LHR (o/e-LHR), observed/expected contralateral and total fetal lung volume (o/e-ContFLV and o/e-TotFLV) ratios, ultrasonographic fetal lung volume/fetal weight ratio (US-FLW), observed/expected contralateral and main pulmonary artery diameter (o/e-ContPA and o/e-MPA) ratios and the contralateral vascularization index (Cont-VI). The outcomes were neonatal death and severe postnatal pulmonary arterial hypertension (PAH). RESULTS: Neonatal mortality was 64.8% (70/108). Severe PAH was diagnosed in 68 (63.0%) cases, of which 63 died neonatally (92.6%) (P < 0.001). Gestational age at diagnosis, side of the defect and polyhydramnios were not associated with poor outcome (P > 0.05). LHR, o/e-LHR, liver-up, o/e-ContFLV, o/e-TotFLV, US-FLW, o/e-ContPA, o/e-MPA and Cont-VI were associated with both neonatal death and severe postnatal PAH (P < 0.001). Receiver-operating characteristics curves indicated that measuring total lung volumes (o/e-TotFLV and US-FLW) was more accurate than was considering only the contralateral lung sizes (LHR, o/e-LHR and o/e-ContFLV; P < 0.05), and Cont-VI was the most accurate ultrasound parameter to predict neonatal death and severe PAH (P < 0.001). CONCLUSIONS: Evaluating total lung volumes is more accurate than is measuring only the contralateral lung size. Evaluating pulmonary vascularization (Cont-VI) is the most accurate predictor of neonatal outcome. Estimating the probability of survival and severe PAH allows classification of cases according to prognosis.

A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia.

OBJECTIVE: Severe pulmonary hypoplasia and pulmonary arterial hypertension are associated with reduced survival in congenital diaphragmatic hernia (CDH). We aimed to determine whether fetal endoscopic tracheal occlusion (FETO) improves survival in cases of severe isolated CDH. METHODS: Between May 2008 and July 2010, patients whose fetuses had severe isolated CDH (lung-to-head ratio < 1.0, liver herniation into the thoracic cavity and no other detectable anomalies) were assigned randomly to FETO or to no fetal intervention (controls). FETO was performed under maternal epidural anesthesia supplemented with fetal intramuscular anesthesia. Tracheal balloon placement was achieved with ultrasound guidance and fetoscopy between 26 and 30 weeks of gestation. All cases that underwent FETO were delivered by the EXIT procedure. Postnatal therapy was the same for both treated fetuses and controls. The primary outcome was survival to 6 months of age. Other maternal and neonatal outcomes were also evaluated. RESULTS: Twenty patients were enrolled randomly to FETO and 21 patients to standard postnatal management. The mean gestational age at randomization was similar in both groups (P = 0.83). Delivery occurred at 35.6 ± 2.4 weeks in the FETO group and at 37.4 ± 1.9 weeks in the controls (P < 0.01). In the intention-to-treat analysis, 10/20 (50.0%) infants in the FETO group survived, while 1/21 (4.8%) controls survived (relative risk (RR), 10.5 (95% CI, 1.5-74.7), P < 0.01). In the received-treatment analysis, 10/19 (52.6%) infants in the FETO group and 1/19 (5.3%) controls survived (RR, 10.0 (95% CI, 1.4-70.6) P < 0.01). CONCLUSION: FETO improves neonatal survival in cases with isolated severe CDH.

Should patients with esophageal atresia be submitted to esophageal substitution before they start walking?

Esophagocoloplasty and gastric transposition are two major methods for esophageal substitution in children with esophageal atresia, and there is broad agreement that these operations should not be performed before the children start walking. However, there are some reported advantages of performing such operations in the first months of life or in the neonatal period. In this study, we compared our experience with esophageal substitution procedures performed in walking children with esophageal atresia, with the outcomes of children who had the operation before the third month of life reported in the literature. The purpose of this study was to establish if we have to wait until the children start walking before indicating the esophageal replacement procedure. From February 1978 to October 2009, 129 children with esophageal atresia underwent esophageal replacement in our hospital (99 colonic interpositions and 30 gastric transpositions). The records of these patients were reviewed for data regarding demographics, complications (leaks, graft failures, strictures, and graft torsion), and mortality and compared with those reported in the two main articles on esophageal replacement in the neonatal period or in patients less than 3 months of age. The main complication of our casuistic was cervical anastomosis leakage, which sealed spontaneously in all except in four patients. One patient of the esophagocoloplasty group developed graft necrosis and three patients in the gastric transposition group had gastric outlet obstruction, secondary to axial torsion of the stomach placed in the retrosternal space. The long-term outcome of the patients in both groups was considered good to excellent in terms of normal weight gain, absence of dysphagia, and other gastrointestinal symptoms. The comparisons of the main complications and mortality rates in walking children with esophageal substitutions performed in the first months of life showed that the incidences of cervical anastomotic leaks and graft failures were similar, but mortality rate in the first few months of life was significantly greater than that observed in our group of patients (P= 0.001). Based on the comparison of our results with those of published series, we conclude that the recommendation of performing esophagocoloplasty or total gastric transposition in children with esophageal atresia after they start walking is still valid.

Sirolimus in pediatric liver transplantation: a single-center experience.

BACKGROUND AND AIMS: Liver transplantation (OLT) in children has seen significant improvements in recent years. Long-term immunosuppressive strategies have focused on avoiding the risks of long-term immunosuppression, particularly nephrotoxicity, de novo malignancy and late infections. Since its introduction in renal transplantation in 1999, sirolimus (SRL) has been used by an increasing number of liver transplant centers. The aim of this study was to review the experience using SRL in pediatric liver transplant recipients at a single center. METHODS: Between 1989 and 2006, 318 children underwent OLT including 13 who were converted to SRL therapy because of tacrolimus-related side effects. The indications were posttransplant lymphoproliferative disease (PTLD; n = 11), nephrotoxicity (n = 1), and de novo autoimmune hepatitis (n = 1). One patient with PTLD previously concurrently displayed chronic rejection. SRL dosages ranged between 0.4 and 5 mg/d. The median duration of follow-up was 18 months. RESULTS: PTLD recurred in 1 patient. There were no episodes of acute rejection. One child developed hyperlipidemia that resolved with diet and medication. CONCLUSIONS: Conversion from tacrolimus to SRL in selected pediatric liver transplant recipients is safe. Children with PTLD may benefit from immunosuppression with SRL after liver transplantation.

"Rex shunt" for the treatment of portal vein thrombosis after pediatric liver transplantation: a case report.

BACKGROUND AND PURPOSE: Late portal vein thrombosis (PVT) can be extremely well tolerated, although portal hypertension and other consequences of the long-term deprivation of portal inflow to the graft may be hazardous, especially in young children. Recently, the "Rex shunt" has been used successfully to treat these patients. We now report the initial experience with this novel technique. METHODS: A 3-year-old girl with PVT at 7 months after whole organ cadaveric liver transplant displayed portal hypertension with an episode of gastrointestinal bleeding, requiring a mesenteric-portal surgical shunt ("Rex shunt") using a left internal jugular vein autograft. RESULTS: Upon current follow-up of 6 months, postoperative Doppler ultrasound confirmed shunt patency. Endoscopic status was significantly improved after surgery with resolution of portal hypertension. There was no recurrence of bleeding. CONCLUSIONS: The mesenteric-portal shunt ("Rex shunt"), using a left internal jugular vein autograft, should be considered for children with late PVT after liver transplantation. Although this is an initial experience, we may conclude that this technique is feasible, with great potential benefits and low risks for these patients.

Extensive Hepatectomy as an Alternative to Liver Transplant in Advanced Hepatoblastoma: A New Protocol Used in a Pediatric Liver Transplantation Center.

BACKGROUND: Surgery is a key factor in the treatment of hepatoblastoma, but choosing between an aggressive resection and liver transplant may be an extremely difficult task. The aim of this study was to describe the outcomes of patients with advanced hepatoblastoma: pretreatment extent of disease (PRETEXT)/post-treatment extent of disease (POST-TEXT) III and IV undergoing aggressive resections or living donor liver transplant in cases involving the entire liver. Based on this experience, a new protocol for the treatment of these patients was proposed. METHODS: A retrospective study included patients with advanced hepatoblastoma (POST-TEXT III and IV) who were referred for a liver transplant from 2010 to 2017. RESULTS: A total of 24 children were included: 13 (54.2%) were male, with a median age at diagnosis of 42 months (range, 15-120 months), and a history of prematurity was identified in 20.8% of the patients. Ten cases (41.7%) were staged as PRETEXT/POST-TEXT III, and 12 cases (50.0%) were staged as PRETEXT/POST-TEXT IV. Two patients were referred after posthepatectomy recurrence. Five patients underwent a liver transplant, with recurrence and death in 2 patients (40.0%) within a mean period of 6 months. In the extensive hepatectomy group, there was recurrence in 6 patients (31.6%), with disease-free outcomes and overall survival in 63.2% and 94.7% of patients, respectively. CONCLUSION: In cases of advanced hepatoblastoma, an extensive surgical approach is a valuable option. The fact that the team was fully prepared to proceed with living donor liver transplant allowed the surgeon to be more aggressive and to switch to transplantation when resection was not possible.

Total gastric transposition is better than partial gastric tube esophagoplasty for esophageal replacement in children.

Whenever the surgeon uses the stomach as an esophageal substitute, either one of two techniques is generally performed: total gastric transposition or gastric tube esophagoplasty. No existing reports compare the complications associated with these two surgical procedures. The purpose of this study is to review the authors' experience with total gastric transposition and verify whether this technique is superior to gastric tube esophagoplasty in children by comparing the main complications with those reported in the publications of gastric tubes esophagoplasties in the English language literature published in the last 38 years. A total of 35 children underwent total gastric transposition according to the classical technique. Most of these patients (27, or 77.1%) had long gap esophageal atresia. The most frequently observed complications were compared to those reported in nine studies of gastric tube esophagoplasty comprising 184 patients. Mortality and graft failure rates were also compared. Seven patients (20.0%) presented with leaks, all of which closed spontaneously. Six children were reoperated, three experienced gastric outlet obstruction secondary to axial torsion of the stomach placed in the retrosternal space and the other three experienced delayed gastric emptying that required revision of the piloroplasty. There were two deaths (5.7%) and no graft failure. Strictures were observed in five patients (14.2%) and all of these were resolved with endoscopic dilatations. Six patients had diarrhea that spontaneously resolved. In the late follow-up period, all patients were on full feed and thriving well. The comparisons with gastric tube patients demonstrated that the total gastric transposition group presented with significantly less leaks and strictures (P = 0.0001 and 0.001, respectively). The incidence of death and graft failure was not statistically different. In conclusion, gastric transposition is as a simple technical procedure for esophageal replacement in children with satisfactory results, and is superior to gastric tube esophagoplasty.

Gastroesophageal reflux disease in children: efficacy of Nissen fundoplication in treating digestive and respiratory symptoms. Experience of a single center.

Fundoplication has been commonly performed in neurologically impaired and normal children with complicated gastroesophageal reflux disease. The relationship between gastroesophageal reflux disease and respiratory diseases is still unclear. We aimed to compare results of open and laparoscopic procedures, as well as the impact of fundoplication over digestive and respiratory symptoms. From January 2000 to June 2007, 151 children underwent Nissen fundoplication. Data were prospectively collected regarding age at surgery, presence of neurologic handicap, symptoms related to reflux (digestive or respiratory, including recurrent lung infections and reactive airways disease), surgical approach, concomitant procedures, complications, and results. Mean age was 6 years and 9 months. Eighty-two children (54.3%) had neurological handicaps. The surgical approach was laparoscopy in 118 cases and laparotomy in 33. Dysphagia occurred in 23 patients submitted to laparoscopic and none to open procedure (P = 0.01). A total of 86.6% of patients with digestive symptoms had complete resolution or significant improvement of the problems after the surgery. A total of 62.2% of children with recurrent lung infections showed any reduction in the frequency of pneumonias. Only 45.2% of patients with reactive airway disease had any relief from bronchospasm episodes after fundoplication. The comparisons demonstrated that Nissen fundoplication was more effective for the resolution of digestive symptoms than to respiratory manifestations (P = 0.04). Open or laparoscopic fundoplication are safe procedures with acceptable complication indices and the results of the surgery are better for digestive than for respiratory symptoms.

Effects of immunosuppressants on hepatocyte cell mitosis during liver regeneration in growing animal models of partial hepatectomy.

OBJECTIVE: We sought to evaluate the effects of immunosuppressant drugs (corticosteroid, cyclosporine [CsA], and tacrolimus [Tac]) on liver regeneration in growing animals submitted to 70% hepatectomy. MATERIALS AND METHODS: Newborn and weaning rats were submitted to 70% hepatectomy receiving separately methylprednisolone, CsA, or Tac. All animals were sacrificed 24 hours after the procedure. The remnant liver lobes were subjected to histomorphometric analyses with determination of hepatocyte mitotic index. RESULTS: Administration of immunosuppressants did not change the mitotic index of the regenerating liver in newborn animals. In weaning rats, methylprednisolone reduced the mitotic index (P = .01) and Tac caused a greater increase in this rate (P = .001). CsA had no effect on mitotic index. The number of hepatocyte mitoses in newborn animal livers was greater than that in weaning animal livers (P = .001). CONCLUSION: In situations in which intense, fast processes of liver regeneration are crucial, the advantages of the use of Tac must be considered, such as in pediatric transplant patients.

Remote Ischemic Preconditioning Is Efficient in Reducing Hepatic Ischemia-Reperfusion Injury in a Growing Rat Model and Does Not Promote Histologic Lesions in Distant Organs.

OBJECTIVE: Ischemic preconditioning (IPC) was developed to diminish ischemia-reperfusion injury (IRI). There are two main ways of performing it: direct ischemic-preconditioning (DIP) and remote ischemic-preconditioning (RIP). The objectives of this study were to investigate local and systemic effects of DIP and RIP in liver IRI. METHODS: Thirty-two weaning rats (50-70 g body weight; 21 days old) were divided into 4 groups: control (C); ischemia followed by reperfusion (IR); DIP followed by ischemia and reperfusion; and RIP followed by ischemia and reperfusion. In the IR group, the vascular pedicles of medial and left lateral liver lobes were clamped for 60 minutes and then unclamped. In the DIP group, a 10-minute cycle of ischemia followed by a 10-minute reperfusion of the same lobes was performed before 60 minutes of ischemia. In the RIP group, three 5-minute cycles of clamping and unclamping of the femoral vessels were performed before liver ischemia. The animals were euthanized 24 hours after the surgical procedures. RESULTS: The serum levels of liver enzymes were significantly lower in the RIP group compared to the control and IR groups and to the DIP group. The scores of histologic hepatic lesions were significantly lower in RIP animals than those of IR animals (P = .002) and similar to the C group animals. The Bax/BCl-xl relation was lower in the DIP group than that in the RIP group (P = .045) and no differences were observed in histologic analyses of kidney, lung, intestine, and heart. CONCLUSION: In young animals, the beneficial effects of RIP are more evident than those of DIP.

Comparison of the Results of Living Donor Liver Transplantation Due to Acute Liver Failure and Biliary Atresia in a Quaternary Center.

OBJECTIVE: The objective of this study was to compare the complications, outcomes, and survival prevalence in patients undergoing living donor liver transplantation due to biliary atresia (BA) or acute liver failure (ALF). RESULTS: In the period of June 1998-July 2016, 199 children underwent living transplantation due to BA or ALF. Of these 199, 184 were included in the analysis. The average age, weight, and body mass index of BA patients were lower than those of ALF (P < .001). The chi-square test showed a higher prevalence of infection in transplant recipients due to BA (P = .0001) and a higher prevalence of hepatic artery stenosis in those who underwent transplantation due to ALF (P = .001). In the multivariate analysis, the infection remains statistically more prevalent in the BA group (95% confidence interval [CI], 0.20-0.60), while hepatic artery stenosis loses significance. The mortality rate was similar in both groups and the survival in 5 years also. The prevalence of hepatic artery thrombosis, portal vein thrombosis/stenosis, biliary stenosis, and acute and chronic cellular rejection showed no statistical difference between the two groups. CONCLUSION: Living donor liver transplantation should be a valid option in cases of fulminant hepatitis with an indication for liver transplantation, especially in places where the number of cadaverous donors is low and the length of time on the waiting list is high.

Effect of ifosfamide on bone healing.

The effect of ifosfamide on bone healing was tested in a controlled experiment of fibular osteotomy in immature rabbits. Standardized shaft osteotomy was implemented in 10 experimental subjects (group 2) and 10 controls (group 1). Experimental animals received a 50 mg/kg ifosfamide dose by intraperitoneal injection on the fourth post-operative day, and for five days thereafter, while controls received injections of distilled water. After five weeks, all animals were submitted to pharmacological euthanasia and the resulting bone callus samples were studied with histomorphometry, using hematoxylin-eosin stain. Group 2 presented smaller bone volume (69.03% versus 84.98%), larger fibrosis volume (30.96% versus 15.02%), and larger resorption surface (22.02% versus 16.17%) than group 1 (all p< or = 0.05). We conclude that ifosfamide is able to alter the physiological bone healing process by producing a less mature callus (characterized by a smaller quantity of bone tissue), a larger quantity of fibrous tissue, and a smaller resorption surface.

Liver regeneration model in growing rats with hepatic artery ligation: histologic and molecular studies.

BACKGROUND: Liver transplantation is an effective treatment for irreversible liver diseases. The incidence of hepatic artery thrombosis remains high. Our objective was to analyze the effect of ligature of the hepatic artery on liver regeneration in a growing animal model. METHODS: Seventy-five male Wistar rats were divided into the following 3 groups: group 1 (sham, G1): incision without intervention; group 2 (G2): 70% hepatectomy; group 3 (G3): 70% hepatectomy and ligation of the hepatic artery. Preceding the 70% hepatectomy, a hepatic artery ligature was performed with resection of a segment of the artery. The liver specimens were stained with hematoxylin-eosin, and immunohistochemical staining for Ki-67 was performed. The expression of the interleukin (IL) 6 gene was studied by means of reverse-transcription polymerase chain reaction. RESULTS: G2 and G3 demonstrated similar tendencies toward an increase in the gain weight ratio over time. The mitotic activity was significantly lower at 72 hours in G3 than in G2. There was no difference between Ki-67 staining between G2 and G3. The expression of the IL-6 gene was present in all of the groups, lower in G1, with no difference between G2 and G3. CONCLUSIONS: The experimental model was feasible and adequate for these investigations. Hepatectomy stimulated hepatocyte proliferation, and the obstruction of the arterial flow did not affect liver regeneration.

Long-term stability of lipid emulsions with parenteral nutrition solutions.

The stability of the mixture of peripheral vein parenteral nutrition (PN) solution with 10% lipid emulsions (Intralipid or Lipofundin MCT) was tested during a prolonged period of refrigerated storage. The analysis included gross visual examination of the bottle, pH determination, and examination by electron microscope. The mixtures of fat emulsions with PN solution demonstrated no physical instability or pH alteration. Examination under electron microscope revealed no alterations after 4 wk, but the surface layer of fat globules was disrupted after 10 and 18 wk. This study demonstrates that complete nutritive mixtures can be prepared and stored in refrigeration for at least 4 wk before clinical use.

Effect of branched-chain amino acids and insulin on postinjury protein catabolism in growing animals.

Muscle proteolysis continues to occur in hypercatabolic states despite the administration of carbohydrates and proteins. Recent clinical and experimental studies have demonstrated that, under catabolic conditions, treatment with either branched-chain amino acids (BCAA) or insulin may decrease negative nitrogen balance. However, the use of BCAA-enriched solutions to inhibit muscle proteolysis has never been tested in growing animals. A study was therefore undertaken to assess the effectiveness of such solutions, with or without insulin, as compared to a more balanced amino acid solution, in preventing or diminishing postinjury protein catabolism in growing animals. Fifteen-day-old rabbits, exposed to standard moderate trauma in the form of crushing the muscle mass of one rear thigh, received one of two amino acid formulations--a balanced amino acid solution (18.8% BCAA) or a 35% BCAA-enriched solution--for 96 hr. Insulin was given to subgroups of both series. The results indicate that: (1) nitrogen balance in nontraumatized animals is clearly superior when balanced amino acids are administered; (2) BCAA-enriched solutions may decrease postinjury muscle protein catabolism; (3) after trauma, insulin also has a nitrogen-conserving effect, which is demonstrated when it is combined both with BCAA-enriched (35%) and balanced amino acid (18.8%) solutions. However, a better nitrogen balance is achieved when insulin is associated with the balanced amino acid solution.