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PubMed1995

Culture of bladder epithelium from cystoscopic biopsies of patients with interstitial cystitis.

Interstitial cystitis is a chronic disease of unknown etiology characterized by bladder pain and urinary frequency and urgency. The epithelium may be critical in its pathogenesis; the hallmarks of the disease are visible epithelial defects (Hunner's ulcers and epithelial ruptures). Areas denuded of epithelium are commonly seen, and defects in epithelial permeability are characteristic. We report here the culture and characterization of epithelial cells from cystoscopic bladder biopsies obtained from 7 female patients with interstitial cystitis. Within 4 to 14 days cellular outgrowths appeared from explants incubated in cell medium. Monolayers reached confluence after 6 weeks. Cells of the monolayer were cytokeratin-positive and smooth muscle actin-negative, confirming their epithelial origin. They exhibited epithelial cell ultrastructure including intermediate filaments and junctional complexes. Vesicles bounded by a trilaminar plasma membrane and lateral interdigitations were also present. This is the first report of the culture of bladder epithelium from interstitial cystitis patients. Epithelial cells may be targets for initiating agents and inflammatory effects of interstitial cystitis and should be useful for studies of the pathogenesis of this disease.

Adult↗
PubMed1997

Improvement in interstitial cystitis symptom scores during treatment with oral L-arginine.

PURPOSE: Urinary nitric oxide synthase activity is decreased in patients with interstitial cystitis. Since nitric oxide may be an important determinant of the symptoms and immunological responses associated with interstitial cystitis, patients with this disease were treated with oral L-arginine, the substrate for nitric oxide synthase. MATERIALS AND METHODS: Ten patients took 1.5 gm. L-arginine orally daily for 6 months. Interstitial cystitis symptoms were surveyed before and during the 6-month trial. RESULTS: Oral L-arginine treatment resulted in a significant decrease in urinary voiding discomfort, lower abdominal pain and vaginal/urethral pain. Urinary frequency during the day and night also significantly decreased. CONCLUSIONS: This self-controlled study provides evidence that long-term oral L-arginine improves interstitial cystitis related symptoms.

Adult↗
PubMed1997

Inflammatory cell types and clinical features of interstitial cystitis.

PURPOSE: We tested whether the types of inflammatory cells seen on bladder biopsies were associated with other clinical features and urinary markers of interstitial cystitis. MATERIALS AND METHODS: Bladder biopsies from 30 interstitial cystitis patients were evaluated by immunohistochemical staining for T cells, B cells, macrophages and human leukocyte antigen-DR positive cells. These findings were tested for associations with clinical features and urinary markers of interstitial cystitis using alpha = 0.01 because multiple tests were performed. RESULTS: Overall severity of inflammation was significantly associated with age at symptom onset, symptom relief after bladder distention and urinary interleukin-6 levels. Patients with severe inflammation had trends toward smaller bladder capacity under anesthesia, increased bladder vascularity and mucosal cracks, lower urinary MUC-1 glycoprotein levels and absence of bloating as a symptom. B cell staining was significantly associated with severe inflammation, symptom relief after distention and absence of bloating as a symptom. T cell staining was significantly associated with severe inflammation and age at symptom onset. Human leukocyte antigen-DR staining had trends with symptoms, including presence of bloating, constant urge to void and absence of burning. Macrophage staining did not associate with any features tested at the alpha = 0.05 level. CONCLUSIONS: Interstitial cystitis patients with severe inflammation have different age, treatment response and urinary marker levels than those with mild inflammation. These findings suggest that the 2 patient groups have different underlying pathophysiologies. The significant associations for T and B cell staining were similar to those for overall inflammation.

B-Lymphocytes↗
PubMed1987

Noncomparative, open label, multicenter trial of cefixime for treatment of bacterial pharyngitis, cystitis and pneumonia in pediatric patients.

Cefixime, a new third generation oral cephalosporin antibiotic, was evaluated for safety and efficacy in the treatment of 206 children with acute bacterial pharyngitis, cystitis or pneumonia. Each patient had a throat, urine or sputum culture before therapy and was treated with a 10- to 14-day course of cefixime, 8 mg/kg once daily. Bacterial pathogens were isolated in 167 of 206 (81.1%). Streptococcus pyogenes (73.7% of isolates) and Escherichia coli (9.6%) were the most common Gram-positive and Gram-negative organisms, respectively. All patients were evaluable for safety, and 109 (52.9%) with pharyngitis (96) or cystitis (13) were evaluable for efficacy. Clinical failure occurred in 2 of 109 (1.8%) patients, both with pharyngitis; bacteriologic failure occurred in 1 patient with pharyngitis and 1 with cystitis. Five patients with pneumonia caused by possible pathogens also improved while taking cefixime. Drug-related adverse side effects occurred in 50 of 206 patients (24.3%); these were generally mild and led to discontinuing the antibiotic in only 4 patients (1.9%). The most common were diarrhea or loose stools (33 of 206, or 16%). Results of this study suggest that cefixime given once daily to children is safe and effective in the treatment of streptococcal pharyngitis and bacterial cystitis.

Adolescent↗
PubMed1999

Interstitial cystitis.

Interstitial cystitis is a complex inflammatory condition of the bladder. The pathophysiology of interstitial cystitis is incompletely understood, although altered epithelial permeability, mast cell activation and sensory afferent nerve upregulation play critical roles. A unified understanding of the pathogenesis of interstitial cystitis is emerging and this will hopefully lead to the introduction of novel therapies for pain and irritative voiding symptoms. Interstitial cystitis is a common disease among women and is frequently misdiagnosed as prostatitis and benign prostatic hyperplasia among men.

Animals↗
PubMed2002

Interstitial cystitis: an update.

PURPOSE OF REVIEW: Interstitial cystitis is a chronically progressive, severely debilitating, heterogeneous syndrome affecting the urinary bladder, mainly associated with urgency, frequency and pain. Though known for over a century, its etiology is poorly understood and universally effective treatments are lacking. This review focuses on recently published literature on the disorder. RECENT FINDINGS: Appropriate diagnostic tests for interstitial cystitis remain uncertain. The diagnostic criteria developed by the US National Institutes of Health represent research definitions which are subject to controversial debate for their overenthusiastic clinical application. The diagnosis is made clinically and by cystoscopy with hydrodistention and sometimes biopsy when other pathologies have been excluded. In symptomatic patients, glomerulations upon bladder distension are indicative but not pathognomonic for nonulcerative interstitial cystitis. Patients with ulcerative disease represent a separate subgroup with distinct characteristics and treatment implications. The role of bladder permeability tests remains controversial. Promising noninvasive markers for interstitial cystitis have been described but are not yet clinically available. Validated symptom scores are appropriate to assist in diagnostics and to monitor disease course and treatment efficacy. Lately investigated hypotheses for causative factors include occult or resistant microorganisms, urothelial hyperpermeability, neurogenic or hormonal pathomechanisms, and mast cell activation. Increasing evidence for a genetic susceptibility is emerging. SUMMARY: Among the multitude of oral, intravesical, interventional and complementary treatments suggested few studies have high levels of evidence. Newly proposed agents must await further controlled studies. Treatment remains empiric until radical surgical procedures should ultimately be considered for severe refractory cases.

Animals↗
PubMed2003

Involvement of nitric oxide and hyperbaric oxygen in the pathogenesis of cyclophosphamide induced hemorrhagic cystitis in rats.

PURPOSE: We evaluated the relationship between nitric oxide and hyperbaric oxygenation in the pathogenesis and treatment of cyclophosphamide induced hemorrhagic cystitis in rats. MATERIALS AND METHODS: Cyclophosphamide (100 mg/kg) was injected in male Sprague-Dawley rats for cystitis induction. Animals were treated before and the day after cyclophosphamide injection with 100 mg/kg of the nitric oxide substrate L-arginine, 20 mg/kg of the nonselective nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester and 20 mg/kg of the selective inducible nitric oxide synthase inhibitor S-methylisothiourea. Animals were exposed to hyperbaric oxygen (2.8 atmospheres absolute for 90 minutes twice daily) with or without the administration of L-arginine and nitric oxide synthase inhibitors. RESULTS: Cyclophosphamide injection resulted in severe cystitis. S-methylisothiourea produced marked inhibition of cyclophosphamide induced bladder tissue damage. L-arginine and L-NG-nitroarginine methyl ester failed to a show meaningful protective effect. Hyperbaric oxygen protected the bladder only against ulceration. Moreover, hyperbaric oxygen did not contribute to the protective effects of L-arginine, L-NG-nitroarginine methyl ester or S-methylisothiourea. CONCLUSIONS: Nitric oxide produced by inducible nitric oxide synthase is an important mediator in the pathogenesis of cyclophosphamide induced cystitis. Hyperbaric oxygen has a beneficial effect on repairing bladder damage rather than on bladder protection.

Animals↗
PubMed2004

The historical origins of interstitial cystitis.

PURPOSE: We identify early descriptions of interstitial cystitis and trace its evolution as a clinical entity during the 19th century. MATERIALS AND METHODS: Primary and secondary source documents relating to interstitial cystitis, bladder inflammation and bladder stones were reviewed. RESULTS: What is believed to be the earliest published record of interstitial cystitis appeared in an 1836 textbook by the Philadelphia surgeon Joseph Parrish, who documented a syndrome of chronic frequency, urgency, dysuria and pelvic pain he called "tic doloureux of the bladder." Tic doloureux was a contemporaneous diagnosis used to describe painful, idiopathic disorders of nerves. Parrish attributed this term to his mentor, Dr. Phillip Syng Physick, who applied it to patients with severe lower urinary tract symptoms with no discernible etiology, with the most common etiology during the 19th century being bladder stones. A review of archival material from the Philadelphia College of Physicians indicates that by 1808 Physick had developed a concept of bladder inflammation, a "bladder ulcer," that produced lower urinary tract symptoms in the absence of bladder stone. CONCLUSIONS: By 1808 Philip Syng Physick had described an inflammatory condition of the bladder producing the same lower urinary tract symptoms as a bladder stone. By 1836 he had expanded this concept to include a chronic frequency, urgency and pain syndrome occurring in the absence of demonstrable etiology. We propose that these are the earliest known descriptions of bladder inflammation and interstitial cystitis.

Cystitis, Interstitial↗
PubMed2005

Clinical manifestations and functional outcomes in children with eosinophilic cystitis.

PURPOSE: Eosinophilic cystitis is a rare disorder, with fewer than 30 pediatric cases reported in the literature. We describe our experience with pediatric eosinophilic cystitis during a 20-year period. MATERIALS AND METHODS: Four children referred to our institution were subsequently diagnosed with eosinophilic cystitis between 1984 and 2004. A retrospective chart review was performed to assess clinical presentation, diagnosis, treatment and outcomes. RESULTS: Mean patient age at presentation was 10.8 years (range 5 to 18) and male-to-female ratio was 3:1. All 4 patients presented with irritative urinary symptoms, including 3 with dysuria and/or gross hematuria and 2 with urinary frequency, lower abdominal pain and/or a concomitant urinary tract infection. Allergic diseases (asthma, allergic rhinitis, etc) were present in 3 patients, and a formal allergen skin test was positive in 2 of those tested. A bladder mass mimicking malignancy was documented in 2 patients. Three patients had symptom resolution with conservative treatment, while 1 had development of an unremitting tumefactive process that eventually required partial cystectomy and bladder augmentation. CONCLUSIONS: Eosinophilic cystitis is a rare condition with a wide range of clinical manifestations. Children can present with a bladder mass mimicking sarcoma, underscoring the need for biopsy before diagnosis and treatment of a presumed oncological process. The condition usually follows a benign course, although unremitting progression remains a possibility.

Adolescent↗
PubMed2005

Cyclosporine A and pentosan polysulfate sodium for the treatment of interstitial cystitis: a randomized comparative study.

PURPOSE: In a previous retrospective analysis, cyclosporine A (CyA) was highly efficient in treating patients with interstitial cystitis. A prospective randomized study with this immunosuppressive agent was warranted. We compared CyA to pentosan polysulfate sodium (PPS) in patients with interstitial cystitis. MATERIALS AND METHODS: A total of 64 patients with interstitial cystitis meeting the National Institute of Diabetes and Digestive and Kidney Diseases criteria were enrolled in a randomized prospective study. Patients were randomized in a 1:1 ratio to 1.5 mg/kg CyA twice daily (27 women, 5 men) or 100 mg PPS 3 times daily (26 women, 6 men) for a period of 6 months. The primary end point was daily micturition frequency, and secondary end points were mean and maximal voided volume, number of nocturia episodes, O'Leary-Sant symptom and problem indexes, visual analogue scale for pain, and subjective global response assessment. RESULTS: CyA was superior to PPS in all clinical outcome parameters measured at 6 months. Micturition frequency in 24 hours was significantly reduced in the CyA arm compared to the PPS arm (-6.7 +/- 4.7 vs -2.0 +/- 5.1 times). The clinical response rate (according to global response assessment) was 75% for CyA compared to 19% for PPS (p <0.001). Although there were more adverse events in the CyA arm than in the PPS arm, 29 patients completed the 6-month followup in both groups. CONCLUSIONS: CyA is more effective than PPS in interstitial cystitis.

Adult↗
PubMed2006

Recent developments of intravesical therapy of painful bladder syndrome/interstitial cystitis: a review.

PURPOSE OF REVIEW: Painful bladder syndrome/interstitial cystitis is a chronic sterile inflammatory disease of the bladder of unknown cause. It is characterized by bladder pain, urinary frequency, urgency, and nocturia. Although there are plenty of theories, the cause of the condition remains obscure. An abundance of treatments has been suggested, but very few have been subjected to proper controlled trials. This review focuses on the recently published literature on intravesical therapy strategies in painful bladder syndrome/interstitial cystitis. RECENT FINDINGS: Bladder irrigation with different agents has been used during years in an attempt to treat painful bladder syndrome/interstitial cystitis. The background for this is the existing theories about urothelial dysfunction. The 'traditional' agent for glycosaminoglycan substitution is hyaluronic acid. Often used are heparin and dimethyl sulfoxide, the actions of which are not quite clear but supposedly on an anti-inflammatory basis. Other agents for intravesical treatment are Bacillus Calmette-Guerin vaccine and botulinum toxin, and some recent studies have pointed to resiniferatoxin and RDP58. SUMMARY: Painful bladder syndrome/interstitial cystitis persists as a challenging syndrome in urology. Intravesical instillation therapy has basically not changed during the last few years, although some studies have disconfirmed some regimens. Intensive research may hopefully result in more effective treatments in the future.

Administration, Intravesical↗
PubMed1995

Distribution of virulence factors in Escherichia coli isolated from urine of cystitis patients.

The distribution of 7 urovirulence factors, such as type 1 pilus (pil), pilus associated with pyelonephritis (pap), S fimbriae (sfa), afimbrial adhesin I (afaI), hemolysin (hly), aerobactin (aer) and cytotoxic necrotizing factor 1 (cnf1) was examined by a DNA colony hybridization test among 194 Escherichia coli strains isolated from the urine of cystitis patients and in 80 strains isolated from the stool specimens of healthy adults. All virulence factors examined, except pil, were significantly more frequently detected among the cystitis isolates than among the fecal isolates. When individual virulence factors were analyzed against the others, an association was discernible which was not apparent when all 7 virulence factors were considered collectively. There was an apparent correlation between the genotypes and serotypes of the E. coli strains from the cystitis patients. From the data presented, it was proposed that genetic detection of virulence factors would be useful for rapid diagnosis of cystitis, especially in patients without severe pyuria or bacteriuria.

Acute Disease↗
PubMed1993

Search for mycobacteria in interstitial cystitis using mycobacteria-specific DNA probes with signal amplification by polymerase chain reaction.

The aetiology of interstitial cystitis is not known. Various infective agents have been postulated and although recognised as perpetrators of chronic inflammatory conditions, mycobacteria have never been satisfactorily excluded from interstitial cystitis. If present in interstitial cystitis tissue, mycobacteria exist either in very small numbers or in forms which contemporary staining techniques fail to recognise. We used a polymerase chain reaction with mycobacteria-specific DNA probes and found no evidence of mycobacterial involvement in 8 cases of proven interstitial cystitis.

Cystitis↗
PubMed2005

The potassium sensitivity test: a predictor of treatment response in interstitial cystitis.

OBJECTIVE: To determine whether the potassium sensitivity test (PST) can be used to predict the response to treatment with intravesical sodium hyaluronate in patients with interstitial cystitis. PATIENTS AND METHODS: Thirty-eight patients diagnosed with interstitial cystitis were recruited; each had a PST, carried out in a double-blind fashion, followed by six weekly doses of intravesical sodium hyaluronate. The patients were assessed before and after treatment using a self-administered interstitial cystitis symptom index (CSI) and problem index (PI). The clinical response was defined as none (<25% improvement in clinical symptoms), mild (>25%), moderate (50-75%) and excellent (>75%). RESULTS: The PST was positive in 23 and negative or indeterminate in 13 patients; two patients withdrew from the study. Overall 20 of 36 (55%) patients reported an improvement after six doses of intravesical sodium hyaluronate, but 17 (74%) with a positive PST improved, compared to only five (22%) with a negative test (P = 0.03). There was an improvement in the CSI after treatment in both groups, but a significant improvement in the PI only in patients with a positive PST (P = 0.01). The magnitude of change for the CSI and PI was significantly greater in the positive than in the negative group (CSI, P = 0.043; PI, P < 0.001). There were no major complications. Three patients complained of pain after the test, and two with a positive and one with a negative PST developed a urinary tract infection. CONCLUSIONS: Although the role of the PST in the diagnosis of interstitial cystitis requires further clarification, the test helps to predict the response to treatment with glycosaminoglycan-substitution therapy.

Adjuvants, Immunologic↗
PubMed2006

L6-S1 spinal nerve stimulation reduces micturition frequency in anaesthetized rats with cyclophosphamide-induced cystitis.

OBJECTIVE: To further investigate the rationale for using spinal nerve stimulation (SNS) for treating bladder overactivity associated with cystitis in a rat model of cyclophosphamide-induced cystitis, as several studies suggested that symptoms associated with chronic cystitis could be treated using stimulation of sacral spinal nerves, but the mechanisms by which it works are unknown. MATERIALS AND METHODS: Cystitis was induced by i.p. injection of cyclophosphamide 48 h before the experiments in anaesthetized male rats. Neurograms were taken by placing a recording electrode onto the pelvic nerve and a stimulating electrode on either the L6 or S1 ipsilateral spinal nerves. Two selected intensities were then evaluated for SNS in control and cyclophosphamide-treated rats during cystometry. RESULTS: Cyclophosphamide resulted in significant bladder overactivity. There was no apparent difference in the neurograms generated in response to SNS of the S1 and L6 spinal nerves, and between cyclophosphamide and control rats. Intensities of 200 microA (Adelta-fibre-specific) and 2 mA (Adelta+ C-fibres) were chosen for SNS. Continuous SNS at 200 microA significantly reduced the frequency of voiding and non-voiding contractions in cyclophosphamide-treated rats. SNS at 2 mA resulted in the abolition of voiding contractions, accompanied by continuous leakage of urine. CONCLUSION: SNS recruiting only Adelta-fibre produced fewer voiding contractions in cyclophosphamide-treated rats, to a level similar to that from the control rats. These results support the ability of SNS to decrease bladder overactivity in a pathophysiological model of chemical irritation of the bladder.

Animals↗
PubMed2006

Oral treatment with a vitamin D3 analogue (BXL628) has anti-inflammatory effects in rodent model of interstitial cystitis.

OBJECTIVE: To investigate the effects of a vitamin D3 analogue (BXL628) in a model of chronic cystitis, as calcitriol analogues might be an interesting new therapeutic option for interstitial cystitis, for although the cause of the disease remains unclear, the increase in mast cells in the mucosa and detrusor muscle are significant. MATERIALS AND METHODS: We devised a mouse model of allergen-induced allergic cystitis that is associated with the up-regulation of genes for interleukin-13, FcepsilonRIalpha and mast cells-derived proteases, a massive inflammatory reaction in the bladder tissue, and augmented levels of mast cell-derived protease 1 (MMCP1) detected in mouse sera. RESULTS: Oral administration of BXL628 significantly reduced the expression of interleukin-13, FcepsilonRIalpha and MMCP1 in the bladder. Furthermore, histological analysis showed a decrease in oedema and leukocyte infiltration in the bladder wall. BXL628 treatment reduced serum MMCP1 levels, indicating an effect on mast cell degranulation in vivo. CONCLUSIONS: Vitamin D3 analogues may successfully be used as anti-inflammatory agents in allergen-mediated inflammatory reactions. Moreover, the modulatory effect shown on mast cell activation by the BXL628 analogue strongly supports its potential therapeutic use in a possibly mast cell-dependent disease such as human interstitial cystitis.

Animals↗
PubMed2006

A new minimally invasive technique for treating radiation cystitis: the argon-beam coagulator.

OBJECTIVE: To assess the effectiveness of the argon-beam coagulator used endoscopically for treating radiation cystitis, as radiotherapy is commonly used for treating pelvic tumours of urological origin, but intractable bleeding related to radiation cystitis remains a serious complication and requires a difficult long-term follow-up, for which cystoscopic methods of management have traditionally had limited success. PATIENTS AND METHODS: We assessed seven patients with radiation cystitis; they were treated with argon-beam coagulation after a cystoscopic evaluation. RESULTS: With a mean follow-up of 15 months, one treatment was used in six patients, with a second treatment required in one. CONCLUSION: The argon-beam coagulator appears to be a safe, well tolerated and minimally invasive treatment in patients with radiation cystitis.

Argon↗
PubMed1989

[Effect of insulin on the incidence of experimental Serratia marcescens cystitis in diabetic mice--relationship between insulin therapy and urea nitrogen content].

The effect of insulin on the incidence of experimental Serratia marcescens cystitis in alloxan-induced diabetic mice was studied. The symptoms in diabetes were improved by injection of insulin (1 I.U./b.i.d.) for 3 days. Diabetic mice treated with insulin showed lower susceptibility to cystitis with S. marcescens than non-treated diabetic mice, but slightly higher than normal mice. It was, therefore, suggested that the insulin treatment was important for prevention of S. marcescens cystitis. The prevention of cystitis in insulin-treated diabetic mice was possibly due to the increase of urea nitrogen that inhibits the growth of S. marcescens in urine.

Animals↗