<i>Escherichia coli</i>O157:H7 and the Hemolytic–Uremic Syndrome

Boyce, Thomas G.; Swerdlow, David L.; Griffin, Patricia M.

doi:10.1056/nejm199508103330608

Cited by 517 publications

(340 citation statements)

References 54 publications

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“…EHEC strains of serotype O157:H7 have caused both the largest number of outbreaks and epidemics that have involved the greatest numbers of patients. Strains with this serotype have also caused the majority of sporadic STEC infections (34)(35)(36). Although EHEC O157:H7 strains contain large plasmids similar to those of EPEC, they lack the genes required for synthesis of BFP.…”

Section: Two Divergent Groups Of Epecmentioning

confidence: 99%

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Pathogenesis and evolution of virulence in enteropathogenic and enterohemorrhagic Escherichia coli

Donnenberg¹,

Whittam²

2001

J. Clin. Invest.

237

169

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Section: Two Divergent Groups Of Epecmentioning

confidence: 99%

“…HUS is a microangiopathic hemolytic anemia characterized by disseminated capillary thrombosis and ischemic necrosis (34). The kidneys are the end organs most severely affected, but ischemic necrosis of the intestines, central nervous system (stroke), and indeed any organ may occur.…”

Section: Two Divergent Groups Of Epecmentioning

confidence: 99%

Pathogenesis and evolution of virulence in enteropathogenic and enterohemorrhagic Escherichia coli

Donnenberg¹,

Whittam²

2001

J. Clin. Invest.

237

169

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“…1 There is a well-documented association between infection with E. coli strain O157:H7 and the occurrence of HUS. 2,3 Individuals infected with the human immunodeficiency virus have an increased incidence of TTP. 4 TM also occurs in relation to pregnancy; TTP tends to occur in the ante-partum period while HUS is more frequent post-partum.…”

mentioning

confidence: 99%

Thrombotic microangiopathy following allogeneic bone marrow transplantation is associated with intensive graft-versus-host disease prophylaxis

Paquette

Tran

Landaw³

1998

Bone Marrow Transplant

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Summary:Thrombotic microangiopathy (TM), manifesting clinically as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome, is an uncommon complication after bone marrow transplantation (BMT). A retrospective analysis of potential risk factors for TM following allogeneic BMT was performed. Clinical data were analyzed from seven patients diagnosed with severe TM and 409 patients who underwent BMT during the same time period and who survived for at least 100 days afterwards. Six of the seven patients with TM received intensive GVHD prophylaxis consisting of cyclosporine, methotrexate and glucocorticoids, whereas only 66 of the 409 patients without TM received this regimen (P Ͻ 0.001, Fisher's exact test). This regimen was administered to patients older than 40 years, or recipients of a mismatched or unrelated allograft. Univariate analysis also revealed an increased risk of TM associated with the use of an unrelated bone marrow donor (P = 0.02), but no significant association with patient age or gender, diagnosis, amount of prior chemotherapy, transplant conditioning regimen or severity of GVHD. A multivariate exact logistic regression analysis revealed that only the type of GVHD prophylaxis had a significant impact on the risk for TM. The combined use of cyclosporine, methotrexate and glucocorticoids as GVHD prophylaxis may predispose to the development of TM following BMT. Keywords: thrombotic thrombocytopenic purpura; hemolytic uremic syndrome; bone marrow transplantation; graftversus-host disease Thrombotic microangiopathy (TM) is a pathological process characterized by occlusion of the microvasculature by hyaline thrombi resulting in microangiopathic hemolytic anemia, thrombocytopenia and end organ dysfunction. Clinically, TM manifests as hemolytic uremic syndrome (HUS) when the renal vasculature is primarily affected, or as thrombotic thrombocytopenic purpura (TTP) when there is diffuse vascular involvement. The onset of TM has been associated with infection by a variety of bacterial or viral pathogens. 1 There is a well-documented association between infection with E. coli strain O157:H7 and the occurrence of HUS. 2,3 Individuals infected with the human immunodeficiency virus have an increased incidence of TTP. 4 TM also occurs in relation to pregnancy; TTP tends to occur in the ante-partum period while HUS is more frequent post-partum. 1 Administration of chemotherapy, especially mitomycin C, has been associated with the development of HUS. 5 These various etiologies are thought to share the ability to induce injury to the vascular endothelium. Plasma exchange is highly effective therapy for TTP; HUS may also respond to this therapy. 3,6 TM is an uncommon complication of allogeneic bone marrow transplantation (BMT). More than 63 cases of TM have been reported to occur in this setting. 7 The first case of TM following allogeneic BMT was observed during the earliest use of cyclosporine (CsA) prophylaxis for graftversus-host disease (GVHD). 8 Subsequently, the occurrence of TM was found to be signifi...

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“…As components of cellular receptors for microbes and their toxins (Karlsson 1989), glycolipids are also of worldwide importance: cholera toxin, shiga toxin and the verotoxin of Escherichia coli-an important cause of renal failure and the haemolytic-uraemic syndrome-immediately come to mind (Brown et al 1991;Boyce et al 1995). Through the systematic genetic 'knockout' approach taken by Dr Proia, however, we learned of the involvement of complex gangliosides in interleukin 2 signalling in T cells and of the role of GM3 gangliosides in the modulation of insulin receptor activity (Proia 2003).…”

Section: Role Of Glycolipidsmentioning

confidence: 99%

Future perspectives for glycolipid research in medicine

Cox

2003

Phil. Trans. R. Soc. Lond. B

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Medical interest in glycolipids has been mainly directed to the rare and complex glycosphingolipid storage disorders that are principally caused by unitary deficiencies of lysosomal acid hydrolases. However, glycolipids are critical components of cell membranes and occur within newly described membrane domains known as lipid rafts. Glycolipids are components of important antigen systems and membrane receptors; they participate in intracellular signalling mechanisms and may be presented to the immune system in the context of the novel CD1 molecules present on T lymphocytes. A knowledge of their mechanism of action in the control of cell growth and survival as well as developmental pathways is likely to shed light on the pathogenesis of the glycosphingolipid storage disorders as well as the role of lipid second messengers in controlling cell mobility and in the mobilization of intracellular calcium stores (a biological role widely postulated particularly for the lysosphingolipid metabolite sphingosine 1-phosphate). Other sphingolipid metabolites such as ceramide 1-phosphate may be involved in apoptotic responses and in phagocytosis and synaptic vesicle formation. The extraordinary pharmaceutical success of enzymatic complementation for Gaucher's disease using macrophage-targeted human glucocerebrosidase has focused further commercial interest in other glycolipid storage diseases: the cost of targeted enzyme therapy and its failure to restore lysosomal enzymatic deficiencies in the brain has also stimulated interest in the concept of substrate reduction therapy using diffusible inhibitory molecules. Successful clinical trials of the iminosugar Nbutyldeoxynojirimycin in type 1 Gaucher's disease prove the principle of substrate reduction therapy and have attracted attention to this therapeutic method. They will also foster important further experiments into the use of glycolipid synthesis inhibitors for the severe neuronopathic glycosphingolipidoses, for which no definitive treatment is otherwise available. Future glycolipid research in medicine will be directed to experiments that shed light on the role of sphingolipids in signalling pathways, and in the comprehensive characterization and their secretory products in relation to the molecular pathogenesis of the storage disorders; experiments of use to improve the efficiency of complementing enzymatic delivery to the lysosomal compartment of storage cells are also needed. Further systematic screening for inhibitory compounds with specific actions in the pathways of glycosphingolipid biosynthesis will undoubtedly lead to clinical trials in the neuronopathic storage disorders and to wider applications in the fields of immunity and cancer biology.

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Escherichia coliO157:H7 and the Hemolytic–Uremic Syndrome

Cited by 517 publications

References 54 publications

Pathogenesis and evolution of virulence in enteropathogenic and enterohemorrhagic Escherichia coli

Pathogenesis and evolution of virulence in enteropathogenic and enterohemorrhagic Escherichia coli

Thrombotic microangiopathy following allogeneic bone marrow transplantation is associated with intensive graft-versus-host disease prophylaxis

Future perspectives for glycolipid research in medicine

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