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Experimental cytoxan cystitis and prevention by acetylcysteine.

Cytoxan (cyclophosphamide) given to rats intraperitoneally produced a severe cystitis within four hours with marked inflammatory edema and hemorrhagic ulcerations of the mucosa. An in vivo staining test with methylene blue showed deep staining of the urothelium as has been demonstrated with other types of urothelial injuries; uninjured urothelium does not stain. The cytoxan cystitis is probably not due to cytoxan itself, but to a breakdown product acrolein, an aldehyde appearing in the urine. Rat experiments demonstrated that acrolein instilled intravesically produced a cystitis similar to that found with cytoxan injected intraperitoneally. The cystitis due either to cytoxan or acrolein was prevented by simultaneous intravesical administration of an aldehyde inactivating agent, acetylcysteine (mucomyst).

Acetylcysteine↗

Bladder calculi enveloped by extensive cystitis glandularis: case report.

We report a case of 2 large calculi encased within a 15 gm. tumor of cystitis cystica and cystitis glandularis. The patient presented with acute right epididymitis. An excretory urogram showed 2 bladder calculi. Cystoscopy revealed a mass around the stones resembling adenocarcinoma of the bladder base. Transurethral resection of the tumor and cystolitholapaxy were performed. The final diagnosis was bladder calculi within a mass of cystitis cystica and cystitis glandularis. A review of the literature failed to reveal a similar case.

Adult↗

Effects of AH-9700, (+)-pentazocine, DTG and oxybutynin on micturition in anesthetized rats with acetone-induced cystitis.

We investigated the effects of AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl] pyrrolidine fumarate; a novel sigma receptor ligand), (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG) (two typical sigma receptor ligands), and oxybutynin (a currently used anti-pollakiuria drug) on cystometrograms in anesthetized rats with 30% acetone-induced cystitis. Compared to sham-treated rats, acetone-treated cystitis models exhibited an increase in urinary frequency during continuous filling cystometry. Intravenous administration of AH-9700 (1-5 mg/kg), (+)-pentazocine or DTG to the rats with cystitis dose-dependently prolonged micturition intervals and increased the micturition threshold pressure. Oxybutynin (1 mg/kg. i.v.) also extended micturition intervals, but decreased the micturition pressure. These results indicate that AH-9700, (+)-pentazocine and DTG improve abnormal frequent urination caused by acetone-induced cystitis in a manner different from that of oxybutynin.

Acetone↗

Epithelial coating techniques in the treatment of interstitial cystitis.

OBJECTIVES: To review the newer methods of treatment of interstitial cystitis using techniques that coat the epithelium to maintain its integrity relative to permeability. METHODS: The technique of employing sulfated polysaccharides in the treatment of interstitial cystitis both orally and intravesically were reviewed as well as the concepts supporting the use of such technology, including a review of the role glycosaminoglycans (mucus) play in the regulation of epithelial permeability. Also reviewed were the methods that can be employed to detect aberrations of epithelial permeability as seen in the interstitial cystitis syndrome. RESULTS: The techniques of detecting epithelial permeability problems and appropriate therapy for this using polysaccharides, such as heparin and pentosanpolysulfate, are presented. This article also discusses the point that these techniques will result in long-term remissions in patients with the IC syndrome who respond to these treatments. CONCLUSIONS: The use of sulfated polysaccharides, both orally and intravesically, is an effective long-term treatment for many people with the interstitial cystitis syndrome.

Anti-Inflammatory Agents, Non-Steroidal↗

Intravesical thiotepa-induced eosinophilic cystitis.

Eosinophilic cystitis is a rare form of an allergic cystitis. Factors such as food allergens, parasites, and drugs have been implicated in the genesis of eosinophilic cystitis. Associated risk factors include bronchial asthma, atopic diseases, and environmental allergens. Intravesical mitomycin is a reported causative agent. We report the first case of eosinophilic cystitis that developed after intravesical instillation of thiotepa for treatment of superficial bladder cancer.

Adult↗

An unusual presentation of emphysematous cystitis.

Emphysematous cystitis is a rare disorder most commonly seen in women and associated with urinary tract infections and poorly controlled diabetes mellitus. We report the case of a 76-year-old woman who presented with diarrhea and abdominal discomfort, and emphysematous cystitis was revealed on the abdominal X-ray series. This case is unique in that the patient had no evidence of urinary tract infection, diabetes, or recent instrumentation. As the patient was treated for emphysematous cystitis (bladder irrigation and intravenous antibiotics), the diarrhea rapidly resolved and the radiographic abnormalities of the emphysematous cystitis also resolved. This may suggest a causal relationship, although a specific mechanism is unknown.

Aged↗

The uroprotection of mesna on cyclophosphamide cystitis in rats. Its consequences on behaviour and brain activities.

We studied the uroprotective effect of mesna, at doses of 40-300 mg/kg/i.p., in single or fractioned injections, on the development of cyclophosphamide (CP, 100 mg/kg/i.p.) cystitis in rats. The study concerns the histological, behavioural and nervous aspects of the disease. The specific effects of mesna, when injected alone, have also been considered. The mesna itself does not have specific deleterious effects, except at a dose of 300 mg/kg which provokes a moderate vesical inflammation although without consequence on the animal's behaviour. Mesna offers good protection against CP cystitis for only certain posologies. The uroprotective effects of mesna reach maxima at doses of 40-100 mg/kg and for fractioned injections given over the entire time frame of the urinary toxic release. The uroprotective effects of other posologies are only partial. The nervous activities were studied through the expression of Fos protein. The repetitive intraperitoneal injection of mesna induced a spinal activity and a preferential contralateral activity of the trigemino/reticular areas of the brainstem spinal cord junction--an effect which was reduced in the presence of CP. The prevention of cystitis by mesna was accompanied only by a reduction in spinal Fos activity, the supraspinal activities remaining high and in strict relationship with the vagal afferent activity. In conclusion, the uroprotective effect of mesna, which requires appropriate posologies, has led to the confirmation of the spinal actions of the CP cystitis, probably via the pelvic nerve, but did not allow a clear distinction between the consequences of the systemic (vagal) and local (spinal, pelvic) actions of CP at supraspinal level.

Animals↗

Antibiotic prescribing for cystitis: how well does it match published guidelines?

PURPOSE: Cystitis is one of the most common bacterial infections seen by physicians in outpatient settings. Published clinical guidelines by the Infectious Disease Society of America and other organizations have been established to enable effective treatment, while attempting to decrease cost and limit antibiotic resistance. METHODS: Insurance claims data for employees and dependents of a single Midwest corporation, with Preferred Provider Organization coverage, diagnosed with cystitis between 1996 and 1999 were matched to prescription drug claims for those who filled an antibiotic prescription within 3 days of diagnosis. RESULTS: For acute and recurrent cystitis physicians prescribed trimethoprim-sulfamethoxazole 37% and 18% respectively. The other most common antibiotics prescribed were the broad-spectrum flouroquinolones, and nitrofurantoin. The mean duration for these prescriptions was 10 days regardless of whether the infection was acute or recurrent. CONCLUSIONS: The first line recommended antibiotic, trimethoprim-sulfamethoxazole, was prescribed in 37% of acute infections, and for considerably longer than the suggested 3-day course of therapy. Steps should be taken to educate physicians and patients on the choice and dosage of antibiotics for cystitis to minimize emergence of antibiotic resistance.

Adolescent↗

Glycosaminoglycans excretion in interstitial cystitis.

Glycosaminoglycans (GAGs) have been identified histochemically and biochemically in urothelium. They have been suggested to have an anti-adherence effect at the bladder surface important in the urothelial defence against bacterial and carcinogenic insult. The aim of this study was to investigate urinary GAGs excretion in patients with interstitial cystitis. Urinary GAG excretion was determined in patients with interstitial cystitis (n:34; 16 males, 18 females) and healthy subjects (n:34; 16 males, 18 females). Urinary GAG determinations were made by the dimethymethylene blue method. Student's t-test was used for statistical analysis of the results. Urinary GAG excretion was found to be elevated significantly in patients with interstitial cystitis (14.45+/-2.02 mg/g Cr) as compared to healthy subjects (10.11+/-2.3 mg/g Cr) (p<0.01). There was no significant difference in urinary GAG excretion between males and females in either the healthy subjects or in the patients. Determination of urinary GAG excretion may be an important non-invasive test in the investigation of patients with interstitial cystitis.

Biomarkers↗

Protective effect of berberine on cyclophosphamide-induced haemorrhagic cystitis in rats.

The urotoxicity of cyclophosphamide and the protective effect of the herb berberine were investigated in this study. Administration of 150 mg/kg cyclophosphamide intraperitoneally caused a serious haemorrhagic cystitis in rats after 12 hr, including bladder oedema, haemorrhage, and dramatic elevation of nitric oxide metabolites (nitrite+nitrate) in urine and in plasma. To explore whether cyclophosphamide-induced cystitis could be prevented by berberine, rats were pretreated with a single dose or two doses of berberine at 50, 100, or 200 mg/kg intraperitoneally then challenged with cyclophosphamide (150 mg/kg, intraperitoneally). The results indicated that pretreatment of rats with berberine could reduce cyclophosphamide-induced cystitis in a dose-dependent manner. Furthermore, we found that two doses of berberine showed greater protection against cyclophosphamide urotoxicity than when given a single dose. In addition, our data shows that a single dose of 200 mg/kg berberine, or two doses of 100, and 200 mg/kg berberine could completely block cyclophosphamide-induced bladder oedema and haemorrhage, as well as nitric oxide metabolites increase in rat urine and plasma. In conclusion, our findings suggest that berberine could be a potential effective drug in the treatment of cyclophosphamide-induced cystitis, and provides us with the bright hope in the prevention and treatment of cyclophosphamide urotoxicity.

Animals↗

Hyperbaric oxygen in the treatment of refractory haemorrhagic cystitis.

Haemorrhagic cystitis is a common and often debilitating complication of chemotherapy for which treatment is frequently unsatisfactory. With over 80 cases reported of radiation-induced cystitis treated successfully with hyperbaric oxygen, attention is now turning to the treatment of chemotherapeutic agent-induced cystitis. We report a case of haemorrhagic cystitis occurring after autologous peripheral blood stem cell transplantation for multiple myeloma. The patient had received cyclophosphamide and busulfan and had BK and adenoviruria. The haemorrhage was refractory to multiple conventional treatments but resolved after a course of hyperbaric oxygen.

Adenoviruses, Human↗

Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis.

OBJECTIVES: To determine whether nerve growth factor (NGF) is elevated in painful conditions of the urinary bladder (idiopathic sensory urgency, interstitial cystitis and painful chronic cystitis). PATIENTS AND METHODS: Sixteen women patients were recruited from the Urodynamic Clinic at The Elizabeth Garrett Anderson Hospital, London. Four each had idiopathic sensory urgency (mean age 34 years, range 24-51), chronic cystitis (mean age 51 years, range 40-79) and interstitial cystitis (mean age 41 years, range 29-53). Four women who had genuine stress incontinence on cystometry but with no irritative symptoms were used as controls (mean age 45 years, range 35-54). The levels of NGF were determined in bladder biopsies from all women and biopsy sections were immunostained to detect NGF. RESULTS: The levels of NGF were higher in samples from all three painful bladder conditions than in samples from controls. Immunostaining showed increased NGF expression in the urothelium, most marked in patients with idiopathic sensory urgency. CONCLUSIONS: The increased level of NGF may explain several clinical and pathological features in these conditions, including sensitization of nociceptor fibres and increased numbers of mast cells. We propose that anti-NGF treatment may be a rational and effective treatment in intractable bladder pain.

Adult↗

Urinary levels of substance P and its metabolites are not increased in interstitial cystitis.

OBJECTIVES: To determine whether interstitial cystitis is associated with the increased release of substance P from the bladder wall into urine, by measuring urinary excretion rates of substance P and its metabolites in women with interstitial cystitis and in a control group of women with stress incontinence and normal bladder function. PATIENTS AND METHODS: Catheter urine was collected from 13 patients and 10 controls during a water diuresis ( approximately 10 mL/min) before and after instilling the bladder with 100 mL of water. The contribution of the bladder wall to urinary substance P peptides was assessed by measuring the change in substance P peptide levels after 2 min of bladder stasis before and after instillation. RESULTS: Absolute substance P excretion rates were similar in patients with interstitial cystitis and controls; 2 min of bladder stasis reduced the substance P excretion rate (P = 0.03) and increased the excretion rate of substance P metabolites (P = 0.01). CONCLUSIONS: The release of substance P from the bladder wall was not increased in patients with interstitial cystitis.

Chromatography, High Pressure Liquid↗

Antibiotic treatment for five days is effective in children with acute cystitis.

UNLABELLED: Short courses of antibiotics are often recommended to treat children with acute cystitis despite lack of firm evidence to support such management. The aim of this study therefore was to analyse the short-term outcome of such treatment. The retrospective analysis included 300 children (252F, 48M) fulfilling the criteria of first-time acute cystitis and managed according to a protocol recommending 5 d treatment. In 214 (71%) the treatment was given according to the protocol and in the others for 7 or 10 d. Nitrofurantoin was used in 150 (50%) and trimethoprim without or with sulfonamide in 129 (43%). The short-term results were excellent with 96% of the children being free from symptoms at the first follow-up visit after a median of 6 d. Only 2 girls had persisting bacteriuria and thus the frequency of bacteriological treatment failure was 1%. Recurrence within 30 d occurred in 4 girls (2%). CONCLUSION: A 5 d treatment with antibiotics is adequate in children with acute cystitis. Routine follow-up visits after a first acute cystitis may not be necessary, providing that the bacteria causing the infection are sensitive to the prescribed antibiotic and that there is no history of defective bladder or bowel emptying.

Acute Disease↗

BK virus infection in hematopoietic stem cell transplant recipients: frequency, risk factors, and association with postengraftment hemorrhagic cystitis.

Blood samples from 132 consecutive hematopoietic stem cell transplant recipients were obtained and tested weekly for BK virus DNA by use of quantitative real-time PCR. Forty-four patients (33%) developed BK viremia at a median of 41 days (range, 9-91 days) after transplantation. Patients with hemorrhagic cystitis that occurred after platelet engraftment had higher levels of viremia than did patients without hemorrhagic cystitis (median, 9.7x10(3) vs. 0 copies/mL; P=.008) and patients with hemorrhagic cystitis that occurred before platelet engraftment (median, 9.7x10(3) vs. 0 copies/mL; P=.0006). BK viremia also was strongly associated with postengraftment hemorrhagic cystitis in a time-dependent analysis (P=.004).

BK Virus↗

Urovirulence determinants in Escherichia coli isolates causing first-episode and recurrent cystitis in women.

To assess the prevalence of urovirulence determinants among Escherichia coli isolates from women with acute uncomplicated cystitis, 121 isolates from 87 women with first-episode or recurrent cystitis and 156 fecal isolates from 52 women without recent urinary tract infection were tested using DNA probes for P fimbriae, hemolysin, aerobactin, and diffuse adhesin and for expression of hemolysin and P and F adhesins. P fimbrial genotype (P = .002), hemolysin phenotype (P = .007), and the diffuse adhesin determinant (P = .03), but not aerobactin, were found more frequently in E. coli from women with acute cystitis, and expression of the F adhesin (41%) was more common than the P adhesin (24%; P = .001). E. coli isolates that caused cystitis in women using diaphragms had fewer virulence determinants than those from nonusers (P = .04), suggesting that diaphragm use may allow infection with less virulent E. coli.

Acute Disease↗

Florid cystitis glandularis of intestinal type with mucin extravasation: a mimic of adenocarcinoma.

Six florid examples of cystitis glandularis of intestinal type associated with focal mucin extravasation into the stroma are reported. Several of the cases caused major diagnostic difficulty with regard to their distinction from adenocarcinoma. Five patients had masses that simulated a bladder neoplasm. Patients ranged from 27 to 65 (average 46) years of age and complained of hematuria or irritative symptoms. Four patients were treated only by transurethral resection. One patient underwent partial cystectomy because of an erroneous diagnosis of adenocarcinoma and another total cystectomy because of a neurogenic bladder. Microscopic examination showed numerous glands lined by intestinal type epithelium, conforming to the appearance of the intestinal variant of cystitis glandularis. All cases had at least a minor component of typical cystitis glandularis, and it was prominent in four cases. All six cases had foci of basophilic mucin in the stroma, and this was prominent in four cases. Rounded aggregates of mucin were occasionally surrounded by compressed connective tissue cells, simulating mucinous cysts. In favour of a benign interpretation were the absence of epithelial cells in the extravasated mucin, the lack of atypicality of the cells lining the intestinal type glands in all but one case, a generally orderly distribution of the glands, and their lack of infiltration of the muscularis propria, although they abutted the latter in several cases. Follow-up from 2 to 14 years is available for three of the cases and has been uneventful, the longest follow-up being in the case diagnosed as adenocarcinoma. These cases illustrate the extent to which cystitis glandularis may mimic a neoplasm on gross evaluation and the propensity of mucin extravasation to cause diagnostic difficulty, a finding documented only rarely previously.

Adenocarcinoma↗

Radiation or chemotherapy cystitis with "pseudocarcinomatous" features.

BACKGROUND: The features of radiation or chemotherapy cystitis mimicking invasive urothelial cancer are not widely known. DESIGN: A search of the consultation files from our institution between January 1996 and September 2003 identified 20 patients with bladder biopsies showing cystitis mimicking invasive urothelial cancer. RESULTS: The mean age at diagnosis was 69 years (range, 40-85 years); 80% were males. Complete history was not available in 1 patient. Seventeen patients had a history of pelvic irradiation (15 prostate cancer and 2 endometrial cancer). Two patients had systemic chemotherapy (1 metastatic colon cancer and 1 mixed connective tissue disease). All patients presented with hematuria. The mean time from radiation and/or chemotherapy to presentation was 27 months (range, 0-84 months). All cases showed epithelial proliferation that mimicked invasive cancer within the lamina propria, with marked proliferation seen in 45% of cases. Mild to moderate nuclear pleomorphism was seen in all cases. A characteristic feature was the presence of pseudoinvasive urothelial nests wrapping around the vessels associated with fibrin deposition. Most cases did not show any mitoses (75%). Ulceration was seen in 39% of cases. All cases showed some degree of hemorrhage, fibrin deposition and fibrin thrombi, fibrosis, and acute and chronic inflammation, with hemosiderin identified in 60% of cases. Edema and vascular congestion were common features (95% and 80%, respectively). Thickened vessels and vascular changes associated with radiation injury were identified in 75% of cases. Seventeen patients were followed for a mean of 9 months (range, 0.25-37 months), and none developed bladder cancer. CONCLUSIONS: Radiation or chemotherapy cystitis can show epithelial proliferations that may be confused with invasive urothelial carcinomas. Other findings characteristic of radiation or chemotherapy cystitis, such as hemorrhage, fibrin, and vascular changes, are often seen in association with the epithelial proliferations and are helpful in distinguishing it from invasive cancer. Pathologists must be aware that these changes may be seen with a remote radiation or chemotherapy history, where this information may not be provided or known at the time of the biopsy evaluation.

Adult↗