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Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation.

BK virus (BKV) load in urine alone or in combination with acute graft-versus-host disease (GVHD) was correlated to development of hemorrhagic cystitis (HC). BKV load in combination with acute GVHD discriminated the best, while BKV and viral load alone, but not GVHD, still showed predictive ability for HC.

Adult↗

Catheter-induced cystitis: evaluation by cystosonography.

The bladders of 23 patients with indwelling catheters were examined by ultrasound and cystoscopy. Twelve of the 23 showed changes consistent with bullous cystitis, a catheter-induced reaction of the bladder mucosa that may simulate a bladder tumor on intravenous urography and sonography. The changes seen included a thickened mucosa that was smooth in the early stages, becoming redundant and polypoid in later stages. The mucosa was usually hypoechoic and the lesions were localized on the posterior wall or were diffuse and more severe, depending on the length of catheterization. It is concluded that the sonographic findings in the appropriate clinical setting are suggestive of this entity. Although cystoscopy is not often indicated, cystoscopic findings are diagnostic and biopsy is, therefore, unnecessary.

Aged↗

EGF and HB-EGF modulate inward potassium current in human bladder urothelial cells from normal and interstitial cystitis patients.

Interstitial cystitis (IC) is an idiopathic condition characterized by bladder hyperalgesia. Studies have shown cytokine and purinergic signaling abnormalities in cultured bladder urothelial cells (BUC) from IC patients. We performed single-cell electrophysiological studies in both normal and IC BUC. A strongly inward rectifying potassium current with conductance of the Kir2.1 channel was identified in normal BUC. This current was significantly reduced in IC BUC. Kir2.1 protein and mRNA were detected in both IC and normal BUC. Epidermal growth factor (EGF) caused a dose-dependent decrease in the inward potassium current in normal BUC. EGF is secreted in higher amounts by IC BUC and is known to decrease Kir2.1 conductance by phosphorylation of Kir2.1. Genistein, a nonspecific phosphorylation inhibitor, increased the inward potassium current in IC BUC and blocked the effect of EGF on normal BUC. Treatment of IC BUC with heparin-binding epidermal growth factor-like growth factor (HB-EGF), previously shown to be secreted in lower amounts by IC BUC, significantly increased inward potassium current. These data show that the inward potassium current in BUC can be modulated by EGF and HB-EGF. Changes in BUC membrane potassium conductance caused by altered levels of EGF and HB-EGF may therefore play a role in the pathophysiology of IC.

Cells, Cultured↗

Augmented extracellular ATP signaling in bladder urothelial cells from patients with interstitial cystitis.

Interstitial cystitis (IC) is an idiopathic hypersensory condition of the bladder associated with increased urinary ATP and increased stretch-activated ATP release by bladder urothelial cells (BUCs), suggesting augmented purinergic signaling in the bladder. To test this theory further, monolayers of cultured BUCs derived from bladder biopsies obtained from patients with IC and control patients were stimulated with 10-30 microM ATP with subsequent measurement of extracellular ATP levels using the luciferin-luciferase assay. Stimulation with 30 microM ATP resulted in IC supernatant containing several-fold more ATP than control BUCs initially, followed by a slower decrease in ATP levels. This difference in ATP levels was not completely due to activity of cellular ecto-ATPase, because blockade with ARL67156 did not normalize the difference. Exposure to hypotonic solutions resulted in similar extracellular ATP concentrations in IC and control BUCs, but there was a slower decrease in ATP levels in IC supernatants. Treatment of IC BUCs with 10-40 microM suramin, a nonspecific P2 receptor antagonist, significantly attenuated the IC BUC response to extracellular ATP, restoring IC BUCs to a control phenotype. Pretreatment of IC BUCs with 20 ng/ml of heparin-binding EGF-like growth factor (HB-EGF), which previously has been shown to be decreased in IC urine specimens, also restored IC BUCs to a control phenotype with respect to response to ATP stimulation. In conclusion, IC BUCs have augmented extracellular ATP signaling that could be blocked by suramin and HB-EGF. These findings suggest the possible development of future novel therapeutic techniques.

Adenosine Triphosphatases↗

Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis.

Purinergic mechanisms appear to be involved in motor as well as sensory functions in the urinary bladder. ATP released from efferent nerves excites bladder smooth muscle, whereas ATP released from urothelial cells can activate afferent nerves and urothelial cells. In the present study, we used immunohistochemical techniques to examine the distribution of purinoceptors in the urothelium, smooth muscle, and nerves of the normal cat urinary bladder as well as possible changes in the expression of these receptors in cats with a chronic painful bladder condition termed feline interstitial cystitis (FIC) in which ATP release from the urothelium is increased. In normal cats, a range of P2X (P2X(1), P2X(2), P2X(3), P2X(4), P2X(5), P2X(6), and P2X(7)) and P2Y (P2Y(1), P2Y(2), and P2Y(4)) receptor subtypes was expressed throughout the bladder urothelium. In FIC cats, there is a marked reduction in P2X(1) and loss of P2Y(2) receptor staining. Both P2X(3) and P2Y(4) are present in nerves in normal cat bladder, and no obvious differences in staining were detected in FIC. Smooth muscle in the normal bladder did not exhibit P2Y receptor staining but did exhibit P2X (P2X(2), P2X(1)) staining. In the FIC bladder smooth muscle, there was a significant reduction in P2X(1) expression. These findings raise the possibility that purinergic mechanisms in the urothelium and bladder smooth muscle are altered in FIC cats. Because the urothelial cells appear to have a sensory function in the bladder, it is possible that the plasticity in urothelial purinergic receptors is linked with the painful bladder symptoms in IC.

Adenosine Triphosphate↗

Disruption of guinea pig urinary bladder permeability barrier in noninfectious cystitis.

Although most cell membranes permit rapid flux of water, small nonelectrolytes, and ammonia, the apical membranes of bladder epithelial umbrella cells, which form the bladder permeability barrier, exhibit strikingly low permeabilities to these substances. In cystitis, disruption of the bladder permeability barrier may irritate the bladder wall layers underlying the epithelium, causing or exacerbating inflammation, and increasing urinary frequency, urgency, and bladder pain. To determine the effects of inflammation on the integrity of the permeability barrier, guinea pigs were sensitized with ovalbumin, and the bladders were exposed subsequently to antigen by instillation on the urinary side. Inflammation of the bladder wall markedly reduced transepithelial resistance of dissected epithelium mounted in Ussing chambers and increased water and urea permeabilities modestly at 2 h and more strikingly at 24 h after induction of the inflammation. Transmission and scanning electron microscopy of bladders at 30 min and 24 h after antigen exposure revealed disruption of tight junctions, denuding of patches of epithelium, and occasional loss of apical membrane architecture. These permeability and structural effects did not occur in nonsensitized animals in which the bladders were exposed to antigen and in sensitized animals exposed to saline vehicle rather than antigen. These results demonstrate that inflammation of the underlying muscle and lamina propria can disrupt the bladder permeability barrier by damaging tight junctions and apical membranes and causing sloughing of epithelial cells. Leakage of urinary constituents through the damaged epithelium may then exacerbate the inflammation in the underlying muscle layers.

Animals↗

Changes in human bladder epithelial cell gene expression associated with interstitial cystitis or antiproliferative factor treatment.

Explanted bladder epithelial cells from patients with interstitial cystitis (IC) have been shown to differ from explanted control cells in several ways, including production of an antiproliferative factor (APF), altered production of certain epithelial growth factors, and rate of proliferation. To better understand the role of the APF in abnormal bladder epithelial cell proliferation in IC, we studied gene expression patterns in normal bladder epithelial cells treated with APF vs. mock APF and compared them to expression patterns in IC vs. normal cells using microarray analysis. Oligo-dT-primed total cellular RNA was labeled with [(33)P]dCTP and hybridized to GeneFilter GF211 microarray membranes (Research Genetics) containing cDNA for 3,964 human genes. Thirteen genes that function in epithelial cell proliferation or differentiation were consistently differentially expressed in both IC (compared with control) and APF-treated (compared with mock APF-treated) normal bladder epithelial cells. The general pattern of gene expression in IC and APF-treated cells suggested a less proliferative phenotype, with increased expression of E-cadherin, phosphoribosylpyrophosphate synthetase-associated protein 39, and SWI/SNF complex 170-kDa subunit, and decreased expression of vimentin, alpha2-integrin, alpha1-catenin, cyclin D1, and jun N-terminal kinase 1; these findings were confirmed for the structural gene products (E-cadherin, vimentin, alpha2-integrin, and alpha-catenin) by immunohistochemistry. These results are compatible with the previously noted decreased proliferation rate of IC and APF-treated normal cells, and indicate that the mechanism whereby APF inhibits cell proliferation may involve both downregulation of genes that stimulate cell proliferation along with upregulation of genes that inhibit cell growth.

Adolescent↗

Urinary bacterial flora of women with urethral syndrome and interstitial cystitis.

The aerobic and anaerobic bacterial flora in the first voided and in the midstream urine of healthy females (n = 5) and female patients with either urethral syndrome (US) (n = 5) or interstitial cystitis (IC) (n = 14) were studied. Bacteria were grown on media enabling isolation of fastidious and aerobic as well as obligatory anaerobic species. In healthy females only gram-positive rods were found whereas US patients also harbored streptococci. Patients with IC presented also with Enterobacteriae and anaerobic bacteria. Five IC patients with severe symptoms were treated with metronidazole; 2 out of 3 patients with anaerobic bacteria in the pretreatment specimens had no anaerobes after metronidazole therapy and in 1 patient streptococci disappeared after the therapy. One patient with severe symptoms and Bacteroides fragilis in the midstream urine became symptom-free after 2 weeks of metronidazole treatment. Although there is uncertainty whether the US and IC are not related to an infectious etiology, the bacterial flora in urethral and in midstream urine in these conditions differs considerably from that of healthy females.

Adolescent↗

Emphysematous cystitis following brain contusion.

Emphysematous cystitis is a rare disorder most commonly seen in patients with urinary tract infection and diabetes mellitus. We present a nondiabetic case of a 46-year-old woman with this entity following brain contusion.

Brain Injuries↗

Encrusted cystitis and pyelitis.

Encrusted cystitis (EC) and encrusted pyelitis (EP) are rare chronic inflammatory diseases of the bladder and renal pelvis, respectively, and are characterized by mucosal inflammation with deposits of ammonium magnesium phosphate on the urothelium. Corynebacterium urealyticum is the pathogen responsible in the vast majority of cases. We report 4 cases of EC and 1 case of EP. In 1 case of EC Ureaplasma urealyticum was isolated as the microorganism responsible. To the best of our knowledge, U. urealyticum-induced EC has never been reported previously.

Adult↗

Eosinophilic cystitis presenting as urinary retention.

OBJECTIVE: To evaluate the incidence, etiology, diagnosis, therapy and results in patients with eosinophilic cystitis (EC), with special attention to patients with urinary retention as presenting symptom. PATIENTS AND METHODS: Between 1988 and 1999, 3 patients with EC were diagnosed. One patient presented with urinary retention, without other symptoms. All patients were evaluated for symptoms, urine culture, hematology including cell differentiation, blood chemistry, cystoscopy and intravenous urography. The international literature was reviewed for incidence, etiological factors, diagnostic procedures, therapies and outcome of EC presenting with urinary retention. RESULTS: Two male patients presented with pain, frequency of micturition and nocturia. One female patient presented with urinary retention. One patient had an urinary tract infection. One patient showed eosinophilia of the peripheral blood. Intravenous urography revealed hydroureteronephrosis in 2 patients (1 unilateral and 1 bilateral). Cystoscopy showed tumor-like lesions in 2 patients. Therapy consisted of oral or intravesical corticosteroids or transurethral resection of the lesions. All patients were cured. A review of the literature revealed that 14 patients with EC (10%) presented with urinary retention; the majority (79%) being children and women. All patients returned to normal miction following therapy. CONCLUSIONS: The clinical presentation of EC is varied. When the lesion is located at or near the bladder neck, it may present as urinary retention. In children and women with urinary retention, EC must be considered in the differential diagnosis. Corticosteroids are the mainstay of efficient therapy.

Adrenal Cortex Hormones↗

Spontaneous bladder rupture due to chronic cystitis 20 years after cystolithotomy.

Spontaneous bladder rupture is a very rare condition. The majority of the cases are due to long-term indwelling catheters, radiation, or acute infravesical obstruction. Spontaneous rupture of the bladder due to inflammation is extremely rare. A case of intraperitoneal bladder rupture due to chronic cystitis is reported. Exploratory laparotomy and partial cystectomy were performed. Diagnosis and treatment are discussed.

Chronic Disease↗

Urodynamic study and potassium sensitivity test for women with frequency-urgency syndrome and interstitial cystitis.

PURPOSE: The intravesical potassium chloride (KCl) sensitivity test has been used to detect urothelial leakage in patients with frequency-urgency syndrome and interstitial cystitis (IC). It is unclear whether urodynamic studies can predict a positive KCl test. This study compared the urodynamic results for women with different KCl responses who suffered from frequency-urgency syndrome and IC. METHODS: A total of 196 women suffering from frequency, urgency and/or bladder pain were enrolled in this study. These patients underwent a urodynamic study with a concurrent KCl test. The urodynamic results were compared between the patients who had positive and those who had negative KCl tests and between the patients with and without characteristic IC under cystoscopic hydrodilatation. RESULTS: Among 196 women, 138 (70.4%) had a positive and 58 (29.6%) a negative KCl test. Among the patients with a positive KCl test, 128 underwent cystoscopic hydrodilatation: 44 were proven to have characteristic IC, and 84 were not. Patients with a negative KCl test had a larger residual urine volume and a higher incidence of poor relaxation of the urethral sphincter than those with a positive test. However, patients with a positive KCl test and proven IC did not differ in urodynamic parameters from non-IC patients. The symptom of bladder pain could not predict a positive KCl test nor characteristic IC either. CONCLUSIONS: This study shows that no specific urodynamic parameter or specific symptoms can predict a positive KCl test in patients with frequency-urgency syndrome or IC. Patients with bladder pain at full bladder and a positive KCl test had only a 45.2% chance to have characteristic IC.

Administration, Intravesical↗

Does interstitial cystitis urine include possible factors effecting the nociceptive system of the spinal cord?

INTRODUCTION: We investigated the effect of interstitial cystitis (IC) urine on bladder layers and nociceptive centers in the spinal cord with determination of nerve growth factor (NGF), neuronal nitric oxide synthase (nNOS) and c-fos expressions. MATERIAL AND METHODS: Female rats were instilled into the bladder IC urine (Group-IC), normal urine (Group-NU) and saline (Group-S). NGF, nNOS and c-fos activity were determined in the L6-S1 medulla spinalis with identification of mast cell and NGF activity on bladder layers. RESULTS: There was more NGF expression cell density in the bladder wall that was determined immunohistochemically in control and IC urine instillation groups than Group-S. While there was no difference in nNOS, NGF and c-fos activity between spinal cord regions except the lateral dorsal horn of the L6 section, localization of activities was different in Group-IC. CONCLUSIONS: The characteristics of the bladder wall and its nociceptive afferents after human urine instillation of some toxic compounds might be causative factors for IC. However, it is barely hard to conclude that different toxic compounds should be causative factors in IC urine in the pathogenesis of IC.

Administration, Intravesical↗