title: A light- and electron-microscopic histopathological study of human bladder mucosa after intravesical resiniferatoxin application.
abstract: OBJECTIVE
  To determine the morphology of bladder mucosa and the integrity of its mucin coat in patients with detrusor hyper-reflexia treated with intravesical resiniferatoxin.
  
  
  METHODS
  Seven patients with detrusor hyper-reflexia were treated intravesically with resiniferatoxin dissolved in 10% ethanol in saline (50 nmol/L solution in two and 100 nmol/L in five). Patients were clinically evaluated by a voiding chart and filling cystometry before and 3 months after each resiniferatoxin application. In addition, they underwent cystoscopy and bladder biopsies at 22-33 months after the first instillation and at 7-23 months after the last one. Tissue samples for light microscopy were fixed in 4% paraformaldehyde, embedded in paraffin and stained with haematoxylin-eosin or periodic acid-Schiff reagent (PAS). Those for electron microscopy were fixed in 5% glutaraldehyde and embedded in resin.
  
  
  RESULTS
  The resiniferatoxin instillation was not painful. Three months after treatment the mean voiding frequency decreased and five incontinent patients became continent. The maximum cystometric capacity increased in all patients; at cystoscopy the bladders appeared normal. On light microscopy the urothelium was of normal morphology and stained with PAS in the luminal cells and in the basement membrane. Mononuclear inflammatory cells were occasionally apparent in the lamina propria. On electron microscopy epithelial cells were visible in a thick basal lamina. Superficial cells had the usual irregular contour and contained numerous membrane-coated vesicles. In the lamina propria, unmyelinated axonal profiles with occasional varicosities could be identified.
  
  
  CONCLUSIONS
  Intravesical resiniferatoxin improved urinary frequency, incontinence and bladder capacity in patients with detrusor hyper-reflexia, causing no morphological change in the bladder mucosa. The PAS reactivity of the carbohydrate moieties present in the mucin coat and the basement membrane was unchanged by resiniferatoxin.
authors.affiliation: Department of Urology, Hospital São João, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Silva
authors.forename: A
authors.initials: A
authors.lastname: Avelino
authors.forename: C
authors.initials: C
authors.lastname: Souto-Moura
authors.forename: F
authors.initials: F
authors.lastname: Cruz
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D001706:Biopsy / Q000379:methods; D004224:Diterpenes / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008853:Microscopy / Q000379:methods; D008854:Microscopy, Electron; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology; D009103:Multiple Sclerosis / Q000150:complications; D009498:Neurotoxins / Q000008:administration & dosage*; D012021:Reflex, Abnormal / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology; D001745:Urinary Bladder Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
chemical_list: D004224:Diterpenes; D009498:Neurotoxins; C024353:resiniferatoxin