Reversal of cancer cachexia in rats by cimaterol and supplemental nutrition.

The anabolic beta 2-agonist cimaterol was used in conjunction with supplemental nutrition to reverse cancer-induced cachexia and malnutrition in tumor-bearing rats. Cimaterol was administered to tumor-bearing rats receiving total parenteral nutrition or enteral nutrition for 10 days, beginning 2 weeks after subcutaneous transplantation of methylcholanthrene sarcoma. A significant increase occurred in both muscle weight and muscle protein in animals receiving cimaterol in conjunction with either enteral or parenteral feeding, compared to food fed tumor-bearing animals. Muscle protein content was increased significantly by 16% in cimaterol-treated rats maintained on parenteral nutrition and by 11% in cimaterol-treated enterally fed rats compared with the respective tumor-bearing controls. Urinary concentrations of 3-methylhistidine, an estimation of muscle turnover or catabolism, were significantly reduced in both tumor-bearing groups treated with cimaterol compared to 3-methylhistidine levels of the untreated tumor-bearing groups. The anabolic effects of cimaterol were expressed in the presence of a large tumor burden resulting in reversal of muscle depletion and muscle breakdown regardless of the route of supplemental nutrition. Thus, beta 2-agonists may be considered as a possible therapy for cancer cachexia.

Anorexia following the systemic injection of amylin.

The intravenous injection of 100 micrograms/kg of rat amylin reduced food intake in schedule-fed rats for 1 h of an 8 h measurement period. Associated with this brief anorexia was a hyperglycemic response, observed 30 min after a subsequent amylin administration. Determination of neurochemical alterations revealed increased concentration of serotonin in the hypothalamus and decreased level of the dopamine metabolite, 3-methoxytyramine, in the corpus striatum. Since similar neurochemical alterations were observed following the systemic injection of glucose, both the neurochemical changes and anorexia following intravenous amylin treatment may be secondary to hyperglycemia.

Vaginal obstruction.

Congenital anomalies that result in vaginal obstruction often present with an abdominal mass in the newborn period. Knowledge of the embryological development of the genitourinary tract and its variations is needed to properly evaluate the neonatal patient and to initiate therapy. Because of a high incidence of associated anomalies, a complete urologic evaluation should be undertaken before a definitive surgical repair. The methods of treatment for the various causes of vaginal atresia have shown long-term success and have resulted in appropriate psychosocial and sexual maturation.

Parenteral vs enteral nutrition in tumor-bearing rats.

The development of cachexia may complicate cancer therapy, yet controversy exists concerning its nutritional management. For example, use of total parenteral nutrition (TPN) may not be appropriate because of gut atrophy, possible stimulation of tumor growth, and lack of total host protein repletion. In the present experiment, host and tumor responses were compared after identical parenteral or enteral nutritional supplementation (EN). Eighteen days after subcutaneous inoculation of adult male Fischer-344 rats with fresh methylcholanthrene-induced sarcoma (tumor-bearing [TB] rats), catheters were placed into either the external jugular vein or the stomach. Four days later, rats were started on an 11-day course of either TPN or EN with a Freamine-III-based formula (amino acids = 6%, dextrose = 21.5%, lipid = 1.5%). When the rats were killed, there was no difference in tumor weight between the various TB groups. Carcass weight was increased significantly in both the TB-TPN and TB-EN groups, and there was an elevation in gastrocnemius protein content in both groups compared with the TB-rat food group. Small intestine protein was preserved in the TB-EN group to the level observed in the control-rat food animals. Total lipids in the liver were increased in both TB-TPN and TB-EN groups; however, the magnitude of the increase was less in the TB-EN animals. Neither treatment resulted in complete protein repletion of tumor-bearing rats. EN may be more appropriate than TPN in that gut mass is preserved. The maintenance of gut mucosa may prove to be beneficial in the treatment of the depleted, immunocompromised, and metabolically stressed host.

Extracorporeal membrane oxygenation in the management of cardiac failure secondary to myocarditis.

While most patients with viral myocarditis have a relatively uncomplicated clinical course, a small number of patients will present with cardiogenic shock unresponsive to standard medical therapy. We describe the clinical course of three patients who developed profound cardiac failure secondary to a documented viral myocarditis. Each patient was managed using venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support using the right common carotid artery/internal jugular vein for cannulation. While undergoing ECMO support, each patient developed elevated left-sided cardiac chamber pressures with resultant pulmonary edema. This was managed by balloon atrial septostomy in two cases and combined blade/balloon atrial septostomy in one case. Excellent decompression of the left heart was achieved in each patient. Two patients were successfully weaned from ECMO and are currently alive, with one demonstrating residual cardiac dysfunction. One patient developed global myocardial necrosis and ultimately died. This small series demonstrates a role for ECMO in the management of cardiac failure due to acute viral myocarditis unresponsive to medical therapy. Our experience also suggests that balloon atrial septostomy may be useful to decompress the left atrium and ventricle of patients with acute myocarditis while on ECMO.

Myocardial calcification: a predictor of poor outcome for myocarditis treated with extracorporeal life support.

Myocarditis is an inflammatory disease of the myocardium with a variety of causes. It is potentially reversible, and has been treated successfully with extracorporeal life support (ECLS). With increasing severity, myocarditis results in significant damage to myocardial cells. Dystrophic calcification of the myocardium may occur, serving as a marker of severe damage. At the authors' institution, from July 1990 to January 1992, five patients (four neonates, one 5 year old) with severe myocarditis refractory to medical management were treated with venoarterial ECLS. Three survived (60%) and two died. All patients were female, and their age range was 2 weeks to 5 years. Nonsurvivors had significant myocardial calcification, which was detected by a chest roentgenogram as well as a two-dimensional echocardiogram; the three survivors had no evidence of calcification. The nonsurvivors had minimal recovery of myocardial function and subsequently had their ECLS discontinued at 83 and 169 hours, respectively. The authors conclude that the development of progressive myocardial calcification in conjunction with a lack of recovery of cardiac function is a sign of severe myocardial damage and poor prognosis. Continuation of ECLS in this setting may not be warranted.

Pediatric hepatic trauma: does clinical course support intensive care unit stay?

PURPOSE: The objective of this study is to determine if grade of liver injury predicts outcome after blunt hepatic trauma in children and to initiate analysis of current management practices to optimize resource utilization without compromising patient care. METHODS: A retrospective review of 36 children who had blunt hepatic trauma treated at a pediatric trauma center from 1989 to present was performed. Hepatic injuries graded (AAST Organ Injury Scaling) ranged from grade I to IV. Injury Severity Score (ISS), Glasgow Coma Score (GCS), transfusion requirements, liver transaminase levels, associated injuries, intensive care unit (ICU) length of stay, and survival were analyzed. RESULTS: Mean (+/-SEM) age was 6.6+/-0.8 years, mean grade of hepatic injury was 2.4+/-0.2, mean ISS was 17+/-2.6, mean GCS was 13+/-1, and mean transfusion was 15.4 mL/kg of packed red blood cells (PRBC). There were three deaths with a mean ISS of 59+/-9 and a mean GCS of 3+/-0. Death was not associated with a high-grade liver injury, survivors versus nonsurvivors, 2.3+/-0.2 versus 2.7+/-0.3, but was associated with ISS, 13+/-1.4 versus 59+/-9 (P = .005) and GCS, 14+/-1 versus 3+/-0 (P = .005). Only one patient (grade III, ISS = 43) underwent surgery. There were no differences in mean ISS or GCS between grades I to IV patients. The hepatic injury grades of patients requiring transfusion versus no transfusion were significantly different, 3.4+/-0.2 versus 2.2+/-0.2 (P = 0.04). Abused patients had high-grade hepatic injuries and significant laboratory and clinical findings. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher in grade III and IV injuries than in grades I and II, 1,157+/-320 versus 333+/-61 (P= .02) and 1,176+/-299 versus 516+/-86 (P= .04), respectively. No children with grade I or II injury had a transfusion requirement or surgical intervention. There were no liver-related complications. CONCLUSIONS: Mortality and morbidity rates in pediatric liver injuries, grades I to IV, correlate with associated injuries not the degree of hepatic damage. ALT, AST, and transfusion requirements are significantly related to degree of liver injury. Low-grade and isolated high-grade liver injuries seldom require transfusion. Blunt liver trauma rarely requires surgical intervention. In retrospect, the need for expensive ICU observation for low-grade and isolated high-grade hepatic injuries is questionably warranted.

Selective management of pediatric pancreatic injuries.

BACKGROUND: Despite trauma being the most common cause of pediatric pancreatitis, the diagnosis and management is often difficult. METHODS: The hospital course, diagnostic and surgical procedures, and complications for all children with traumatic pancreatitis evaluated at a Regional Level I Trauma Center were reviewed retrospectively. RESULTS: Twelve of 3,500 children (0.35%, mean age, 8.7 +/- 1.2 years) were reviewed. Intraoperative diagnosis was made in three after penetrating trauma. Nine children sustained blunt pancreatic trauma (BPT) with serial radiographic imaging confirming the diagnosis in seven. Serial serum amylase levels, when performed, were normal in two and elevated in six, but did not predict injury severity or need for further intervention. Endoscopic retrograde cholangiopancreatography was performed in three children and indicated the need for surgical intervention in two and prevented planned laparotomy in one. Two children underwent computed tomography-guided fluid drainage. Pseudocysts developed in five children. Mortality rate from penetrating injuries was 66% with no deaths from BPT. CONCLUSIONS: A combination of serial radiographic, laboratory, and ERCP findings will improve the diagnosis and management of BPT. Penetrating or main ductal injuries require surgical intervention, and fluid collections may require drainage, but, otherwise, most BPT can be managed nonoperatively with minimal morbidity and mortality.

Initial assessment and management of pediatric trauma patient.

The initial evaluation and treatment of the pediatric trauma patient require an organized, thorough approach. All patients must be assumed to have multiple injuries until proven otherwise. Resuscitation efforts should be aggressive to avoid the onset of irreversible shock. The ability to recognize and effectively treat shock are all that are required in the vast majority of injured patents in order to gain stability. The adequate assessment and treatment of the ABCs will provide adequate treatment of the patient's other injuries, leading to an overall improvement in morbidity and mortality. Thus, the ABCs play an essential role in the initial evaluation and treatment of the pediatric trauma patient.

Aortic aneurysm resulting from umbilical artery catheterization: case report, literature review, and management algorithm.

Aortic aneurysms in infants and children are quite rare. The use of umbilical artery catheters in the management of critically ill neonates has been associated with infection and subsequent aneurysm formation. There have been 46 cases reported (including our own); most of the aneurysms have been located in the abdominal aorta and have displayed saccular morphology. Through an analysis of the literature, we identified two factors that had significant correlation with improved survival: diagnosis before surgery and surgical repair (P <.05). This report presents the case of a 23-day-old neonate with an abdominal aortic aneurysm and hypertension. On the basis of our literature review, we offer a management algorithm for this rare but very serious complication of umbilical artery catheterization.

Effects of increased beta 2-agonist dose in tumor-bearing animals.

Cachexia and malnutrition are major contributing causes of significant morbidity and mortality in the cancer patient. Although supplemental nutrition alone does not reverse the cachectic process, the use of anabolic beta 2-adrenergic agonists in conjunction with supplemental nutrition does significantly reverse cachectic processes in tumor-bearing (TB) animals. To determine the most efficacious dose of the beta 2-agonist cimaterol (CIM), male Fischer-344 rats with dorsal subcutaneous methylcholanthrene sarcomas were maintained on supplemental enteral nutrition via surgically placed gastrostomy tubes. TB rats were given daily subcutaneous injections of either saline (Sal) or one of three doses of CIM for seven days. TB-Sal animals demonstrated significant cachexia with decreased extensor digitorum longus and gastrocnemius muscle dry weight and protein content. There was a significant increase in both extensor digitorum longus and gastrocnemius muscle dry weight and protein content in all treatment groups compared with TB controls. The greatest increase was in the 0.30 mg/kg CIM treatment group. Increased cardiac mass was associated with increasing dosage, with the greatest effect being observed in the 0.60 mg/kg CIM treatment group. This dosage, however, was associated with a decreased effect on muscle weight and protein content compared with the 0.30 mg/kg CIM dose. Thus the peak anabolic effect in TB animals was reached with the 0.30 mg/kg dose of CIM. Therefore, use of the beta 2-agonist CIM may prove useful in the treatment of cancer-induced cachexia.

Hepatic arterial pseudoaneurysm: a rare complication of blunt abdominal trauma in children.

We report a child who developed a hepatic artery pseudoaneurysm following blunt hepatic injury. This is a rare complication of hepatic trauma in children. The imaging evaluation and clinical management of hepatic artery pseudoaneurysms are presented.

An unusual late complication of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) now is managed frequently successfully without surgical intervention. NEC may result in strictures, which present after the acute inflammatory process has resolved. Strictures usually present as obstruction in the first year or two of life. A case report is presented of an 11-year-old child who had symptoms from a previously undiagnosed NEC stricture as a result of pica when coins obstructed the stricture. As treatment of NEC continues to improve, more and later complications of this disease can be expected. J Pediatr Surg 36:1853-1854.

The significant relationship between platelet count and haemorrhagic complications on ECMO.

Haemorrhagic complications, which occur in up to 35% of infants during extracorporeal membrane oxygenation (ECMO), often produce devastating sequelae. Although many complex factors interact to control haemostasis, platelet number and function has significant impact on the development of primary haemostasis. The optimum platelet count on ECMO, however, has not been defined. At our institution prior to August 1987, platelet counts were maintained at greater than 100,000/mm3. After August 1987, however, platelet counts of greater than 200,000/m3 were maintained. In a retrospective study, patients were randomly chosen from these two treatment periods: group 1--March 1986 to July 1987; and group 2--June 1988 to June 1989. The average platelet count, platelets administered, hours on ECMO, and bleeding complications were compared to each other and to the July 1992 ELSO Registry. There was a significant difference in average platelet counts between group 1 and group 2. However, the amount of platelets administered per kg per day was similar. There was a significant difference in overall bleeding complications between Group 2 (12%) and the ELSO Registry (35%) (p < 0.01). There was a trend towards decreased complications in all subgroups, although sample size precluded significance. We conclude that increasing platelet counts to greater than 200,000/mm3 decreases the overall bleeding complication rate. This advantage is achieved without a continuous need for increased platelet administration once the desired level is reached and without an increase in perfusion time, mechanical complications, or mortality.

Anticatabolic effect of the beta 2-agonist cimaterol in vivo in tumor-bearing animals.

Loss of lean body mass occurs in cancer and may adversely affect outcome. The beta 2-agonist cimaterol increases muscle mass and protein content in tumor-bearing animals, in part by decreasing protein degradation, but the effect of the drug on protein synthesis remains uncertain. To determine the influence of cimaterol on protein synthesis, a methylcholanthrene sarcoma was transplanted sc into the dorsum of male Fischer-344 rats. After 3 weeks of tumor growth, tumor-bearing and control animals received daily sc injections of the beta 2-agonist cimaterol (0.15 mg/kg) for 5 days. Rate of protein synthesis was measured using iv [3H]-phenylalanine (25 microCi/100 g body wt) and cold phenylalanine (150 mumole/100 g body wt) in a flooding dose. Extensor digitorum longus muscles were harvested 10 min later, homogenized, and assayed for [3H]-phenylalanine uptake (bound) (dpm/mg muscle) and tissue-specific (free) radioactivity to determine protein synthesis rate (Ks: %/24 hr). There was a significant increase in protein synthesis rate in control and tumor-bearing animals receiving cimaterol compared to that in freely feeding, food-deprived, or matched-carcass-weight nontumor-bearing controls, as well as compared to that in tumor-bearing controls. We conclude that the anabolic effects of cimaterol are due to both decreased protein degradation and increased muscle protein synthesis. Therefore, beta 2-agonists may prove useful in prevention and/or treatment of cancer cachexia.

The New Injury Severity Score and the evaluation of pediatric trauma.

BACKGROUND: To compare the effectiveness of the Injury Severity Score (ISS) and New Injury Severity Score (NISS) in predicting mortality in pediatric trauma patients. METHODS: NISS, the sum of the squares of a patient's three highest Abbreviated Injury Scale scores (regardless of body region), were calculated for 9,151 patients treated at four regional pediatric trauma centers and compared with previously calculated ISS values. The power of the two scoring systems to predict mortality was gauged through comparison of misclassification rates, receiver operating characteristic curves, and Hosmer-Lemeshow goodness-of-fit statistics. RESULTS: Although there were significant differences in mean NISS and ISS values for each hospital, differences in the predictive abilities of the two scoring systems were insignificant, even when analysis was restricted to the subgroup of patients with severe or penetrating injuries. CONCLUSION: The significant differences in the predictive abilities of the ISS and NISS reported in studies of adult trauma patients were not seen in this review of pediatric trauma patients.

Effect of cross-sectional imaging on negative appendectomy and perforation rates in children.

PURPOSE: To compare negative appendectomy and perforation rates in children who underwent ultrasonography (US), computed tomography (CT), or no imaging before urgent appendectomy. MATERIALS AND METHODS: All children who underwent urgent appendectomy during a 4(1/2)-year period were identified in a surgical billing database. Pathology reports were coded as negative or as showing acute inflammation or perforation. Imaging up to 14 days before appendectomy or abscess drainage was noted, and imaging-based diagnoses were compared with pathologic findings. Patient age and sex were recorded. RESULTS: Two hundred ninety-nine children, 176 (59%) male and 123 (41%) female (mean age, 10.4 years; age range, 1--21 years), underwent urgent appendectomy. One hundred twenty-six (42%) underwent no imaging, 121 (41%) underwent US with or without CT, and 52 (17%) underwent CT only; 44 (15%) underwent both US and CT. There were significantly higher rates of appendectomy with normal pathologic findings ("negative appendectomy") in patients who underwent no imaging (14% [18 of 126]) or US (17% [20 of 121]) versus the rates in those who underwent CT only (2% [one of 52]) (P =.02 and P =.007, respectively). The negative appendectomy rate was 7% in 96 patients who underwent CT with or without prior US. The perforation rates were not significantly different. CONCLUSION: As compared with children who underwent no preoperative imaging and those who underwent US, children who underwent CT had a significantly lower negative appendectomy rate, without a significantly higher perforation rate.

Prevalence of unsuspected abdominal aortic aneurysms in male veterans.

Abdominal aortic aneurysms (AAA) are potentially lethal arterial lesions that are best managed by elective surgical repair. However, asymptomatic AAAs may go undetected on routine physical examination or patients with such lesions may not consult a physician. To determine the prevalence of asymptomatic AAAs in a high-risk population, we retrospectively reviewed all abdominal CT scans on veterans > 50 years of age that had been ordered for indications other than aneurysmal disease during a recent 10-month period. Of the 111 patients studied, 15 (13.5%) had suprarenal and/or infrarenal AAAs (one patient had both). Patients with AAAs were significantly older (p = 0.0001) and were heavier tobacco users (p = 0.003). For patients > 60 years of age with peripheral vascular occlusive disease and a history of tobacco use, there was a 29.2% prevalence for AAA compared with 0% in those without any of these risk factors (p = 0.04). There was a very definite trend suggesting that patients with peripheral vascular disease (p = 0.06) were more likely to have an AAA. Because of the high prevalence of AAAs found in this population we then conducted a prospective study over a 24-month period during which patients > 60 years of age with known peripheral vascular disease and a history of smoking who presented to the vascular laboratory for evaluation of problems not related to AAA were asked to undergo an abdominal CT scan. Fifty-six volunteers agreed to participate in the study. Seven patients had AAAs and one patient had an isolated iliac aneurysm, for a 14.3% overall prevalence of aneurysms.2+ d

Evaluation of suspected appendicitis in children and young adults: helical CT.

PURPOSE: To evaluate the accuracy of helical computed tomography (CT) for the diagnosis of appendicitis in children and to assess the utility of CT in establishing alternative diagnoses. MATERIALS AND METHODS: The medical records of 154 children (median age, 12 years; age range, 1-20 years) who were suspected to have appendicitis and who underwent CT were reviewed. The gastrointestinal tract was opacified in 151 of 154 patients: Only orally administered contrast material was used in 126 patients; only rectally administered contrast material, in 21 patients; and both oral and rectal contrast material, in four patients. CT findings were correlated with surgical and histopathologic findings or with clinical follow-up findings. RESULTS: Sixty-four CT scans were interpreted as positive for appendicitis and included 58 true-positive and six false-positive scans. Ninety scans were interpreted as negative and included 87 true-negative and three false-negative scans. CT had a sensitivity of 95% and a specificity of 94% for the diagnosis of appendicitis. In addition, in 32 (34%) of 93 patients without appendicitis, an alternative diagnosis was established on the basis of CT findings. CONCLUSION: Helical CT is useful in a pediatric population to diagnose or exclude appendicitis and to establish an alternative diagnosis.