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PubMed1995

Increased number of substance P positive nerve fibres in interstitial cystitis.

OBJECTIVE: To explore the presence of the neuropeptide substance P (SP) in the bladders of rats and humans and to investigate its relationship to mast cells (MCs) in interstitial cystitis (IC), a bladder disorder which occurs mostly in women and is characterized by frequency of voiding, nocturia and debilitating suprapubic pain. PATIENTS, MATERIALS AND METHODS: Bladder biopsies from eight women with untreated IC (mean age 36 years, range 29-58) and five control patients with no IC were analysed and compared with each other and with bladder tissue from 12 rats. Immunohistochemistry and image analysis were used to examine the density of SP-positive nerve fibres and their relationship with MCs. RESULTS: SP-containing nerve fibres were present in the bladder of both rats and humans. They were increased only in the submucosa, but not in the detrusor, of IC patients and were frequently seen in juxtaposition to MCs. CONCLUSION: SP, a neuropeptide secreted from sensory nerve endings, has been implicated in the pathophysiology of pain and has been shown to trigger MC secretion. Moreover, MC secretion by SP is augmented by oestradiol and bladder MCs have been shown to express high affinity oestrogen receptors. A functional relationship between SP and MCs may explain the pathophysiology of the neuro-inflammatory and painful nature of IC.

Adult↗
PubMed1995

Substitution cystoplasty for intractable interstitial cystitis.

OBJECTIVE: To assess the results of substitution cystoplasty for the treatment of intractable interstitial cystitis (IC). PATIENTS AND METHODS: Thirty-two patients (29 women and three men; mean age 58 years, range 24-74) with intractable IC resistant to conservative therapy who had undergone substitution cystoplasty between 1983 and 1992 were reviewed. Their bladder capacities were measured pre-operatively and related to the outcome of treatment. RESULTS: All but two of the 22 women with a bladder capacity of < 250 mL under anaesthetic were improved (five) or cured (15) of their symptoms. The results in women with larger bladder capacities were much less reliable, with only two of seven being cured of their symptoms. The three men all had a good result. Those who had undergone supratrigonal cystectomy were more likely to void spontaneously, but four patients developed pyelonephritis from associated reflux. Subtotal cystectomy reduced the likelihood of reflux and, although there were too few patients for statistical significance, probably increased the chance of cure at the expense of increasing the need for intermittent self-catheterization (ISC). CONCLUSIONS: Pre-operative bladder capacity under anaesthetic is the most reliable predictor of outcome of substitution cystoplasty for treating intractable IC in women. It is contra-indicated if bladder capacity is > 250 mL. Supratrigonal cystectomy is a quick and easy operation and is preferable in the older patient. Subtotal cystectomy with reimplantation of the ureters is preferable in the younger patient, even though it may increase the need for ISC.

Adult↗
PubMed1995

Elevated mast cell tryptase in the urine of patients with interstitial cystitis.

OBJECTIVE: To investigate the number of tryptase positive bladder mast cells and the level of urine tryptase in interstitial cystitis (IC), a bladder disorder which occurs mostly in women and is characterized by suprapubic pain, frequency and nocturia. PATIENTS AND METHODS: Bladder biopsies from 37 women with IC and 15 control women with other bladder conditions (age range 18-63 years) were obtained during diagnostic bladder distension and frozen immediately. Mast cells positive for tryptase were identified by immunohistochemistry and evaluated by light microscopy. Tryptase was measured by solid phase radioimmunoassay in urine samples, collected immediately (spot) and during a period of 24 h, obtained from normal women volunteers, controls and patients with IC. To adequately quantify tryptase, the physiologically active tetramer was dissociated to inactive monomers with supersaturated NaCl (6.0 M), and then dialysed. RESULTS: The patients' spot urine sample tryptase levels were indistinguishable from those of controls, which included the normal women volunteers. However, the tryptase levels in 24 h urine samples were greatly elevated only in patients with IC, both before (P < 0.005), and especially after NaCl treatment and dialysis (P < 0.001). CONCLUSION: These results indicate that the tryptase levels of 24 h urine samples, combined with methylhistamine levels and the clinical criteria presently used, may possibly help to better identify IC.

Adolescent↗
PubMed2004

Sacral neuromodulation decreases narcotic requirements in refractory interstitial cystitis.

OBJECTIVE: To assess the efficacy of long-term sacral neuromodulation (InterStim(R), Medtronic Inc., Minneapolis, MN) in treating chronic pelvic pain associated with interstitial cystitis (IC, a symptom complex of urinary urgency, frequency and pelvic pain, often necessitating narcotics) refractory to standard therapy. PATIENTS AND METHODS: Twenty-one patients (17 female, four male, mean age 45.5 years, range 17-68) with refractory IC with chronic pelvic pain were reviewed retrospectively. In these patients a mean of six previous treatments for IC had failed. All patients had had cystoscopy and hydrodistension to confirm their diagnoses. All had a permanent InterStim device implanted by one surgeon (K.M.P.) between 2000 and 2002, after responding to a temporary test. Data were collected from chart reviews and patient questionnaires. Intramuscular morphine dose equivalents (MDEs) were calculated before and after implantation. RESULTS: All 21 patients responded to the questionnaire; the mean (range) follow-up after implantation was 15.4 (7.4-23.1) months. Eighteen patients used chronic narcotics before the InterStim and 20 reported moderate or marked improvement in pain afterward. The mean MDE decreased from 81.6 to 52.0 mg/day (36%) after implantation (P = 0.015). Four of 18 patients stopped all narcotics after InterStim implantation. CONCLUSIONS: Sacral neuromodulation decreases narcotic requirements and subjective pelvic pain in patients with refractory IC. Further decreases in MDE are anticipated as dose reductions continue in patients who improved.

Adolescent↗
PubMed2004

P2X and P2X receptor expression in human bladder urothelium and changes in interstitial cystitis.

OBJECTIVE: To investigate whether the expression of P2X(3) receptors (implicated in the pathophysiology of pain) is altered in human bladder urothelium from patients with interstitial cystitis (IC, a major symptom of which is pain), and as P2X(2) receptors can be co-expressed with P2X(3) receptors, to assess their expression also. PATIENTS AND METHODS: Bladder tissue samples were collected from patients undergoing cystectomy or radical prostatectomy. Patients with IC were diagnosed using the international criteria. RNA protein expression levels of both receptors were evaluated using reverse transcription-polymerase chain reaction (PCR), real-time quantitative PCR and Western blot analysis. RESULTS: P2X(2) was expressed in the human urothelium, in a glycosylated form. There was less gene expression of P2X(3) in IC urothelium, whereas P2X(2) gene expression was unchanged. This contrasted with the protein expression, which was increased for both P2X(2) and P2X(3). CONCLUSION: This is the first report of the expression of the P2X(2) receptor in human bladder urothelium. There was greater protein expression of both P2X(2) and P2X(3) in IC bladder urothelium which did not directly correlate with the gene expression. Changes in expression of P2X(2) and P2X(3) receptors may contribute to the pain that patients with IC have, and might provide novel drug targets.

Blotting, Western↗
PubMed2005

A prospective, double-blind, randomized cross-over study evaluating changes in urinary pH for relieving the symptoms of interstitial cystitis.

OBJECTIVE: To provide evidence for the clinical efficacy of changes in urinary pH on the pain associated with interstitial cystitis (IC). PATIENTS AND METHODS: A prospective, randomized, double-blind cross-over study was conducted with 26 women with IC between 2000 and 2002, consisting of cross-over instillations of urine at physiological pH (5.0), and neutral buffered pH (NaH(2)PO(4) buffered to pH 7.5). The outcome measured was the subjective symptom of pain assessed using a visual analogue scale at baseline, after the initial instillation of solution, at washout, and after the crossover instillation. Data were analysed using repeated-measures analysis of variance. RESULTS: There was no statistically significant difference between the mean (sd) change from baseline pain scores after instilling neutral buffered solution, at 0.50 (2.78), and acidic solution, at 0.33 (3.43) (P = 0.85). Secondary outcomes were analysed, including baseline variability and treatment-order effects; neither were significantly different between the groups. CONCLUSIONS: There was no statistically significant difference in subjective pain scores on instilling urine at physiological pH or sodium-phosphate buffered saline in these patients with IC. Further work is required to define the role, if any, of urinary pH in the pathophysiology and treatment of IC.

Acetic Acid↗
PubMed1987

P-fimbriated Escherichia coli in children with acute cystitis.

P-fimbriation of Escherichia coli is an important factor in the pathogenesis of childhood pyelonephritis. The present study investigates children with single episodes of symptomatic non-febrile urinary tract infection, i.e. cystitis, with respect to clinical appearance and bacteriology, especially the frequency of P-fimbriated E. coli. The study included 75 children, 57 of whom had their first attack of urinary tract infection. E. coli was the causative agent in 88% (66/75) of the infections, and 48% (32/66) of E. coli strains were P-fimbriated. No association was found between identification of P-fimbriated E. coli at index infection and proneness to reinfection during the following six-month period. It is suggested that P-fimbriated E. coli is a virulence factor even in lower urinary tract infections, when occurring in single, symptomatic episodes.

Acute Disease↗
PubMed2005

Eosinophilic cystitis and its management.

Eosinophilic cystitis (EC) is a rare clinicopathological condition characterized by transmural inflammation of the bladder predominantly with eosinophils, associated with fibrosis with or without muscle necrosis. The cause of EC remains unclear, although it has been associated with various aetiological factors, such as allergy, bladder tumour, bladder trauma, parasitic infections and chemotherapeutic agents. EC is, probably, caused by the antigen-antibody reaction. This leads to the production of various immunoglobulins, which, in turn, cause the activation of eosinophils and initiates the inflammatory process. The most common symptom complex consists of frequency, haematuria, dysuria and suprapubic pain. Cystoscopy and biopsy are the gold standard for diagnosis. Additional laboratory evidence supporting the diagnosis includes proteinuria, microscopic haematuria and peripheral eosinophilia, the last one occurring in few patients. There is no curative treatment for this condition. Current treatment modalities include transurethral resection of the bladder lesion along with non-specific medical therapy, such as non-steroidal anti-inflammatory agents or steroids. Because the lesion tends to recur in spite of the above therapy, long-term follow-up is mandatory.

Algorithms↗
PubMed1997

Potentiating effect of EDTA-Tris on the activity of antibiotics against resistant bacteria associated with otitis, dermatitis and cystitis.

Possible synergistic effects of the combination of EDTA-tromethamine (EDTA-Tris) and three antimicrobial agents (cephaloridine, kanendomycin and enrofloxacin) against resistant Gram-positive and Gram-negative bacteria are reported. Bacteria were isolated from eight cases of chronic otitis externa, five cases of chronic dermatitis and four cases of recurrent cystitis in dogs which had previously been treated with one of the three antibiotics without success. Animals exposed to EDTA-tromethamine plus the antibiotic recovered completely within 10 days, and were controlled clinically and bacteriologically for 180 days. Local irrigation with EDTA-tromethamine solution was well tolerated and no side effects were recorded.

Animals↗
PubMed1998

Interstitial cystitis: a neuroimmunoendocrine disorder.

Interstitial cystitis (IC) is a sterile bladder condition occurring primarily in females. It is characterized by frequency, nocturia, and suprapubic pain. IC symptoms are exacerbated during ovulation and under stress, thus implicating neurohormonal processes. The most prevalent theories to explain the pathophysiology of IC appear to be altered bladder lining and increased number of activated bladder mast cells. A defective bladder glycosaminoglycan (GAG) layer could allow penetration of allergic triggers, as well as chemicals, food preservatives, drugs, toxins, and adherent bacteria, all of which can activate bladder mast cells. Vasoactive, nociceptive, and proinflammatory molecules released can lead to immune cell infiltration and can sensitize neurons to secrete neurotransmitters or neuropeptides that can further activate mast cells. Mast cell-derived proteases can directly cause tissue damage, and it is noteworthy that urine tryptase is elevated in IC. Bladder mast cells are located close to neuronal processes, which are increased in IC, and they can be activated in situ by acetylcholine (ACh) and substance P (SP). Such activation is augmented by estradiol, which acquires significance in view of the fact that human bladder mast cells express estrogen receptors, but few progesterone receptors, which may explain the worsening of IC symptoms during ovulation. Finally, acute psychological stress in rats leads to mast cell activation that can be reduced by depletion of SP or neutralization of peripheral immune corticotropin-releasing hormone (CRH). These findings suggest that IC could be a syndrome with neural, immune, and endocrine components, in which activated mast cells play a central role.

Animals↗
PubMed1992

[A clinical study on postantibiotic effect (PAE) and its application to chemotherapy for complicated cystitis with an automatic simulator of urinary drug concentration].

In an in vitro complicated cystitis model, the concentrations of the urinary antimicrobial agents were determined using a computer-controlled automatic urine concentration simulator. The effects on the bacterial count curves showing the presence or absence of PAE in antimicrobial agents were studied by comparing the times required for regrowth to the concentration at the initial inoculation, i.e., effective regrowth time (ERT). The following results were obtained. 1. When beta-lactam antimicrobial agents (such as AMPC and CFIX) with no PAE against the gram-negative rods were tested, the ERT of the gram-negative rods were about two hours shorter than that of the gram-positive coccus. 2. When new quinolone antimicrobial agents (such as OFLX) and aminoglycosides (such as ISP) that possess PAE against both the gram-positive and negative organisms were used there was no difference between ERT of the gram-negative rods and gram-positive coccus. Therefore, it was demonstrated that the presence or absence of PAE is also reflected in the cell number curve in the case of this in vitro model, more closely related to clinical cases, when the antibiotics is simulated in urinary concentration shifting.

Amoxicillin↗
PubMed1992

[Significance of the combined treatment with isepamicin and piperacillin in an in vitro model for complicated cystitis operated by automatic simulator apparatus for urinary concentration].

Isepamicin (ISP) and piperacillin (PIPC) were shifted to the urinary concentration by employing an in vitro complicated cystitis model operated by a computer-controlled automatic simulator for urinary concentration, and administrated to bacteria in the urinary bladder model (Pseudomonas aeruginosa: P. aeruginosa, initial cell concentration: 10(7) cfu/ml). In this case, effects by single treatment with ISP or PIPC on cell number curves were examined. Further, significance of the combined treatment with ISP and PIPC were investigated by changing the order of each treatment. And following the results were obtained. 1. In a single treatment with PIPC the cell concentration was minimum (10(4) cfu/ml) at 9th hour after its treatment and thereafter, regrowth to the same level as the initial concentration was observed at 16th hour. 2. In the case of single treatment with ISP, the cell concentration became minimum (10(2) cfu/ml) at 13th hour after the treatment and raised to the same concentration as the initial one at 25th hour. 3. In the combined treatment, the cell concentration was minimum (less than 10(1) cfu/ml) at 26th hour in the case of prior treatment with ISP. Thereafter, regrowth was observed and the cell concentration at 42nd hour reached to the initial cell concentration. 4. In simultaneous treatment with ISP and PIPC, the cell concentration at 24th hour was minimum (10(1) cfu/ml) and reached to the same level as the initial one after regrowth. From these results, it was found that the combined treatment with ISP and PIPC caused more reduction of the cell concentration than either single treatment. Further, regrowth of the cells was suppressed for longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Simulation↗
PubMed1993

Macrophages in the urine in acute bacterial cystitis.

In the previous study in this series of studies concerning the role of macrophages in urinary tract infection, we attempted to detect macrophages in the urine of acute bacterial cystitis patients by nonspecific esterase staining of urinary sediment, however none of the leukocytes stained, probably because of cell damage caused by the urine and by centrifugation. In the present study, detection of macrophages in urine was again attempted, this time by prompt transfer of urinary leukocytes to culture medium after minimum centrifugation, 1 hr culture in a glass bottom chamber and non-specific staining of leukocytes adhering to glass. Macrophages in urine were detected by this method, and they comprised 5.9% of the adherent leukocytes, although macrophage spreading, which implies macrophage activation and is often seen in the early stage of nonbacterial prostatitis, was hardly ever observed. The percentages of adherent leukocytes were not correlated with urine osmolarity, probably because the effect of urine was minimized by prompt transfer of urinary leukocytes to culture medium after the urine samples had been collected. There have been quite few studies involving culture of urinary leukocytes in the past. Our simple techniques, such as prompt transfer of urinary leukocytes to culture medium after centrifuging with minimum gravity and for a minimum period of time, appear to be useful in the study of urinary leukocytes using other cells which appear in urinary tract infection, as well as cytokines and antibiotics, to clarify cellular mechanisms of defenses in urinary tract infection.

Acute Disease↗
PubMed1988

Activity of E-3846, a new fluoroquinolone, in vitro and in experimental cystitis and pyelonephritis in rats.

The in vitro antibacterial activity of E-3846, a new fluoroquinolone carboxylic acid derivative with a pyrrol ring substituent at position 7, was evaluated in comparison with norfloxacin and ciprofloxacin. E-3846 was more active than the reference quinolones against Staphylococcus species, including methicillin-resistant strains. E-3846 was similar to ciprofloxacin and more active than norfloxacin against Streptococcus (Enterococcus) faecalis. In general, E-3846 was more active than norfloxacin against members of the family Enterobacteriaceae, but less active than ciprofloxacin. For Pseudomonas aeruginosa, the MICs giving 90% inhibition for E-3846, norfloxacin, and ciprofloxacin were 2, 1, and 0.25 micrograms/ml, respectively. The activity of E-3846 increased at acid pH; in contrast, acid pH caused a pronounced decrease in the activity of norfloxacin and ciprofloxacin. In vivo, E-3846 demonstrated excellent therapeutic efficacy in treating experimental S. faecalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa cystitis and pyelonephritis in rats.

Animals↗
PubMed2005

Virulence genotype and phylogenetic origin in relation to antibiotic resistance profile among Escherichia coli urine sample isolates from Israeli women with acute uncomplicated cystitis.

To clarify the virulence and phylogenetic implications of antimicrobial agent resistance in Escherichia coli, 100 E. coli isolates from urine samples of Israeli women with acute uncomplicated cystitis were analyzed by molecular phylotyping and virulence genotyping for comparison with resistance phenotypes. The differences between the isolates that were resistant and susceptible to trimethoprim-sulfamethoxazole and ampicillin were minimal. In contrast, ciprofloxacin resistance was associated with greatly reduced inferred virulence and categorical shifts away from the highly virulent phylogenetic group B2, which explained much of the virulence effect. The results of amplification fingerprinting suggested that most ciprofloxacin-resistant isolates represented unique clonal groups and were not derived from clonal groups with more highly virulent susceptible isolates. These findings suggest that virulence and antimicrobial resistance are not mutually exclusive in E. coli clinical isolates. Instead, the relationship between virulence and antimicrobial resistance varies according to the particular resistance phenotype; for ciprofloxacin resistance, the relationship is strongly influenced by phylogenetic background. The basis for the concentration of ciprofloxacin resistance in non-B2 phylogenetic groups remains unknown.

Acute Disease↗
PubMed1979

In vitro adherence of radioactively labeled Escherichia coli in normal and cystitis-prone females.

Numerous investigators report data obtained using an in vitro quantitative assay for measuring bacterial adherence to epithelial cells. We found this assay to contain significant sources of error in the large variation in number of bacteria bound per cell and in the dependence on the investigator's visual counting of bacteria bound per cell. In the modified assay described here, we eliminated the need for visual counting of bacteria by incorporating the use of radioactively labeled Escherichia coli. This allowed quantitation of bacterial adherence to as many as 50,000 vaginal cells, whereas the visual counting system limits the determination to perhaps 50 cells. We feel that the use of radioactively labeled bacteria in place of the visual counting system increases the validity and sensitivity of this assay. Using the modified method, we found no statistically significant differences among values for adherence of E. coli type 04 to the vaginal cells of control and cystitis-prone women at either pH 6.4 or 4.0.

Adhesiveness↗
PubMed2006

Role of phase variation of type 1 fimbriae in a uropathogenic Escherichia coli cystitis isolate during urinary tract infection.

Type 1 fimbrial phase-locked mutants of uropathogenic Escherichia coli cystitis isolate F11 were used to assess the role of the invertible element during urinary tract infection. Compared to the wild type, the phase-locked off mutant was attenuated, and constitutive production of type 1 fimbriae by the phase-locked on mutant did not provide a competitive advantage.

Animals↗
PubMed1999

PCR detection of adenovirus in a bone marrow transplant recipient: hemorrhagic cystitis as a presenting manifestation of disseminated disease.

Adenoviruses (AdV), causing fatal disseminated infections in bone marrow transplant (BMT) recipients, are associated not only with hemorrhagic cystitis (HC) but also with hepatitis, conjunctivitis, and viral interstitial pneumonia. The importance of this virus as a cause of disseminated disease, however, has remained underappreciated. AdV infection has been diagnosed primarily through the use of cell culture. The fact that cell culture is insensitive for detecting this virus has hindered recognition of the role that AdV may play in morbidity and mortality in BMT recipients. To emphasize these points, we describe a patient who presented with HC due to AdV serotype 11, genotype c, and died with disseminated infection. In addition to cell culture, this study used a newly developed PCR-based method, capable of detecting all AdV serotypes tested, including different genotypes of serotype 11. The PCR result was positive in all culture-positive samples, including samples of urine, conjunctiva, and bronchoalveolar lavage (BAL). Importantly, the PCR method provided evidence of urinary shedding of AdV in a pretransplant, culture-negative specimen and showed dissemination in a subset of culture-negative specimens, including BAL, blood, and bone marrow samples. The lack of widespread awareness of the fact that localized infections may presage dissemination, and the previous associated lack of rapid, sensitive diagnostic assays, has impaired recognition of AdV infections in patients undergoing BMT. Early detection may contribute to therapy modification and avoidance of unwarranted diagnostic procedures. It may also assist in epidemiologic control of this highly infectious pathogen and lead to a renewed interest in preventive and therapeutic approaches.

Adenovirus Infections, Human↗