Articular manifestations after the administration of intravesical BCG.
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Adjuvants, Immunologic↗
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Reiter's syndrome after administration of intravesical bacille Calmette-Guérin.
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Administration, Intravesical↗
[Bladder wall permeability to to topically administered cisplatin].
The aim of the study was quantitation of cisplatinum in the wall of normal urinary bladder, tumor tissue, inflamed mucosa and blood in intravesical administration of cisplatinum. The samples of the tissue were radiated in the flow of heat neutrons 5 x 10(12)-5 x 10(13) neut/cm followed by radiochemical purification of the material and platinum assay in the tissue using analyser LP-4900 with semiconductor radiation detector. The samples were taken from 32 patients with transitional cancer of the bladder. Tumor tissue contained platinum in amounts 33.7 times exceeding those in normal tissue after intravesical administration of 100 mg of the drug. After intravenous administration of 100 mg cisplatinum normal bladder tissue and tumor tissue contained almost similar quantities of the drug. Thus, tumor tissue absorbs more cisplatinum than normal tissue of the bladder in intravesical administration.
Administration, Intravesical↗
Expression of functional nicotinic acetylcholine receptors in rat urinary bladder epithelial cells.
Although nicotinic acetylcholine receptors in both the central and peripheral nervous systems play a prominent role in the control of urinary bladder function, little is known regarding expression or function of nicotinic receptors in the bladder epithelium, or urothelium. Nicotinic receptors have been described in epithelial cells lining the upper gastrointestinal tract, respiratory tract, and the skin. Thus the present study examined the expression and functionality of nicotinic receptors in the urothelium, as well as the effects of stimulation of nicotinic receptors on the micturition reflex. mRNA for the alpha3, alpha5, alpha7, beta3, and beta4 nicotinic subunits was identified in rat urothelial cells using RT-PCR. Western blotting also confirmed urothelial expression of the alpha3- and alpha7-subunits. Application of nicotine (50 nM) to cultured rat urothelial cells elicited an increase in intracellular Ca2+ concentration, indicating that at least some of the subunits form functional channels. These effects were blocked by the application of the nicotinic antagonist hexamethonium. During in vivo bladder cystometrograms in urethane-anesthetized rats, intravesical administration of nicotine, choline, or the antagonists methyllycaconitine citrate and hexamethonium elicited changes in voiding parameters. Intravesical nicotine (50 nM, 1 microM) increased the intercontraction interval. Intravesical choline (1-100 microM) also affected bladder reflexes similarly, suggesting that alpha7 nicotinic receptors mediate this effect. Intravesical administration of hexamethonium (1-100 microM) potentiated the nicotine-induced changes in bladder reflexes. Methyllycaconitine citrate, a specific alpha7-receptor antagonist, prevented nicotine-, choline-, and hexamethonium-induced bladder inhibition. These results are the first indication that stimulation of nonneuronal nicotinic receptors in the bladder can affect micturition.
Administration, Intravesical↗
Immediate administration of intravesical mitomycin C after tumour resection for superficial bladder cancer.
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Administration, Intravesical↗
Vesical-renal reflex: diuresis and natriuresis activated by intravesical capsaicin.
In the last years the role of capsaicin sensitive innervation, in the activation of the micturition reflex, has been reported in many papers. In our experience, upon the intravesical administration of capsaicin in humans, we noticed an increase of diuresis. No interaction is known about the sensory innervation of the bladder and renal function, so we studied the possibility of the existence of a vesical-renal reflex arc. Twenty-one patients (9 men and 12 women) were randomised to receive intravesical infusion of saline solution containing 10 microM capsaicin. Urine output, glomerular renal filtrate (GRF) and effective plasma renal flow (EPRF), measured by Technetium-99m diethylenetetramine-penta-acetic acid (DTPA) renal scintigraphy, were recorded over twenty minutes before and after the intravesical administration of capsaicin. Urine density, [Na+] and [K+] concentration, and prostaglandin E2 excretion were also determined before and after intravesical administration of capsaicin or vehicle. Installation of saline solution containing 10 microM capsaicin produced a significant increase of mean urine output, an increase of GRF, of EPRF and of [Na+] and [K+] urine concentration. An increase, not statistically significant, was observed of PgE2 excretion. None of the patients treated with vehicle showed any modification of parameters examined. The present findings demonstrate a hitherto unrecognized effect: increased diuresis following selective chemical stimulation of bladder efferents with capsaicin. The renal diuretic response to intravesical capsaicin represents a working hypothesis about the possible involvement of a vesical-renal reflex arc organized at spinal or supraspinal level.
Administration, Intravesical↗
Intravesical instillation of drugs in patients with detrusor hyperactivity.
Intravesical administration of drugs may inhibit detrusor hyperactivity. Intravesical drug administration might be clinically useful in patients with detrusor hyperactivity, particularly in patients with neurogenic etiology using CIC. The therapeutic usefulness has to be documented in controlled studies. The mechanisms of action and the potency of the individual substances can not be decided from the present investigations. However, no finding contradicts that the known pharmacological properties of the drugs used are responsible for the effects noted. The different responsiveness to intravesical drugs between patients with neurogenic and non-neurogenic etiology might be due to pathophysiological differences. By intravesical administration of drugs the tissue concentration obtainable within the bladder wall is higher than the one obtainable by systemic administration. The optimal relation between tissue and serum concentrations can be achieved by a careful preparation of the drug solution and by titration of the dose. No side effects were found in the studies and no clinically significant side effects have been reported by other investigators. The risk of late side effects is unknown. The serum concentrations found in man and rabbit, after intravesical instillation of terodiline, indicate that by this route of administration terodiline may be safely used, in spite of the side effects reported at systemic administration. For evaluation of the diagnostic usefulness further documentation of the mechanisms of action and of the pathophysiology are needed.
Administration, Intravesical↗
Immediate administration of intravesical mitomycin C after tumour resection for superficial bladder cancer.
OBJECTIVE: To assess the feasibility and safety of administering intravesical mitomycin C in theatre immediately after transurethral resection of bladder tumour (TURBT). PATIENTS AND METHODS: A protocol was developed to allow the safe administration of mitomycin C in theatre immediately after TURBT. Over a 32-month period all patients not excluded by the protocol were given mitomycin C in theatre after TURBT, and any adverse events reported. RESULTS: In all, 177 instillations were carried out; there were two minor patient-related complications, and no staff-related adverse events. CONCLUSION: The immediate administration of mitomycin C in theatre after TURBT is feasible and safe for patients and staff. It provides the earliest and surest prophylaxis against tumour cell re-implantation at TURBT.
Administration, Intravesical↗
[Fluorescence cystoscopy using 5-aminolevulinic acid].
BACKGROUND: Fluorescence diagnosis has an increasing importance in different medical fields. In the presented paper, comparison of cystoscopy in white light with fluorescence cystoscopy after intravesical administration of 1 g of 5-aminolevulinic acid is presented. METHODS AND RESULTS: From the group of 63 persons examined, no difference between findings in white and blue light was found in 39 cases. In 21 patients more pathological spots were found in blue light (10 cases) or, in agreement with histology, pathology was detected in the blue light only (11 cases). CONCLUSIONS: The intravesical administration of 5-aminolevulinic acid had no side effects. Our study has definitely proved the advantages of fluorescence cystoscopy.
Administration, Intravesical↗
Intravesical protamine sulfate and potassium chloride as a model for bladder hyperactivity.
OBJECTIVES: An acute animal model for hyperactive bladder in rats was developed using intravesical infusion of protamine sulfate (PS), an agent thought to break down urothelial barrier function, and physiologic concentrations of potassium chloride (KCl). METHODS: Continuous cystometrograms (CMGs) were performed in urethane-anesthetized female rats by filling the bladder (0.04 mL/min) with normal saline followed by intravesical infusion of a test solution consisting of either KCl (100 or 500 mM) or PS (10 or 30 mg/mL) for 60 minutes. Subsequently, the 10 mg/mL PS-treated animals were infused intravesically with 100, 300, or 500 mM KCl. Some animals were pretreated with capsaicin (125 mg/kg subcutaneously) 4 days before the experiments. RESULTS: Unlike KCl (100 or 500 mM) or a low concentration of PS (10 mg/mL) alone, the intravesical administration of a high concentration of PS (30 mg/mL) produced irritative effects with a decreased intercontraction interval (by 80.6%). After infusion of a low concentration of PS, infusion of 300 or 500 mM KCl produced irritative effects (intercontraction interval decreased by 76.9% or 82.9%, respectively). The onset of irritation occurred more rapidly after 500 mM KCl (10 to 15 minutes) than after 300 mM KCl (20 to 30 minutes). Capsaicin pretreatment delayed the onset (approximately 60 minutes) and reduced the magnitude (intercontraction interval decreased by 35.5%) of irritative effects. CONCLUSIONS: Intravesical administration of KCl after PS treatment activates capsaicin-sensitive afferents and detrusor muscle and presumably capsaicin-resistant afferents. Modest, noncytotoxic affronts to urothelial barrier function can result in dramatic irritative responses. This model may be useful in the study of bladder irritation and hyperactivity.
Administration, Intravesical↗
Clinical application of radioimmunoimaging with 99mTc-BDI-1 in the diagnosis of bladder cancer.
OBJECTIVE: To evaluate the clinical application of radioimmunoimaging (RII) with 99mTc-BDI-1 in the diagnosis of bladder cancer. METHODS: 32 patients with bladder cancer and 5 with normal bladder were studied. RII was performed 1 hour after intravesical administration of 111-222 MBq 99mTc-BDI-1 followed by washing out and perfusing bladder with 50 ml PBS. The radioactivity ratio of target over background (CT/CB) was calculated. RESULTS: The radiochemical purity of 99mTc-BDI-1 was greater than 95%. RII showed radioactive accumulation area for most of bladder cancers but no radio-active concentration for normal bladder. The sensitivity and specificity were 91.7% and 81.8% respectively with the assignment of the positive criterion of CT/CB > or = 1.40. There was no statistical difference in sensitivity between tumors with diameters > or = 1 cm (1.0-4.2 cm) and < 1 cm (0.2-0.8 cm). CT/CB was related to the pathological grade (G1-G3) of the tumor. CONCLUSIONS: RII by intravesical administration provides a new noninvasive method for the diagnosis of bladder cancer in morphology and in nature of tumor with high sensitivity and specificity. It may be used for the early diagnosis of bladder cancer, follow-up after surgery, and diagnosis of in situ tumor.
Administration, Intravesical↗
Electromotive administration of intravesical lidocaine in patients with interstitial cystitis.
Six patients with long-standing interstitial cystitis (IC) were treated with intravesical electromotive drug-assisted (EMDA) therapy using lidocaine (1.5%) and 1:100,000 epinephrine in aqueous solution. A stainless-steel silver-coated anode placed through an 18F Foley catheter was positioned in the urinary bladder, and a 5 x 10-cm dispersion electrode (cathode) was placed on the suprapubic skin, which was well lubricated with conductive jelly. The two electrodes were connected to a pulsed DC generator, and electrical current was slowly ramped from 0 to 15 mA while the lidocaine and epinephrine were in the urinary bladder. After 40 minutes of current application, the bladder was hydraulically dilated to maximum tolerance. Significant bladder dilatation was achieved without systemic symptoms. Post-treatment, voiding symptoms decreased, as did suprapubic and perineal pain, and in four patients, the results have been durable.
Administration, Intravesical↗
Comparative effects of intravesical versus extravesical administration of ZD6169 and cromakalim on the response of the in vitro rat whole bladder to field stimulation.
Potassium channel openers are currently being evaluated for their inhibitory effect on hyperreflexia. Increasing potassium permeability results in a hyperpolarization of the smooth muscle membrane and a reduction in calcium entry. This stabilizes the membrane and should result in the reduction of spontaneous contractile activity. Potassium channel agonists have been shown to be effective in the reduction of hyperreflexia secondary to outlet obstruction in rats, and certainly have been shown to reduce the contractile response of isolated tissues to a number of different agonists. In addition, intravesical administration of potassium channel openers have been shown to be effective against hyperreflexia (in rabbits) using intravesical administration, although relatively high concentrations had to be employed. Using an in vitro whole bladder model (rat), our current study compares the potency and efficacy of intravesical versus extravesical administration of two potassium channel openers for the inhibition of field-stimulated contraction. The results demonstrate that (1) the extracellular administration of ZD6169 and cromakalim were equally effective inhibitors of the contractile response to field stimulation, (2) low frequency stimulation was inhibited to a significantly greater degree than high frequency stimulation, (3) intravesical administration of ZD6169 was equally effective at inhibiting the response to low frequency field stimulation when compared to extravesical administration, (4) intravesical administration was less effective than extravesical administration at high frequency stimulation (although the inhibition was still statistically significant), and (5) intravesical administration of cromakalim did not inhibit field stimulation.
Amides↗
[Intravesical oxybutynin hydrochloride in the treatment of urge incontinence in the elderly].
PURPOSE: This study was carried out to determine the effectiveness of intravesical oxybutynin hydrochloride on urinary urge incontinence in elderly people. METHODS: The subjects consisted of 13 patients with an average age of 75 years who demonstrated uninhibited detrusor contraction on cystometrogram. The trial protocol consisted of a pretreatment cystometrogram followed by the intravesical administration of 10 ml solution containing 5 mg oxybutynin hydrochloride (pH 5.85). The urodynamic studies were repeated one hour later. RESULTS: The mean bladder capacity before and after one hour of intravesical oxybutynin hydrochloride was 161 +/- 62 ml and 196 +/- 71 ml (mean +/- 1 S.D., n.s.). The rate of improvement was 15.4% (2 cases) in all 13 patients. Four patients out of 13 patients continued intravesical administration of the solution twice daily. Urinary incontinence disappeared in two patients and incontinence was markedly decreased in one. In the remaining patient, urinary incontinence did not change because of increased residual urine. Three patients have continued this therapy over one years and no side effects were observed. In these patients, residual urine volume did not increase. CONCLUSION: It is suggested that intravesical oxybutynin hydrochloride is an effective option of therapy for intractable urge incontinence in elderly people, however, the immediate posttreatment cystometrogram was not predictive of the response to intravesical therapy on overactive bladder in the elderly.
Administration, Intravesical↗
Whole bladder photodynamic therapy with 5-aminolevulinic acid using a white light source.
OBJECTIVES: To determine whether whole bladder photodynamic therapy after intravesical administration of 5-aminolevulinic acid using a white light source would destroy urothelial carcinoma. We sought to define the optimal target group of patients for this therapy. The side effects of treatment were also assessed. METHODS: We performed whole bladder photodynamic therapy with 100 J/cm(2) white light 2 to 4.5 hours after intravesical administration of 17% 5-aminolevulinic acid in 12 patients with recurring, multifocal, Stage pTa, grade I to III, urothelial tumors of the bladder and carcinoma in situ. RESULTS: Immediately after whole bladder irradiation, histologic examination of biopsies taken from flat suspicious lesions showed no viable cells; remnants of malignant cells were found in papillary tumors. Of the 12 patients, 11 returned for follow-up examination. At a median follow-up of 18 months (range 3 to 25), 3 of the 7 patients with carcinoma in situ and 2 of the 4 patients with papillary tumors were free of disease. In all patients, urinary frequency and urgency subsided within 3 weeks. No decreased bladder capacity or systemic side effects were observed. CONCLUSIONS: Our preliminary data show that whole bladder photodynamic therapy with intravesically applied 5-aminolevulinic acid using a white light source is effective in destroying flat malignant lesions of the bladder such as carcinoma in situ. The procedure is easy to perform and is not associated with any major side effects. The findings warrant long-term and multicenter studies.
Administration, Intravesical↗
Localization of avidin in superficial bladder cancer: a potentially new approach for radionuclide therapy.
OBJECTIVE: To verify whether native avidin, made radioactive through the binding with technetium-99m labeled biotin (99mTc-biotin), selectively accumulated in superficial tumor tissues following intravesical administration. METHODOLOGY: A total of fifteen patients with transitional cell bladder cancer were instilled intravesically with radiolabeled avidin. Cold biopsies were obtained from macroscopically normal and tumor tissues before transurethral resection (TUR) and the radioactivity in the samples was measured. RESULTS: Increased accumulation of radiolabeled avidin was observed in tumor tissue compared to normal bladder tissue and in some cases, remarkably high quotients of uptake (q) in tumor versus normal tissues were determined (86 and 44). The three patients instilled with a deglycosylated avidin at neutral pI, who served as a control, showed no significant uptake in either tumor or normal urothelium and no difference in relative uptake (q=1.0). CONCLUSION: This pilot study indicated that intravesical administration of radiolabeled avidin resulted in a preferential accumulation in tumor tissue compared to normal urothelium. The instillation of radiolabeled avidin warrant further investigations in order to explore the possibility to treat superficial bladder neoplasms locally by replacing 99mTc with high energy beta emitting radionuclides associated with biotin.
Aged↗
The development of liposomes containing interferon alpha for the intravesical therapy of human superficial bladder cancer.
Current therapy of human superficial bladder cancer includes the intravesical administration of antitumor drugs and immunomodulators. The purpose of these studies was to determine whether phospholipid liposomes that bind to human bladder cancer cells can improve the delivery of interferon alpha (IFN-alpha) to neoplastic urothelium. The antiproliferative activity of free IFN-alpha and IFN-alpha encapsulated in liposomes was assessed in vitro against the human transitional cell carcinoma line 253J. The cells were exposed to free and liposome-encapsulated IFN-alpha for short periods ranging from 30 minutes to four hours, and inhibition of cell growth was determined three days later. The production of greater than 25 percent cytostasis of 253J cells by free IFN-alpha required four hours of continuous exposure. In contrast, IFN-alpha encapsulated in liposomes produced 35 percent and 60 percent cytostasis after a 30-minute and four-hour exposure, respectively. Liposome-encapsulated IFN-alpha was also effective (50 percent cytostasis) against a subline of 253J cells selected for resistance against free IFN-alpha. Liposomes containing IFN-alpha were stable in the presence of human urine. In vivo studies in mice showed that intravesical administration of radiolabeled IFN-alpha or radiolabeled liposomes did not yield significant systemic absorption and deposition in distant organs. Collectively, these results suggest that the encapsulation of IFN-alpha within multilamellar liposomes may augment its antiproliferative activity, overcome some forms of tumor cell resistance to IFN-alpha, and prove useful for intravesical therapy of superficial bladder cancer.
Administration, Intravesical↗
Clinical pharmacokinetics of 5-aminolevulinic acid in healthy volunteers and patients at high risk for recurrent bladder cancer.
5-Aminolevulinic acid (ALA) is a precursor of protoporphyrin IX (PpIX) that is being evaluated for use in photodiagnosis and phototherapy of malignant and nonmalignant disorders. Previous clinical studies using topical, oral, and intravesical administration have been conducted in attempts to determine the optimal route of administration for ALA. The purpose of these studies was to examine the systemic pharmacokinetics and elimination of ALA, the bioavailability of ALA after oral and intravesical doses, and the factors that affect ALA concentrations in the bladder during intravesical treatment. The disposition of ALA was evaluated in six healthy volunteers receiving single intravenous and oral doses (100 mg) and eight patients at high risk for recurrent bladder cancer receiving an intravesical dose (1.328 g) of ALA. The mean (+/-S.D.) plasma area under the plasma concentration-time curve from time 0 to infinity of PpIX (0.20 +/- 0.11 microg small middle dot h/ml) after intravenous administration of ALA was not significantly different from that observed after oral administration of ALA (0.15 +/- 0.11 microg*h/ml; P = 0.49). ALA terminal half-life was approximately 45 min after intravenous or oral administration. The oral bioavailability of ALA was approximately 60%. After intravesical administration, urine production was largely responsible for decreases in ALA concentration in the bladder, with less than 1% being absorbed into the systemic circulation. In summary, oral and intravenous administration of ALA at these doses results in modest plasma levels of PpIX. Regional administration (i.e., intravesical) of ALA resulted in a significant pharmacokinetic advantage, with urinary bladder being exposed to concentrations approximately 20,000-fold higher than systemic circulation.
Administration, Intravesical↗