[Intravesical administration of estriol as a possible form of therapy of sensory urge incontinence].
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Administration, Intravesical↗
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Influence of intravesical administration of tumor necrosis factor alpha and systemic gamma-interferon on murine bladder cancer: lack of dose response.
The effect of intravesical administration of high dose recombinant tumor necrosis factor-alpha (rTNF) and in combination with systemic recombinant gamma-interferon (rIFN) on murine bladder cancer was studied. RTNF was given at 12.5 micrograms/mouse on days 7, 11 and 15 after tumor instillation or at 2.5 micrograms/mouse on days 7, 9, 11, 13 and 15. Some groups were also injected i.v., 24-h prior to each rTNF treatment with rIFN at a dose of 1.3 micrograms/mouse. RTNF treatment suppressed tumor growth up to 48% of control, although the difference was not statistically significant. Combined administration of rIFN did not provide additional benefit.
Administration, Intravesical↗
Intravesical administration of radiolabeled antitumor monoclonal antibody in bladder carcinoma.
Tumor associated AUA1 monoclonal antibody and 11.4.1. nonspecific monoclonal antibody, which does not react with human tissues, were radiolabeled with 111In and administered intravesically to 23 patients undergoing cystoscopy for bladder carcinoma. The antibody solution remained in the bladder for 1 h and then was washed out prior to cystoscopy. Tumor and nontumor samples were obtained during cystoscopy and were counted in a gamma counter. Conventional and immunoperoxidase staining with both antibodies were also performed. AUA1 reacted with all bladder carcinomas while 11.4.1. was negative in all cases. The mean uptake of AUA1 at 2, 24, and 48 h after the instillation (expressed as 10(3) x percentage of injected dose/g of tissue) was: 6.12 +/- 5.50 (SD), 1.70 +/- 2.57, 0.30 +/- 0.17 in the tumors and 0.32 +/- 0.50, 0.22 +/- 0.30, 0 in the nontumor areas, and for 11.4.1. it was: 0.075 +/- 0.075, 0.025 +/- 0.025 in the tumors and 0.30 +/- 0.42, 0.15 +/- 0.26 in the nontumor areas. The uptake of AUA1 by the tumors correlated with the tumor grade. There was no radioactivity in the blood at 2 h, and at 1, 2, and 3 days after the instillation. Our results indicate that intravesical administration of radiolabeled monoclonal antibody AUA1 targets selectively to tumor tissue without any significant normal tissue uptake. This finding might allow the development of a nontoxic and specific therapeutic approach for superficial bladder carcinoma.
Administration, Intravesical↗
Penetration of misonidazole after intravesical administration in cases of carcinoma of the bilharzial bladder.
The penetration of misonidazole was studied by a semiquantitative T.L.C. method after intravesical administration 2 h before total cystectomy in cases of carcinoma of the Bilharzial bladder. In 5 out of 7 cases misonidazole was found at a concentration of the order of 0.4 mg/g in the superficial and deep parts of the tumour, but not in normal bladder tissues.
Humans↗
Experimental hyperreflexia: effect of intravesical administration of various agents.
In anesthetized rabbits, we can induce a significant degree of spontaneous activity in the urinary bladder by placing a ligature around the proximal portion of the external urethra. Previous studies characterized the activity as primarily reflex in nature, since intravesical hexamethonium selectively inhibited the hyperreflexia. In this current study we determined the effect of intravesical administration of a variety of compounds to inhibit the induced hyperreflexia. The following agents were tested at concentrations of 1, 10, 100 and 500 mumol/l (intravesically): verapamil, cromakalim, nifedipine, diltiazem, and atropine; lidocaine was tested in 0.05, 0.5 and 5% solutions. The results are summarized as follows: (1) Lidocaine was the most effective agent tested, virtually eliminating both the amplitude and frequency of the spontaneous activity at the lowest concentration (0.5%). (2) Verapamil and nifedipine were somewhat more potent than cromakalim and diltiazem. Atropine sulfate was the least potent, inhibiting both the amplitude and frequency of the hyperreflexia by less than 50% at 500 mumol/l. (3) In all cases, the amplitude of the spontaneous activity was inhibited to a significantly greater degree than the frequency of the spontaneous activity. (4) In general, there was no effect of any of the agents on mean arterial pressure at 1 or 10 mumol/l. At 100 and 500 mumol/l, all agents except for lidocaine and cromakalim decreased arterial pressure. These two agents produced no consistent fall in blood pressure at any concentration. In conclusion, the acute hyperreflexic (rabbit) preparation provides a highly reproducible and consistent model for the study of the effect of drugs on hyperreflexia.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Comparison of emepronium bromide with intravesical administration of lidocaine gel in women with urge incontinence].
In the treatment of urge incontinence, drug therapy predominates. In a prospective randomised study on treatment of females with motor urge incontinence, intravesically administered lidocaine-gel and oral emepronium bromide were compared using clinical and urodynamic parameters. From 30 patients, 15 women were treated for 3 weeks with repeated intravesical lidocaine gel instillations whilst the other 15 had a peroral emepronium bromide medication. The intravesical lidocaine gel installation proved more efficient compared with peroral emepronium bromide therapy with regard to the parameters of imperative micturition, occurrence of detrusor contractions as well as number of urinary frequencies per diem. Intravesical application of lidocaine-gel is particularly indicated in patients with increased sensitivity against parasympathicolytics and anticholinergics.
Administration, Intravesical↗
Comparison of intravenous and intravesical administration of chloro-aluminum sulfonated phthalocyanine for photodynamic treatment in a rat bladder cancer model.
Photodynamic therapy is an experimental treatment of superficial bladder tumors. Photofrin, a mixture of porphyrins, is the only photosensitizer in clinical use in the U.S.A. and its major side effect is prolonged cutaneous phototoxicity. In order to circumvent this problem of phototoxicity, new photosensitizers are being examined. Cutaneous phototoxicity may also be minimized by local administration of photosensitizer. Therefore, in this study, we investigated the photosensitizer chloro-aluminum sulfonated phthalocyanine (CASPc) in vivo in a rat bladder carcinoma model, and compared two different routes of CASPc administration. AY-27 rat bladder carcinoma cells were transplanted into rat bladders. Eight days after tumor transplantation the biodistribution of CASPc in bladder, skin, muscle and bladder tumor was determined by fluorescence measurements after dye extraction. Photosensitizer administered by intravenous injection and intravesical instillation, were compared. The concentration of CASPc in bladder and bladder tumor after intravenous injection and intravesical instillation was similar. The ratio of dye uptake between tumor and normal bladder after either administration was approximately two. Although no systemic absorption of the photosensitizer was observed after intravesical instillation, there was no reduction in tumor uptake or in the ratio between tumor to normal surrounding tissue. Therefore, no systemic side effects of skin phototoxicity are expected upon intravesical instillation. The microscopic biodistribution of CASPc after intravenous injection and intravesical instillation was also compared. After intravenous injection, the photosensitizer was distributed within the whole tumor with increased fluorescence around the microvasculature. In the normal bladder wall, weak fluorescence was seen in the area of the vasculature in the submucosa and the muscularis. After intravesical instillation, strong fluorescence was detected only at the tumor surface and in normal urothelium; no fluorescence was found in other areas of the tumor or in submucosa or muscularis. A comparison of the photodynamic treatment of model bladder tumors showed that tumor destruction after either method was similar but that there were less side effects to normal bladder wall after intravesical instillation of the CASPc. Intravesical administration of photosensitizers may, therefore, be a viable alternative to intravenous injection with potential for reduced systemic and normal tissue toxicity.
Administration, Intravesical↗
Facilitation of reflex micturition by intravesical administration of [beta Ala8]-neurokinin A (4-10), a selective NK-2 tachykinin receptor agonist.
We have determined the ability of [beta Ala8]-NKA(4-10), a selective agonist for NK-2 tachykinin receptors to stimulate micturition in anesthetized rats and guinea-pigs. In both species, the intravesical instillation of the peptide at microM concentrations reduced bladder capacity and residual volume, indicating a facilitatory effect on reflex micturition. At these concentrations, no plasma extravasation was produced as determined by the Evans blue content of the organ. In experiments on the isolated rat or guinea-pig bladder strips, the NK-2 receptor agonist induced powerful contractions. In a in vitro model of the guinea-pig whole bladder the intravesical instillation of the NK-2 agonist facilitated the occurrence of rhythmic contractile activity. It is concluded from these studies that intravenous administration of [beta Ala8]-NKA(4-10) exerts a facilitatory effect on the micturition reflex, presumably involving the ability of the NK-2 receptor agonist to cross the urothelium and stimulate smooth muscle contraction.
Administration, Intravesical↗
[Massive secondary psoriasiform dermatitis secondary to intravesical administration of mitomycin C].
We report on a patient who had been submitted to vesical diverticulectomy. Pathological examination of the surgical specimen revealed G2T1 urothelial carcinoma. Intravesical chemotherapy with mitomycin C was instituted. Following the sixth instillation, the patient developed widespread psoriasiform dermatitis and required admission to hospital. Remission was achieved with drug withdrawal and symptomatic treatment. The literature is reviewed.
Aged↗
[Pharmacodynamics of dibunol in the blood of patients with bladder neoplasms following oral and intravesical administration].
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Administration, Oral↗
Intravesical recombinant tissue plasminogen activator for the prevention of implantation-mediated bladder tumor recurrence.
The mechanism by which intravesical recombinant tissue plasminogen activator (rTPA) prevents tumor cell adherence to injured bladder surfaces, and the optimal parameters for the in vivo use of rTPA for adherence prevention, were evaluated. Intravesical rTPA decreased tumor cell adherence to sites of urothelial injury as a direct function of drug concentration in the intravesical fluid. Recombinant TPA concentrations of 1 mg/ml and 0.1 mg/ml significantly decreased tumor cell adherence relative to the control group. The efficacy of rTPA in removing adherent cells was time-dependent with maximal activity occurring at 15 min or later following intravesical administration. Intravesical rTPA effectively reduced the size of the tumor inoculum when administered either concomitant with, or subsequent to, tumor cell exposure. The relative efficacy of these two approaches was dependent upon the presence of serum in the intravesical fluid. Administration of rTPA concomitant with tumor cell exposure proved more effective in the absence of serum, while postadherence administration was more effective in the presence of 10% fetal calf serum. The addition of exogenous plasminogen to the rTPA solution did not increase anti-adherence activity relative to rTPA alone. However, blockade of endogenous plasminogen conversion with systemically administered epsilon-amino-caproic acid reversed the anti-adherence activity of exogenous rTPA. In vitro experiments evaluating cellular adherence to fibrin substrate confirmed that rTPA's anti-adherence activity was dependent on the presence of plasminogen. Exogenous rTPA administered immediately following tumor cell adherence decreased tumor cell implantation in animals receiving low to moderate tumor inoculums. These data suggest that rTPA prevents cellular adherence as a result of plasminogen activation and subsequent fibrinolysis. Intravesical rTPA administered in sufficient concentration for relatively short periods of time effectively reduces the adherent tumor inoculum and alters implantation as an inverse function of the tumor inoculum. This approach represents a novel strategy which may prove applicable for the prevention of implantation-mediated tumor recurrence at sites of surgical trauma.
Administration, Intravesical↗
Percutaneous, oral, or intravesical BCG administration: what is the optimal route?
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Administration, Cutaneous↗
Intravesical BCG administration in the guinea pig. Histomorphological aspects.
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Administration, Intravesical↗
Intravesical BCG administration in the guinea pig. II. Immunohistochemical characterization of cellular infiltrate after one or two cycles of intravesical BCG.
The intravesical administration of bacillus Calmette-Guérin (BCG) is used as an adjuvant therapy after transurethral resection for superficial bladder cancer in man. The aim of this study was to characterize with monoclonal antibodies the cellular infiltrates in the bladder wall occurring after one or two cycles, each comprising six weekly intravesical BCG administrations in guinea pigs. BCG-RIVM and BCG-TICE were instilled once a week in undamaged bladders at weeks 1-6 and 11-16, respectively, and retained in the bladder for 1 h. Autopsy was performed 1 week after the last BCG administration at weeks 7 and 17. By routine histology, a single BCG course induced scattered focal infiltrates consisting of minor to severe accumulations of mononuclear cells. After two cycles of BCG, a much more severe inflammatory reaction sometimes occupying almost the total bladder mucosa was noted. The major component of this inflammation was mononuclear cells, mainly lymphocytes, while typical BCG granulomas were occasionally observed. In general, the epithelial layer of the bladder showed no visible alterations. Immunohistochemical staining showed that the majority of mononuclear cells present in the infiltrate were T-cells. Widely scattered B-cells and macrophages were also present, but were much fewer in number than the T-cells. In general, T-helper/inducer cells were more frequent than T-suppressor/cytotoxic cells. Pseudofollicles, also noted after H&E staining, consisted mainly of B-cells. The second series of BCG administrations produced pseudofollicles in the infiltrates in all animals investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Impaired immune response by isoniazid treatment during intravesical BCG administration in the guinea pig.
At present, isoniazid (INH) is being used prophylactically to reduce the side effects of intravesical BCG therapy for superficial bladder cancer, although it is not clear whether or not this reduces the antitumor efficacy of BCG. In this study the impact of INH treatment on the immune response after repeated intravesical BCG administration was investigated in guinea pigs. INH was given on the 3 days around each BCG instillation. We found that the administration of INH severely impaired the immunological effects of BCG. The induction of mononuclear cell infiltration in the bladder wall was reduced. Enlargement of the regional lymph nodes (weight and number of cells), and increase of MHC Class II expression on the lymph node cells, normally observed after intravesical BCG administration, were inhibited by INH. Systemic immunity, measured by the DTH reaction in the skin to PPD, was also diminished due to the combined treatment of BCG with INH. When INH was administered during the last 4 of 6 BCG instillations, the immune response to BCG was still impaired. A five-fold increase of the dose of BCG did not overcome the effect of INH. INH probably did not exert a direct suppression of the immune system of the guinea pig as the DNCB skin reactivity was not influenced. Although INH concentrations in the urine were high at the onset of the instillation, in vitro experiments indicated that the effect of INH may not be caused by killing of the BCG organisms shortly after application in the bladder. In conclusion, our data in guinea pigs suggest that the use of INH may impair the immune response to intravesical BCG. As this response may be important for the antitumor effect of BCG, urologists should be cautious with the prophylactic use of INH. The influence on the antitumor efficacy is now investigated in man.
Administration, Intravesical↗
Impaired immune response by isoniazid treatment during intravesical BCG administration in the guinea pig.
At present, isoniazid (INH) is being used prophylactically to reduce the side effects of intravesical BCG therapy for superficial bladder cancer, although it is not clear whether or not this reduces the antitumor efficacy of BCG. In this study the impact of INH treatment on the immune response after repeated intravesical BCG administration was investigated in guinea pigs. INH was given during 3 days starting on the day prior to the BCG administration. It was found that the administration of INH severely impaired the immunological effects of BCG. The induction of mononuclear cell infiltration in the bladder wall was reduced. Enlargement of the regional lymph nodes (weight and number of cells), and increase of Major Histocompatibility Complex (MHC) class II expression on the lymph node cells, normally observed after intravesical BCG administration, were inhibited by INH. Systemic immunity, measured by the DTH reaction in the skin to PPD, was also diminished due to the combined treatment of BCG with INH. A five-fold increase of the dose of BCG did not overcome the effect of INH. INH probably did not exert a direct suppression of the immune system of the guinea pig as the DNCB skin reactivity was not influenced. Although INH concentrations in the urine were high at the onset of the instillation, in vitro experiments indicated that the effect of INH was probably not caused by killing of the BCG organisms shortly after application in the bladder. In conclusion, our data in guinea pigs suggest that the use of INH may impair the immune response to intravesical BCG. As this response may be important for the antitumor effect of BCG, urologists should be cautious with the prophylactic use of INH. The influence on the antitumor efficacy is now investigated in man.
Administration, Intravesical↗
Intravesical instillation of adriamycin in the presence or absence of verapamil for the treatment of superficial bladder cancer: preliminary report of a collaborative study.
A case-controlled collaborative study on the intravesical administration of Adriamycin in the presence or absence of verapamil, a calcium-channel blocker, as chemotherapy of superficial bladder cancer was carried out at two universities, Okayama and Kagoshima, and their affiliated hospitals. Although little is known about the expression of P-glycoprotein in superficial bladder cancer, it may be a cause of multidrug resistance (MDR). Verapamil was used as an inhibitor of P-glycoprotein. Arm A consisted of Adriamycin given at 50 mg/50 ml saline, and arm B constituted Adriamycin given at 50 mg/40 ml saline plus 5 ampules (10 ml) of injectable verapamil. The drugs were instilled into the bladder for 3 consecutive days in each of 3 consecutive weeks for a total of 9 instillations. No significant difference in antitumor effects was observed between arm A and arm B. Recurrent tumors responded better than did primary tumors to both arm-A and arm-B treatments (P = 0.012). In both treatment arms, significant differences (P = 0.031) in the response rate were found between tumors with diameters of less than 1 cm and those measuring 1-3 cm in diameter. Although the number of evaluable patients was limited, recurrent subjects who had previously received Adriamycin instillations responded in both treatment arms.
Administration, Intravesical↗
Urinary interleukins in patients receiving intravesical Bacillus Calmette-Guerin therapy for superficial bladder cancer.
Intravesical administration of Bacillus Calmette-Guerin (BCG) causes a localized cell-mediated immune response. The intensity of this inflammatory response may be gauged by measuring the levels of both interleukin-2 (IL-2) and an inhibitor of interleukin-2 (IL-2-IN) activity in the urine during the hours after a BCG instillation. The levels of urinary IL-2 and IL-2-IN in the sixth week of BCG therapy predicted the subsequent clinical course in a group of 25 patients (P less than 0.01). Measurement of urinary IL-2 and IL-2-IN activity may be used to identify accurately those patients likely to develop a tumor recurrence, thereby sparing them the risk associated with inadequately treated bladder cancer. Since IL-2 and IL-2-IN are competitive with respect to biologic activity, and since relatively high urinary levels of either IL-2 or IL-2-IN activity correlated with a favorable clinical course, the authors conclude that the presence of bioactive IL-2 in urine is not required for the prevention of recurrent superficial bladder cancer.
Administration, Intravesical↗