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As you know, for penile erection, a sufficient amount of testosterone-induced nitric oxide is needed in the smooth muscle of the penile arterial wall. With aging, LOH syndrome and so on, the serum testosterone level decreases, resulting in a decline of penile erectile function. Furthermore, it is known that the enzyme PDE5 in the penile artery wall also inhibits that function. Even so, it may be safe to say that decreasing testosterone is the major factor for erectile dysfunction, excepting severe diabetic arterial sclerosis. Currently, however, almost all doctors treat ED cases with a PDE5-Inhibitor only. From my understanding of the above-mentioned mechanism of erection, I think this medical treatment is not scientific and only a half measure. Cases in which PDE5-inhibitors alone are effective are limited to those in which sufficient NO is maintained to barely induce erection unless inhibited by PDE5. Aging males, especially, have lower NO levels caused by low testosterone. These cases cannot be cured satisfactorily by PDE5 inhibitors alone, even if the men can somehow achieve sexual intercourse. Therefore, I cannot understand or agree with the treatment method using a PDE5-Inhibitoralone without checking the testosterone level. Furthermore, simple temporal recovery of sexual activity does not revitalize the male fundamental physiology, that is, sleep-related erection and morning erection. And a more important problem is that latent psychological disorders should be thoroughly investigated for patients consulting about so-called ED. It is even said that it is lucky for a patient to have a chance to consult about ED, since it means that the doctor will check for other disorders; for example, metabolic syndrome so on. More aged men are beginning to feel loss of motivation and poor physiological condition after the climacteric stage, with loss of morning erection, even if they do not express complaints. These problems are mostly caused by a decline in testosterone, which latently accelerates arterial sclerosis and vascular disorders, shortening the male life span. Such patients with low levels of free testosterone complaining of ED should be treated with testosterone substitution and a PDE9-inhibitor (especially long-acting Cialis) for a period of at least 2-3 months. This treatment will restore the male physiological functions of sleep-related erection and morning erection and as well as treating many symptoms of LOH syndrome at the same time. However, the most important effect of revitalization of male physiology is surely the restoration of the self-actualization and dignity of maleness to patients. That should be considered the most clinically significant outcome.

茨城県里美村と北海道島牧村の40～79歳の男性住民を対象に, 同一検者, 同一方法により前立腺集団検診を施行し, これらの結果を比較検討した. 1)里美村と島牧村における癌発見率はそれぞれ0.39%, 0.63%であったが, この差は有意ではなかった. 2)里美村と島牧村の間で, 前立腺容積, I-PSS及び最大尿流率の分布に大きな差を認めなかった, We performed mass screening for prostate diseases in the village of Satomi-mura, in Ibaraki Prefecture for males between 40 and 79 years old (participation rate; 21%). The findings were compared to those obtained by mass screening in the village of Shimamaki-mura, in Hokkaido Prefecture, conducted by the same examiners in a consistent manner (participation rate; 47%). When we considered the difference in biopsy rates between the two sites, the detection rate of prostate cancer in Satomi-mura was similar to that in Shimamaki-mura. There were no apparent differences in distribution of prostate volume, the International Prostate Symptom Score (I-PSS) and maximum flow rate between the two sites for each 10-year-age group. Our findings suggested that there was little site difference in the detection rate of prostate cancer and voiding condition between the two villages.

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.

1) Commercial kitを用いた唾液中テストステロンの測定は標準血清を50pg/mlへ希釈し, 標準曲線を作成することで十分可能となり, エーテル抽出操作を含め約5時間で行いえた。2)加齢に伴い唾液中テストステロン濃度が低下し, 40代以降すべての年代で20～30代に比して有意に低下していた。これは血中遊離テストステロンの加齢に伴う変化と同様であった, Measurement of the level of free testosterone is important in the evaluation of testicular function. Because most of the testosterone in the saliva is in the free form, measurement of the salivary testosterone level is considered to be effective for the evaluation of testicular function. In the present study, a commercial kit was employed to measure the salivary testosterone level, and the change in the salivary testosterone level with age was investigated. The subjects of this study were 76 males, 20-89 years of age, with no endocrinological diseases. The concentration of testosterone in the saliva was measured for each of the subjects, and for 34 of the subjects the concentrations of total testosterone and free testosterone in the serum were also measured at the same time. Standard serum was diluted to have a testosterone concentration of 50 pg/ml, and the results indicated that it was sufficiently possible to measure the salivary testosterone. The coefficient of correlation between the salivary testosterone concentration and the serum total testosterone concentration was 0.479 (p < 0.01), while the coefficient of correlation between the salivary testosterone concentration and the serum free testosterone concentration was 0.732 (p < 0.001). These findings thus indicate that the correlation between the salivary testosterone concentration and the serum free testosterone concentration is better than that between the salivary testosterone concentration and the serum total testosterone concentration. It was also demonstrated that the salivary testosterone concentration decreased significantly with aging after the fifth decade of life. The correlation coefficient for that relationship was -0.606 (p < 0.001), and the change was similar to that seen in the serum free testosterone concentration as a function of aging. The findings suggested that measurement of the salivary testosterone concentration with the commercial kit is useful for the evaluation of testicular function.

前立腺肥大症患者を対象としてTZP-4238 (TZP群)の性的機能に対する影響および自覚的排尿障害に対する有効性, 安全性, 有用性を酢酸クロルマジノン(CMA群)を対照薬にして, 二重盲検法により検討した。その結果, 性機能に与える影響はTZP 1.25mg/日投与群は45.1%, CMA 50mg/日投与群は71.4%と有意にTZP群が少ないこと, しかも排尿障害への臨床効果はTZP群45.9%, CMA群50.0%とほぼ同等であるという成績をえている。また他の副作用についても両薬剤間に差は認められなかった, Using chlormadinone acetate (CMA) as the control drug, a double-blind study was carried out to examine not only the effects of 17 alpha-acetoxy-6-chloro-2-oxa-4, 6-pregnadiene-3, 20-dione (TZP-4238;) on subjective urinary symptoms but also, especially, that on the sexual function in patients with benign prostatic hypertrophy (BPH). The clinical efficacy rate in relation to the subjective urinary symptoms was about the same in the two treatment groups; 45.9% in the TZP-4238 group and 50.0% in the CMA group. However, the incidence of adverse effects on the sexual function showed a marked difference between the two groups. The TZP-4238 group revealed a lower suppressive effect on the function than the CMA group (45.1% vs. 71.4%). In relation to their causation of other adverse effects, there were no differences between the two drugs. Accordingly, in consideration of the facts that TZP-4238 with less influence on the sexual function affords a superior quality of life to elderly patients, while achieving effective treatment by means of a convenient single daily administration, TZP-4238 was surmised to be a more useful drug than CMA as an antiandrogen for the treatment of BPH.

1)小委員会判定が可能であった症例における有効率は急性細菌性前立腺炎(ABP)で100%(15/15), 慢性細菌性前立腺炎(CBP)で66.7%(18/27)と満足すべき成績がえられた。細菌学的効果はABPで100%(15/15), CBPで81.5%(22/27)の菌陰性化率であった。2)自他覚的副作用は100例中8例に, 臨床検査値異常変動は71例中9例にみられたが, いずれも臨床上特に問題となるものではなかった。3) ABPでは7日間, CBPでは14日間の投与期間で薬剤の有効性は評価可能である。4) ABPではE. coliをはじめとするGNRがおもな起炎菌であり, CBPでは, GNRあるいはE. faecalisは半数弱の症例でしか分離されず, 他の症例ではCNSが検出された, The clinical efficacy of temafloxacin (TMFX) was evaluated in the patients with acute prostatitis (AP: 31 cases) and chronic prostatitis (CP: 75 cases), and the criteria for clinical evaluation on bacterial prostatitis by the Japanese UTI Committee were re-examined. The clinical efficacy of TMFX on prostatitis was examined. The number of the evaluable cases by doctors in charge were 30 and 68 for AP and CP, respectively. The efficacy rates were as high as 96.7% for AP and 80.9% for CP. In the patients whose efficacy could be evaluated by the Committee, the efficacy rates were as high as 100% (15/15) for acute bacterial prostatitis (ABP) and 66.7% (18/27) for chronic bacterial prostatitis (CBP). The bacteriological eradication rates were 100% (15/15) for ABP and 81.5% (22/27) for CBP. Adverse drug reactions were observed in 8 of 100 cases (total evaluable cases) but they clinically did not consist any problems. Abnormal laboratory test findings were observed in 9 of 71 cases (total evaluable cases), whose changes were all slight and did not clinically cause any problem. Therefore, TMFX was concluded to be highly useful in the treatment of ABP and CBP. The criteria for clinical evaluation on bacterial prostatitis were re-examined. Concerning the treatment period, comparison of the evaluation at Day 7 with that at Day 14 in ABP revealed that the efficacy was evaluable at Day 7. In the same way, comparison of the evaluation at Day 14 with that at Day 28 in CBP revealed that the efficacy was evaluable at Day 14. Concerning the pathogens, in ABP, the major pathogens were considered to be GNR as well as E. coli. On the other hand, in CBP, GNR and E. faecalis, that were generally authorized to be pathogens, were detected in less than half of the patients, and CNS were detected in the other patients. Among the CNS cases, there were some cases that showed no relationship between improvement of clinical symptoms and bacterial response. Therefore, it is necessary to perform further studies on this matter. In conclusion, regarding the criteria for clinical evaluation on bacterial prostatitis proposed by the Japanese UTI committee, the treatment period for evaluation of efficacy was appropriate, and it is necessary to perform further studies in order to determine the pathogens in bacterial prostatitis.

1)125, 250, 375および500mgの用量の単回経口投与を受けた計11名の患者では副作用を認めなかった。2)375, 750, 1, 125および1, 500mg/日の用量の1日3分割経口投与を連日28日間行ったところ, 1, 500mg/日の投与を受けた4例中1例に胃部不快感, 悪心・嘔吐, 食欲不振の副作用症状を認めた。他の用量を投与された9例では副作用の訴えはなかった。3)臨床検査値の異常は375mg/日群の3例では認められなかったが, 他の用量群で9例中5例にトラスアミナーゼの上昇を認めた。特に, 1, 500mg/日群では評価可能な3例の全例に異常値を見た。4)LHの濃度の有意な上昇を認めた。5)客観的効果が各群において3例中2例に観察された。また, 疼痛, 排尿障害, PSの改善が認められた。6)投与後速やかに吸収され, 大部分が水酸化を受けたOH-フルタミドとして血液中に存在していた。また, 単回投与と比べ, 連日投与後のOH-フルタミドの半減期には大差を認めなかったがCmaxおよびAUCは増加していた。7)第2相臨床試験の試験用量としては, 375mg/日から1, 125mg/日の範囲が望ましいと結論された, A phase I study of orally administered flutamide (a pure anti-androgen) was performed in 26 patients with prostatic cancer. No side effects were observed in 11 patients receiving single doses of either 125, 250, 375 or 500 mg. However, in the daily dosing schedule of 375, 750, 1125 and 1, 500 mg/day doses, where medication was taken in three divided doses, discomfort in the stomach, nausea, vomiting and anorexia were experienced in one of the four patients receiving the highest dose of 1, 500 mg. Nine patients receiving the other doses did not complain of toxic symptoms. Laboratory values did not change in the three patients receiving the lowest 375 mg/day dose, but elevation of transaminase was observed in five of the nine patients given higher doses. This elevation was observed in all the three patients receiving 1, 500 mg/day dose. Among the serum hormone levels, significant increases of luteinizing hormone were observed. As for efficacy, objective responses were observed in two of the three patients in each of the four daily dosing groups. Improvement of pain, voiding obstruction symptoms, and performance status were also observed. Flutamide was found to be absorbed rapidly and to exist as a hydroxylated form (hydroxy-flutamide) in the plasma. The half-life of hydroxy-flutamide was similar in the single and daily administration, but the peak concentration and area under the concentration versus time curve in the daily administration became greater than those in the single administration. In conclusion, flutamide should be examined for efficacy and safety using doses of 375 to 1, 125 mg/day in the phase II study.

1)内分泌療法未治療の前立腺癌症例に対し, 375mg/日の用量で単独療法として使用しえる。この際, testosterone産生阻害療法に比し, 「生活の質」が保たれる。2)内分泌療法再燃例に対しても, ある程度その効果が期待できる。3)フルタミドと他の精巣性testosterone阻害剤との併用で, その併用効果が期待できる。4)また, LH-RHアナログの投与によるflare-up現象をフルタミドを併用することにより予防することが可能である, The phase II study of flutamide, a pure anti-androgen, was performed to estimate the clinical doses on 165 hormone untreated or treated patients with prostatic cancer. The hormone-untreated patients were given orally flutamide of 90, 375, 750 or 1, 125 mg/day in three divided doses daily for 12 weeks. Responses were not observed at the 90 mg/day dose except for improvement of clinical symptoms. However, an objective response rate of 48.8-46.7% was obtained at 375-1, 125 mg/day doses. In hormone-treated patients including cases refractory to the previous hormonal treatment, the objective response rates were 13.3 and 8.3% in 375 and 750 mg/day flutamide groups, respectively. Side effects such as gynecomastia, nausea, vomiting, diarrhea, and abnormal laboratory findings such as the elevation of hepatic transaminases were observed. The incidence increased dose-dependently. Determinations of serum hormone levels revealed an increase in testosterone levels by the use of flutamide. In conclusion 375 mg/day of flutamide is the optimal dose in monotherapy for hormone-untreated patients with prostatic cancer, where the quality of life can be maintained compared with therapies involving testosterone suppression. This dose is also expected to show some efficacy in cases refractory to hormone treatment.

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.

1)内分泌療法を行った372例中117例に局所, 全身性の再燃を認めた.再燃を認めた症例の1/4は局所再燃であり, 残りは全身性の再燃であった.2)再燃までの期間(平均月数)はstage B:45.9, C:36.8, D:29.3であった.局所腫瘍のみの非再燃率は治療5年目で90%であったが, 全身性の再燃についての5年目の非再燃率はstage C, Dでそれぞれ71.7%, 67.4%であった.3)再燃から癌死までの期間は, stageにかかわらず平均12～21ヵ月であった.4)全身性再燃と内分泌療法の初期総合効果, 病理組織学的所見との関係では, stage Bでは著効例, 有効例が無効例より, SAT 1が2, 3より非再燃率が高かった.stage C, Dでは著効例のみが, 有効例, 無効例より非再燃率が高く, 病理組織学的所見との関係ではstage DでSATのgradeの悪化に伴う非再燃率の低下を認めた, Prostate carcinomas are well known to be initially responsive to endocrine therapy. However, a significant number of the patients experience a relapse from endocrine therapy during the follow-up period. We clinically analyzed various aspects of the relapse which indicate a limitation in the effectiveness of endocrine therapy for prostate carcinoma. In a total of 372 patients, 117 (31.5%) had some evidence of local relapse such as regrowth of the primary lesion, or a generalized relapse such as re-elevation of total acid phosphatase, reactivation of previously present metastasis or the new appearance of metastasis, during endocrine therapy. Of these, one-fourth had local relapse alone and the remainder showed generalized relapse. The interval from the start of the treatment to the time of relapse tended to become shorter; 45.9 months (mean) in stage B, 36.8 in stage C and 29.3 in stage D, according to the stage progression. As to the non-relapse rate of the primary lesion, no differences were found among the stage, with the rate being approximately 90% at the fifth year in each stage. However, the generalized relapse-rate tended to increase with the stage progression. In the generalized relapse, the patients of stage C or D showed a non-relapse rate of 71.7% or 67.4%, respectively. Most of the generalized relapse appeared within five years following start of endocrine therapy in these advanced stages. The interval from relapse to prostate carcinoma-related death in patients with the generalized relapse was 9 approximately 21 months, and those in stage D tended to show a a poorer prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

治療開始6ヵ月間(初期治療)を, 内分泌療法を主体に治療した未治療前立腺癌497例を対象とした.このうち, 初期治療が内分泌療法のみであった内分泌療法単独群は443例である.1)前立腺局所反応の程度とstageとの間には明らかな相関はなかった.各stageにおける前立腺局所反応の程度と予後とは良く相関した.すなわち, 前立腺局所が治療後"平坦化"あるいは"縮小"した群の生存率, 生存期間は"不応"群より明らかに良好であり, この変化が予後を予測する上で有用と考えられた.2)病理組織学的所見のうちSATのgradeは, 前立腺局所反応の程度とは明らかに相関していた, We have already pointed out by the use of multivariate analysis that local response of the prostate is one of the important prognostic factors in patients receiving endocrine therapy. Herein, we investigated how the local response to endocrine therapy affects the survival rate or the survival period. We also studied the relationship between the local response and histopathological findings. The local response of prostate was not correlated with the stage progression. Sixty-seven percent of the patents in each stage had an initially favorable local response of the prostate, in which the primary tumor became flattened or reduced by endocrine therapy. By contrast, the local response of the prostate was well correlated with the prognosis in each stage. Patients with a flattened or reduced primary lesion following endocrine therapy showed a higher survival rate or a longer survival period than those with the unchanged lesion. This result has confirmed that the local response of prostate to endocrine therapy is useful in predicting clinical courses of patients. Grade of structural atypism (SAT), one of the pathological findings, had a correlation with local response of the prostate. With an elevation of the SAT grade, the proportion of patients with unchanged primary lesion was increased.

腎癌症例においてIAPとISSを測定し, その腫瘍マーカーとしての意義を検討した.1) IAP, ISSとも各stage別の平均値は正常上限値を上回り, 特にM1群で高値を示した.また両者の実測値は非常によく相関した.2)両者ともstageの進行に伴ってその陽性率は上昇した.3)両者とも臨床経過とある程度相関して変動した.4)有転移症例において, 正常上限値の2倍以上の高値群は2倍以下の群に比して, 予後不良な傾向が両者ともに認められた.以上より, IAP, ISSは腎癌における腫瘍マーカーとして有用である.5) IAPもしくはISSとTPA, ferritinの三者でのcombination assayは臨床的に有意義である, To clarify their usefulness as markers for renal cell carcinoma, serum immunosuppressive acidic protein (IAP) and serum immunosuppressive substance (ISS) were evaluated by TIA (turbidometric immunoassay) for IAP and by SRID (single radial immunodiffusion) for ISS. The mean level of IAP and ISS was beyond each upper normal limit (500, 700 micrograms/ml) in every stage, and especially high in the M1 group. The levels of IAP and ISS were significantly correlated with each other. The determination of IAP and ISS levels after treatment showed a good correlation to the clinical course of the disease. The positive rates of IAP and ISS increased as the stages progressed, respectively. When the influences of pretreatment IAP and ISS level on survival period were investigated, the low IAP or ISS level group (less than two times of the upper normal limit) tended to have a better prognosis than the high level group (more than two times of the upper normal limit) in the M1 patients. These findings suggested that IAP and ISS could be used as markers for monitoring a disease and predicting the prognosis in patients with renal cell carcinoma. As for the positive rate in the combination assay for IAP, TPA and ferritin, or ISS, TPA and ferritin, more than 80% of the patients with low stage renal cell carcinoma had at least one positive marker. This suggested that the combination assay of these three markers was clinically valuable as a disease monitor in patients with renal cell carcinoma.

CPRは1回0.5 gまたは1.0 gを, CAZは1回1.0 gを1日2回, 点滴静注により5日間連続投与し, 臨床効果はUTI薬効評価基準により評価した.総投与症例530例中効果判定が可能であった症例はCPR 1日1 g投与群141例, CPR 1日2 g投与群136例, CAZ 1日2 g投与群140例であった.CPRは複雑性尿路感染症に対してCAZと同様に有用性の高い薬剤である, 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.

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.

Urethritis in males and cervicitis in females, which were sexually transmitted diseases, were treated with NY-198, a new quinolone antibiotic, and its efficacy was studied. Seventeen male patients with gonorrheal urethritis were administered a single 300 mg dose of NY-198. The efficacy rate on the 3rd day after administration was 100%, but it was 85.7% on the 7th day due to recurrence in 1 patient. The results of treatment of non-gonorrheal infections were as follow. In this treatment, NY-198 was administered in a daily dose of 600 mg in 3 divided doses for 14 consecutive days. In the treatment of chlamydial urethritis of males, the efficacy rate in 26 patients was 84.6% on the 7th day and 84.0% on the 14th day in 25 patients. In the treatment of chlamydial cervicitis, the efficacy rate was 100% on both the 7th (3/3) and 14th (6/6) days. In the treatment of non-gonorrheal and non-chlamydial cervicitis, the efficacy rate was 100% on the 7th day (1/1) and 50% (1/2) on 14th day. The efficacy rate in all 40 males with non-gonorrheal urethritis was 85.0% on the 7th day and 88.9% for 36 patients on the 14th day, while that in all 4 females with cervicitis was 100% on the 7th day and 87.5% on the 14th day. No side effects were seen in any of the patients. Overall, NY-198 had an efficacy rate of 80% in the treatment of chlamydial infections. NY-198 was found to be a useful drug which is efficacious in the treatment of all STD-related microbes such as gonococci and chlamydia.

The efficacy of single administration of NY-198 in the treatment of gonococcal infections was studied employing male patients with gonorrheal urethritis and female patients with gonorrheal cervicitis. The clinical efficacy was evaluated on the basis of the efficacy rates which was estimated on each observation day for each patient. In the male patients, NY-198 was administered in a dose of 200 mg in 25 cases and a dose of 400 mg in 65 cases. The rate of eradication of N. gonorrhoeae (i.e. efficacy) on the 3rd day of administration was 96% in the 200 mg administration group and 100% in the 400 mg administration group. On the 7th day after administration, the eradication rate was 100% in both the 200 mg and 400 mg administration groups. When the eradication rate on the 7th day was statistically estimated for patients who returned to the hospital only on the 3rd day, it was 97.9% in the 200 mg administration group. In the female patients, NY-198 was administered in a dose of 200 mg to 4 cases and a dose of 400 mg to 5 cases. The eradication rate on each observation day was 100% in both dosage groups. In conclusion, single administration of NY-198 in a dose of 200 mg or 400 mg was highly effective, and considered to be a therapeutic method highly useful clinically.

We studied the epidemiology of 109 cases of gonococcal infections (105 males with urethritis and 4 females with cervicitis), together with the basic and clinical effects of cefetamet pivoxil in the cases. The peak of age distribution of the male patients was in the younger half of their twenties, and all of the 4 female cases were between 20 and 39 years old. The major source of infections in the males younger than 25 years old was their girl friends or so-called pick-up friends, and that of the males older than 25 years old workers serving at an amusement center, for example, bars and so-called special massage parlor, which accounted for about three fourths of the male cases between 35 and 44 years old. The distribution of the MIC (inoculum size; 10(6) CFU/ml) of Cefetamet against beta-lactamase non penicillinase producing Neisseria gonorrhoeae (non-PPNG) ranged from 0.025 to 0.1 microgram/ml and that against beta-lactamase producing Neisseria gonorrhoeae ranged from 0.025 to 0.05 microgram/ml. The isolation rate of PPNG was 10.2% (9/88). In male patients with gonococcal urethritis, the efficacy rate was 100% on days 3 and 7 for 1, 000 mg single dose and 7-day treatment and 500 mg single dose treatment. One of the cases treated with 250 mg single dose therapy was unchanged at 3, but the efficacy rate of the remaining cases was 100% at day 7. Complicated urethritis with C. trachomatis was noticed in 25.7% (5/105) of the male urethritis and in 25.0% (1/4) of the female cervicitis cases. The only side effect was diarrhea observed in 1 of the 124 case (0.8%).

A prostate mass screening was performed in 6 towns in Shiribeshi area in Hokkaido Prefecture on 384 males who were over 50 years old. The screening included digital palpation, uroflowmetry, blood sampling for tumor markers, questionnaire for voiding disturbances and transrectal sonography. Prostatic carcinoma was found in 9 (2.3%) of 384 males. An incidence of benign prostatic hypertrophy was 15.6% in 384 males. Atypical hyperplasia was found in 4 among 35 biopsied cases. Incidence of voiding disturbance such as retardation, prolongation and nocturia significantly increased with age as well as prostate size.

We investigated how histopathological features, such as structural atypism (SAT), nuclear anaplasia (NAN) and Gleason's pattern, influence the prognosis of patients receiving endocrine therapy. Patients with SAT 3 or NAN 3 clearly had a lower survival rate and a shorter survival period than those with other grades of SAT or NAN and this tendency was more prominent in the high stage than low stage. Patients with a higher grade of SAT or NAN had a poorer prognosis as well, when only cancer-related death was considered in the calculation of survival and survival period. The results described above suggest that the grade of SAT and NAN is one of most influential factors for prognosis. In the analysis for the prognosis of patients according to grade of mean value of SAT + NAN, there were differences in prognosis among mean value of SAT + NAN 2-4, 5 and 6. This indicated that the combined grading system would provide more information to the prediction of prognosis. Patients with Gleason's primary (or secondary) pattern 1 and 2, or 3 and 4 had a better survival than those with pattern 5 in the analysis when only cancer-related death was considered. This was coincident with the result that the survival rate for each Gleason's sum 2-3, 4-5, 6, 7-8 and 9-10 was different. Consequently, Gleason's pattern influenced the rate of cancer-related deaths, and this pattern may be another important factor for predicting the prognosis.

Of 572 patients with prostatic carcinoma, 497 received endocrine therapy as the initial treatment. These patients were surveyed in a cooperative research study by members from five universities. Prognosis, causes of death and side effects of estrogen therapy were studied. The prognosis of patients who had received endocrine therapy became worse, as the stage progressed. The prognosis of those who had received a combination of estrogen therapy with castration tended to be better than that of those who had received estrogen therapy alone. Similarly, the prognosis of those who had received a combination of progesterone therapy with castration tended to be better than that of those who had had progesterone therapy alone. No relationship was found between estrogen doses (low, medium and high) and prognosis, although a precise comparison among the three could not be made because of the smaller number of patents with low doses. A high dose of estrogen may not always be the indication, rather a medium dose such as 300 mg diethylstilbestrol diphosphate may be clinically appropriate. The cause of death could be identified in 303 patients who had received endocrine therapy. Cancer-related death was the most frequent (63.7%), and cardio- or cerebrovascular death accounted for only 14.2% of the cases. When this analysis was confined to the patients who had received estrogen therapy, estrogen administration seemed to be the cause of cardio- or cerebrovascular death of 16.1% of the patients. Daily dosing of estrogen was not definitely related to the incidence, or the interval to cardio- or cerebrovascular death. However, among the patients who had died of cardio- or cerebrovascular disease, 50% of the patients who had received a medium or high dose of estrogen tended to die within two years after treatment, while 50% of those who had received a low dose died within three years.

The general trend on the treatment for prostatic carcinoma has been changing from endocrine therapy alone to an alternative type according to stage. We evaluated clinically the favorable and unfavorable outcome of endocrine therapy in Japan, so that others will be appropriately evaluated. In a cooperative study made by members of five universities, 572 patients with clinically or histologically reconfirmed prostatic carcinoma were entered in this retrospective study. We studied the true influence of prognostic factors on the prognosis of 497 patients with prostatic carcinoma who had received endocrine therapy, employing multivariate analyses, such as quantification method II, multiple regression analysis and Cox's proportional hazard model. Twelve factors were considered in the study; "age", "stage", "histological findings (structural atypism = SAT, nuclear anaplasia = NAN, Gleason's primary and secondary pattern)", "pretreatment level of total acid (ACP) and of alkaline phosphatase (ALP)", "castration performed or not performed", "doses of estrogen", "type of response of local prostatic tumor and of ACP to endocrine therapy". Analysis of the "importance" of a prognostic factor by a partial correlation determined by quantification method II, revealed "stage" to have the greatest "importance" on prognosis throughout the entire period. "Response of local prostatic tumor", "response of ACP" and "Gleason's primary pattern" tended to be important factors for prognosis, in particular, in the first half period, and "age" and "Gleason's secondary pattern" were important in the latter half. Multiple regression analysis revealed the "stage", once again to be the most influential factor on the prognosis for the entire observation period. Also "response of local prostatic tumor", "SAT" and "Gleason's primary pattern" affected the patients' prognosis in the first half of the observation period. In the latter half, "age" became more of an influential factor than "histological findings". Analysis with Cox's proportional hazard model revealed that "response of ACP", "stage", "age", "Gleason's primary and secondary pattern", and "response of local prostatic tumor" were definitely the more influential prognostic factors, of which chi-square values (or t values) were statistically significant. Comparison of the significant factors in each multivariate analysis revealed that common influential prognostic factors, such as "age", "stage", "histological findings (mainly Gleason's primary and secondary pattern)", "response of local prostatic tumor" and "response of ACP" were coincident to the clinical impression. The clarification of these factors would be clinically beneficial when treating patients with endocrine therapy.

Allylestrenol (ALE) and chlormadinone acetate (CMA) were administered to patients with prostatomegaly by the double-blind method, and a self-assessment questionnaire method developed by the authors was used to study the influence of these two antiandrogens on their sexual function. Each test drug was orally administered to 58 patients, in a daily dosage of 50 mg for 12 consecutive weeks. The questionnaires consisted of 6 categories each consisting of 5 questions, or 30 questions in total. The 6 categories were "sexual desire, " "erectile capacity" and "ejaculation, " which relate to the sexual function, and "living environment (including the frequency of sex), " "dysuria" and "dummy (personality)." Each question was graded into 0-10 points, and each patient was requested to circle the number which best described his status. The scores were compiled and statistically analyzed. Many patients were senile. Evaluable answers were obtained for 99 (85.3%) of the 116 patients. Factor analysis based on the preadministration scores confirmed the contents of the questionnaires to be appropriate for the objectives of the present study. Multiple regression analysis revealed a high correlation between the self-assessment scores and objective data (nocturnal penile tumescence values; NPT values) when dropout cases due to a decrease in the sexual function and non-replying cases were excluded. The self-assessment questionnaire method was concluded to be as useful an objective test method as the NPT measurement for examining the sexual function. Aggravation of the "frequency of urination during night" was conspicuous in the CMA group, and there was a significant difference (p less than 0.05) in this parameter between the two groups. Except for this parameter, dysuria was improved in both administration groups, and there was no significant difference in the efficacy of the two drugs. Both drugs tended to suppress overall sexual function, but the suppression was less severe in the ALE group. Especially the suppression was significantly (p less than 0.05) lower in the ALE group regarding the 3 parameters of "contact sexual arousal, " "contact erection" and "morning erection", which are included in the category of "sexual desire" or "erectile capacity." Also, suppression of "frequency of sex" and "intensity of sexual desire" tended to be lower in the ALE group at a level of significance of p less than 0.1. Regarding questions in the category of "ejaculation, " the incidence of non-replies was high in both groups, but its rate was higher in the CMA group.