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Although invasive and expensive, the pressure-flow study is known as the reference standard for the diagnosis of bladder outlet obstruction. We investigated the usefulness of ultrasound-estimated bladder weight (UEBW) as a predictor of the need for surgery for benign prostatic hyperplasia (BPH).A total of 97 consecutive male patients50 years old with lower urinary tract symptoms (LUTS) were prospectively enrolled in this study. The surgery rate was correlated with the UEBW, the results of uroflowmetry, the postvoid residual urine volume, prostate volume, and International Prostate Symptom Score.Surgery for BPH was performed in 37 of the 97 patients studied. The surgery rate was associated with a high UEBW (or=35 g), severe LUTS (International Prostate Symptom Score ofor=20), a voided volume of100 mL at free uroflowmetry, and poor uroflow (maximal flow rate of10 mL/s). Multivariate analysis revealed that severe LUTS and a high UEBW were the risk factors for surgery for BPH.The results of our study have shown that the UEBW can be regarded as a useful parameter to identify patients with LUTS who are at risk of needing surgery for BPH.

蛍光眼底造影は, 眼科領域では網脈絡膜疾患の診断, 治療効果の判定に不可欠な検査法である. しかしその造影剤として用いられるフルオレッセイン-ナトリウム (NaFI) による副作用発現は稀ではなく, また透析患者におけるNaFIの薬物動態は知られていない. そこでまず基礎的検討として比色法によるNaFIの濃度測定法を検討し, 次に血液透析 (HD) 患者におけるNaFlの透析性を調べた. NaFIはHDにより速やかに除去され, 血中濃度は透析4時間で前値の17.5%, 5時間で14%に低下した. NaFIのクリアランス (Mean±SD) は1時間値20.2±20.1ml/min, 2時間値30.8±19.1ml/minであった. またNaFIのHD患者における非透析時の半減期は約21時間で健常者では約1.1時間であった. 以上よりNaFIは比較的良好な透析性を有すること, 非透析時は半減期が極めて長いこと, 副作用も稀ではないことなどからHD患者の蛍光眼底造影後は, NaFIの残存を防ぐ意味からも速やかにHDを行いNaFIを除去することが望ましいと考えられた.

1990年1月1日から12月31日の1年間に大阪府下で維持透析を受けた慢性腎不全患者を対象に後天性多嚢胞化萎縮腎 (acquired cystic disease of the kidney, ACDK) の発生率ならびに腎癌併発件数に関する調査を行った. 大阪府下で維持透析を実施している施設は133施設で総患者数は7,379名であった. ACDKの調査に回答のあった施設は118施設で, 回収率は88.7%であった. 118施設中59施設 (50%) がACDKの有無についての検査を年1-2回 (平均1.6回) 行っていた. 検査方法は59施設すべてが超音波検査を行い, 1施設を除いた58施設がCT検査を併用していた.59施設の総患者 (3,271名) を対象にACDK発生率ならびに腎摘除術の件数の調査では3,271名中, ACDKは男性501名, 女性257名, 計758名 (23.2%) であった. 男女比は約2:1で男性に多く, ACDK発生率は透析歴の長期化とともに経年的に増加し10-12年で44%のピークに達した. 12年を超えるとむしろ発生率は34-36%に低下した. ACDKの患者15例に腎癌の併発があり (男性15例, 女性0例), 腎摘除術を受けていた. 透析歴が長くなるほど腎癌の合併率が高くなる傾向にあった.

The reduction of platelet aggregation and adhesion is essential for preventing thrombus formation during extracorporeal circulation. This report addresses some performances of peptidyl antithrombogenic agents which bind to the adhesive site of fibrinogen. This was based on the recent finding that the sequence of the binding domain of the platelet membrane receptor to fibrinogen was identified as TDVNGDGRHDL (one-letter amino acid code; Thr-Asp-Val-Asn-Gly-Asp-Gly-Arg-His-Asp-Leu), entitled B12. The addition of B12 and shorter-chain analogue peptides dose-dependently suppressed platelet aggregation and adhesion onto a fibrinogen-coated surface. The shorter the amino acid sequence, the less effective was inhibition. The inhibitory effect on platelet adhesion in vivo was significant under continuous infusion of B12. These inhibitory effects were compared with those by a receptor-binding RGD (Arg-Gly-Asp) peptide, which is the common active site to adhesive proteins.

The authors examined interleukin-2 (IL-2) production and interferon gamma (IFN gamma) production of peripheral blood mononuclear cells in 28 patients with renal cell carcinoma and 17 control subjects. The peripheral blood was obtained prior to the initiation of therapeutic procedures. The patients were divided into two groups according to tumor size, less than or equal to 5 cm and greater than 5 cm. The production of IL-2 and IFN gamma was measured by immunoradiometric assay. As a result, in the patients with tumors greater than 5 cm, IL-2 and IFN gamma production was impaired. However, in the patients with tumors less than or equal to 5 cm, IFN gamma production was enhanced, though IL-2 production was not significantly different from that of the control subjects. There was no significant correlation between IL-2 production and IFN gamma production.

The proportions of different hepatic microsomal cytochrome P450s expressed in uremic rats were studied with specific antibodies and with a steroid hydroxylase assay. In male uremic rats, the hepatic levels of P450 2C11, a male-specific form, and 3A2, a male-dominant form, were decreased to about 30% at 5 weeks after the induction of uremia. These changes were paralleled by decreases in the activities of testosterone 2 alpha-, 16 alpha-, and 6 beta-hydroxylation. The level of P450 2A1, abundant in immature rats, was increased 2-fold by uremia and accompanied by an increase in testosterone 7 alpha-hydroxylation activity. The levels of P450 2C6 and 2E1 were not changed by uremia. The levels of male-specific and male-dominant forms such as P450 2C11 and 3A2 are affected by the serum level of testosterone, which was decreased in the male rats with uremia. Therefore, castrated rats were prepared to compare the effects of testosterone on hepatic cytochrome P450s in uremic rats with those in castrated rats. When testosterone was administered to the castrated rats, the decreased levels of both P450 2C11 and 3A2 returned to normal. However, the administration of testosterone to the uremic rats did not prevent the decrease in the levels of these P450s. In female rats, changes in the levels of cytochrome P450s were not as great during uremia as those in male uremic rats. The level of P450 2C12, a female-specific form, was not changed; the level of P450 2A1 was increased by 50%, that of 3A2 which is barely detected in female rats was increased by 60%, and that of 2E1 was increased by 25%. These results suggested that the changes in the hepatic levels of cytochrome P450s were affected by factors other than testosterone in uremic rats.

Bladder tumors were induced in rats by the oral administration of 0.025% N-butyl-N-(hydroxybutyl) nitrosamine (BBN). In order to study the suppressive effects of rat interferon-alpha (IFN-alpha) on induction of carcinogenesis in vivo, rats were treated with IFN-alpha i.m. twice a week. The treatment began at 5th week of BBN administration. The bladder mucosa was observed macroscopically and microscopically, and NK activity was examined. The results were as follows. 1) There was no significant difference in the bladder to body weight ratio between the BBN + IFN-alpha and BBN groups in during stage A (10th-14th week when changes in the mucous membrane such as hypertrophy in the bladder wall or vascular formation are observed). This ratio in the BBN + IFN-alpha group was less than that in the BBN group in during stages B and C (15th-19th week and 20th-30th week respectively when tumors are visually recognizable). 2) The rate of carcinogenesis in the BBN + IFN-alpha group was less than that in the BBN group in stages A and C. 3) The pathological grade and stage of the bladder cancer in the BBN + IFN-alpha group were lower than those in the BBN group in stages B and C. 4) There was no significant difference in NK activity between the two groups in stage A, but NK activity of the BBN + IFN-alpha group was higher than that of the BBN group in stage B. 5) These findings substantiated the hypothesis that IFN-alpha can suppress tumor-growth in BBN induced bladder carcinoma.

A prospective noncontrolled study of the safety and potential efficacy of the metallic stent was performed on 32 patients with benign prostatic hypertrophy. Mean age was 76.6 years (range, 56-98 years), and mean prostatic volume was 24.2 cm3. The patients were selected on the basis of a quantitative symptom score (QSS), uroflowmetry measurements, and residual urine volume (RU). Nineteen patients had urinary retention and remaining 13 patients had moderate symptoms and signs of prostatism. Placing the stent was successfully done in 31 patients (97%). It took 15 minutes to place the stent using transabdominal and/or endorectal sonography. After 3 months, 27 patients (87%) showed improved QSS. In patients with dysuria, maximum flow rate (MFR) and RU before treatment were 6.9 +/- 1.7 ml/sec and 112.3 +/- 61.8 ml, respectively. After treatment, they improved to 12.3 +/- 2.7 ml/sec and 12.7 +/- 6.7 ml, respectively. On the other hand, all patients who had urinary retention were able to urinate just after treatment, and MFR and RU were 12.9 +/- 3.6 ml/sec and 24.4 +/- 43.3 ml, respectively. Evaluation on the basis of improvement in MFR and reduction in RU showed that the stent was effective in 71% of total patients (22 out of 31 patients), 94% of the patients with urinary retention (17 out of 18 patients). The overall clinical efficacy of this stent was 68% (21 patients). There were no major complications such as urge incontinence and urinary tract infection during follow-up. Although proximal migration of the stent was observed in 6 patients, the stent could be taken out and replaced in 4 patients. From the above results, we conclude that the metallic stent is useful for the treatment of prostatism and urinary retention.

The effect of ciclosporin (CS) on cardiac output (CO) and regional blood flow was studied using the microsphere method in heminephrectomized rats with and without renal arterial clamping prior to the administration of CS. The effect of a calcium (Ca) channel blocker, verapamil, was also examined on CS-induced nephropathy. CS at a dose of 40 mg/kg per day was given orally using a gastric tube for 7 days. Verapamil was given in the drinking water for 7 days. Significant increases in blood urea nitrogen (BUN) and serum creatinine (sCr) with a significant decrease in renal inulin clearance (CIn) were noted after 7 days of CS administration in both intact and ischemic-kidney groups, indicating the development of CS-induced nephropathy. The ischemic-kidney group showed a significantly severe nephropathy as compared with the intact-kidney group. As for change in CO and regional blood flow, CS caused a significant decrease in CO, renal blood flow (RBF) and brain blood flow, while hepatic arterial blood flow and muscular blood flow significantly increased. The renal outer cortical blood flow decreased markedly while the inner cortical blood flow remained unchanged. Although verapamil slightly but significantly decreased mean arterial blood pressure in CS-treated rats, CO and its distribution did not change. BUN and sCr were not significantly ameliorated in the intact-kidney group. However, in the ischemic-kidney group, verapamil caused a significant improvement in RBF, ameliorating CS-induced elevation of BUN and sCr, and a decrease in CIn.(ABSTRACT TRUNCATED AT 250 WORDS)

腹膜透析療法施行中に掻痒感を訴え, その言動より, 原疾患である疥癬が陰蔽され, 皮膚寄生虫妄想症と診断したが, その後に疹部の検鏡より疥癬と診断し, 内服および外用治療により皮膚掻痒感および皮膚寄生虫妄想症も軽快した症例を経験したので報告したい. 治療法としては疥癬虫の虫体, 虫卵を検出し, 適切な薬物療法を施行するしかなく, 早期に診断を行うことが重要である.

近年, 透析液の細菌やエンドトキシンによる汚染の増強とhigh-flux膜の使用により, エンドトキシンのサブユニットやフラグメントが患者血液内に侵入している危険性が指摘されている. そこで著者は, avidin-biotinの強い親和性と抗原抗体反応の特異性を利用したenzyme-linked immunosorbent assay (ELISA) 法を用いて, 透析患者血液中のエンドトキシン抗体を測定した. まず最初に透析液中の細菌の分離・培養と同定, さらにこれより温フェノール法を用いてエンドトキシンの抽出を行った. さらにこの抽出したエンドトキシンとE. coli J-5のエンドトキシンが, ELISA法において交差反応を示すことを確認した. 次に加熱処理した菌体で免疫した家兎より得た標準エンドトキシン抗体について, immuno-blottingを行い抗体価の確認を行った. さらにこの標準エンドトキシン抗体を用いてELISA法による検量線を作製し, 抗体陽性の規準を設定した. 以上の予備実験に基づいて, 透析患者101名と健康対照者21名についてE. coli J-5のエンドトキシンを抗原として血液中のエンドトキシン抗体を測定した.結果は, 正常対照群では21名中4名 (19%), 従来の膜を使用した群では54名中14名 (26%) が抗体陽性であり, 一方high-flux膜使用患者では47名中28名 (60%) が抗体陽性であり, x2 (カイ自乗) 検定の結果, 前2者に比較し有意に高値を示した. この結果は, 特にhigh-flux膜使用患者において, 透析液中のエンドトキシンが血液内に侵入していることを強く示唆するものであった.

CAPD療法施行中にみられた食事性カイロペリトネウム合併患者に対し, 食事成分中の脂肪の摂取が排液混濁の誘因になり得るかを確かめるため長鎖中性脂肪 (LCT) および中鎖中性脂肪 (MCT) の経口負荷試験を行い, 排液混濁現象を再現しえた. 排液成分の分析結果より, 排液中のtriglycerides, β-lipoprotein, total lipids, chylomicronsの各対クレアチニン濃度比は, LCT経口摂取後著明に増加し, 排液は混濁した. MCT摂取後は排液混濁現象はみられず, triglycerides, total lipidsの対クレアチニン濃度比は低下した. 以上により食事性カイロペリトネウム合併患者では, LCTの経口摂取により腹膜透析液中へ各脂質の漏出の亢進が起こり, 混濁現象につながると考えられた.

腎移植後透析再導入した症例を対象にして, 維持透析患者としてみた現在の透析状況, 腎移植前の透析状態との比較, および患者の意識調査を行った.現在の透析状態では, 各種検査成績は概ね良好であった. しかし, erythropoietinを使用中の症例が, 9例中7例と多くみられた. また, 個々の症例でみると, 再導入直後で, ステロイド剤を投与中の症例には易感染性が認められた. 移植前と再導入後の比較においては, 血中尿素窒素 (BUN), 尿酸, 血清クレアチニン (Cr), 赤血球数, ヘマトクリット値 (Ht) 等は差がみられなかった.患者の意識調査の結果は, 移植の前後で, 移植に対する考え方の変化がみられた. すなわち, 移植前は移植の方が良いと考えていた人が多かったのに対し, 再導入後は透析の方が良いと思っている人の方が多くなっている. また, 再度の移植に対しては, 受けたいという人は, 9例中4例で, うち3例はもっと移植技術が改善したらという条件付であり, 移植に対する心理的抵抗が窺われた. 無条件で再移植を希望する1例は, 移植3年後に7-10日に1回の不定期透析で再導入し, 徐々に回数を増やした症例であり, 今後透析再導入の方法についての再検討も必要であると思われた.

1 x 10(5) cells of FAMFT-induced bladder cancer cell line (MBT-2) were injected into the right leg of the C3H/He mice. 10 days later, these animals with the same tumor size were divided into four groups. Group 1 is the control with no treatment. Group 2 underwent interleukin 2 (IL-2) treatment for 10 days since the 11th day after tumor inoculation. Group 3 received just one CPM injection on the 10th day. Group 4 had a combination therapy of CPM, followed by IL-2. Group 1 and 2 exhibited enlargement of tumor size, resulting in the death of all animals. Administration of CPM led to temporary disappearance of tumor, followed by local tumor recurrence in all cases. However, combined therapy with IL-2 showed complete remission of the tumors. Natural killer cell activity measured by the 51Cr release assay of the spleen cells using Yac-1 cells as target cells 20 days after tumor inoculation was found to be significantly higher in group 2 and 4, while lymphokine-activated killer cell activity of the spleen cells against P-815 cells showed no significant difference between the four groups.

We measured urinary N-acetyl-β- D -glucosaminidase (NAG) excretion before and after extracorporeal shock wave lithotripsy (ESWL) with a view to study the underlying factors which aggr

A multicenter cooperative study was designed to evaluate the efficacy and safety of FR-860 as an anticoagulant in hemodialysis. Sixty-five stable maintenance hemodialysis patients were enrolled into the study from fourteen institutions in Japan. 4 cases were excluded from the efficacy analysis because of protocol deviation (a violation of the concomitant drugs). The period of the study was fixed at two weeks. Dosage requirements were 15.0-20.0 anti-Xa units/kg as a bolus and 7.5-10.0 anti-Xa units/kg/hr for continuous hourly administration. Total dosage of FR-860 (F) was 2, 505±127 anti-Xa units compared to that of a conventional heparin (CH) dose of 6, 124 ±190 units. No difference in the residual blood in the extracorporeal circuit was observed between the F and CH groups. The hemostatic time at the puncture site after the completion of dialysis was significantly shortened in the F group (7.9±0.7 min) in comparison with the CH group (11.4±1.1 min; p

Patients with advanced malignant neoplasms have a variety of abnormal lymphocyte functions. We examined the PHA blastogenic response, interleukin-2 (IL-2) production and interferon-gamma (IFN-gamma) production of lymphocytes in 39 bladder cancer patients and 20 control subjects. Correlation between these parameters was also studied. IL-2 production was measured by 3H-thymidine-labelled CTLL-2 assay, and IFN-gamma production was measured by immunoradiometric assay using 2 mouse monoclonal antibodies. As a result, in high stage bladder cancer patients, the PHA blastogenic response, IL-2 production and IFN-gamma production were impaired. However, these parameters were not significantly different between low stage bladder cancer patients and control subjects. There was a significant correlation between the PHA blastogenic response and IL-2 production but no significant correlation between the PHA blastogenic response and IFN-gamma production.

Patients with advanced malignant neoplasms have a variety of abnormal lymphocyte and monocyte functions. We examined the PHA (phytohaemagglutinin) blastogenic response of lymphocytes and interleukin-1 (IL-1) production of monocytes in 40 bladder cancer patients and 16 control subjects. The correlation between the 2 parameters was also studied. The PHA blastogenic response was measured by the incorporation of 3H-thymidine into lymphocytes. IL-1 production was assayed by the murine thymocyte 3H-thymidine incorporation assay. As a result, the PHA blastogenic response and IL-1 production were significantly lower in the high stage bladder cancer patients compared to the control subjects and low stage patients. However, there was no significant correlation between the 2 parameters. Furthermore, with the addition of indomethacin, IL-1 production in the control subjects and low stage patients improved to the same degree, but it did not reach the control level in the high stage patients.

A 53-year old male with multiple pulmonary metastases from a renal cell carcinoma was treated with high dose recombinant interleukin-2 (rIL-2). rIL-2 was administered intravenously, and the dose was gradually increased to a subsequent daily dosage of 3 x 10(6) units for a total amount of 470 x 10(6) units. After 3 months, plain chest film and chest computerized tomography revealed a remarkable reduction in pulmonary metastases. There were no side effects except general fatigue and fever. Immunological studies revealed an increase in lymphocytes and enhancement of natural killer activity. These results suggested that rIL-2 is effective for pulmonary metastases from renal cell carcinoma.

In order to study the effects of high energy shock wave exposure on the kidney in extracorporeal shock wave lithotripsy (ESWL) using Dornier HM3, renal hemodynamics and renal function before and after ESWL were analyzed by 99mTc-DTPA renoscintigraphy. Various urinary enzyme activities (LDH, GOT, GPT, NAG, gamma-GTP) and low molecular protein concentrations (alpha 1-microglobulin, beta 2-microglobulin) before and after ESWL were also compared. In the early phase of the renoscinitgram obtained in the 1st min after injection of 99mTc-DTPA, the time required to reach maximum radioactivity was significantly prolonged after ESWL in both the affected and contralateral kidney. This indicated that renal blood flow decreased in both the affected and contralateral kidney immediately after ESWL. An analysis of the 30-min renoscintigram showed that urinary clearance was delayed in the affected kidney in spite of no overt obstruction due to stone fragments. As for urinary enzyme activities and low molecular protein concentrations, they were standardized by urinary creatinine concentration measured at the same time. Urinary LDH, GOT, GPT and NAG activities remarkably increased on the day of ESWL followed by a decrease close to pretreatment levels on the 4th day, though these levels were still significantly higher than pretreatment levels. Urinary gamma-GPT activity was significantly higher than the pretreatment level only on the day of ESWL. Urinary alpha 1-microglobulin and beta 2-microglobulin concentrations significantly increased on the day of ESWL and were still high on the 4th day.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to remove contaminated endotoxin from dialysis systems, we prepared and investigated two novel endotoxin adsorbing materials, Polymyxin-Sepharose (PxSeph) and polyporous polyethylene hollow fiber membrane (EHF). PxSeph was prepared by covalently immobilizing polymyxin B on Sepharose 4B beads by CNBr coupling method. It adsorbed various endotoxins with a high affinity constant and could effectively remove endotoxin from aqueous solution and human plasma. EHF also removed endotoxins from contaminated water by filtration through EHF modules, and its adsorption nature was demonstrated. Both PxSeph and EHF are stable in physiological conditions and proved to be useful adsorbents for removal of contaminated endotoxin from the hemodialysis systems.

An asynchronous case of triple primary malignant tumors of bladder, stomach and lung was reported. The patient was treated by total cystectomy and ileal conduit plasty for a bladder tumor in 1978 and subtotal gastrectomy and Billroth-I plasty for a gastric cancer in 1984. In 1987, a lung cancer was found and the biopsy revealed a small cell carcinoma. Though combined chemotherapy was done, he died from the lung cancer 2 years later. Fulfilling the Warren and Gate's criteria, this case may be said to be an asynchronous case of triple primary cancers.

The platelet adhesion on adhesive protein-coated surfaces was significantly reduced by the addition of the synthetic tetrapeptide, RGDS (Arg-Gly-Asp-Ser), which was identified as the common amino acid sequence of adhesive site of adhesive proteins. The inhibitory effect was also observed for leukocyte(WBC) in complement-inactivated serum. No significant effect was observed for WBC in complement-activated serum. These indicate that the RGDS ligand-receptor mechanism operates on adhesive protein-adsorbed surfaces for both cellular systems and that activated complement factor (C3b)-membrane receptor (CR3) interaction operates for WBC as the complement is activated.

CAPD療法施行時の排液混濁は, 腹膜炎以外の原因による場合は稀である. 我々は食事性に排液混濁をきたしたと考えられたCAPD患者を経験し, 排液成分の検討から以下の結果を得た. 1. 排液中の細胞成分は腹膜炎合併例と比べて少なく, 細菌は検出されなかった. 2. 食事性排液混濁時, 排液中の総蛋白, アルブミン, 総脂質, β-リポ蛋白, コレステロール濃度はCAPD患者の腹膜炎合併例と同程度に高値であり, 中性脂肪の濃度は腹膜炎合併例より有意に高値であった. 3. 食事性排液混濁例では, 排液が肉眼的に透明な平常時でも総脂質, リン脂質, コレステロール濃度は正常CAPD患者の排液中より高濃度であった. 4. 食事性排液混濁例では脂肪乳剤の静脈内投与では排液混濁はみられなかった. 以上から, 食事性排液混濁例では, 食事摂取によるリンパの増流に伴って腹腔内へ蛋白や脂質が漏出し排液混濁をきたしたと考えられた. これらの症例では排液の混濁は一過性で栄養状態に大きな変化はみられず, 特に治療は必要としなかった.

Red blood cell (RBC) aluminum (Al) in patients with renal failure on different treatments was studied. Nondialyzed renal failure patients had high levels of RBC Al, but low serum Al levels. However, their RBC Al levels were lower than those of patients on hemodialysis (HD) and continuous ambulatory peritoneal dialysis. In addition, HD patients who were not given Al-containing medications showed high levels of RBC Al, which suggests that there may be a source of Al other than medications. When desferrioxamine (DFO) was administered to these HD patients, the changes in RBC Al levels after DFO infusion were independent of those in serum Al levels and blood hemoglobin levels. In an in vitro study, RBC Al was removed using an ultrafiltration membrane, which showed that RBC Al exists in a bound form. These results suggest that Al accumulates in RBCs of renal failure patients independently of serum Al levels, and that the improvement of anemia by DFO may not be due to the direct removal of RBC Al.

慢性腎不全に伴う著明な貧血 (ヘモグロビン濃度6.22±0.11g/dl: mean±SE) を呈する血液透析患者25例に遺伝子組換えヒトエリスロポエチン (rEPO) を1回3,000U, 週3回8週間投与し臨床効果の評価を行った. また同時にrEPO投与前後においてリンパ球機能等免疫学的検査を実施し, 本剤の免疫系に及ぼす影響について検討した.この結果, 投与1週後より網赤血球数が有意に増加し, 2週後より赤血球数, ヘモグロビン濃度, ヘマトクリット値が有意に増加し, その後さらに増加を続けた. 投与8週後のヘモグロビン濃度は8.22±0.18g/dl (18例) となった. また貧血の改善に伴い自他覚症状の改善・消失, 心胸比の低下等をもたらし, 中止例を除外すると全例が有効であった.免疫学的パラメータに対する影響としては, PPDによる皮内反応試験で投与後, その面積 (長径×短径) が有意に増加し, 細胞性免疫能の改善が示唆された. またリンパ球サブセットOKT3の有意の上昇を認めたが, B-リンパ球数, 免疫グロブリンIgAは有意に低下した. 一方リンパ球幼若化反応およびIL2産生能等その他のパラメータでは変化は認められなかった. これらのことより, 本剤投与による免疫系に及ぼした作用は短期的なものと考えられるが, rEPOの免疫系に対する作用は特異的なものではないことが予想された.副作用は6例に認められたが, 投与を中止した症例は2例であった.

Extracorporeal shook wave lithotripsy (ESWL) was performed for the treatment of 1277 urolithiasis patients at Osaka City University Hospital from July, 1985 to December, 1988. A total of 1788 ESWL treatments were carried out using Dornier HM3 kidney lithotripter. 964 patients (75.5%) underwent only one ESWL treatment, while 313 patients (24.5%) more than two ESWL treatments. We retrospectively examined the factors for requiring more than two ESWL treatments. Not only stone number, size and location, but fragility were considered to be the main causes for requiring more than two ESWL treatments. According to component analysis of ureteral stones, which were hard and resistant to shock wave, calcium apatite content of these stones turned out to be high (p less than 0.001). As for fragility, the residual stones created by ESWL were more difficult to be disintegrated that the nontreated stones of the same size (p less than 0.05). "Fragility" of the stones before shock wave and residual stones after ESWL are considered to be a major problem in ESWL treatment of urinary stones to be solved in the years to come.

A multicenter study with recombinant human erythropoietin (rh-EPO) was carried out. Of 172 hemodialysis patients with anemia selected for the study from 20 hospitals and clinics, 77 were males and 95 females (mean age 53.9 years). A starting dose of 1,500 U of rh-EPO (Epoetin beta) was administered intravenously at the end of every dialysis session. If the efficacy was not acceptable, the dose was increased to 3,000 U. When the target hematocrit was achieved (30%), the total dose was decreased. The results of the study were excellent relative to those of other multicenter studies with regard to efficacy, safety, and changes in laboratory data. The incidence of hypertension was lower in our study compared with other reports because we used a low initial dose. The efficacy of rh-EPO therapy was determined earlier and more reliably by reticulocytes than by hematocrit or hemoglobin. Prompt iron supplement therapy is recommended with careful observation of serum iron and ferritin.

It is well known that red blood cell (RBC) and reticulocyte counts increase when anemic hemodialysis patients receive repeated administrations of recombinant human erythropoietin(rh-EPO). However, the early response of reticulocyte has not been reported precisely. In this study, reticulocyte counts and its fractions were observed in 8 maintenance hemodialysis patients after a single intravenous administration of 60 u/Kg of rh-EPO. The peripheral blood cells taken from the patients were stained with auramine 0, which bound to RNA and caused fluorescence. R-1000 (Sysmex, Kobe, Japan) analyzed the reticulocytes and classified the stained cells into three groups by the intensity of fluorescence. The number of highly fluorescent reticulocyte, which was young and large, increased and reached its highest level on day 4 after a single administration of rh-EPO. The reticulocyte counts paralleled these changes, but RBC counts did not change after administrations of rh-EPO. These data suggest that the observation of reticulocytes and its fractions in hemodialysis patients after a single administration of rh-EPO could tell us whether reticulocytes are responsive to rh-EPO or not, and this could be called as EPO test.

We investigated the effect of combination therapy with interleukin 2 (IL-2) and cyclophosphamide (CPM) in C3H/HeN mice implanted with mouse bladder tumor cells (MBT2). MBT2-bearing mice were treated with a single intraperitoneal injection of 120 mg/kg CPM on day 10 and/or subcutaneous administration of 5 x 10(4) units IL-2/day from day 11 to day 20. As a result, the growth of tumor in mice treated with IL-2 alone was slightly suppressed. On the other hand, regression was observed in all mice treated with CPM alone, although regrowth of tumor was seen in all of them. However, when IL-2 was administered with CPM, regrowth of tumor was completely suppressed. An immunologic study was done that showed cytotoxicity against YAC-1 and P815 in the spleen cells was suppressed in mice treated with CPM alone, but that both recovered to control levels when IL-2 was administered with CPM. Cytotoxicity against MBT2 in the spleen cells was most elevated in mice treated with both IL-2 and CPM. These findings suggested that clinical evaluation of combination therapy with IL-2 and CPM may be worthwhile.

A cytochrome P-450 (P-450), designated P-450HK omega, has been isolated and purified from human kidney microsomes to a specific content of 13 nmoles of P-450/mg of protein. P-450HK omega showed an apparent molecular weight of 52,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Absolute spectra of the oxidized form indicated that this P-450 was largely in the low-spin state and partly in the high-spin state. It catalyzed the omega- and (omega-1)-hydroxylation of fatty acids such as laurate, myristate, and palmitate, with no activity toward prostaglandin A1, benzphetamine, 7-ethoxycoumarin, or 7-ethoxyresorufin. The first 35 NH2-terminal amino acid sequence of P-450HK omega had about 70% homology with those of rabbit kidney fatty acid omega-hydroxylases of the P-450 IVA gene subfamily, P-450ka-1, P-450ka-2, and P-450kd, except for four undetermined residues. Moreover, Western blot and immuno-inhibition studies showed that P-450HK omega reacted with an antibody against the rabbit kidney fatty acid omega-hydroxylase. The results suggest that P-450HK omega is a member of the same P-450 gene family (IVA subfamily) as the rabbit enzymes. In addition, the terminal sequence of P-450HK omega also showed 54% homology with that of P-450k-2, a fatty acid omega-hydroxylase from rat kidney microsomes. To our knowledge, this is the first time that a P-450 specific for fatty acid omega-hydroxylase activity has been isolated to homogeneity from human tissues.

A 74-year-old male was urgently admitted to our hospital because of consciousness disturbance. Laboratory data showed remarkable hypercalcemia (7.8 mEq/L), hypophosphatemia, low % TRP, low intact PTH level, normal nephrogenic cyclic AMP and normal 1,25 (OH)2D level. Serum bone Gla protein, which was thought to express osteoblastic activity, was low. Serum tartarate resistant acid phosphatase and urinary excretion of hydroxyproline, which were thought to express osteoclastic activity, were high. CT scan showed an enlarged mass in the left renal pelvis, which was found to be a squamous cell carcinoma (SCC) by biopsy through percutaneous nephroscopy. Bone scintigram appeared normal. Therefore, we diagnosed it as renal pelvic SCC with humoral hypercalcemia of malignancy (HHM) and performed left nephrectomy. After nephrectomy, serum calcium returned to normal. But after a few weeks, lung metastasis appeared and serum calcium was reelevated. As to PTH related protein (PTHrP) which was thought to induce HHM, PTHrP content of the resected tumor measured by RIA assay was 13 pmol/g wet weight of tissue, which suggested that this tumor might have been producing PTHrP.

We reviewed our experience of the application of a new urethral stent (PROSTAKATH) for 8 patients with prostatic outflow obstruction from December 1989 to March 1990. 6 patients had required the Foley catheter for several months because of chronic urinary retention. 2 were dys-uric patients having a higher bladder residual urine volume. All were in a high risk group for surgery. 7 out of the 8 patients were treated successfully. The stent was not placed in one. All 7 patients in whom the urethral stent was placed voided freely after placement of the stent. Bladder residual urine was not detected by the ultrasound sonography except in one patient. The urethral stent used in this study was a spring-like spiral with an outside diameter of 21 Fr, it is made of gold-plated stainless steel. Under local anesthesia, it can be easily inserted using a 6-7 Fr. ureteral catheter as a guide wire under ultrasonic scanning guidance. During the follow-up period of 5-8 months, 1 patient had an episode of migration of the stent to the bladder 2 months later, which was removed endoscopically, and a new stent was placed. Side effects were observed in 2 patients; one complained of strong discomfort and the other suffered from urge incontinence. Both symptoms were ameliorated during the follow-up period. We conclude that the urethral stent is an effective device as a non-invasive treatment of prostatic outflow obstruction.

Hyperthermic treatment was performed in 31 patients with benign prostatic hypertrophy (BPH). Eight patients of them had a urethral catheter because of urinary retention. The prostate was heated trans-rectally to 43-45 degrees C. The treatment consisted of 10 sessions of 60 min. each. To evaluate this treatment, the following parameters were determined before, during and one week after the last hyperthermia session: subjective symptoms score, and residual urine volume, uroflowmetry and transrectal ultrasound of the prostate as objective data. Symptoms score improve in all patients. Of 8 patients with a catheter, the catheter could be removed from 4 patients. There was no significant change in prostate volume, but significant decreases of residual urine volume, and increases of maximum flow rate and mean flow rate were observed. No adverse reactions were seen. Judging from the above results, this treatment is considered to be useful for patients with BPH.

We measured the mineral content of urinary tract stones by dual photon absorptiometry, which is widely used for the analysis of bone mineral content, and compared the values of the stones by dual photon absorptiometry (DPA values) with the results of an in vitro fracture study as well as those of an in vivo extracorporeal shock wave lithotripsy treatment study. The results of a preliminary experiment showed that the DPA values of 20 urinary tract stones reflected actual stone mineral content. As a result of the in vitro fracture study, the DPA value calculated by volume of a struvite stone, which was the most easily disintegrated, was the lowest (0.53 g/cm3). The DPA values of calcium oxalate monohydrate and apatite stones, which poorly disintegrated, were the highest (0.98, 1.01 g/cm3). The DPA value of calcium oxalate dihydrate, which moderately disintegrated, was 0.86 g/cm3. By the in vivo extracorporeal shock wave lithotripsy treatment study, the total DPA values of stones measured before extracorporeal shock wave lithotripsy treatment in 12 patients were 0.73 +/- 0.34 g in successful cases and 1.92 +/- 0.43 g in unsuccessful cases with a significant difference between the two (p less than 0.05). These results showed that the measurement of stone mineral content by dual photon absorptiometry was useful in predicting the fragility of stones against shock waves before performing extracorporeal shock wave lithotripsy treatment for patients with urinary tract stones.

We investigated the effect of combination therapy with interleukin 2 (IL-2) and Bacillus Calmette-Guerin (BCG) on C3H/HeN mice implanted with mouse bladder tumor cells (MBT2). MBT2-bearing mice were treated with a local injection of BCG into the tumor at a dose of 1 mg/day for a total of 3 times and/or a 10-day continuous subcutaneous infusion of 5 x 10(4) units IL-2/day from day 11 to day 20. As a result, the growth of the tumor in mice treated with IL-2 alone was slightly suppressed, while tumor growth was hardly suppressed in mice treated with BCG alone. However, when IL-2 was administered with BCG, tumor growth was strongly suppressed and mean survival time was prolonged. Natural killer cell activity in the spleen cells was most elevated in mice treated with IL-2 and BCG, while lymphokine-activated killer cell activity was not observed in all groups. Lymphocyte subset analysis showed that there was little change in the ratio of Lyt2-positive lymphocytes or that of L3T4-positive lymphocytes. These findings suggested that clinical evaluation of combination therapy with IL-2 and BCG may be worthwhile.

Authors studied the effects of several biological response modifiers (BRMs) on bladder carcinoma. On carcinogenesis in BBN-induced bladder carcinoma rats, Schizophyllan (SPG) showed inhibition of body weight loss and thymus weight loss. Bladder weight increase was also inhibited. SPG prolonged cancer-bearing survival time, and postponed malignant changes of bladder mucosa. On thymocytes of SPG-treated cancer-bearing rats, rosette-forming thymocytes increased. In clinical study, SPG, OK-432, ubenimex and kampo medicine were used as BRMs. As a result, the number of suppressor-inducer T cells increased, and in cytotoxic T cells a slow fall was observed. On helper-inducer T cells, a slow rise and decrease were noticed in the SPG group, and the reverse tendency was seen in the ubenimex and OK-432 group.

Antitumor effect of recombinant human tumor necrosis factor alpha (TNF) alone or in combination with various anticancer chemotherapeutic agents was tested using an in vitro antiproliferative assay on four human renal carcinoma cell lines (VMRC-RCW, VMRC-RCZ, Caki-1 and A-498). When the dose-dependent effect of TNF was studied, none of the four cell lines showed a 50% or more inhibition even at a concentration of 10,000 U/ml of TNF, so that the susceptibility to TNF was low. An enhancing effect of TNF on the cytotoxic effect of almost all the chemotherapeutic agents tested was observed against VMRC-RCZ and A-498. Against VMRC-RCW and Caki-1, the combination of TNF with the chemotherapeutic agents did not result in an enhancing effect. Mitomycin C showed an enhancing effect of TNF against all four cell lines. These results suggested that the combined treatment of TNF with chemotherapeutic agents may have favorable results in clinical trials.

A clinical study was made on 108 male patients who underwent cystectomy. The posterior urethra and partial anterior urethra were removed in 47 cases, half of the perpendicular urethra was removed in 13 cases and the anterior urethra up to the fossa navicularis was removed in 48 cases. Out of 60 cases without urethrectomy, urethral recurrence was observed in 13 cases (21.7%), while no recurrence was observed in the cases treated with urethrectomy. The average period of time from cystectomy to urethral recurrence was 24.7 months (11-39 months). Urethral cancer of such early stages as pIa and pIb were found in 3 and 6 cases, respectively. Stage pT2 was found in 4 cases. Grade 1 cancer was found in 3 cases, grade 2, in 5 cases, and 3 in 5 cases. The proximal end of the perpendicular urethra was found to be the most frequent site for recurrence with 11 cases exhibiting recurrence at this location and 2 cases at the mid-portion of the perpendicular urethra. Many cases exhibited multiple recurrence of tumor of visually grayish, velvety and non-papillary type which was histologically all transitional cell carcinoma. Bladder tumor with higher grade tended to cause urethral cancer recurrence with higher grade. Bladder tumors at multiple locations from the trigone to the lateral and posterior walls tended to cause recurrence in the urethra (p less than 0.05). Of all the cases, 10 cases underwent urethrectomy and 2 cases penectomy. 12 cases received chemotherapy and 5 cases radiation therapy as postoperative adjuvant treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

SUMMARY Cellular immunity of thymus lymphocytes in uraemic rats was studied. Severe and moderate uraemia was induced in rats, and sham-operated and normal rats were used as the controls. As a result, the response of thymus lymphocytes to concanavalin A (Con A) significantly decreased in severely uraemic rats, but did not change in moderately uraemic rats. However, when the thymus lymphocytes were pretreated with thymosin fraction 5, the response to Con A was ameliorated in severely uraemic rats. There was a significant correlation between the effect of thymosin fraction 5 on Con A response and Con A response of thymus lymphocytes. In addition, serum from severe uraemic rats suppressed the response of normal thymus lymphocytes to Con A. These results indicate that severe uraemia may cause an impairment in maturation of thymus lymphocytes, which can be improved by thymosin fraction 5 in vitro.

The metabolism of arachidonic acid, lauric acid and prostaglandin A1 by rat hepatic microsomes and multiple forms of cytochrome P-450 purified from rat hepatic microsomes was studied. Arachidonic acid was hydroxylated by hepatic microsomes of male rats by omega- and (omega-1)-hydroxylation. Phenobarbital treatment of rats decreased the hydroxylation activity slightly, but 3-methylcholanthrene treatment increased the hydroxylation activity 2-fold. However, lauric acid and prostaglandin A1 omega- and omega-1)-hydroxylation activities decreased after treatment with phenobarbital and 3-methylcholanthrene. Arachidonic acid and lauric acid were metabolized with similar ratios of omega- and (omega-1)-hydroxylation, but prostaglandin A1 was efficiently metabolized at the omega-position by hepatic microsomes of untreated male rats. In a reconstituted system with purified cytochromes P-450, P450 UT-1, UT-2 (P-450h), MC-1 (P-450d) and MC-5 (P-450c) effectively hydroxylated arachidonic acid at both the omega- and (omega-1)-position. P450 UT-8 hydroxylated arachidonic acid only at the omega-position. P450 DM (P-450j) hydroxylated arachidonic acid at the (omega-1)-position efficiently. Lauric acid was also hydroxylated by P450 UT-1, UT-2, PB-1, PB-2, MC-1, IF-3 (P-450a) and DM, at the (omega - 1)-position only. Only P450 UT-8 could hydroxylate laruic acid at the omega-position. Prostaglandin A1 was efficiently and specifically metabolized by P450 UT-8 with omega-hydroxylation. P450 UT-2 and PB-1 could hydroxylate prostaglandin A1 by (omega-1)-hydroxylation, but with low activity.

Endotoxins are often seen in dialysate. They are derived from Gram-negative bacteria especially Pseudomonas, E. coli and Serratia. Endotoxins are large-molecular-weight substances with an average molecular weight of 108. These large units can be divided into subunits down to a molecular weight of 10,000 which are thought to pass through dialyzer membranes. To investigate this, endotoxin antibody levels were measured in two groups of patients on chronic regular hemodialysis, a low-flux group using cellulosic membrane dialyzers (cuprophanR and cuproammonium rayon (CAR) and a high-flux group using synthetic polymer membrane dialyzers (PMMA, EVAL). Using an ELISA based on standard endotoxin antibodies the percentages of patients in the low flux group with endotoxin antibodies were 26.9% with Cuprophan and 25% with CAR, not significantly different from a normal control group. In the PMMA and EVAL groups, it was 53.6% and 68.4% respectively. Back filtration of dialysate into blood is understood as the main reason for the entry of endotoxin in patients treated with high-flux dialyzers

The effects of extracorporeal shock-wave (SW) exposure on the kidney were investigated in dogs using a Dornier kidney lithotriptor HM3. The SW was generated by spark discharge at 20 KV and was focused on the lower part of either kidney. Before and after the exposure of 500 and 1000 shots of SW, the renal blood flow of the affected and contralateral kidney was measured by the microsphere method. The blood flow of the affected kidney decreased, but was comparable to that of the contralateral kidney immediately after the 1000 shots of SW. Renal scintigraphy using 99mTc-DTPA was performed before the exposure of SW, and 30 minutes, 1 week, 2 weeks and 4 weeks after the exposure. The renograms were evaluated by the following parameters: Tmax (time required to reach maximum radioactivity), RAmax ratio (maximum radioactivity of the affected kidney/that of the contralateral kidney) and T1/2 (the half-life of elimination). Tmax was significantly prolonged for the affected kidney 30 minutes after the exposure, while that for the contralateral kidney was shortened. The RAmax ratio was decreased 1 week after the exposure. T1/2 was significantly prolonged 30 minutes after the exposure, which was observed till 2 weeks later. The scintigraphy also showed a slight enlargement of affected site. The histological study showed a hemorrhage in the peritubular space, indicating rupture of the peritubular capillaries. In conclusion, the main effect of SW exposure on the kidney was the rupture of the peritubular capillaries, resulting in temporary and reversible deterioration of renal function.

We retrospectively reviewed 32 patients who underwent parathyroidectomy at our hospital for the last fourteen years. 1) Clinical appearance of primary hyperparathyroidism was in younger age in women. 2) In previous history or at the time of PTX, 9 patients had malignant tumors including 6 thyroid cancers, 36% of the patients with out bone related symptoms had a remarkable decrease in bone mineral content. 3) After PTX, none of patients had recurrent urolithiasis and bone mineral content of all patients was significantly increased in a short time. In addition, upper GI complaints were improved, or hypertension was partially normalized. However, renal insufficiency remained unchanged. 4) In preoperative localization study, Ultrasound sonography (US) demonstrated the best accuracy rate of 88% when only one gland was involved. US was able to detect multiple gland involvement only in 20% of 5 cases. 5) Hypercalciuria was recognized as one of the risk factors of stone formation in patients with primary hyperparathyroidism.

The correlations between the degree of atherosclerosis, plasma prostaglandins (PGs) and plasma lipids were examined in maintenance hemodialyzed patients with and without diabetes mellitus. The degree of atherosclerosis was evaluated by pulse wave velocity (PWV) of the aorta. Plasma PGs were radioimmunoassayed. PWV was significantly higher in hemodialyzed patients compared to sex- and age-matched healthy controls. PWV correlated with the plasma thromboxane A2 (TXB2) level and TXB2/6-keto-PGF1 alpha ratio in hemodialyzed patients, without a significant difference between the diabetic and nondiabetic groups. The plasma lipid profile was type IV of the WHO classification in both the diabetic and nondiabetic groups, and PWV did not correlate with these lipid abnormalities. Though not significantly, the decreases in plasma PGE2 and 6-keto-PGF1 alpha and the increase in TXB2 correlated with the degree of type IV hyperlipidemia. The results suggest that plasma PG abnormalities might correlate with the degree of atherosclerosis in hemodialyzed patients.