Comparison of mid catheter collection and suprapubic aspiration of urine for diagnosing bacteriuria due to fastidious micro-organisms

We examined 40 female patients for the presence of fastidious bacteria in the bladder by culture of mid catheter and suprapubic aspiration urine specimens. Gardnerella vaginalis and Ureaplasma urealyticum were the most frequently isolated fastidious species. The suprapubic aspirate was positive in 3 patients with more than 10(5) colony-forming units per ml. Gardnerella vaginalis and 7 with more than 10(2) colony-forming units per ml. Ureaplasma urealyticum in the mid catheter urine specimen, while it was negative for bacteria in 6 patients with less than 10(4) colony-forming units per ml. coryneform bacilli or lactobacilli in the mid catheter urine specimen. The results show that culture of mid catheter urine samples provides a reasonable guide to the presence of bacteriuria owing to fastidious micro-organisms and can be used when a suprapubic aspiration specimen cannot be obtained easily.     

Culture of mid catheter urine collected via an open-ended catheter: a reliable guide to bladder bacteriuria

Colony counts were compared from urine samples obtained by suprapubic aspiration and via a short, wide bore, open-ended urethral catheter. We studied 30 female patients in whom suprapubic aspiration of bladder urine was necessary to confirm the presence of bacteriuria with conventional or fastidious organisms. Catheterization was done immediately following suprapubic aspiration. Culture results of mid catheter urine specimens were similar to those from suprapubic aspiration urine specimens in 27 of 30 patients, a result considerably superior to that obtained with a conventional side-hole catheter. We conclude that a short, wide bore, open-ended catheter should be used to obtain urine specimens from female patients. Results confirm catheter specimens to be a satisfactory alternative to bladder aspiration of urine for detection of bacteriuria caused by fastidious micro-organisms or in patients with low numbers of conventional urinary tract pathogens.     

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 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.     

Interstitial cystitis: early diagnosis, pathology, and treatment.

In a retrospective review, 52 patients with interstitial cystitis have been studied. Patients with persistent lower tract irritative symptoms, repeatedly sterile urine, and negative urine cytology must be suspected of having interstitial cystitis, and a diagnosis of urethral syndrome in such patients is highly questionable until cystoscopy under anesthesia has been performed. We believe that the finding of multiple petechia-like hemorrhages (glomerulations) on the second distention of the bladder is the hallmark of interstitial cystitis, and that a reduced bladder capacity and a Hunner's ulcer represent a different (classic) stage of this disease. In all stages, the characteristic histologic finidng is submucosal edema and vasodilation. The presence of eosinophils and mast cells is variable, and even in the classic disease the muscularis often appears to be normal. Immuno fluorescent studies and laboratory tests, including the fluorescent antinuclear antibody test (FANA), have not helped us to diagnose (or investigate) interstitial cystitis. Bladder instillations with a 0.4 per cent solution of oxychlorosene sodium (Clorpactin WCS-90) have provided remarkable relief for many patients with this disease, particulary those with the classic form.     

DETECTION OF EUBACTERIA IN INTERSTITIAL CYSTITIS BY 16S rDNA AMPLIFICATION

Objective

To determine what role non-culturable microorganisms play in the etiology of interstitial cystitis (IC).

Materials and Methods

Thirty patients fulfilling NIH criteria for the diagnosis of interstitial cystitis and sixteen control patients with culture negative urine gave written informed consent and underwent bladder biopsy. Polymerase chain reaction (PCR) using two sets of universal primers for bacterial 16S rDNA was performed on urine from the cystoscope and on a cold cup bladder biopsy specimen. Of the PCR positive bladder biopsies, three patients with interstitial cystitis and three controls were randomly selected and cloned. Ten clones from each were sequenced and putative taxonomic assignments made.

Results

12/26 (46%) IC and 5/12 (42%) control urine specimens and 16/30 (53%) and 9/15 (60%) bladder biopsies were PCR positive, respectively. The bacterial populations in the two patient groups tested appeared to be different based upon analysis of the 16S rRNA sequences.

Conclusions

Both IC and control patients had non-culturable bacteria in their bladders. A random sampling of the two populations revealed that the bacterial populations are different, suggesting a possible link between one or more bacterial species and IC.     

膀胱疼痛综合征相关症状的鉴别诊断及临床意义

目的探讨鉴别诊断在女性膀胱疼痛综合征／间质性膀胱炎诊断中的重要意义。方法回顾2005年至2011年间42例转诊到广州医科大学附属广州市第一人民医院的膀胱疼痛综合征／间质性膀胱炎（IC）女性患者的临床资料。患者平均年龄49（26～69）岁,IC病程14（6～24）个月。通过详细分析病史及辅助检查（如尿动力学检查、尿道膀胱镜检、排尿期膀胱尿道造影、尿流率、剩余尿量测定、磁共振等）来探讨这些Ic病例是否存在其他泌尿系疾病,以及这些新发现的其他疾病经治疗后IC症状的改善情况。站栗尿动力学检查发现10例（24％）存在膀胱出口梗阻;排尿期膀胱尿道造影联合尿流率和剩余尿量发现16例（38％）存在远端尿道狭窄;核磁共振发现5例（12％）存在尿道憩室;尿道膀胱镜检发现21例（50％）膀胱三角区严重黏膜充血、滤泡增生明显,部分黏膜下可见弥漫脓包形成,5例（12％）存在尿道外口狭窄。42例患者根据新发现的病变进行相应的治疗,如膀胱出口梗阻或尿道外口狭窄接受尿道扩张、尿道松解术或者尿道外口成形术;膀胱炎接受经尿道膀胱黏膜电灼术;尿道憩室接受尿道憩室切除术等。42个患者中,26例（62％）的症状明显改善或完全消失,16例（38％）症状元改善。平均随访时间18（6～36）个月。结论膀胱疼痛综合征／间质性膀胱炎因与泌尿系统其他疾病的症状相似而容易被混淆。只有做好缜密的鉴别诊断才能避免误诊。     

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.     

女性顽固性尿频尿急78例原因分析

目的探讨引起女性顽固性尿频尿急等下尿路症状的原因。方法本组患者78例,年龄23～8548.8±15.6岁。临床表现为尿频、尿急,伴尿痛25例、下腹部或耻骨上区疼痛53例,病程44.5±50.6个月。尿道触诊及按摩,尿液分析及培养;泌尿系超声、IVU;麻醉下尿道膀胱内窥镜检查、膀胱水扩张及黏膜活检。间质性膀胱炎诊断采用NIDDK标准;腺性膀胱炎及内翻性乳头状瘤的诊断根据病理结果;尿道腺炎根据尿道按摩前后尿液白细胞变化、尿道有无触痛及尿道镜检进行诊断。结果间质性膀胱炎37例,水扩张后镜下均有丝球状出血,其中合并hunner溃疡2例;尿道腺炎18例,其中尿道腺管开口处可见脓点11例;腺性膀胱炎17例;内翻性乳头状瘤6例。结论对于顽固性的尿频、尿急,伴有尿痛、下腹部或会阴部疼痛,病程较长,而尿常规正常及尿培养阴性者应进行包括尿道、尿液及膀胱尿道内窥镜等详细的系统检查,可使绝大多数患者获得明确的诊断,以便得到正确的治疗。     

Stimulated release of urine histamine in interstitial cystitis.

The diagnosis of interstitial cystitis is primarily made based on clinical and cystoscopic findings with exclusion of other bladder diseases. Despite all of the efforts at definitive identification, interstitial cystitis lacks universal objective findings. Mast cell activation with associated histamine release has been postulated as an etiological factor leading to the symptom complex associated with interstitial cystitis. To investigate this hypothesis, a 3-step controlled prospective study was conducted. In step 1 reliability of urine histamine assay was critically examined, and the assay was established to be simple, reliable and valid. In step 2 random spot urine histamine levels (basal state) were measured in 25 noninterstitial cystitis and 15 interstitial cystitis patients (22.1 +/- 0.95 ng./ml. versus 19.2 +/- 1.19 ng./ml.). There was no significant difference in the random urine histamine levels between the 2 groups (p greater than 0.05). In step 3 urine histamine levels were measured before and after hydrodistention (acute stimulation) in 7 noninterstitial cystitis controls and 6 newly diagnosed interstitial cystitis patients under general anesthesia. The urine histamine-to-creatinine ratio was used to correct for the dilutional effect of normal saline used during hydrodistention. The urine histamine-to-creatinine ratios of the control group showed no significant difference before and after hydrodistention. However, the difference in the urine histamine-to-creatinine ratios of the interstitial cystitis group compared to the controls before and after hydrodistention was highly significant (p less than 0.001). Although measurement of random spot urine histamine alone (basal state) was not found useful to make the diagnosis of interstitial cystitis, measurement of urine histamine before and immediately after hydrodistention (acute stimulation) may become an important objective parameter to assist in the diagnosis of interstitial cystitis.     

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.     

Bladder stretch alters urinary heparin-binding epidermal growth factor and antiproliferative factor in patients with interstitial cystitis

PURPOSE: The etiology of interstitial cystitis is unknown. Urine from patients with interstitial cystitis has been shown to inhibit urothelial proliferation through a putative antiproliferative factor and to contain decreased levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) compared to controls. Stretch of detrusor smooth muscle cells is known to stimulate HB-EGF production. Because bladder hydrodistention sometimes alleviates the symptoms of interstitial cystitis, we determined whether the stretch stimulus of hydrodistention alters antiproliferative factor activity and/or HB-EGF in interstitial cystitis urine specimens. MATERIALS AND METHODS: Urine was collected immediately before, and 2 to 4 hours and 2 weeks after hydrodistention from 15 patients with symptoms and cystoscopic findings compatible with interstitial cystitis and 13 controls. Hydrodistention was performed with the subject under general or regional anesthesia and bladders were distended to 80 cm. water 3 times. Urinary HB-EGF was measured by enzyme-linked immunosorbent assay and urinary antiproliferative factor activity was determined by measuring 3H-thymidine uptake by normal human bladder urothelial cells. RESULTS: Hydrodistention significantly increased urinary HB-EGF in patients with interstitial cystitis toward normal control values (before distention p = 0.003, 2 weeks after distention p = 0.67). Urine antiproliferative factor activity decreased significantly after hydrodistention in patients with interstitial cystitis. However, antiproliferative factor activity in interstitial cystitis and control specimens was still statistically different 2 weeks after distention (before distention p = 0.0000004, 2 weeks after distention p = 0.04). CONCLUSIONS: Bladder stretch increased HB-EGF and conversely reduced antiproliferative factor activity in urine from patients with interstitial cystitis but not controls up to 2 weeks after distention. These results provide additional evidence for the possible role of antiproliferative factor and decreased HB-EGF in the pathophysiology of interstitial cystitis. To our knowledge this is also the first human study to show that in vivo bladder stretch can alter urinary factors that regulate cell growth.     

导尿管伴随性尿路感染及其防治

为探讨导尿管伴随性尿路感染（UTIc）的发生、发展规律及防治措施，对57例留置导尿管患者随机分组进行观察，具体方法是隔日收集尿液送细菌培养，当尿培养细菌数＞105／ml时定为尿路感染。结果3组患者随插管时间的延长，尿培养细菌阳性率逐日增加．3组间相应无效的细菌感染率有显著性差异（P＜0．05）．认为全身应用有效抗生素配合0．1％新洁尔灭定时冲洗导尿管并清除尿道口分泌物，可延缓UTIc的发生，对短期留置导尿管的患者，此法是一种较好的预防感染的方法，但对长期留置导尿管而发生感染的患者仍难以奏效．     

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.     

Polypoid cystitis unrelated to indwelling catheters

Since polypoid cystitis (PC) is generally caused by indwelling catheter use, in order to evaluate the patients with PC unrelated to a intravesical catheter, a retrospective analysis of the records of the Pathology Department of Turgut Özal Medical Center was performed and this revealed 8 patients. Mean age of the 2 female and 6 male patients was 48 years (28 to 70). None of the patients had bacterial growth in urine cultures. All cases were diagnosed incidentally by radiologic and cystoscopic examinations in the evaluation of different conditions, such as hematuria, ovarian abscess, bladder carcinoma, erectile dysfunction, neurogenic bladder, benign prostate hyperplasia and unexplained dysuria. At the beginning, all patients were diagnosed mistakenly as bladder carcinoma. The definitive diagnosis was made after histopathologic examinations of transurethrally resected specimens. Patients were followed for 6 months to 2 years after first diagnosis. No recurrence was established during follow-up. The final urologic examinations which were done currently, were normal.In conclusion, PC is a benign lesion and should be considered in the differential diagnosis of transitional cell carcinoma of the bladder.     

Urinary excretion of a metabolite of histamine (1,4-methyl-imidazole-acetic-acid) in painful bladder disease

Thirteen patients with interstitial cystitis (detrusor mastocytosis) and 12 other patients with painful bladder disease without mastocytosis collected 24-h urine specimens that were analysed for the major metabolite of histamine, 1,4-methyl-imidazole-acetic-acid (1,4-MIAA), by reversed phase ion-pair high performance liquid chromatography. The median urinary excretion of 1,4-MIAA was 3.34 mg/24 h (range 1.47-4.66) in the patients with detrusor mastocytosis and 1.75 mg/24 h (range 0.18-4.30) in the other patients with a painful bladder (P less than 0.01). It was concluded from this study that patients with a painful bladder and detrusor mastocytosis had a significantly elevated urinary excretion of 1,4-MIAA compared with other painful bladder patients without mastocytosis, whose urinary excretion of 1,4-MIAA was within the normal range (0.72-2.34 mg/24 h). We suggest that the urinary excretion of 1,4-MIAA might be useful in the diagnosis of interstitial cystitis.     

Alternate Occurrence of Allergic Disease and an Unusual Form of Interstitial Cystitis

Background : It has been postulated that interstitial cystitis can be induced by an allergy. This is partly based on the observation that many patients with interstitial cystitis also have allergic diseases. In this study, an allergic evaluation was conducted on patients with interstitial cystitis complicated by bronchial asthma, a typical allergic disease.
Methods : Clinical histories were obtained and biopsy specimens from the vesical walls of the study patients were examined histologically. Cutaneous tests and IgE radioallergosorbent tests (RAST) were performed. Further, intravesical provocation tests were carried out using IgE RAST-positive antigens, and histamine release assays were performed on the vesical biopsy specimens using anti-lgE antibodies.
Results : Five of 6 patients alternately exhibited symptoms of allergic disease and bladder symptoms. The eosinophil and mast cell counts in the vesical biopsy specimens of these 5 patients were increased. Furthermore, an intravesical provocation test performed using the IgE RAST-positive antigen was positive in 4 patients. The mean vesical biopsy specimen histamine release was 1 7.7% for patients with interstitial cystitis with bronchial asthma which was significantly higher than that for interstitial cystitis patients without bronchial asthma (8.9%) or the control group (4.5%). The prognosis of patients with interstitial cystitis with allergic complications was relatively good.
Conclusion : Patients with bronchial asthma exhibited hypersensitivity both generally and locally in the bladder. The alternation phenomenon was observed between the hypersensitive organs.     

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.     

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.     

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.