Influence of FK 506 on renal blood flow.
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Biomedical subjects
Publications and source records attributed to Y Aso.
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The expert committees, which met in Paris in June 1991 under the patronage of WHO to establish a consensus concerning BPH, adopted the recommendations summarised in this report. Despite certain criticisms which can be made, these recommendations offer the advantage of simplicity and uniformity, thereby constituting a "universal language". This will facilitate comparison of patients and therapeutic results, both in everyday practice and in the course of clinical trials. These recommendations will be periodically re-evaluated in the light of clinical experience and technological progress.
To elucidate the relationship between cyclosporine (Cs) nephrotoxicity and renal blood flow (RBF), we carried our experiments using rats. Adult male Wistar strain rats each weighing about 100 g were used. Rats were divided into 2 groups; the Cs group (Cs 50 mg/kg/day was intraperitoneally given for 10 consecutive days) and the control group (normal saline solution for 10 consecutive days). The renal cortical blood flow was measured in each group by electrolytic hydrogen gas clearance method. We also carried out renal angiography with barium sulfate (BaSO4). Then we measured blood vessel area/renal sagittal section area ratio and the diameter of interlobar arteries. The Cs group showed a significant decrease of renal cortical blood flow compared with the control group. On the other hand there was no significant change in renal angiogram. In conclusion, Cs decreased renal cortical blood flow. We suppose that vascular resistance increased following afferent arteriolopathy caused by Cs administration.
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To investigate the efficacy and the safety of RU23908 for the treatment of prostatic cancer, an early phase 2 study with the oral administration of 150 or 300 mg daily was performed in 47 patients with stage C or D prostatic cancer at 15 institutions from April 1987 to June 1988. Forty patients were evaluable for efficacy. Concerning the effect on the object lesion, the results of the overall evaluation revealed that complete or partial response (CR + PR) was obtained in 34 of the 40 cases (85.0%). As to the effect classified by site, CR + PR were observed in 35 out of the 40 cases with primary lesion (87.5%), in 10 of the 22 cases with bone metastasis (45.5%), in 5 of the 6 cases with lymph node metastasis (83.3%) and CR was observed in one case with lung metastasis. In the PAP evaluation, 33 out of the 34 cases were judged to be CR + PR (97.1%). The improvement rate of clinical symptoms was 88.9% for bone pain, 83.3% for dysuria and 45.5% for performance status. Adverse reactions were observed in 29 of the 47 cases (61.7%) investigated and 7 cases (14.9%) were withdrawn. During the study period of 12 weeks and the subsequent period of continued administration, 6 cases (12.8%) and 2 possible cases of interstitial pneumonia were diagnosed. From the above results, the treatment of prostatic cancer with RU23908 150 mg/day or 300 mg/day in combination with surgical castration showed an excellent clinical effect compared to conventional endocrine therapy, but has a problem of safety. Therefore, this drug may be expected to be a highly useful therapeutic drug, if safely is improved in the future by reviewing the dose.
We carried out a randomized multi-center study comparing cefpirome (CPR) 0.5 g b.i.d. (1 g group), 1.0 g b.i.d. (2 g group) and ceftazidime (CAZ) 1.0 g b.i.d. (CAZ group) in the treatment of complicated urinary tract infections. Patients who were over 16 years old and had underlying urinary tract disease, with bacteriuria of more than 10(4) cells ml or more and pyuria of more than 5 WBCs/hpf (x 400) or more were randomly allocated to receive either 0.5 g of CPR, 1.0 g of CPR or 1.0 g of CAZ twice a day for 5 days by intravenous drip infusion. The overall clinical efficacy of the treatment was evaluated by the criteria of the Japanese UTI Committee as excellent, moderate or poor, on the basis of the changes in pyuria and bacteriuria. A total of 530 patients were treated. Of these, 141 patients in the 1 g group, 136 in the 2 g group, and 140 in the CAZ group were evaluable for clinical efficacy. No significant differences in background characteristics were observed among the treatment groups. The overall clinical efficacy rate of the 1 g group, the 2 g group and the CAZ group was 80.1%, 76.5% and 71.4%, respectively. The differences were not statistically significant. The overall bacteriological eradication rate of the 1 g group, the 2 g group and the CAZ group was 81.0%, 88.1% and 83.8%. The differences were not statistically significant either. Against the enterococcus group, however, eradication rates were higher significantly in the 1 g and 2 g groups than in the CAZ group. The incidence of adverse reactions was 2.2% in the 1 g group, 0.6% in the 2 g group and 2.9% in the CAZ group. Abnormal laboratory data after medication were observed in 10.8% of the 1 g group, 12.1% of the 2 g group and 10.2% of the CAZ group, the difference not being statistically significant. There were no serious untoward reactions to medication. From the results obtained in this study, we consider that CPR is at least as useful as CAZ in the treatment of complicated urinary tract infections.
A randomized controlled phase III clinical trial comparing TAP-144-SR (TAP) and diethylstilbestrol diphosphate was conducted for patients with prostatic cancer. Patients with Stage B, C, or D disease, who were previously untreated, were enrolled. TAP-144-SR 3.75 mg was administered subcutaneously at 4-week intervals for 12 weeks (a total of 3 injections) in the TAP-144-SR group, while 100 mg of diethylstilbestrol diphosphate was administered orally three times a day (before meals) for 12 weeks in the control group. A total of 141 patients were enrolled using a centralized telephone registration system. Four of these patients were ineligible, and there were 3 drop-outs who never received drugs because they withdrew their consents to participate in the trial. These 7 were excluded from the evaluation, and as a result, 134 patients (66 in the TAP group and 68 in the control group) were evaluable in safety and efficacy. Between the two groups, there were no significant differences in patient characteristics, except the age distribution. Clinical response rates (CR+PR) in evaluable patients according to the criteria of Japanese Prostatic Cancer Study Group were 54.5% in the TAP group and 47.1% in the control group. In addition, the rates according to the criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria were 7.6% in the TAP group and 8.8% in the control group and 18.2% in the TAP group and 20.6% in the control group, respectively. Using any of the three criteria, there were no significant differences in response rate between the two groups. The incidence of side effects was 64.1% in the TAP group and 95.4% in the control group; the incidence being significantly higher in the control group (p less than 0.001; chi 2-test). Therefore, the overall safety was significantly greater in the TAP group than in the control group (p less than 0.001; chi 2-test). On the basis of the efficacy and safety the clinical usefulness rate of TAP-144-SR was significantly higher than that of diethylstilbestrol diphosphate (p = 0.038; U-test). In conclusion, TAP-144-SR was confirmed to be more useful than diethylstilbestrol diphosphate as a standard drug for hormonal therapy of prostatic cancer.
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We treated 34 patients with staghorn calculi by fiberoptic transurethral nephrolithotripsy with a flexible nephroureteroscope and an electrohydraulic lithotriptor. Of the 34 patients 30 (88.2%) were treated successfully. There were 17 patients each with complete and partial staghorn calculi. There was no difference in the success ratio and the rate of residual fragments between the 2 groups. However, post-procedural fever, sepsis and extrapelvic extravasation were observed more frequently in patients with complete than with partial staghorn calculi. Countermeasures to avoid complications must be developed in the future. However, we believe that fiberoptic transurethral nephrolithotripsy is a safe and effective treatment for staghorn calculi. This procedure also should be recommended, as well as the combination of percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy.
A recently synthesized alpha 1-blocker, (R)(-)-5-[2-[[2-(o-ethoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide hydrochloride (YM617), was evaluated in 270 patients with benign prostatic hypertrophy in a double-blind study. After 2 weeks on placebo the patients were assigned at random to 4 groups: group P--placebo, group L--0.1 mg., group M--0.2 mg. and group H--0.4 mg. of YM617. Comparing the placebo to the treatment period, subjective symptoms, such as nocturia and urgency, were significantly decreased in group H (p less than 0.01). The sensation of incomplete voiding was significantly improved in groups M and H (p less than 0.01). However, the differences among the groups were statistically insignificant. Residual urine volume was significantly decreased in groups L, M and H after instillation of saline into the bladder (p less than 0.01) but not in group P. The maximum and average flow rates were significantly increased in groups L, M and H (p less than 0.01) but not in group P. Average flow rate showed significant differences between groups M or H versus group P. Neither orthostatic hypotension nor a decrease in blood pressure was noted. Adverse side effects and changes in laboratory data were all slight and disappeared when the second tests were performed. In summary, the irritative and obstructive symptoms caused by benign prostatic hypertrophy were decreased and urodynamic studies were markedly improved by the alpha 1-blocker, YM617. The drug seems to be useful in the treatment of patients with benign prostatic hypertrophy.
Renal function and blood pressure were assessed in 139 patients after unilateral nephrectomy. Followup ranged from 1 to 57 years, with a mean of 13.0 +/- 1.1 (standard error). Serum creatinine, creatinine clearance, beta 2-microglobulin clearance and blood pressure remained stable during followup. No significant effect of years after unilateral nephrectomy, blood pressure or cause of nephrectomy was observed on creatinine clearance. However, urine excretion of protein (correlation coefficient 0.475, p less than 0.01) and N-acetyl-beta-D-glucosaminidase (correlation coefficient 0.464, p less than 0.01) increased as a function of years after unilateral nephrectomy. Creatinine clearance tended to be low in elderly patients or patients who underwent nephrectomy at an advanced age. Our studies show that despite the late development of proteinuria and tubular injury, unilateral nephrectomy is not associated with deterioration in kidney function or elevation of blood pressure during long-term followup.
Because the pulsed dye laser can be transmitted through a thin, flexible quartz fiber a small caliber ureteroscope and flexible ureterorenoscope are applicable. Therefore, the use of a rigid or flexible ureterorenoscope was combined with laser lithotripsy to treat upper urinary tract calculi. All 14 ureteral stones below the pelvic brim were removed successfully with a rigid 7.2F (outer diameter) ureteroscope and 14 of 16 stones above the pelvic brim were removed with a flexible ureterorenoscope. Laser monotherapy was effective in 24 cases and the complementary use of forceps or electrohydraulic lithotripsy was required in 4. Two stones were lost from the visual field during endoscopic manipulation. There was no complication requiring surgical correction. The combined use of these instruments is highly successful and safe for the treatment of upper urinary tract calculi.
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A nonisothermal method was applied to shelf-life estimation of commercial vitamin A preparations. The usefulness and limitations of the nonisothermal method, as predicted by computer simulation, were validated. Degradation of vitamin A palmitate followed zero-order kinetics, and non-Arrhenius behavior was suggested for the rate constant. The nonisothermal method predicted a higher shelf-life value than the isothermal method for a syrup preparation, and vice versa, for an injection preparation. Analysis of the results suggested that the nonisothermal method provides better estimates of shelf lives than the isothermal method when drug degradation does not follow the Arrhenius equation near ambient conditions.
Urine specimens from 120 patients attending urologic clinics were screened by blot hybridization for the presence of a polyomavirus DNA. Detected viral DNA was then identified as BK or JC by fine restriction enzyme analysis. BK and JC viral DNA was found in 5 (4%) and 35 (29%) patients, respectively. Detection rates were compared among three age groups: 0-29, 30-59, and 60-89 years. Detection of JC viral DNA increased with age and reached the highest value (45%) in the group aged 60-89 years. For BK viral DNA a correlation between detection and age was not clear because the rate of detection was low, although the highest rate (9%) occurred in the oldest group. To confirm the active urinary excretion of polyomavirus DNA in older patients, urine specimens from 23 patients (60-90 years) treated at an internal medicine clinic were examined for viral DNA. BK and JC viral DNA were in 2 (9%) and 12 patients (52%), respectively. These results suggest that JC virus is frequently reactivated in older individuals.
In the urological field, one of the most effective drugs is doxorubicin. A cooperative phase II study on pirarubicin (THP), a new anthracycline with less cardiotoxicity than doxorubicin, was performed in 14 institutions for treating urological tumors. THP was administered intravenously 3 or more times (as one course, 30-40 mg/m2 once a week, every 3 weeks or 20 mg/m2 2 consecutive days a week every 3 weeks). Fifty-four of the 63 patients included in this study were evaluable. An overall efficacy rate was 18.5% (10/54), consisting of transitional cell carcinoma 24.3% (9/37; bladder cancer 6/27 (22.2%), tumors of the renal pelvis and ureter 3/10 (30.0%), and prostatic cancer 1/15 (6.7%). Adverse effects were mostly slight especially alopecia (15.9%, WHO grade 1:7 patients and grade 2:3 patients), and there was no problem attributable to cardiotoxicity of THP. Leukocytopenia was seen for 65.1% (grade 1:14 patients, grade 2:13 patients, grade 3:13 patients, and grade 4:1 patients). The nadir was observed about 2 weeks later and it took about 2 weeks for the recovery. Thus, it can be concluded that the usefulness of THP in treating urological tumors is comparable to or better than that reported for doxorubicin. Based on the above results, a combination regimen including THP has been investigated in Japan.
We molecularly cloned JC polyomavirus DNAs from urine samples of eight nonimmunosuppressed patients and two healthy individuals. The cloned viral DNAs all contained an archetypal regulatory sequence from which various regulatory sequences of JC polyomavirus isolates derived from patients with progressive multifocal leukoencephalopathy could have evolved by deletion and amplification.
The clinical efficacy and safety of 3.75 or 7.5 mg leuprorelin acetate depot given subcutaneously once every 4 weeks was evaluated in a collaborative study of 81 patients with untreated prostatic cancer. Efficacy of treatment was assessed using criteria based on a meeting of the Prostatic Cancer Study Group funded by the Japanese Ministry of Health and Welfare and using National Prostatic Cancer Project criteria. Japanese criteria enabled evaluation of individual parameters, unlike the National Prostatic Cancer Project system which classified a patient as unevaluable if one evaluation parameter was unavailable. Leuprorelin acetate depot suppressed serum luteinizing hormone, follicle stimulating hormone and testosterone concentrations. Objective response rates of the prostate, bone metastases, serum prostatic acid phosphatase and soft tissue metastases, and subjective dysuria and pain responses were comparable to those found with conventional hormone therapy. Leuprorelin acetate depot was well tolerated, with no significant differences in response to the two doses.