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Haemolytic uraemic syndrome of childhood - Heterogeneity, outcome and neutrophil involvement in pathogenesis

Fitzpatrick, Margaret M; (1994) Haemolytic uraemic syndrome of childhood - Heterogeneity, outcome and neutrophil involvement in pathogenesis. Doctoral thesis (M.D), UCL (University College London). Green open access

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Abstract

This thesis involves clinical and laboratory studies undertaken to elucidate the different clinical manifestations and prognosis of the haemolytic uraemic syndrome (HUS) of childhood, and the role of polymorphonuclear leucocytes in the pathogenesis of this disorder. An historical review, a classification and views on pathogenesis, treatment and outcome of childhood HUS are elaborated in Chapter 1. The primary subdivision of HUS in children is assumed to be those cases with prodromal diarrhoea (D+ HUS) and those without (D- HUS). An overall summary of the children presenting to the Hospital for Sick Children, Great Ormond Street, London, with a diagnosis of HUS between 1966 and 1991 is presented in Chapter 2. The clinical and laboratory features, response to treatment, and outcome of idiopathic D- HUS is reviewed in Chapter 3. In Chapter 4 a retrospective case control study to identify risk factors at presentation for the development of neurological disease in D+ HUS is described. A long-term follow-up study to evaluate the outcome of renal function in infants and children after an episode of D+ HUS (1966-85) , and a prospective single blind study using duplex Doppler ultrasound in the investigation of occult nephropathy following D+ HUS are presented in Chapter 5. In the second half of the thesis 3 laboratory studies examining the role of polymorphonuclear leucocytes (PMNLs) in the pathogenesis of D+ HUS are described. The first study examines PMNL adherence and subsequent injury to the endothelium with PMNLs and plasma from children with D4- HUS (Chapter 6) . PMNL activation in HUS is evaluated in Chapter 7 by the measurement of complexed elastase in plasma. Possible mechanisms of PMNL involvement are explored in Chapter 8 with the measurement of cytokines interleukin-8 and tumour necrosis factor a, together with complexed elastase, in HUS plasma. These studies emphasize the heterogeneity of the disorder, implicate PMNLs as having a role in pathogenesis and raise the possibility that agents which suppress PMNL recruitment, activation and adhesion to endothelium have a potential therapeutic role in the more severe forms of this disorder.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Haemolytic uraemic syndrome of childhood - Heterogeneity, outcome and neutrophil involvement in pathogenesis
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10102496
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