INCREASED URINARY LEUKOTRIENE E4 AND EOSINOPHIL PROTEIN X EXCRETION IN PATIENTS WITH INTERSTITIAL CYSTITIS

PURPOSE: The role of cysteinyl containing leukotriene C4, D4 and E4, and eosinophil protein X in interstitial cystitis is unknown. Leukotriene E4, the end product of cysteinyl containing leukotrienes, and eosinophil protein X are markers of the activation of mast cells and eosinophils, respectively. Cysteinyl containing leukotrienes are potent and specific chemoattractants for eosinophils. We compared the urinary excretion of leukotriene E4 and eosinophil protein X in patients with interstitial cystitis and in healthy controls. MATERIALS AND METHODS: Morning spot urine samples from nine patients with interstitial cystitis who fulfilled National Institute of Diabetes and Digestive and Kidney Diseases criteria were collected on the day of cystoscopy with biopsies. Aliquots of urine specimens were immediately centrifuged and the supernatants were stored at -80C until use. Urine samples from 9 healthy women served as controls. Urinary leukotriene E4 and eosinophil protein X were measured by enzyme immunoassay and radioimmunoassay, respectively. All determinations were performed in duplicate and normalized to urine creatinine. RESULTS: Leukotriene E4 and eosinophil protein X were significantly increased in the morning urine of patients with interstitial cystitis compared with controls. The mean urinary excretion of leukotriene E4 plus or minus standard deviation was 148.8 +/- 62.5 and 62.2 +/- 17.5 ng./mmol. creatinine in patients and controls (p = 0.003), while the mean urinary excretion of eosinophil protein X was 109.7 +/- 70.4 and 43.7 +/- 22.0 microg./mmol. creatinine, respectively (p = 0.01). All urine cultures were negative. The mean mast cell count in detrusor biopsies in the interstitial cystitis group was 41 cells per mm.2 (range 5 to 84). Eosinophilic granulocytes were occasionally observed in the submucosa but not in the detrusor. CONCLUSIONS: Our study shows that patients with interstitial cystitis and detrusor mastocytosis have increased urinary leukotriene E4 and eosinophil protein X. It is possible that cysteinyl containing leukotrienes and eosinophil protein X are involved in the pathogenesis of interstitial cystitis. Urinary leukotriene E4 and eosinophil protein X may be useful markers for assessing the grade of activation of mast cells and eosinophils in patients with interstitial cystitis and/or for confirming the diagnosis. However, it remains to be investigated whether the increase in urinary leukotriene E4 and eosinophil protein X correlates with interstitial cystitis symptoms.     

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.     

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.     

Clinical guidelines for interstitial cystitis/bladder pain syndrome

The clinical guidelines for interstitial cystitis and related symptomatic conditions were revised by updating our previous guidelines. The current guidelines define interstitial cystitis/bladder pain syndrome as a condition with chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by other urinary symptoms, such as persistent urge to void or urinary frequency in the absence of confusable diseases. The characteristic symptom complex is collectively referred as hypersensitive bladder symptoms. Interstitial cystitis/bladder pain syndrome is divided into Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis and bladder pain syndrome represent interstitial cystitis/bladder pain syndrome with Hunner lesions and interstitial cystitis/bladder pain syndrome without Hunner lesions, respectively. So-called non-Hunner-type interstitial cystitis featured by glomerulations or bladder bleeding after distension is included in bladder pain syndrome. The symptoms are virtually indistinguishable between Hunner-type interstitial cystitis and bladder pain syndrome; however, Hunner-type interstitial cystitis and bladder pain syndrome should be considered as a separate entity of disorder. Histopathology totally differs between Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis is associated with severe inflammation of the urinary bladder accompanied by lymphoplasmacytic infiltration and urothelial denudation, whereas bladder pain syndrome shows little pathological changes in the bladder. Pathophysiology would also differ between Hunner-type interstitial cystitis and bladder pain syndrome, involving interaction of multiple factors, such as inflammation, autoimmunity, infection, exogenous substances, urothelial dysfunction, neural hyperactivity and extrabladder disorders. The patients should be treated differently based on the diagnosis of Hunner-type interstitial cystitis or bladder pain syndrome, which requires cystoscopy to determine the presence or absence Hunner lesions. Clinical studies are to be designed to analyze outcomes separately for Hunner-type interstitial cystitis and bladder pain syndrome.     

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.     

Uronate peaks and urinary hyaluronic acid levels correlate with interstitial cystitis severity

PURPOSE: Levels of uronate, a basic component of urothelial glycosaminoglycans, are increased in urine specimens of patients with interstitial cystitis with severe symptoms. In this study we examined the urinary glycosaminoglycan profile and correlated the profile and urinary hyaluronic acid (a glycosaminoglycan) levels with symptom severity. MATERIALS AND METHODS: Urine specimens and completed O'Leary-Sant interstitial cystitis symptom and problem indexes questionnaires were obtained from 29 patients with interstitial cystitis, 14 normal individuals, and 14 patients with other benign pelvic and bladder conditions. Patients with interstitial cystitis were divided into group 1-1 or both indexes less than 50% maximum score, and group 2-both indexes 50% of maximum score or greater. All patients met the National Institutes of Diabetes and Digestive and Kidney Diseases criteria except regarding glomerulation. In a followup study 30 urine specimens were collected from 8 patients with interstitial cystitis and from 4 normal individuals during 12 months. The urinary glycosaminoglycan profile was determined by gel filtration chromatography. Glycosaminoglycan peaks were analyzed by polyacrylamide gel electrophoresis. Urinary hyaluronic acid levels were determined by the hyaluronic acid test. RESULTS: Group 2 urine specimens contained 3 uronate peaks, whereas urine specimens from normal individuals and patients in group 1 contained 1 or 2 peaks. Peak 1 consisted of macromolecular glycosaminoglycans whereas peaks 2 and 3 contained oligosaccharides. Urinary hyaluronic acid levels were 3 to 4-fold increased in group 2. Glycosaminoglycan profile and hyaluronic acid levels detected interstitial cystitis severity with 83% sensitivity, and 89.7% and 74.4% specificity, respectively. Interstitial cystitis urothelial cells/tissues also over expressed hyaluronic acid synthase 1 (which synthesizes hyaluronic acid) compared to normal urothelial cells/tissues. In the followup study urinary uronate levels, glycosaminoglycan profile and hyaluronic acid levels detected patients with severe symptoms with 73% sensitivity and 87% to 94% specificity. In both studies uronate, glycosaminoglycan profile and hyaluronic acid levels significantly correlated with interstitial cystitis severity (p <0.001). CONCLUSIONS: Urinary glycosaminoglycan profile, uronate content and hyaluronic acid levels are potentially useful markers for monitoring interstitial cystitis severity, and are likely to be involved in interstitial cystitis pathophysiology.     

ACTIVATION OF THE KALLIKREIN KININ SYSTEM IN INTERSTITIAL CYSTITIS

PURPOSE: We investigated whether the kallikrein kinin system is activated in interstitial cystitis by measuring urinary excretion rates of kinin peptides, active and total kallikrein, and the kininase neutral endopeptidase in women with interstitial cystitis. We compared these excretion rates to a control group of women with stress incontinence and normal bladder function. MATERIALS AND METHODS: Catheter urine was collected from subjects during a water diuresis (approximately 10 ml. per minute) before and after distention of the bladder with 100 ml. water. The contribution of the bladder wall to urinary kinins was assessed by measuring the change in kinin levels after 2 minutes of bladder stasis before and after distention. RESULTS: Absolute bradykinin and kallidin excretion rates were similar in women with interstitial cystitis and control subjects. Two minutes of bladder stasis after bladder distention increased urinary bradykinin (p = 0.02) but not kallidin excretion rates. Active and total kallikrein excretion rates were similar in patients with interstitial cystitis and control subjects. Neutral endopeptidase excretion rates were reduced in the initial urine collection from subjects with interstitial cystitis but were similar in both groups during later collection periods. CONCLUSIONS: These data provide evidence for increased bradykinin levels in the bladder wall of subjects with interstitial cystitis, which may be due in part to reduced neutral endopeptidase levels. These increased bradykinin levels may participate in the pathogenesis and symptomatology of interstitial cystitis.     

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 -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 -arginine in patients with interstitial cystitis and to study the effects of -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 -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 -arginine (189 ± 72 ppb). There was no significant change in the symptom scores at either dose after 5 weeks of -arginine treatment.Conclusions. -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.     

Hyaluronic Acid: An Effective Alternative Treatment of Interstitial Cystitis,Recurrent Urinary Tract Infections,and Hemorrhagic Cystitis?

OBJECTIVES: Hyaluronic acid is a protective barrier of the urothelium. A damaged glycosaminoglycan layer may increase the possibility of bacterial adherence and infection. This damage is proposed to be a causative factor in the development of interstitial cystitis, common urinary tract infections, and hemorrhagic cystitis due to posthematopoietic stem cell transplantation. The aim of this article was to review the available data regarding the use of hyaluronic acid as an alternative treatment of the above-mentioned conditions. METHODS: Articles relevant to our review that were archived by September 2006 were retrieved from PubMed. RESULTS: Nine relevant studies were identified and evaluated. Hyaluronic acid was administered intravesically at a dose of 40 mg every week for 4-6 wk; patients with noted improvement received two additional monthly doses. Short-term responses of patients with interstitial cystitis, hemorrhagic cystitis, and recurrent urinary tract infections were 30-73% (7 studies), 71% (1 study), and 100% (1 study), respectively. The treatment was well tolerated except for occasional development of bacterial cystitis. The cost of each intravesical installation of hyaluronic acid is 120 UK pounds (excluding the cost of the urinary catheterization). CONCLUSIONS: The available clinical data regarding the effectiveness of hyaluronic acid as a potential treatment of patients with interstitial cystitis, recurrent urinary tract infections, and hemorrhagic cystitis are limited. There is need for randomized controlled trials for further investigation of this important therapeutics question; these clinical trials should be disease-specific, blinded, and controlled, and of a sufficient number of patients. Until such studies are available, intravesical instillation of hyaluronic acid cannot be unquestionably endorsed for use for the aforementioned diseases.     

Bladder epithelial cells from patients with interstitial cystitis produce an inhibitor of heparin-binding epidermal growth factor-like growth factor production

PURPOSE: The etiology of interstitial cystitis is unknown. We previously identified an interstitial cystitis urine factor, antiproliferative factor, that inhibits proliferation of bladder epithelial cells in vitro and complex changes in epithelial growth factor levels, including profound decreases in heparin-binding epidermal growth factor-like growth factor (HB-EGF). Bladder and renal pelvic catheterization of patients with interstitial cystitis indicated that the antiproliferative factor is made and/or activated in the distal ureter or bladder. Therefore, we determined whether bladder epithelial cells from interstitial cystitis cases produced the antiproliferative factor and whether purified antiproliferative factor could alter production of growth factors known to be abnormal in interstitial cystitis. MATERIALS AND METHODS: Antiproliferative factor activity was determined by 3H-thymidine incorporation into primary bladder epithelial cells. The antiproliferative factor was purified by size fractionation followed by sequential chromatography involving ion exchange, hydrophobic interaction and high performance liquid chromatography. HB-EGF, epidermal growth factor, insulin-like growth factor and insulin-like growth factor binding protein 3 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Bladder epithelial cells from patients with interstitial cystitis produced a single antiproliferative factor with the same purification profile as that purified from interstitial cystitis urine. Purified antiproliferative factor specifically inhibited HB-EGF production by bladder epithelial cells in vitro, and the effect of interstitial cystitis urine or purified antiproliferative factor on bladder cell proliferation was inhibited by recombinant human HB-EGF in a dose dependent manner. Similar to urine HB-EGF, serum HB-EGF was also significantly lower in interstitial cystitis cases than in controls. CONCLUSIONS: Bladder epithelial abnormalities in interstitial cystitis may be caused by a negative autocrine growth factor that inhibits cell proliferation by down-regulating HB-EGF production. Furthermore, decreased levels of urine and serum HB-EGF indicate that interstitial cystitis may be a urinary tract manifestation of a systemic disorder.     

Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: a systematic review

PURPOSE: In women symptoms of interstitial cystitis are difficult to distinguish from those of painful bladder syndrome and they appear to overlap with those of urinary tract infection, chronic urethral syndrome, overactive bladder, vulvodynia and endometriosis. This has led to difficulties in formulating a case definition for interstitial cystitis, and complications in the treatment and evaluation of its impact on the lives of women. We performed a systematic literature review to determine how best to distinguish interstitial cystitis from related conditions. MATERIALS AND METHODS: We performed comprehensive literature searches using the terms diagnosis, and each of interstitial cystitis, painful bladder syndrome, urinary tract infection, overactive bladder, chronic urethral syndrome, vulvodynia and endometriosis. RESULTS: Of 2,680 screened titles 604 articles were read in full. The most commonly reported interstitial cystitis symptoms were bladder/pelvic pain, urgency, frequency and nocturia. Interstitial cystitis and painful bladder syndrome share the same cluster of symptoms. Chronic urethral syndrome is an outdated term. Self-reports regarding symptoms and effective antibiotic use can distinguish recurrent urinary tract infections from interstitial cystitis in some but not all women. Urine cultures may also be necessary. Pain distinguishes interstitial cystitis from overactive bladder and vulvar pain may distinguish vulvodynia from interstitial cystitis. Dysmenorrhea distinguishes endometriosis from interstitial cystitis, although many women have endometriosis plus interstitial cystitis. CONCLUSIONS: In terms of symptoms interstitial cystitis and painful bladder syndrome may be the same entity. Recurrent urinary tract infections may be distinguished from interstitial cystitis and painful bladder syndrome via a combination of self-report and urine culture information. Interstitial cystitis and painful bladder syndrome may be distinguished from overactive bladder, vulvodynia and endometriosis, although identifying interstitial cystitis and painful bladder syndrome in women with more than 1 of these diseases may be difficult.     

The use of dimethyl sulfoxide in the treatment of intractable urinary frequency

Intravesical instillation of dimethyl sulfoxide (DMSO) was used in the treatment of patients with intractable urinary frequency due to chronic prostatitis, chronic cystitis, tuberculous contracted bladder and interstitial cystitis. Before the application of this therapy, all 4 patients were examined carefully to rule out cases of acute infectious diseases of the urinary tract, active urinary tuberculosis, neurogenic bladder and carcinoma in situ of the bladder. Three of the four patients achieved an excellent response both subjectively and objectively. In the United States, intravesical instillation of DMSO had already been established as the specific method in the treatment of interstitial cystitis and no side effects have been reported so far. Therefore, we recommend the use of intravesical instillation of DMSO more commonly in various forms of intractable urinary frequency.     

Efficiency of questionnaires used to screen for interstitial cystitis

PURPOSE: Questionnaires for the evaluation of interstitial cystitis are widely used, but their value in discriminating interstitial cystitis from other diagnoses among patients with urological symptoms has not been determined. We assessed the validity of 2 frequently used interstitial cystitis questionnaires-the O'Leary-Sant Symptom Index and Problem Index and the Pain, Urgency, Frequency Symptom Scale-for screening for interstitial cystitis. MATERIALS AND METHODS: The Pain, Urgency, Frequency Symptom Scale and the O'Leary-Sant Symptom Index and Problem Index were administered to the same 220 patients at a urology clinic before diagnosis. Questionnaire scores between patients with and without interstitial cystitis, as well as among diagnostic groups, were compared by parametric and nonparametric analyses. Receiver operating characteristic curves were constructed to determine the efficiency of each questionnaire in discriminating between patients with and without interstitial cystitis. RESULTS: Interstitial cystitis was distinguishable from the other diagnoses using both questionnaires (p <0.001). Separate analyses of bother and symptom scores yielded similar results. Receiver operating characteristic curves demonstrated the Pain, Urgency, Frequency Symptom Scale to be more efficient than the O'Leary-Sant Symptom Index and Problem Index in detecting interstitial cystitis in this population with an optimal cutoff value of 13 or greater. CONCLUSIONS: While the Pain, Urgency, Frequency Symptom Scale and the O'Leary-Sant Symptom Index and Problem Index questionnaires distinguish interstitial cystitis from other urinary tract pathologies, neither questionnaire demonstrates sufficient specificity to serve as the sole diagnostic indicator. These questionnaires should not be used to define interstitial cystitis, but can be used to screen patients with urinary tract symptoms to identify those who should be further examined for interstitial cystitis or to follow those who have already been diagnosed.     

Pathophysiology of interstitial cystitis

Interstitial cystitis/bladder pain syndrome is a chronic pain syndrome whose causes remains elusive with no generally accepted treatment. A hallmark of functional pain syndromes such as interstitial cystitis/bladder pain syndrome is pain in the absence of demonstrable pathology of the viscera or associated nerves. Patients with chronic pain experience a greater impairment in quality of life than healthy controls. In addition, interstitial cystitis/bladder pain syndrome symptoms can frequently overlap with other conditions including irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, anxiety disorders, and a number of other syndromes not directly related to the urinary bladder. Because of the complex pathophysiology, a number of animal models have been studied over the years to better understand mechanisms underlying patient symptoms. These models can include: bladder centric, complex mechanisms and psychological and physical stress models. Such animal models can aid in the investigation of aspects of interstitial cystitis/bladder pain syndrome that cannot be pursued in humans as well as to develop and test potential therapies. In addition, the search for urinary factors that may be a cause of interstitial cystitis/bladder pain syndrome has resulted in the discovery of a number of potential targets that could serve as predictive biomarkers which can aid in early diagnosis and treatment of this chronic disorder.     

Diurnal cortisol variations and symptoms in patients with interstitial cystitis

PURPOSE: Little attention has focused on systemic factors that may allow a state of chronic bladder inflammation to be established and maintained in interstitial cystitis cases. Abnormalities of the hypothalamic-pituitary-adrenal feedback system result in poorer regulation of the inflammatory response and are present in many chronic inflammatory and pain conditions, of which some have high co-morbidity with interstitial cystitis. MATERIALS AND METHODS: A total of 48 patients with interstitial cystitis and 35 healthy, age matched controls collected 24-hour urine samples and 3 days of salivary samples at 7 to 8 a.m., 4 to 5 p.m. and 8 to 9 p.m. for cortisol analysis. In addition, they completed a concurrent symptom questionnaire. Prospective symptom diaries also were completed in the month before sampling. RESULTS: Mean urinary or salivary cortisol did not differ in patients and controls. However, patients with interstitial cystitis and higher morning cortisol had significantly less pain and urgency, while those with higher urinary free cortisol reported less overall symptomatology (p <0.05). Relationships with morning cortisol were also observed when controlling for co-morbid conditions known to be affected by the hypothalamic-pituitary-adrenal axis, such as fibromyalgia, chronic fatigue and rheumatoid arthritis. Patients with morning cortisol less than 12.5 nmol./l. were 12.8 times more likely to report high urinary urgency than those with values above this cutoff. CONCLUSIONS: These findings imply that regulation of the hypothalamic-pituitary-adrenal axis may be associated with interstitial cystitis symptomatology and there may be different diurnal hypothalamic-pituitary-adrenal patterns in patients with interstitial cystitis who do and do not have co-morbid conditions. These findings may have treatment implications for patients with interstitial cystitis who have early morning cortisol deficiencies.     

Sacral neuromodulation reprogramming: is it an office burden?

Our objective was to evaluate the burden of sacral neuromodulation (SNM) reprogramming and the reasons for reprogramming, and to correlate these with the underlying diagnosis. A retrospective review of 50 consecutive subjects implanted with SNM was completed from November 2002 through December 2005. Of the 50 SNM implants, 47 subjects had adequate follow-up. The mean age was 53.1 (22-90 years) with 83% women. Of the SNM performed, 91.5% were done for urinary urgency, frequency, or incontinence and 47.4% of those had interstitial cystitis. Overall, 239 programming visits were recorded, and subjects on average had two reprogramming visits per year. There was no correlation with number of reprogramming events and patient age, sex, reason for implantation, or diagnosis. These data suggest that the number of reprogramming episodes is small, and the majority is done as part of routine follow-up. No additional burden was seen in subjects with interstitial cystitis.     

A case of interstitial cystitis that developed alternately with bronchial asthma

The patient was a 46-year-old man. His chief complaints were urinary frequency and pain on urination. They first appeared one year earlier. The patient had had a history of bronchial asthma and urticaria. Vesical capacity decreased and vesico-cutaneous developed. The urine sediment contained eosinophils and vesico ureteral reflux was observed. The bladder tissues contained a moderate amount of eosinophils, lymphocytes and plasma cells. The total IgE was 360 IU/ml. The IgE RAST score and immediate reaction to the skin tests were all negative. The Arthus and delayed-type reaction skin tests were positive to various Eumycetees and foods. Provocation tests by eating foods such as eggs, meats, and shellfish reproduced the above-mentioned bladder disorders. The patient was therefore put on a diet that restricted the amount of animal protein consumed except for white meat fishes, and a mast cell membrane stabilizer was administered. The interstitial cystitis improved but the asthma aggravated. The cystitis was found to develop alternately with asthma.     

躯体功能及总体健康感在女性间质性膀胱炎治疗过程中的变化

目的探讨间质性膀胱炎（IC）治疗前后躯体功能（PF）及总体健康感（GH）的变化。方法2005年5月-2009年5年,依据症状及膀胱镜检查诊断间质性膀胱炎31例,其中23例符合美国国立糖尿病、消化病和。肾病研究所（NIDDK）的诊断标准。所有患者开始均口服阿米替林25mg,1次／d。治疗一周效果不佳者加服阿米替林至50mg／d,最大不超过100mg／d。对效果不佳或不能耐受阿米替林副作用的患者加用500g／L二甲基亚砜50mL膀胱灌注连续10次（其中4例用500g／L二甲基亚砜50mL＋10000u低分子肝素钠灌注）,总疗程3个月。观察指标：O’Leary间质性膀胱炎症状指数及问题指数、PF及GH。结果31例患者均完成治疗,25例患者取得良好的效果,6例患者效果较差。结论随着女性IC患者病情好转其躯体功能得到改善,患者的总体健康满意度提高。     

Intravesical bacillus Calmette-Guerin and dimethyl sulfoxide for treatment of classic and nonulcer interstitial cystitis: a prospective, randomized double-blind study

PURPOSE: We conducted a prospective, double-blind study with a crossover design of intravesical bacillus Calmette-Guerin (BCG) and dimethyl sulfoxide to determine whether patients with classic and nonulcer interstitial cystitis, respectively, might benefit from either regimen. MATERIALS AND METHODS: A total of 21 patients, including 11 with classic and 10 with nonulcer interstitial cystitis, randomly underwent treatments with intravesical BCG or dimethyl sulfoxide and, if not improved, were treated with the other substance after a washout period. All 21 patients were evaluated with symptom questionnaires, including a visual analog pain scale and voiding diaries. RESULTS: Regardless of regimen, there was no improvement in maximal functional capacity. There was a reduction in urinary frequency following dimethyl sulfoxide treatment but only in the classic subtype (p <0.05), whereas no reduction was seen following BCG in either subtype. A substantial pain decrease was noted in classic (p <0.05) as well as nonulcer (p <0.05) interstitial cystitis following dimethyl sulfoxide. CONCLUSIONS: Intravesical BCG has been presented as a promising new option for treatment of interstitial cystitis. We failed to demonstrate benefit from this treatment. Dimethyl sulfoxide had no positive effect on maximal functional capacity but resulted in a significant reduction in pain and urinary frequency, although only in patients with classic interstitial cystitis.     

上尿路梗阻与伴发慢性膀胱炎的相关性临床研究

目的：探讨上尿路梗阻与伴发慢性膀胱炎之间的相关性.方法：通过尿液细菌培养、膀胱镜和输尿管镜检查,对350例上尿路梗阻患者进行前瞻性研究.结果：350例上尿路梗阻中,75例（21.43%）伴发慢性膀胱炎;254例肾盂、输尿管结石性上尿路梗阻中,伴有慢性膀胱炎51例（20.08%）;96例其他原因上尿路梗阻中,伴有慢性膀胱炎24例（25.00%）（P＞0.05）.在75例慢性膀胱炎中,非细菌性膀胱炎58例（58/350,16.57%）,其中腺性膀胱炎38例（10.86%）,膀胱白斑病11例（3.14%）,增生性膀胱炎9例（2.57%）.58例上尿路梗阻伴发慢性非细菌性膀胱炎中,6例（10.34%）尿液细菌培养阳性;275例不伴有膀胱炎中,27例（9.82%）尿液细菌培养阳性（P＞O.05）.16例上尿路梗阻伴有慢性非细菌性膀胱炎患者获术后随访,其中10例膀胱病灶区炎症消失.但其他6例炎症仍较严重而需进一步治疗.结论：上尿路梗阻与伴发慢性膀胱炎之间具有相关性,长期上尿路梗阻可诱发慢性非细菌性膀胱炎的发生,其发病机制需进一步深入研究.