Search

ビカルタミド1日1回50mg群, 80mg及び100mgを12週間投与する3群比較の無作為化非盲検試験を実施した. 1)登録症例は124例で, 適格例は122例であった. 2)総合効果における奏効率は50mg群, 80mg群及び100mg群でそれぞれ50.5%, 61.0%及び53.7%であった. 3)PSAに対する奏効率は50mg群, 80mg群及び100mg群でそれぞれ84.2%, 92.7%及び97.6%であった. 4)副作用発現率は3群ほぼ6割で副作用による中止例は80mg群の1例のみで, 安全度において3群間に有意差はなかった.主な副作用は乳房腫脹, 乳房圧痛等であった, To investigate the efficacy and safety of bicalutamide (Casodex(R)) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks ; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40); 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 ing group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

We treated two children with 2, 8-dihydroxyadenine urolithiasis for over 7 years. The male prepositus was admitted to the hospital because of anuria when he was 10 months old. Bilateral urinary stones had caused the anuria. The stones were 2, 8-dihydroxyadenine and his APRT activity was low. He has been treated with about 5.0 mg/kg/day of allopurinol without purine diet restriction. His sister, 3 years old at that time, also was found to have a renal stone. She has been treated with about 3.3 mg/kg/day of allopurinol without restricting purine. The allopurinol therapy without purine-restriction resulted in normal growth of both children with neither the recurrence of stone nor renal impairment.

動脈瘤のあるドナー腎を用いた生体腎移植の1例を報告した。1)腎は十分に灌流して冷却すれば阻血によく耐え, 2時間程度であれば血流再開後の腎機能の発現に影響を与えない。2)予想阻血時間が2時間程度なら灌流液は乳酸加リンゲル液で十分である。3)ドナー腎に動脈瘤があっても体外腎手術を適用すれば移植が可能である, A case of living related renal transplantation using a kidney with renal arterial aneurysm is reported. The size of the renal arterial aneurysm was 15 mm in diameter. After ex vivo aneurysm removal, the graft was transplanted to the right iliac fossa. The total ischemic time was 79 minutes, and the urine flow started 5 minutes after declamping. In Japan, eight patients are reported to have successfully received a renal graft after removing its aneurysm extracorporeally. Renal transplantation is possible even when the donor kidney has a renal arterial aneurysm.

特発性高Ca尿症66例について検討した。1)尿中Ca排泄量はthiazide投与前に比し, 投与期間中有意に減少した。2) group formation rateはthiazide投与後有意に低下した。3)副作用として高尿酸血症, 低カリウム血症, 耐糖能異常などがあった, The prophylactic effect of hydrochlorothiazide on stone formation was studied in 66 patients with calcium urolithiasis, (49 men and 17 women between 25 and 76 years old, mean 52.2 +/- 11.7 years) due to idiopathic hypercalciuria. Urinary calcium excretion was significantly decreased during treatment when compared to the baseline value. The stone formation rate was also significantly reduced when compared with that before treatment. With regard to side effects, hyperuricemia was observed in 21 patients, hypokalemia in 9 patients, hypotension in 3 patients, and glycosuria in 4 patients. Thiazide treatment was concluded to be effective for preventing the recurrence of calcium stones in patients with idiopathic hypercalciuria. However, this therapy should be used only in conjunction with the careful monitoring of possible adverse reactions.

Between August, 1986 and August, 1992, 16 combination chemotherapies with etoposide (100 mg/body, day 1-5), ifosfamide (50 mg/kg, day 1, 3, 5), peplomycin (5 mg/body, day 1-5) were performed on 13 patients with endocrine therapy-relapsed advanced prostatic cancer. Seven trials were performed on 5 patients who received DESP (diethylstilbestrol diphosphate) (500 mg/body, day 1-5) with the chemotherapy. In 9 trials performed on 9 patients who did not receive DESP, there was no response case. In 7 trials with DESP, one trial had a partial response (PR) (14%) and 4 remained objectively stable (stable) (57%). As to adverse effects, myelosuppression was observed in all trials but there was no lethal toxicity. The one-year survival rate of these patients treated with the chemotherapy alone and combined DESP were both about 20%. Therefore we should find a more effective treatment for endocrine relapsed prostatic cancer.

33症例の上部尿路結石患者にアメリカ製Biolithos MARK 3を用いてESWLの臨床治験を行った。治療後1ヵ月目の効果判定では, 有効率は72.7%でありほぼ満足のいく結果がえられた。特に問題となるような副作用・合併症もなく外来通院・無麻酔・鎮痛剤の投与なしでもESWL施行が可能であった, The results of clinical use of an extracorporeal shock wave lithotripter (Biolithos MARK III) are presented. From May 1991 through February 1992, a total of 50 sessions were carried out on 33 patients with upper urinary tract stones. Treatments were performed on an outpatient basis, and none of the patients needed anesthesia or analgesia. One month after the last session, 18 patients (54.5%) were free from stone fragments and 6 (18.2%) had stone fragments equal to or smaller than 4 mm. The over-all successful rate obtained by these categories was 72.7%. After treatment no serious complications were observed. Although gross hematuria appeared in almost all patients, pain was noted in only 5 patients. Laboratory data after treatments showed slight and transient changes. It is concluded that Biolithos MARK III is useful and safe in the management of upper urinary tract stones on an outpatient basis.

全国多施設の共同研究により, 腎細胞癌に対するn-TNFとn-IFN-αの併用療法による有効性と安全性を検討した.1)腎細胞癌31例においてPRが4例認められ奏効率は12.9%であった.IFN-αが前治療に使用された症例にも有効例が認められたことより, 本併用療法の有用性が示唆された.2)副作用は(35例/36例)に認められ, おもな自他覚的副作用は発熱72.2%, 悪寒・戦慄69.4%, 食欲不振22.2%, 全身倦怠感16.7%であり, おもな臨床検査値異常は白血球減少47.2%, 血小板減少22.2%, GOT上昇16.7%, GPT上昇13.9%であった.ほとんどの症例が解熱剤等の処置あるいは無処置で投与継続可能であった.本併用療法による副作用の増強はほとんどなかった, The combination therapy with natural type human tumor necrosis factor (n-TNF; MHR-24) and human lymphoblastoid interferon-alpha (n-IFN-alpha; MOR-22) was investigated for antitumor effect against renal cell carcinoma in a multiclinic cooperative study throughout Japan. The "Response criteria of Japan Society for Cancer Therapy" were followed for the handling of subjects and the evaluation of antitumor effect. MHR-24 was administered at a daily dosage of 5, 000-10, 000 JRU by intravenous drip and MOR-22 at a dosage of 5, 000, 000 IU daily was administered intramuscularly at the same time. Both drugs were administered for 4 weeks or longer. A total of 36 patients were enrolled as subjects in the study. None of them were classified as ineligible. Five patients, were classified as imperfectly evaluable, and 31, as evaluable for the results of treatment. The responses in the evaluable patients were partial response (PR) in 4 patients, minor response (MR) in 3 patients, no change (NC) in 14 patients and progressive disease (PD) in 10 patients, with a response rate of 12.9%. Adverse reactions to the therapy were investigated in all 36 patients. The frequent subjective and objective reactions that occurred were fever, rigors and shivering, anorexia, and generalized malaise, and the frequent abnormal laboratory findings were leukopenia, thrombocytopenia, elevation of GOT, and elevation of GPT.

実験には体重約100 gのWistar系成熟雄ラットを使用した.実験群は, Cs投与群(Cs群)と対照群の2群とし, 動物数は各群7匹とした.Cs群の各ラットには, 1日体重1 kg当り50 mgのCsを10日間連日腹腔内投与した.対照群の各ラットには, 溶媒として用いた生理食塩水(生食)だけを10日間連日腹腔内投与した.Cs投与により, 腎皮質の組織血流量は減少した.この原因として, 小葉間動脈より末梢の細い血管系に変化が起き, 末梢血管抵抗が上昇した可能性が考えられた.Cs投与でRAA系が活性化されることから, 障害が生ずるのは糸球体の輸入細動脈である可能性が大きい, 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.

TAP-144-SRの前立腺癌に対する比較対照試験をリン酸ジエチルスチルベストロールを対照薬として行った.有効性では, 前立腺癌の判定基準の適格例で, TAP群54.5%(36/66), 対照群47.1%(32/68)のPR例が得られ, 両群間に有意差はみられなかった.病巣別効果や自他覚症状に対する効果でも両群間に差はみられなかった.PAPなど腫瘍マーカーに対して対照群の方が有意に優れる効果を示した.内分泌効果では両群とも全例で血清testosteroneがcastration levelに低下した.安全性については, 副作用発現率はTAP群64.1%(41/64)に対し, 対照群は95.4%(62/65)と有意に高く, 対照群で4例が副作用のため試験が中止された.主治医判定による全般安全度では"問題あり"と判定された症例はTAP群6.3%(4/64), 対照群36.9%(24/65)であった.主治医判定による有用度では"有用"以上でみると, TAP群65.6%(42/64), 対照群52.3%(34/65)であった, 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.

1. We performed RNase protection assays and in situ hybridization to investigate the ratio of the three alpha1-adrenoceptor subtype mRNAs, alpha1a, alpha1b and alpha1d, in human proximal urethra, and their localization in urethral cross-sections. As revealed by the RNase protection assays, alpha1a was the predominant subtype mRNA in both male and female urethral samples. Alpha1d mRNA was detected only in the female sample, and alpha1b mRNA was not detected in any of the samples tested. The ratio of the abundance of the subtype mRNAs, alpha1a:alpha1b:alpha1d, was 100:0:0 in the male urethra and 90:0:10 in the female urethra. 2. In situ hybridization studies showed no significant differences in the cross-sectional distribution of alpha1-adrenoceptor subtype mRNAs between male and female urethras. Intense alpha1a staining was observed in the smooth muscle of the urethra, but alpha1b and alpha1d staining was much less intense. 3. Of the three cloned alpha1 subtypes, alpha1a is the most likely to be responsible for the contraction of the human urethra. Owing to the side effects of nonselective alpha1 drugs, alpha1-selective drugs may be clinically superior to nonselective drugs for the treatment of urethral disorders.

To investigate the efficacy and safety of bicalutamide (Casodex(R)) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks ; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40); 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 ing group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.