Medical and Pediatric OncologyVolume 28, Issue 2 p. 149-153 Proceedings of the Children's Hospital of Western Ontario Tumor Board Massive intra-atrial Wilms' tumor: A treatment dilemma Giulio J. D'Angio MD, Corresponding Author Giulio J. D'Angio MD Department of Radiation Oncology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104Department of Radiation Oncology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104Search for more papers by this authorYousif H. Matloub MD, Yousif H. Matloub MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorMarc D. Le Gras MD, Marc D. Le Gras MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorHerschel C. Rosenberg MD, Herschel C. Rosenberg MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorA. Rashid Dar MD, A. Rashid Dar MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorDavid Girvan MD, David Girvan MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorAlan H. Menkis MD, Alan H. Menkis MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorTim Brown MD, Tim Brown MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorR. Morrison Hurley MD, R. Morrison Hurley MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this author Giulio J. D'Angio MD, Corresponding Author Giulio J. D'Angio MD Department of Radiation Oncology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104Department of Radiation Oncology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104Search for more papers by this authorYousif H. Matloub MD, Yousif H. Matloub MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorMarc D. Le Gras MD, Marc D. Le Gras MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorHerschel C. Rosenberg MD, Herschel C. Rosenberg MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorA. Rashid Dar MD, A. Rashid Dar MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorDavid Girvan MD, David Girvan MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorAlan H. Menkis MD, Alan H. Menkis MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorTim Brown MD, Tim Brown MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorR. Morrison Hurley MD, R. Morrison Hurley MD Departments of Pediatrics, Radiation Oncology, Surgery, Pediatric Cardiac Surgery, and Radiology, University of Western Ontario, London, Ontario, CanadaSearch for more papers by this author First published: 07 December 1998 https://doi.org/10.1002/(SICI)1096-911X(199702)28:2<149::AID-MPO12>3.0.CO;2-BCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume28, Issue2February 1997Pages 149-153 RelatedInformation

Haemolytic uraemic syndrome (HUS) remains the leading cause of acute renal failure in children. Although anEscherichia coli-produced verotoxin (VT) has been implicated in the pathogenesis of HUS, the precise mechanisms of disease are not well defined. We hypothesise that the pathogenesis of renal failure in HUS includes the binding ofE. coli VT to the glomerular mesangial cell, with consequent effects on renal function. Using human paediatric mesangial cells. we studied the binding and biological effects of the purified verotoxin VT-1. We isolated, purified and characterised paediatric glomerular mesangial cells. The mesangial cells were characterised by their immunoreactivity with both smooth muscle actin and vimentin antibodies, and lack of immunoreactivity with cytokeratin or factor VIII antibodies. Using an fluorescein isothiocyanate-conjugated VT (10−7–10−8 M), we demonstrated specific binding to the mesangial cell membrane by immunofluorescence microscopy. We also demonstrated a dose-dependent inhibition of mesangial cell mitogenesis at concentrations from 10−9 to 10−17 M. Our data demonstrate that VT-1 binds to paediatric human glomerular mesangial cells and this binding results in specific biological actions, including an inhibition of cell mitogenesis.

Gram-negative sepsis/septic shock in the newborn continues to be a major medical problem, causing high mortality. Hyperglycemia followed by hypoglycemia is a common symptom in endotoxic shock. However, the mechanism of newborn glucoregulatory response to endotoxin has not been well understood. Paradoxically, monocyte-phagocytes can contribute to shock by overwhelming secretion of cytokines and also host defense by detoxifying endotoxin. Since monocyte-phagocyte function is immature in the newborn, this study was performed to evaluate Kupffer cell's role in liver glycogenolysis during endotoxic shock. Endotoxin (LPS) induced hyperglycemia in 10-day-old rats, and increased net glucose output in the isolated perfused liver. 1) Cytarabine decreased Kupffer cell function (decreased hepatic colloid carbon uptake) and blunted LPS-increased liver net glucose output in the Cytarabine + LPS-treated group (104 +/- 4 vs. 146 +/- 3 micrograms/min/g wet liver in the LPS-treated group: P < .001). 2) Indomethacin (IND) suppressed LPS-induced liver net glucose output in the LPS + IND-treated group (133 +/- 5 vs. 146 +/- 3 micrograms/min/g wet liver, P < .05). Thus, prostaglandins were suggested to contribute to glycogenolysis in the 10-day-old rat liver. 3) Phorbol 12-myristate 13-acetate (PMA) increased liver net glucose output (166 +/- 4 micrograms/min/g wet liver), and H-7, a protein kinase C inhibitor, blunted PMA-induced liver glucose output (140 +/- 2 micrograms/min/g wet liver, P < .05). H-7 enhanced LPS-induced liver net glucose output (196 +/- 9 micrograms/min/g wet liver, P < .01). Therefore, protein kinase C may not be the dominant cell signaling system for LPS stimulation in suckling rat Kupffer cells.

Infants undergoing open-heart surgery with hypothermic cardiopulmonary bypass experience markedly elevated lactate and glucose levels. Reports in infants less than 10 kg show the elevated lactate to be progressive during the operative period. The pathogenesis of the hyperglycemia is not clear but may be caused by excess glucose administration, inadequate insulin response, or glucose regulatory hormone levels of glucagon, cortisol, and growth hormone. The purpose of this study is to confirm these findings and to investigate their pathogenesis. Serial blood samples were taken preoperatively, intraoperatively, and postoperatively during hypothermic cardiopulmonary bypass in nine infants of less than 10 kg. Samples were analyzed for levels of lactate, glucose, and regulatory hormones insulin, growth hormone, glucagon, and cortisol. Our study did not show a progressive accumulation of lactate. The elevated lactate level appears to come from the pump prime solution. The hyperglycemia is also from the pump prime solution, and there do not appear to be elevated levels of regulatory hormones intraoperatively. Insulin response during hypothermia is blunted; however, on rewarming the patient in the immediate postoperative period, a brisk insulin response is seen. The changes in levels of lactate and glucose and the regulatory hormones return to baseline at 24 hours with no further significant changes in the next 48 hours.

Maternal anogenital licking (MAGL) has been studied to understand the mechanism of maternal behaviour. The present study showed that rats had glycosuria at the concentration of 18-20 mg/dl and glucose was the preference of postpartum rats. MAGL increased on suckling rats separated for 24 h. However, wiping anogenital region attenuated the increase of MAGL. Therefore, glucose preference of postpartum rats may be involved in MAGL.

Gram-negative sepsis septic shock continues to produce significant mortality and therefore remains a major medical problem. Vasodilators have been studied in the treatment of circulatory shock. However, the effectiveness of calcium channel blockers in the treatment of newborn endotoxic shock has not been well documented. In the present study, diltiazem, a calcium channel blocker, and nitroprusside, a vasodilator, were used for the treatment of endotoxic shock in 10-day-old rats. Mortality rate, hemodynamics, and glucose metabolism were monitored. Diltiazem at a dose of 0.3 mg/kg attenuated the hypotension, bradycardia, hypoglycemia, and lactacidemia in newborn endotoxic shock. Diltiazem treatment resulted in reduced 24-hour mortality. However, 0.6 mg/kg diltiazem enhanced the hypotension, bradycardia, and lactacidemia in endotoxic shock. Nitroprusside blunted the hypoglycemia and decreased the mortality rate among rats with endotoxic shock. Afterload reduction may be responsible for the beneficial effects of 0.3 mg/kg diltiazem and nitroprusside. Diltiazem at a dose of 0.3 mg/kg reduced the lactacidemia of endotoxic shock more than nitroprusside. Therefore the effects of diltiazem may be due not only to afterload reduction but also to inhibition of cellular calcium influx. We conclude that 0.3 mg/kg diltiazem and 1.0 mg/kg nitroprusside are beneficial for the treatment of endotoxic shock in newborn rats.

The newborn is very susceptible to gram-negative sepsis/septic shock. The mortality of newborn endotoxic shock continues to be high. Since lipid A is responsible for the toxic effects of lipopolysaccharide, anti-lipid A antibodies may prevent endotoxic shock in the newborn. This study showed that both anti-lipid A monoclonal IgG (A78S1) and anti-lipid A monoclonal IgM (A523) decreased the mortality of endotoxic shock in 10 day old rats. Prophylactic administration of A78S1 and A523 to the pregnant rat decreased the mortality of endotoxic shock in their 0-day-old offspring. Prophylaxis was due to transplacental passage of A78S1 treatment. The mechanism of prophylaxis remains unclear in A523 treatment.

Gram-negative sepsis/septic shock causes significant mortality in newborns. However, there has been no established method for newborn endotoxic shock treatment. Prostaglandins play a role in endotoxic shock. Cepharanthine is a biscoclaurine alkaloid that primarily inhibits phospholipase A2. Therefore, the effects of cepharanthine have been studied on endotoxic shock in newborn rats. Cepharanthine decreased the 24 h mortality of endotoxic shock in a dose-related manner. At the dose of 0.2 mg kg-1 it effectively reduced the mortality from 90 to 21% in newborn rats. It also induced hyperglycaemia in control rats and blunted the hypoglycaemia of endotoxic shock. Cepharanthine did not suppress body weight gain nor did it delay death as seen with glucocorticoid treatment. We conclude that cepharanthine is beneficial in the treatment of newborn endotoxic shock.

Neonatal sepsis is a significant health problem. However, to our knowledge, the temporal substrates and insulin response to endotoxin have not been characterized in the young animal to guide the investigations of glucoregulation in septic shock in the newborn. We characterized the temporal response to endotoxin in the developing rat. Sprague-Dawley rats were given intraperitoneal Salmonella enteritidis endotoxin in high and low lethal doses to zero, ten and 28 day old rats. Mortality, temporal glucose, lactate, hepatic glycogen and insulin were monitored. Mortality experiments show the ten day old rat is 300 times as sensitive to endotoxin as the 28 day old rat. Plasma glucose concentration increased in the high mortality groups by 120 minutes in the zero and ten day old rats (102 +/- 4 milligrams per deciliter, 119 +/- 6 milligrams per deciliter, respectively, and by 60 minutes in the 28 day old rats (223 +/- 12 milligrams per deciliter). The plasma glucose level decreased to 52 +/- 3 milligrams per deciliter by 240 minutes in the ten day old and by 180 minutes to 99 +/- 8 milligrams per deciliter in the 28 day high mortality groups. Peak lactic acid levels in the high lethality groups were zero day 2.8 +/- 0.2 millimoles per liter in zero day old rats, 3.3 +/- 0.2 millimoles per liter in 28 day old rats. Glycogen in the liver decreased rapidly by 120 minutes in all age groups. Plasma insulin concentration did not elevate significantly in zero and ten day old rats. In the 28 day old rat, insulin concentration increased by 120 minutes to 52 +/- 17 microunits per milliliter. Insulin glucose ratios were also elevated in the 28 day old endotoxin treated rat, indicating hyperinsulinemia. Thus, temporal substrates and insulin responses to endotoxin differ with animal age.

To better understand molecular mechanisms of glucose transport in shock, we studied glucose transporter isoform mRNA abundance after injection of S. enteritidis endotoxin (40mg/kg) or saline. Six to 8 hours after injection, endotoxin-treated animals compared to controls became hypoglycemic (44±6 vs. 111±4 mg/dl) and lactacidemic (5.9±0.5 vs. 1.3±0.1). At such times, tissue RNA was isolated and hybridized to Riboprobes for GLUT1 (erythrocyte), GLUT2 (liver), and GLUT4 (muscle/fat) glucose transporter isoforms and expressed as percent of control. GLUT1 mRNA abundance was increased in fat (660%, p<.05), soleus muscle (314%, p<.05), and liver (871%, p<.001) of endotoxin-treated rats. Soleus muscle GLUT4 mRNA levels were increased (+33%, p<.02), while liver GLUT2 mRNA levels were markedly decreased (−58%, p<.01). The overall increase in GLUT1 mRNA abundance accompanied by lowered liver GLUT2 mRNA levels may either cause or reflect profoundly altered glucose transport.

Neonatal sepsis is a significant health problem. However, to our knowledge, the temporal substrates and insulin response to endotoxin have not been characterized in the young animal to guide the investigations of glucoregulation in septic shock in the newborn. We characterized the temporal response to endotoxin in the developing rat. Sprague-Dawley rats were given intraperitoneal Salmonella enteritidis endotoxin in high and low lethal doses to zero, ten and 28 day old rats. Mortality, temporal glucose, lactate, hepatic glycogen and insulin were monitored. Mortality experiments show the ten day old rat is 300 times as sensitive to endotoxin as the 28 day old rat. Plasma glucose concentration increased in the high mortality groups by 120 minutes in the zero and ten day old rats (102 +/- 4 milligrams per deciliter, 119 +/- 6 milligrams per deciliter, respectively, and by 60 minutes in the 28 day old rats (223 +/- 12 milligrams per deciliter). The plasma glucose level decreased to 52 +/- 3 milligrams per deciliter by 240 minutes in the ten day old and by 180 minutes to 99 +/- 8 milligrams per deciliter in the 28 day high mortality groups. Peak lactic acid levels in the high lethality groups were zero day 2.8 +/- 0.2 millimoles per liter in zero day old rats, 3.3 +/- 0.2 millimoles per liter in ten day old rats and 4.6 +/- 0.3 millimoles per liter in 28 day old rats. Glycogen in the liver decreased rapidly by 120 minutes in all age groups. Plasma insulin concentration did not elevate significantly in zero and ten day old rats. In the 28 day old rat, insulin concentration increased by 120 minutes to 52 +/- 17 microunits per milliliter. Insulin glucose ratios were also elevated in the 28 day old endotoxin treated rat, indicating hyperinsulinemia. Thus, temporal substrates and insulin responses to endotoxin differ with animal age.

Journal of Parenteral and Enteral NutritionVolume 14, Issue 5 p. 552-553 Letter No Shortcuts To Height B.W. Henry M.S., R.D., B.W. Henry M.S., R.D. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorP.A. Middaugh R.D., C.N.S.D., P.A. Middaugh R.D., C.N.S.D. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorJ. Bourboulas B.S., J. Bourboulas B.S. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorK. Amer R.N., M.S., K. Amer R.N., M.S. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorC. Laporte R.N., C. Laporte R.N. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorD. Tholl PHARMD., D. Tholl PHARMD. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorC.E. Menendez M.D., C.E. Menendez M.D. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorR.M. Hurley M.D., R.M. Hurley M.D. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorW.P. Zeller M.D., W.P. Zeller M.D. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this author B.W. Henry M.S., R.D., B.W. Henry M.S., R.D. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorP.A. Middaugh R.D., C.N.S.D., P.A. Middaugh R.D., C.N.S.D. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorJ. Bourboulas B.S., J. Bourboulas B.S. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorK. Amer R.N., M.S., K. Amer R.N., M.S. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorC. Laporte R.N., C. Laporte R.N. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorD. Tholl PHARMD., D. Tholl PHARMD. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorC.E. Menendez M.D., C.E. Menendez M.D. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorR.M. Hurley M.D., R.M. Hurley M.D. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this authorW.P. Zeller M.D., W.P. Zeller M.D. Pediatric Enteral and Parenteral Nutrition Team Loyola University of Chicago Stritch School of Medicine Maywood, ILSearch for more papers by this author First published: 01 September 1990 https://doi.org/10.1177/0148607190014005552Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Leleiko NS, Luder E., Fridman M., et al: Nutritional assessment of pediatric patients admitted to an acute-care pediatric service utilizing anthropometric measurements. JPEN 9: 166–168, 1985 2Hamill PVV, Drizd TA, Johnson CL, et al: Physical growth: National Center for Health Statistics Percentiles. Am J Clin Nutr 607–629, 1979 3Fomon SJ: Nutritional disorders of children: Prevention, screening, and follow-up. Health Services Administration, Washington, DC, United States Printing Office, 1976 Citing Literature Volume14, Issue5September 1990Pages 552-553 ReferencesRelatedInformation