民夫 藤田’s scientific contributions

MK-0787/MK-0791をUTIを主とした感染症や,感染防止目的で35例36回,原則として1日0.5 g×2を10日間以上にわたり投与した.1)評価可能26例で有効以上は,治療初期で88.5%,終了時で92.3%であった.有用性についても全く同様の成績を得た.P. aeruginasa等を含む分離菌35株の全てが治療後除菌された.投与後出現菌は,真菌類が多かった.2)長期投与の方が短期投与に比べて,有用性が高い傾向を認めた.3)副作用として,嘔吐による中止例が1例あった.臨床検査値異常では,血小板減少1件,好酸球増多1件,GOT上昇2件,GPT上昇3件,γ-GTP上昇1件をみたが,変動幅は小さく,中止により可逆的であった MK-0787 (Imipenem)/MK-0791 (Cilastatin sodium), a new compound of Thienamycin, was administered in treatment of 35 patients (36 cases) with chronic complicated UTI or for prevention of serious infections with much complicated factors. The patients were principally treated at a daily dose of 1 g for over 10 days. The efficacy rate of 26 patients who were evaluable in the early phase (4-7 days) was 88.5%, while it became up to 92.3% in the final phase judgment. As for clinical usefulness, the result was obtained to be as high as that of the clinical efficacy. In bacteriological study, 35 strains were clinically isolated including 7 strains of P. aeruginosa from UTI. All the strains disappeared with an eradication rate of 100% after treatment. Strains appearing after Imipenem/Cilastatin sodium treatment mainly consisted of fungi. Usefulness judgements tended to be greater in the final phase than in the early phase. As for side effects, vomiting was recorded in one case, in which the administration was discontinued. In laboratory findings there were 3 cases with elevated GPT, 2 cases with elevated GOT, one case with elevated gamma-GTP, one with thrombocytopenia, and one with eosinophilia each, but these abnormal values were slight and transient. In summary our clinical study showed that Imipenem/Cilastatin sodium was a very effective antibiotic in treatment on moderate or serious UTI or preventive use for infections in compromised hosts. Considering the features of this agent, it might be more effective and useful for clinical use in treatment on polymicrobial infections including stubborn organisms than any other antimicrobial compounds. Furthermore, it was safe and well tolerable in a long term treatment.

34例の複雑性因子が多く,かつ重症な感染症の治療や感染防止にCAZ 1回1 gを1日2回9～30日にわたり静注または点滴静注し,感染症25例に対して著効6例,有効14例,やや有効例4,無効1例であり,また,術後感染防止上も75%の有効率を得た.副作用は無かったが,検査上肝機能異常4例,及び白血球減少症1例が認められた CAZ was administered to 34 patients in the field of urology for treatment or prevention of serious infections with many complicated factors. The duration of treatment ranged from 9 to 30 days, the most frequent being 14 days, which was the duration originally set as the standard. As the results CAZ was considered to be one of the drugs of choice in the cases requiring long-term treatment, from the viewpoint of both efficacy and usefulness.

55～83歳の前立腺肥大症患者35例において,本剤1.5 mg/日投与群と3.0 mg/日投与群とを比較したが,主治医による自覚症状改善度,他覚所見改善度,全般改善度,概括安全度,有用度の判定,並びに判定委員会による薬剤効果の判定において,両群間に統計学的有意差が認められず,初回投与量は1.5 mg/日が至適と考えられた.12週間投与した症例で特徴的な副作用はなかった.主治医判定における12週後の改善度は,4週後の改善度に比べ低かった.しかし判定委員会判定で自覚症状の重症度及び他覚所見は,12週後では4週に比べ,より改善が認められた Thirty-five patients with prostatic hyperplasia were entered into a randomized controlled study using bunazosin hydrochloride(alpha 1-adrenergic blocker). Eighteen patients were allocated to be treated with an initial dose of 1.5 mg/day (group 1) and 17 patients received an initial dose of 3.0 mg/day (group 2). Subjective symptoms and parameters of urodynamic studies were evaluated after 4 weeks and 12 weeks. There were 5 withdrawals or exclusions within 4 weeks and 6 within 12 weeks. Therefore, 15 patients in group 1 and 15 patients in group 2 were eligible for evaluation at 4 weeks, 12 patients in group 1 and 11 patients in group 2 were eligible for evaluation at 12 weeks. The rates of the improvement in subjective symptoms such as retarded urination, protracted urination, weakened urinary stream, abdominal straining on voiding, and sense of residual urine were 40%, 25% in group 1 and 46.7%, 36.4% in group 2, at 4 weeks and at 12 weeks, respectively. The rate of improvement in objective parameters of the urodynamic study such as voiding volume, residual volume, maximum flow rate and average flow rate were 26.7%, 16.7% in group 1 and 26.7%, 20.0% in group 2, at 4 weeks and at 12 weeks, respectively. Thus, these improvements were not correlated with the dosage of drug. Adverse effects such as diarrhea, mild headache, palpitation and gastric disturbance were observed in 2 patients in group 1, and 3 patients in group 2. In the 24 patients treated with the drug over 12 weeks, there were no specific adverse effects due to prolonged administration. These findings showed that bunazosin hydrochloride is beneficial for the treatment of prostatic hyperplasia, and could be safety administered for a prolonged period of time up to 12 weeks.

Stage B, Cの限局性前立腺癌50例に対し,腹腔鏡下骨盤内リンパ節郭清を施行した. 1)後腹膜的到達法は経腹的操作に比較して合併症は少なく,出血量の有意な減少,手術時間の短縮がみられ,minimally invasive surgeryとして優れた術式といえる. 2)両側の骨盤内リンパ節郭清を行えた48例のうちリンパ節転移は19例に認められたが,術中凍結切片による迅速病理検査では7例がfalse negativeであった. 3)Stage C,低分化癌以外にstage B,高分化,中分化癌のうちPSADが0.5ng/ml/ml以上の症例ではリンパ節転移の可能性が高いと考えられた We report the clinical results and efficacy of laparoscopic pelvic lymphadenectomy for localized prostate cancer. This procedure was followed by radical prostatectomy, when metastasis was not found in the frozen section, and by optional treatment, such as transurethral resection (TUR) or castration, other than radical prostatectomy when metastasized nodes were found. We performed transperitoneal laparoscopic lymphadenectomy on 30 patients and extraperitoneal approach on 20 between April, 1992 and September, 1995. The patients were between 52 and 78 years old. Nineteen, patients had stage B1, 17 stage B2 and 14 stage C cancer. Bilateral obturator nodes were dissected. We could not perform laparoscopic lymphadenectomy on two patients because of adhesion. The average operation time and blood loss were 166 minutes and 151 ml, respectively, in the transperitoneal group, while 142 minutes and 126 ml in the extraperitoneal group. The average number of removed nodes was 12 in the transperitoneal group and 10 in the extraperitoneal group. The extraperitoneal approach is a safer and useful procedure. Nodal metastasis were found in 12 patients by frozen section. Additional positive nodes were found in 7 patients by a further study. Two were not harvested laparoscopically and 5 were ascertained only by permanent section. Therefore, the two-staged operation might be preferable. Nodal metastasis was likely to be found in localized prostate cancer patients with clinical stage C, poorly differentiated cancer, or prostatic specific antigen density (PSAD) over 0.5 ng/ml/ml. Laparoscopic pelvic lymphadenectomy might be indicated for these cases.

Bilateral nephrocarcinoma in a 57-year-old woman was treated successfully with simultaneous bilateral nephrectomy and hemodialysis. The patient is well now over 3 years and 7 months after operation without recurrence of tumor. The literature was reviewed and the methods of the treatment were also discussed.

Phenoxybenzamine was administered to the patients who visited our clinics complaining of difficulty in urination. Total of 107 patients, 99 male patients and 8 female patients, were treated with phenoxybenzamineand symptomatic improvement was observed in 83 (77.6%). Diagnosis included were bladder neck contracture (58 cases), benign prostatic hyperplasia (24 cases) and others including neurogenic bladder dysfunction and chronic prostatitis etc. (25 cases). Effective rate was higher in elderly patients. No difference in effective rate was noticed between 5 mg/day group and 10 mg/day group. Urodynamic studies were done in some of the cases. Uroflowmetry was done in 13 cases, including 11 good and 2 poor cases. Improvement in flowmetric data was noticed in all good cases and no improvement in poor cases. In urethral pressure profiling, decrease in UPmax was also noticed in good cases. Surgery was indicated in the patients of benign prostatic hyperplasia who had had frequent recurrence of urinary retention previous to medication and in bladder neck contracture who did notrespond to phenoxybenzamine. Transurethral resection was done in 12 of 24 cases of benign prostatic hyperplasia andin 5 of 58 of bladder neck contracture. Histological diagnosis of the latter was fibromuscular hyperplasia in all cases. Nasal stiffness, light headedness, palpitation, thirst, vesical irritation symptoms, lethargy and malaise were the untoward reactions noticed and in 12 patients medication was discontinued because of these reactions. Phenoxybenzamine call be. administered to the patients suffering from urinary obstruction for symptomatic relief and for deciding precise indication of surgery.

1973年9月から1979年11月までの6年間に行なわれた生体腎同種移植患者50例,51回の移植後の補液管理について検討した.受腎者の補液管理の方法の相違により,グループ1:中心静脈圧を観察しつつ,移植1時間ごとに尿量を測定し,その同量を補液,グループ2:中心静脈圧,一部スワンガンツカテーテルを挿入し,さまざまのパラメーターを観察しつゝ心不全が起こらない限り,尿量と無関係に可及的大量の補液を行なった,2群に分けた.腎移植後1週間以内に血清クレアチニンが2.5 mg/dl以下に低下しない症例を,移植後急性尿細管壊死発生症例(虚血性障害発生群),2.5 mg/dl以下に低下した症例を機能良好群と定義した.検討成績では,グループ1の術中および術当日の補液量はグループ2と比べあきらかに少なかった.またグループ1の術中および術当日尿量はグループ2と比べ有意に少なかった.グループ1はグループ2に比し,術後血清クレアチニンの低下が遅延し,クレアチニンクリアランスが低い傾向がみられたが統計的有意差はみられなかった.グループ1の術当日のFENaはグループ2より高い傾向を示した.グループ1の機能良好群の血流再開5時間後,10時間後,15時間後,20時間後のCVPの平均値はグループ2の機能良好群の各々の平均と比べあきらかに低かったが,グループ1, 2の虚血性障害発生群との間に差を認めなかった.グループ1の急性尿細管壊死の発生頻度は22例中8例(36.3%)で,グループ2の29例中3例(10.3%)と比べ,あきらかに高かった.グループ1の1年移植腎実測生着率は72.4%で,グループ2の75.9%と差はみられなかった.グループ1の1年患者実測生存率は77.3%で,グループ2の96.6%に比しあきらかに低かった.以上より,生体同種腎移植後は心不全が起こらないかぎり,術後尿量にかゝわらず可及的大量の補液をすることが,移植後急性尿細管壊死による腎障害の防止に重要であることを強調した A major concern during the early post-transplantation period is fluid management. This study analyzes the difference between two approaches to fluid management in 49 subjects who had had renal transplants plus one subject who had had two renal transplants because of chronic rejection. All patients were divided into two groups. In group 1 (LDI-22), the urine lost each hour was replaced with an equal volume of half normal saline and 5 % glucose in water, and in group 2 (LD23-51), massive fluid management with half or quarter saline was undertaken, cardiac parameters were checked and the administration of fluids was controlled by a Swan-Ganz catheter to avoid cardiac failure, additional fluids being administered when the Swan-Ganz catheter reading was lower than normal. The cases in which serum creatinine after one postoperative week remained above 2.5 mg/dl were classified as acute tubular necrosis (ATN), and those with lower values as non-ATN. The average volume of infusion during operation (1l46±490 vs 2698±939 ml/m2BSA) and on transplant day (2262±892 vs 2897 ±855 ml/m2BSA) was significantly smaller in Group I (P<O. 005). The average urine output during operation (187 ± 135 vs 524±306 mljm2BSA) and on the transplant day (2125± 1399 vs 3548 ± 1435 ml/m2BSA) was also significantly smaller in Group I (P<0.005). Postoperative serum creatinine reduction in Group I was some what delayed, but the delay was not statistically significant. FENa during the first postoperative day was higher in Group (4. 38±3. 20 vs 2. 75±1. 75%). The GVP monitored for 20 hours after declamping in the cases without ATN was significantly lower in Group 1 than in Group 2, but, in the cases with ATN, the difference between Group 1 and 2 was not statistically significant. The incidence of cases with ATN was significantly higher in Group 1 (36.3 vs 10.3%) (P<0.01). The actuarial one-year graft survival was 72.4% in group 1 and 75.9% in Group 2 and the difference was not statistically significant. The actuarial one-year patient survival rate was lower in Group 1 (77.3 vs 96.6%) (P<0.05). From the data described above, it might be tentatively concluded that checking the cardiac parameters to avoid cardiac failure "and massive fluid management through the use of the Swan-Ganz catheter might be useful in preventing postoperative ATN in living related renal allogreft recipients.

αインターフェロンを用いて尖圭コンジローム18例の治療を試みた.1)局所投与を行った17例中完全消失は,6例に認めた.2)総投与量が12×106単位を越えた,11例での完全消失は5例であった.3)完全消失例の6ヵ月以内の再発は認められなかった Eighteen cases of condyloma acuminata were treated by human lymphoblastoid interferon (HLBI). Seventeen were male and one was female. Five cases were recurrent cases. Except one patient, all the patients were administered HLBI by intralesional injection. Five patients were treated by single injection. Others were given 2 to 8 injections during one to 5 weeks. Total dose varied from 3 x 10(6) to 24 x 10(6) U. Of the eighteen patients, 6 showed a complete response and 3 a partial response (greater than 50% reduction in size of the lesion). In 5 of the 11 patients (45%) who were treated with a total dosage of more than 12 x 10(6) U, the lesion was completely cleared. Six patients who showed a complete response did not experience recurrent disease during the 6-month follow-up period. In conclusion, intralesional administration of HLBI for condyloma acuminata proved to be effective.

Cisplatin was administered to eleven patients bearing urogenital malignancies to evaluate clinical efficacy. (1) In testicular tumor cases combination therapy with cisplatin, bleomycin and vinblastine was very effective resulting in 100% efficacy rate. Effect of this combination regimen was noticed in every tumor of germ cell origin and malignant interstitial cell tumor suggesting wide anti-tumor spectrum of this regimen. (2) Efficacy of cisplatin against prostatic cancer was noticed only in 25% of cases by single administration of this drug. Therefore, combination with anti-androgen therapy or other anti-cancer chemotherapeutics should be considered. (3) Efficacy of single administration of cisplatin was noticed in no case ofuroepithelial tumors. Therefore, radiation therapy and other anti-cancer drugs should be combined to obtain anti-tumor effect against malignancies of uroepithelial origin. (4) Renal toxicity and ototoxicity could be avoided by confluent fluid administration combined with diuretics. Therefore, this drug seemed relatively safe to be administered to any case in this respect. However, administration of this drug to aged patients was hindered by rather severe gastrointestinal symptoms.

クラミジア性尿道炎患者に対して1日600 mgのOfloxacinを14日間投与した.1) 26例全例でクラミジアは陰性化した.2)排尿痛,尿道違和感など自覚症状は全例で消失した.3)初尿中多形核白血球(PMN),尿道分泌物の量および尿道分泌物中PMNの改善率は薬剤投与14日目で各々15/22,21/22,20/21と良好であった.4)総合臨床効果は薬剤投与7日目,14日目,21日目で各々15/24, 18/22, 19/21であった.5)副作用は2例に認められが,軽症であった.6)薬剤の投与期間は約2週間が適切と考えられた Clinical effects of ofloxacin (OFLX) in the treatment of the patients with chlamydial urethritis was studied. OFLX was administered at a dose of 200 mg, three times daily (600 mg) for 14 days. In all of the 26 patients with chlamydial urethritis, C. trachomatis was eliminated in 7 to 14 days after the start of administration. The subjective clinical symptoms such as pain on urination and abnormal urethral feeling was disappeared in all cases within 7 days after the administration. The objective clinical symptoms, urethral discharge, polymorphonuclear leukocyte (PMNL) in urethral discharge and PMNL in first urine were improved in 94, 68, 91% respectively on 14 days after the administration. Overall clinical efficacy rate of OFLX on 7 days, 14 days and 21 days after the administration in this study was 63, 82, 91% respectively. Whereas subjective symptoms of side effects were noted in 2 patients (7.6%), any additional medical care was needed in none of them. Because of the marked improvement of clinical symptoms and the safety administration, OFLX could be the first regimen to be chosen for the treatment of the patients with chlamydial urethritis.