K R Krishnan

Urethral cytology in spinal cord injury patients performing intermittent catheterisation

Local reactions of the urethral wall are known to occur by repeated introduction of a catheter in the urethra. Urethritis was found in 2-19% of patients practising intermittent catheterisation. Although the use of catheters of smaller size and the liberal use of lubricants may prevent urethral irritation and trauma, it was postulated that hydrophilic catheters (LoFric, Astra Tech Ltd, Stroud, England) induce significantly less trauma than PVC catheters because of the binding of the water molecules to the catheter surface which consists of polyvinylpyrrolidone and sodium chloride. Although urethritis and urethral stricture may represent one end of the spectrum of repeated urethral trauma, minor degrees of inflammation need to be quantitatively determined while assessing two different catheters for intermittent catheterisation. The degree of urethral inflammation in patients practising intermittent catheterisation was studied by urethral cytology and staining the smear by Papanicolaous method. The number of neutrophil polymorphs and epithelial cells in three random high power fields in the urethral smear was counted and the percentage ratio of polymorphs to epithelial cells was calculated. Group 1 comprised 14 patients practising intermittent catheterisation with a PVC catheter and group 2 comprised 17 patients performing intermittent catheterisation with a LoFric catheter. There was no significant difference between the two groups as regards the age, diagnosis, size of the catheter used for intermittent catheterisation and the number of times that they performed catheterisation during a 24 hour period. Urethral cytology revealed a percentage (mean ratio) ratio of polymorphs to epithelial cells of 66 in group 1 and 0.04 in group 2. (< 0.0005). Urethral cytology also revealed a significantly greater number of bacteria in group 1 as compared to group 2 (p <0.01). In conclusion, use of a LoFric catheter for intermittent catheterisation was associated with significantly lesser degree of urethral inflammatory response when compared to the use of a PVC catheter.

Use of Memokath, a second generation urethral stent for relief of urinary retention in male spinal cord injured patients

Memokath (Engineers & Doctors A/S, Hornbaek, Denmark) a second generation urethral stent composed of titanium nickel alloy with shape memory effect was deployed in 10 male spinal cord injured patients with urinary retention. The stent was inserted under sterile conditions via a delivery catheter under fluoroscopic control in seven and with the aid of a flexible cystoscope in three. The proximal end of the stent was positioned at the bladder neck and 50 ml of normal saline at 45 °C was flushed through the stent which resulted in expansion of the distal most four coils of the stent in the proximal bulbar urethra; thus the internal sphincter (bladder neck) and external sphincter zone were kept open by the stent. Urethral stenting helped to achieve complete vesical emptying in all 10 patients. The complications included transient autonomic dysreflexia in two, transient urinary retention due to blood clot in one, and acute urinary tract infection in one patient. With a follow up of 3-7 months, all 10 patients have been aysmptomatic, with residual urine of less than 50 ml. There has been no migration or blocking of the stent. However, these stents require replacement at 12-18 months, but it is a short procedure as the Memokath, when cooled with saline at 4°C, becomes supersoft, enabling its easy and nontraumatic removal. As these stents produce no permanent effect upon the lower urinary tract and their removal is quick, safe and atraumatic, we prefer the second generation nickel titanium alloy stent to transurethral resection of bladder neck, external urethral sphincterotomy or permanent indwelling epithelialising stent, particularly in young spinal cord injured patients who wish to retain their fertility potential.

Effect of intermittent urethral catheterization and oxybutynin bladder instillation on urinary continence status and quality of life in a selected group of spinal cord injury patients with neuropathic bladder dysfunction

Objectives: A comparative assessment of (i) urinary continence status, (ii) quality of life, and (iii) sexuality in spinal cord injury patients prior to, and during intermittent catheterization with adjunctive intravesical oxybutynin therapy (Cystin: manufactured by Leiras Oy, Helsinki, Finland).Setting: A hospital, and community-based study of selected adult, male, spinal cord injury patients registered with the Regional Spinal Injuries Centre, Southport.Patients: Seven patients (mean age: 44.3 years) suffering from neuropathic bladder due to suprasacral spinal cord lesion of traumatic aetiology, and well settled in the community in the north-west of England were the subjects of this study. Before commencing the intermittent catheterization regime, these patients were on penile sheath drainage.Intervention: Intermittent urethral catheterization was performed with sterile, single-use Nelaton catheters 5–6 times a day with intravesical instillation of oxybutynin 5 mg in 30 ml, 1–3 times a day for periods ranging from 14 to 30 months.Outcome measures: Assessment of urinary continence, sexuality, and quality of life was made (i) at the outset before any intervention, (ii) during intermittent catheterization regime, and (iii) when the patients were using the oxybutynin bladder instillation along with intermittent catheterization.Results: Initially all the seven patients were constantly wearing penile sheaths and leg bags. When these patients performed intermittent catheterization 5–6 times in 24 h, they attempted to discard the penile sheath during the day but they were experiencing mild to moderate urine leak between catheterization. They were compelled to wear penile sheaths during night. Subsequently, five patients took oxybutynin by mouth, but developed an unacceptable degree of side-effects necessitating discontinuation of the medication. Following commencement of intravesical oxybutynin therapy, all of them were able to discard the penile sheaths and leg bags during the day as well as during the night. However, on waking-up after a full nights sleep, three patients found dampness of their undergarments 1–2 times per week. None of the patients experienced side-effects attributable either to the intermittent catheterization procedure, or to the intravesical oxybutynin therapy. The number of episodes of urinary infection requiring antibiotic therapy was 0.08/patient/month. All the seven patients noticed a remarkable improvement in the quality of life because they had achieved a high degree of continence. All the seven patients commented on the improved sense of their own sexuality which was attributed to (i) absence of incontinence episodes, (ii) improved self-image, and (iii) not wearing penile sheaths and leg bags.Conclusion: These seven spinal cord injury patients achieved socially acceptable continence with improved quality of life, and enhanced sexuality with the intermittent urethral catheterization regime and intravesical oxybutynin therapy.

p75 nerve growth factor receptor in the vesical urothelium of patients with neuropathic bladder: an immunohistochemical study.

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.

A review of the readmissions of patients with tetraplegia to the Regional Spinal Injuries Centre, Southport, United Kingdom, between January 1994 and December 1995

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.

A retrospective study of hyponatremia in tetraplegic/paraplegic patients with a review of the literature

The aetiology of hyponatremia in tetraplegic patients is multifactorial and includes not only general factors such as the use of diuretics and the intravenous infusion of hypotonic fluids, but also certain mechanisms which operate in the spinal cord injured: decreased renal water excretion due to both intrarenal and arginine vasopressin dependent mechanisms (resetting of the osmostat), coupled with habitually increased fluid intake, and the ingestion of a low salt diet. Between 1984 and 1993 we treated 28 episodes of hyponatremia in 19 patients (males: 10; females: 9). Fourteen were tetraplegic and five paraplegic (thoracic lesion in four and lumbar lesion in one). Six patients were asymptomatic during seven episodes of hyponatremia which were detected during routine blood tests. Seven patients were suffering from an acute chest infection, three had an acute urinary tract infection, one had an infected ischial pressure sore and a 69 year old paraplegic patient had bronchopneumonia as well as sepsis from a gangrenous pressure sore in the supraanal region. The time interval between the onset of paralysis and occurrence of the first episode of hypnoatremia was less than a month in only four of the patients. The lowest plasma sodium level observed was less than 100mmol/l in two, between 100 and 110mmol/l in four, between 111 and 120mmol/l in eight patients, and between 121 and 128mmol/l in 14 cases. Six patients also had hypokalemia (K+ < 3 mmol/l). Only one patient had an elevated plasma creatinine (201umol/l). Treatment of sepsis and fluid restriction were the mainstay of treatment with only two patients receiving hypertonic saline. All patients with underlying sepsis were treated with antibiotics, usually administered intravenously. The outcome was good in 26 of the 28 episodes.Two patients died: a 68 year old tetraplegic patient with consolidation of the left lung, cystadenocarcinoma of both ovaries and squamous cell carcinoma of the forehead who presented with generalised oedema, with a plasma sodium level of 118 mmol/l, and potassium of 2.4 mmol/l and who was treated with 2N saline + postassium + frusemide; she died 1 day later. The only other death was that of a 78 year old female tetraplegic patient who 2 days after sustaining cervical trauma developed hyponatremia because of intravenous infusion of hypotonic fluids given at another hospital, presumably to correct hypotension. She recovered from hyponatremia with fluid restriction, but 3 days later she succumbed to bronchopneumonia and respiratory insufficiency. No patient developed central pontine myelinolysis. No patient with a severe degree of hyponatremia (sodium < 100 mmol/l) had respiratory involvement requiring ventilatory assistance. In conclusion, hyponatremia is seen in tetraplegic patients often in association with sepsis either in the lungs or in the urinary tract, and is best managed by treament of the predisposing factor(s) along with fluid restriction.

The artificial ventilation of acute spinal cord damaged patients: a retrospective study of forty-four patients

The case histories of the 44 ventilated spinal cord damaged patients who have been treated at the Mersey Regional Spinal Injuries Centre prior to 1985 were reviewed.Complications of ventilation were commoner in patients whose ventilation was initiated prior to transfer to the specialised centre. Inappropriate early management before or during transfer to the spinal injuries centre led to the need for ventilation in several cases.Spinal cord damaged patients should be transferred to a specialised comprehensive centre as soon as possible after injury so that the requirement for ventilation can be minimised, the incidence of cardiac and respiratory arrest reduced, optimal methods of ventilation and weaning employed and global emotional and educational support provided from the outset for the patient and his family.

Nerve fibres in urothelium and submucosa of neuropathic urinary bladder: an immunohistochemical study with S-100 and neurofilament.

Intravesical administration of drugs has been used commonly in spinal cord injury patients to suppress detrusor hyperreflexia (eg oxybutynin, verapamil, terodiline) or, to initiate a micturition reflex (eg 15S 15-methyl prostaglandin F2 alpha, protaglandin E2); however, the response has been variable and sometimes, unpredictable. This prompted us to study the presence of nerve fibres in the vesical urothelium and submucosa in mucosal biopsies taken from the dome and trigone (obtained prior to performing a therapeutic procedure eg, vesical lithotripsy, or a diagnostic cystoscopy) in 47 consecutive, unselected paraplegic/tetraplegic patients with a neuropathic urinary bladder. Nerve fibres were demonstrated by routine immunohistochemical technique using commercially available monoclonal and polyvalent antibodies against S-100 (DAKO A/S, Glostrup, Denmark) and Neurofilament (MILAB, Malmo, Sweden). Biopsy specimens were graded for the presence of nerve fibres on a 0-3 scale for urothelium, and superficial/deep submucosa separately in a blind and randomised manner. Virtually no fibre presence was found in one paraplegic patient and no superficial or single fibres were noted in a tétraplégie patient. Absence of C-fibre hyperplasia (Grade 0) was found in nine cases (paraplegic: 4; tétraplégie: 5); Grade 1 hyperplasia was observed in 17 cases (paraplegic: 4; tétraplégie: 13); Grade 2 hyperplasia was seen in 11 cases (paraplegic: 7; tétraplégie 4); and Grade 3 hyperplasia was noticed in eight cases (paraplegic 3: tétraplégie: 5). The magnitude of C-fibre hyperplasia was not significantly different between paraplegic and tétraplégie patients (x2= 4.64; P = 0.3262). The relationship, if any, between the degree of C-fibre hyperplasia and duration of paralysis was studied by categorising patients as < 5 years, and > 5 years of paralysis. No evidence of single fibre or fibre bundle hyperplasia (Grade 0) was seen in five and six cases, grade 1 hyperplasia in six and 11 cases, grade 2 hyperplasia in two and nine cases, and grade 3 hyperplasia in three and five cases respectively in these two categories of patients. (x2=1.92; P = 0.58). The possible relationship between C-fibre hyperplasia in the vesical mucosa/submucosa and (i) the vesical response to intravesical drug administration; (ii) the vesical urothelial proliferation arrest; (iii) the electrical stimulation of urinary bladder by implanted electrodes (sacral anterior root stimulator); and (iv) long-term indwelling urethral Foley catheter drainage, are discussed with illustrative case reports. In conclusion, mucosal biopsy and study of nerve fibres in urothelium and submucosa of neuropathic bladder has helped to generate hypotheses on the association between C-fibre hyperplasia and response to intravesical pharmacotherapy and the predictive value of such a study in identifying those patients who are likely to respond to intravesical pharmacotherapy.

Recurrent bilateral renal calculi in a tetraplegic patient.

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. Percutaenous 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 safetly 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.

Comparative pathology of dome and trigone of urinary bladder mucosa in paraplegics and tetraplegics

Paraplegic/tetraplegic individuals are prone to develop chronic urinary tract infection, urinary calculi and bladder outlet obstruction, and have a 16 to 28 times higher risk for squamous cell bladder cancer. The preferable method of monitoring those patients who are at high risk of developing vesical neoplasia has been an annual check-up inclusive of cystoscopy and cold cup bladder biopsy of all suspicious areas as well as predetermined random sites. It may be desirable to take a biopsy from one site (when there is no suspicious lesion) with a flexible cystoscope while the patient is sitting in the wheelchair itself in the outpatient clinic instead of multiple biopsies from the dome, trigone and both lateral walls of the urinary bladder taken in the operation theatre set-up using a rigid cystoscope with the patient positioned in lithotomy. Before adopting such a cost-saving and more convenient procedure routinely, we evaluated whether any significant additional histopathological findings are obtained by taking bladder biopsies from the dome and the trigone of the urinary bladder instead of just one, be it dome or trigone in the absence of any visible urothelial lesion in the bladder. In forty consecutive tetraplegic/paraplegic patients who did not have any cystoscopically distinguishable urothelial neoplastic lesion such as papilloma, cold cup biopsies of the dome and the trigone were taken randomly before carrying out any diagnostic or therapeutic procedure, eg electrohydraulic lithotripsy of vesical calculi. All the biopsy specimens were evaluated by a pathologist who was unaware of the clinical details and not involved with the primary diagnosis. In 15 cases, significant additional histopathological finding(s) were recorded in the trigone biopsy which were not seen in the dome biopsy (follicular cystitis: n = 4; squamous metaplasia: n = 4; extensive squamous metaplasia with focal atypia: n = 1; limited focal atypia: n = 1; extensive glandular metaplasia: n = 1; intestinal metaplasia and possibly follicular cystitis: n = 1; and follicular cystitis and intestinal metaplasia: n = 1; mild atypia: n = 1; extensive calcification of epithelial denudation: n = 1). Histopathology of dome biopsies revealed significant additional histopathological finding(s) in nine cases (follicular cystitis: n = 2; squamous metaplasia: n = 2; intestinal metaplasia: n = 1; squamous metaplasia and adenomatoid metaplasia and mild atypia: n = 1; features of interstitial cystitis: n = 1; mild dysplasia: n = 1; mild crypt hyperplasia of urothelium with mild atypia: n = 1). Thus in twenty cases (50%), significant additional findings were obtained by taking cold cup random biopsy of the dome as well as the trigone in the absence of any visible morphological changes. Although single site biopsy may be less traumatic, more convenient to the patient as well as to the staff, and cost-saving, in the spinal cord injury patients with neuropathic bladder, it may not be diagnostically adequate even in those patients who do not have any cystoscopically distinguishable lesion in the urinary bladder.