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PubMed2002

Manganese superoxide dismutase gene therapy protects against irradiation-induced cystitis.

Urinary bladder cystitis occurs in patients receiving radiation therapy for pelvic tumors. Radiation-induced formation of superoxide radicals is believed to damage the urothelium, exposing the underlying bladder smooth muscle to urine, culminating in nerve irritation and muscle dysfunction. We tested whether overexpression of MnSOD could decrease superoxide levels and protect the bladder from radiation damage. Pelvic irradiation led to sloughing of urothelial umbrella cells, with decreased transepithelial resistance, increased water and urea permeabilities, and increased expression of inducible nitric oxide synthase. Six months after irradiation, cystometrograms showed elevated intravesical pressures and prolonged voiding patterns. However, urothelia transfected with the MnSOD transgene recovered from radiation injury more rapidly, and detrusor function was much closer to that of control bladders than irradiated bladders without the transgene. We conclude that MnSOD gene therapy is protective, which could lead to its use in mitigating radiation cystitis and preventing dysfunction of the urinary bladder.

Animals↗
PubMed2002

LPS-sensory peptide communication in experimental cystitis.

Stimulation of sensory nerves can lead to release of peptides such as substance P (SP) and consequently to neurogenic inflammation. We studied the role of bacterial lipopolysaccharide (LPS) in regulating SP-induced inflammation. Experimental cystitis was induced in female mice by intravesical instillation of SP, LPS, or fluorescein-labeled LPS. Uptake of fluorescein-labeled LPS was determined by confocal analysis, and bladder inflammation was determined by morphological analysis. SP was infused into the bladders of some mice 24 h after exposure to LPS. In vitro studies determined the capacity of LPS and SP to induce histamine and cytokine release by the bladder. LPS was taken up by urothelial cells and distributed systemically. Twenty-four hours after instillation of LPS or SP, bladder inflammation was characterized by edema and leukocytic infiltration of the bladder wall. LPS pretreatment enhanced neutrophil infiltration induced by SP, increased in vitro release of histamine, tumor necrosis factor-alpha, and interferon-gamma, and significantly reduced transforming growth factor-beta1 release. These findings suggest that LPS amplifies neurogenic inflammation, thereby playing a role in the pathogenesis of neurogenic cystitis.

Administration, Intravesical↗
PubMed2000

Urothelial pathophysiological changes in feline interstitial cystitis: a human model.

Unique barrier properties of the urothelial surface membrane permit urine storage. Interstitial cystitis causes disabling dysuria, and frequency. Similarly, feline interstitial cystitis (FIC) occurs in cats. These studies define the permeability and structural properties of normal and FIC urothelium. To determine the effects of bladder filling, groups were studied before and after hydrodistention. Normal urothelium with or without hydrodistention exhibited high transepithelial resistances (TER) and low water and urea permeabilities, resembling other species. Fluorescence confocal microscopy revealed localization of the marker AE-31 to the apical surface of all umbrella cells in normal urothelium, with the tight junction protein ZO-1 localized to tight junctions. Scanning and transmission electron microscopy revealed uniform distribution of luminal cells with characteristic apical membrane and tight junction morphology. Urothelium in FIC animals displayed reduced TER and increased water and urea permeability following hydrodistention. Structural studies in FIC revealed denuded urothelium, with appearance of AE-31 in underlying epithelial cells. The results demonstrate severe epithelial damage and dysfunction in FIC and suggest novel approaches toward examining the etiology and therapy of IC.

Animals↗
PubMed2000

The role of Borrelia burgdorferi in interstitial cystitis.

BACKGROUND/AIMS: Borrelia burgdorferi spirochete has been found both in bladder biopsies and the urine of patients with Lyme disease (LD) as well as in experimental animals. The urological symptoms in borreliosis resemble those of interstitial cystitis (IC): frequency, urgency and nocturia. The aim of this studies is to find the role of B. burgdorferi in interstitial cystitis. METHODS: We studied antibodies against B. burgdorferi from serum samples of 50 IC patients with two separate EIA tests. Patients with positive serology in both tests underwent cystoscopy and a bladder biopsy was taken. The presence of borrelia DNA was studied with borrelia-specific polymerase chain reaction (PCR), and with universal bacterial PCR. RESULTS: IgM class antibodies to B. burgdorferi were not found, but IgG antibodies were found in four samples (8%). This was higher than in the control material (2%). One patient's sample was strongly positive, whereas three samples were weakly positive. Bladder biopsies taken from the 4 patients were negative for borrelia DNA in both PCR tests. None of the seropositive patients had any symptoms consistent with LD. CONCLUSION: These results indicate that persistent infection of B. burgdorferi has no role in the etiology of IC. On the other hand a connection with a past borrelia infection and IC is not excluded.

Adult↗
PubMed2001

Incidence of Helicobacter pylori in patients with interstitial cystitis.

OBJECTIVE: Chronic gastritis has compelling similarities to interstitial cystitis (IC). It is characterised by chronic pain in a tubular organ. Histologically, epithelial damage, inflammatory response in the lamina propria and epithelial ulcerations are seen. An infective cause was rarely considered until the emergence of Helicobacter pylori over the past 15 years. We have had experience of patients with bladder pain and irritability reporting improvement with antihistamines. It has also been reported that IC symptoms improved dramatically after treatment for H. pylori infection. Previous studies have determined the incidence of H. pylori antibodies in women with IC but we examined bladder material histologically and performed the Campylobacter-like organism (CLO) test on the biopsy specimens. MATERIALS AND METHODS: A prospective controlled study was performed. Patients with urinary symptoms fulfilling the National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC underwent GA cystoscopy at which the macroscopic appearance of the bladder was noted and biopsies were taken. The biopsy material underwent histological examination and CLO test. Control patients who were undergoing cystoscopy for reasons other than investigation of IC also had biopsy taken and the CLO test was performed on these specimens. RESULTS: Five of 15 patients with symptoms and signs of IC had a positive CLO test. Three of 15 patients of the control group had a positive CLO test. With the 2-sided chi(2) test there was no statistical difference between the 2 groups. CONCLUSION: Our small prospective control study does not support the hypothesis that H. pylori is an important component in the pathogenesis of interstitial cystitis.

Cystitis, Interstitial↗
PubMed2000

Sacral nerve stimulation for pain relief in interstitial cystitis.

A 60-year-old woman was treated for severe interstitial cystitis pain using sacral nerve stimulation. Pain and accompanying bladder dysfunction were improved by temporary and permanent sacral nerve stimulation. Six months after implantation of a sacral neuromodulator the patient is pain free and significantly improved on bladder dysfunction. Interstitial cystitis may be an indication for functional electrostimulation.

Cystitis, Interstitial↗
PubMed1999

Urological treatment and clinical course of BK polyomavirus-associated hemorrhagic cystitis in children after bone marrow transplantation.

Hemorrhagic cystitis (HC) is a major complication of bone marrow transplantation (BMT). We describe the clinical course and urological management of BK polyomavirus-associated HC in children after bone marrow transplantation. From 8/88 to 11/95, a total of 117 consecutive pediatric patients received BMT. Nine patients (7. 7%) developed HC after transplantation. HC in all 9 patients was characterized by late onset (day +24 to +50 post-BMT), long duration (1-7 weeks) and the excretion of BK polyomavirus in the urine as confirmed by electron microscopy, DNA hybridization and PCR techniques. Six children developed mild HC (grade 1-2) and were treated successfully by hyperhydration. In 3 patients, severe HC (grade 3-4) over 6 weeks required surgical interventions. In these 3 patients, cystoscopy revealed circumscript papulous tumors as the source of hematuria. Severe and persistent hematuria required blood transfusions, insertion of large suprapubic catheters and permanent bladder irrigation because of recurrent blood clot retention. Attempts to stop the hematuria in 2 of these patients by coagulation and laser vaporization (Nd:YAG) failed to stop the bleeding. Differential diagnosis of hematuria after BMT includes urinary tract infection, cyclophosphamide-induced chemical cystitis and bleeding due to BMT-induced thrombocytopenia. With the increasing number of BMTs in children, urologists may be confronted with BK polyomavirus-associated HC and must consider this in the differential diagnosis of hematuria after BMT.

Adolescent↗
PubMed2003

Eosinophilic cystitis. A rare inflammatory pathology mimicking bladder neoplasms.

PURPOSE: We present a large series of eosinophilic cystitis including 8 cases; 3 of them had tumor-like lesions. MATERIALS AND METHODS: The archives of pathology clinic of Inonu University Medical Faculty were reviewed from 1988 to 2002. The characteristics of patients and their diseases were recorded. Data obtained from 180 cases (172 from the literature and 8 from the present series) was assessed. RESULTS: Seven cases had symptoms such as dysuria, frequency, hematuria, suprapubic pain, and difficulty in voiding. One asymptomatic case with history of bladder carcinoma was diagnosed during routine cystoscopy. The findings were microhematuria in 6 cases, macrohematuria in 2, pyuria in 3, urinary infection in 1, eosinophilia in 1, hyperazotemia in 1, and bladder masses in 3. Cystoscopies detected edematous and erythematous areas in 5 cases and lesions mimicking bladder carcinoma in 3. One case did not take further treatment after cystoscopy and biopsy and completely recovered. Four cases underwent medical therapy with nonsteroidal anti-inflammatory drugs and antihistaminics. They became asymptomatic and control cystoscopies showed no abnormal finding. Two of three patients with mass lesions recovered after steroid therapy following transurethral resection. The lesion in the third recurred and he improved after a second course of steroid therapy. CONCLUSIONS: Eosinophilic cystitis is a rare pathology. Sometimes, it may simulate bladder malignancies. Biopsy is mandatory at diagnosis. Usually, it has a benign course and may be treated with fulguration, analgesics, antihistaminics and steroids, although recurrence is possible.

Adult↗
PubMed2005

Intravesical heparin and peripheral neuromodulation on interstitial cystitis.

INTRODUCTION: We wanted to evaluate the therapeutic effect of intravesical heparin and peripheral neuromodulation on patients with interstitial cystitis. MATERIALS AND METHODS: From March 2002 to August 2003, 8 female and 2 male subjects conform to the NIDDK criteria and not responsive to the previous conventional treatments were included in the study. Wisconsin pain scores, maximal cystometric capacities, and night and day voiding frequencies were determined and these studies were repeated in the 2nd and 12th months of the treatment with 10,000 units intravesical heparin and peripheral neuromodulation. Frequency of the treatment was once a week during first 8 weeks, once in 2 weeks in the following 8 weeks, and once in 3 weeks four times. Then, it was decreased to once a month. RESULTS: The mean follow-up period was 13 months (12-16 months). Day and night voiding frequency were significantly better in the 2nd and 12th months, when compared to pretreatment values. The Wisconsin pain scores were 62.5 +/- 13.9% and 62.8 +/- 15.2% in the 2nd and the 12th months, respectively. The average increase in the maximum cystometric capacity was 54.8 +/- 27.4% and 52.5 +/- 31.6% in the 2nd and the 12th months, respectively. CONCLUSIONS: Intravesical heparin and peripheral neuromodulation combination seems to be an alternative for patients with interstitial cystitis not responsive to other treatments.

Administration, Intravesical↗
PubMed1985

Permeability characteristics of the rat urinary bladder in experimental cystitis and after overdistension.

The permeability characteristics of the rat urinary bladder were investigated in experimental cystitis achieved by xylene/Escherichia coli, after dimethylsulfoxide (DMSO) exposure and 3 and/or 10 days after overdistension. The changes were found to be comparable between experimental cystitis and DMSO treatment, whereas those after overdistension were specifically different in nature. Passive increases in NaCl permeability were shown to be accompanied by functional, metabolic impairment of the urothelium. It has been suggested that the concept of an almost impermeable 'blood-urine barrier' is completely misleading under these circumstances. This should be taken into account in future clinical considerations.

Animals↗
PubMed1986

N-(3',4'-dimethoxycinnamoyl)anthranillic acid, an antiallergic compound, induced eosinophilic cystitis.

Eosinophilic cystitis developed in an asthmatic patient after therapy with the antiasthmatic agent, Tranilast. The progress of this patient and the histopathologic findings of bladder biopsy specimens are reported. A review of recent publications on the possible causative correlations is presented. It appears judicious to perform bladder biopsy if common chemotherapy fails to improve bladder irritability in patients receiving Tranilast therapy. If a diagnosis of eosinophilic cystitis induced by Tranilast is established, immediate withdrawal of the drug with or without steroid therapy is recommended.

Cystitis↗
PubMed1991

Colocystoplasty for the treatment of severe interstitial cystitis.

Twelve patients with end-stage interstitial cystitis and intractable symptoms resistant to conservative measures underwent supratrigonal cystectomy and colocystoplasty, comprising 7 right colocystoplasties and 5 open-loop sigmoidocystoplasties. Mean follow-up was 4.7 years. Ten patients had complete relief of pain and a decrease in frequency, while 2 patients required cystectomy and urinary diversion because of persistent symptoms or infection and incontinence. Bladder function was evaluated urodynamically in 11 patients. The bladder capacities in the right colocystoplasties were between 325 and 800 ml (mean 495), compared with 180 and 500 ml (mean 345) in the sigmoideocystoplasties. Two patients suffered from mild urge incontinence. All the patients retained their sensation of bladder fullness and voided without difficulty. In only 3 cases was a procedure needed to lower the bladder outflow tract resistance. Most patients did not need long-term antibiotics. No impairment in renal function was noted. In view of the good results achieved colocystoplasty can be recommended more often for the treatment of interstitial cystitis, detubularized right colocystoplasty being the operation of choice.

Adult↗
PubMed1995

Acute hemorrhagic cystitis caused by adenovirus after kidney transplantation.

We report on 10 kidney transplant patients with acute hemorrhagic cystitis caused by adenovirus, accompanied by the deterioration of kidney function. They developed macrohematuria with urgency, frequency and micturition pain for more than 7 days within 1 year after transplantation. Adenovirus type 11 was isolated from the urine of 6 patients, and complement-fixing antibody became positive in 9 patients. Hematuria and irritative voiding symptoms disappeared without any specific treatment; however, serum creatinine rapidly increased. The histological findings of the biopsy specimens indicated that renal impairment was attributed to acute rejection in some cases and virus-associated nephropathy in other cases. Acute hemorrhagic cystitis caused by adenovirus is an interesting complication after kidney transplantation, especially with regard to kidney impairment and treatment.

Adenoviridae Infections↗
PubMed1996

Acute hemorrhagic cystitis by adenovirus type 11 with and without type 37 after kidney transplantation.

We report 2 kidney transplant patients with acute hemorrhagic cystitis. Adenovirus type 11 was isolated in the urine of both patients and in 1 patient adenovirus type 37 was also isolated. Each developed macrohematuria with urgency, micturition pain, elevated fever and functional deterioration of the transplanted kidney possibly due to acute rejection. These symptoms and laboratory data suggesting renal impairment persisted for approximately 4 weeks after therapy for acute rejection had been started without any specific additional treatment for adenovirus. Serum creatinine levels returned to slightly higher values than before this episode. Histological findings of biopsy specimens from the transplanted kidney in 1 patient indicated that renal impairment was attributable to acute rejection. According to the clinical results of our cases, there were no remarkable differences between adenovirus type 11 infection with or without type 37 infection. Acute hemorrhagic cystitis caused by the adenovirus is an interesting complication after kidney transplantation, especially with regard to kidney impairment and treatment.

Acute Disease↗
PubMed1997

Results of treatment of refractory interstitial cystitis with intravesical hyaluronic acid.

Interstitial cystitis is a chronic benign disease of the bladder that causes bothersome and debilitating symptoms and mainly affects women. Since interstitial cystitis (IC) might result from a defective glycosaminoglycan layer of the bladder epithelium, we conducted a trial of hyaluronic acid (HA), used intravesically, to test its activity in the treatment of this disease. A total of 10 patients with typical findings of IC were included. Following bladder catheterisation, the patients received a dose of 40 mg, weekly for 6 weeks, and then monthly. Response to therapy was evaluated by comparing the pre-treatment and post-treatment symptom scores and voiding diaries. There was a 30% positive response rate at week 6, which was maintained until week 24. No significant local or general side-effects were noted during the course of treatment. Although we recorded a low incidence of success in our group of patients, the results of our limited study were satisfactory in the group of responsive patients (30%), who had no relapses during the observation period of 6 months. The intravesical administration of HA was well tolerated in all cases.

Administration, Intravesical↗
PubMed1984

A light and electron microscopic study of urothelium from patients with chronic cystitis.

Urothelial tissues from two groups of patients were examined by light and transmission electron microscopy. Group A (n = 7) had no evidence of clinical or morphological abnormality. Group B (n = 9) consisted of patients with recurrent bacterial and abacterial cystitis. 6 of the 9 patients in group B showed hyperplastic urothelium in their biopsy specimens. The superficial cells contained a significantly greater number of immature cells when compared to controls (p less than 0.001). As it has been shown that bacteria attach more easily to immature cells, it is possible that their persistent presence among the luminal cells of the bladder epithelium is a contributory factor to the recurrence of cystitis.

Chronic Disease↗
PubMed1976

Treatment of interstitial cystitis with immunosuppression and chloroquine derivatives.

Azathioprine, an immunosuppressive agent, was given to 38 patients presenting with intestinal cystitis. Pain disappeared completely in 22 patients and pollakiuria did the same in 20 patients, including two very severe cases with very contracted bladder. Chloroquine or oxychloroquine, usually combined with salicylate, was given to 22 patients. Pain disappeared in 11 patients and pollakiuria in 4 patients. No effect was noted in 10 patients in the azathioprine group and in 8 patients in the chloroquine group. The remaining patients had partial alleviation. The results are analyzed separately for various grades of severity. Spontaneous cure can be expected only in 11% of cases of interstitial cystitis calculated from a large series. Immunosuppression or chloroquine derivates are indicated for patients who do not respond to other treatments.

Autoimmune Diseases↗