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PubMed1998

Increased urinary hyaluronic acid and interstitial cystitis.

PURPOSE: We compared urinary levels of hyaluronic acid in patients who met the National Institute for Diabetes, and Digestive and Kidney Diseases criteria for interstitial cystitis and in age matched healthy female controls. MATERIALS AND METHODS: Urinary hyaluronic acid was measured by solid phase radiometric assay using hyaluronic acid binding protein. Hyaluronic acid and symptom scores were compared in interstitial cystitis patients who gave multiple urine samples during treatment. Since hyaluronic acid changed with treatment in some patients, 17 samples from untreated interstitial cystitis patients were selected and compared with 17 control samples. RESULTS: Mean plus or minus standard deviation urinary hyaluronic acid concentrations were similar in the 2 groups (interstitial cystitis group 574 +/- 496, controls 512 +/- 324 ng./ml., p = 0.77). When normalized to creatinine urinary hyaluronic acid was significantly higher in interstitial cystitis patients (interstitial cystitis group 674 +/- 220, controls 446 +/- 220 ng./mg. creatinine, p = 0.0019). Urinary creatinine concentrations did not differ significantly (interstitial cystitis group 842 +/- 715, controls 1,162 +/- 516 mg./l., p = 0.12). CONCLUSIONS: Urinary hyaluronic acid was higher in interstitial cystitis patients than healthy controls. Since bladder hyaluronic acid is below the epithelium, this finding may indicate leakage across the epithelium into the urine in interstitial cystitis patients.

Adult↗
PubMed1999

Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients.

PURPOSE: The 2 prominent features of interstitial cystitis are pain and increased numbers of mast cells in the bladder. In this pilot study we determined the concentration of soluble mediators associated with activation of sensory neurons and/or mast cells that were present in the urine. MATERIALS AND METHODS: The study groups included 4 interstitial cystitis patients, 7 kidney donors with no history of bladder disease as negative controls, 6 bladder cancer patients and 7 patients with urinary tract infection as reference controls. Urine samples were assayed for different soluble mediators using immunoassays for tryptase (a marker for mast cell activation), neurotrophic factors (markers of neuronal plasticity) and chemokines (markers of inflammatory cell activity). Results were normalized based on creatinine concentration. RESULTS: There was a marked increase in the average amounts of tryptase and 3 neurotrophic factors in patient urine. Interestingly, the mediator profile in the urine of bladder cancer patients was indistinguishable from that of interstitial cystitis patients with respect to these same 4 proteins. There was no difference between normal control and urinary tract infection urine samples. CONCLUSIONS: These findings may account for several clinical and pathological features found in interstitial cystitis and bladder cancer. Although preliminary due to the limited numbers of patients, they also suggest that increased levels of neurotrophin-3, nerve growth factor, glial cell line-derived neurotrophic factor and tryptase in the urine could serve as a basis for adjunct diagnosis, monitoring and treatment of interstitial cystitis.

Adult↗
PubMed1997

Interstitial cystitis: unexplained associations with other chronic disease and pain syndromes.

OBJECTIVE: To determine the prevalence of concomitant disease in individuals with interstitial cystitis and to compare these results to the general population. METHODS: We used a questionnaire-based study evaluating 12 disease processes and a survey of interstitial cystitis characteristics. The population was 2,405 individuals with interstitial cystitis who responded to the initial survey and an additional 277 individuals who were randomly selected and individually contacted. RESULTS: Allergies, irritable bowel syndrome, and sensitive skin were the most common diseases in the interstitial cystitis population. In comparison to the general population, individuals with interstitial cystitis are 100 times more likely to have inflammatory bowel disease and 30 times more likely to have systemic lupus erythematosus. In addition, allergies, irritable bowel syndrome, sensitive skin, and fibromyalgia have an increased association with interstitial cystitis. CONCLUSIONS: Interstitial cystitis has, as yet, an unexplained association with certain other chronic disease and pain syndromes.

Adult↗
PubMed2000

The association of elevated urinary total to sulfated glycosaminoglycan ratio and high molecular mass hyaluronic acid with interstitial cystitis.

PURPOSE: A decrease in the glycosaminoglycan (GAG) layer on the urothelium is believed to be one of the possible causes of interstitial cystitis. Consequently, GAG-like substances and hyaluronic acid (HA) have been prescribed for treating this condition. To delineate the possible role of GAG and HA in the interstitial cystitis disease process, we compared the urinary levels of total GAGs (sulfated + non-sulfated), sulfated GAGs and HA in interstitial cystitis patients and normal controls. We also examined different HA species present in the urine of interstitial cystitis patients. MATERIALS AND METHODS: The total GAG and sulfated GAG levels in urine specimens of normal individuals (n = 20) and interstitial cystitis patients (n = 25) were determined by utilizing the carbazole reaction assay and the Farndale method, respectively, and were expressed as microg./mg. creatinine. Urinary HA levels were measured by applying the HA test and were expressed as ng./mg. creatinine. Gel filtration column chromatography was used to examine the profile of urinary GAGs and HA species. RESULTS: Total urinary GAGs were 2.5 to 4-fold elevated in interstitial cystitis patients with moderate to severe symptoms (Group 2; 76.2 +/- 24.8) when compared with those in normal individuals (19.9 +/- 2.5) and patients with mild symptoms (Group 1; 30.4 +/- 5.1) (p <0.001). Three urinary GAG peaks were detected in both normal and interstitial patients. However, each GAG peak from interstitial cystitis patient urine was 3 to 5-fold higher than that from normal patient urine. The sulfated GAG levels, however, remained unchanged among normal individuals (1.4 +/- 0.22), Group 1 (2.2 +/- 0.96) and Group 2 (1.6 +/- 0.38) patients (p >0.05). Consequently, the ratio of total GAGs to sulfated GAGs was elevated 3 to 3.5-fold in Group 2 patients (49.9 +/- 13.9) in comparison to that in normal individuals (16.7 +/- 2.5) and group 1 patients (14.4 +/- 4.6) (p <0.001). Urinary HA levels were marginally elevated in Group 2 patients (821. 4 +/- 247.9) when compared with those in the normal group (337.3 +/- 106.1) and Group 1 patients (540.9 +/- 166.5). In addition, a distinct high molecular mass HA species was present only in Group 2 patients. CONCLUSIONS: The increased ratio of total GAGs to sulfated GAGs and marginally elevated HA levels in urine indicate that the GAG layer is altered in interstitial cystitis patients. However, these results are in contrast to the accepted concept that a reduction in urothelial GAGs causes interstitial cystitis. The high molecular mass HA species detected in patients with severe symptoms may play a role in the pathophysiology of this disease.

Adult↗
PubMed2001

Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis.

PURPOSE: Extracellular adenosine triphosphate (ATP) has been shown to mediate inflammation and nociception and, therefore, it may have a role in symptoms associated with interstitial cystitis. We theorized that the bladder uroepithelium releases ATP in response to stretch and, furthermore, this process is augmented in interstitial cystitis. MATERIALS AND METHODS: We quantitated ATP using the luciferin-luciferase assay. Urinary ATP levels were compared in 35 patients with interstitial cystitis and in 33 normal controls after pH correction. Cultured interstitial cystitis and normal urothelial cells from the bladder biopsies of 5 patients each were stretched with the Flexcell 2000 machine (Flexcell International Corp., McKeesport, Pennsylvania) and supernatant ATP concentrations were measured. RESULTS: Mean urinary ATP plus or minus standard error of mean was significantly higher in patients with interstitial cystitis than in controls (L value 985 +/- 161 versus 377 +/- 27, p = 0.0007). Supernatant ATP released by stretched interstitial cystitis cells was stretch intensity dependent when comparing 0%, 10% and 20% elongation, and was also significantly higher in stretched interstitial cystitis than in stretched normal cells. CONCLUSIONS: Adenosine triphosphate was significantly elevated in the urine of individuals with interstitial cystitis and the stretch activated release of ATP was augmented in interstitial cystitis urothelium. Increased extracellular ATP may have a role in mechanosensory transduction and to our knowledge it represents a novel hypothesis.

Adenosine Triphosphate↗
PubMed2002

[Interstitial cystitis: update on pathogenesis, diagnosis, and treatment].

OBJECTIVES: Interstitial cystitis is a nosological entity of which many etiological, diagnostic and therapeutic features were unknown until recently, so that we had the objective to review new knowledge acquired during the last decade to offer an update in the disease. METHODS: A bibliographic review on interstitial cystitis is performed with special interest in national and international authors who have experience and large case series. RESULTS: Among the multiple etiopathogenical theories proposed in the past, the hypothesis to be highlighted, that is gaining strength, is the altered bladder urothelium permeability or hemato-urinary barrier alteration, with the aggression of toxic substances contained in urine in high concentrations like potassium. Epidemiologically, some authors think the disease is present in the population in a higher frequency than it is diagnosed, and it may be found in many women with the misdiagnosis of recurrent urinary tract infections. Regarding diagnosis, a new test is proposed to help clinical diagnosis: the potassium test, which consists in the endovesical instillation of this ion at high concentrations reproducing the symptoms. Finally, in the medical treatment it is demonstrated the efficacy of drug associations over monotheraphy (heparinoids, antihistaminic and antidepressant drugs), looking for the correction of the physiopathological abnormalities caused by the disease. Psicologic support and continuous information to the patient about the disease continue to be one of the mainstays of this multimodal therapy. New options like neural stimulation have appeared, although its results are not conclusive so that further studies must be done. CONCLUSIONS: New knowledge about interstitial cystitis allow us to better understand the chain of events happening in it. An early clinical diagnosis, now reinforced with a positive potassium test, is key to start medical treatment (drug combination) targeted to stop the pathogenic process, because it is more effective in the early phases of the disease. For that purpose, the Urologist must have this disease in mind.

Cystitis, Interstitial↗
PubMed1997

Epithelial coating techniques in the treatment of interstitial cystitis.

OBJECTIVES: To review the newer methods of treatment of interstitial cystitis using techniques that coat the epithelium to maintain its integrity relative to permeability. METHODS: The technique of employing sulfated polysaccharides in the treatment of interstitial cystitis both orally and intravesically were reviewed as well as the concepts supporting the use of such technology, including a review of the role glycosaminoglycans (mucus) play in the regulation of epithelial permeability. Also reviewed were the methods that can be employed to detect aberrations of epithelial permeability as seen in the interstitial cystitis syndrome. RESULTS: The techniques of detecting epithelial permeability problems and appropriate therapy for this using polysaccharides, such as heparin and pentosanpolysulfate, are presented. This article also discusses the point that these techniques will result in long-term remissions in patients with the IC syndrome who respond to these treatments. CONCLUSIONS: The use of sulfated polysaccharides, both orally and intravesically, is an effective long-term treatment for many people with the interstitial cystitis syndrome.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Interstitial cystitis and endometriosis in patients with chronic pelvic pain: The "Evil Twins" syndrome.

OBJECTIVE: To determine the prevalence of interstitial cystitis and endometriosis in patients with chronic pelvic pain. METHODS: A prospective analysis was conducted in 178 women with CPP who presented with bladder base/anterior vaginal wall and/or uterine tenderness, with or without irritative voiding symptoms. The Potassium Sensitivity Test was used to assess bladder epithelial dysfunction. Patients were evaluated with concurrent laparoscopy and cystoscopy with hydrodistention. RESULTS: Laparoscopic findings among the 178 patients with chronic pelvic pain supported a diagnosis of endometriosis in 134 (75%) patients, and cystoscopy confirmed a diagnosis of interstitial cystitis in 159 (89%) patients. Both interstitial cystitis and endometriosis were diagnosed in 115 patients (65%). The Potassium Sensitivity Test was positive in 146 (82%) patients, with 140 (96%) of these patients diagnosed with interstitial cystitis and 105 (72%) with endometriosis. CONCLUSIONS: Results of this prospective study show that interstitial cystitis and endometriosis may frequently coexist in patients with chronic pelvic pain. A positive Potassium Sensitivity Test accurately predicted the presence of interstitial cystitis in 96% of these patients with chronic pelvic pain, as confirmed by cystoscopic hydrodistention. It is necessary to consider the diagnosis of endometriosis and interstitial cystitis concurrently in the evaluation of patients with chronic pelvic pain to avoid unnecessary delay in identifying either condition.

Adolescent↗
PubMed1990

Recurrent interstitial cystitis following cystoplasty: fact or fiction?

The severity of symptoms in interstitial cystitis may necessitate surgical treatment in approximately 10% of the patients. Substitution cystoplasty provides satisfactory results in most of these cases, while avoiding the need for urinary diversion. It has been suggested that interstitial cystitis may affect the bowel segment used in this form of operation. We studied bowel segments removed from cystoplasties in 5 patients with interstitial cystitis and compared these to bowel used for lower urinary reconstruction for other disorders in 6 patients. All segments showed varying degrees of inflammation, fibrosis and mastocytosis but there was no difference between the 2 groups for these features. We conclude that inflammation and fibrosis is the usual reaction of bowel to exposure to urine, and they do not represent a specific spread of interstitial cystitis in those patients. However, this reaction does mimic the histological appearance of interstitial cystitis in the bladder and may suggest a model for this disease.

Adult↗
PubMed1994

The role of the mast cell in interstitial cystitis.

The bladder mast cell contains many granules, each of which can secrete many vasoactive and nociceptive molecules. A number of conditions, such as extreme cold, drugs, neuropeptides, stress, trauma, and toxins, can trigger the mast cell to secrete some of its contents; they, in turn, can sensitize sensory neurons, which can further activate mast cells by releasing neurotransmitters or neuropeptides. Additionally, the mast cell can directly cause vasodilation and bladder mucosa damage while also attracting inflammatory cells, thus causing many of the problems seen in interstitial cystitis. The mast cell appears to be involved in the pathogenesis of interstitial cystitis. Although it is not pathognomonic of the disease, mastocytosis does occur in a significant subset of interstitial cystitis patients. Because interstitial cystitis is now regarded as a syndrome caused by multiple factors, it is conceivable that one cause of interstitial cystitis is associated with bladder mastocytosis and mast cell activation. The fact that mast cells are also increased in patients with transitional cell carcinoma of the bladder does not diminish the importance of mastocytosis in interstitial cystitis, because the mast cells are not activated in carcinoma but are activated in interstitial cystitis. Perhaps the common strand between these two bladder diseases is the putative allergens/carcinogens in bladder urine that breach the protective lining of the bladder and then elicit an immune response in the bladder wall. Furthermore, the majority of patients with a history of bladder tumors receive multiple courses of intravesical chemotherapy (such as thiotepa) or immunotherapy (bacille Calmette-Guerin), and it is possible that these agents damage the bladder lining or provoke an inflammation in the bladder wall. The theory of a defective/deficient bladder glycosaminoglycan layer in interstitial cystitis is also consonant with this putative chain of events in the pathogenesis of interstitial cystitis. Thus these two theories interstitial cystitis causation--a glycosaminoglycan deficiency and bladder mastocytosis--may well operate in concert to cause bladder inflammation and the symptoms of interstitial cystitis. Clinicians may be at a distinct disadvantage because they are faced with a multitude of potential mast cell triggers and numerous mediators secreted. It may, therefore, be advisable to block or inhibit the mast cell from responding to many of these various stimuli. Specific mast cell mediators should be assayed as possible diagnostic tools, and potential mast cell inhibitors should be tried under controlled conditions to determine the extent of therapeutic benefit.

Animals↗
PubMed1993

Interstitial cystitis: women at risk for psychiatric misdiagnosis.

Interstitial cystitis (IC) is a form of painful bladder disease, characterized by chronic urinary urgency, frequency, and pain without evidence of bacterial infection. Ninety percent of patients with IC are women. Somatization disorder is a psychiatric diagnosis, given most often to women who report a variety of symptoms, such as dysmenorrhea, burning in sex organs, dyspareunia, irregular menstrual periods, and painful urination. Because diagnosis of interstitial cystitis may take many years, health care providers must be alert to the risks of the overdiagnosis of psychiatric problems and the underdiagnosis of interstitial cystitis.

Adult↗
PubMed1999

The urinary glycoprotein GP51 as a clinical marker for interstitial cystitis.

PURPOSE: GP51 is a urinary glycoprotein with a molecular weight of 51 kDa. This glycoprotein is produced and secreted by the transitional epithelium of the genitourinary tract, and has been isolated from human urine. Studies have demonstrated that GP51 levels are decreased in bladder biopsies of patients with interstitial cystitis. We evaluated urinary GP51 in a noninvasive manner as a clinical marker of interstitial cystitis. MATERIALS AND METHODS: Urinary GP51 levels were measured using antigen inhibition enzyme-linked immunosorbent assay. In blinded fashion we analyzed for quantitative differences 24-hour urine samples of 36 patients with interstitial cystitis and 23 normal controls who were age matched within 5 years (mean age 47.3). We also evaluated GP51 in random urine specimens of 17 normal controls, 14 patients with interstitial cystitis and 11 subjects who had undergone cystectomy to determine whether urinary GP51 is mainly produced by the bladder, which is the site of interstitial cystitis. To ascertain the specificity of urinary GP51 to interstitial cystitis urine samples of 34 patients with other urological diseases were measured and compared with findings in the samples of 15 with interstitial cystitis. RESULTS: Low GP51 levels appeared to be unique to the interstitial cystitis state compared to normal (p = 0.008). GP51 in patients with interstitial cystitis and in those who underwent cystectomy was lower (p < 0.001) than in normal controls. These findings suggest that the major source of urinary GP51 is the bladder. Also, we observed lower GP51 levels in interstitial cystitis than in other urinary tract diseases (p < 0.0001). CONCLUSIONS: Our study substantiates the possibility of using GP51 as a clinical marker for diagnosing interstitial cystitis by a noninvasive urinary assay.

Biomarkers↗
PubMed1996

Discrimination between the ulcerous and the nonulcerous forms of interstitial cystitis by noninvasive findings.

PURPOSE: We determined whether the classification of interstitial cystitis cases into ulcer and nonulcer categories from cystoscopic findings could be corroborated with epidemiological data relating to demographics, risk factors, symptoms, pain and psychosocial factors. MATERIALS AND METHODS: We surveyed 565 interstitial cystitis patients (111 with and 454 without ulcer), and from univariate analyses we found 10 noninvasive variables to be significantly associated with the presence of Hunner's ulcers. The 3 multivariate statistical methodologies of discriminant analysis, logistic regression and recursive partitioning were used to classify ulcer versus nonulcer cases from these variables. The retrospective and prospective performances from each methodology were also analyzed. RESULTS: Retrospectively, resubstitution error rates of all 3 methodologies were small, with overall misclassification rates of 19.1% with linear discriminant, 14.7% with logistic regression and 8.0% with recursive partitioning. Prospectively, the overall misclassification rates increased slightly to 20.0% with linear discriminant, 15.8% with logistic regression, and 15.9% with recursive partitioning. CONCLUSIONS: The classification of interstitial cystitis into distinct categories of Hunner's ulcer (classic interstitial cystitis) and nonulcer based on cystoscopic findings can be corroborated with epidemiological evidence. The 2 categories may represent different manifestations of the underlying disease pathophysiology.

Adult↗
PubMed2003

Sacral neuromodulation for the symptomatic treatment of refractory interstitial cystitis: a prospective study.

PURPOSE: The efficacy of sacral neuromodulation for the treatment of symptoms in patients with refractory interstitial cystitis was evaluated. MATERIALS AND METHODS: A total of 25 patients with a mean age of 47 years and refractory interstitial cystitis were prospectively evaluated with a trial of sacral nerve stimulation. Patients who demonstrated 50% improvement in frequency, nocturia, voided volume and average pain qualified for permanent sacral nerve stimulator implantation. Treatment success was measured by voiding diary, report of average pain, and response to the Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index. RESULTS: Of the 25 patients 17 qualified for permanent sacral nerve stimulator implantation. At an average of 14 months followup mean daytime frequency and nocturia improved from 17.1 to 8.7 and 4.5 to 1.1, respectively (p <0.01). Mean voided volume increased from 111 to 264 ml. (p <0.01). Report of average pain decreased from 5.8 to 1.6 points on a scale of 0 to 10 (p <0.01). Interstitial Cystitis Symptom and Problem Index scores decreased from 16.5 to 6.8 and 14.5 to 5.4, respectively (p <0.01). Of the 17 patients 16 (94%) with a permanent stimulator demonstrated sustained improvement in all parameters at the last postoperative visit. CONCLUSIONS: Results of this prospective clinical study demonstrate that sacral neuromodulation is a safe and effective treatment for the dysfunctional voiding and pelvic pain in patients with interstitial cystitis who are refractory to other forms of treatment.

Adult↗
PubMed1999

[Two cases of interstitial cystitis complicated with migraine].

Two cases of interstitial cystitis complicated with migraine and atopic tendency are reported. In the bladder tissue of the two cases, mast cells were increased and in one case which was observed with immunohistochemical staining, most of the mast cells among muscle layers were chymase-positive mast cells. We considered that the degranulation of mast cells was related with the cause of interstitial cystitis and migraine.

Aged↗
PubMed1997

Excretion of fluorescein in the urine of women with interstitial cystitis.

PURPOSE: Altered bladder permeability may have a role in the pathogenesis of interstitial cystitis. Fluorescein, a fluorescent dye of molecular weight 325, has been used to assess membrane permeability. Orally ingested fluorescein normally is rapidly conjugated to glucuronate by the liver and excreted in the urine. MATERIALS AND METHODS: To test its use as a marker of bladder permeability, we administered fluorescein orally to 6 patients with interstitial cystitis who satisfied National Institutes of Health, National Institute for Diabetes and Digestive and Kidney Diseases criteria and to 6 normal female control subjects. After emptying the bladder and collection of a baseline blood sample, fasted subjects ingested 20 mg. fluorescein and blood samples were collected 1, 2, 3, 4 and 24 hours later. Urine was collected during each of the first 4 hours, and then from 4 to 10, 10 to 16 and 16 to 24 hours. Urine volume was measured, and all plasma and urine samples were analyzed for fluorescein. RESULTS: Plasma fluorescein concentrations (ng./ml.) were significantly (p < 0.05) higher in interstitial cystitis patients than in control subjects at 1 and 2 hours after fluorescein ingestion. Urine fluorescein excretion (mg.) was significantly (p < 0.05) lower in interstitial cystitis patients than in control subjects at 4 to 10 hours after fluorescein ingestion, and for the entire 24 hours. CONCLUSIONS: The increased fluorescein concentration in the plasma and decreased excretion in the urine of interstitial cystitis patients suggest that fluorescein may be a useful marker of altered membrane permeability.

Adult↗
PubMed2004

Interstitial cystitis, chronic nonbacterial prostatitis and chronic pelvic pain syndrome in men: a common and frequently identical clinical entity.

PURPOSE: In this ongoing review we characterize interstitial cystitis in men, identifying multiple clinical factors in the diagnosis and treatment of men with interstitial cystitis. MATERIALS AND METHODS: An ongoing and retrospective chart review of 92 men with interstitial cystitis within our large single specialty practice was performed. Presenting complaints, duration of symptoms, epidemiology, and clinical and physical findings were reviewed. RESULTS: All patients met National Institute for Diabetes and Digestive and Kidney Diseases criteria for the diagnosis of interstitial cystitis. Of the patients 83% were white and 17% were American Indians of Cherokee descent. Average patient age at diagnosis was 51 years and average duration of symptoms was 8.8 years. The most commonly reported initial complaints were mild suprapubic discomfort, which rapidly progressed in an average of 21/2 years to severe suprapubic discomfort, severe dysuria and severe urinary frequency. Sexual dysfunction occurred in 60% of patients with painful ejaculation. The most common physical findings were suprapubic tenderness to palpation and anterior rectal wall tenderness on digital rectal examination. Of the patients 40% had microscopic hematuria. All patients demonstrated severe glomerulations under anesthesia with cystoscopy and hydraulic distention of the bladder. Average bladder volume was 510 cc. CONCLUSIONS: Interstitial cystitis in males appears to be more common than historically reported. Interstitial cystitis in males and patients with chronic pelvic pain syndrome and chronic nonbacterial prostatitis share many clinical findings. A higher incidence of interstitial cystitis had been found in American Indian males of Cherokee descent and deserves further investigation.

Chronic Disease↗