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PubMed1996

Distinctive ultrastructural pathology of nonulcerative interstitial cystitis: new observations and their potential significance in pathogenesis.

Ultrastructural study of the bladder in interstitial cystitis has, so far, been limited, mainly to the urothelium. The present study was conducted first to study in detail the ultrastructural features of all tissue components of the bladder wall in nonulcerative interstitial cystitis and second to derive clues from the observed changes to pathogenesis of the disease. Endoscopic biopsies of urothelium with attached suburothelium, and muscularis, were obtained from both lesional and nonlesional areas in 5 female patients with unequivocal clinical diagnosis of interstitial cystitis. The specimens were processed for electron microscopic study by standard methods and subjected to comprehensive ultrastructural study of urothelium, suburothelium, detrusor muscle cells, intrinsic blood vessels, and intrinsic nerves. A distinctive combination of peculiar muscle cell profiles, injury of intrinsic vessels and nerves in muscularis and suburothelium, and discohesive urothelium was observed in lesional and less markedly in nonlesional samples of all specimens. Marked edema of various tissue elements and cells appeared to be a common denominator of many observed changes. Edema of muscle cells resulted in characteristic querciphylloid profiles, so designated because of peripheral bosselation of cell sarcoplasm with a lobed perimeter resembling that of an oak leaf. Urothelial changes disrupted the true permeability barrier, consisting of asymmetric unit membrane and triple epithelial junctions of surface (umbrella) cells. Vascular lesions included endothelial cell injury and suggested sluggishness of intrinsic microcirculation. Neural changes included a combination of degenerative and regenerative features, some expressing neural plasticity. The observed ultrastructural changes appear to be sufficiently distinctive to be diagnostic in specimens submitted for pathologic confirmation of nonulcerative interstitial cystitis. The changes do not support a primary pathogenetic role of mast cells or a selectively deficient glycosaminoglycan layer. They do suggest, however, a pathogenesis based on a potentially self-perpetuating process of neurogenic inflammation that can trigger a biologically potent cascade of events, including a leaky urothelium and mast cell activation. As proposed, neurogenic inflammation consolidates various proposals advanced as the pathogenesis of interstitial cystitis and can readily accommodate infectious, immunologic, and autoimmunologic mechanisms as factors that contribute to development or chronicity of the disease.

Adult↗
PubMed2001

Percutaneous sacral nerve root neuromodulation for intractable interstitial cystitis.

PURPOSE: We evaluated the efficacy of percutaneous sacral nerve root neuromodulation in women with refractory interstitial cystitis. MATERIAL AND METHODS: We prospectively evaluated 15 consecutive women with a mean age of 62 years who had refractory interstitial cystitis to determine the efficacy of percutaneous stimulation of the S3 sacral roots. The mean duration of symptoms before evaluation was 5.2 years. All women fulfilled the National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases criteria for the diagnosis of interstitial cystitis and were unresponsive to standard oral or intravesical therapy. The response to treatment was assessed using pain scores, urinary diary variables and quality of life surveys. RESULTS: Mean voided volume during treatment increased from 90 to 143 ml. (p <0.001). Mean daytime frequency and nocturia decreased from 20 to 11 and 6 to 2 times (p = 0.012 and 0.007, respectively). Mean bladder pain decreased from 8.9 to 2.4 points on a scale of 0 to 10 (p <0.001). As indicated by the Short Urinary Distress Inventory and SF-36 Health Survey, the quality of life parameters of social functioning, bodily pain and general health significantly improved during the stimulation period. Of the women 73% requested to proceed to complete sacral nerve root implantation. CONCLUSION: Women with intractable interstitial cystitis respond favorably to percutaneous sacral stimulation with significant improvement in pelvic pain, daytime frequency, nocturia, urgency and average voided volume. Permanent sacral implantation may be an effective treatment modality in refractory interstitial cystitis but further long-term evaluation is required.

Adult↗
PubMed1998

Effects of L-arginine treatment on symptoms and bladder nitric oxide levels in patients with interstitial cystitis.

OBJECTIVES: Nitric oxide (NO) is involved in host defense reactions, and NO production is elevated in various inflammatory disorders. We have found very high levels of luminal NO in the urinary bladder of patients with interstitial cystitis. Oral treatment with low doses of L-arginine, the substrate for NO production, has been reported to alleviate symptoms in patients with interstitial cystitis. The aim of our investigation was to evaluate the effect of higher doses of L-arginine in patients with interstitial cystitis and to study the effects of L-arginine on NO production in the bladder. METHODS: Nine women (age 69+/-3 years) with interstitial cystitis were treated daily with 3 or 10 g of L-arginine for 5 weeks. Symptoms were evaluated with an interstitial cystitis symptom score index, and NO production was measured. Patients with stress incontinence (n=18) were used as control subjects for measurement of NO levels. RESULTS: NO concentration in the urinary bladder was markedly elevated in the patients with interstitial cystitis (239+/-60 ppb) compared with the control patients (15+/-2 ppb). NO levels did not change in the patients with interstitial cystitis after oral treatment with L-arginine (189+/-72 ppb). There was no significant change in the symptom scores at either dose after 5 weeks of L-arginine treatment. CONCLUSIONS: L-arginine treatment in the doses used in this study did not change NO production in the urinary bladder in patients with interstitial cystitis. Furthermore, the patients in our study did not notice any relief of their symptoms.

Aged↗
PubMed2006

Advances in the treatment of interstitial cystitis.

Recent years have brought dramatic advances in the clinician's ability to offer effective pharmacotherapy to patients who have interstitial cystitis. Medical treatments have been developed and applied to reduce the interstitial cystitis symptoms of pelvic pain and urinary urgency/frequency, and to address underlying causes of the disorder. In addition, advances in the understanding of the natural history of interstitial cystitis have revealed that it is insidiously progressive and the classical definition--rare, severe and difficult to treat--is in fact the relatively uncommon, advanced stage of a disorder that affects most individuals in a mild-to-moderate and readily treatable form. This recognition has led to the identification of large numbers of previously unsuspected cases of interstitial cystitis, and the successful treatment of many individuals in the early stages of interstitial cystitis when it is far more responsive to therapy. A heparinoid-based multimodal medical regimen can effectively control symptoms and address disease pathophysiology in the majority of cases. Intravesical therapeutic solutions are new and promising adjunctive therapies that can offer immediate symptom relief during symptom flares, and for patients who are just beginning medical therapy.

Administration, Intravesical↗
PubMed1994

Self-care regimens for patients with interstitial cystitis.

For those who suffer from interstitial cystitis, living with the condition is a challenge that requires creativity, patience, determination, and a sound set of coping mechanisms. Because of the high percentage of gynecologic and systemic manifestations of interstitial cystitis, a customized treatment regimen is often necessary to achieve the therapeutic goal of a remission in symptoms. Treatment philosophies should be based on the proposed causative mechanisms, and a multimodality approach to therapy is usually successful. Self-care regimens give the patient a sense of control by active participation in treatment, which often improves coping mechanisms. Treatment of the sequelae of chronic pain (anxiety and depression) often improves response to overall therapy. Remission is the goal, coping is the key, and creativity opens the door to treating this most perplexing of conditions.

Cystitis↗
PubMed1977

Intestinocystoplasty in treatment of interstitial cystitis.

Nine cases of interstitial cystitis treated by intestinocystoplasty are reviewed. The longest follow-up is seventy-eight months. Two patients have since died of unrelated causes. The results reveal seven symptomatic cures and two failures. Long-term renal and vesical function have been well maintained.

Adult↗
PubMed1994

Is interstitial cystitis an infectious disease?

Interstitial cystitis (IC) is manifest by years of urinary frequency, urgency, and bladder pain and on cystoscopy, is diagnosed by petechial hemorrhages or ulcers. The etiology is unknown; the prominent theories are that IC is an autoimmune disease or is linked to increased permeability of the bladder mucosa. Although sought, no infectious agent has ever been identified. The disease has many characteristics of a chronic infection and the author's opinion is that an infectious disease has not been properly ruled out. To do so would require culture of bladder epithelium (not just urine) using special culture and non-culture techniques such as polymerase chain reaction. Infection can easily be integrated into the autoimmune and permeability theories of IC pathogenesis. A possible analogue for this disease is chronic gastritis in which Helicobacter pylori has been identified as an etiological agent.

Bacteria↗
PubMed1989

The enigma of interstitial cystitis--an autoimmune disease?

Interstitial cystitis (IC) is characterised by recurrent inflammation and destruction of bladder tissue without obvious cause. To determine whether this self-perpetuating disease is the result of an autoimmune disorder, we studied 26 patients with IC of mean duration 5 years and compared the results with those of a control group of similar age and sex with other urological complaints. We performed a standard autoimmune profile and looked for specific antibodies to normal human bladder in the serum, using an indirect immunofluorescence technique. Deep bladder biopsies were examined by conventional histology and cryostat sections were studied with peroxidase-conjugated anti-human antibodies in a search for immunoglobulin deposition within the bladder. Seventeen of 26 patients with IC (65%) and 5 of 14 controls (36%) demonstrated non-organ-specific antibodies; 40% of those with IC had anti-nuclear antibodies; 18 IC patients (75%) and 4 of 10 controls (40%) had anti-bladder antibodies present in the serum, but 5 healthy volunteers showed no such antibody activity. There was no statistically significant difference between the two groups for either type of antibody (Fisher's exact test). Only 5 of 17 patients with IC (29%) showed immunoglobulin deposition in the bladder epithelium, a similar proportion to controls (38%); 4 of these 5 had circulating anti-bladder antibodies present in the serum. Although IC patients demonstrated a non-specific increase in antibody formation, this was not significantly different from a similar group of other urological patients. The lack of specificity makes this immunological response more likely to be a secondary phenomenon associated with inflammatory damage to the bladder rather than the primary cause of the disease.

Adult↗
PubMed2002

Complementary and alternative therapies as treatment approaches for interstitial cystitis.

The management of interstitial cystitis (IC) is predominantly the reduction of the symptoms of frequency, urgency, and pain. Multimodal treatment approaches for IC are helpful in customizing therapy for individual patients. Complementary and alternative therapies are a quintessential addition to the therapeutic armamentarium and frequently include dietary modification, nutraceuticals, bladder training, neuromodulation, stress reduction, and sex therapy. Dietary modification involves elimination of bladder irritants, fluid regulation, and a bowel regimen. Nutraceuticals studied for the treatment of IC include calcium glycerophosphate, L-arginine, mucopolysaccharides, bioflavinoids, and Chinese herbs. Bladder training is effective after pain reduction. The neuromodulation of high-tone pelvic-floor muscle dysfunction is achieved with physical therapy and acupuncture. Stress reduction and sex therapy are best administered by a qualified stress manager and sex therapist. Multimodal, nonconventional management may add efficacy to the treatment of IC.

Journal Article↗
PubMed1994

Laser therapy for interstitial cystitis.

Laser treatment for interstitial cystitis patients should be limited to those who are positively diagnosed and have failed more conservative forms of therapy. The results are not as beneficial for patients with intractable pain but show only signs of glomerulation. When the laser is used within the proper power settings and the amount of energy applied during any one operative procedure is limited, the treatment is safe and can be very beneficial.

Cystitis↗
PubMed1994

The etiology of interstitial cystitis.

The cause of interstitial cystitis remains unknown. Potential causes including infection, vascular alterations, psychological aberrations, bladder surface alterations, toxic agents, neurologic disorders, and autoimmune responses have been investigated. To date, no compelling evidence for any hypothesized cause is available. Recently, several animal models have been described that may provide a basis for fundamental biologic studies that may aid in answering this important question.

Animals↗
PubMed1992

Tamm-Horsfall protein as a marker in interstitial cystitis.

It has been suggested that immunohistochemical staining for Tamm-Horsfall protein in bladder epithelium may be a marker for interstitial cystitis. Of bladder biopsies from 14 interstitial cystitis patients only 3 demonstrated positive staining for Tamm-Horsfall protein within the mucosa, whereas 2 of 11 control biopsies showed positive Tamm-Horsfall protein results. In addition, staining in 4 ureteral specimens from interstitial cystitis patients and 4 controls was negative in all cases. An effort to detect this protein in enterocystoplasty specimens also showed a negative pattern. Our study does not confirm the Tamm-Horsfall protein as permeating either the bladder epithelium in interstitial cystitis or bowel mucosa in enterocystoplasty. This finding does not necessarily mean that these surfaces are not permeable to substances of smaller molecular size, nor does it define whether this is of importance in the etiology of interstitial cystitis. However, it does suggest that this technique does not allow detection of a marker for the disease.

Adult↗
PubMed1977

Inflammatory carcinoma of the bladder and interstitial cystitis.

Two patients were treated for interstitial cystitis after having had bladder biopsies that did not reveal tumor. However, in both cases an aggressive carcinoma of the bladder later proved to be present when simple cystectomy for the "benign" disease was done. The masquerade of carcinoma of the bladder as interstitial cystitis and the pitfalls inherent in making the correct diagnosis are emphasized. The possibility of underlying bladder carcinoma should be excluded in any patient who presents with symptoms of chronic cystitis. Urinary cytology is most helpful but repeated bladder biopsy with careful serial sectioning may be necessary to establish the diagnosis of malignancy. It is not known whether the carcinomas were primary or secondary developments in our cases. The term inflammatory carcinoma of the bladder is proposed to call the attention of clinicians and pathologists to this lethal imitator.

Adult↗
PubMed1989

Scanning electron microscopic findings in interstitial cystitis.

Scanning electron microscopy (SEM) was performed on transurethral resection biopsies from 13 patients with classic interstitial cystitis. Biopsies from 9 patients with stress incontinence served as controls. The SEM appearance of the bladder surface in interstitial cystitis varied considerably, exhibiting small round and large polygonal cells. The proportion of cells displaying round uniform and pleomorphic microvilli was high and sometimes dominated the area examined. SEM characteristics earlier assigned to bladder tumours were detected in patients with interstitial cystitis and, at a lower frequency, also in control patients. The mucin layer covering the urothelial cells seemed reduced in interstitial cystitis compared with control specimens. Surface characteristics specific for interstitial cystitis were, however, not detected by SEM.

Adult↗
PubMed2004

Posterior tibial nerve stimulation in patients with intractable interstitial cystitis.

OBJECTIVE: To evaluate the efficacy of intermittent percutaneous posterior tibial nerve stimulation (PPTNS) in patients with refractory interstitial cystitis. PATIENTS AND METHODS: One man and 13 women (mean age 58.3 years) with suprapubic or perineal pain were enrolled in a prospective open study, in which they had 10 weekly sessions of PPTNS. Their mean duration of symptoms was 8.3 years. All patients were previously diagnosed as having interstitial cystitis according to the National Institute of Diabetes and Digestive and Kidney Diseases criteria. The response to the treatment were assessed using voiding diary, visual analogue scale diary for a pain index, and the Interstitial Cystitis Problem Index (ICPI), O'Leary/Sant Interstitial Cystitis Symptom Index (ICSI) and the 36-item short-form health survey (SF-36) quality-of-life questionnaire. RESULTS: Of the 14 patients, 13 completed the 10 weeks of treatment with no complications; 12 continued treatment for a short period after the study. There were no statistically significant changes in pain scores, voiding frequency and volumes, or in the ICPI, ICSI and SF-36 scores. However, there was an improvement in some patients, with one having complete resolution of the pain. CONCLUSION: Intermittent PPTNS in patients with refractory interstitial cystitis has no significant clinical effect over 10 weeks of treatment.

Adult↗
PubMed2006

Interleukin-6, histamine, and methylhistamine as diagnostic markers for interstitial cystitis.

OBJECTIVES: To examine the specificity and sensitivity of the inflammatory markers histamine, methylhistamine, and interleukin-6 (IL-6) in the urine of patients with interstitial cystitis compared with that in healthy controls. METHODS: A total of 40 women with interstitial cystitis and 29 healthy controls collected 24-hour urine samples. During the 24 hours before urine collection, all participants refrained from consuming foods and medications that could contain bioactive amines. Methylhistamine and histamine were measured using radioimmunoassay kits and were normalized to urinary creatinine levels; IL-6 was measured using enzyme-linked immunosorbent assay. The data were analyzed by t tests, logistic regression analysis, and receiver operating characteristics. RESULTS: IL-6 and histamine were significantly greater in the patients with interstitial cystitis than in the controls (P = 0.0003 and P = 0.038, respectively). The methylhistamine levels were also greater in the patients with interstitial cystitis than in the controls, but the results did not reach significance (P = 0.063). Using a combination of IL-6 and methylhistamine/creatinine, cutoff points were established. Using these cutoff points, the sensitivity was 70.0%, specificity 72.4%, positive predictive value 77.8%, and negative predictive value 63.6%. CONCLUSIONS: All three markers--histamine, methylhistamine, and IL-6--were greater in the patients with interstitial cystitis than in the controls. A combination of methylhistamine and IL-6 could be used as a sensitive and specific marker for interstitial cystitis.

Adult↗
PubMed1979

Interstitial cystitis.

Twenty histologically proven cases of interstitial cystitis were investigated in an attempt to find evidence of a possible autoimmune mechanism in its aetiology. HLA tissue typing was performed, autoantibody profiles were obtained, and a questionnaire of the patients' past history completed, especially with respect to other autoimmune conditions. An experiment was designed to test the effect of sodium cromoglycate on rat bladders. The results are discussed in relation to the management of patients with interstitial cystitis.

Aged↗