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Prevention of recurrent acute cystitis by methenamine hippurate: double blind controlled crossover long term study.

In a randomised, double blind, long term, crossover study 1 g twice daily of methenamine hippurate was compared with placebo for its preventive effect on recurrent attacks of acute cystitis. Methenamine hippurate and placebo were interchanged every six months for two years. During one of the years patients took 250 ml extra fluid every morning and evening. Out of 21 enrolled patients, 14 completed the first year and 13 both years of treatment, which permitted the evaluation of 27 patient years. There were 52 episodes of acute cystitis caused by reinfection: 41 occurred during placebo treatment and only 11 during the methenamine hippurate regimen (p less than 0.01). Extra fluid intake did not reduce the incidence of acute cystitis, nor did it reduce the effect of methenamine hippurate. Methenamine hippurate is an effective prophylactic agent against recurrent acute cystitis and has the advantage of not inducing cross resistance to conventional antibiotics.

Acute Disease↗

Do urethral Escherichia coli cause abacterial cystitis?

To determine whether Escherichia coli in or near the urethra caused symptoms of abacterial cystitis, the results of serial cultures from the vaginal introitus of 92 patients with recurrent cystitis were compared with symptoms at clinic visits when they were abacteriuric. Similar comparisons were made in 15 of these patients using cultures from the external urethral meatus and proximal urethra. E coli were grown from the vaginal introitus, urethral meatus and proximal urethra at 41, 66 and 26% of visits respectively. Overall they were not significantly more often isolated when patients had cystitis, and the serotype was unrelated to symptoms. E coli was cultured significantly more often from the introital swabs of symptomatic intermittently bacteriuric (IB) women than from symptomatic persistently non-bacteriuric (NB) patients; and more often from symptomatic than from asymptomatic IB patients, although this difference was not significant. These findings were consistent with previous suggestions that symptoms of apparently "abacterial" cystitis in IB patients are due to occult coliform infection. We found no direct evidence that E coli were the cause of symptoms in persistently non-bacteriuric women, or that urethral colonisation caused them. However E coli were isolated from the introitus of control women only half as often as from both intermittently bacteriuric and persistently non-bacteriuric patients.

Adult↗

Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis.

Corticotropin-releasing factor (CRF) is a prominent neuropeptide involved in micturition reflexes, and different roles in these reflexes have been suggested. These studies examined the expression of CRF in the urinary bladder and lumbosacral sacral parasympathetic nucleus (SPN) in response to cyclophosphamide (CYP)-induced cystitis (4 h, 48 h, or chronic) in rats. The expression of CRF receptors, CRF(1) and CRF(2), was examined in urinary bladder from control and CYP-treated rats. Urinary bladder and lumbosacral spinal cord were harvested from rats killed by isoflurane (4%) and thoracotomy. CRF protein expression in whole urinary bladders significantly (P < or = 0.01) increased with 48 h or chronic CYP treatment. CRF immunoreactivity (IR) was increased significantly (P < or = 0.01) in the urothelium and SPN after CYP treatment. CRF IR nerve fibers increased in density in the suburothelial plexus and detrusor smooth muscle whole mounts with CYP-induced cystitis. CRF(2) receptor transcript was expressed in the urothelium or detrusor smooth muscle, and CRF(2) receptor expression increased in whole bladder with CYP-treatment, whereas no CRF(1) receptor transcript was expressed in either urothelium or detrusor. Immunohistochemical studies demonstrated CRF(2) IR in urinary bladder nerve fibers and urothelial cells from control animals, whereas no CRF(1) IR was observed. These studies demonstrated changes in the expression of CRF in urinary bladder and SPN region with CYP-induced cystitis and CRF receptor (CRF(2)) expression in nerve fibers and urothelium in control rats. CRF may contribute to urinary bladder overactivity and altered sensory processing with CYP-induced cystitis.

Animals↗

Region-specific changes in the phosphorylation of ERK1/2 and ERK5 in rat micturition pathways following cyclophosphamide-induced cystitis.

Chronic inflammation of the urinary bladder generates hyperalgesia and allodynia. Growing evidence suggests a role of ERK in mediating somatic and visceral pain processing. In the present studies, we characterized and compared the activation of two ERK isoforms, ERK1/2 and ERK5, in micturition pathways, including the urinary bladder, lumbosacral dorsal root ganglia (DRG), and spinal cord in adult female and male rats before and after cyclophosphamide (CYP)-induced bladder inflammation. Results showed differential activation of ERK1/2 and ERK5 in these regions following cystitis. The level of phospho-ERK1/2 but not phospho-ERK5 was increased in the urinary bladder; the level of phospho-ERK5 but not phospho-ERK1/2 was increased in DRG; and the level of phospho-ERK1/2 but not phospho-ERK5 was increased in lumbar spinal cord following cystitis compared with control. Cystitis-induced upregulation of phospho-ERK1/2 and phospho-ERK5 was time dependent and showed similar patterns in female and male rats. The level of phospho-ERK1/2 in bladder was increased at 2 and 8 h after CYP injection; the level of phospho-ERK5 in DRG was increased at 8 and 48 h after CYP injection; and the level of phospho-ERK1/2 in lumbar spinal cord was increased at 48 h after CYP injection. The result that phospho-ERK5 was exclusively increased in DRG neurons, while phospho-ERK1/2 was increased in the spinal cord and the urinary bladder after cystitis, suggests a region-specific effect of neurotrophins on micturition pathways following bladder inflammation.

Animals↗

Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes.

Pituitary adenylate cyclase activating polypeptide (PACAP) peptides are expressed and regulated in sensory afferents of the micturition pathway. Although these studies have implicated PACAP in bladder control, the physiological significance of these observations has not been firmly established. To clarify these issues, the roles of PACAP and PACAP signaling in micturition and cystitis were examined in receptor characterization and physiological assays. PACAP receptors were identified in various tissues of the micturition pathway, including bladder detrusor smooth muscle and urothelium. Bladder smooth muscle expressed heterogeneously PAC(1)null, PAC(1)HOP1, and VPAC(2) receptors; the urothelium was more restricted in expressing preferentially the PAC(1) receptor subtype only. Immunocytochemical studies for PAC(1) receptors were consistent with these tissue distributions. Furthermore, the addition of 50-100 nM PACAP27 or PACAP38 to isolated bladder strips elicited transient contractions and sustained increases in the amplitude of spontaneous phasic contractions. Treatment of the bladder strips with tetrodotoxin (1 muM) did not alter the spontaneous phasic contractions suggesting direct PACAP effects on bladder smooth muscle. PACAP also increased the amplitude of nerve-evoked contractions. By contrast, vasoactive intestinal polypeptide had no direct effects on bladder smooth muscle. In a rat cyclophosphamide (CYP)-induced cystitis paradigm, intrathecal or intravesical administration of PAC(1) receptor antagonist, PACAP6-38, reduced cystitis-induced bladder overactivity. In summary, these studies support roles for PACAP in micturition and suggest that inflammation-induced plasticity in PACAP expression in peripheral and central micturition pathways contribute to bladder dysfunction with cystitis.

Animals↗

Alterations in spinal cord Fos protein expression induced by bladder stimulation following cystitis.

These studies examined Fos protein expression in spinal cord neurons synaptically activated by stimulation of bladder afferent pathways after cyclophosphamide (CYP)-induced bladder inflammation. In urethan-anesthetized Wistar rats with cystitis, intravesical saline distension significantly (P </= 0.0005) increased the number of Fos-immunoreactive (IR) cells observed in the rostral lumbar (L1, 35 cells/section; L2, 27 cells/section) and caudal lumbosacral (L6, 120 cells/section; S1, 96 cells/section) spinal cord compared with control animals, but Fos protein expression in the L5 segment was not altered. The topographical distribution of Fos-IR cells was also altered in the lumbosacral spinal cord. The majority of Fos-IR cells were distributed in the dorsal commissure (45%), with smaller percentages in the sacral parasympathetic nucleus (25%), medial dorsal horn (20%), and lateral dorsal horn (10%). These results demonstrate that urinary bladder distension produces increased numbers and an altered distribution pattern of Fos-IR cells after cystitis. This altered distribution pattern resembles that following noxious irritation of the bladder in control animals. Pretreatment with capsaicin significantly reduced the number of Fos-IR cells induced by bladder distension after cystitis. These data suggest that chronic cystitis can reveal a nociceptive Fos expression pattern in the spinal cord in response to a non-noxious bladder stimulus that is partially mediated by capasaicin-sensitive bladder afferents.

Acetic Acid↗

Presence of mucosal change in the urinary bladder in nonhematuric patients with long-term exposure and/or accumulating high-dose cyclophosphamide. Possible significance of follow-up cystoscopy on preventing development of cyclophosphamide-induced hemorrhagic cystitis.

OBJECTIVE: Cyclophosphamide (CPA)-induced hemorrhagic cystitis is sometimes difficult to manage. We investigated the mucosal changes in patients subjected to CPA therapy in relation to the duration and accumulating dose of CPA. METHODS: Fifteen patients, all of whom were receiving CPA, were studied. Investigation of the dose and duration of CPA administration, urinalysis and cystoscopy was performed. RESULTS: The total doses of CPA administered ranged from 2.5 to 237.0 g, and the duration of administration ranged from 4 to 130 months. Four patients with hematuria (micro or macro) showed various degrees of mucosal hyperemia and telangiectasia. Of 11 patients without microhematuria, 6 patients also revealed mucosal changes distinctive of CPA-induced hemorrhagic cystitis. CPA-induced cystitis with no hematuria insidiously progressed in the patients who received CPA orally at a total dose of more than 40 g and/or for longer than 36 months. CONCLUSION: Early mucosal lesion of the urinary bladder, which will most likely be followed by CPA-induced hemorrhagic cystitis, may develop prior to the appearance of microscopic hematuria. Periodic prophylactic cystoscopy is recommend in patients receiving CPA.

Adult↗

Psychological factors related to interstitial cystitis.

Psychological factors related to interstitial cystitis were studied in 31 women. The control group consisted of 24 women with acute bacterial cystitis. The subjects were tested with psychological methods. Results showed that traditional signs of psychic pathology were not related to the symptoms of interstitial cystitis but psychic helplessness and inadequacy in coping with problems was found in the patients. Sexual problems were prominent. Results do not refer to the psychological origin of interstitial cystitis but stress that psychological factors have to be taken into consideration in the treatment of these patients.

Adaptation, Psychological↗

Granular cystitis in girls. Long-term follow-up.

Granular cystitis or 'papular cystitis' is a very common form of cystitis in young girls. In this paper we show the evolution of this affliction in women after puberty. In a series we were able to follow up leukoplakia or follicular cystitis patients to the age of 16 years.

Adolescent↗

APF, HB-EGF, and EGF biomarkers in patients with ulcerative vs. non-ulcerative interstitial cystitis.

BACKGROUND: Interstitial cystitis (IC) is a chronic bladder disorder, with symptoms including pelvic and or perineal pain, urinary frequency, and urgency. The etiology of IC is unknown, but sensitive and specific biomarkers have been described, including antiproliferative factor (APF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and epidermal growth factor (EGF). However, the relative sensitivity of these biomarkers in ulcerative vs. nonulcerative IC is unknown, and these markers have yet to be validated in another laboratory. We therefore measured these markers in urine from patients with or without Hunner's ulcer, as well as normal controls, patients with bladder cancer, and patients with bacterial cystitis, at the First Hospital of China Medical University. METHODS: Urine specimens were collected from two groups of Chinese IC patients (38 IC patients with Hunner's ulcers, 26 IC patients without Hunner's ulcers), 30 normal controls, 10 bacterial cystitis patients and 10 bladder cancer patients. APF activity was determined by measuring 3H-thymidine incorporation in vitro, and HB-EGF and EGF levels were determined by ELISA. RESULTS: APF activity (inhibition of thymidine incorporation) was significantly greater in all IC patient urine specimens than in normal control specimens or in specimens from patients with bacterial cystitis or bladder cancer (p < 0.0001 for each comparison). Urine HB-EGF levels were also significantly lower and EGF levels significantly higher in both groups of IC patients than in the three control groups (p < 0.0001 for each comparison). Although APF and HB-EGF levels were similar in ulcerative and nonulcerative IC patients, EGF levels were significantly higher in IC patients with vs. without ulcers (p < 0.004). CONCLUSION: These findings indicate that APF, HB-EGF and EGF are good biomarkers for both ulcerative and nonulcerative IC and validate their measurement as biomarkers for IC in Chinese patients.

Adult↗

Hemorrhagic cystitis following high-dose chemotherapy and bone marrow transplantation in children with malignancies: incidence, clinical course, and outcome.

Two hundred ninety-one courses of high-dose chemotherapy (HDC) with bone marrow transplantation (BMT) in children with malignancies were reviewed in order to assess the incidence, clinical course, outcome, and predisposing factors of hemorrhagic cystitis. Hemorrhagic cystitis occurred in 19 HDC courses (6.5%). Three patients had grade I hematuria linked to thrombopenia, nine had grade II hematuria despite platelet levels greater than 50 x 10(9)/L, and seven had grade III hematuria with clots and bladder obstruction. Severe complications occurred in grade III patients, but no deaths were directly linked to the cystitis. Fourteen patients recovered within two to 120 days of onset. The other patients died before the cystitis resolved, either of a relapse of the malignancy or of infection. Predisposing factors were age (increased incidence in older children), conditioning regimen containing cyclophosphamide, previous vesical irradiation, association with prolonged aplasia, and hepatic complications. The role of busulfan was also probable. No viral agent was found.

Adolescent↗

Effects of NSAIDs on bladder function in normal and cystitis rats: a comparison study of aspirin, indomethacin, and ketoprofen.

To clarify the potential usefulness of non-steroidal anti-inflammatory drugs, NSAIDs, for patients with overactive bladder, we examined the effect of NSAIDs on urodynamic parameters in normal and cystitis rats and compared their ulcerogenic activity in the gastrointestinal mucosa. Cystometry was performed after administration of the conventional NSAIDs, aspirin, indomethacin, or ketoprofen. Prostaglandin levels were measured in the bladder of cystitis rats pretreated with NSAIDs. Furthermore, the ulcerogenic responses were examined. NSAIDs increased bladder capacity without any effect on micturition pressure in normal rats in the following rank order of potency: ketoprofen > or = indomethacin > or = aspirin. In cystitis rats, bladder capacity was increased and micturition frequency was decreased. The levels of prostaglandin were significantly increased in cystitis rats. All NSAIDs inhibited the increment of prostaglandin levels at doses equal to that effective in the improvement of bladder functions. When administered intraduodenally, both ketoprofen and indomethacin induced lesions in the gastrointestinal mucosa. However, aspirin had no significant effect. We demonstrate that NSAIDs are effective in animal models of disease, most likely by suppressing by prostaglandin synthesis. Since aspirin, in contrast to ketoprofen or indomethacin, did not cause any gastrointestinal lesions, aspirin might be the NSAIDs treatment of choice for overactive bladder.

Animals↗

[A case of cystitis glandularis. Its relationship to bladder carcinoma].

A 41-year-old male was admitted to the hospital for frequent urination and severe retardation before voiding. Roentgenography revealed exophytic lesions which were located mainly in the trigone of the bladder, and he underwent transurethral resection. The pathological diagnosis was cystitis glandularis. There was no literature which reported cystitis glandularis causing urinary disturbance. This case, moreover, had been diagnosed as cystitis glandularis 13 years before by endoscopical biopsy. The origin of cystitis glandularis and its potentiality as a pre-malignant lesion were discussed from the clinical course for over 10 years.

Adult↗

[Drug induced cystitis due to ketotifen fumarate--a case report].

Tranilast, an antiallergic drug, is well known as a causal drug of cystitis, and a report is made here of our experience of 1 case of drug-induced cystitis ascribable to ketotifen fumarate. A 13-year-old female had been taking anti-asthmatic drugs orally since the onset of athmatoid attacks, from age of 5. The attacks intensified from the age of 12, because of this she began to take various anti-asthmatic drugs orally. She visited another hospital, due to pollakisuria, in November, 1990, and received treatment for cystitis. However, the symptoms were not alleviated, and she visited our department on January 9, 1991. By urinalysis, large counts of leukocytes and erythrocytes were observed in a visual field of the sediment. Remarkable reddening was observed over the urinary bladder in the patient's cystoscopic findings. Treatment was given at our department, on an outpatient basis, with various antibacterial drugs for approximately one month, but her symptoms were not alleviated, pollakisuria and aseptic pyuria persisted. The patient had never taken tranilast; oral intake of ketotifen fumarate and saibokutou was discontinued on February 13, due to a suspicion of drug-induced cystitis, and her symptoms subsequently disappeared. On February 22, she took ketotifen fumarate orally again, on her own, due to asthmatoid attack, and her symptoms returned. The oral intake of ketotifen fumarate was again discontinued, and alleviation of the symptoms and normalization of the urinary findings were again observed. As a result, lymphocyte stimulation tests on all the drugs the patient had ever taken, only ketotifen fumarate turned out to be positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Eosinophilic cystitis. A survey].

The purpose of this study was to evaluate the incidence, diagnostic criteria and treatment of eosinophilic cystitis in the period 1989-94 in Denmark. A questionnaire was sent to all Danish surgical, urological and pathological-anatomical departments. Fifty-six patients were diagnosed as having eosinophilic cystitis at the surgical departments and 135 patients were diagnosed at the pathological-anatomical departments. The treatment was most often instillation of steroids in the bladder or oral antihistamine. Success of treatment was generally acceptable. The questionnaire confirmed that eosinophilic cystitis is a rare disease. We recommend the pathological-anatomical departments to use certain diagnostic criteria for eosinophilic cystitis. The treatment is symptomatic. A diagnostic number from the Danish Health Board is needed.

Adult↗

[Cystitis glandularis].

OBJECTIVE: To discuss the presenting features, diagnosis and treatment of cystitis glandularis. METHODS/RESULTS: 15 patients consulted for voiding syndrome, hematuria, hypogastric pain and chronic cystitis. Ten patients were evaluated by IVP which showed bilateral ectasia in 6, an abnormal renal pelvis in one and the remaining three patients were normal. Eight patients were evaluated by cystography which showed a reduced bladder capacity in three, bilateral reflux in three and an abnormal bladder wall in two patients. Urinalysis was performed in all 15 patients; only 5 patients showed a positive culture. These 5 patients had recurrent episodes and underwent cystoscopy and biopsy and/or TUR. Sixty percent was associated with a foreign body, lithiasis, bladder exstrophy, pelvic lipomatosis and BPH. Diagnosis was based on the histological findings; 40% had a bladder tumor. CONCLUSIONS: Patients with cystitis glandularis present with voiding syndrome and chronic cystitis. The IVP, US and cystographic findings are usually normal or may indicate a tumor. Diagnosis is based on the histological findings.

Cystitis↗

The efficacy of chemically-stabilized chlorite-matrix (TCDO) in the management of late postradiation cystitis.

Carcinoma of the uterine cervix is the most common cancer of women in Thailand. The most frequent complication after pelvic radiation for uterine cancer is radiation cystitis. The management of severe late postradiation cystis is far from satisfactory. The objective of this study was to evaluate the efficacy of chemically-stabilized chlorite-matrix (TCDO) in patients with severe radiation cystitis. This study was conducted at the Department of Obstetrics and Gynecology, Ramathibodi Hospital and the Department of Radiology, Siriraj Hospital between September 1997 and September 1998. Twenty patients with grade 3 radiation cystitis after radiotherapy were enrolled into this study. TCDO was administered at a dose of 0.5 ml/kg body weight per day on 5 consecutive days as intravenous infusion over 4 hours. The response rate after the first cycle was 80 per cent with 30 per cent of the patients showing complete response. The follow-up time (13 patients) ranging from 1-9 months revealed no recurrent bleeding. There were no side effects from TCDO therapy. The result suggests good efficacy of TCDO in the treatment of postradiation cystitis.

Adult↗

[Choice of antibiotics in uncomplicated cystitis; application of 'system of objectified judgement analysis' (SOJA) method].

OBJECTIVE: To determine the drug of choice for the treatment of uncomplicated cystitis. METHOD: Drug selection was performed by means of the so-called 'system of objectified judgement analysis' (SOJA) method by a working group of 11 persons. The following selection criteria were used: pharmacokinetics, interactions, probability of hitting (the probability that the microorganism is sensitive to the antibiotic), development of resistance, specific use in urinary tract infections, efficacy, side effects, dosage-frequency, duration of treatment, cost and documentation. The following drugs were included in the study: amoxicillin (with or without clavulanic acid), nitrofurantoin, sulfamethizole, trimethoprim, co-trimoxazole, ciprofloxacin, norfloxacin, ofloxacin and fosfomycin trometamol. RESULTS: Fosfomycin and nitrofurantoin slow release showed the highest scores. The main selection criteria that determined the selection of a drug were especially specific use in urinary tract infections, development of resistance, probability of hitting and cost. CONCLUSION: Fosfomycin and nitrofurantoin slow release best fulfill the requirements for drugs in the treatment of uncomplicated cystitis. No comparative studies have been performed with the 3-day treatment of uncomplicated cystitis with nitrofurantoin slow release or with trimethoprim. Fluoroquinolones play no important part in the treatment of uncomplicated cystitis, mainly because of the risk of development of resistance.

Anti-Infective Agents↗