Chronic lymphocytic leukaemia, synchronous small cell carcinoma and squamous neoplasia of the urinary bladder in a paraplegic man following long-term phenoxybenzamine therapy.

STUDY DESIGN: A case report. OBJECTIVE: To raise awareness among spinal cord clinicians of the possible carcinogenic effect of phenoxybenzamine and of the rare occurrence of small cell carcinoma in the neuropathic bladder. SETTING: Regional Spinal Injuries Centre and District General Hospital, Southport, Merseyside, United Kingdom. CASE REPORT: A 28-year-old man sustained a fracture dislocation of L-1 with consequent paraplegia (ASIA impairment scale A). Phenoxybenzamine treatment enabled his indwelling catheter to be discarded in favour of a penile sheath, but it caused unacceptable dizziness and was stopped after 7 years. After 20 years, he developed chronic lymphocytic leukaemia, which was treated with chlorambucil and fludarabine. After 2 years, investigation of bilateral hydronephrosis revealed a primary small cell carcinoma of the bladder with coexistent squamous dysplasia. Uraemia supervened and, declining active treatment, the patient died 3 weeks after diagnosis. CONCLUSION: Phenoxybenzamine, a known carcinogen in rodents, is likely also to be carcinogenic in humans, and patients with spinal cord injury who have received the drug for any significant period of time, need close follow-up to allow early detection of cancer. Phenoxybenzamine should not be prescribed on a long-term basis, and should instead be replaced with a selective alpha-blocker.

Delayed complications of discontinuation of intrathecal baclofen therapy: resurgence of dyssynergic voiding, which triggered off autonomic dysreflexia and hydronephrosis.

STUDY DESIGN: Case report. OBJECTIVES: To report insidious development of autonomic dysreflexia and hydronephrosis due to dyssynergic voiding following discontinuation of intrathecal baclofen therapy. SETTING: Regional Spinal Injuries Centre, Southport, UK. METHODS: A male patient with paraplegia at T-5 (ASIA-A) had implantation of Medtronic Synchromed 8615 s programmable pump to control intractable spasms. After 4 years, the baclofen pump needed replacement because of battery exhaustion. At this time, he was taking oxybutynin 2.5 mg twice a day. He wore a penile sheath and performed intermittent catheterisation three times a day. Intravenous urography showed no dilatation of pelvicalyceal systems or ureters. During the course of the next 4 months, the dose of baclofen had to be increased gradually to 820 microg/day in order to control the spasms. Investigations revealed disconnection of the tube from the pump. The patient decided to undergo explantation of the pump and discontinue intrathecal baclofen therapy altogether. Following removal of the pump, he was prescribed baclofen 20 mg four times a day and diazepam 5 mg twice a day. He continued penile sheath drainage with oxybutynin 2.5 mg twice a day. Although spasms were controlled with oral baclofen and diazepam, he started getting transient, mild headache during reflex voiding. After nearly 2 years, he developed unbearable and pounding headache while passing urine. RESULTS: The dose of oxybutynin was increased to modified release formulation, 20 mg, once daily. He was prescribed modified release alfuzosin 10 mg once a day. Indwelling urethral catheter drainage was instituted. Intravenous urography showed dilation of left renal pelvis and calyces, and left ureter. After a fortnight, the dose of modified release oxybutynin was increased further to 25 mg once a day. After a month, he started performing self-catheterisation every 3 h and symptoms of autonomic dysreflexia subsided completely. A follow-up intravenous urography performed 6 months later, showed normal appearances of the left kidney. CONCLUSION: Spinal cord injury patients, in whom intrathecal baclofen therapy is terminated, need close monitoring of their urological status. Medications, which are prescribed for neuropathic bladder, and the method of bladder drainage, may need suitable changes, as discontinuation of intrathecal baclofen therapy can result in reappearance of detrusor-sphincter dyssynergia in previously susceptible patients.

Pseudo-tumours of the urinary tract in patients with spinal cord injury/spina bifida.

OBJECTIVE: To raise awareness of pseudo-tumours of urinary tract, as pseudo-tumours represent benign mass lesions simulating malignant neoplasms. Accurate diagnosis helps to avoid unnecessary surgery in spinal cord injury patients. SETTING: Regional Spinal Injuries Centre, Southport, UK CASE REPORTS: Pseudo-tumour of kidney: A 58-year-old man with tetraplegia developed a right perirenal haematoma while taking warfarin; ultrasound and CT scanning showed no evidence of tumour in the right kidney. The haematoma was drained percutaneously. After 8 months, during investigation of a urine infection, ultrasound and CT scan revealed a space-occupying lesion in the mid-pole of the right kidney. CT-guided biopsy showed features suggestive of an organising haematoma; the lesion decreased in size over the next 13 months, thus supporting the diagnosis. Pseudo-tumour of urinary bladder: A frail, 34-year-old woman, who had spina bifida, marked spinal curvature and pelvic tilt, had been managing her neuropathic bladder with pads. She had recurrent vesical calculi and renal calculi. CT scan was performed, as CT would be the better means of evaluating the urinary tract in this patient with severe spinal deformity. CT scan showed a filling defect in the base of the bladder, and ultrasound revealed a sessile space-occupying lesion arising from the left bladder wall posteriorly. Flexible and, later, rigid cystoscopy and biopsy demonstrated necrotic slough and debris but no tumour. Ultrasound scan after 2 weeks showed a similar lesion, but ultrasound-guided biopsy was normal with nothing to explain the ultrasound appearances. A follow-up ultrasound scan about 7 weeks later again showed an echogenic mass, but the echogenic mass was seen to move from the left to the right side of the bladder on turning the patient, always maintaining a dependent position. The echogenic bladder mass thus represented a collection of debris, which had accumulated as a result of chronic retention of urine and physical immobility. CONCLUSION: Recognising the true, non-neoplastic nature of these lesions enabled us to avoid unnecessary surgical procedures in these patients, who were at high risk of surgical complications because of severely compromised cardiac and respiratory function.

Flawed trial of micturition in cervical spinal cord injury patients: guidelines for trial of voiding in men with tetraplegia.

STUDY DESIGN: A retrospective study. OBJECTIVES: (1) To raise awareness of flawed trial of micturition (TOM) in male spinal cord injury (SCI) patients; and (2) to present guidelines for trial of voiding in male SCI patients. SETTING: Regional Spinal Injuries Centre, Southport, UK. METHODS: Trial of micturition in male SCI patients refers to discarding indwelling catheters and establishing them on balanced voiding with penile sheath drainage. We describe seven SCI patients, whose trial of micturition was flawed. RESULTS: Two patients (C-6 and C-4 tetraplegia respectively) developed severe autonomic dysreflexia (headache, sweating, and increase in blood pressure) 2-3 h after removal of urethral catheter. A C-4 tetraplegic developed severe urinary infection after TOM. Four patients with tetraplegia started retaining increasing amounts of urine and developed urinary infections/autonomic dysreflexia/hydronephrosis 1-21 months after they were established on sheath drainage after TOM. CONCLUSION: During TOM, patients with cervical SCI could develop autonomic dysreflexia, urinary infection, or hold progressively increasing volumes of residual urine. TOM should be guided by videourodynamics. SCI patients need alpha-blockers, and anticholinergics if voiding pressures are >40-50 cm H(2)O. If high urethral resistances are found, sphincterotomy and/or bladder neck incision will help the patients to void by triggering. SCI patients, who had undergone successful TOM, require meticulous follow-up including urodynamics. Intermittent catheterisation without adequate medications based on cystometrogram may be hazardous, and may result in upper tract damage. Facilities for supplementary catheterisation (three to four times a day) should be available in the community if a patient is unable to maintain complete, low-pressure, emptying of bladder.

Detection of early squamous metaplasia in bladder biopsies of spinal cord injury patients by immunostaining for cytokeratin 14.

STUDY DESIGN: A prospective, immunohistochemical study of bladder biopsies taken from spinal cord injury (SCI) patients. OBJECTIVES: To investigate whether cytokeratin 14 immunostaining may be useful to detect early squamous metaplasia in bladder biopsies from patients with SCI. SETTING: Southport, United Kingdom. METHODS: Biopsy of bladder mucosa was taken from adults with SCI, while they underwent an elective therapeutic procedure in the urinary tract. A total of, 54 biopsies, which showed transitional epithelium only with no evidence of squamous metaplasia on routine H&E staining, formed the study group. In all, 22 biopsies, which showed squamous metaplasia on routine H&E staining, acted as controls. All biopsies were benign with no evidence of dysplasia or malignancy. Immunohistochemical staining for cytokeratin 14 was performed on all biopsies in a single batch, using a standard avidin-biotin complex method. RESULTS: All control biopsies showed positive immunostaining for cytokeratin 14 in basal and parabasal cells in areas of squamous metaplasia. Of the 54 biopsies, which showed only transitional epithelium on H&E staining, immunohistochemistry for cytokeratin 14 showed no staining in 47 biopsies. The remaining seven biopsies showed positive immunostaining for cytokeratin 14 in the epithelium, in individual cells or clusters of basal cells, revealing unexpected early squamous metaplasia in these biopsies. CONCLUSION: Immunostaining for cytokeratin 14 identifies an early phenotypic switch from transitional to squamous epithelium in bladder mucosa. Cytokeratin 14 staining is sufficiently sensitive to identify early squamous metaplasia, which is not yet evident on examination of routine H&E stained sections. This early identification may be of use in alerting physicians to change bladder management regimens to prevent predisposition to recurrent urinary infection and progression of squamous metaplasia. A cost/benefit analysis should be performed to assess the feasibility of routine cytokeratin 14 immunostaining of bladder biopsies from SCI patients.

Protocol of a prospective cohort study of the effect of different methods of drainage of neuropathic bladder on occurrence of symptomatic urinary infection, and adverse events related to the urinary drainage system in spinal cord injury patients.

BACKGROUND: To present a protocol of a prospective, cohort study in which four groups of spinal cord injury (SCI) patients will participate. (Patients with indwelling urethral catheter; patients who perform intermittent catheterisation without wearing a penile sheath; patients who perform intermittent catheterisation and wear penile sheath as well; and patients with penile sheath drainage). OBJECTIVES: (1) What is the incidence of symptomatic urinary infection in men with spinal cord injury who use different types of bladder drainage? (2) Which are predisposing factors for the occurrence of symptomatic urinary infection in men with spinal cord injury who practise different methods of bladder drainage? (3) What is the incidence of catheter and urinary drainage system-related adverse events in the four groups of SCI patients? PATIENTS: The criteria for inclusion are as follow: (1) Male patients with neuropathic bladder due to spinal cord injury, who are registered with the Regional Spinal Injuries Centre, Southport, England. (2) Age: 18 years or above. (3) Patients who are willing to give informed consent for participation in the study. (4) Patients willing to be contacted every two weeks by a staff of the spinal unit for 36 months. (5) Patients who are willing to maintain an accurate record of adverse events related to urinary catheter and urinary drainage system and predisposing factors for the occurrence of symptomatic urinary infection. (6) Patients, who are stabilised in a particular method of bladder drainage, and therefore, unlikely to make a permanent change in the method of bladder drainage (e.g. from penile sheath drainage to the use of long-term indwelling catheter) during a foreseeable future. METHODS: The participants will be observed for a period of 36 months. A staff of the spinal injuries unit will contact the participants by telephone every two weeks on a mutually agreed day and time. The information obtained during this standardised telephonic interview conducted once in two weeks will be entered in a database. When a participant develops symptom(s) suggestive of urinary infection, he will undergo urine and blood tests, and imaging studies of the urinary tract. CONCLUSION: This study will provide information regarding the occurrence of symptomatic urinary infection, predisposing factors for development of urinary infection, and adverse events related to urinary catheter and urinary drainage system in SCI patients using different methods of bladder drainage.

Community-care waiting list for persons with spinal cord injury.

OBJECTIVES: To disseminate the concept of community care waiting lists for spinal cord injury (SCI) patients with particular reference to carer support for management of neuropathic bladder by a regime of intermittent catheterisation. METHODOLOGY: The surgical waiting list focuses only on operative procedures, and ignores the wider requirements for ensuring satisfactory rehabilitation of people with spinal cord injury in the community. A community-care waiting list for individuals with spinal cord injury should include the following aspects of community care: (1) Home adaptation; (2) Provision of appropriate mobility needs (including wheelchair and cushion); (3) Equipment for comfortable living (including provision of hoist, pressure relieving mattress); (4) Psychological support for spinal cord injury patients and their partners; (5) Nursing home or residential care placement where appropriate; (6) Carer support for global management of complex needs associated with spinal cord injury (eg neuropathic bladder and bowel). RESULTS: Whereas full physical adaptation of the home can wait for some time after discharge, carer support for intermittent catheterisation is required from the first day after discharge from a spinal unit. Lack of such support means that some SCI patients are discharged with long-term indwelling urinary catheters, even though clean intermittent catheterisation is known to be the safest regime for managing the neuropathic bladder. Therefore, the absence of a community care waiting list means that best practice cannot be achieved for some tetraplegic subjects. CONCLUSION: We believe that a community care waiting list for bladder management will help to provide optimum care for neuropathic bladder and, hopefully, reduce the complications related to long-term indwelling catheters in spinal cord injury patients.

Expression of matrix metalloprotease and tissue inhibitor of metalloprotease genes in human anterior cruciate ligament.

Women are more susceptible to anterior cruciate ligament (ACL) injuries than men performing similar athletic activities. Because tissue remodeling may affect ligament strength, we assessed expression of tissue remodeling effector genes in the human ACL. Specifically, we surveyed ACL for RNAs encoding all known matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) by reverse transcription/polymerase chain reaction (RT-PCR). These experiments revealed that mRNAs encoding nine of sixteen MMPs and all four TIMPs are present in the normal ACL. The nine expressed proteases were MMPs 1-3, 7, 9, 11, 14, and 17 (collagenase 1, gelatinase A, stromelysin 1, matrilysin, gelatinase B, stromelysin 3, and membrane types 1 and 4, respectively), and MMP-18. Genes for MMPs 8, 10, 12, 13, 15, and 16 appeared not to be expressed in ACL, as their mRNAs were not detected using RT-PCR conditions that did yield positive signals from other tissues (testis or bone). We conclude that numerous genes encoding tissue remodeling effector proteins are expressedin the human ACL.

Unpredicted spontaneous extrusion of a renal calculus in an adult male with spina bifida and paraplegia: report of a misdiagnosis. Measures to be taken to reduce urological errors in spinal cord injury patients.

BACKGROUND: A delay in diagnosis or a misdiagnosis may occur in patients with spinal cord injury (SCI) or spinal bifida as typical symptoms of a clinical condition may be absent because of their neurological impairment. CASE PRESENTATION: A 29-year old male, who was born with spina bifida and hydrocephalus, became unwell and developed a swelling and large red mark in his left loin eighteen months ago. Pyonephrosis or perinephric abscess was suspected. X-ray of the abdomen showed left-sided staghorn calculus. Since ultrasound scan showed no features of pyonephrosis or perinephric abscess, he was prescribed a prolonged course of antibiotics for infection presumed to arise from the site of metal implant in spine. He developed a discharging sinus, following which the loin swelling and red mark subsided. About three months ago, he again developed a red mark and minimal swelling in the left loin. Ultrasound scan detected no abnormality in the renal or perinephric region. Therefore, the red mark and swelling were attributed to pressure from the backrest of his chair. Five weeks later, the swelling in the left loin burst open and a large stone was extruded spontaneously. An X-ray of the abdomen showed that he had extruded the central portion of the staghorn calculus from left kidney. With hindsight, the extruded renal calculus could be seen lying in the subcutaneous tissue of left loin lateral to the 10th rib in the X-ray of abdomen, which was taken when he presented with red mark and minimal swelling. CONCLUSION: This case illustrates how mistakes in diagnosis could occur in spinal cord injury patients, and highlights the need for corrective measures to reduce urological errors in these patients. Voluntary reporting of urological errors is recommended to facilitate learning from our mistakes. In the patients who have marked spinal curvature, ultrasonography of kidneys and perinephric region may not be entirely reliable. As clinical symptoms and signs may be non-specific in SCI patients, they require prompt, detailed and occasionally, repeated investigations. A joint team approach by health professionals belonging to various medical disciplines, which is strengthened by frequent, informal and honest discussions of a patient's clinical condition, is likely to reduce urological errors in SCI patients.

Parathyroid hormone-related protein (1-34) and urothelial redifferentiation in the neuropathic urinary bladder.

STUDY DESIGN: A comparative study of immunostaining for parathyroid hormone-related protein (1-34) (PTHrP (1-34)) in the vesical epithelium of biopsies obtained from patients with non-neuropathic bladder and those with neuropathic bladder. OBJECTIVES: To investigate the immunostaining for PTHrP (1-34) in the control cases and in neuropathic bladders showing (1) normal transitional epithelium, (2) hyperplastic transitional epithelium, and (3) squamous metaplasia. SETTING: Regional Spinal Injuries Centre, and Department of Cellular Pathology, Southport & Ormskirk Hospitals NHS Trust, Southport, Department of Pathology, Royal Liverpool University Hospital and the Departments of Clinical Chemistry and Cell Biology, The University of Liverpool, Liverpool, England. METHODS: Cold cup biopsies of bladder mucosa were taken from patients suffering from neuropathic urinary bladder when they were undergoing a therapeutic procedure in the urinary tract. Immunohistochemistry was performed on these biopsy specimens using a rabbit polyclonal antibody raised to a synthetic peptide corresponding to human PTHrP (1-34). Control group (n=10) consisted of archival biopsies taken from non-neuropathic bladders. RESULTS: In the control group, the transitional epithelium showed no immunostaining, or at the most, very faint positive staining was seen in the transitional epithelium of non-neuropathic bladder. Positive immunostaining to PTHrP (1-34) was seen in the normal transitional epithelium of neuropathic bladder in nine of 13 cases. Hyperplastic transitional epithelium showed positive immunostaining for PTHrP (1-34) in 11 of 13 biopsies from patients with neuropathic bladder. Immunostaining for PTHrP (1-34) was observed in the metaplastic squamous epithelium in 14 of 17 cases with neuropathic bladder. CONCLUSION: The transitional epithelium of non-neuropathic bladder showed no immunostaining, or at the most, very faint positive staining for PTHrP (1-34). In contrast to this, positive immunostaining for PTHrP (1-34) was observed more frequently in the vesical epithelium of neuropathic bladder. This observation opens up avenues for innovative therapy with PTHrP or its analogues for possible modulation of urothelial differentiation in the neuropathic bladder.

Fatal intestinal perforation secondary to fragmentation of a Celestin tube.

BACKGROUND/AIMS: Oesophageal intubation remains one of the principal methods of palliation for an obstructing oesophageal carcinoma. We present a case which illustrates a rare but fatal complication of this procedure. METHODS: A 60-year-old female with oesophageal cancer presented with total dysphagia 9 months following insertion of a Celestin tube for palliation. Oesophagoscopy revealed a bolus obstruction which was successfully cleared. Two days later she developed generalised peritonitis and subsequently died. RESULTS: A post-mortem examination demonstrated fragmentation and displacement of the distal part of the Celestin tube resulting in perforation of the small bowel. CONCLUSION: Celestin tube disintegration is a risk associated with long-term use, and routine replacement is indicated in patients with a prolonged survival to avoid this complication.

Gastrointestinal autonomic nerve sarcoma presenting as a giant intra-abdominal cyst.

Gastrointestinal autonomic nerve sarcomas are rare tumours. A 36-year-old man presented with abdominal pain, distension and constipation. Abdominal ultrasound and CT scanning demonstrated a giant cystic intra-abdominal mass. Laparotomy confirmed a large cystic mass arising from the ileum with multiple metastases. Immunohistochemical staining was positive for vimentin, neuronal-specific enolase and PGP9.5. This is the first reported case to present as a giant intra-abdominal cyst. Specialist histopathological and immunohistochemical analysis is essential to establish the diagnosis of this rare tumour.

Xanthogranulomatous funiculitis and epididymo-orchitis in a tetraplegic patient.

STUDY DESIGN: A case report of xanthogranulomatous funiculitis and epididymo-orchitis. Xanthogranulomatous inflammation is an uncommon, non-neoplastic process characterised by destruction of tissue, which is replaced by a striking cellular infiltrate of lipid-laden macrophages. CASE REPORT: A 21-year male sustained complete tetraplegia at C-6 level, after a fall in 1998. The neuropathic bladder was managed with an indwelling urethral catheter. He had many unsuccessful trials of micturition. Sixteen months after the cervical injury, he noticed swelling of the left side of the scrotum following removal of a blocked catheter. He was prescribed antibacterial therapy. Four weeks later, physical examination revealed a hard and irregular swelling encompassing the testis, epididymis and spermatic cord. The clinical diagnosis was epididymo-orchitis progressing to pyocele. Through a scrotal incision, the swollen testis, epididymis and diseased segment of the spermatic cord were removed en masse. Histopathology showed extensive areas of necrosis, with xanthogranulomatous inflammation in the spermatic cord and to a lesser extent in the testis/epididymis. CONCLUSION: Repeated episodes of high-pressure urinary reflux along the vas deferens during dyssynergic voiding, and subsequent interstitial extravasation of urine together with chronic, low-grade, suppurative infection possibly led to development of xanthogranulomatous inflammation in the testis and the epididymis. Since tissue destruction is a feature of xanthogranulomatous inflammation, the definite and curative treatment is either complete (or, where applicable, partial) excision of the affected organ in most of the cases.

Immunohistochemical study of parathyroid hormone-related protein in vesical transitional epithelium of patients with spinal cord injury.

INTRODUCTION: Parathyroid hormone-related protein (PTHrP), in addition to the well-established role in endochrondral bone development, is believed to be an important mediator of cellular growth and differentiation in a number of non-bony tissues. OBJECTIVES: To compare the immunohistochemical staining of vesical transitional epithelium to antibodies raised to synthetic peptides of PTHrP composed of amino acid sequences 43 - 52 and 127 - 138 in patients with spinal cord injury (SCI) and neuropathic bladder (n=14), and control patients with intact neuraxis and no history of bladder cancer (n=10). SETTING: Male SCI patients registered with Regional Spinal Injuries Centre, Southport, England. INTERVENTION: Endoscopic cold cup biopsy from the trigone of the urinary bladder was taken from patients with SCI while they were undergoing a therapeutic procedure in the urinary bladder. The control samples of bladder biopsies were taken from the archives of the Department of Histopathology, District General Hospital, Southport. Immunohistochemistry was performed using rabbit antibodies raised against synthetic peptides of human PTHrP (43 - 52) and PTHrP (127 - 138). The biopsies were examined for immunostaining of transitional epithelium. RESULTS: Of the 14 biopsies of SCI patients, positive immunostaining using antibodies to both the PTHrP peptides was found in four cases; five biopsies showed positive immunostaining only to anti-PTHrP (43 - 52); and five biopsies showed no immunostaining with either of the PTHrP peptides. In contrast, transitional epithelium in the biopsy specimens of ten control subjects with no history of bladder cancer showed no immunostaining with either of the PTHrP peptides. CONCLUSION: This study revealed that the transitional epithelium of neuropathic urinary bladder exhibits increased predilection for positive immunohistochemical staining for PTHrP (43 - 52), and to a lesser extent, to PTHrP (127 - 138), as compared to the vesical transitional epithelium of able bodied individuals with no history of vesical malignancy. The possible role of PTHrP in the cellular differentiation of urothelium of neuropathic bladder, and thereby, in the pathogenesis of cystitis in SCI patients, needs to be explored.

Conversion efficacy and safety of repeated doses of ibutilide in patients with atrial flutter and atrial fibrillation. Study Investigators.

BACKGROUND: A study was conducted to determine the efficacy and safety of ibutilide fumarate versus placebo in the acute termination of atrial flutter and fibrillation. METHODS AND RESULTS: Two hundred sixty-two patients aged 28 to 88 years with atrial flutter or fibrillation duration of 3 hours to 90 days were randomly assigned in a 5:1 ratio (ibutilide:placebo) to receive two 10-minute infusions, 10 minutes apart, of ibutilide (1 mg) or placebo. Patients were hospitalized and monitored by telemetry for 24 hours, with follow-up 72 hours later. Seventy-three (34.9%) of 209 evaluable ibutilide recipients had termination of atrial flutter or fibrillation within 1.5 hours compared with 0 (0%) of 41 placebo recipients. Those with atrial flutter had a higher success rate. At hour 24, 86.3% remained in normal or alternative sinus rhythm. Of the patients who received ibutilide, 2.3% experienced drug-related sustained polymorphic or monomorphic ventricular tachycardia and recovered after intervention. Additionally, 7.3% experienced nonsustained polymorphic or monomorphic ventricular tachycardia. Other frequent medical events in ibutilide recipients were generally also noted in the placebo group. CONCLUSIONS: Ibutilide is effective and safe for acute termination of atrial fibrillation or atrial flutter.

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.