References

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The Basis of the Acute Phase of Verotoxin-Induced HUS: Molecular risk factors

Presented by Clifford A. Lingwood, PhD

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109. Haicheur, N., Bismuth, E., Bosset, S., Adotevi, O., Warnier, G., Lacabanne, V., Regnault, A., Desaymard, C., Amigorena, S., Riccardi-Castagnoli, P., Goud, B., Fridman, W.-H., Johannes, L. and Tartour, E. (Submitted) The B-subunit of Shiga toxin fused to a tumor antigen elicits CTL and targets dendritic cells to allow MHC class I restricted presentation of peptides derived from exogenous antigens.

110. Lechardeur, D., Sohn, K.-J., Haardt, M., Joshi, P. B., Monck, M., Graham, R. W., Beatty, B., Squire, J., O'Brodovich, H. and Lukacs, G. L. (1999) Metabolic instability of plasmid DNA in the cytosol: a potential barrier to gene transfer. Gene Ther 6, 482-97.

111. Facchini, L. and Lingwood, C. (submitted) A Verotoxin 1 B subunit - lambda Cro chimeric protein specifically targets DNA to globotriaosyl ceramide.

122. Foster, D. B., M. Abul-Milh, et al. (2000). "Enterohemorrhagic Escherichia coli induces apoptosis which augments bacterial binding and phosphatidylethanolamine exposure on the plasma membrane outer leaflet." Infect Immun 68(6): 3108-3115.

113. Fraser, M., M. Chernaia, et al. (1994). "Crystal structure of the holotoxin from Shigella dysenteriae at 2.5A resolution." Struct Biol 1: 59-64.

114. Fujii, J., Y. Kinoshita, et al. (1996). "Magnetic resonance imaging and histopathological study of brain lesions in rabbits given intravenous verotoxin 2." Infect Immun 64(12): 5053-5060.

115. Fujii, J., Y. Kinoshita, et al. (1998). "Neurotoxicity of intrathecal Shiga toxin and protection by intrathecal injection of anti-Shiga toxin 2 antiserum in rabbits." Microbial Pathogenesis 25: 139-146.

116. Hurley, B. P., M. Jacewicz, et al. (1999). "Shiga toxins 1 and 2 translocate differently across polarized intestinal epithelial cells." Infect Immun 67(12): 6670-6677.

117. Kitov, P. I., J. M. Sadowska, et al. (2000). "Shiga-like toxins are neutralized by tailored multivalent carbohydrate ligands." Nature 403: 669-672.

118. Newburg, D., P. Chaturvedi, et al. (1993). "Susceptibilty to hemolytic-uremic syndrome relates to erythrocyte glycosphingolipid patterns." J Infect Dis 168: 476-479.

119. Palermo, M. S., M. F. Alves Rosa, et al. (1999). "Depletion of liver and splenic macrophages reduces the lethality of Shiga toxin-2 in a mouse model." Clin Exp Immunol 116: 462-467.

120. Paton, A. W., R. Morona, et al. (2000). "A new biological agent for treatment of Shiga toxigenic Escherichia coli infections and dysentery in humans." Nature Med 6(3): 265-270.

121. Ramegowda, B., J. Samuel, et al. (1999). "Interaction of Shiga toxins with human brain microvascular endothelial cells: cytokines as sensitizing agents." J Infect Dis 180: 1205-1213.

122. Rosenshine, I., S. Ruschkowski, et al. (1996). "A pathogenic bacterium triggers epithelial signals to form a functional bacterial receptor that mediates actin pseudopod formation." EMBO J 15(11): 2613-2624.

123. Sakiri, R., B. Ramegowa, et al. (1998). "Shiga toxin type 1 activates tumor necrosis factor-a gene transcription and nuclear translocation of the transcriptional activators nuclear factor-kB and activator protein-1." Blood 92(2): 558-566.

124. Taylor, F., V. Tesh, et al. (1999). "Characterization of the baboon responses to Shiga-like toxin." Am J Pathol 154(4): 1285-1299.

125. van Setten, P., V. van Hinsbergh, et al. (1998). "Monocyte chemoattractant protein-1 and interleukin-8 levels in urine and serum of patents with hemolytic uremic syndrome." Pediat Res 43: 759-767.

126. Pruimboon-Brees, I.M.; Morgan, T.W.; Ackermann, M.R.; Nystrom, E.D.; Samuel, J.E.; Cornick, N.A.; Moon, H.W.; "Cattle lack vascular receptors for Escherichia coli 0157:H7 Shiga toxins," Proc Nat Acad Sci, USA 97: 10325-10329

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Plasma Exchange in the Treatment of Thrombotic Thombocytopenic Purpura/Hemolytic Uremic Syndrome with Long Term Follow Up and Prognosis

Presented by Gail Rock, MD

1. Rock, GA. Management of Thrombotic Thrombocytopenic Purpura. British Journal of Haematology 2000; 109(3), 496-507.

2. Rock G, Porta C, Bobbio-Pallavicini E. TTP treatment in year 2000. Haematologica 2000; 85: 410-419.

3. Rock G, Porta C, Bobbio-Pallavicini E. Thrombotic thrombocytopenic purpura treatment in year 2000. Haematologica 2000; 85: 410-419.

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Escherichia coli O157:H7 of the GI Tract: Complications Beyond Diarrhea

Presented by Phillip I. Tarr, MD

1. Brandt JR, Joseph MW, Fouser LS, Tarr PI, Zelikovic I, McDonald RA, Avner

ED, McAfee NG, Watkins SL, "Cholelithiasis following Escherichia coli O157:H7-associated hemolytic uremic syndrome." Clin Infect Dis 1995 Jan;20(1):1-8

2. Tarr PI, "Escherichia coli O157:H7: clinical, diagnostic, and epidemiological aspects of human infection," Clin Infect Dis. 1995; 20(1):1-8

3. Tarr PI and Neill MA, "Escherichia coli O157:H7," Gastroenterology Clinics of North America, 2001, in press.

4. Tapper D, Tarr P, Avner E, Brandt J, Waldhausen J, "Lessons learned in the management of hemolytic uremic syndrome in children," J Pediatr Surg 1995 Feb;30(2):158-63

5. Rodriguez, L. A G., Ruigmez, A.; "Increased risk of irritable bowel syndrome after bacterial gastroenteritis: cohort study," BMJ 1999;318:565-566

6. Neal KR, Hebden J, Spiller R, "Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome: postal survey of patients," BMJ 1997 Mar 15;314(7083):779-82

7. Hasler, WL and Owyang, C. Irritable Bowel Syndrome. In Textbook of Gastroenterology, Yamada, T, et al, eds. 1999. Philadelphia, Lippincott Williams & Wilkins, Pages 1884 - 1909.

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Diabetes and HUS

Presented by Richard Mauseth, MD

1. W.L. Robson, A.K. Leung, R. Brandt, C. Trevenen and D.K. Stephure, Hyperglycemia in Diarrhea Associated Hemolytic Uremic Syndrome; Nephron (1995); 71:54-58

2. S.P. Andreoli, J.M. Bergstein, Development of Insulin-Dependent Diabetes Mellitus During the Hemolytic Uremic Syndrome; J. Pediatrics (1982); 100:541-545.

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Longterm Renal Outcomes of Diarrhea-Associated HUS

Presented by John Brandt, MD

Dr. Brandt's references can be found on his slides.

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Long-term Consequences of HUS: the ENCHLOSE Network

Presented by Piero Ruggenenti, MD; Coauthored by Giuseppe Remuzzi, MD

1. The GISEN Group: Randomized placebo controlled trial of effect of ramipril on decline in glomerular filtration risk and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 349:1857-1863, 1997.

2. Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G, for the GISEN Group: Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Lancet 352:1252-1256, 1998.)

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Hemolytic Uræmic Syndrome: The 'eart of the matter

Presented by Garry Cornel MB, BS, FRCS (C)

1. Ray CG, Portman JN, Stamm SJ, Hickman RO (Children's Orthopedic Hospital and Medical Centre, Seattle, Wa.), "Hemolytic-uremic syndrome and myocarditis. Association with Coxsackie B virus infection." Amer J Dis Child; 122,418-420:1971.

Abstract:

Two consecutive patients with the hemoIytic-uremic syndrome were found to have severe, life-threatening myocardial disease during the acute phase of their illness. In one case, immunofluorescent studies detected the presence of coxsackie B4 viral antigen in the renal tissue, and in the other case, coxsackie virus B4 was isolated from the blood and throat. In both patients, significant neutralizing antibody titer rises to coxsackie B4 antigen were demonstrated. The findings lend further support to the theory that enteroviral infections may play a role in the etiology of at least some cases of HUS.

2. Poulton J,* Taylor CM, DeGiovanni JV* (Departments of *Cardiology and Nephrology, The Children's Hospital, Ladywood, Birmingham), "Dilated cardiomyopathy associated with haemolytic uraemic syndrome," Br. Heart J. 57: 181-183 (1987)

Abstract:

In two children with the haemolytic uraemic syndrome, dilated cardiomyopathy occured in the absence of hypertension, or fluid or electrolyte disturbance. These cases presented with acute left ventricular failure. Echocardiography showed left ventricular dilatation and reduced contractility. There was also ventricular wall thickening, which persisted. Twelve other children with haemolytic uraemic syndrome had prospective echocardiography. Eleven of them showed no evidence of cardiomyopathy and in one transient dilatation and reduced contractility developed without clinical signs.

3. Richard L. Siegler. (University of Utah School of Medicine, Salt Lake City, Utah), "Cardiovascular Involvement in the Hemolytic Uremic Syndrome," Kaplan B, ed; Hemolytic syndrome and thrombocytopenic purpura. Dekker 1992

Abstract: Cardiovascular involvement in the form of salt and water retention (peripheral edema, pulmonary venous congestion), and hypertension occurs frequently in the hemolytic uremic syndrome (HUS). Occasionally, heart failure occurs as a result of persistent severe hypertension, and rarely, cardiomyopathy from thrombotic microangiopathy (TMA) of the heart muscle.

4. Birk PE, Chakrabarti S, Lacson AG, Ogborn MR, (Department of Pediatrics and Child Health, Children's Hospital of Winnipeg, University of Manitoba, Canada), "Cardiac tamponade as a terminal event in the hemolytic uremic syndrome in childhood," Pediatric Nephrology. 8(6):754-5, 1994 Dec.

Abstract:

The case of a 6-year-old Inuit female with the epidemic form of hemolytic uremic syndrome (HUS) with myocardial involvement and probable cardiac tamponade is presented. This case illustrates the multisystemic nature of the syndrome, and to our knowledge, cardiac tamponade as a probable terminal event in HUS has not been reported previously.

5. Black MD, Coles JG, Williams WG, Rebeyka IM, Trusler GA, Bohn D, Gruenwald C, Freedom RM, (Department of Cardiovascular Surgery, Hospital for Sick Children, Toronto, Ontario, Canada), "Determinants of success in pediatric cardiac patients undergoing extracorporeal membrane oxygenation," Annals of Thoracic Surgery. 60(1):133-8, 1995 Jul.

Abstract:

BACKGROUND. The purpose of this retrospective study is to determine the possible predictors of successful cardiac recovery using extracorporeal membrane oxygenation (ECMO) and the practical limits of ECMO support. METHODS. Information was gathered on 31 consecutive children with myocardial failure who could not be resuscitated with other means and underwent ECMO at the Hospital for Sick Children before January 1994. RESULTS. Of the children who underwent ECMO as a means of cardiac rescue, 14/31 (45%) were weaned successfully. Two distinct groups of children were evident based on their initial indications for ECMO: those who had postcardiotomy myocardial dysfunction (n = 25) and those with cardiomyopathy or myocarditis (n = 6). Children with residual defects after cardiotomy (n = 10) did not survive ECMO. Four of the 6 children with cardiomyopathy or myocarditis were weaned successfully. In either group of patients, ECMO support beyond 6 days failed to resuscitate the myocardium; all attempts to violate this "time barrier" in our study inevitably failed. CONCLUSIONS. Postcardiotomy residual defects are a contraindication to ECMO. If children with residual defects are excluded, successful weaning from ECMO can be achieved in almost 70%, with almost all recovery occurring with the first 6 days of ECMO.

6. Abu-Arafah I. Gray E. Youngson G. Auchterlonie I. Russell G. (University of Aberdeen, Department of Child Health, Foresterhill), "Myocarditis and haemolytic uraemic syndrome," Archives of Disease in Childhood. 72(1):46-7, 1995 Jan.

Abstract

A 13 year old girl is reported who presented with haemolytic uraemic syndrome (HUS) due to Escherichia coli 0157:H7 infection. She died during the acute phase of the illness after an episode of unexplained sudden circulatory collapse. Postmortem examination confirmed the diagnosis of HUS and showed histological evidence of myocarditis manifested by the presence of inflammatory cell infiltration in the myocardium and around the conducting system.

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Neuropsychological Sequelae of HUS: A Positive Outcome

Presented by Elaine Orrbine

Elaine Orrbine's References are embedded in her PowerPoint slides.