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Haemorrhagic cystitis associated with adenovirus in a patient with AIDS treated for a non-Hodgkin's lymphoma.

Adenovirus-induced haemorrhagic cystitis has been reported chiefly in bone marrow or kidney transplant recipients. We report here on an HIV-positive patient treated for a Burkitt's lymphoma who developed gross haematuria associated with fever and burning urination. Usual causes of haematuria were ruled out: lithiasis, urinary tract lesions, glomerulonephritis, mycobacterium and schistosoma infections, and drug toxicity. Adenovirus was detected by cellular cultures and BK/JC virus DNA sequences were detected using a polymerase chain reaction method. Because BK/JC virus shedding is very common (75%) in HIV patients receiving chemotherapy, our data strongly suggest that adenovirus was responsible for the haemorrhagic cystitis in our patient. In conclusion, adenovirus should be considered as a potential cause of haemorrhagic cystitis in AIDS patients whose immunosuppression is aggravated by cytotoxic drugs.

Acquired Immunodeficiency Syndrome↗

Efficacy of mesna in preventing further cyclophosphamide-induced hemorrhagic cystitis.

Mesna is a sulfhydryl compound that reacts with the metabolites of cyclophosphamide that are excreted in the urine and may produce bladder wall irritation. Mesna is converted in the blood to a biochemically inactive compound that is reduced back to mesna in the kidneys. In this way it has the potential to protect the bladder mucosa without interfering with the antineoplastic effect of cyclophosphamide. Twenty-two patients who had developed hemorrhagic cystitis from cyclophosphamide were treated again with cyclophosphamide and mesna prophylaxis. A total of 68 cycles of cyclophosphamide were given with mesna, with a median of three cycles per patient. A recurrence of cystitis was prevented in all but one patient. Thus, mesna is effective in preventing recurrent cystitis in patients receiving further cyclophosphamide.

Adolescent↗

Virulence factors and O groups of Escherichia coli isolates from patients with acute pyelonephritis, cystitis and asymptomatic bacteriuria.

The relationship between the presence of bacterial virulence factors and the severity of urinary tract infection (UTI) was analized in this study. The production of alpha-hemolysin (Hly), the expression of P-fimbriae and the mannose-resistant hemagglutination (MRHA) type IVa (associated with the presence of P-fimbriae), were all detected more frequently in Escherichia coli strains from acute pyelonephritis than in strains isolated from cystitis and asymptomatic bacteriuria. In contrast, the production of cytotoxic necrotizing factor type 1 (CNF1) and the expression of MRHA types III and IVb were distributed uniformly between strains causing different clinical categories of UTI. Thus 88% of the E. coli strains from acute pyelonephritis showed some of the virulence factors investigated in this study, whereas only 60% (p < 0.01) and 56% (p < 0.01) repectively of the strains isolated from cystitis and asymptomatic bacteriuria possessed virulence factors. There were no significant differences in the prevalence of virulence properties between strains isolated from patients with or without complicating factors. Only 16% (p < 0.001) of the fecal isolates from healthy individuals showed virulence factors. The virulence factors were concentrated in strains belonging to 10 (O1, O2, O4, O6, O7, O14, O18, O22, O75 and O83) of the 12 serogroups most frequently detected in uropathogenic E. coli strains. The majority of uropathogenic O4, O6, O14, O22, O75 and O83 E.coli strains were Hly+CNF1+ and expressed P-fimbriae or MRHA type III, whereas the strains of serogroup O18 were Hly+CNF1- and P-fimbriated. Among O1 and O7 strains we found Hly-CNF1-strains that expressed P-fimbriae. Among O2 strains we found Hly+CNF1+ strains that expressed P-fimbriae or MRHA type III and other Hly-CNF1-strains that possessed P-fimbriae. We conclude that E.coli strains isolated from pyelonephritis show virulence factors more frequently than those from cystitis and asymptomatic bacteriuria, and that strains that cause urinary tract infections in Spain belong to the same serogroups as uropathogenic E.coli isolated in other areas of the world. Our results support the special pathogenicity theory and suggest that many cases of serious urogenital disease may be caused by a limited number of P-fimbriated E.coli strains that usually produce alpha-hemolysin.

Acute Disease↗

Evidence for the involvement of bradykinin in chemically-evoked cystitis in anaesthetized rats.

The effect of Hoe 140, a potent bradykinin B2 receptor antagonist, on the micturition reflex and detrusor hyperreflexia induced by chemical cystitis has been investigated in anaesthetized rats. Hoe 140 (1-100 nmol/kg i.v.) produced a dose-dependent blockade of the contraction of the rat urinary bladder induced by i.v. administration of bradykinin (100 nmol/kg) without affecting the response produced by the selective tachykinin NK-1 receptor agonist, [Sar9] substance P (SP) sulfone (1 nmol/kg i.v.). At doses which produce selective and long-lasting blockade of bradykinin receptors in the urinary bladder, Hoe 140 did not modify urodynamic parameters in normal rats. Intravesical instillation of xylene in female rats decreased bladder capacity and increased micturition frequency. These effects also occurred in rats pretreated with capsaicin as adults. Hoe 140 did not modify xylene-induced cystitis. Intraperitoneal administration of cyclophosphamide (150 mg/kg, 48 h before) decreased bladder capacity and increased micturition frequency. These effects of cyclophosphamide were abolished in rats pretreated with capsaicin as adults. Hoe 140 increased bladder capacity and decreased micturition frequency in rats pretreated with cyclophosphamide. Addition of bradykinin (10 mumol/l) to the medium in the superfused rat urinary bladder preparation evoked a prompt increase in the outflow of calcitonin gene-related peptide like immunoreactivity (CGRP-LI). Hoe 140 (3 mumol/l) inhibited (by about 50%) the CGRP-LI out-flow stimulated by bradykinin. These findings demonstrate the participation of bradykinin, through B2 receptors, in the genesis of detrusor hyperreflexia during cyclophosphamide-induced cystitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cyclophosphamide cystitis as a model of visceral pain in rats. A survey of hindbrain structures involved in visceroception and nociception using the expression of c-Fos and Krox-24 proteins.

The evoked expression of the immediate early gene-encoded proteins c-Fos and Krox-24 was used to study activation of hindbrain neurons as a function of the development of cyclophosphamide (CP) cystitis in behaving rats. CP-injected animals received a single dose of 100 mg/kg i.p. under transient volatile anesthesia and survived for 1 to 4 h in order to cover the whole postinjection period during which the disease develops. CP-injected groups included: (1) animals with minor simple chorionic edema, an early characteristic of inflammation (1 h postinjection); (2) animals with well-developed simple chorionic edema (2 h postinjection); (3) animals with mild inflammation (chorionic edema accompanied by epithelial cleavage; 3 h postinjection); and (4) animals with complete inflammation (4 h postinjection). In addition to onset of chorionic edema, the earliest postinjection period also included the general aspects of the nervous reaction consecutive to the injection process (handling, transient volatile anesthesia and postanesthesia awakening, abdominal pinprick, CP-blood circulating effects). Controls included both noninjected animals and saline-injected animals surviving for the same times as CP-injected ones. Quantitative results come from c-Fos expression. It has been shown that: (1) saline injection is a significant stimulus for only nucleus O and central gray pars alpha and nucleus medialis of the dorsal vagal complex; (2) all structures driven by CP injection (nucleus O and central gray pars alpha, locus coeruleus, Barrington's nucleus and parabrachial area mostly in its ventral and lateral subdivisions, dorsal vagal complex, ventrocaudal portion of lateral bulbar reticular formation) responded vigorously shortly after injection, but only two (dorsal vagal complex, ventrocaudal portion of lateral bulbar reticular formation) showed increased or renewed activity when cystitis completely developed, i.e., when noxious visceral inputs reached highest levels. Regarding the sequential activation of these structures in relation to postinjection time, evidence is given that: (1) a large variety of hindbrain structures are differentially involved in either the general reaction consecutive to the injection process or to various degrees of cystitis; (2) these structures extend from the brain-spinal cord to the pons-mesencephalon transitional junction levels; (3) the two structures most powerfully driven by visceronociceptive inputs are also the most caudal ones, being located at the brain-spinal cord junction level; and (4) the dorsal vagal complex could be the main hindbrain visceral pain center, with three particular subdivisions, the nucleus medialis, nucleus commissuralis, and ventralmost part of area postrema, being involved.

Animals↗

Viruses and interstitial cystitis: adenovirus genomes cannot be demonstrated in urinary bladder biopsies.

Microbes may be involved in the pathogenesis of interstitial cystitis (IC). Adenoviruses and BK virus (BKV) can infect epithelial cells in urinary bladder and they are causative agents for hemorrhagic cystitis. We therefore studied the presence of adenovirus and BKV genomes in urinary bladder tissue specimens of patients with IC using polymerase chain reaction (PCR) and in situ hybridization (ISH). Controls were specimens from cases with transitional cell carcinoma of the bladder. Nucleic acids were extracted from paraffin sections of the bladder tissue for PCR. Primers detecting all adenovirus types were used. In situ hybridization was carried out for the paraffin sections using digoxigenin-labeled DNA probes for adenovirus and BKV. The adenovirus DNA PCR was able to detect one to two infected cells/specimen. All the seven IC cases studied and six controls were negative for adenovirus DNA by PCR and ISH. The ISH test for BKV genomes was also considered negative in IC cases and controls. The specimens which were negative in PCR tests yielded a signal with beta-globin primers, thus being amplifiable. We conclude that adenovirus and BKV do not play a major pathogenetic role in interstitial cystitis.

Adenoviridae↗

Xanthogranulomatous cystitis as a cause of elevated carcinoembryonic antigen mimicking recurrent colorectal cancer. Report of a case.

We report a case of xanthogranulomatous cystitis that developed in a patient with a history of colon cancer. While undergoing adjuvant chemotherapy with fluorouracil and levamisole, rising carcinoembryonic antigen (CEA) levels and the appearance of a pelvic mass, suspicious for recurrent cancer, were identified. Exploratory laparotomy demonstrated the presence of a benign condition of the bladder, xanthogranulomatous cystitis, which was resected by partial cystectomy. CEA levels have normalized. This is the first reported case of xanthogranulomatous cystitis producing an elevated CEA level.

Carcinoembryonic Antigen↗

Successful treatment of radiation cystitis with hyperbaric oxygen therapy: resolution of bleeding event and changes of histopathological findings of the bladder mucosa.

To assess the effect of hyperbaric oxygen (HBO) therapy on radiation cystitis, clinical and histopathological characteristics were examined. Three women with radiation cystitis were treated with HBO therapy. Macrohaematuria was arrested in all patients. Cystoscopy demonstrated abnormal telangiectasia and inflammatory mucosa before treatment. After HBO therapy, the inflammatory mucosae were healed. However, abnormal vessels did not completely disappear. Histopathologically, the epithelium was atrophic and dilated lymph vessels and inflammatory cells were seen in the submucosa. These changes improved after treatment. HBO therapy is effective against radiation cystitis. With improvement of the clinical symptoms also the cystoscopic and histopathological findings changed favourably.

Aged↗

Eosinophilic cystitis induced by mitomycin-C.

Eosinophilic cystitis is an unusual form of cystitis which is characterized by irritative voiding symptoms and haematuria. In the report herein two adult cases of eosinophilic cystitis treated with intravesical Mitomycin-C instillations for prophylaxis of bladder carcinoma are presented and the literature is reviewed.

Administration, Intravesical↗

Interstitial cystitis in a woman with systemic mastocytosis.

Studies have reported detrusor mastocytosis in patients with interstitial cystitis. The author describes a patient with systemic mastocytosis who was confirmed to have detrusor mastocytosis and interstitial cystitis. She responded to therapy with pentosanpolysulfate. The literature on systemic mastocytosis and the role of mast cells in the pathophysiology of interstitial cystitis are reviewed.

Anti-Inflammatory Agents, Non-Steroidal↗

Interstitial cystitis coexisting with vulvar vestibulitis in a 4-year-old girl.

Interstitial cystitis (IC) is a disorder that is difficult to diagnose and is thought to be uncommon in children. We report the first case of IC coexisting with vulvar vestibulitis in a 4-year-old girl. She presented with urinary symptoms and pelvic and vulvar pain. Cystoscopic and histological investigation confirmed interstitial cystitis and vulvar vestibulitis. Gynecologists are often called upon to deal with symptoms referable to the genital tract. It is important to always include interstitial cystitis in the differential diagnosis of urinary symptoms associated with pelvic pain.

Analgesics, Non-Narcotic↗

Nitric oxide synthases and cyclophosphamide-induced cystitis in rats.

The role of inducible (iNOS) and neuronal nitric oxide (nNOS) synthases and of tachykinin NK1 receptors on the pathogenesis of cyclophosphamide (CYP)-induced cystitis was investigated, in rats. CYP-induced cystitis was characterized by large increases in bladder-protein plasma extravasation (PPE), increases in the urinary excretion of nitric oxide (NO) metabolites and histological evidences of urothelial damage, edema, extensive white blood cell infiltrates and vascular congestion of the bladder. The specific iNOS inhibitor, S-methylthiourea (MITU), produced marked inhibition (>90%) of CYP-induced increases in PPE associated with amelioration of tissue inflammatory changes. Treatment with 7-nitroindazole (7-NI; 20, 40 and 80 mg/kg), a selective nNOS inhibitor, did not significantly reduce CYP-induced increases in PPE and failed to produce histological improvement. In addition, treatment with MITU, but not with 7-NI, inhibited the increases in the urinary excretion of NO metabolites induced by CYP treatment. WIN 51,708 (17-beta-hydroxy-17-alpha-ethynyl-androstano[3,2-b]pyrimido[1,2-a]benzimidazole; WIN), a selective NK1-receptor antagonist, reduced the increases in EPP and ameliorated the inflammatory changes in the bladder induced by CYP. However, the maximal degree of protection achieved with WIN was significantly less than that produced by MITU. Combined treatment with the iNOS inhibitor and the NK1 antagonist produced no greater effect than that produced by the iNOS inhibitor alone. Our results suggest that NO plays a fundamental role in the production of the cystitis associated with CYP treatment. The iNOS, and not nNOS, seems responsible for the inflammatory changes. Part of the increases in NO may due to activation of NK1 receptors by neuropeptides such as substance P possibly released from primary afferent fibers.

Animals↗

Botulinum toxin type A may improve bladder function in a rat chemical cystitis model.

The purpose of this study was to investigate the effect of botulinum toxin type A on bladder function and histology in a rat chemical cystitis model. The study included 41 female Sprague-Dawley rats with chemical cystitis induced by intravesical instillation of hydrochloric acid. The acid instillation was repeated monthly to maintain chronic inflammation. The treatment group (n=21) received 2-3 units of botulinum toxin type A injected into the bladder detrusor at the 3, 6, 9 and 12 o'clock positions, and the control group (n=20) underwent saline injection into the bladder detrusor at the same positions. Urodynamic studies were performed in all rats before the treatment and at death. The rats were killed at 1 week, 2 weeks, 1 month and 2 months after treatment. The bladders were removed and examined histologically for mast cells and inflammatory changes. The cystometric findings showed that, at the beginning and end of the experiment, the increases in the maximum bladder capacity and compliance were significantly higher in the treatment group than in the control group (P=0.000 and P=0.025, respectively). The histological studies revealed similar mast cell counts and leukocyte infiltration for the treatment and control groups. In conclusion, in this rat chemical cystitis model, botulinum toxin type A injected into the bladder detrusor led to a functional improvement. Thus, botulinum toxin type A injection may be an alternative, minimally invasive choice to other surgical treatment options in the treatment of a chronic inflammatory condition to improve deteriorated bladder function.

Animals↗

Imaging findings of hemorrhagic cystitis in pediatric oncology patients.

In pediatric oncology patients, hemorrhagic cystitis may be a life-threatening complication of bone-marrow transplantation, chemotherapy, and/or radiation therapy. The inciting agent in urine can affect the entire urothelium from the renal collecting system to the bladder, and the severity of disease can vary. The radiologist often plays a key role in the diagnosis, follow-up, and occasionally the treatment of hemorrhagic cystitis and its complications. This review discusses the imaging findings in the kidneys and bladder in patients with hemorrhagic cystitis both before and after treatment for this disease. Findings on two-dimensional sonography, color Doppler and power Doppler sonography, computed tomography, magnetic resonance imaging, antegrade pyleography, and cystography are presented.

Bone Marrow Transplantation↗

Chemotherapy for leukaemia following previous pelvic radiotherapy is associated with severe enteritis and haemorrhagic cystitis.

We describe two patients who developed extensive ulceration, haemorrhage and necrosis of bladder or bowel following treatment with intensive chemotherapy for acute leukaemia. Major surgical intervention was required in both cases. Both patients had previously undergone pelvic radiotherapy for gynaecologic malignancy and had suffered symptoms of chronic radiation-induced cystitis and enteritis. Bowel and bladder histology showed evidence of chronic radiation cystitis or enteritis. We postulate that combined mucosal toxicity secondary to cytotoxic therapy and chronic radiation-induced damage to bowel or bladder mucosa resulted in critical ischaemia, ulceration and necrosis of bowel and bladder. Caution must be exercised in the treatment of patients receiving intensive chemotherapy if there is a history of chronic radiation enteritis or cystitis, and dosage reductions may be justified.

Adult↗

Contribution of antioxidants to preventive effect of mesna in cyclophosphamide-induced hemorrhagic cystitis in rats.

PURPOSE: The aim of this study was to evaluate whether combination of antioxidants and mesna may prevent cystitis induced by cyclophosphamide better than mesna alone. MATERIALS AND METHODS: A total of 46 male Sprague-Dawley rats were divided into six groups. Five groups received single dose of cyclophosphamide (CP, 100 mg/kg) intraperitoneally with the same time intervals: group 2 received CP only, group 3 received mesna (21.5 mg/kg for three times), group 4 beta-carotene (20 mg/kg for two times) and mesna, group 5 received alpha-tocopherol (20 mg/kg for two times) and mesna, and group 6 received melatonin (5 mg/kg for two times) and mesna on the day of CP injection. Group 1 served as control. RESULTS: CP injection resulted in severe cystitis. Mesna has showed meaningful but not full protection against CP toxicity. Although beta-carotene did not show any additional beneficial effect when combined with mesna, alpha-tocopherol and especially melatonin with mesna resulted full protection that the pathologist, blinded to the slides, could not differ from sham control. CONCLUSION: Oxidants may be important in the pathogenesis of CP-induced cystitis. Melatonin and alpha-tocopherol may help to ameliorate bladder damage along with other drugs such as mesna and diuretics.

Animals↗

Clinical course and treatment of haemorrhagic cystitis associated with BK type of human polyomavirus in nine paediatric recipients of allogeneic bone marrow transplants.

UNLABELLED: Of a total of 117 bone marrow transplant (BMT) recipients in the period from August 1988 to November 1995, 9 (7.7%) developed haemorrhagic cystitis. This condition was characterized in all nine patients by late onset (day +24 to +50 post-BMT), long duration (1 to 7 weeks), and the excretion of BK virus in the urine, as confirmed by electron microscopy, DNA hybridization and PCR analysis. Adenovirus was not involved. The serological assessment of BK virus-specific IgM and IgG pre- and post-BMT is consistent with viral reactivation in all patients, although a primary infection cannot be absolutely excluded in a single patient. A significant correlation between the use of high-dose busulphan (16 mg/kg) in the preparative regimen and development of haemorrhagic cystitis (P = 0. 0003) was evident. The severe course of the disease in two patients resulted in bladder tamponade; bleeding could not be inhibited with coagulation and laser treatment. Deterioration was prevented by bladder irrigation via a suprapubic catheter. Remission occurred spontaneously in all patients. CONCLUSION: BK virus induced haemorrhagic cystitis in a paediatric bone marrow transplantation recipients is characterized by late onset, long duration, viral reactivation and correlates to high-dose busulphan. Severe bleeding could not be influenced by surgical intervention.

Adolescent↗

Interstitial cystitis and ileus in pediatric-onset systemic lupus erythematosus.

A girl aged 11 years presented with autoimmune hemolytic anemia with thrombocytopenia, and subsequently developed severe abdominal pain, vomiting, and pollakiuria. X-ray findings of her abdomen demonstrated paralytic ileus with intestinal wall thickening. Intravenous pyelography revealed bilateral hydroureter with mild hydronephrosis and contracted bladder. Pathological examination of her bladder revealed interstitial cystitis, with evidence of focal deposition of IgG and C3 in a granular pattern on small blood vessel walls. She was diagnosed as having systemic lupus erythematosus (SLE) associated with paralytic ileus and chronic interstitial cystitis. Although initiation of high-dose prednisolone therapy resulted in a gradual improvement in clinical symptoms, reducing the dosage of prednisolone caused a relapse. To our knowledge, the combination of paralytic ileus and chronic interstitial cystitis is quite uncommon in pediatric-onset SLE.

Child↗