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PubMed2005

[Recurrent urinary tract infections].

Recurrent urinary tract infections (RUTI) are a frequent clinical problem in sexually active young women, pregnant or postmenopausal women and in patients with underlying urological abnormalities. The present chapter reviews RUTI based on their classification: relapses, which usually occur early (< 1 month), are caused by the same microorganism and are associated with underlying urological abnormalities, and reinfections, which usually occur later and are caused by a new distinct microorganism (or by the same microorganism usually located in the rectum or uroepithelial cells). The pathogenesis of RUTI is reviewed and the risk factors associated with RUTI in premenopausal women (usually related to sexual activity), postmenopausal women (in whom estrogen deficiency has a significant effect on the vaginal Lactobacillus flora), and in pregnant women are discussed. Likewise, an extensive review of the distinct therapeutic strategies to prevent RUTI is provided: self-treatment of cystitis, continuous antibiotic prophylaxis, postcoital antibiotic prophylaxis, topical vaginal estrogens, Lactobacillus, cranberry juice, intravesical administration of non-virulent E. coli strains and vaccines, among others. Several diagnostic-therapeutic algorithms are included. These algorithms are based on the type of urinary infection (relapse-reinfection), on the type of patient (young, postmenopausal, or pregnant women) and on the number of episodes of RUTI.

Adolescent↗

PubMed2006

Behavioral profiling of human transitional cell carcinoma ex vivo.

Outcome studies of many types of cancer have revealed that tumors of indistinguishable histologic appearance may differ significantly in aggressiveness and in their response to therapy. A strategy that would enable early identification of patients at high risk for disease progression and allow screening of multiple therapeutic agents simultaneously for efficacy would improve clinical management. We have developed an orthotopic organ culture model of bladder cancer in which quantum dot-based fluorescent imaging approaches are used to obtain quantitative measurements of tumor cell behavior. Human transitional cell carcinoma (TCC) cells are labeled with quantum dot nanoparticles, and the cells instilled into the rat bladder in vivo, after which the bladder is excised and cultured ex vivo. Cell implantation, proliferation, and invasion into the organ wall are monitored using epifluorescence imaging and two-photon laser scanning confocal microscopy. Using this approach, we were able to assign distinct phenotypes to two metastatic bladder cancer cell lines based on different patterns of invasiveness into the bladder wall. We also showed that established tumor cell masses regressed following intravesical administration of the chemotherapeutic drug thiotepa. Collectively, these findings suggest that this assay system, which we have named EViTAS (for ex vivo tumor assay system), can recapitulate salient aspects of tumor growth in the host and is amenable to behavioral profiling of human cancer.

Animals↗

PubMed1995

Evaluation of cellular immunity following bacillus Calmette-Guérin therapy in patients with superficial bladder cancer.

Despite its marked effectiveness in the prevention of tumor recurrences, a great deal of information on the mode of action of Bacillus Calmette-Guérin (BCG) as an antitumor therapy modality is still lacking. In this prospective study, by performing lymphocyte subset analysis and quantitative assessment of delayed hypersensitivity skin reactions before transurethral resection of the detected tumor and 3-6 months after intravesical BCG administration in 23 patients with superficial bladder carcinoma, we tried to demonstrate the immunostimulatory effect of BCG therapy. We had 4 recurrences at 6 months' follow-up. Evaluation of lymphocyte subset analysis readings in our group revealed a statistically significant difference (p < 0.05) in CD4+/CD8+ ratio between baseline values and that obtained following BCG administration at 3 and 6 months. However, there was no statistically significant increase of this value in 4 patients who had tumor recurrences. Evaluation of delayed hypersensitivity skin test score results revealed a statistically significant increase in the whole group at 3 months of follow-up (p < 0.05) but the same evaluation at 6 months of follow-up showed no statistically significant difference with respect to this evaluation. Again, no statistically significant difference was found in 4 patients who had tumor recurrences. These results support the idea that BCG-associated antitumor activity is an immune-mediated reaction and the assessment of T-lymphocyte subsets together with quantitative evaluation of delayed hypersensitivity skin reactions would give us a definite idea about the immunotherapeutic effects of BCG in such patients.

Administration, Intravesical↗

PubMedDate not supplied

A pilot open label study of Cystoprotek in interstitial cystitis.

Interstitial cystitis (IC) is a disorder of the urinary bladder characterized by urgency, frequency, nocturia and suprapubic pain. IC occurs primarily in women and symptoms are exacerbated by stress, ovulatory hormones and certain foods. IC pathogenesis is unknown, but the most consistent findings involve some dysfunction of the bladder glycosaminoglycan (GAG) protective layer and a high number of activated bladder mast cells. There is no effective therapy even through intravesical administration of dimethylsulfoxide (DMSO) or oral pentosanpolysulfate (PPS) have had variable success. A dietary supplement, CystoProtek, was formulated with the natural GAG components chondroitin sulfate and sodium hyaluronate to provide urothelial cytoprotection, together with the flavonoid quercetin that has anti-inflammatory properties and inhibits activation of mast cells. Thirty-seven female patients diagnosed by the NIDDK criteria who had failed all forms of therapy took six softgel CystoProtek capsules per day for 6 months. Global assessment scale was reduced from 9.0 +/- 2.9 to 4.3 +/- 2.1 (p < 0.05); moreover, the O'Leary/Sant Symptom Index decreased from 15.3 +/- 3.1 to 6.9 +/- 4.2 (p < 0.05) and the Problem Index from 13.1 +/- 3.7 to 5.4 +/- 4.0 (p <0.05). These results are very promising and warrant a larger study that may permit further analyses with respect to other, especially atopic, comorbid diseases.

Adult↗

PubMed2001

New agents for the medical treatment of interstitial cystitis.

Interstitial cystitis (IC) is a painful, sterile, disorder of the urinary bladder characterised by urgency, frequency, nocturia and pain. IC occurs primarily in women but also in men with recent findings indicating that chronic, abacterial prostatitis may be a variant of this condition. The prevalence of IC has ranged from about 8 - 60 cases/100,000 female patients depending on the population evaluated. About 10% of patients have severe symptoms that are associated with Hunner's ulcers on bladder biopsy; the rest could be grouped in those with or without bladder inflammation. Symptoms of IC are exacerbated by stress, certain foods and ovulatory hormones. Many patients also experience allergies, irritable bowel syndrome (IBS) and migraines. There have been various reports indicating dysfunction of the bladder glycosaminoglycan (GAG) protective layer and many publications showing a high number of activated bladder mast cells. Increasing evidence suggests that neurogenic inflammation and/or neuropathic pain is a major component of IC pathophysiology. Approved treatments so far include intravesical administration of dimethylsulphoxide (DMSO) or oral pentosanpolysulphate (PPS). New treatments focus on the combined use of drugs that modulate bladder sensory nerve stimulation (neurolytic agents), inhibit neurogenic activation of mast cells, or provide urothelial cytoprotection, together with new drugs with anti-inflammatory activity.

Analgesics↗

PubMed2006

The overactive bladder: review of current pharmacotherapy in adults. Part 1: pathophysiology and anticholinergic therapy.

Overactive bladder is a syndrome characterised by urinary urgency, with or without urge incontinence, and usually with frequency and nocturia. It affects millions of people of all ages worldwide and causes significant morbidity, especially in terms of health-related quality of life. It poses a huge economic burden on health resources. Managing such patients involves a thorough history, physical examination and the use of pertinent investigations before the initiation of treatment. Therapy consists of lifestyle changes, bladder training, anticholinergics, second-line agents such as resiniferatoxin instillation or botulinum toxin injections into the bladder in refractory cases and, finally, in intractable cases, surgery. In the first part of this review of pharmacotherapy for the treatment of this condition, the focus is on the pathophysiological factors potentially involved in overactive bladder and covers the wide range of currently available first-line anticholinergic agents. Treatment algorithms are suggested on the basis of current literature.

Administration, Cutaneous↗

PubMed2006

The use of isotopes in the determination of absolute bioavailability of drugs in humans.

Absolute bioavailability studies in humans are not routinely performed as part of the drug registration process. They tend to be reasonably demanding, not least because toxicology data are required to support intravenous administration of a drug. Moreover, the classical crossover design of an absolute bioavailability study can suffer from artefacts caused by concentration-dependent pharmacokinetics. Many of the problems associated with absolute bioavailability studies can be alleviated using isotopically labelled drugs. Stable isotopes have been used in the performance of absolute bioavailability studies in humans for > 30 years. More recently, the advantages of using radiolabelled drugs have been expanded by using the ultrasensitive technology of accelerator mass spectrometry. Isotopic labelling not only allows for the accurate and efficient determination of absolute bioavailability, but can also provide information on first-pass effects and other pharmacokinetic parameters.

Administration, Intravesical↗

PubMed2001

Cellular photodestruction induced by hypericin in AY-27 rat bladder carcinoma cells.

In a recent clinical study we showed that hypericin accumulates selectively in urothelial lesions following intravesical administration of the compound to patients. In the present study the efficacy of hypericin as a photochemotherapeutic tool against urinary bladder carcinoma was investigated using the AY-27 cells (chemically induced rat bladder carcinoma cells). The uptake of hypericin by the cells increased by prolonging the incubation time and increasing the extracellular hypericin concentration. Photodynamic treatment of the cells incubated with 0.8 and 1.6 microM hypericin concentrations resulted in remarkable cytotoxic effects the extent of which depended on the fluence rates. Photoactivation of 1.6 microM hypericin by 0.5, 1.0 or 2.0 mW/cm2 for 15 min resulted in 3, 30 and 95% of the antiproliferative effect, respectively. Increasing the photoactivating light dose from 0.45 to 3.6 J/cm2 resulted in a five-fold increase in hypericin photodynamic activity. Irrespective of the fluence rates and irradiation times incubation of the cells with 10 microM hypericin induced rapid and extensive cell death in all conditions. The type of cell death (apoptosis or necrosis) induced by photoactivated hypericin depended largely on the hypericin concentration and the postirradiation time. At lower hypericin concentrations and shorter postirradiation times apoptosis was the prominent mode of cell death; increasing the hypericin concentration and/or prolonging the postirradiation time resulted in increased necrotic cell death. Cell pretreatment with the singlet oxygen quencher histidine, but not with the free-radical quenchers, significantly protected the cells from photoactivated hypericin-induced apoptosis, at least when a relatively low concentration (1.25 microM) was used. This result suggests the involvement of a Type-II photosensitization process. However, cells treated with higher hypericin concentrations (2.5-5 microM) were inadequately protected by histidine. Since hypericin is thus shown to be a potent and efficient photosensitizer, and since the conditions used were the same as when hypericin is used clinically to locate early-stage urothelial carcinoma lesions, hypericin may well become very important for the photodynamic treatment of superficial bladder carcinoma.

Animals↗

PubMed1994

Clinical pharmacokinetics of epirubicin.

Epirubicin (4'-epidoxorubicin) is a new anthracycline that has activity similar to doxorubicin (adriamycin) in a variety of solid neoplasms and haematologic malignancies. Importantly, epirubicin causes less cardiotoxicity than doxorubicin. There is extensive distribution of epirubicin into tissues and the elimination of the drug is predominantly biliary, with less than 15% of the drug excreted in the urine. The metabolism of epirubicin is characterised by complex biotransformation to relatively or totally inactive metabolites, including a 13-dihydro derivative, epirubicinol, 2 glucuronides and 4 aglycones. Quantitatively, the glucuronides of epirubicin and epirubicinol are very important, and this pathway, which is unique to epirubicin metabolism in humans, might explain the better tolerability of this drug compared with doxorubicin. Epirubicin pharmacokinetics may be described by a 3-compartment model, with median half-life values of 3.2 minutes, 1.2 and 32 hours for each phase. Total plasma clearance is 46 L/h/m2 and volume of distribution at steady-state is 1000 L/m2. The pharmacokinetics of epirubicin appears to be linear for doses up to the maximal tolerated dose of 150 to 180 mg/m2. Both intraperitoneal and intravesical administration of epirubicin are feasible, but remain of a rather restricted interest. The area under the plasma concentration-time curve of epirubicin is fairly well correlated with the relative kill of white blood cells. Therefore, epirubicin clearance can be used to predict haematological toxicity.

Aging↗

PubMed2005

Clinical pharmacokinetics of trospium chloride.

Trospium chloride, a quaternary amine with anticholinergic properties, is used for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and urinary frequency. The pharmacokinetics of trospium chloride have been investigated in healthy volunteers, in patients with renal and hepatic impairment, and in those with symptoms of overactive bladder, after oral, intravenous and intravesical administration. After oral administration, absorption of the hydrophilic trospium chloride is slow and incomplete. Peak plasma concentrations (Cmax) of approximately 4 ng/mL are reached 4-5 hours after administration of a 20 mg immediate-release preparation. The mean bioavailability is approximately 10% and decreases by concomitant food intake (to a mean of 26% of the fasting area under the plasma concentration-time curve [AUC]). Trospium chloride displays dose proportional increases in AUC and Cmax after a single dose within the clinically relevant dose range (20-60 mg). The mean volume of distribution is approximately 350-800 L. The drug is minimally (mean approximately 10%) metabolised to spiroalcohol by hydrolysis, is 50% plasma protein bound and does not cross the blood-brain barrier. Urinary excretion of the parent compound plays a major role in the disposition of the drug, with a mean renal clearance of 29 L/h (accounting for approximately 70% of total clearance) and a mean elimination half-life ranging from 10 to 20 hours. Elimination of the drug is slowed in patients with renal insufficiency, and population pharmacokinetic modelling has demonstrated that drug clearance is correlated with serum creatinine concentration. Thus, dose reduction is needed in patients with severe renal impairment (i.e. creatinine clearance < 30 mL/min). To date, no clinically relevant pharmacokinetic drug-drug interactions have been identified; the drug does not bind to any of the drug metabolising cytochrome P450 enzymes. The pharmacokinetics of the drug are compatible with twice-daily administration. A once-daily schedule may also be appropriate, but this regimen needs formal clinical evaluation.

Administration, Oral↗

PubMed2001

Contrast-enhanced harmonic imaging for the diagnosis of vesicoureteral reflux in pediatric patients.

OBJECTIVE: Harmonic imaging using phase or pulse inversion technology is a new sonographic diagnostic modality that has the potential to produce images of a higher quality than can be obtained with the conventional method. The aim of this study was to compare both types of harmonic modalities--tissue and contrast harmonic imaging--with the fundamental imaging mode in contrast-enhanced B-mode sonographic diagnosis of vesicoureteral reflux. SUBJECTS AND METHODS: Fifty-four children presenting for diagnostic examination of vesicoureteral reflux underwent standard sonography of the urinary tract in the fundamental mode, followed by intravesical administration of a galactose-based contrast medium containing microbubbles. The contrast-enhanced sonography was conducted by scanning the bladder and each kidney in transverse and longitudinal planes, from ventral and dorsal views, consecutively in B-mode using fundamental, contrast harmonic, and tissue harmonic imaging modalities. Soft-touch buttons on the console screen were used to alternate between the three imaging options, so that switching from one modality to the other could be done almost instantaneously. For comparison, in each patient, we selected one set of contrast-enhanced images of the bladder and two sets, one ventral and one dorsal, of the kidney. In a series, the images were compared and ranked from 1 to 3, with 1 being the best, with regard to sonomorphology (demarcation of the retrovesical space and renal pelvis as the potential sites to look for vesicoureteral reflux) and reflux detection and conspicuity, if present. RESULTS: In all, 248 sets of images were available for comparison. The delineation of both the retrovesical space and the renal pelvis was found to be best with tissue harmonic imaging in 84% and 96% of the image sets, respectively (p < 0.01). Forty-one sets of images were compared from 27 kidney-ureter image units of 22 children (41%) with reflux. The refluxing microbubbles were much more conspicuous in the harmonic imaging mode (tissue harmonic, 100%; contrast harmonic, 93%) than in the fundamental mode (p < 0.01). In eight kidney-ureter units, the reflux was detected only by using the harmonic imaging modalities. CONCLUSION: Visualization of the urinary tract and detection of ultrasound contrast media is significantly improved by the use of the harmonic imaging modalities. When both fundamental and harmonic imaging options are available, we recommend harmonic imaging for contrast-enhanced sonographic diagnosis of vesicoureteral reflux.

Adolescent↗

PubMed1998

Targeted diagnosis and treatment of superficial bladder cancer with monoclonal antibody BDI-1.

OBJECTIVE: To explore the application of monoclonal antibody (McAb) to targeted treatment of bladder carcinoma through a series of in vitro and in vivo studies carried out in animal model and patients with bladder carcinoma. METHODS: Monoclonal antibody BDI-1 against bladder carcinoma was prepared by the lymphocyte hybridoma technique. McAb was conjugated with 99mTc by direct reduction method. Momodin (MD) was covalently linked to McAb by SPDP method. Radioimmunoimaging of nude mice xenografts and patients with bladder carcinoma were performed with BDI-1-99mTc conjugates. An immunotoxin (BDI-1-MD) was inducted via a catheter into the bladder. Targeted treatment with BDI-1-MD was carried out in 18 patients. RESULTS: This study showed the specificity of McAb, and clear imaging of nude mice bearing xenografts. Distribution analysis of 99mTc-BDI-1 in nude mice showed the highest value of T/NT in bladder tumor. Targeted diagnosis and treatment for patients by intravesical administration are very safe and effective. CONCLUSION: The bladder cancer seems an ideal model for diagnostic and therapeutic approaches using regional administration of McAb conjugates via a catheter direct into the bladder.

Animals↗

PubMed2000

Cystometric evaluation of bladder function in non-anesthetized mice with and without bladder outlet obstruction.

PURPOSE: To develop a model for cystometric study of bladder function in the awake mouse, and to characterize urodynamically and immunohistochemically the non-obstructed and infravesically obstructed mouse bladder. MATERIALS AND METHODS: Non-obstructed Balb/CJ mice, and mice with bladder outlet obstruction after surgical, partial ligation of the urethra underwent continuous cystometry as previously described for rats. Bladders were also investigated by immunohistochemistry. RESULTS: During the period of cystometry, reproducible micturition patterns were obtained. Marked differences in the urodynamic parameters between non-obstructed and obstructed mice were revealed. In mice subjected to urethral obstruction, micturition pressure (p <0.05), threshold pressure (p <0.05), bladder capacity (p <0.001), micturition volume (p <0.001), and residual volume (p <0.05) increased significantly. There was no difference in basal pressure or compliance between non-obstructed and obstructed mice. Non-voiding bladder activity was consistently recorded in obstructed mice; both frequency and amplitude increased significantly (p <0.01). Compared with non-obstructed bladders, obstructed bladders showed hypertrophy of the bladder wall and various degrees of "patchy denervation" of the detrusor. When tested in non-obstructed mice capsaicin, prostaglandin E2 (intravesical administration) and apomorphine (subcutaneous administration) induced bladder overactivity. CONCLUSIONS: Continuous cystometry can be reproducibly performed in awake, freely moving non-obstructed mice and mice with bladder outflow obstruction. The changes induced by infravesical obstruction in mice were similar to those previously found in rats. This model may be useful for investigations of genetically modified mice.

Animals↗

PubMed2000

Endoscopic fluorescence diagnosis and laser treatment of transitional cell carcinoma of the bladder.

Recurrent bladder cancer is due to tumor cell implantation, incomplete resection, and multicentric neoplastic changes throughout the bladder. The possibilities of 5-Aminolevulinic acid-induced fluorescence endoscopy (AFE), a highly sensitive method in detecting bladder cancer and laser energy as treatment to lower the recurrence rate in bladder cancer, are evaluated. After intravesical administration of AFE Protoporphyrin IX, a tumor-selective manner is excited by a xenon-arc lamp (wavelength 400 to 410 nm) to emit red fluorescence. Suspicious lesions can be detected by their red fluorescence and are electroresected or treated with laser energy. Complete resection or destruction of all tumors in the bladder is crucial to prevent recurrent and invasive growth of transitional cell carcinoma. AFE detects malignant lesions in the bladder with a sensitivity of 98% and Cis in 100%, respectively. Laser treatment of superficial bladder cancer lowers the local recurrence rate and reduces the risk of viable tumor cell implantation.

Aminolevulinic Acid↗

PubMedDate not supplied

Oxidative stress of red blood cells during Bacillus Calmette-Guerin intravesical instillations.

Although Bacillus Calmette-Guerin (BCG) intravesical instillation is widely accepted as a very effective modality in treating bladder carcinoma in situ, and in preventing superficial bladder cancer recurrence, its mechanism of action is not yet fully understood. The antitumor effects of BCG are mostly related to local immunological events but a systemic activation of the immune system cannot be excluded. The objective of the present study was to estimate the systemic production of oxidants during intravesical BCG treatment. Systemic production of oxidants was estimated by assessing the red blood cells (RBC) oxidative stress in twelve patients undergoing BCG immunotherapy for bladder carcinoma in situ. RBC oxidative stress induced by peroxynitrite was determined by luminol-enhanced chemiluminescence. During the treatment period, the RBC oxidative stress revealed a biphasic curve of changes: after an initial 5-fold increase, it dropped to pretreatment levels following the 4th instillation. Intravesical BCG administration induced systemic production of oxygen free radicals that may reflect a systemic activation of the immune system.

Administration, Intravesical↗

PubMed2001

In vivo photodynamic activity of hypericin in transitional cell carcinoma bladder tumors.

In a recent clinical study, we showed that hypericin accumulates selectively in urothelial lesions of the bladder following intravesical administration of the compound in patients. This observation infers that hypericin, a potent photosensitizer, could be used as a selective photodynamic therapy (PDT) tool against superficial bladder cancer. In the present study we investigated the in vivo PDT activity of hypericin in transition cell carcinoma (TCC) tumors of the bladder. Both the distribution and tumor PDT response were carried out using subcutaneous heterotopic AY-27 TCC tumors in syngeneic rats. For both PDT and distribution studies, hypericin (1 or 5 mg/kg) was injected intravenously 0.5, 6 or 24 h before PDT or distribution evaluation. The data show that hypericin is a potent photosensitizer in the treatment of TCC tumors in vivo and that the interval between drug administration and photo-irradiation has a dramatic effect on the PDT outcome. Using a 0.5 h interval between drug administration and photo-irradiation the tumor regrowth study indicated that no tumor mass could me measured 9-10 days after PDT. On the contrary, lengthening the time interval between drug administration and photo-irradiation resulted in a gradual loss of PDT efficiency in these tumors. For instance, while the 6 h drug interval protocol produced a moderate PDT activity in which the tumor sizes decreased to about 50% of their original sizes 11-16 days after photo-irradiation, the 24 h interval protocol was even less effective. The distribution data indicate that the PDT efficiency of hypericin in TCC tumors corresponded to the plasma concentrations rather than to the over all concentrations in the tumor. It is therefore conceivable that the mechanism of PDT efficacy of hypericin in TCC tumors is through indirect (vascular effects) rather than through direct effects (cellular destruction) of hypericin in these tumors. In conclusion, our data indicate that hypericin is a potent photosensitizer against AY-27 TCC tumors and that the PDT efficacy of hypericin is largely determined by photosensitizer distribution in the tumor at the time of photo-irradiation.

Animals↗

PubMed1998

Stability of reconstituted freeze-dried Bacille Calmette-Guérin used for intravesical immunotherapy for bladder cancer.

The product monographs for the commercially available products of Bacille Calmette-Guérin (BCG) state they must be used immediately following reconstitution. We hypothesized that the viability of the reconstituted preparations of BCG would not be altered for a period of up to 4 hours thus allowing a longer time interval between full preparation and its intravesical administration. Vials of freeze-dried ImmuCysttrade mark (Connaught Laboratories) and TICEtrade mark BCG (Organon-Teknika) were fully reconstituted in approximately 50 ml of saline and aliquots of the fully reconstituted product were serially diluted and inoculated onto freshly prepared Lowenstein-Jensen slants and colony counts were conducted at 0, 2, and 4 hours. The colony counts of the freeze-dried preparations of BCG varied between 0.1 and 0.3 x 108 and between 0.6 and 1.1 x 108 per reconstituted volume at 4 hours for the Connaught and TICE strains, respectively. There was no decrease in the colony counts between 0 and 4 hours for either product. There were no significant differences in the viability of the fully reconstituted freeze-dried preparation of BCG for up to 4 hours after complete reconstitution. These findings would suggest some latitude may be provided for institutions where the product is fully reconstituted prior to its actual administration.

Journal Article↗

PubMed2001

Reducing mucus production after urinary reconstruction: a prospective randomized trial.

PURPOSE: After transposition into the urinary tract, intestinal segments continue to produce mucus. We determine the effectiveness of muco-regulatory drugs, including N-acetylcysteine, aspirin and ranitidine, in reducing mucus secretion and urine viscosity in patients with transposed segments. MATERIALS AND METHODS: Our trial was a prospective randomized, double-blind placebo controlled crossover study involving 12 patients who underwent ileal conduit and 31 who underwent bladder reconstruction. Each treatment lasted 3 weeks with a 2-week washout. Pretreatment and posttreatment 24-hour urine samples were analyzed for mucin and viscosity after papain digestion, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and periodic acid-Schiff assay. A disease specific questionnaire and SF-36 quality of life survey were completed. RESULTS: According to the questionnaire, mucus production did not decrease with time in 67% of patients. Mucin comprised 3% of the total nondialyzable material in urine (65 mg./24-hour for ileal conduit and 60 mg./24-hour for bladder reconstruction). Analysis of questionnaires and laboratory results failed to demonstrate any benefit of taking muco-regulatory agents compared with placebo. CONCLUSIONS: The use of N-acetylcysteine, aspirin and ranitidine did not result in a reduction in mucin production, urine viscosity or improvement in quality of life.

Acetylcysteine↗