N Thiruchelvam

Publications (14)31.51 Total impact

• Article: Modeling the urinary tract—computational, physical, and biological methods

  C.H. Fry, P. Sadananda, D.N. Wood, N. Thiruchelvam, R.I. Jabr, R. Clayton
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  ABSTRACT: Models of the lower urinary tract are used to understand better the physiological and pathological functions of the tract and to gain insight into the relative importance of different components. The key requirement of a model is described, namely: to involve a continuous iteration with experiment; whereby experiments provide parameters and validation for components of the model, which is then used to generate hypotheses, which are tested experimentally. Different types of models are described: computational models that describe mathematically the whole urinary tract or components; physical models useful especially in testing medical devices; and tissue-engineered models. The purpose of modeling is first described in terms of the ability of models to predict the properties of the system of interest, using components that have a physiological interpretation, and to gain insight into the relative importance of different components. Examples are used to illustrate the use of modeling the urinary tract with reference to the different categories listed above. Neurourol. Urodynam. Neurourol. Urodynam. 30:692–699, 2011. © 2011 Wiley-Liss, Inc.
  Neurourology and Urodynamics 06/2011; 30(5):692 - 699. · 2.96 Impact Factor
• Article: Modeling the urinary tract-computational, physical, and biological methods.

  C H Fry, P Sadananda, D N Wood, N Thiruchelvam, R I Jabr, R Clayton
  [show abstract] [hide abstract]
  ABSTRACT: Models of the lower urinary tract are used to understand better the physiological and pathological functions of the tract and to gain insight into the relative importance of different components. The key requirement of a model is described, namely: to involve a continuous iteration with experiment; whereby experiments provide parameters and validation for components of the model, which is then used to generate hypotheses, which are tested experimentally. Different types of models are described: computational models that describe mathematically the whole urinary tract or components; physical models useful especially in testing medical devices; and tissue-engineered models. The purpose of modeling is first described in terms of the ability of models to predict the properties of the system of interest, using components that have a physiological interpretation, and to gain insight into the relative importance of different components. Examples are used to illustrate the use of modeling the urinary tract with reference to the different categories listed above.
  Neurourology and Urodynamics 06/2011; 30(5):692-9. · 2.96 Impact Factor
• Article: The double wire technique: an improved method for treating challenging ureteroileal anastomotic strictures and occlusions.

  N Thiruchelvam, M Harrison, A C Page
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  ABSTRACT: Up to 10% of patients who undergo ileal conduit urinary diversion may go on to develop ureteroileal anastomotic stenosis (UIAS); this can lead to recurrent urinary tract infections and deterioration in renal function. Classical management has been open revision of the anastomosis. We describe a novel technique that allows balloon dilatation and ureteral stent placement in a retrograde fashion. All patients in this study had undergone radical cystectomy and ileal conduit formation with Wallace type end-to-end refluxing uretero-intestinal anastomosis. After initial retrograde loopogram, a 6F MPA-1 catheter and an 0.035 inch extra stiff guide was passed to the distal ostium. Subsequently, a customised 8F bright tip MPA-1 guiding catheter was advanced over the guide wire which allowed effective splinting of the equipment to facilitate greater control of a second catheter and guide wire combination to access the stenotic or occluded anastomosis. Results show that a total of ten anastomoses were treated; nine anastomoses were successfully treated with a primary retrograde approach with no intra or post-procedural complications. After a mean follow-up of 19 months (5-33 months), as assessed by ascending loopograms, all anastomoses remained open. In conclusion, morbidity of open surgery has resulted in the popularization of endourological techniques in treating anastomotic stenoses. However, key to these endourological techniques is access to the anastomosis; typically, this has been via a percutaneously placed nephrostomy. The ideal route to the anastomosis is via a retrograde approach; we have illustrated a safe and successful novel technique that utilized two guidewires and a guiding catheter, allowing retrograde ureteral access.
  The British journal of radiology 03/2007; 80(950):103-6. · 2.11 Impact Factor
• Article: Ca2+ regulation in detrusor smooth muscle from ovine fetal bladder after in utero bladder outflow obstruction.

  C Wu, N Thiruchelvam, G Sui, A S Woolf, P Cuckow, C H Fry
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  ABSTRACT: We characterized intracellular Ca(2+) regulation in fetal bladders following outflow obstruction by examining the Ca(2+) response to agonists in smooth muscle cells. Severe bladder outflow obstruction was induced in male fetal sheep by placing a urethral ring and urachal ligation midway through gestation at 75 days. Fetuses were examined 30 days after surgery. Intracellular Ca(2+) in single smooth muscle cells isolated from the bladder wall was measured with epifluorescence microscopy using fura-2(AM) during exposure to agonists, such as carbachol and adenosine triphosphate, and to other activators, such as caffeine and KCl. Detrusor smooth muscle cells from obstructed bladders had resting intracellular Ca(2+) similar to that in sham operated controls. The maximal response to carbachol was decreased following obstruction (p <0.05). Construction of dose-response curves also demonstrated higher EC(50) (p <0.05). However, these changes were not mirrored by caffeine evoked Ca(2+) release, which was not significantly different between the obstruction group and sham operated controls. Kinetic analysis of carbachol transients further revealed an attenuated maximal rate of increase in obstructed bladders (p <0.01). The magnitude of intracellular Ca(2+) to purinergic neurotransmitter adenosine triphosphate was also found to be smaller in cells from obstructed bladders (p <0.05), although transmembrane influx by high K depolarization was not significantly affected. Muscarinic and purinergic pathways were down-regulated in fetal detrusor muscle following outflow obstruction. These major functional receptors appeared to be more susceptible to obstruction than other Ca(2+) regulators. Their impairment may contribute to the compromised contractile function seen in in utero bladder outflow obstruction.
  The Journal of Urology 03/2007; 177(2):776-80. · 3.75 Impact Factor
• Article: Ca2+ regulation in detrusor smooth muscle from developing fetal sheep bladders.

  C Wu, G Sui, N Thiruchelvam, P Cuckow, C H Fry
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  ABSTRACT: Sheep fetus is a useful model to study in utero bladder outflow obstruction but little is known about cell physiology of fetal bladders. To remedy this defect we have characterised intracellular Ca(2+) regulation in fetal sheep myocytes of different developmental ages. Fetal detrusor myocytes had a similar resting [Ca(2+)](i) to adult cells and exhibited transient [Ca(2+)](i) increases in response to carbachol, ATP, high-K, caffeine and low-Na. The carbachol transients were abolished by atropine and caffeine; the ATP response was blocked by alpha,beta-methylene ATP; high-K-evoked [Ca(2+)](i) rises were antagonised by verapamil. The maximal responses to carbachol, high-K, caffeine and low-Na in fetal cells were similar to those of adult counterparts, whilst the ATP response was smaller (p < 0.05). These variables were largely similar between the three gestational groups with the exception of ATP-induced response between early fetal and adult bladders (p < 0.05). Dose-response curves to carbachol demonstrated an increase of potency between mid-gestation and early adulthood (p < 0.05). These data show that muscarinic receptors coupled to intracellular Ca(2+) release, P2X receptor-linked Ca(2+) entry, depolarisation-induced Ca(2+) rise via L-type Ca(2+) channels, Na(+)/Ca(2+) exchange and functional intracellular Ca(2+) stores are all operational in fetal bladder myocytes. Whilst most of Ca(2+) regulators are substantially developed and occur at an early fetal age, a further functional maturation for cholinergic sensitivity and purinergic efficacy continues throughout to adulthood.
  Cell Calcium 05/2006; 39(4):367-74. · 3.77 Impact Factor
• Article: The management of hydronephrosis in patients undergoing TURBT.

  N Thiruchelvam, G Ubhayakar, H Mostafid
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  ABSTRACT: Previous studies have shown the negative prognostic correlation of hydronephrosis in bladder cancer; however, practical uncertainties remain regarding the management of these patients. We retrospectively reviewed the notes of patients undergoing TURBT over a three year period and recorded the management and outcome of patients with hydronephrosis. Six percent with bladder cancer had hydronephrosis. Nearly all the cases had muscle invasive disease. At TURBT, the ureteric orifice was seen in 41%; in the remaining 59% of patients, the ureteric orifice was involved and resected. This resolved the hydronephrosis in only one patient (who had superficial disease). Hydronephrosis in bladder cancer is associated with a poor prognosis. The hydronephrosis does not resolve with resection alone. As awaiting it's resolution may delay definitive treatment, we suggest aggressive management of hydronephrosis from the time of initial diagnosis with ureteric stenting in order to protect renal units and optimize renal function prior to further definitive treatment of bladder cancer.
  International Urology and Nephrology 02/2006; 38(3-4):483-6. · 1.47 Impact Factor
• Article: Do patients with frank haematuria referred under the two-week rule have a higher incidence of bladder cancer?

  N Thiruchelvam, H Mostafid
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  ABSTRACT: The new NHS guaranteed that everyone with suspected cancer would be able to see a specialist within 2 weeks of their GP deciding that they need to be seen urgently. We investigated whether referrals under the two-week rule for frank haematuria results in a clinically significant advantage over normal referral pathways in patients with suspected bladder cancer. Patients referred for frank haematuria specifically under the two-week cancer rule were prospectively recorded over a 2-year period. Results of haematuria investigations were compared to a control group of routine frank haematuria referrals. Of the 32 patients in each group, four bladder cancers were found in the 2-week rule group and five bladder cancers were found in the control group (P > 0.05). The number of other demonstrable urological causes of frank haematuria was also the same in the two groups. The incidence of bladder cancer and other urological pathologies is the same irrespective of referral pattern. It is not clear whether seeing such patients within 2 weeks confers any clinically significant advantage over conventional referral pathways. Not all patients with macroscopic haematuria are referred or seen under the two-week rule, this has considerable clinical governance implications for all departments of urology.
  Annals of The Royal College of Surgeons of England 09/2005; 87(5):345-7. · 1.23 Impact Factor
• Article: Bladder wall tension during physiological voiding and in patients with an unstable detrusor or bladder outlet obstruction.

  N Thiruchelvam, M L Godley, Prof C H Fry
  BJU International 06/2004; 93(7):1117-8. · 2.84 Impact Factor
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  Available from: rsmjournals.com

  Article: Emergency dorsal slit for balanitis with retention.

  N Thiruchelvam, P Nayak, H Mostafid
  Journal of the Royal Society of Medicine 05/2004; 97(4):205-6. · 1.41 Impact Factor
• Article: A preliminary study of natural-fill radiotelemetered ovine fetal cystometry.

  N Thiruchelvam, M L Godley, M K Farrugia, P M Cuckow
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  ABSTRACT: To determine whether fetal cystometric studies by radiotelemetry are feasible in the fetal lamb, and potentially suitable for chronically monitoring fetal bladder pressures in an experimental fetal model of bladder outlet obstruction (BOO), as in utero BOO (e.g. caused by posterior urethral valves) results in significant postnatal bladder dysfunction but the pathophysiological progression of fetal bladder maldevelopment remains poorly understood. The procedure required fetal sheep surgery and anaesthesia. Radiotelemetry implants comprised catheters that transmitted pressure fluctuations to an implant body; data were then transmitted using radio frequency to a receiver that passed this information to a computer. Four fetuses were used with different methods of catheter placement to optimize the technique. Recordings were possible in three of the four sheep; during observation there were: (i) quiet periods with no abdominal or bladder pressure rises; (ii) synchronous activity in the bladder and abdomen; and (iii) discriminate activity, associated with intravesical activity only. Four patterns of discriminate bladder activity were observed, defined as void, immature void, staccato activity and 'unstable' type activity. Radiotelemetry cystometry for long-term monitoring is feasible in the experimental fetus without causing death or morbidity, or inhibiting growth. The method can discriminate reproducible patterns of detrusor activity. Recorded 'voiding' types were consistent between experiments and as reported in other fetal animal studies.
  BJU International 03/2004; 93(3):382-7. · 2.84 Impact Factor
• Article: A novel device for reconstituting and delivering intravesical chemotherapy.

  N Thiruchelvam, H Mostafid
  BJU International 10/2003; 92(4):492. · 2.84 Impact Factor
• Article: Neurotransmission and viscoelasticity in the ovine fetal bladder after in utero bladder outflow obstruction.

  N Thiruchelvam, C Wu, A David, A S Woolf, P M Cuckow, C H Fry
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  ABSTRACT: Fetal bladder outflow obstruction, predominantly caused by posterior urethral valves, results in significant urinary tract pathology; these lesions are the commonest cause of end-stage renal failure in children, and up to 50% continue to suffer from persistent postnatal bladder dysfunction. To investigate the physiological development of the fetal bladder and the response to urinary flow impairment, we performed partial urethral obstruction and complete urachal ligation in the midgestation fetal sheep for 30 days. By electrical and pharmacological stimulation of bladder strips, we found that muscarinic, purinergic, and nitrergic mechanisms exist in the developing fetal bladder at this gestation. After bladder outflow obstruction, the fetal bladder became hypocontractile, producing less force after nerve-mediated and muscarinic stimulation with suggested denervation, and also exhibited greater atropine resistance. Furthermore, fetal bladder urothelium exerted a negative inotropic effect, partly nitric oxide mediated, that was not present after obstruction. Increased compliance, reduced elasticity, and viscoelasticity were observed in the obstructed fetal bladder, but the proportion of work performed by the elastic component (a physical parameter of extracellular matrix) remained the same. In addition to denervation, hypocontractility may result from a reduction in the elastic modulus that may prevent any extramuscular components from sustaining force produced by detrusor smooth muscle.
  AJP Regulatory Integrative and Comparative Physiology 06/2003; 284(5):R1296-305. · 3.34 Impact Factor
• Article: Congenital obstructive uropathy: its origin and contribution to end-stage renal disease in children.

  A S Woolf, N Thiruchelvam
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  ABSTRACT: Most children with end-stage renal failure are born with abnormal kidneys, with fetal obstructive uropathy accounting for about half these cases. Posterior urethral valves (PUV) is overwhelmingly the most common, specific diagnosis, and is confined to boys. In general, the condition is sporadic, although familial cases have been reported, perhaps suggesting that genetic factors play a role in pathogenesis. PUV can present antenatally, detected on routine fetal ultrasonography, or postnatally, when it is associated with renal failure and bladder dysfunction. Advances in postnatal surgery and medical management have reduced the mortality in PUV, but it is uncertain whether antenatal diagnosis or treatment (eg, with vesicoamniotic shunts) improves long-term renal outcome. Other disorders associated with human fetal obstructive uropathy are urethral atresia, the prune belly syndrome, and multicystic dysplastic kidney. The nephropathy associated with fetal obstructive uropathy is renal dysplasia and comprises undifferentiated and metaplastic tissues. Several studies in animals and in humans suggest that fetal urine flow impairment causes deregulation of renal precursor cell turnover and expression of growth factor/survival and transcription factor genes. Furthermore, some of these morphologic and molecular changes can be ameliorated experimentally by fetal surgical decompression or administration of specific growth factors.
  Advances in Renal Replacement Therapy 08/2001; 8(3):157-63.
• Article: Ca2+ regulation in detrusor smooth muscle from developing fetal sheep bladders

  C. Wu, G. Sui, N. Thiruchelvam, P. Cuckow, C.H. Fry
  [show abstract] [hide abstract]
  ABSTRACT: Sheep fetus is a useful model to study in utero bladder outflow obstruction but little is known about cell physiology of fetal bladders. To remedy this defect we have characterised intracellular Ca2+ regulation in fetal sheep myocytes of different developmental ages. Fetal detrusor myocytes had a similar resting [Ca2+]i to adult cells and exhibited transient [Ca2+]i increases in response to carbachol, ATP, high-K, caffeine and low-Na. The carbachol transients were abolished by atropine and caffeine; the ATP response was blocked by α,β-methylene ATP; high-K-evoked [Ca2+]i rises were antagonised by verapamil. The maximal responses to carbachol, high-K, caffeine and low-Na in fetal cells were similar to those of adult counterparts, whilst the ATP response was smaller (p < 0.05). These variables were largely similar between the three gestational groups with the exception of ATP-induced response between early fetal and adult bladders (p < 0.05). Dose–response curves to carbachol demonstrated an increase of potency between mid-gestation and early adulthood (p < 0.05). These data show that muscarinic receptors coupled to intracellular Ca2+ release, P2X receptor-linked Ca2+ entry, depolarisation-induced Ca2+ rise via L-type Ca2+ channels, Na+/Ca2+ exchange and functional intracellular Ca2+ stores are all operational in fetal bladder myocytes. Whilst most of Ca2+ regulators are substantially developed and occur at an early fetal age, a further functional maturation for cholinergic sensitivity and purinergic efficacy continues throughout to adulthood.
  Cell Calcium.