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PubMed2004

A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis.

PURPOSE: We conducted a prospective study to examine the safety and efficacy of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC). MATERIALS AND METHODS: The study comprised 44 women and 6 men who all met the symptom criteria of the National Institute of Diabetes, Digestive and Kidney Diseases for IC. The patients were randomly assigned to amitriptyline or placebo. Patients were prospectively treated for 4 months with a self-titration protocol that allowed them to escalate drug dosage in 25 mg increments in 1 week-intervals (maximum dosage 100 mg). The change from baseline in the O'Leary-Sant IC symptom and problem index was the primary outcome parameter. Changes in functional bladder capacity and frequency (48-hour voiding log), and intensity of pain and urgency (visual analog scales) were chosen as secondary outcome parameters. RESULTS: Two patients (1 on amitriptyline, 1 on placebo) dropped out of the study due to side effects. Thus, the data of 48 patients (24 patients in each group) were available for evaluation. Mean symptom score decreased from 26.9 to 18.5 in the amitriptyline group compared with 27.6 to 24.1 in the placebo group (p = 0.005). Pain and urgency intensity improved statistically significantly in the amitriptyline group compared with the placebo group (p <0.001). The frequency and functional bladder capacity improved to a much greater degree in the amitriptyline group but the differences were not statistically significant (p = 0.063, p = 0.083). Anticholinergic side effects were reported by all except 2 patients in the amitriptyline group (92%) and by 5 patients in the placebo group (21%). Mouth dryness was the most frequent side effect reported in the amitriptyline group (79%). CONCLUSIONS: Amitriptyline therapy for 4 months is safe and effective for treating IC. A statistically significant change in the symptom score and statistically significant improvement of pain and urgency intensity compared with placebo were observed. Anticholinergic side effects constitute the major drawback of amitriptyline treatment for IC.

Adult↗
PubMed2004

Possible mechanisms inducing glomerulations in interstitial cystitis: relationship between endoscopic findings and expression of angiogenic growth factors.

PURPOSE: Glomerulation has been one of the requisite criteria for the diagnosis of interstitial cystitis (IC) but the mechanisms for glomerulation remain unclear. Therefore, we investigated the relationship between the cystoscopic findings of vascular events and the expression of angiogenic growth factors in IC bladders to identify the possible mechanisms inducing glomerulations in IC. MATERIALS AND METHODS: In 45 patients suspected of having IC continuous, fixed point cystoscopic observation was performed during hydrodistention using spinal anesthesia. Bladder biopsies were performed in these cases and in an additional 5 asymptomatic cases. Thereafter, the expression of platelet derived endothelial cell growth factor/thymidine phosphorylase (PDECGF/TP) was measured by enzyme-linked immunosorbent assay. Immunohistochemical staining for PDECGF/TP and vascular endothelial growth factor was also performed. RESULTS: Of 45 symptomatic patients 38 had glomerulations during cystoscopic examination. In these patients during hydrodistention the blood flow in bladder wall vessels was interrupted by whitish fibrous bundles. Thereafter petechial bleeding began from capillaries distal to obstructed vessels during bladder emptying. PDECGF/TP expression in patients with glomerulation was significantly higher than in symptomatic patients without glomerulation or asymptomatic patients (p < 0.001). In patients with glomerulations a high positive rate for PDECGF/TP (97.4%) and vascular endothelial growth factor (68.4%) staining was observed, while no positive staining was found in asymptomatic patients. CONCLUSIONS: Glomerulations during hydrodistention are highly associated with the over expression of angiogenic growth factors in the bladder. Thus, it seems likely that neovascularization promoted by angiogenic growth factors has an important role in the pathogenesis of IC, inducing glomerulations during hydrodistension.

Adult↗
PubMed2004

Comorbidity of interstitial cystitis with other unexplained clinical conditions.

PURPOSE: The aims of this review are 1) to consider the hypothesis that interstitial cystitis (IC) is not a single disease entity in all patients by reviewing the evidence for the presence of IC subtypes and for the comorbidity of various unexplained clinical conditions in some patients with IC, and 2) to describe recent results obtained in humans and in cats with severe feline IC (FIC) that suggest the presence of an underlying neuroendocrine abnormality. MATERIALS AND METHODS: The IC literature concerning comorbidity with other disorders was reviewed and these findings were compared with those of investigators studying the comorbid disorders and comparable data on cats with FIC. RESULTS: A significant overlap of symptoms exists among a number of unexplained clinical conditions and a common stress response pattern of increased sympathetic nervous system function in the absence of comparable activation of the hypothalamic-pituitary-adrenal axis occurs in a subset of patients with many of these conditions. A comparable pattern exists in cats with FIC, which also includes increased corticotropin releasing factor activity and decreased adrenocortical reserve. CONCLUSIONS: Further investigation of the stress response system of patients with IC seems merited, which may provide novel approaches to therapy in some patients.

Animals↗
PubMed2004

Is urine methylhistamine a useful marker for interstitial cystitis?

PURPOSE: We determined whether urine methylhistamine (MH) is associated with other clinical features and bladder biopsy findings in interstitial cystitis (IC). MATERIALS AND METHODS: Urine MH and University of Wisconsin symptom scores were measured before and 1 month after bladder distention for IC. Bladder biopsies were done at the time of distention. In new patients with IC who met cystoscopic criteria urine MH was compared before and after distention, and changes in urine MH were compared with changes in symptom scores. Pre-distention urine MH was tested for associations with the results of a symptom questionnaire, symptom response after distention, cystoscopic findings and bladder biopsy findings. RESULTS: There were no significant associations between urine MH and symptom scores, response to bladder distention, cystoscopic findings or bladder biopsy features, including mast cell count by tryptase staining. Urine MH was similar in new patients with IC who did vs did not meet cystoscopic criteria. Urine MH was similar in new vs chronically treated patients with IC. CONCLUSIONS: Urine MH is unlikely to be useful as an objective marker of the response to bladder distention, as a method to predict which patients will respond to bladder distention or as a noninvasive substitute for bladder biopsy and mast cell counts by tryptase staining.

Adult↗
PubMed2005

Bladder Adelta afferent nerve activity in normal cats and cats with feline interstitial cystitis.

PURPOSE: Symptoms associated with interstitial cystitis (IC) (urinary frequency, urgency and pain) resemble those in cats diagnosed with feline IC (FIC). Patients with IC also show enhanced sensitivity to intravesical application of KCl solution. In the current study we compared the effect of bladder distention and intravesical infusion of KCl solution on Adelta bladder afferent nerve activity in normal and FIC cats. MATERIALS AND METHODS: Cats were anesthetized with alpha-chloralose (60 to 70 mg/kg intravenously). Single and multiunit afferent nerve activity was recorded with platinum electrodes from fibers dissected from the transected pelvic nerve. Bladder Adelta afferents were activated by bladder distention at constant pressures (5 to 80 cm H2O) by infusing saline or KCl solution (80 to 300 mM). RESULTS: Increasing bladder pressure by saline infusion over a range of constant pressures (5 to 80 cm H2O) increased afferent firing in normal and FIC cats. However, the slope of the pressure-firing curve was significantly steeper in cats with FIC. In normal cats KCl infusion (80 to 300 mM) into the bladder produced a pressure-firing curve similar to that induced by saline infusion. However, in FIC cats KCl at concentrations of 150 to 300 mM produced almost complete inhibition of afferent firing at pressures between 30 and 80 cm H2O. CONCLUSIONS: These data suggest that 1) bladder Adelta afferents in FIC cats are more sensitive to pressure changes than are afferents in normal cats and 2) the inhibition of afferent firing by high concentrations of KCl in FIC cats is likely the result of afferent nerve depolarization and it is consistent with the idea of increased permeability of bladder epithelium in FIC.

Afferent Pathways↗
PubMed2005

Do the National Institute of Diabetes and Digestive and Kidney Diseases cystoscopic criteria associate with other clinical and objective features of interstitial cystitis?

PURPOSE: We compared urine markers, bladder biopsy findings and clinical features of patients with symptoms of interstitial cystitis (IC) who did or did not meet the cystoscopic criteria defined by the National Institute of Diabetes and Digestive and Kidney Diseases. MATERIALS AND METHODS: Urine markers and symptom questionnaires were measured before and 1 month after bladder distention for IC. Bladder biopsies were taken at the time of distention. At distention patients were defined as meeting or not meeting the National Institute of Diabetes and Digestive and Kidney Diseases established cystoscopic criteria for IC. The 2 patient groups were compared. RESULTS: Urine marker levels were similar for the 2 groups, including antiproliferative factor, epidermal growth factor, heparin binding epidermal growth factor-like growth factor, cyclic guanosine monophosphate, interleukins 6 and 8, and methylhistamine. Bladder biopsy features were similar for the 2 groups. Bladder capacity with the patients under anesthesia was higher in those who did not meet the criteria (median 750 vs 1,000 ml, p = 0.005). Median age at symptom onset was 26 years in both groups. On the University of Wisconsin symptom scale patients who met the criteria had higher scores for daytime frequency (p = 0.002) and nocturia (p = 0.01). Symptom characteristics and symptom response after bladder distention were similar for the 2 groups. CONCLUSIONS: Patients who met the cystoscopic criteria had worse daytime frequency and nocturia, and lower bladder capacity under anesthesia. However, the 2 groups had similar urine markers and bladder biopsy findings. The cystoscopic criteria do not appear to identify a distinct pathophysiological subset of patients with IC symptoms.

Adult↗
PubMed2005

Abnormal urinary potassium metabolism in patients with interstitial cystitis.

PURPOSE: If most patients with interstitial cystitis (IC) have epithelial leakage allowing urinary K to penetrate the interstitium and provoke symptoms, urinary K should be lower in untreated patients than in healthy subjects and it should increase with successful heparinoid treatment. This study tested these hypotheses. MATERIALS AND METHODS: Na, K and creatinine (Cr) were determined in spot urine samples from new, symptomatic, untreated patients with IC meeting all National Institute of Diabetes and Digestive and Kidney Diseases clinical diagnostic criteria, returning patients with IC reporting 50% or greater symptom improvement after 4 or greater months of oral heparinoid therapy and control subjects, and in 24-hour urine samples from new untreated patients and controls. RESULTS: In spot urine specimens of 37 new patients with IC K-to-Cr ratios were significantly lower than in 18 controls (0.51 vs 0.88 mg/mg Cr, p = 0.001). A total of 50 successfully treated patients with IC had significantly higher K-to-Cr ratios than those in 37 new patients (0.66 vs 0.51 mg/mg Cr, p = 0.025). Na-to-Cr ratios in the 3 groups were not significantly different. In 24-hour urine specimens 30 new patients had lower average K (31.0 vs 46.2 mEq/l, p = 0.01) and lower K-to-Cr ratios (0.43 vs 0.52 mg K/mg Cr, p = 0.01) than in 47 controls, while Na was not significantly different. CONCLUSIONS: Our finding of lower urinary K in new, untreated patients supports the concept of abnormal epithelial permeability and K absorption in IC. Higher urinary K in successfully treated vs untreated patients may reflect decreasing urinary K absorption due to mucosal repair and a resulting decrease in epithelial permeability. K/mg Cr appears accurate for normalizing urinary K.

Absorption↗
PubMed2005

Correlation between 2 interstitial cystitis symptom instruments.

PURPOSE: Two statistically validated interstitial cystitis (IC) symptom instruments have been used in clinical research. In this study we report what is to our knowledge the first direct comparison of the University of Wisconsin Symptom Instrument (UWI) with the O'Leary-Sant instruments, that is the IC Symptom Index (ICSI) and IC Problem Index (ICPI). MATERIALS AND METHODS: A convenience sampling of 107 patients with IC evaluated at the urology clinic at our institution from March through August 2000 were asked to complete ICSI, ICPI and UWI. The scores were analyzed and graphed. RESULTS: Mean ICSI, ICPI and UWI scores +/- SD were 12.6 +/- 4.3, 10.5 +/- 3.8 and 25.5 +/- 10.8, respectively. UWI and ICSI scores correlated at r = 0.80 (p <0.01) and ICSI/ICPI scores correlated at r = 0.83 (p <0.01). ICSI and ICPI contain 4 symptom-problem pairs. There are relevant differences in the correlation of symptom severity (ICSI question) and its associated problem (ICPI question). The symptom of urgency correlated best with the associated problem (r = 0.84), followed by nocturia (r = 0.82), pain (r = 0.70) and frequency (r = 0.68). CONCLUSIONS: The ICSI and UWI symptom instruments correlate strongly in a large population of patients with IC. The data presented will aid in interpreting the literature. A relatively poor correlation between pain symptom-problem pairs in the O'Leary-Sant instruments is probably an artifact of wording. The word pressure appears in ICPI but not in ICSI. We suggest using parallel wording of the pain symptom-problem pair containing the identical phrase, burning, pain, discomfort or pressure, to improve the ICSI/ICPI correlation and more accurately reflect the clinical condition.

Adult↗
PubMed2005

Efficacy of prednisone for severe refractory ulcerative interstitial cystitis.

PURPOSE: We know that bladder inflammation has been noted in some patients with interstitial cystitis (IC). Studies with corticotherapy were performed about 50 years ago. Since that time few studies have been done with corticotherapy. We evaluated the efficacy of prednisone in patients with chronic severe IC with Hunner's ulcers unresponsive to first line therapies. MATERIALS AND METHODS: A prospective study was performed on 14 patients with evidence of ulcerative IC between 1998 and 2003. The patients received 25 mg of prednisone daily for 1 to 2 months and the dose was then tapered to the minimum required for relief of symptoms. Efficacy was evaluated with the O'Leary symptom and problem index and a 6-point pain scale. RESULTS: Of the 14 patients 9 (64%) were still using prednisone at the end of the study with an average followup of 16 months. In these 9 patients a 38% reduction (p <0.005) in the total score of the O'Leary index was observed. Pain was decreased by 88% (p = 0.0001). There were 5 patients who dropped out of the study due to lack of improvement or side effects. Overall results for the whole cohort included a reduction of 22% (p <0.02) of the total score of O'Leary index and a 69% improvement in pain control (p <0.001). CONCLUSIONS: These results suggest that a trial of prednisone should be considered in patients with severe ulcerative IC otherwise unresponsive to conventional treatment. Improvement in pain control was particularly impressive in this group of patients.

Aged↗
PubMed2005

Psychophysical evidence of hypersensitivity in subjects with interstitial cystitis.

PURPOSE: We quantified differences in somatic and visceral sensation in healthy subjects and subjects with interstitial cystitis (IC). MATERIALS AND METHODS: A total of 13 subjects with IC and 13 healthy subjects answered psychological questionnaires and underwent psychophysical testing of thermal and pressure thresholds for sensation as well as the ischemic forearm test of pain tolerance. A subset of subjects also underwent bladder sensory testing with the determination of 3 consecutive cystometrograms. Ratings of intensity and unpleasantness were determined. RESULTS: Subjects with IC were significantly more sensitive to deep tissue measures of sensation related to pressure, ischemia and bladder than healthy subjects. Cutaneous thermal pain measures were similar in the 2 groups. Psychological measures indicated higher reactivity in subjects with IC. CONCLUSIONS: Similar to other visceral pain disorders, such as irritable bowel syndrome, hypersensitivity to somatic stimuli was noted in subjects with IC. This suggests altered central mechanisms in the processing of sensory events from the bladder.

Adult↗
PubMed2005

Urinary uronate and sulfated glycosaminoglycan levels: markers for interstitial cystitis severity.

PURPOSE: Urologists frequently rely on symptom and problem indexes to monitor patients with interstitial cystitis (IC). Uronic acid is a component of most glycosaminoglycans (GAGs), which is a protective bladder urothelium coating. We evaluated whether urinary uronate and sulfated GAG levels correlate with IC severity and we characterized urinary GAG species. MATERIALS AND METHODS: Urine samples, and a completed O'Leary-Sant IC symptom and problem index questionnaire were obtained from 37 patients with IC and 14 normal individuals. Patients with IC were in group 1-1 or 2 indexes less than 50% the maximum score or group 2-each index 50% or greater the maximum score. All patients fulfilled National Institute of Diabetes and Digestive and Kidney Diseases criteria except glomerulations. Urinary uronate was fractionated using cetyltrimethylammonium bromide (CETAB). Uronate and sulfated GAG levels in urine, CETAB precipitates and CETAB supernatants were measured by the Bitter and Muir, and Farndale assays, respectively, and normalized to creatinine in microg/mg creatinine. GAG species were analyzed by agarose gel electrophoresis. RESULTS: Mean urinary uronate levels were increased in group 2 compared with normal and group 1 values regardless of glomerulations and treatment (1,614 +/- 904.6 vs 612.4 +/- 327.2 and 593.8 +/- 422.1 microg/mg creatinine, respectively, p <0.001). A small portion of urinary uronate was CETAB precipitable, representing macromolecular GAGs. Uronate levels in CETAB precipitates and CETAB supernatants were approximately 2.8-fold increased in group 2 (8.0 +/- 5.07 and 1,393 +/- 671.9 microg/mg creatinine, respectively) compared with normal and group 1 values (p <0.001), and they contained fast and slow moving GAG species. Uronate and sulfated GAG had 80% and 88% sensitivity, and 92.3% and 69.2% specificity, respectively, to detect IC severity. CONCLUSIONS: The majority of urinary GAGs likely exist as small oligosaccharides. Urinary uronate and sulfated GAG levels are increased in patients with IC who have severe disease. They may become useful markers for monitoring IC.

Adult↗
PubMed2005

Reinvestigation of patients with a diagnosis of interstitial cystitis: common things are sometimes common.

PURPOSE: We tested the accuracy of the diagnosis and the value of each step of the diagnostic process in a group of patients undergoing reinvestigation of interstitial cystitis (IC). MATERIALS AND METHODS: A total of 61 patients with a provisional diagnosis of IC underwent systematic reinvestigation by a pathway involving a thorough history and physical examination, a rigorous search for urinary infection, frequency volume records, urodynamics and cystoscopy under general anesthesia. Abnormalities detected in the course of this pathway were treated before proceeding with further investigation. RESULTS: The diagnosis of IC was confirmed or considered possible in only 34 cases (55%). Common alternative diagnoses included recurrent urinary tract infections, detrusor overactivity and vaginal candidiasis. Of 5 male patients only 1 was confirmed to have IC. The original diagnosis was overturned by history and physical examination (including urine cultures) in 11 cases, by urodynamic investigation in 11 and by cystoscopy in 5. CONCLUSIONS: While IC remains a diagnosis of exclusion, active exclusion of all possible causes of similar symptoms using a thorough investigative algorithm is imperative. Urodynamic investigation, together with a thorough history and physical examination, remains an important component of the diagnostic pathway.

Adolescent↗
PubMed2005

Long-term results of amitriptyline treatment for interstitial cystitis.

PURPOSE: We performed a prospective, open label study to examine the safety and efficacy of the long-term administration of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC). MATERIALS AND METHODS: A total of 94 patients were stratified into 2 groups, namely a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) group of those who fulfilled NIDDK criteria for IC and a nonNIDDK group of those who presented with characteristic IC symptoms but met at least 1 NIDDK exclusion criterion. Amitriptyline was received strictly at bedtime following an established self-titration protocol without a limitation of the maximum daily dose. Patients reporting improvement in a global response assessment questionnaire were considered treatment responders. Further efficacy measures were changes in pain and urgency, functional bladder capacity and frequency. Changes in the O'Leary-Sant IC index and rating of overall satisfaction with the therapeutic outcome were also reported. RESULTS: Mean study followup +/- SD was 19.0 +/- 12.5 months. The response rate was 64% (60 patients). The overall mean dose was 55 mg (range 12.5 to 150). Side effects occurred in 79 patients (84%), including dry mouth in 79% and weight gain in 59%. Patient overall satisfaction with the therapeutic result was excellent or good in 43 (46%). The dropout rate was 31% (29 patients) after a mean treatment period of 6 weeks at a mean dose of 70 mg. Nonresponse to treatment was the primary reason for dropout in all cases, while side effects contributed to dropout in 25 (86%). Improvement in the various IC symptoms was statistically significant compared with baseline. CONCLUSIONS: Long-term administration of amitriptyline is a feasible, safe and effective treatment for IC, provided that the drug is used judiciously to minimize adverse effects. The therapeutic response to amitriptyline was uniformly observed in patients fulfilling NIDDK criteria and in those with the pure clinical diagnosis of IC.

Administration, Oral↗
PubMed2005

Menstrual cycle affects bladder pain sensation in subjects with interstitial cystitis.

PURPOSE: Using psychophysical methods we compared the effect of the menstrual cycle on bladder sensation in subjects with the diagnosis of interstitial cystitis (IC) and in controls. MATERIALS AND METHODS: Female participants with normal menstrual cycles, including 7 with IC and 8 healthy controls, were recruited into this study. They completed daily diaries related to bladder pain and other body pain, and tracked daily micturition frequency. In a subset formal psychophysical testing of thermal and ischemic pain was performed at 2 times of the menstrual cycle, corresponding to the luteal and follicular phases. Cystometrograms were performed at the same time. RESULTS: Subjects with IC had higher pain scores and frequency than controls throughout the entire menstrual cycle. Pain scores were highest in the perimenstrual period in subjects with IC and controls. Micturition frequency was highest in the perimenstrual period in subjects with IC. Cystometric evaluation of a first need to void and the evocation of bladder pain demonstrated that lower intravesical volume and pressure were necessary to evoke bladder pain during the follicular period than during the luteal period in subjects with IC, although there was no effect on the first need to void. CONCLUSIONS: These findings are consistent with clinical lore that suggests a perimenstrual flare in pain in subjects with IC. To our knowledge it also demonstrates for the first time a menstrual cycle effect on bladder sensory function in subjects with IC. This suggests a potential role of gonadal hormones on bladder sensory processing and, therefore, a potential role for hormonal modulation as a therapeutic modality in this patient population.

Age Distribution↗
PubMed2005

Regulation of tight junction proteins and bladder epithelial paracellular permeability by an antiproliferative factor from patients with interstitial cystitis.

PURPOSE: Previous reports have suggested that the bladder epithelial barrier may be compromised in interstitial cystitis (IC). Antiproliferative factor (APF) is a small glycoprotein made specifically by bladder epithelial cells in patients with IC that induces changes in expression of certain epithelial cell proteins and profoundly inhibits cell growth. Therefore, we confirmed the increased permeability and decreased tight junction formation of bladder epithelial cell monolayers grown from biopsies in patients with IC compared to cells from normal controls. We then determined the effect of APF on the permeability of normal bladder epithelial cell monolayers and the expression of tight junction proteins. MATERIALS AND METHODS: Permeability was determined by measuring the C-mannitol and H-inulin flux between cells in confluent monolayers on Transwell culture plates (Corning, Corning, New York). Tight junction formation was assessed by immunofluorescence microscopy and the expression of specific proteins was determined by Western blot. RESULTS: APF treatment caused significant increases in the paracellular permeability of normal bladder epithelial cell monolayers and the attenuation of tight junctions compared to mock APF, similar to changes seen in IC cells. APF treatment also decreased expression of the tight junction proteins zonula occludens-1 and occludin. CONCLUSIONS: Because of its apparent effects on bladder epithelial cell tight junctions and paracellular permeability in vitro, APF may contribute to the leakiness of the bladder epithelial barrier seen in IC.

Adolescent↗
PubMed2005

Prevalence of interstitial cystitis symptoms in women: a population based study in the primary care office.

PURPOSE: We estimated the prevalence of urinary symptoms related to interstitial cystitis (IC) in women in a primary care practice and confirmed in the United States the results of a Finnish population based prevalence study. MATERIALS AND METHODS: Every female patient presenting to our office for a routine office visit between January 9, 2004 and September 24, 2004 was evaluated for urinary symptoms using 2 validated surveys, namely the O'Leary-Sant (OLS) IC symptom and problem index, and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. RESULTS: Of the 1,218 women in the study group 13 (1.1%) reported severe symptoms and problems (12 or greater on the OLS survey), including 7 (0.6%) who met previously established criteria for probable IC. In the same population scores on the PUF questionnaire indicated that 154 women (12.6%) likely had IC. CONCLUSIONS: Based on previously published criteria for use of the OLS survey the prevalence of urinary symptoms corresponding to probable IC in our study population (575/100,000 or 0.57%, 95% CI 150 to 1,000) was similar to the 0.45% rate previously reported. However, the results of the PUF questionnaire indicated that the prevalence of IC in women may actually be much higher (12,600/100,000 or 12.6%, 95% CI 10,700 to 14,500). We suggest that the true prevalence of IC in women may be somewhere between these 2 extremes. Further investigation of these questionnaires as screening tools for IC is warranted. IC may be more common in women than previously reported.

Adolescent↗
PubMed2004

Hemorrhagic cystitis in children undergoing bone marrow transplantation: a putative role for simian virus 40.

BACKGROUND: Late-onset hemorrhagic cystitis (HC) is a well-known severe complication of bone marrow transplantation (BMT), both in adults and in children. Protracted postengraftment HC is associated with graft-versus-host disease and viral infections, mainly caused by BK virus (BKV) or adenovirus (AV). This study investigated whether simian virus 40 (SV40) DNA sequences can be detected in specimens from pediatric patients affected by severe postengraftment HC. METHODS: The clinical diagnosis of HC was made in 7 of 28 BMT children. DNA from peripheral blood mononuclear cells (PBMC) and urine sediment cells and supernatants was analyzed by polymerase chain reaction (PCR) for human cytomegalovirus (HCMV), AV, BKV, JC virus (JCV), and SV40. DNA filter hybridization and sequencing was carried out in SV40-positive samples. RESULTS: SV40 footprints were detected in two of seven cases of HC. Specific SV40 DNA sequences were detected by PCR and by filter hybridization both in urine and in PBMC samples at the HC onset and during the follow-up. The DNA sequencing proved that the amplicons belonged to the SV40 wild-type. Urine samples of the two HC cases tested negative by cell cultures, PCR, or both for HCMV, BKV, JCV, and AV. CONCLUSIONS: The detection of SV40 DNA sequences suggest that this simian polyomavirus could be involved, at least in some cases, in the HC occurring in children after BMT.

BK Virus↗
PubMed1984

Sequential study of bacterial clearance in experimental cystitis.

Clearance of Escherichia coli in experimental cystitis was studied in the diuresing mouse model. Urine was collected daily; sediment was isolated by cytocentrifugation and either stained or treated with fluorescent antibodies directed against mouse immunoglobulins. During the initial phase of the infection the bacteria were either free and dispersed or adhering to epithelial cells but not generally to polymorphonuclear cells (PMNs). Subsequently, the bacteria adhered to each other, to epithelial cells and to PMNs, were phagocytosed by the latter and showed strong fluorescence. It is postulated that the appearance of opsonising and agglutinating antibodies in conjunction with activity of the PMNs is involved in bacterial clearance.

Adhesiveness↗