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PubMed2004

Interstitial cystitis: how should we diagnose it and treat it in 2004?

PURPOSE OF REVIEW: During the last 2 years, two international and two European meetings have taken place and a European Society formed dealing only with interstitial cystitis. A separate committee for interstitial cystitis was formed during the last WHO International Consensus Meeting on urinary incontinence. As a consequence, new concepts and recommendations are evolving, for example the nomenclature is changing from interstitial cystitis to painful bladder syndrome/interstitial cystitis. RECENT FINDINGS: At an international meeting in Kyoto, the scientific basis for diagnosis and treatment of painful bladder syndrome/interstitial cystitis was reviewed, confirming the poor evidence for many diagnostic procedures and treatments. There are two main reasons for this: an internationally accepted definition is lacking and the disease is rare, making clinical trials difficult. A meeting in Copenhagen resulted in a standardization of the procedures for evaluation and the creation of a European Society for the Study of Interstitial Cystitis. Increased concentration of nitric oxide in the urine of patients with Hunner's ulcer may help to separate ulcer from non-ulcer patients. A prospective, randomized, placebo-controlled multicenter study failed to show a statistically significant effect of the antihistamine hydroxine or pentosan polysulfate sodium compared with placebo. The study confirmed the difficulties in recruiting patients for large-scale trials, which could be one of the reasons for the negative result. The effect of the traditional treatment with amitriptyline was confirmed in a prospective, placebo-controlled study. SUMMARY: Standardized evaluation of patients with painful bladder syndrome/interstitial cystitis will benefit both patients and science. An internationally accepted definition of the condition appears to be in sight, which will make epidemiological and research studies easier.

Cystitis, Interstitial↗
PubMed2004

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

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

Chronic Disease↗
PubMed1987

Local and systemic antibody responses accompany spontaneous resolution of experimental cystitis in cynomolgus monkeys.

Cynomolgus monkeys were infected intravesically with two different strains of uropathogenic Escherichia coli. A quantitative enzyme-linked immunosorbent assay method was used to monitor secretory and serum immune responses to the induced cystitis. Anti-E. coli secretory immunoglobulin A (sIgA) and IgG urinary antibodies were generated as a result of the cystitis. Urinary sIgA levels against the E. coli strains tested were highest at 25 to 31 days after cystitis induction, and urinary IgG levels were highest at 31 to 45 days after induction. Anti-E. coli IgM was not detected in the urine. The antibody response in serum was characterized by IgM, IgG, and IgA immunoglobulin production. IgM levels in serum rose at 14 days after cystitis induction and were sustained for another 1 to 2 weeks. Increases in serum IgG levels began at 7 to 21 days of infection and persisted in some cases for up to 70 days. Serum IgA to the infecting E. coli was produced within 1 week after cystitis induction and remained at elevated levels throughout the course of the cystitis. These results demonstrate the capacity of primates to spontaneously resolve a cystitis and to mount both local and systemic immune responses against the infecting bacteria.

Animals↗
PubMed2000

Stress and symptomatology in patients with interstitial cystitis: a laboratory stress model.

PURPOSE: Although patients with interstitial cystitis frequently report symptom exacerbation due to stress, to our knowledge this association has not been empirically examined. We evaluated the effects of a laboratory mental stress challenge on symptoms of urgency and pain in patients with interstitial cystitis and healthy controls. MATERIALS AND METHODS: A total of 14 females with interstitial cystitis and 14 age matched controls participated in a laboratory session, including a 60-minute baseline measurement, 25 minutes of mental stress tasks and 75 minutes of recovery. Acute symptoms of pain and urgency were assessed at voiding 15 minutes before the stressor, and 25, 70 and 100 minutes after stressor onset. Chronic symptoms were evaluated by questions from the Interstitial Cystitis Data Base survey. RESULTS: Patients reported significantly greater pain and urgency than controls at all 4 voidings (p <0.005). Pain increased in patients from the prestressor point to 25 minutes after stressor onset (p <0.005), remained elevated at 70, and decreased between 70 and 100. At 100 minutes patient pain remained significantly elevated above baseline (p = 0.018). Patient urgency was significantly elevated over baseline by 70 minutes after stressor onset (p <0.001) and significantly decreased between 70 and 100 minutes (p <0.002). Controls had no symptom changes with stress. CONCLUSIONS: These findings indicate that an acute stressor evokes increased symptoms of pain and urgency in patients with interstitial cystitis but not in controls. Findings are consistent with sympathetic effects on inflammatory processes in interstitial cystitis. However, further evaluation of the mechanisms underlying stress related interstitial cystitis symptom exacerbation is needed to provide a more comprehensive understanding of these phenomena.

Adult↗
PubMed2002

Over expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in patients with interstitial cystitis and bladder carcinoma.

PURPOSE: We examined whether the expression of angiogenic factors, such as platelet-derived endothelial cell growth factor/thymidine phosphorylase (PDEGF/TP) and transforming growth factor-beta, in bladder tissue correlates with the severity of symptoms, such as urinary urgency and bladder pain, in patients with bladder carcinoma and interstitial cystitis. MATERIALS AND METHODS: Bladder biopsy was performed in 32 patients with bladder carcinoma, including 19 with interstitial cystitis and 3 controls. Immunohistological staining for PDEGF/TP, transforming growth factor-beta and CD44 was performed in bladder specimens. PDEGF/TP in bladder tissues was also measured by enzyme-linked immunosorbent assay to examine the correlation of the expression of this factor with painful symptoms in patients with bladder carcinoma or interstitial cystitis. RESULTS: Immunohistochemical staining showed that PDEGF/TP stained in the submucosal layer beneath the basement membrane in bladder tissues of patients with interstitial cystitis and peritumoral areas of those with bladder carcinoma. In addition, PDEGF/TP, transforming growth factor-beta and CD44 stained in the same submucosal region and staining was observed at deeper submucosal levels in interstitial cystitis cases with severe rather than mild bladder pain. Quantitative analyses revealed that mean PDEGF/TP expression plus or minus standard deviation in tumor tissues of 10 patients with bladder carcinoma and pain was significantly higher than in tumor tissues of 22 with asymptomatic bladder carcinoma (129.3 +/- 70.7 versus 37.6 +/- 29.2 units per mg. protein). The mean expression of PDEGF/TP in peritumoral mucosa of patients with bladder carcinoma and pain was also significantly higher than in those with asymptomatic bladder carcinoma (75.5 +/- 42.1 versus 12.6 +/- 5.4 units per mg. protein). For interstitial cystitis mean expression in 6 patients with severe bladder pain was significantly higher than in 13 with moderate pain (79.2 +/- 59.2 versus 16.6 +/- 17.5 units per mg. protein). Mean expression in bladder tissues of controls was less than 2.3 units per mg. protein. CONCLUSIONS: These results suggest that angiogenic factors, such as PDEGF/TP and transforming growth factor-beta, may be involved in the inflammatory process to induce painful symptoms in patients with interstitial cystitis or bladder carcinoma. Proteoglycans such as CD44 may contribute to the presentation of these soluble angiogenic factors at the inflammation site.

Aged↗
PubMed2002

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.

Adult↗
PubMedDate not supplied

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

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

Adolescent↗
PubMed1998

An epidemiologic study of cystitis among Muslim women attending an out-patients clinic in Karachi.

Cystitis is considered to be one of the most common infections afflicting women of all age groups. It has been suggested that personal hygiene customs may influence the prevalence of cystitis. In this study, 130 women of child bearing age attending the out-patients clinic were interviewed in order to determine the frequency of cystitis and its associated risk factors including personal hygiene practices. Twenty seven percent of the women reported suffering from cystitis atleast once in the past, comparable to reported studies from the United States but higher than reported from other Muslim countries. Sixty-three percent of women reported their first episode during pregnancy and a significant relationship was observed between parity and cystitis (p value < 0.000). However, personal hygiene practices following micturition or sexual intercourse bore no significant association with cystitis. Cystitis, commonly reported among Pakistani married women, occurs primarily during pregnancy. Preventive measures during pregnancy are suggested.

Adult↗
PubMed1997

Severe cystitis associated with tiaprofenic acid.

OBJECTIVE: To review the UK spontaneous reports of urinary disorders associated with tiaprofenic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) and put them into context of the usage of these preparations in the UK. METHODS: Suspected adverse drug reaction (ADR) reports of urinary disorders associated with tiaprofenic acid and other NSAIDs received by the UKs spontaneous ADR reporting scheme were analysed. RESULTS: Between 1982, when tiaprofenic acid was introduced in the UK, and August 1994, 69 cases of cystitis were reported, with a further 32 reports describing related urinary symptoms including frequency, dysuria and haematuria. Only eight cases of cystitis were reported for all other NSAIDs. The duration of treatment with tiaprofenic acid before the onset of urinary symptoms varied markedly (range 2 days to > 3 years). In patients in whom a drug-induced cause was suspected and the drug was stopped promptly, recovery usually occurred within weeks. However, many patients continued on long-term treatment with tiaprofenic acid and underwent extensive investigations to determine the cause of their urinary symptoms. On cystoscopy and biopsy, the findings were similar to interstitial cystitis. Most patients with chronic cystitis recovered after withdrawal of tiaprofenic acid, but some patients had surgery before the drug was stopped. CONCLUSION: Tiaprofenic acid can cause severe cystitis. These reports highlight the importance of taking a full drug history in patients with unexplained chronic cystitis. Tiaprofenic acid should be stopped immediately in all patients developing urinary symptoms.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women.

CONTEXT: Guidelines for the management of acute uncomplicated cystitis in women that recommend empirical therapy in properly selected patients rely on the predictability of the agents causing cystitis and knowledge of their antimicrobial susceptibility patterns. OBJECTIVE: To assess the prevalence of and trends in antimicrobial resistance among uropathogens causing well-defined episodes of acute uncomplicated cystitis in a large population of women. DESIGN: Cross-sectional survey of antimicrobial susceptibilities of urine isolates collected during a 5-year period (January, May, and September 1992-1996). SETTING: Health maintenance organization. PATIENTS: Women aged 18 to 50 years with an outpatient diagnosis of acute cystitis. MAIN OUTCOME MEASURES: Proportion of uropathogens demonstrating in vitro resistance to selected antimicrobials; trends in resistance over the 5-year study period. RESULTS: Escherichia coli and Staphylococcus saprophyticus were the most common uropathogens, accounting for 90% of the 4342 urine isolates studied. The prevalence of resistance among E coli and all isolates combined was more than 20% for ampicillin, cephalothin, and sulfamethoxazole in each year studied. The prevalence of resistance to trimethoprim and trimethoprim-sulfamethoxazole rose from more than 9% in 1992 to more than 18% in 1996 among E coli, and from 8% to 16% among all isolates combined. There was a statistically significant increasing linear trend in the prevalence of resistance from 1992 to 1996 among E coli and all isolates combined to ampicillin (P<.002), and to cephalothin, trimethoprim, and trimethoprim-sulfamethoxazole (P<.001). In contrast, the prevalence of resistance to nitrofurantoin, gentamicin, and ciprofloxacin hydrochloride was 0% to 2% among E coli and less than 10% among all isolates combined, and did not change significantly during the 5-year period. CONCLUSIONS: While the prevalence of resistance to trimethoprim-sulfamethoxazole, ampicillin, and cephalothin increased significantly among uropathogens causing acute cystitis, resistance to nitrofurantoin and ciprofloxacin remained infrequent. These in vitro susceptibility patterns should be considered along with other factors, such as efficacy, cost, and cost-effectiveness in selecting empirical therapy for acute uncomplicated cystitis in women.

Acute Disease↗
PubMed2002

Cystitis-induced upregulation of tyrosine kinase (TrkA, TrkB) receptor expression and phosphorylation in rat micturition pathways.

This study examined tyrosine kinase receptor (Trk) expression and phosphorylation in lumbosacral dorsal root ganglia (DRG) after acute (8 or 48 hours) or chronic (10 days) cyclophosphamide (CYP)-induced cystitis. Increases in the number of TrkA-immunoreactive (IR) cell profiles were detected in the L1 and L6 DRG (four-fold; P < or = 0.01) and the S1 DRG (1.5-fold; P < or = 0.05) but not in the L2, L4, and L5 DRG with CYP-induced cystitis of acute and chronic duration compared with control rats. The number of TrkB-IR cell profiles increased in the L1 and L2 DRG (L1: 2.6-fold; L2: 1.4-fold; P < or = 0.05) and in the L6 and S1 DRG (L6: 2.2-fold; S1: 1.3-fold; P < or = 0.05) only after acute CYP treatment (8 hours). After CYP treatment, the percentage of bladder afferent cell profiles expressing TrkA-IR (approximately 50%; P < or = 0.05) increased in L1 and L6 DRG. The percentage of bladder afferent cell profiles expressing TrkB-IR (approximately 45%; P < or = 0.05) in L1, L2, L6, and S1 DRG also increased compared with control cell profiles. The increase in TrkA-IR in bladder afferent cells occurred 8 hours after CYP treatment and was maintained in L1 DRG with chronic (10 days) CYP-induced cystitis. However, the increase in bladder afferent cells expressing TrkB-IR only occurred at the most acute time point examined (8 hours). TrkA-IR and TrkB-IR cell profiles also demonstrated phosphorylated Trk-IR with acute and/or chronic CYP-induced cystitis. These results demonstrated that CYP-induced cystitis increases the expression and phosphorylation of Trk receptors in lumbosacral DRG. Expression of neurotrophic factors in the inflamed urinary bladder may contribute to this increased expression, and neurotrophic factor and Trk interactions may play unique roles in decreased urinary tract plasticity with CYP-induced cystitis.

Acute Disease↗
PubMed1987

Chronic cystitis: excretion of epidermal growth factor (EGF)/urogastrone (URO).

To investigate the role of epidermal growth factor (EGF)/urogastrone (URO) in the cytoprotection of the urothelium in the urinary bladder we measured the concentration of EGF/URO by radioimmunoassay in urine from patients with chronic cystitis. The series comprised 12 patients with classical interstitial cystitis, 10 young females with recurrent bacterial cystitis and 12 children with recurrent cystitis together with sex- and age-matched controls. The results showed no variation in the substance concentration of EGF/URO in urine from cystitis patients and control groups. A negative correlation was found between 1) the urinary concentration of EGF/URO and increasing age, and 2) the excretion of EGF/URO per mol creatinine. The present study did not show a decreased output of EGF/URO in patients with chronic cystitis. Further studies are necessary in the evaluation of the physiological role of EGF/URO in the urinary tract.

Adolescent↗
PubMed2006

Expression of fractalkine and fractalkine receptor in urinary bladder after cyclophosphamide (CYP)-induced cystitis.

Alterations in the expression of the chemokine, fractalkine (CX3CL1), were examined in the urinary bladder after cyclophosphamide (CYP)-induced cystitis of varying duration: acute (4 h or 48 h), or chronic (10 day). CYP-induced cystitis significantly (p<or=0.01) increased fractalkine protein expression in the urinary bladder with acute (48 h) and chronic CYP treatment. Western blot analysis also demonstrated significantly (p<or=0.01) increased fractalkine expression in the whole urinary bladder with acute (1.5-2.2-fold) and chronic (3-fold) CYP-induced cystitis. Immunohistochemistry for fractalkine-immunoreactivity revealed little fractalkine-IR in control or acute (4 h) CYP-treated rat urinary bladders except in a vascular bed but showed no colocalization with nerve fibers in the suburothelial plexus in any experimental group. However, expression was significantly (p<or=0.001) upregulated in the urothelium with 48 h or chronic CYP treatment. Similarly, fractalkine receptor (CX3CR1)-IR was significantly (p<or=0.001) upregulated in the urothelium with 48 h or chronic CYP treatment. These studies demonstrated upregulation of the chemokine, fractalkine, in the urinary bladder and specifically in the urothelium with CYP-induced cystitis. Chemokines, and specifically, fractalkine, may be another class of neuromodulatory agents upregulated in the urinary bladder that can affect micturition function and sensory processing with cystitis and may represent novel, drug targets for cystitis.

Analysis of Variance↗
PubMed2007

Bladder necrosis following hydrodistention in patients with interstitial cystitis.

PURPOSE: Bladder hydrodistention is used to diagnose and treat patients with interstitial cystitis. This procedure has been shown to have minimal morbidity and provide symptomatic relief in a subset of patients with interstitial cystitis. We report our experience with almost total bladder necrosis after hydrodistention at 2 institutions. To our knowledge this rare complication has not been previously reported in the literature. We also reviewed the literature regarding complications of hydrodistention and discuss their possible etiology. MATERIALS AND METHODS: We report 3 cases of bladder necrosis after therapeutic hydrodistention for interstitial cystitis at 2 institutions. All records were reviewed, and the clinical presentation, findings and treatments are discussed. A literature review was performed to evaluate the effectiveness and complications of hydrodistention for interstitial cystitis. RESULTS: There were 2 female and 1 male patient between ages 29 and 46. All patients had a previous diagnosis of interstitial cystitis and had been previously treated with hydrodistention. All patients presented with severe abdominal pain and had necrosis of the entire bladder wall with sparing of the trigone. Two patients were treated with supratrigonal cystectomy. A review of the literature revealed little data on the effectiveness of hydrodistention for interstitial cystitis. CONCLUSIONS: Vesical necrosis is a rare but devastating complication of hydrodistention. It can occur in young patients in the absence of a contracted bladder and it usually presents as severe postoperative abdominal pain. At exploration bladder necrosis with sparing of the trigone was observed. All patients required enterocystoplasty.

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↗
PubMed1994

Abnormal flow cytometry profiles in patients with interstitial cystitis.

Flow cytometry was performed on bladder cells from patients with interstitial cystitis and control patients. Cells were processed in standard fashion for flow cytometry with propidium iodide staining and analysis was restricted to samples with sufficient cells for cytokeratin gating and acceptable coefficients of variation. Of 14 interstitial cystitis patients 4 (29%) demonstrated aneuploid deoxyribonucleic acid (DNA) profiles as evidenced by a discrete peak with a DNA index of 1.2 or greater in the cytokeratin positive population. The aneuploid peak accounted for up to 54% of the cytokeratin positive population in these samples. No such aneuploid DNA profiles were evident in specimens obtained from control patients. A significant DNA tetraploid population, as evidenced by a 4C (G2) peak greater than 20%, was observed in 6 of 14 interstitial cystitis patients (43%) and 8 of 11 controls (72%). Manual counting of the per cent of binucleated cytokeratin positive cells in the cytokeratin stained population and nuclear preparations of several samples for flow analysis indicate that apparent DNA tetraploidy in the interstitial cystitis and control patients is due to an abundance of binucleated cells. Aneuploid DNA profiles on barbotage specimens from interstitial cystitis patients may reflect a real karyotypic abnormality or altered chromosome complement (true aneuploidy), abnormal chromatin structure or abnormal cytoplasmic binding of the propidium iodide stain. This finding may signal an underlying abnormality of the epithelial cell population in some patients with the clinical diagnosis of interstitial cystitis.

Adult↗
PubMed1992

Interstitial cystitis: increased sympathetic innervation and related neuropeptide synthesis.

To investigate the possibility of a neural deterioration of the bladder wall in interstitial cystitis, bladder tissue from 10 patients with interstitial cystitis was compared with that from 10 control subjects by means of immunohistochemistry. An enhanced innervation of the bladder in the submucosa and detrusor muscle was found to represent an increase of sympathetic but not cholinergic neurons. In interstitial cystitis the number of neurons positive for vasoactive intestinal polypeptide and neuropeptide Y was higher and carried a larger number of axonal varicosities, whereas the number of neurons positive for substance P and calcitonin-gene-related peptide was not significantly different in both groups. We conclude that interstitial cystitis is associated with increased sympathetic outflow into the bladder and altered metabolism of vasoactive intestinal polypeptide and neuropeptide Y. Since similar changes have been observed in other inflammatory diseases of a presumably autoimmune nature, such as rheumatoid arthritis, Crohn's disease and colitis ulcerosa, the pathophysiology of interstitial cystitis may share common pathways with the latter. Experience in these diseases may facilitate a better understanding of the pathophysiology of interstitial cystitis and suggest new therapeutic concepts.

Adrenergic Fibers↗
PubMed1988

Interstitial cystitis is associated with intraurothelial Tamm-Horsfall protein.

A defective barrier between the urine and urothelium has been suggested as an etiology for interstitial cystitis. With immunohistochemical techniques we assayed the bladder biopsies of 14 interstitial cystitis patients and 10 normal controls for intraurothelial Tamm-Horsfall protein to assess indirectly the in vivo permeability of the urothelium. Eight pathological controls, including bladder biopsies from 3 patients with inflammation owing to infection or catheterization and biopsies of 5 transitional cell carcinomas of the bladder, also were assayed. Superficial intraurothelial Tamm-Horsfall protein was identified in the biopsies from 10 of 14 interstitial cystitis patients (71 per cent) but only 1 of 10 controls (10 per cent) (p less than 0.01). Tamm-Horsfall protein was not identified in biopsies from the pathological controls. In 6 of 7 cases when more than 1 biopsy was available for analysis the findings were identical in each specimen. There was a direct correlation between the density of detrusor mast cells and the demonstration of intraurothelial Tamm-Horsfall protein. Seven of the 9 evaluable interstitial cystitis patients with intraurothelial Tamm-Horsfall protein but only 1 of 4 without intraurothelial Tamm-Horsfall protein experienced a favorable response to intravesicle oxychlorosene sodium (p greater than 0.05). These data suggest that abnormal permeability of the urothelium is associated with and a possible cause of interstitial cystitis and that the demonstration of intraurothelial Tamm-Horsfall protein in bladder biopsy specimens may prove to be useful as a diagnostic test for interstitial cystitis.

Administration, Intravesical↗