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PubMed2004

Transdermal posterior tibial nerve laser therapy is not effective in women with interstitial cystitis.

PURPOSE: Interstitial cystitis (IC) is a debilitating condition which causes irritative bladder symptoms, pain and a decrease in health status. The pathophysiology is poorly understood so therapeutic options are diverse. Percutaneous posterior tibial nerve stimulation is an effective treatment and pulsed transdermal laser stimulation is an established technique for pain management. We evaluated the efficacy of transdermal laser stimulation of the posterior tibial nerve for patients with IC. MATERIALS AND METHODS: Women meeting the National Institutes of Health National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC were prospectively recruited and randomized to treatment (29) or placebo (27) cohorts in a double-blind trial. At home the patient performed laser therapy daily for 30 seconds over the SP6 acupuncture point for 12 weeks. Measures at baseline and at 84-day followup included the 7-day voiding diary, the Interstitial Cystitis Problem Index, Interstitial Cystitis Symptom Index and RAND 36-Item Health Survey questionnaires. RESULTS: There were no significant differences between the treatment and control cohorts on any of the measures. However, there was a significant decrease between baseline and 12-week followup in the amount voided, symptom problems and severity, and on all 8 SF-36 scales. There was no significant effect of fluid intake. CONCLUSIONS: This study demonstrated no difference between the active and sham device. However, it is interesting that treatment and control cohorts experienced similar improvements, suggesting that the control cohort improvements may have been due to participants' belief that they were receiving active treatment from the stimulator. These findings provide support for investigating placebo effects in randomized trials.

Cystitis, Interstitial↗
PubMed2004

[Epidural spinal cord stimulation for interstitial cystitis].

INTRODUCTION: Interstitial cystitis, a chronic inflammatory disorder of the bladder wall, is highly painful and incapacitating. Urinary frequency and urgency develop, as well as nocturia, dysuria, perineal pain and reduction of bladder capacity. The condition seems to arise from a variety of factors with multiple and diverse pathogenic mechanisms and is refractory to medical and surgical treatment. Because treatments are ineffective and recent studies have implicated an inflammatory neurogenic mechanism in the pathogenesis of interstitial cystitis, neuromodulation by epidural spinal cord stimulation has been suggested for treating patients in whom other measures have failed. CASE DESCRIPTION: A 66-year-old woman with a 9-year history of urinary incontinence, urinary urgency and suprapubic pain was diagnosed of interstitial cystitis. She was referred to our pain clinic with persistent symptoms after repeated attempts to treat the condition medically. After implantation of a cephalocaudal (retrograde) epidural spinal cord stimulator, pain decreased 80% and the improvement has been maintained with no complications. CONCLUSION: Results from this and previous reports allow us to state that retrograde epidural spinal cord stimulation seems to be a relatively non-invasive therapeutic approach for treating interstitial cystitis that is refractory to conventional treatments.

Aged↗
PubMed2002

Long-term results of trigone-preserving orthotopic substitution enterocystoplasty for interstitial cystitis.

PURPOSE: Interstitial cystitis is a chronic debilitating condition mainly affecting women. Conservative treatment often produces unsatisfactory results and the identification of the best surgical treatment modality is difficult. We evaluate retrospectively the long-term results of trigone-preserving cystectomy followed by orthotopic substitution enteroplasty for women suffering from interstitial cystitis. MATERIALS AND METHODS: The study comprised 18 women with a mean age of 55.9 years. All surgical interventions were performed by 1 surgeon. All patients completed a voiding log and were interviewed about symptoms. Renal ultrasonography was done to evaluate the upper urinary tract. Followup data also comprised blood chemistry studies, including vitamin B12 blood levels and blood gas analysis. Pain and lower urinary tract problems were measured using a validated self-assessment symptom index. RESULTS: Ileocoecal augmentation was performed in 10 women and ileal substitute was done in 8. After a mean followup of 57 months 14 patients are completely pain-free, 12 void spontaneously and 15 report complete resolution of dysuria. Three patients perform intermittent self-catheterization and 1 woman prefers a suprapubic catheter for control of urinary hypercontinence. These 4 patients underwent ileoplasty. Surgery failed to relieve symptoms in 2 of the 18 patients. Surgery achieved a statistically highly significant improvement of diurnal and nocturnal voiding frequencies, functional bladder capacity and symptom index score. CONCLUSIONS: Substitution enterocystoplasty is a valuable and safe therapeutic option for patients with intractable interstitial cystitis resistant to conservative therapy. In our series use of the ileocecal bowel segment showed better functional results.

Adult↗
PubMed2000

Supratrigonal cystectomy and ileocystoplasty in management of interstitial cystitis.

BACKGROUND: Interstitial cystitis is a chronic non-infectious inflammatory disease of the bladder of unknown aetiology which is characterized by irritative voiding symptoms and suprapubic pain related to bladder filling. Surgical treatment is indicated in severely symptomatic patients when medical therapies have failed, usually after a period of several years. The authors' experience with a modified technique of ileocystoplasty following supratrigonal cystectomy performed in five patients with interstitial cystitis is presented here. METHODS: A modified technique of bladder augmentation using ileum following supratrigonal bladder resection is described. RESULTS: All patients experienced relief from their symptoms. No patient had residual bladder pain and urinary frequency settled down in all. Bladder capacity was increased significantly. Three patients voided spontaneously postoperatively and two required clean intermittent self-catheterization. CONCLUSIONS: Supratrigonal cystectomy and ileocystoplasty can be a satisfactory option in refractory cases of interstitial cystitis. A simplified technique of ileal bladder construction that provides satisfactory bladder capacity is presented. Most urologists are familiar with ileal surgery, having used the ileum as a conduit after cystectomy for urinary diversion.

Aged↗
PubMed2004

Prevalence of interstitial cystitis in first-degree relatives of patients with interstitial cystitis.

OBJECTIVES: To compare, in a pilot study, the prevalence of interstitial cystitis (IC) among first-degree relatives of patients with IC with the prevalence of IC in the general population. Often the first evidence that a disease may have a genetic susceptibility is the demonstration of family aggregation of the disease. METHODS: Members of the Interstitial Cystitis Association (ICA) were mailed a survey inquiring about the prevalence of the disease or consistent symptoms in first-degree family members (parents, siblings, and/or children). The same survey instrument was used in telephone interviews of a randomly selected sample of nonrespondents to determine the degree of responder bias. RESULTS: Of 2581 respondents to the mail-in survey, 101 (3.9%) reported 107 first-degree relatives with IC. The subsequent telephone interviews with 346 randomly selected nonrespondents revealed little selection bias in the mail-in survey. These measurements, plus data-based assumptions of proportions of those self-reporting IC who actually met the hydrodistension requirements for the diagnosis of IC, suggest that women, 31 to 73 years old who were first-degree relatives of patients with IC, themselves had a prevalence of IC of 995/100,000. A comparison of this with the number approximating the prevalence in the general population of American women of this age (60/100,000) indicates a risk ratio for IC in adult female first-degree relatives of 17. CONCLUSIONS: Adult female first-degree relatives of patients with IC may have a prevalence of IC 17 times that found in the general population. This, together with previously reported evidence showing a greater concordance of IC among monozygotic than dizygotic twins, suggests, but does not prove, a genetic susceptibility to IC.

Adult↗
PubMed2001

Current controversies that adversely affect interstitial cystitis patients.

Interstitial cystitis (IC) remains a diagnosis of exclusion, based on the symptoms of urinary urgency, frequency, and pelvic pain in the absence of other definable causes. Certain areas of controversy in the field of IC research have a significant adverse affect on patients. Many physicians still do not believe that IC exists, or else believe that it is a rare postmenopausal condition. This can cause significant delays in diagnosis and treatment. It is particularly problematic in children, whose symptoms are often diagnosed as "voiding dysfunction" and are thought to be self-limiting. It can also be problematic for men, who are often unsuccessfully treated for prostatitis over the course of many years, and for whom the diagnosis of IC is never entertained. In some cases, when no diagnosis is made, patients are left to live with severe, debilitating symptoms and have nowhere to turn for help. Resistance to treating severe nonmalignant pain with opioid medication further compounds this problem and has led to suicide in this patient population. The "gold standard" of cystoscopy with hydrodistention is now being questioned, and an overreliance on the potassium test, which has a high false-negative rate, may lead to significant underdiagnosis of IC. New urinary markers hold promise for both diagnostic as well as therapeutic potential, but are not yet commercially available. IC may be an organ-specific disease in some patients and a systemic condition in others. Many patients have multiple disorders and have no physician to manage their overall health. The Interstitial Cystitis Association believes that the best way to address these unresolved areas of knowledge is to: (1) educate patients on all available diagnostic and therapeutic options so that patients, with the help of their physicians, can make the best informed decisions possible, and (2) aggressively pursue all avenues of research, particularly epidemiology.

Age Factors↗
PubMed1999

Preliminary study on urinary cytokine levels in interstitial cystitis: does intravesical bacille Calmette-Guérin treat interstitial cystitis by altering the immune profile in the bladder?

OBJECTIVES: To obtain preliminary urinary cytokine data on subjects with active interstitial cystitis (IC), subjects with IC in remission after bacille Calmette-Guérin (BCG), and control (non-IC) subjects. IC is a severe, debilitating bladder disease of unknown etiology and no cure. In controlled clinical trials, intravesical BCG has been shown to be an effective and durable treatment for IC. The durability of this treatment led us to speculate on the mechanism by which intravesical BCG may treat IC. Evidence exists that IC may be mediated by an abnormal immune profile within the bladder. Intravesical BCG is known to stimulate the immune system of the bladder. METHODS: Fresh voided urine was collected from 15 subjects with active IC, 9 subjects with IC who received intravesical BCG and had been in remission for an average of 2.6 years, and 11 non-IC subjects. The urine was immediately centrifuged, aliquoted, and frozen in liquid nitrogen. At the time of urine collection, a validated IC questionnaire was completed. The enzyme-linked immunosorbent assay technique was used to determine levels of urinary cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor (TNF), human granulocyte-macrophage colony stimulating factor (hGM-CSF), IL-1beta, and interferon-gamma (IFN-gamma). RESULTS: Cytokines IL-4, IL-10, IL-12, TNF, hGM-CSF, IL-1beta, and IFN-gamma were not detected. Significant elevations in symptom scores and IL-2, IL-6, and IL-8 were found in the urine of subjects with active IC compared with subjects with IC in remission and control subjects. The urinary cytokine levels and symptom scores were identical in the IC group who had received BCG and the control group. CONCLUSIONS: Elevations in symptom scores and urinary cytokine levels were seen in subjects with active IC, suggesting an abnormal immune profile in this disease. Subjects with IC in remission after receiving BCG had identical cytokine levels and symptom scores as non-IC control subjects. Intravesical BCG may be effective in treating IC by correcting an aberrant immune imbalance in the bladder, leading to long-term symptomatic improvement. A prospective study is ongoing to further investigate the role of the immune system in IC.

Adjuvants, Immunologic↗
PubMed2003

Comparison of APF activity and epithelial growth factor levels in urine from Chinese, African-American, and white American patients with interstitial cystitis.

OBJECTIVES: Interstitial cystitis (IC) is a chronic bladder disorder for which the etiology is unknown. We have previously shown that antiproliferative factor (APF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and epidermal growth factor (EGF) are sensitive and specific biomarkers for IC in white American patients. Because little is known about the epidemiology of this disorder, it is unclear whether these factors would also be useful biomarkers for IC in patients from different racial groups and/or geographic locations. METHODS: Urine specimens were collected from Chinese, white American, and African-American women with IC and age and race-matched asymptomatic normal control women. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells in vitro. The HB-EGF and EGF urine levels were determined by enzyme-linked immunosorbent assay. RESULTS: The Chinese, African-American, and white American women with IC had significantly greater urine APF activity (P <0.000001, P = 0.0008, and P <0.000001, respectively), lower urine HB-EGF levels (P <0.000001, P = 0.02, and P <0.000001, respectively), and greater urine EGF levels (P <0.000001, P = 0.002, and P <0.000001, respectively), than their matched asymptomatic controls. CONCLUSIONS: These findings confirm the utility of APF, HB-EGF, and EGF as biomarkers for IC in patients from three different racial groups and two different countries.

Adult↗
PubMed1996

Carbachol-induced bladder mast cell activation: augmentation by estradiol and implications for interstitial cystitis.

OBJECTIVES: Interstitial cystitis (IC) is a painful, sterile bladder disorder that occurs primarily in women, many of whom also experience allergies with symptoms that worsen perimenstrually. Increased numbers of activated bladder mast cells have recently been implicated in the pathophysiology of IC. These mast cells express high-affinity estrogen receptors and are located close to increased bladder nerves, many of which contain the neuropeptide substance P (SP). We therefore investigated whether the neurotransmitter acetylcholine (ACh) and SP could activate bladder mast cells and whether estradiol could influence this effect. METHODS: Bladder pieces from male Sprague-Dawley rats were perfused with carbachol (the stable analogue of ACh), SP, or the mast cell secretagogue compound 48/80 (C48/80) with or without preincubation with beta-estradiol. The effect of carbachol was also investigated after pretreatment with the muscarinic antagonist atropine. Mast cell activation was assessed by release of 3H-serotonin and morphologic evidence of secretion by light and electron microscopy. RESULTS: Carbachol triggered rat bladder mast cell serotonin release in a dose-dependent manner, an effect increased by tissue pretreatment with estradiol and blocked by atropine. The effect of carbachol was accompanied by ultrastructural evidence of mast cell activation and was stronger than that obtained by either C48/ 80 or SP. CONCLUSIONS: Bladder mast cell activation is neurogenically mediated and augmented by estradiol, findings that could possibly explain the painful symptoms of IC and its prevalence in women, as well as the worsening of symptoms perimenstrually.

Acetylcholine↗
PubMed2003

Intercurrent autoimmune conditions in classic and non-ulcer interstitial cystitis.

OBJECTIVE: Interstitial cystitis (IC) is known to be one of the most bothersome conditions encountered in urological practice. It is frequently divided into two subtypes: classic and non-ulcer. Several authors have reported on autoantibodies in patients with IC and clinical and histopathological findings show similarities with those in some autoimmune disorders. Furthermore, IC has been shown to be associated with autoimmune diseases such as systemic lupus erythematosus, Sjögren's syndrome and autoimmune diseases of the thyroid gland. Our aim was to study the occurrence of associated autoimmune conditions in patients with IC diagnosed according to the National Institutes of Health/National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criteria. MATERIAL AND METHODS: Our sample of IC patients consisted of 129 with classic IC and 93 with non-ulcer IC. Clinical records, including micturition charts, were surveyed, and a more in-depth interview was obtained by means of a telephone call. Autoimmune disorders, diagnosed by Swedish clinicians according to acknowledged diagnostic criteria, were registered. RESULTS: Allergy was the most common IC-associated condition, 41% of all patients with classic IC and 47% of all patients with non-ulcer IC having some type or degree of hypersensitivity/allergy. Rheumatoid arthritis occurred in 13% of patients with classic IC and in 4% with non-ulcer IC. Inflammatory bowel disease was not diagnosed in any of the patients with non-ulcer IC whereas 2.3% of the patients with classic IC had either ulcerative colitis or Crohn's disease, approximately 33 times the prevalence seen in the general population. CONCLUSION: It appears that systemic and autoimmune disorders are more prevalent in the IC population than in the general population.

Adult↗
PubMed2004

Intravesical nitric oxide production discriminates between classic and nonulcer interstitial cystitis.

PURPOSE: Interstitial cystitis (IC) is one of the most bothersome conditions in urological practice. There are 2 subtypes, classic and nonulcer IC, with similar symptoms but different outcomes with respect to clinical course and response to treatment. Histologically there are fundamental differences between the 2 subtypes, classic IC presenting a severe abnormality of the urothelium and characteristic inflammatory cell infiltrates while inflammation is scant in nonulcer IC. Regulation of urinary nitric oxide synthase activity has been proposed to be of importance for immunological responses in IC. We present evidence of a profound difference between the 2 subtypes concerning nitric oxide production, mirroring the differences in inflammatory response in IC. MATERIALS AND METHODS: A total of 17 patients with both subtypes and active disease as well as patients with disease in remission were included in the study, all diagnosed according to National Institute for Diabetes and Digestive and Kidney Diseases criteria. Luminal nitric oxide was measured in the bladder of patients using a chemiluminescence nitric oxide analyzer. RESULTS: All patients with classic IC had high levels of NO. None of the other patients had any significant increase in NO levels in the bladder. The NO level in patients with classic IC was not related to symptoms but rather to the assignment to this specific subgroup of IC. The highest levels of NO were found in patients in the initial phase of classic IC. CONCLUSIONS: The difference in NO evaporation between classic and nonulcer IC allows for subtyping of cases meeting National Institute for Diabetes and Digestive and Kidney Diseases criteria without performing cystoscopy. The findings in the present series together with previous findings clearly demonstrate that the 2 subtypes of IC represent separate entities. This separation further emphasizes the need to subtype all cases included in all scientific matters, ensuring that the 2 subtypes are evaluated separately in clinical studies.

Adult↗
PubMed2004

Urinary conduit formation using a retubularized bowel from continent urinary diversion or intestinal augmentations: ii. Does it have a role in patients with interstitial cystitis?

PURPOSE: Interstitial cystitis (IC) may require surgical treatment in a minority of patients in whom conservative treatment failed. This treatment includes enterocystoplasty (ECP), or continent or incontinent urinary diversion with or without cystourethrectomy. Patients with IC who underwent ECP or continent urinary diversion (CUD) occasionally have recurrent pain in the augmented bladder or continent pouch. In these patients a new ileal conduit is frequently constructed. Using part of the continent urinary diversion or bladder augmentation patch to make the ileal conduit has been reported. However, there may be some concern with performing the procedure in patients with IC because of the theoretical risk of continued pain in the converted ileal segment. We evaluated the role of conduit formation using retubularized bowel from ECP or CUD in patients with IC. MATERIALS AND METHODS: A total of 11 patients with a mean age of 45 years underwent conduit formation using the augmentation patch of ECP or part of the continent urinary reservoir. Patients were followed by history, physical examination, laboratory tests and urography. RESULTS: Followup was 20 to 80 months. One patient continued to have pelvic pain. None of the patients had residual pain in the conduit. One patient had intermittent pain in the conduit 32 months after conversion. Two patients had ureteral obstruction requiring ureteral reimplantation revision. No patient complained of new gastrointestinal problems. CONCLUSIONS: Retubularization of a previously used bowel segment from ECP or CUD to form a urinary conduit seems to be an acceptable alternative in patients with IC.

Cystitis, Interstitial↗
PubMed2006

EGF and HB-EGF modulate inward potassium current in human bladder urothelial cells from normal and interstitial cystitis patients.

Interstitial cystitis (IC) is an idiopathic condition characterized by bladder hyperalgesia. Studies have shown cytokine and purinergic signaling abnormalities in cultured bladder urothelial cells (BUC) from IC patients. We performed single-cell electrophysiological studies in both normal and IC BUC. A strongly inward rectifying potassium current with conductance of the Kir2.1 channel was identified in normal BUC. This current was significantly reduced in IC BUC. Kir2.1 protein and mRNA were detected in both IC and normal BUC. Epidermal growth factor (EGF) caused a dose-dependent decrease in the inward potassium current in normal BUC. EGF is secreted in higher amounts by IC BUC and is known to decrease Kir2.1 conductance by phosphorylation of Kir2.1. Genistein, a nonspecific phosphorylation inhibitor, increased the inward potassium current in IC BUC and blocked the effect of EGF on normal BUC. Treatment of IC BUC with heparin-binding epidermal growth factor-like growth factor (HB-EGF), previously shown to be secreted in lower amounts by IC BUC, significantly increased inward potassium current. These data show that the inward potassium current in BUC can be modulated by EGF and HB-EGF. Changes in BUC membrane potassium conductance caused by altered levels of EGF and HB-EGF may therefore play a role in the pathophysiology of IC.

Cells, Cultured↗
PubMed2005

APF, HB-EGF, and EGF biomarkers in patients with ulcerative vs. non-ulcerative interstitial cystitis.

BACKGROUND: Interstitial cystitis (IC) is a chronic bladder disorder, with symptoms including pelvic and or perineal pain, urinary frequency, and urgency. The etiology of IC is unknown, but sensitive and specific biomarkers have been described, including antiproliferative factor (APF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and epidermal growth factor (EGF). However, the relative sensitivity of these biomarkers in ulcerative vs. nonulcerative IC is unknown, and these markers have yet to be validated in another laboratory. We therefore measured these markers in urine from patients with or without Hunner's ulcer, as well as normal controls, patients with bladder cancer, and patients with bacterial cystitis, at the First Hospital of China Medical University. METHODS: Urine specimens were collected from two groups of Chinese IC patients (38 IC patients with Hunner's ulcers, 26 IC patients without Hunner's ulcers), 30 normal controls, 10 bacterial cystitis patients and 10 bladder cancer patients. APF activity was determined by measuring 3H-thymidine incorporation in vitro, and HB-EGF and EGF levels were determined by ELISA. RESULTS: APF activity (inhibition of thymidine incorporation) was significantly greater in all IC patient urine specimens than in normal control specimens or in specimens from patients with bacterial cystitis or bladder cancer (p < 0.0001 for each comparison). Urine HB-EGF levels were also significantly lower and EGF levels significantly higher in both groups of IC patients than in the three control groups (p < 0.0001 for each comparison). Although APF and HB-EGF levels were similar in ulcerative and nonulcerative IC patients, EGF levels were significantly higher in IC patients with vs. without ulcers (p < 0.004). CONCLUSION: These findings indicate that APF, HB-EGF and EGF are good biomarkers for both ulcerative and nonulcerative IC and validate their measurement as biomarkers for IC in Chinese patients.

Adult↗