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Title: Nerve growth factor and lower urinary tract dysfunction
Author: Vijaya, Gopalan
ISNI:       0000 0004 5349 6257
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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The polypeptide nerve growth factor (NGF) has been explored extensively over the span of six decades since its detection with amazing discoveries from its neurotrophic action to tissue healing properties. In lower urinary tract there is substantial evidence linking NGF and lower urinary tract dysfunction (LUTD). Over recent years the role of urinary NGF [UrNGF] in diagnosing LUTD as well as monitoring treatment response has been investigated extensively. However, the available studies report conflicting data regarding an association between lower urinary tract symptoms [LUTS] and UrNGF, and there is limited evidence for the validity and reliability of urinary NGF assays. In a quest to explore the role of UrNGF as a LUTS biomarker, levels were measured in patients with LUTD, prolapse and asymptomatic controls. This thesis hypotheses that measurement of NGF is of no value in LUTD and prolapse. Therefore the aims were to evaluate the diagnostic and discriminant ability of UrNGF measurement in LUTD and to test the reliability of NGF assays. The other objective was to study the association between UrNGF levels and cystoscopic and histology findings of bladder inflammation in women with overactive bladder [OAB] to explore the link between NGF and inflammation. Change in UrNGF levels after cystocele repair was studied, since bladder wall stretching has been postulated as one of the causes for increased NGF levels. Finally UrNGF levels before and after antibiotic treatment for refractory OAB were measured with the aim to evaluate its role to assess treatment response. On test retest reliability analysis of 13 samples there was almost perfect reliability with an Intraclass correlation coefficient of 0.889; 95%[C.I=0.676-0.965; p<0.001]. Urinary NGF was significantly but non-specifically increased in symptomatic patients [n=205] when compared to controls [n=31](13.33 vs. 2.05 ng NGF/ g Cr, Mann Whitney test; p <0.001) However ROC analysis, demonstrated poor discriminant ability between either different symptomatic groups or urodynamic groups. Using a cut off of 13.0 ng NGF/ g creatinine the test provides a sensitivity of 81%, but a specificity of only 39 % for overactive bladder. UrNGF levels were not associated with cystoscopic or histology findings of inflammation and did not improve after anterior repair in women who had an improvement in OAB symptoms. However in the study done to explore the role of urinary NGF as a biomarker to assess treatment response, NGF levels were found to decrease significantly after six weeks of antibiotic therapy in women with refractory OAB symptoms [n=35 patients] (Wilcoxon Signed rank test; p=0.015). This was associated with improvement in OAB symptoms. UrNGF does not appear to be a good diagnostic biomarker but may have a role as a marker of treatment response, hence may have limited role in assessment of women with LUTD.
Supervisor: Khullar, Vikram; Regan, Lesley; Mathias, Christopher Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available