[Intravesical chemotherapy of adriamycin and verapamil in patients with recurrent superficial bladder cancer: preliminary report].
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Biomedical subjects
Publications and source records attributed to H Ohmori.
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Cefroxadine (CXD) was administered to patients with acute uncomplicated cystitis (AUC) in a dose of 250 mg t.i.d. for 3-7 days. The patients were divided into 2 groups (less than 70 and greater than or equal to 70 years old) and clinical efficacy and incidents of recurrence were assessed. 1. Out of 83 patients treated, clinical efficacy was evaluated in 62 patients including 10 elder patients on the 3rd day and in 47 patients including 9 elder patients on the 7th day. In both groups clinical efficacy rates were 100% on the 3rd and 7th day. 2. Among 24 patients including 7 elder patients, who showed excellent response on the 7th day, recurrence was examined on the 14th day. The recurrence rate was 0% by the criteria proposed by the UTI committee in Japan. However, two patients (under 70 years of age) among them were considered as positive for recurrence by doctors in charge. Consequently, in both aged groups CXD showed excellent results in the treatment of AUC.
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We evaluated the effects of 4'-epi-Adriamycin (EPI), a derivative of Adriamycin (ADR), in intravesical instillation chemotherapy. The patients received two courses of three daily instillations of 50-80 mg EPI dissolved in 30 ml physiological saline on 3 consecutive days, with an interval of 4 days between courses. Full evaluation was possible in 33 of 35 patients with superficial bladder tumors treated with EPI. Complete response was observed in 4 cases and partial response in 14 cases, giving a response rate of 55%. Side effects such as pollakiuria and pain on micturition occurred in 9 cases. EPI appears to be an effective agent for intravesical instillation chemotherapy in patients with superficial bladder tumors.
A combination of 50 to 80 mg. per m.2 cis-platinum and 30 to 50 mg. per m.2 doxorubicin or 30 to 50 mg. per m.2 tetrahydropyranyl-doxorubicin instead of doxorubicin was infused into the bilateral internal iliac artery for the treatment of 20 patients with T3 or T4 advanced bladder cancer. Angiotensin II was administered together with these chemotherapeutic agents by means of an infusion pump at a rate of 1.5 to 2.0 micrograms. per minute for 20 minutes for both sides. Among the 20 patients complete (9) and partial (8) responses were obtained after only 1 or 2 courses of this intra-arterial treatment. Histological examination showed severe tumor destruction with no viable cells in 6 and no tumor in 4 of the 15 evaluable cases. Selective enhancement of regional blood flow in the tumor region after intra-arterial infusion of angiotensin II was observed by continuous target arterial 81mkrypton infusion. Intra-arterial chemotherapy with combined angiotensin II may be clinically useful for treatment of primary or metastatic bladder carcinoma.
The electrical properties of rat Purkinje cells and synapses from granule cells were studied in dissociated cell cultures. To identify the cells we used an immunohistochemical method and recorded voltage-gated and synaptic currents with the patch-clamp technique (the whole-cell mode). Cultured Purkinje cells generated action potentials similar to those recorded from in vitro slices or in vivo preparations. Early Na, late Ca inward current, and K outward currents were distinguished by ion substitution under voltage clamp. We also recorded spontaneous synaptic currents in Purkinje cells cultured with granule cells. These synaptic currents reversed direction at the membrane potential of 2.5 mV, which was similar to currents induced by L-glutamate. Therefore, these are most likely excitatory synaptic currents from granule cells. Since these properties of Purkinje cells examined here are similar to those in situ, the cells in dissociated cell cultures offer a great opportunity to study biophysical properties of identified neurons in the central nervous system.
When murine lymphocytes were cultured in RPMI-1640 medium containing fetal calf serum (FCS) for more than 3 d without added antigens, suppressor T cells (Ts) that suppressed in vitro antibody responses to sheep erythrocytes, dinitrophenyl-Ficoll and trinitrophenyl (TNP)-lipopolysaccharide nonspecifically were induced spontaneously. Thus, we failed to detect the activities of antigen-specific Ts that are generated by priming the lymphocytes in vitro with a specific antigen under these experimental conditions. To avoid the induction of nonspecific Ts, we examined various culture conditions and found that nonspecific Ts were not induced only when a specific lot of FCS (NSF 107) was used. When the lymphocytes were cultured with Keyhole limpet hemocyanin (KLH) in NSF 107-containing culture medium, we could detect KLH-specific Ts activity that specifically suppressed the secondary response to TNP-KLH without the interference of nonspecific Ts. Similar experiments were successful if we used FCS that was previously treated at 70 degrees C for 10 min instead of native ones. Immunoelectrophoretic analysis revealed that the level of a component belonging to alpha-globulin fraction was markedly low in NSF 107 as compared with all other lots of FCS that could induce nonspecific Ts. Removal of this component from FCS by an immunoadsorbent resulted in the loss of capacity to induce nonspecific Ts. On the other hand, when the lymphocytes were cultured in the presence of varying amounts of this component, nonspecific Ts were generated in a dose-dependent manner.
When murine lymphocytes were cultured in a cystine-deficient RPMI-1640 medium containing 10% fetal calf serum, approximately 70% of the cells died in 48 h. In the presence of 5 X 10(-4) M L-cystine, 70-80% of the lymphocytes remained viable under the same condition. The decrease of the viability was also effectively inhibited when cystine was replaced by the following thiol compounds; 2-mercaptoethanol (2-ME), dithiothreitol (DTT), cysteamine and glutathione (GSH). Oxidized DTT, an intramolecular disulfide that was resistant to the reduction by the lymphocytes, did not show a protective effect in contrast to DTT. On the other hand, 2-hydroxyethyldisulfide was readily reduced to 2-ME by the lymphocytes and improved lymphocyte viability as effectively as 2-ME. These observations suggest that thiol groups are responsible for the improvement of lymphocyte viability under a cystine-deficient condition. The viabilities of both T cells and B cells were equally improved by 2-ME. The intracellular level of GSH remained constant in the presence of cystine but dropped rapidly in its absence. 2-ME could not reverse this decrease of GSH level. These protective effects of thiol compounds on lymphocyte viability are discussed in relation to their capacities to activate murine lymphocytes.
Lipoic acid (Lip) was examined for its effect on the in vivo antibody response in mice. It was found that Lip significantly restored the suppressed antibody response to sheep erythrocytes (SRBC) in cyclophosphamide-injected mice when it was orally administered at 25 mg/kg twice a day for 4 consecutive days after immunization. On the other hand, Lip-administration did not affect the antibody response in normal mice immunized with SRBC. Normal or cyclophosphamide-treated mice were primed with horse erythrocytes (HRBC) and were given either saline or Lip for 3 consecutive days. HRBC-specific helper T cell activity of their spleen cells were compared by coculturing these cells with trinitrophenyl (TNP)-keyhole limpet hemocyanin-primed spleen cells in the presence of TNP-HRBC as the antigen. A significant restoration of the suppressed helper T cell activity was observed in the Lip-administered group. However, the helper T cell activity was not affected significantly by Lip-administration in normal mice. Lip could also partially restore the helper T cell activities that were suppressed by the treatment with hydrocortisone or X-ray irradiation.
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A phase II study of a new anthracycline anti-cancer antibiotics, epirubicin (EPI), was undertaken in 71 patients with urothelial malignancies; 40 with advanced urothelial malignancies and 31 with superficial bladder cancer. Out of them 32 patients with advanced stage of urothelial cancer were evaluated for the systemic use of EPI, while 30 patients with superficial bladder cancer for intravesical use. Intravenous administration of this new anticancer antibiotic, at a dosage of 60 mg/m2 every three weeks, showed the response rate of 20.0% for advanced bladder cancer and 14.3% for renal pelvic and ureteral tumors. In cases of superficial bladder cancer, at a dosage of 60 mg/30 ml X 3 day every week in principal, the response rate was 66.7%. Eight out of 30 patients showed complete disappearance of the tumor. Twelve patients also showed more than 50% tumor regression. As for adverse effects no serious cardiotoxicity was demonstrated. Anorexia and other gastrointestinal side effects, such as nausea and vomiting, were also seen. Alopecia and myelosuppression were the major adverse effects among patients with systemic EPI administration. With intravesical use of EPI, cystitis syndrome was the major toxicity. However, no systemic side effects were noted in these cases. In conclusion, EPI was assumed to be effective for the treatment of advanced urothelial tumors and superficial bladder cancer.
A well-controlled comparative study was conducted in order to evaluate the efficacy, safety and usefulness of the monobactam antibiotic aztreonam (AZT) in complicated urinary tract infections (UTI) using cefoperazone (CPZ) as the control drug. Patients with complicated UTI due to Gram-negative bacteria were examined. However, in polymicrobial infections, the cases caused by Gram-negative and Gram-positive bacteria were also examined. Both drugs were administered 1 g, twice a day by intravenous drip infusion for 5 days. Overall clinical efficacy was evaluated by the criteria proposed by the UTI committee in Japan. Of the total 394 cases, the clinical efficacy was evaluated for 152 cases in the AZT group and 143 cases in the CPZ group excluding 99 cases of exclusion or dropout. There was no statistically significant difference in the back ground characteristics between the 2 groups. The overall clinical efficacy rate was 55.3% for AZT and 55.2% for CPZ with difference not significant. As for clinical efficacy, in the monomicrobial infection after postprostatectomy (G-2), AZT was superior to CPZ (P less than 0.05), whereas in the polymicrobial infection without indwelling catheter (G-6), CPZ was superior to AZT (P less than 0.1). The overall bacteriological eradication rate was 77.2% for AZT and 74.5% for CPZ. For Gram-negative bacteria only the eradication rate for AZT (83.2%) was superior to that for CPZ (74.6%). This was probably due to the stability of AZT to beta-lactamase. Side effects were observed in 3 cases out of 201 in the AZT group and 5 cases out of 189 in the CPZ group. No severe abnormal laboratory finding was observed in any group; there was no significant difference between the 2 groups. Consequently, AZT was judged to be an antibiotic with clinical usefulness equal to, or even superior to that of CPZ.
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Intra-arterial infusion chemotherapy in combination with angiotensin II was performed in 5 patients with advanced bladder cancer (all T3M0). The infusion catheter was inserted from a femoral artery into the internal iliac artery. The basic dosage was 70 mg/m2 of Cis-diammine-dichloroplatinum (CDDP) and 40 mg/m2 of Adriamycin (ADM) or 4'-0-tetrahydropyranyl-ADM (THP) in combination with 20-40 micrograms angiotensin II over a total duration of 20 minutes for both sides. Of the 5 patients, 3 CR and 2 PR were obtained by only one or two courses of intra-arterial infusion chemotherapy. Histological examination showed no viable cells in the three CR cases. Intra-arterial infusion chemotherapy in combination with angiotensin II may thus be clinically useful for advanced bladder cancer.