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Title: The role of chronic and recurrent infection in the generation of overactive bladder symptoms in multiple sclerosis
Author: Kupelian, A. S.
ISNI:       0000 0004 7229 7712
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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This thesis provides original evidence that patients with multiple sclerosis may harbour undisclosed urinary infection that generates urothelial inflammation and overactive bladder symptoms. The studies within this thesis examine the performance of recommended diagnostic tests for urinary tract infection, and explore the bacterial ecology of urinary infection and its associated urothelial inflammatory response. The association between lower urinary tract inflammation, bacterial colonisation and the generation of overactive bladder symptoms is explored. A novel therapy with proposed immunomodulatory effects was tested as a candidate treatment for overactive bladder symptoms. The urinary dipstick is the recommended diagnostic test for urinary infection in patients with multiple sclerosis. In patients with chronic lower urinary tract symptoms, the dipstick failed to identify culture-positive bacterial infection in more than half of cases. This failure is compounded by the poor performance of current culture-based diagnosis that employs erroneous quantitative diagnostic thresholds. When a sensitive culture method was deployed and quantitative thresholds rejected, controlled data demonstrated that bacterial urinary infection was evident in sixty percent of patients. Quantitative and qualitative differences in the bacterial ecology of infecting isolates were evident amongst patients and controls. This was associated with increased urothelial inflammation amongst patients. Prospective, controlled data demonstrated that escalating urothelial inflammation, characterised by the expression of pyuria, was associated with increased bacterial load in the lower urinary tract. Pyuria predicted the severity of overactive bladder symptoms and indices of bladder function. Am immunomodulatory treatment for overactive bladder symptoms was tested as part of this work but no therapeutic effects were identified.
Supervisor: Malone-Lee, J. G. ; Mohamed-Ali, V. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available