博 仁藤’s scientific contributions

Analgesic diect of trihydroxybenzene (Dilospan) was evaluated on urolithiasis patients by a simple double blind method with hyoscine-N-butylbromide as the active placebo and glucose as the inert placebo. Seventy-one cases were chosen from six institutions. As to the effect within 5 minutes after injection, Dilospan was significantly superior to the placebos. The effective rate within 30 minutes was 75% in Dilospan, 63% in the active placebo, and 52% in the inert placebo. Dilospan will be valuable in order to control pain in an emergency state.

複雑性尿路感染症に対するDL-8280の有効性,安全性と有用性を客観的に評価するため,Pipemidic acid (PPA)を対照薬とし二重盲検法で比較検討した.DL-8280は1回200 mg, 1日3回,PPAは1回500 mg, 1日4回,を5日間連続経口投与した.総投与例数は311例で,除外,脱落を除く228例(DL-8280群115例,PPA群113例)に対し有効性を評価した.安全性の評価は306例(DL-8280群153例,PPA群153例),有効性の評価は250例(DL-8280群124例,PPA群126例)につきおこなった.両群の背景因子には差はなかった.総合臨床効果は,DL-8280群で著効39.1%,有効80.9%,PPA群それぞれ23.9, 57.5%と比較し有意に高かった.疾患病態群別には,第2群(単独感染,前立腺術後感染症)と第3群(単独感染,上部尿路感染症)を除き,DL-8280群の総合臨床効果はPPA群に比し有意に優っていた.膿尿に対する効果は,正常化率+改善率がDL-8280群で59.1%, PPA群で46.0%で,前者が,優る傾向をみた.細菌尿に対する効果では,DL-8280群の陰性化率は76.5%, PPA群は50.4%で,DL-8280群が有意に優っていた.細菌学的効果では,DL-8280群の分離菌の消失率89.0%に対し,PPA群は72.1%で,有意差であった.グラム陰性桿菌,グラム陽性球菌についてもDL-8280群の消失率は有意に優っていた.主治医による臨床効果はDL-8280群が著効46.1%,有効83.5%で,PPA群はそれぞれ26.5, 61,1%で,前者が有意に優っていた.有用性は,DL-8280群が"非常に満足","満足"合わせて71.8%, PPA群が47.6%でDL-8280群が有意に優っていた.副作用はDL-8280群で11例,PPA群で12例に認め,有意差はなく,大部分は消化器症状で,重篤なものはなかった.臨床検査値悪化もDL-8280群で10例,PPA群で9例にみ,有意差はなかった The clinical efficacy, safety and usefulness of DL-8280 for the treatment of complicated urinary tract infections were compared with those of pipemidic acid (PPA) by a double-blind method. DL-8280 and PPA were orally administered at a daily dose of 600 mg (t.i.d.) and 2.0 g (q.i.d.) for 5 days, respectively. Of the 311 patients who received DL-8280 or PPA, clinical efficacy, safety and usefulness were evaluated in 228 patients (DL-8280, 115; PPA, 113), 306 patients (DL-8280, 153; PPA, 153) and 250 patients (DL-8280, 124; PPA, 126), respectively. There was no significant difference in the background characteristics between the two groups. In the DL-8280 group the overall clinical efficacy was excellent in 39.1% and moderate in 41.7%, the effectiveness rate being 80.9%, whereas in the PPA group it was excellent in 23.9% and moderate in 33.6%, the effectiveness rate being 57.5%. The efficacy in the DL-8280 group was significantly higher than that in the PPA group (P less than 0.001). According to classification by the type of infection, the overall clinical efficacy of DL-8280 in groups except group 2 (monomicrobial infection, post prostatectomy) and group 3 (monomicrobial infection, upper urinary tract infection) was superior to that of PPA, the difference being significant. Pyuria was cleared or improved in 59.1% of the patients treated with DL-8280 and in 46.0% of the patients with PPA. The difference was not significant. Bacteriuria was eliminated in 76.5% in the DL-8280 group and in 50.4% in the PPA group. DL-8280 demonstrated a significantly higher response than PPA (P less than 0.001). Of the bacteria isolated from the DL-8280 group and PPA group 89.0% and 72.1%, respectively, were eradicated after the treatment, a significant difference being observed between the two groups (P less than 0.001). The clinical efficacy evaluated by the doctor in charge was excellent in 46.1% and good in 37.4% of the patients treated with DL-8280 and excellent in 26.5% and good in 34.5% of the patients treated with PPA, the intergroup difference in the efficacy being significant (P less than 0.001). The evaluation of usefulness of DL-8280 and PPA was "satisfactory" for 71.8% and 47.6%, respectively, the difference being significant (P less than 0.001). Side effects were observed in 11 patients (7.2%) in the DL-8280 group and in 12 patients (7.8%) in the PPA group, but none were serious.(ABSTRACT TRUNCATED AT 400 WORDS)

Dibekacin (DKB) was administered to patients with complicated urinary tract infections without any indwelling catheter to evaluate objectively and comparatively the efficacy, safety and usefulness of intravenous drip infusion once daily and twice daily in a well-controlled study. A 50 mg dose of DKB was administered twice a day to group A, and a 100 mg dose was given once a day to group B. In both groups the drug was given by 1-hr i.v. infusion for 5 consecutive days. Drug efficacy was evaluated in 72 (group A: 36, group B: 36) of the 83 patients treated, and the safety was evaluated on 81 patients (group A: 41, group B: 40). There were no significant differences in the background characteristics between the two groups. The overall clinical efficacy judged by the Committee for Evaluation of Clinical Efficacy was "excellent" in 14% and "moderate" in 50% of group A, and "excellent" in 17% and "moderate" in 64% of group B, the efficacy being higher for group B than group A, but the difference was not statistically significant. The overall drug efficacy rate for each type of infection excluding group 2, was slightly higher in group B, but this difference was not significant either. The overall clinical efficacy for each site of infection, was higher for group B but the differences were not significant. The overall clinical efficacy as judged by the attending physicians was "excellent" in 17% and "moderate" in 58% of group A, and "excellent" in 25% and "moderate" in 61% of group B. The intergroup difference was thus smaller than that judged by the Committee. The elimination rates against bacteriuria were 58% for both groups A and B, and the decrease rates including "cleared" were 42% against pyuria for both groups A and B. Bacteriological evaluation, showed that there was no significant difference in the eradication rates, between group A (65%) and group B (70%). But the eradication rate for gram-positive bacteria was 40% in group A and 81% in group B, there being a significant difference (P less than 0.05) between them. The evaluation of usefulness gave 44% and 53% "satisfactory" rates, respectively, for groups A and B. The results for the "average score" were also the same in both groups. There were no side effects in any of the 81 patients examined. Abnormal laboratory test values attributed to the drug were seen only in 3 and 2 patients in groups A and B, respectively, there being no difference between the groups.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

黄体形成ホルモン分泌刺激ホルモン(LHRH)誘導体Buserelin (Hoe766)の前立腺癌に対する有効性と安全性,内分泌動態に検討を加えた.試験1の単回投与は前立腺癌3例と前立腺肥大症7例,試験2および3は病期BないしDの前立腺癌それぞれ40例,70例を対象とした.試験1の単回投与で本剤がLHRHと同様の動態を示し,試験2の3ヵ月間投与で至適用量を検討したところ,500 μg×3/日が初期導入として優れていた.3ヵ月間投与後の有効率は従来の治療法である去勢あるいは抗男性ホルモン剤と遜色がなかった.本剤の長期投与の評価対象は経時的に減少し,特に病期Dの減少率が高かったが,組織分化度別の減少率はほぼ一定であった.副作用は本剤投与後3ヵ月以内に発現し,中止に至った3例を除く6例は本薬の主作用によるもので症状も軽度であった.心血管系や肝障害などは見られなかった.以上より本剤は合併症の多い高齢者の前立腺癌に対し,短期,長期とも副作用の少ない有用性の高い薬剤であると結論できた Seventy three patients with prostatic carcinoma (PC) and 7 patients with benign prostatic hypertrophy (BPH) in 12 institutes subcutaneously received single and multiple doses of Hoe 766, and clinical efficacy, safety and endocrine effects of drug were examined. In a single doses study, six doses were subcutaneously administered to 7 BPH and 3 with PC. Gonadotropin and testosterone levels in the blood were increased following all these doses. In a multiple study, 7 kinds of doses were given to 40 patients with PC. The optimum doses of subcutaneous injection was decided to be 500 x 3 micrograms/day based on gonadotropin and testosterone suppression. Objective response by NPCP's criteria was observed in 35.3% (complete response 5.9%, partial response 29.4%) following 3 months of Hoe 766 treatment. Adverse reactions were observed in 9 cases (12.8%): Treatment was discontinued in 3 cases (eruption in 2, nausea and vomiting in 1), and continued in 6 cases (8.6%) without any treatment required. Buserelin was thus considered to be an effective, safe drug to treat prostatic carcinoma.

Comparative analysis of spasmolytic and analgesic effect of pentazocine 25 mg given orally (PAT) and 15 mg given parenterally (PAI) was performed on a basis of double blind trial in 98 patients who had an acute attack of urinary stone colic. Analgesic effect of PAT become apparent less quickly than PAI; in most cases analgesia was attained after 30 minutes following the administration of PAT. However, PAT was equally effective to PAI if observed for 60 minutes. The side effects were less frequent and minimal in PAT. It was concluded that orally administered pentazocine 25 mg was equally effective to parenteral pentazocine IS mg in the treatment of urinary stone colic.