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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↗

Dimethyl sulfone (DMSO2) in the treatment of interstitial cystitis.

DMSO2 is one alternative for treating interstitial cystitis. Research with this compound is very limited, but side effects have been negligible. The drug may hold promise for interstitial cystitis patients, as well as those suffering from painful bladder (urethral) syndrome.

Administration, Topical↗

Improvement of interstitial cystitis symptoms and problems that developed during treatment with oral IPD-1151T.

PURPOSE: We examined the efficacy of Suplatast Tosilatedouble dagger (IPD-1151T), a new immunoregulator that suppresses helper T cell mediated allergic responses, including IgE production and eosinophilic inflammation for treating patients with interstitial cystitis. MATERIALS AND METHODS: A total of 14 women (average age 43.7 years) with interstitial cystitis, which was nonulcerative in 13 and ulcerative in 1, were treated with 300 mg. IPD-1151T orally daily for 12 months. All patients received laboratory assessments, including hematology (eosinophils and CD20 positive cells) and serum chemistry (IgE, and interleukin-4 (IL-4) and 5, and immunohistochemical analyses of urine leukocytes (CD45RO positive cells as a T cell marker) before treatment. These parameters were also measured 4 and 12 months after continuous treatment. The voiding chart, and interstitial cystitis symptom and problem indexes were evaluated before and after IPD-1151T treatment. RESULTS: IPD-1151T treatment for 1 year resulted in a significantly increased bladder capacity and decreased symptoms, such as urinary urgency, frequency and lower abdominal pain, in patients with nonulcerative interstitial cystitis. These effects also correlated with a reduction in blood eosinophils, CD20 positive cells and IgE, and urine CD45RO positive memory T cells. No major side effects were observed. CONCLUSIONS: Our study suggests that immunological responses are involved in the development of interstitial cystitis symptoms. IPD-1151T could be a new oral agent for treatment of voiding symptoms and bladder pain in patients with interstitial cystitis.

Adjuvants, Immunologic↗

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↗

Increased mast cells of the bladder in suspected cases of interstitial cystitis: a possible disease marker.

Mast cells reportedly have been increased in the detrusor muscle bundles of the bladder in patients with interstitial cystitis. In 30 patients with suspected interstitial cystitis quantification of mast cells within the muscularis and submucosa was done. The results were compared to those obtained from a variety of normal bladder specimens removed surgically (16 specimens) and at autopsy (15), and from bladders with a variety of miscellaneous inflammatory conditions (20). In patients with suspected interstitial cystitis the number of mast cells was increased significantly (p less than 0.001) compared to the 3 control groups. This finding suggests that quantification of mast cells in the muscularis may be a useful marker in the histopathological evaluation of bladder biopsies in patients with suspected interstitial cystitis.

Adult↗

What is the value of cystoscopy with hydrodistension for interstitial cystitis?

OBJECTIVES: To determine the utility of cystoscopy with hydrodistension for the diagnosis and therapy of interstitial cystitis. Cystoscopy with hydrodistension is the most commonly performed diagnostic test and procedure in patients with interstitial cystitis. METHODS: Eighty-four consecutive patients with interstitial cystitis (68 women and 16 men) were studied retrospectively. The patients underwent history and physical examination, urinalysis, and urine culture and filled in a voiding diary and pain urgency frequency questionnaire. Cystoscopy with hydrodistension was performed in 47 patients. Patients who had and had not undergone hydrodistension were compared. Patients who underwent hydrodistension were characterized and followed up for response. RESULTS: The mean patient age was 41 years, mean daily voided volume was 98 mL, mean number of nocturnal episodes was 3, and pain urgency frequency score was 21. Comparing patients undergoing versus not undergoing hydrodistension, pain was reported in 61% versus 25% (P = 0.03), vaginal pain in 62% versus 32% (P = 0.02), and dyspareunia or ejaculatory pain in 67% versus 29% (P < 0.01), respectively. All other parameters were statistically similar. Of the patients undergoing hydrodistension, 43 had follow-up and 24 (56%) reported improvement (mean duration of 2 months). Of the patients with and without improvement, no difference was found in mean age (40 versus 46 years, P = 0.20), duration of symptoms (7 versus 7 years, P = 0.92), anesthetic capacity (722 versus 721 mL, P = 0.99), or glomerulation grade (P = 0.61), respectively. CONCLUSIONS: Cystoscopy with hydrodistension provided little useful information above and beyond the history and physical examination findings. As therapy, 56% of patients reported improvement, but the duration was short lived.

Adolescent↗

Chronic pelvic pain: the occurrence of interstitial cystitis in a gynecological population.

OBJECTIVE: The objective of this study was to determine what relationship exists between interstitial cystitis and chronic pelvic pain in patients. METHODS: A prospective study of 35 women with a complaint of chronic pelvic pain was performed between August 2002 and September 2003. These patients underwent a workup to exclude other causes of pelvic pain and underwent a laparoscopy and a cystoscopy with hydrodistention at 80 cm of hydrostatic water pressure. Results were obtained and quantified. RESULTS: Twenty-eight patients (80%) were diagnosed with interstitial cystitis, 28 were diagnosed with endometriosis (80%), 24 had both disease entities simultaneously (69%), and 32 (91%) had endometriosis, interstitial cystitis, or both. Three patients (9%) had neither and were diagnosed with other pathologies. CONCLUSIONS: Chronic pelvic pain is a major concern for many women in the United States. Patients with chronic pelvic pain have traditionally been difficult to manage. A large percentage of women presenting with chronic pelvic pain have been shown to have endometriosis, interstitial cystitis, or both. Therefore, an appropriate workup for those individuals with chronic pelvic pain involves not only obtaining a good history and performing a good physical examination, but the possibility of a cystoscopy being performed when a laparoscopy has been deemed necessary for diagnosis of the pain. These procedures can serve as both a means for diagnosis and short-term treatment of these problems when encountered.

Chronic Disease↗

The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis.

PURPOSE: The presence of leukotriene D4 receptors in human detrusor myocytes and increased urinary leukotriene E4 in patients with interstitial cystitis and detrusor mastocytosis imply a role for cysteinyl containing leukotrienes as proinflammatory mediators in this disease. We examined the efficacy of the cysteinyl leukotriene 1 receptor antagonist montelukast for treating patients with interstitial cystitis and detrusor mastocytosis. MATERIALS AND METHODS: Ten women in whom interstitial cystitis was diagnosed according to National Institute of Diabetes and Digestive and Kidney Diseases criteria and who also had detrusor mastocytosis with a minimum of 28 mast cells per mm.2 muscle tissue were included in this study. Patients received a single dose of montelukast daily for 3 months. The efficacy of treatment was determined by 24-hour urinary frequency, nocturia and pain using visual analog scales. RESULTS: After 1 month of montelukast treatment there was a statistically significant decrease in 24-hour urinary frequency, nocturia and pain which persisted during the 3 months of treatment. After 3 months 24-hour urinary frequency had decreased from 17.4 to 12 voidings (p = 0.009), nocturia had decreased from 4.5 to 2.8 (p = 0.019) and pain had decreased from 46.8 to 19.6 mm. on a visual analog scale (p = 0.006). No side effects were observed during treatment. CONCLUSIONS: Montelukast treatment resulted in significant improvement in urinary frequency and pain. Its efficacy for decreasing urinary frequency and pain imply a role of leukotriene receptor antagonists for managing interstitial cystitis but further placebo controlled clinical studies are needed.

Acetates↗

Urinary glycosaminoglycan excretion as a laboratory marker in the diagnosis of interstitial cystitis.

Urinary macromolecular uronate and glycosaminoglycan uronate concentrations were determined in 209 urine specimens obtained from 192 interstitial cystitis patients, 47 asymptomatic normal individuals and 32 spinal cord injury patients. As a group the concentration of macromolecular uronate or glycosaminoglycan uronate was significantly less in the interstitial cystitis patients than in the normal controls. Some interstitial cystitis patients showed low values of macromolecular uronate and glycosaminoglycan uronate. Analysis of the population distributions suggested that macromolecular uronate may have significant value in diagnosis of interstitial cystitis.

Adult↗

Modified Thiele massage as therapeutic intervention for female patients with interstitial cystitis and high-tone pelvic floor dysfunction.

OBJECTIVES: To evaluate the effectiveness of transvaginal manual therapy of the pelvic floor musculature (Thiele massage) in symptomatic female patients with interstitial cystitis and high-tone dysfunction of the pelvic floor. METHODS: A total of 21 women with documented interstitial cystitis and high-tone pelvic floor dysfunction underwent transvaginal massage using the Thiele technique twice a week for 5 weeks. Symptoms were evaluated before massage, at protocol conclusion, and at a mean of 4.5 months after therapy completion (long-term follow-up). The response to treatment was evaluated through the O'Leary-Sant Interstitial Cystitis Symptom and Problem Indexes, Likert Visual Analogue Scales for urgency and pain, and Short-Form 12-item (SF-12) Quality-of-Life Scale, and through changes in the physical examination findings using a 5-point modified Oxford Scale to document pelvic floor tenderness. RESULTS: A statistically significant improvement was seen in the Symptom and Problem Indexes of the O'Leary-Sant Questionnaire (P = 0.015 and P = 0.039, respectively), Likert Visual Analogue Scales for urgency and pain (P = 0.001 and P = 0.005, respectively), the Physical and Mental Component Summary from the SF-12 Quality-of-Life Scale (P = 0.049 and P = 0.044, respectively), and the modified Oxford Scale (P <0.05) after protocol completion. At long-term follow-up, the O'Leary-Sant Interstitial Cystitis Symptom and Problem Indexes (P = 0.049 and P = 0.02, respectively), Likert Visual Analogue Scales for urgency and pain (P = 0.004 and P = 0.005, respectively), and modified Oxford Scale for three of four muscles in the pelvic floor (P <0.05) remained significantly improved. CONCLUSIONS: Thiele massage appears to be very helpful in improving irritative bladder symptoms in patients with interstitial cystitis and high-tone pelvic floor dysfunction in addition to decreasing pelvic floor muscle tone.

Adult↗

Effect of interstitial cystitis on drug absorption from urinary bladder.

Our laboratory reported previously the in vivo absorption of salicylate and antipyrine from the urinary bladder of healthy rats. The present study extends these findings to examine the effect of interstitial cystitis on bladder permeability to drugs by comparing the bladder absorption of salicylate in healthy cats and cats with feline interstitial cystitis (FIC). Interstitial cystitis is a lower urinary tract disease and may involve inflammation of the bladder. A 25-mg/kg dose of sodium salicylate was instilled into the bladder and a 6-micrograms/kg i.v. dose of [14C]salicylic acid was administered concomitantly to determine systemic clearance in individual animals. In healthy and FIC cats, the clearance was 0.3 and 0.1 ml.min-1.kg-1, and the bioavailability of the intravesical dose was about 1 and 9%, respectively. The apparent bladder absorption rate constant and the peak plasma concentration in FIC cats were 7 to 8 times that in healthy cats. These data indicate a significantly higher bladder permeability to salicylate due to interstitial cystitis. In order to elucidate the cause of the lower clearance in FIC cats, a second study compared the disposition of a 2-mg/kg i.v. dose of salicylate in healthy and FIC cats. It was found that the lower salicylate clearance in FIC cats was due in part to a decreased metabolism in the disease state and also involved slower drug elimination at the higher plasma concentrations secondary to the more extensive absorption of the intravesical dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Interstitial cystitis in adolescent girls.

Two cases of interstitial cystitis with typical, large bladder ulcerations in adolescent girls are reported. The specific diagnosis was confirmed histologically after full-thickness segmental resection of the bladder wall at the site of the ulceration during subsequent operations. Contrary to other reports based on subjective clinical findings, interstitial cystitis in children is rare when rigid criteria, including careful histological study, are applied. Treatment in children is the same as in adults and should be conservative. A conscientious attempt should be made to exclude infection and tuberculosis as possible contributors to the symptoms of urinary frequency and discomfort, as well as other causes of bladder abnormality. If conservative management fails to relieve symptoms the bladder may be enlarged in some cases by using a segment of intestine.

Adolescent↗

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↗

Interstitial cystitis in a woman with systemic mastocytosis.

Studies have reported detrusor mastocytosis in patients with interstitial cystitis. The author describes a patient with systemic mastocytosis who was confirmed to have detrusor mastocytosis and interstitial cystitis. She responded to therapy with pentosanpolysulfate. The literature on systemic mastocytosis and the role of mast cells in the pathophysiology of interstitial cystitis are reviewed.

Anti-Inflammatory Agents, Non-Steroidal↗

Self-care strategies used for acute attack of interstitial cystitis.

OBJECTIVE: To determine the kinds of self-care used by women with interstitial cystitis and to find effective ways to manage symptoms of acute attack. STUDY DESIGN: One hundred thirty-eight women with interstitial cystitis completed a survey indicating how often they used and how effective they found strategies in four physical self-care subdomains (medication, treatment, diet, and body comfort) and three psychologic self-care subdomains (cognitive/stress reduction, distraction, and help-seeking). RESULTS: Descriptions of symptoms during an "acute attack" are more consistent with symptoms described "at onset" than symptoms experienced "currently." Physical strategies most used for acute attack included use of narcotics, antidepressants, and bladder analgesics, in addition to limiting the diet to bland or starchy foods, wearing loose clothing, taking hot baths, and using a heating pad over the pubis. Psychologic strategies most used included watching television, prayer, and seeking support from a significant other, family members, friends, and other patients with interstitial cystitis. CONCLUSIONS: Some psychologic and physical strategies found to be effective for other chronic pain conditions, such as biofeedback, alternating use of heat/cold, self-hypnosis, and redefining pain sensations were seldom used. Other nonmedical interventions such as massage and imagery, when used, were found to be more moderately to highly effective. Information about self-care and access to support groups may increase exposure to multiple ways of handling acute attacks.

Acute Disease↗

Electrical stimulation in interstitial cystitis.

We treated 14 women with chronic interstitial cystitis with long-term intravaginal or transcutaneous nerve stimulation. Clinical and urodynamic evaluations were done after 6 months to 2 years. Improvement was not immediate but required a considerable period of continuous, daily use of electrical stimulation. The results were favorable--a substantial decrease in pain and frequency of micturition in all patients after long-term treatment. Since the methods seem effective and are simple, cheap and non-destructive electrical stimulation is recommended for all patients with chronic interstitial cystitis.

Aged↗

Interstitial cystitis. An overlooked cause of pelvic pain.

Interstitial cystitis is a disease primarily of young and middle-aged women that is characterized by pelvic pain, urinary frequency, and dyspareunia. Its cause is unknown, but defects in the protective glycosaminoglycan layer of the bladder mucosa may be responsible. The diagnosis is mainly one of exclusion. Cystoscopy reveals characteristic glomerulations in the bladder mucosa. Of the available treatments, the most common are intermittent hydrodilation of the bladder and intermittent intravesical instillation of dimethyl sulfoxide. Other methods and medications are currently under investigation. Although interstitial cystitis is uncommon, its potentially devastating effects may be modified or even averted if primary care physicians are familiar with its presentation and maintain a high index of suspicion.

Cystitis↗

Use of amitriptyline in the treatment of interstitial cystitis.

A total of 25 patients with interstitial cystitis who had failed standard therapy with hydrodistension of the bladder during anesthesia and intravesical dimethyl sulfoxide instillation underwent treatment with the tricyclic antidepressant amitriptyline. The initial dosage of 25 mg. before bed was increased gradually during a 3-week period to 75 mg. at bedtime. Of the patients 20 were able to tolerate the medication for a minimum of 3 weeks and could be evaluated for response. A significant improvement was noted in pain and daytime frequency. Of 9 patients 8 experienced relief of dyspareunia and 11 of 19 reported diminished urinary urgency. Eight patients have experienced virtual total remission of symptoms and have been on the drug for 4 to 28 months. It appears reasonable to consider the use of amitriptyline in patients with interstitial cystitis refractory to standard therapy.

Adult↗