Biomedical subjects
Publications and source records attributed to S Vaidyanathan.
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INTRODUCTION: Nerve growth factor (NGF), apart from its role as a growth factor, appears to be involved in neuroimmune interactions and in tissue inflammation. Low-affinity nerve growth factor receptor (p75 NGFR), if demonstrated in the urothelium, could provide the means for (1) NGF-mediated modulation of the urothelial response to inflammation; (2) NGF-mediated autocrine/paracrine regulation of urothelial proliferation; and (3) p75 NGFR-mediated induction of apoptosis. OBJECTIVES: To investigate the presence of p75 NGFR in the vesical urothelium of patients with neuropathic bladder by immunohistochemical methods. SETTING: A hospital-based study of consecutive, unselected, adult patients of either sex with neuropathic bladder, undergoing procedure on the urinary tract in a Regional Spinal Injuries Centre located in the north-west of England. INTERVENTION: Cold cup biopsies were taken from the trigone of the neuropathic urinary bladder of 26 patients with neuropathic bladder. Immunohistochemical studies were performed using antiNGF-receptor human monoclonal antibody which reacts with the low affinity receptor (p75 NGFR). RESULTS: Both neural and epithelial structures showed positive immunostaining for p75 NGFR. The basal layer of the transitional epithelium showed strongly positive immunostaining for p75 NGFR in all the 26 cases. The luminal layer of transitional epithelium showed varying degree of positive immunostaining in 12 patients. The nerve fibres showed positive immunostaining for p75 NGFR. In many cases, the positively-stained nerve fibres were coursing very close to the basal layer of the urothelium almost entering the urothelium; however, no NGFR-positive intra-epithelial terminals could be seen. The positively-stained single nerve fibres and positively-stained thicker nerve bundles were seen in abundance in the submucosa but they were present in a sparse manner in the muscularis layer. CONCLUSION: The presence of p75 NGFR was demonstrated in the urothelium of neuropathic bladder of all the 26 patients with neuropathic bladder. This observation may have potential therapeutic implications.
Patients with chronic tetraplegia are prone to develop unique clinical problems which require readmission to specialised centres where the health professionals are trained specifically to diagnose, and treat the diseases afflicting this group of patients. An appraisal of the readmission pattern of tetraplegic patients will provide the necessary data for planning allocation of beds for treatment of chronic tetraplegic patients. Hospital records of patients with tetraplegia readmitted to the Regional Spinal Injuries Centre, Southport, UK between 1 January 1994 and 31 December 1995 were analyzed to find out the number of tetraplegic patients who required readmission, reasons for readmission, duration of hospital stay, and mortality among patients readmitted. During the 2-year period, 155 tetraplegic patients were readmitted and 44 of them (28.4%) required more than one readmission (total readmission episodes: 221); these patients occupied 4.5 beds which is equivalent to 11.5% of the total bed capacity of the spinal unit. Among the reasons for the readmissions, evaluation and care of urinary tract disorders topped the list with 96 readmission episodes (43.43%) involving 70 patients; the median hospital stay was 3 days, and 18 patients (26%) required more than one readmission during this period. One hospital bed was occupied by the tetraplegic patients requiring treatment/evaluation of urinary tract disorders. Assessment and treatment of cardio-respiratory diseases was the second most common reason for readmission with 51 readmission episodes pertaining to 27 patients having a median hospital stay of 6 days; 13 patients (48%) were readmitted more than once within this 2-year period. Treatment of cardio-respiratory diseases in chronic tetraplegic patients required 1.2 hospital beds yearly. Only five tetraplegic patients were readmitted for treatment of pressure sore(s); however they had a prolonged hospital stay (median duration: 101 days). Social reasons accounted for 13 readmission episodes concerning nine patients who stayed in the hospital for varying periods (median: 6.5 days; mean: 35 days). Four tetraplegic patients readmitted with acute chest infection expired. An 81 year-old tetraplegic died of myocardial infarction. Urinary sepsis, renal insufficiency, respiratory failure and intra-cerebral haemorrhage accounted for the demise of a 41 year-old tetraplegic patient following surgical removal of a large, impacted stone at the pelviureteric junction. A tetraplegic patient who was admitted with haematuria subsequently underwent cystectomy for squamous cell carcinoma of the urinary bladder; he developed secondaries and expired 5 months later. As more patients with high cervical spinal cord injury survive the initial period of trauma, and as the life expectancy of tetraplegic patients increases, it is likely that greater numbers of tetraplegic patients will be requiring readmission to spinal injuries centre. Although it may be possible to prevent some of the complications of spinal cord injury and hence the need for a readmission, progress in medicine and rehabilitation technology will create additional demands for readmissions of chronic tetraplegic patients in order to implement the newer therapeutic strategies. Thus a change in the pattern of readmission of chronic tetraplegic patients is likely to be the future trend and this should be taken into account while making plans for providing the optimum care to chronic tetraplegic patients.
An 18-year-old male developed C-5 complete tetraplegia following a motor-cycle accident in May 1975. The neuropathic bladder was managed by an indwelling urethral catheter. He developed recurrent episodes of urinary infection with Proteus species. In September 1975, an X-ray of the abdomen revealed small calculi in both the kidneys. In July 1976, he underwent transurethral resection of the bladder neck and division of the external urethral sphincter; subsequently, he was put on a penile sheath drainage. He continued to suffer from repeated episodes of urinary tract infection with Proteus, Providencia, and Pseudomonas species, and he was treated with antibiotics. In 1980, intravenous urography (IVU) showed two large stones in the left kidney with marked caliectasis. The IVU performed in 1984 showed an increase in the size of the calculi in the left kidney which was grossly hydronephrotic. There were clusters of small calculi in the right kidney. The left renal calculi were treated by percutaneous lithotripsy in two sessions. In 1988, an X-ray of the abdomen revealed staghorn calculus in the right kidney and recurrence of stones in the left kidney. The staghorn calculus in the right kidney was treated by percutaneous nephrostolithotomy in two sessions. In 1991, he was admitted with acute urinary infection. IVU showed a stone in the pelviureteric junction with no excretion of contrast in the left kidney. Percutaneous nephrostomy drainage was established followed by left percutaneous nephrostolithotomy. In 1992, he was found to retain large amount of urine in the bladder; subsequently, his mother was taught to perform regular intermittent catheterisations. In 1995, he was admitted with acute urine infection. Abdominal X-ray revealed recurrence of large stones in both kidneys. With multiple sessions of Extracorporeal Shockwave Lithotripsy (ESWL), about 80% clearance was achieved on the left side. Right staghorn renal stone awaits treatment. This case shows that recurrent urinary infection in spinal cord injury patients is a predisposing factor for renal lithiasis. These patients require annual urological evaluation. Urinary tract calculi, if detected, should be dealt with promptly to prevent renal damage due to urinary obstruction and urosepsis. Renal calculi can be treated effectively and safely by ESWL in spinal cord injury patients, thus avoiding the need for an invasive procedure. It is essential to achieve low-pressure, adequate emptying of the urinary bladder in patients with spinal cord injury in order to prevent recurrent urinary infection and its sequelae. Social issues involved in the care of a tetraplegic patient play a vital role in the implementation of ideal medical treatment and need to be addressed promptly to avoid any compromise in the quality of medical care.
INTRODUCTION: Spinal cord injury (SCI) results in disruption of synaptic influences on the sympathetic preganglionic neurones. Remodelling of spinal cord circuits takes place in spinal neurones caudal to cord injury. There is an increased vascular alpha-adrenoceptor responsiveness, and peripheral afferent (bladder) stimulation in SCI subjects induces a marked noradrenaline spillover below the level of spinal lesion. These neurophysiological changes possibly contribute to the development of autonomic dysreflexia, a condition of sympathetic hyper-excitability that develops after cervical, or upper dorsal cord injury with resultant paroxysmal rise in arterial pressure, and provide the scientific basis for the use of terazosin, a once-a-day, selective alpha-one adrenergic blocking drug. OBJECTIVES: The use of terazosin, a long-acting, alpha 1-selective blocking agent was investigated in SCI patients who developed recurrent symptoms of autonomic dysreflexia, eg headache, sweating flushing of the face together with an increase in the arterial pressure. DESIGN: An open, prospective study of the efficacy of terazosin in controlling recurrent autonomic dysreflexia in traumatic tetraplegic/paraplegic patients manifesting clinical features of dysreflexia in the absence of an acute precipitating cause such as a blocked catheter. SETTING: The initial assessment and treatment were carried out in the Spinal Injuries Centre. Subsequently, the patients were followed-up in the community. They were monitored by telephonic interviews, follow-up visits by the patients to the hospital, and home-visits by the staff of the spinal unit. SUBJECTS: Eighteen adults with tetraplegia (female: 1; male: 17), three children with ventilator-dependent tetraplegia and three adult male patients with paraplegia who exhibited recurrent features of autonomic dysreflexia in the absence of an acute predisposing factor for dysreflexia eg performance of an invasive procedure such as cystoscopy, digital evacuation of bowels, or acute urinary retention, were enrolled in this study. INTERVENTION: After discussion with the patients and their carers, terazosin was prescribed with a starting dose of 1 mg in an adult and 0.5 mg in a child administered nocte. The patients were observed for (1) drug-induced hypotension; (2) clinical symptoms due to side effects of terazosin; and (3) continued occurrence of dysreflexic symptoms. Step-wise increments of the dose of terazosin (1 mg in case of adults, and 0.5 mg in a child) was carried out at intervals of 3-4 days, if a patient continued to develop dysreflexia but did not manifest any serious side effect. OUTCOME MEASURES: Complete subsidence of dysreflexic symptoms, or development of an adverse event necessitating termination of the terazosin therapy was the clinical end point. RESULTS: The dysreflexic symptoms subsided completely with the terazosin therapy in all the patients. The twenty-one adult patients required a dose varying from 1-10 mg, whereas the paediatric patients required only 1-2 mg of terazosin. The side effects of postural hypotension and drowsiness were transient, and mild. One tetraplegic patient developed persistent dizziness and therefore, the drug therapy was discontinued. CONCLUSION: In 21 adult and three paediatric spinal cord injury patients manifesting recurrent episodes of autonomic dysreflexia in the absence of an acute predisposing cause, the use of terazosin, a once-a-day, specific alpha-one blocker resulted in complete subsidence of the dysreflexic symptoms. However, one tetraplegic patient required termination of terazosin therapy because of persistent dizziness.
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A total of 85 urine samples from 63 patients with neurogenic bladder, were subjected for pus cell counting and culture. Fifty nine (69.4%) samples showing significant bacterial growth were tested for the presence of antibody coated bacteria (ACB). One serum sample per patient was collected for the estimation of C-reactive protein. E. coli was the commonest bacterial isolate (45.8%) from the clinical samples followed by Ps. aeruginosa (20.3%) and K. pneumoniae (18.6%). Thirty two culture positive samples belonging to 27 patients, were found to be antibody coated. Of all the isolates, K. pneumoniae was antibody coated in higher proportion (63.7%) followed by Ps. aeruginosa (58.3%) and E. coli (55.6%). Immunoglobulin G was found in all the ACB positive samples, where as 87.5% of them were also coated with IgA class of antibodies. All patients with ACB in urine had raised serum CRP levels except one, where as all the rest of the patients had CRP level within normal limit. The presence of pus cells in urine and radiological abnormalities in the urinary tract were significantly higher in ACB positive patients than in ACB negative patients.
Urine leakage from the umbilicus was observed while expressing urine by the Crede manoeuvre in a three-year-old tetraplegic girl with a chronically distended urinary bladder. Intravenous urography (IVU) revealed bilateral hydroureteronephrosis with markedly distended urinary bladder. Regular three hourly intermittent catheterization was advised, and the parents and carers of this child agreed to perform catheterization. There was cessation of urine leak within 48 hours of urethral drainage. Cystography performed two weeks later showed no vesicoureteric reflux; vesicoumbilical fistula was no longer demonstrable. Follow-up IVU, performed after eight and half months of regular intermittent catheterization, showed regression of hydroureteronephrosis. We believe that urine leakage from the umbilicus served two important protective functions in this child, viz. (1) it prevented possible vesical or renal rupture; (2) the striking clinical symptom of urine leak from the umbilicus focussed the attention of the carers to the underlying serious condition of the urinary tract. Further, this case demonstrates that regression of marked hydroureteronephrosis can be achieved by intermittent catheterization performed at regular intervals by devoted parents/carers, in selected cases of spinal cord injury with neuropathic bladder, and vesical outlet obstruction, thus obviating the need for any form of temporary or permanent urinary diversion.
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Spinal cord injury (SCI) patients are at high risk of developing cystitis, and vesical neoplasia. As abnormal growth regulation of urothelium may be a predisposing factor for cystitis and vesical neoplasia, we studied alterations if any, in the expression and localization of epidermal growth factor receptor (EGRF) in the vesical urothelium by an immuno-histochemical technique, using monoclonal mouse anti-human epidermal growth factor receptor antibody (DAKO-EGFRI) in cold-cup biopsies taken from the trigone of the urinary bladder in 18 adult SCI patients who had a neuropathic bladder. Abnormal localisation of EGFR-p, i.e. cytoplasmic, was noted in 13 patients. A linear localization of EGFR-p along the cell membrane of the urothelium, considered as an essential requirement for effective function, was observed in only three cases. Combined cytoplasmic and cell membrane location of EGFR-p was seen in two patients. The three patients with cell membrane location of EGFR-p showed a strong expression of EGFR-p (2+, 2-3+, and 4+, respectively); the intensity of EGFR-p expression in cases of cytoplasmic immunostaining varied considerably. Histopathology revealed denuding cystitis in one; follicular cystitis in four; active inflammatory infiltrate in three; lymphocytic infiltrate in three; squamous metaplasia in six; and intestinal metaplasia in three biopsy specimens. The three specimens showing cell membrane location of EGFR-p were from patients who did not have an indwelling urethral catheter (a paraplegic man practising intermittent self-catheterisation, a tetraplegic patient on penile condom drainage, and a tetraplegic woman with reflex voiding), and histopathology revealed very little inflammatory infiltrate. In contrast, the biopsies from all the nine patients, who were on indwelling urethral catheter drainage and in whom the bladder biopsy revealed varying degree of cystitis, showed only cytoplasmic location of EGFR-p. Similarly, the biopsies from patients with bladder stone (n = 6) showed only cytoplasmic localisation of EGFR-p. In conclusion, abnormalities in vesical urothelial expression in EGFR in SCI patients may play a role in the pathogenesis of cystitis, vesical urothelial metaplasia, dysplasia and neoplasia.
Spinal cord injury (SCI) patients with a neuropathic bladder are more prone to develop catheter-induced urethral trauma than occurs in the general population because many of the SCI patients are on indwelling urethral catheter drainage, or intermittent urethral catheterisation is performed either by them or by their carers. The presenting symptoms of improperly positioned Foley catheter in SCI patients may be at times, peculiar to the SCI patients and these include profuse sweating, bypassing of the catheter, increased spasms, or rarely, full fledged features of autonomic dysreflexia. With the availability of the flexible cystoscope, cystourethroscopy has been performed safely on SCI patients who had sustained catheter-induced urethral trauma, on the bedside, with an immediate, and accurate diagnosis of the extent of urethral trauma, and the presence of urethral false passage(s). Further, flexible cystoscopy has helped to treat the patients with urethral trauma by introducing a flexible tip guide wire under vision into the urinary bladder via the normal urethral channel and subsequently, passing a 12 Fr. Foley catheter over the guide wire, thus avoiding the false passage(s) in the urethra. With this technique, it was possible to avert the need for suprapubic urinary diversion in those SCI patients who had sustained acute urethral trauma. Such endoscopic management of acute urethral trauma in SCI patients is described with illustrative case reports of eight patients seen during a 15 month period.
Two patients with long-standing tetraplegia after spinal cord injury developed reflex penile erection in the operation theatre. One had not received any anaesthesia, and penile erection occurred after introduction of the cystoscope into the urethra, and also autonomic dysreflexia. Intravenous salbutamol, in a dose of 10 micrograms, produced immediate and persistent penile detumescence and salbutamol-induced fall in blood pressure was of therapeutic value. In the second patient, penile erection occurred during general anaesthesia prior to cystoscopy. Immediate and persistent penile detumescence was achieved with intravenous salbutamol 20 micrograms. There was transient fall of blood pressure which responded to intravenous infusion of 0.9% sodium chloride. Salbutamol-induced fall in blood pressure is of therapeutic value in those spinal cord injury patients who develop, in addition to penile erection, autonomic dysreflexia precipitated by urethral instrumentation, or bladder distension with the irrigating fluid. Intravenous salbutamol is preferable to intra-cavernosal phenylephrine, noradrenaline, metaraminol, and epinephrine, or intravenous ephedrine which are contraindicated in patients with hypertension.
Three unusual complications of intermittent self-catheterisation in spinal cord injury patients observed over a period of 30 months are described. (1) Two patients performing intermittent catheterisation with a PVC catheter requiring the use of lignocaine gel to numb the urethra, developed allergic reaction in the form of swelling and erythematous lesions around the external urethral meatus. This rare complication was overcome by switching over to the use of a Lofric catheter instead of a PVC catheter for intermittent catheterisation. (2) Urethral bleeding was observed on three occasions in male paraplegic patients performing intermittent self-catheterisation who had allowed the bladder to become over-distended. Bladder emptying therefore, took nearly 10 min, by which time the Lofric catheter became too sticky in the urethra and required undue force for withdrawal, resulting in trauma to the adherent urethral mucosa and urethral bleeding. By adopting the policy of catheterisation at regular intervals and not allowing the bladder to become distended beyond 450 ml of urine, this complication was never seen again either in these three patients or in any other patient using Lofric catheter for intermittent urethral catheterisation. (3) Failure to drain urine after urethral catheterisation resulting in a panic reaction was observed in a 45 year old woman practising intermittent catheterisation. This unique complication happened because there were no eye holes on the Nelaton catheter.