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Biomedical subjects

J Kumazawa

Publications and source records attributed to J Kumazawa.

At least 145 records · Page 8Linked to original sources

Early and quantitative detection of cisplatin-induced nephrotoxicity by measurement of plasma PSP (phenolsulfonphthalein) half-life in rats.

Renal function following cisplatin injection in rats was assessed by measuring the half-life of plasma PSP. Changes in BUN, creatinine, plasma PSP half-life and urinary N-acetyl-beta-D-glucosaminidase (NAG) levels were determined in rats treated with 6.5 mg/kg i.v. of cisplatin. The highest values of BUN and creatinine were both observed on day 5. Half-life of plasma PSP was significantly prolonged on days 2 through 5 and reached a peak value on day 3. A significant increase in urinary NAG levels appeared on day 2 and the peak value was demonstrated on day 3. BUN, creatinine and plasma PSP half-life were also determined on days 3 and 5 following several doses of i.v. cisplatin. A dose-related increase in plasma PSP half-life was observed on day 3, while dose-related increases in BUN and creatinine levels were found on day 5. The evaluation of cisplatin-induced nephrotoxicity by the plasma PSP test was clearly superior for early detection compared with conventional renal function tests using BUN and creatinine.

Animals↗

[Prophylactic effect of methylprednisolone on cisplatin-induced nephrotoxicity in rats].

Cis-diamminedichloroplatinum (II) (cisplatin) is a very effective antitumor drug, but It has an adverse effect of nephrotoxicity. There are many reports concerning protective agents against cisplatin nephrotoxicity, but clinically useful modalities are very few. In the present study, prophylactic effects of methylprednisolone (MP) on cisplatin-induced nephrotoxicity were examined. Male Sprague-Dawley rats were injected iv with 6.5 mg/kg of cisplatin combined with a subcutaneous MP given sc in various doses at various timing. Rats were killed 5 days after cisplatin injection to determine BUN and serum creatinine levels. BUN and serum creatinine levels in rats pretreated with MP 4 or 2 hr before cisplatin injection were significantly lower than those in rats received cisplatin alone. Our preliminary results suggest that pretreatment with MP is an effective means of protection against cisplatin-induced nephrotoxicity.

Animals↗

Adjuvant chemotherapy with early intravesical instillation of adriamycin and long-term oral administration of 5-fluorouracil in superficial bladder cancer. The Kyushu University Urological Oncology Group.

A randomized controlled trial was performed to study the efficiency of adjuvant chemotherapy with early intravesical instillation of Adriamycin and long-term oral administration of 5-fluorouracil in 275 patients with superficial bladder cancer. All of the patients were randomized into four groups. Group A received early (immediately and 2 days after transurethral resection) instillation of Adriamycin alone; Group B received early instillation of Adriamycin with oral administration of 5-fluorouracil; Group C received delayed (7 days after transurethral resection) instillation of Adriamycin alone; and group D received delayed instillation of Adriamycin with oral administration of 5-fluorouracil. All patients subsequently received instillations weekly for 2 weeks and then every 2 weeks for a further 14 weeks. After 4 months, they received monthly instillations for 8 months. 5-Fluorouracil (groups B and D) was given daily p.o. for 1 year. Evaluation was possible in 187 patients. The postoperative follow-up period for determination of non-recurrence rates was 36 months, during which no significant difference was detected among the four groups. Moreover, no statistically significant difference was found between the early- and delayed-instillation groups. However, the non-recurrence rates obtained in the groups undergoing early instillation were higher than those determined in the delayed-instillation groups during the 36-month follow-up period, and this difference was especially significant at 4 and 5 months. In addition, the early-instillation groups showed significantly higher non-recurrence rates than did the delayed-instillation groups in terms of primary cases (P less than 0.01), tumor size of less than 1 cm (P less than 0.05), multiple tumors (P less than 0.01), pathological stage pTa (P less than 0.01), and histological grades G1 and G2 (P less than 0.05). Groups B and D, which were treated by intravesical instillation of Adriamycin with oral administration of 5-fluorouracil, showed no significant prophylaxis of recurrence during the 36-month follow-up as compared with groups A and C, which received intravesical instillations alone. The main side effect, which required discontinuation of the treatment, was bladder irritation. However, no significant difference in its incidence was found between the early- and delayed-instillation groups. No severe systemic side effect was encountered in this study. These results suggest that early as well as repeated intravesical instillation of Adriamycin is clinically tolerable and may be effective in preventing the recurrence of superficial bladder cancer.

Administration, Intravesical↗

The dipstick test in the diagnosis of UTI and the effect of pretreatment catheter exchange in catheter-associated UTI.

We examined the value of the dipstick test for detecting pyuria and bacteriuria in the diagnosis of urinary tract infection (UTI). The dipstick esterase test could be quickly assessed and could easily detect leukocyte esterase in the urine. This was well correlated with the conventional sedimentation method. The dipstick nitrate reduction method for detecting bacteriuria, however, was not well correlated with the urine culture method. These findings suggested that the dipstick esterase test was a useful method for detecting pyuria in the diagnosis of UTI, but not the dipstick nitrate reduction method. Catheter-associated UTI is the most difficult category of UTI to treat and control. One of the reasons for this is the formation of biofilm around the indwelling catheter. We attempted to evaluate the effect of catheter exchange just before treatment of catheter-associated UTI with either 300 or 600 mg/day of levofloxacin, one of the newer quinolones. However, we are unable to find any apparent effect on the drug's efficacy.

Bacteriuria↗

Calcium blockers enhance cisplatin-induced nephrotoxicity in rats.

To examine the effects of calcium blockers on nephrotoxicity caused by cisplatin, the renal function and renal accumulation of Pt in Sprague-Dawley rats given 6.5 mg/kg i.v. cisplatin simultaneously with several doses of verapamil or nicardipine were evaluated. BUN, serum creatinine and kidney Pt concentrations in rats given more than 5.0 mg/kg of verapamil were significantly higher than those of the control animals injected with 6.5 mg/kg i.v. cisplatin alone, and the increase of each value was dependent upon the dose of verapamil. BUN, creatinine and kidney Pt in rats injected with more than 0.5 mg/kg i.p. nicardipine were also significantly higher than those of the controls. Calcium blockers enhanced the renal accumulation of Pt and the nephrotoxicity of cisplatin.

Animals↗

Cytologic findings of fine needle aspirates in chronic prostatitis.

Cytologic studies in patients with prostatic infection, primarily those with chronic prostatitis, were conducted on samples obtained by the fine needle aspiration method. Infiltration of inflammatory cells such as polymorphonuclear leukocytes and macrophages was observed to a greater extent in patients with chronic bacterial prostatitis as compared to those with chronic nonbacterial prostatitis or prostatodynia. The pathogen was isolated in only one out of 28 patients with chronic bacterial prostatitis. We concluded that fine needle biopsy is useful for assessing patients with prostatic inflammation, but not for detecting microorganisms because of focal colonization of the organisms in the glands.

Bacterial Infections↗

Nonspecific granulomatous prostatitis.

Nonspecific granulomatous prostatitis is a relatively rare disorder of the prostate. We encountered 4 cases of this type of chronic inflammation, including 1 case of xanthogranulomatous prostatitis. In all cases the diagnosis was made by histologic examination of specimens obtained by transurethral resection, retropubic prostatectomy, or transrectal needle biopsy. Echography revealed a hypoechoic lesion in the case of xanthogranulomatous prostatitis, while the other cases showed no specific findings except for the associated adenomas. The major symptoms were frequency and dysuria caused by urinary tract infection or benign prostatic hyperplasia associated with the granulomatous prostatitis.

Aged↗

Transitional cell carcinoma of bladder in thirteen-year-old boy.

We report a rare case of primary epithelial bladder tumor in a thirteen-year-old boy. Histologically, the tumor was that of a solitary and papillary transitional cell carcinoma, grade 1. This tumor was detectable at cystoscopic examination, and cytologic procedures were without benefit for a diagnosis.

Adolescent↗

Establishment and characterization of doxorubicin-resistant human bladder cancer cell line, KK47/ADM.

A human bladder cancer cell line resistant to doxorubicin, KK47/ADM has been established in vitro by exposing KK47 parent cells to progressively higher concentrations of the drug over a period of 16 months. The KK47/ADM was 271 times more resistant to doxorubicin than the KK47 parent. The KK47/ADM exhibited cross-resistance to doxorubicin derivatives (pirarubicin, epirubicin), vinca alkaloids (vinblastine, vincristine) and etoposide, but not to cisplatin, carboplatin, mitomycin C, peplomycin and methotrexate. Unlike the KK47 parent, about 70% of the KK47/ADM cells showed a positive reaction with monoclonal antibody against P-glycoprotein, MRK16. Uptake and efflux studies with [14C]doxorubicin indicated that the resistance exhibited by the KK47/ADM line was mainly due to a lower accumulation of the drug caused by an increased active efflux, and these were reversed in the presence of verapamil. Although verapamil enhanced doxorubicin sensitivity of KK47/ADM, a complete overcoming of the resistance could not be obtained. These two lines with different chemosensitivity are thus considered to be a useful model for developing new chemotherapeutic strategies against multidrug resistant bladder cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Comparative study of cisplatin and carboplatin on pharmacokinetics, nephrotoxicity and effect on renal nuclear DNA synthesis in rats.

To clarify the difference in nephrotoxicity between cisplatin and carboplatin, the pharmacokinetics of platinum, renal function and nuclear DNA synthesis in renal cortical and outer medullary cells were studied in rats which had received cisplatin or carboplatin. Male Sprague-Dawley rats were given either cisplatin or carboplatin intravenously at an equi-toxic dose (LD10 or LD50) and were killed at various times within 7 days after the injection. Cisplatin bound to plasma proteins more avidly than carboplatin. Much more platinum was detectable in the renal nuclei after cisplatin injection than after carboplatin injection. BUN and serum creatinine levels in the rats treated with 8.5 mg/kg of cisplatin were significantly higher than in those treated with 100 mg/kg of carboplatin. Cisplatin markedly suppressed the renal nuclear DNA synthesis both in vivo and in vitro, when compared with carboplatin. It is concluded that the differences in nephrotoxicity between cisplatin and carboplatin are related to their different inhibitory effects on nuclear DNA synthesis in the renal cells.

Animals↗

Ultrastructural alterations and DNA synthesis of renal cell nuclei following cisplatin or carboplatin injection in rats.

To clarify the difference in nephrotoxicity between cisplatin and carboplatin, ultrastructural alterations and DNA synthesis of renal cell nuclei were studied in Sprague-Dawley rats which had received intravenously either cisplatin or carboplatin at an equitoxic dose. Twelve hours after cisplatin injection, nucleolar segregation accompanied by aggregated nuclear heterochromatin was observed in the third segment of the proximal tubules. Seventy-two hours after cisplatin injection, nuclear damage was more widespread while regenerative cells were also observed. Nuclear damage was not observed in the carboplatin-treated rats. Nuclear DNA synthesis of renal cells was suppressed at 8, 12 and 24 h and was accelerated at 72 h after cisplatin injection. Carboplatin did not suppress nuclear DNA synthesis at any time. The results indicate that cisplatin, but not carboplatin, can affect the renal cell nuclei. Cisplatin-induced nephrotoxicity is related to its effects on renal cell nuclei.

Animals↗

Antioxidant effect on renal scarring following infection of mannose-sensitive-piliated bacteria.

Renal scars have been considered to occur in later stages of chronic pyelonephritis. In our experimental pyelonephritis model, bacteria which possessed mannose-sensitive (MS) pili on the surface promoted renal scarring following inoculation to the renal parenchyma. Polyethylene glycol-modified superoxide dismutase (PEG-SOD) and 2-O-octadecylascorbic acid (CV3611) significantly suppressed scarring when administered orally or parenterally during the early stage of kidney infection with MS-piliated bacteria. These findings suggest that the superoxide and other active oxygens play an important role in renal scarring following infection and that PEG-SOD and CV3611 may be agents capable of preventing renal scarring following bacterial pyelonephritis.

Administration, Oral↗

Intravesical therapy with adriamycin plus verapamil in patients with superficial bladder cancer: a pilot study.

Nineteen patients with histologically proven superficial bladder cancer (Ta, T1) were treated with intravesical instillation of 30 mg of adriamycin (ADM) dissolved in 24 ml physiological saline plus 15 mg of verapamil (VR) (6 ml) every day for 10 days. In spite of the short period of treatment, 6 of the 18 evaluable patients (33.3%) showed complete response (CR) and a further 5 (27.8%) showed partial response (PR). Five of the 6 patients with CR were recurrent cases who had previously received prophylactic intravesical instillation chemotherapy including ADM. Irritative urinary symptoms were observed in 11 of the 19 patients (57.9%). However, these symptoms were mild in the majority of patients and the treatment was completed without interruption in all but 1 patient. There was no significant absorption of ADM and VR into the systemic circulation. No clinical evidence of systemic toxicity was observed. These results suggest that combination of ADM and VR has a possibility to be a useful prophylactic intravesical instillation chemotherapy after endoscopic resection of not only primary but also recurrent chemoresistant bladder cancers.

Administration, Intravesical↗

Renal cell carcinoma with unusual metastatic lesions detected by angiography.

The case of a patient with left renal cell carcinoma with two small metastatic lesions in the mesenterium and retroperitoneal fatty tissue is reported. These metastatic lesions were incidentally detected by preoperative routine angiographic examinations. The patient underwent left radical nephrectomy and resection of the metastatic nodules. The usefulness of angiography for detecting metastatic lesions and the possible metastatic pathways of these uncommon lesions are discussed.

Adipose Tissue↗

Flow-cytometric deoxyribonucleic acid analysis of the human bladder cancers with reference to histopathological findings.

Flow-cytometric (FCM) DNA analysis was performed in 534 samples from 140 bladder tumor cases and was compared with histopathological findings. Frequency of DNA aneuploidy was closely correlated with tumor grade. Namely the incidences of DNA aneuploidy were 20% in grade 0 (papilloma), 25.6% in grade 1, 57.7% in grade 2 and 95.7% in grade 3. Invasive tumors showed a significantly higher incidence of DNA aneuploidy than superficial papillary tumors. Frequency of DNA aneuploidy of CIS was between them. Nonpapillary tumors showed a significantly higher incidence of DNA aneuploidy than papillary tumors. Tumors with vessel invasion did show a similarly higher incidence than those without. Approximately 10% of histologically normal mucosa taken from the bladder tumor patients showed DNA aneuploidy. The present study could support possibilities that FCM findings were highly correlated with tumor malignant potentials and were also able to predict precancerous lesions on histologically normal mucosa.

Adenocarcinoma↗

Correlation between the expression of P-glycoprotein and multidrug-resistant phenotype in transitional cell carcinoma of the urinary tract.

The expression of a multidrug-resistant (MDR) gene product, P-glycoprotein, was examined immunohistochemically in 41 transitional cell carcinomas (TCCs) of the urinary tract. In 23 of these, chemosensitivity to adriamycin (ADM) and vinblastine (VBL) was also assessed by a microtiter succinate dehydrogenase inhibition test and the correlation between the expression of P-glycoprotein and MDR phenotype was investigated. P-glycoprotein was detected in 13 (72.2%) of the 18 untreated TCCs of the upper urinary tract (UUT), 6 (31.6%) of the 19 untreated TCCs of the bladder, and all of the 4 TCCs treated with M-VAC chemotherapy, respectively. Fourteen (87.5%) of the 16 TCCs with a positive expression of P-glycoprotein were resistant to ADM and VBL, whereas all of the 4 TCCs sensitive to both drugs were negative in the expression of P-glycoprotein. The succinate dehydrogenase activity of TCCs with a positive expression of P-glycoprotein was significantly higher than that of TCCs with a negative expression of P-glycoprotein (P < 0.05). Thus, there was a good correlation between the expression of P-glycoprotein and MDR phenotype in the chemosensitivity test. These results suggest that intrinsic MDR exists in some TCCs of the urinary tract, particularly UUT, and that the immunohistochemical investigation of P-glycoprotein may be useful for predicting the MDR phenotype in TCCs of the urinary tract.

ATP Binding Cassette Transporter, Subfamily B, Mem↗