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Biomedical subjects

Nikesh Thiruchelvam

Publications and source records attributed to Nikesh Thiruchelvam.

8 recordsLinked to original sources

MRSA in urology: a UK hospital experience.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) infection appears to be increasing, the UK has one of the worst MRSA rates in Europe. As urological patients are at high risk, the aim of this study was to determine the number of newly diagnosed cases of MRSA detected in a urology ward. PATIENTS AND METHODS: The urology department serves an annual local population of greater than 500,000 with 30 inpatient beds and a tertiary population of 1 million. Over a five year period, we retrospectively recorded all patients with a new diagnosis of MRSA. We also determined colonization site and if the diagnosis of MRSA was made in an elective surgical patient or a patient admitted as an emergency. RESULTS: The mean number of newly diagnosed cases of MRSA was 20.6 per year. The percentage of patients with a new diagnosis of MRSA was less than or equal to 1% per year with no significant difference of new cases of MRSA over five years. Emergency patients had a trend towards a mean higher rate of MRSA. The commonest site of MRSA colonization was from catheters (32%) and open wounds (18%). DISCUSSION: MRSA is of concern, as compared to methicillin-sensitive staphylococcus aureus, because it is associated with high rates of clinically relevant infection, increased hospital stay and cost, greater mortality and high vancomycin usage. Mandatory reporting has shown a steady increase in the number of cases of MRSA infection over the past four years. We found that the number of newly diagnosed cases of MRSA was low, at less than or equal to 1% of patients per year. Furthermore, the number of new cases of MRSA remained constant over five years suggesting low acquisition rates in a busy UK urology ward.

Cross Infection↗

Contractile properties of the developing fetal sheep bladder.

AIM: To characterise the developmental changes to the normal bladder by examining the in vitro contractile properties of the fetal sheep detrusor smooth muscle bladder at different gestational ages. METHODS: Three groups of normally developing fetal sheep bladders were investigated: (1) 65-70 days gestation (2nd trimester); (2) 105-110 days (3rd trimester); (3) 135-140 days (term). Isometric contractions in isolated detrusor strips were measured during either electrical field stimulation (EFS) or exposure to agonists: carbachol, alpha-beta methylene-ATP (ABMA) and KCl. RESULTS: There was a significant increase of absolute force elicited by EFS with fetal age. Contractures elicited by carbachol, ABMA and KCl increased between Groups 1 and 2, but not thereafter. The proportional increase of contractions elicited by carbachol and ABMA was also greater between Groups 1 and 2, than for EFS and KCl. CONCLUSIONS: Fetal development between 65 and 140 days in the sheep is associated with increased contractile activation. The data are consistent with an increase of muscle development in the earlier stages (65-110 days). In the later stage (110-140 days) muscle development is complete but functional innervation of the tissue continues.

Adenosine Triphosphate↗

Planning percutaneous nephrolithotomy using multidetector computed tomography urography, multiplanar reconstruction and three-dimensional reformatting.

OBJECTIVE: To assess a modified technique of multidetector computed tomographic urography (CTU) which can reproducibly and accurately map the pelvicalyceal system (PCS) and complex renal calculi, as such information is essential in choosing the optimal percutaneous approach into the PCS for safe and successful percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: Ten consecutive patients with renal calculi underwent a modified four-detector multislice CTU with frusemide, abdominal compression and subsequent injection with contrast medium. After unenhanced CT of the abdomen, a high-resolution contrast-enhanced scan was taken through the kidneys in the pyelographic phase. Data were analysed using multiplanar reconstruction and three-dimensional (3D) reformatting. RESULTS: In 10 CTUs there were three staghorn, two diverticular, 25 calyceal, two infundibular and two renal pelvic calculi; nine showed posterior calyces and good infundibular anatomy, and provided a good map of the PCS. Seven patients had PCNL, with the remaining three having either primary extracorporeal shock wave lithotripsy or conservative management. CTU detected stones in all patients and accurately located their relation to the PCS. With reconstructed images, subjectively the 3D imaging provided an advantage over conventional imaging in optimizing nephrostomy placement. CONCLUSION: CTU with this protocol and post-processing techniques enables an accurate and confident, reproducible prediction of the site, number and size of stones in complex pelvicalyceal anatomy, optimal site(s) for placing the percutaneous track, and potential hazards when placing the track, with no significant increase in the patient's radiation burden. 3D CTU should become the standard imaging method for planning PCNL in selected patients.

Diuretics↗

Urinary outflow obstruction increases apoptosis and deregulates Bcl-2 and Bax expression in the fetal ovine bladder.

During organogenesis, net growth of tissues is determined by a balance between proliferation, hypertrophy, and apoptotic death. Human fetal bladder outflow obstruction is a major cause of end-stage renal failure in children and is associated with complex pathology in the kidney and lower urinary tract. Experimental manipulation of the fetal sheep urinary tract has proved informative in understanding the pathobiology of congenital obstructive uropathy. In this study we used an ovine model of fetal bladder outflow obstruction to examine effects on apoptotic cell death in the developing urinary bladder. While 30 days of obstruction in utero between 75 and 105 days gestation resulted in overall growth of the fetal bladder as assessed by weight, protein, and DNA measurements, we found that apoptosis, as assessed by in situ end-labeling, was up-regulated in fetal bladder detrusor muscle and lamina propria cells and that this was accompanied by a down-regulation of the anti-death protein Bcl-2 and an up-regulation of the pro-death protein Bax. Moreover, activated caspase-3, an effector of apoptotic death, was increased in obstructed bladders. This is the first study to define altered death in an experimental fetal model of bladder dysmorphogenesis. We speculate that enhanced apoptosis in detrusor smooth muscle cells is part of a remodeling response during compensatory hyperplasia and hypertrophy. Conversely, in the lamina propria, an imbalance between death and proliferation leads to a relative depletion of cells.

Animals↗

Effects of in utero bladder outflow obstruction on fetal sheep detrusor contractility, compliance and innervation.

PURPOSE: Congenital bladder outflow obstruction caused by posterior urethral valves is a common cause of end stage renal failure in boys. We hypothesized that fetal bladder outflow obstruction perturbs detrusor contractility and innervation and bladder storage volume-pressure relationships. MATERIALS AND METHODS: 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, when urinary tract dilatation, enlarged bladders and histologically abnormal kidneys were documented. Isolated strips of bladder detrusor from sham operated and obstructed fetuses were subjected to electrical field stimulation, carbachol, KCl and alpha-beta methylene-adenosine triphosphate. Whole bladder storage characteristics were determined by filling cystometry and bladder innervation was investigated by immunohistochemistry and Western blot. RESULTS: Tension-frequency contractility studies showed that obstructed fetal bladder strips were significantly hypocontractile versus sham operated controls in response to electrical field stimulation and the specific agonists carbachol, KCl and alpha-beta methylene-adenosine triphosphate. Hypocontractility was greater with nerve mediated stimulation than with carbachol, suggesting relative denervation. Reduced innervation was confirmed by S100 and protein gene product 9.5 immunohistochemistry and by measuring a significant reduction in protein gene product 9.5 protein expression using Western blot. Filling cystometry showed that obstructed fetal bladders appeared more compliant (Delta V/Delta P, where Delta V is the change in volume and Delta P is the change in pressure) with larger capacity, more flaccidity and yet retained stress relaxation. CONCLUSIONS: In response to severe experimental fetal bladder outflow obstruction the bladder becomes large and hypocontractile, and has aberrant innervation.

Animals↗