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A 42-year-old man was admitted to our hospital because of lumbago and tachycardia-induced heart failure. Transthoracic echocardiography revealed impaired left ventricular function and a ball mass of thrombus in the left ventricle (LV). He was found to have systemic embolism in the spleen, kidneys, brain, and limbs. The patient was treated with limb thrombectomy followed by anticoagulation. Seven days after the direct factor Xa inhibitor, rivaroxaban, was initiated, transthoracic echocardiography was repeated, revealing disappearance of the LV thrombus without any clinical signs of cardiogenic embolism. His heart failure responded well and the LV wall motion had improved. This case suggests rivaroxaban has fibrinolytic effects on thrombi even in the LV.

P(論文), Serous membrane (SM) covers inner surface of abdominal, thoracic and pericardial cavities, aswell as outer surface of organs inside the cavities. It consists of surface mesothelial cells andloose connective tissue. Between them, a thim layer of basement membrane (BM) is located. Type IVcollagen is major constituent of BM, and consists of 6 different a(IV) chains, a1(IV) through a6(IV).Chain-specific functions are assumed by a chain-specific manner of localization. The a(IV) chaincomposition of skin, covering outer surface of the body, is demonstrated to have a1(IV), a2(IV), a5(IV),and a6(IV) chains, whereas that of SM, covering inner surface of the body, is yet to be analyzed. Abdominal wall, small intestine, thoracic wall, lung, pericardium and epicardium of humanmaterials were used in this study. Chain-specific monoclonal antibodies (mAbs) used were H11(for a1), H22 (for a2), H31 (fo a3), H43 (for a4), H53 (for a5) and H63 (for a6). Fresh frozen sectionswere stained with indirect immunofluorescence staining using the mAbs. Four out of six a(IV) chains, a1, a2, a5 and a6, were demonstrated in BM beneath themesothelial cells of all types of SMs, whereas only capillary BM consisted of a1 and a2. Besides,epicardial SM expressed a3 and a4 moderately as extra components. The a(IV) chain composition was same as those of epidermal skin BM. Therefore, these a(IV)chains are designated to be essential for BM covering inside and outside of the body.

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)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.

We performed a long-term follow-up of 4 patients with penile cancer who underwent hyperthermotherapy from August 1985 until August 1992. Hyperthermia was applied using a frequency of 350 MHz with a waveguide applicator twice a week for 60 min each for an average of 9.5 times (varying from 6 to 13 times). The total heating time that the temperature of urethra could be kept above 42 degrees C, was 166 min on the average (ranging from 0 to 463 min). Two patients classified as stage I according to the Jackson classification and 1 patient classified as stage IV underwent combined radiotherapy and received an average radiation dose of 53 Gy (range, 40-70 Gy). Among these patients 2 underwent combined chemotherapy with bleomycin or peplomycin. Malignant cells disappeared posttherapeutically and in August 1992, after an average of 5 years and 9 months (varying from 4 years 6 months to 6 years 10 months), the patients were free of recurrences. The one patient on stage IV had extensive invasion of the abdominal wall, but still recovered completely. One patient on stage III underwent combined chemotherapy and hyperthermotherapy, but heating had obviously been insufficient. There was a residue of malignant cells after the treatment and we performed a penectomy. Regarding functional preservation of the penis a multidisciplinary therapy incorporating hyperthermotherapy can be expected to increase the curativity. This indicates that it could induce in an advanced case, where an operation would be difficult, complete remission.

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.

前立腺癌に対するRU 23908の有効性および安全性を検討するため, stage C, Dの前立腺癌患者47例に1日1回150または300 mg経口投与による早期第2相臨床試験を行った.対象病巣に対する効果では, 総合効果判定は40例中CR+PRが34例, 部位別効果は原発巣では40例中CR+PRが35例, 骨転移では22例中10例, リンパ節転移では6例中5例, 肺転移は1例のみにみられCRであり, PAP判定では34例中CR+PRは33例であった.臨床症状に対する改善率は骨疼痛8/9例, 排尿障害25/30例, P.S. 15/33例であった.副作用は調査症例数47例中29例にみられ, 中止例は7例あった.特殊な副作用として間質性肺炎が試験期間の12週以後の継続投与期間も含めて6例に認められ, その他2例では出現の可能性が否定できないと判定された, 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.

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.

65歳男, 1)臀部慢性膿皮症を伴った難治性会陰部尿道皮膚瘻に対し, 抗結核療法後に複数の外科的治療を施行し良好な結果がえられた. 2)尿路の瘻孔に続発した臀部慢性膿皮症の報告は本邦初である. 3)複雑な尿道狭窄及び瘻孔は, 結核病変の可能性も念頭において初期治療を誤らないことが重要である, A 65-year-old male was hospitalized because of micturition pain and urinary oozing from several fistulas on the perineal and the left gluteal skin. Oozing had been present for about 50 years, after receiving mass resection of his left scrotum or perineum, and left orchiectomy. The main focus was on the left dorsal site of the anus. Compression around this area produced malodorous grayish pus discharge from many fistulas, although the anus was intact. Although he had histories of spinal caries and renal tuberculosis, both pus and urine cultures showed Staphylococcus spp. and no growth of Mycobacterium tuberculosis. Urethrocystography showed urethral stenosis at bulbar urethra and leakage from a site just proximal to the stenosis. Antibiotics for tuberculosis were administrated for fear of recurrent tuberculosis for 6 months. Cystostomy formation and debridement were performed, followed by en-bloc resection and mesh-skin graft after two weeks. Internal urethrotomy was performed six months after the surgery, and subsequently cystostomy removed. After three and a half years, although there was no local recurrence and no difficulty of urination, he died of cholangio-carcinoma. There are many reports of chronic perianal pyoderma subsequent to hemorrhoid or subcutaneous abscess; however, this might be the first report on a case originating from fistulas in the urinary tract.

Mutations of proto-oncogene c-kit in gastrointestinal stromal tumors (GISTs) are considered to cause a constitutive activation of KIT responsible for their oncogenesis. Imatinib has therapeutic potential for GISTs because of its inhibitory effect on KIT kinase activity. However, no study has been published concerning the effects of imatinib on GIST cells with various types of KIT mutation. To investigate the effects of imatinib on various c-kit mutations found in GISTs, cell proliferation and apoptosis assays were performed in two GIST cell lines with different KIT mutations. One of the cell lines, GIST-T1, revealed a heterozygous deletion of exon 11 in the c-kit, while the other cell line, GIST882, possessed a homozygous missense mutation of exon 13 in the c-kit gene. Imatinib inhibited proliferation and induced apoptosis in both cell lines. Imatinib potently suppressed proliferation of the GIST882 cell line at the concentration of 1.0 microM, whereas it inhibited the GIST-T1 at 0.1 microM. In two types of activating mutant KIT, imatinib could inhibit the constitutive activation of both types of KIT mutant, although the antiproliferative effect on GIST882 was weaker than on GIST-T1. Western blot analysis revealed that apoptosis related proteins were activated or suppressed by imatinib in both cell lines in the respective manner. Our results suggest that the apoptotic signal trans-duction caused by imatinib in GISTs is susceptible to various types of KIT mutation.