Therapeutic Research

目的：過活動膀胱患者に対しコハク酸ソリフェナシンを投与し，新規投与例と他の抗コリン薬からの切替投与例に分けて，その臨床効果を比較検討した。対象と方法：コハク酸ソリフェナシンで 4週間以上治療された 76 例（新規 32 例，切替 44例）の過活動膀胱患者を対象に，治療前後で過活動膀胱症状質問票（OABSS）と QOL スコアおよび残尿量を比較検討した。結果：OABSS は新規例で全項目が改善し，切替例でも切迫性尿失禁以外の全項目が改善した。男女別の検討では，女性は新規例と切替例の全項目が改善したが，男性は新規例と切替例の OABSS 合計点，新規例の切迫性尿失禁，切替例の尿意切迫感が改善したが，ほかの項目は改善傾向はあったが有意ではなかった。QOL スコアは新規例および切替例ともに改善した。残尿量に有意な変化はなかった。有害事象は新規例で 7 例（21.9％），切替例で 14 例（31.8％）に認められた。結論：コハク酸ソリフェナシンは，過活動膀胱患者の症状改善に有用と考えられた。

骨粗鬆症性楔状圧迫骨折による姿勢変化に伴って起こる疾患のなかで逆流性食道炎（reflux esophagitis：RE）は高齢者に比較的多く確認されている。その治療について，H2 receptorantagonist（H2RA）の初期投与に加えエルカトニンの投与により，骨粗鬆症性における疼痛緩和効果と，RE によるびらんも消失することをすでに報告した。われわれはこれらの結果を参考にして，慢性腰痛，心窩部痛または胸やけを訴え，前屈姿勢を呈する 10 症例の骨粗鬆症性楔状圧迫骨折患者において，エルカトニンの単剤投与と理学療法による治療を検討した。全例において，心窩部痛，胸やけは治療開始 1 週間で緩解し，慢性腰痛は 2 週間で改善した。RE については種々の原因が報告されているが，高齢者では骨粗鬆症による楔状圧迫骨折に伴って前屈姿勢となり，その結果，腹腔内圧が増加し，食道裂孔ヘルニア（hiatal hernia：HH）から RE を発症することが考えられる。これらの疾患は従来の腰痛治療に使用される NSAIDsや骨粗鬆症に対するビスフォスホネート製剤投与により惹起される胃腸障害が，患者の症状をさらに増悪させ，難治性となる可能性もある。cost−benefit を考慮しても，エルカトニンの投与と理学療法の併用療法は RE を伴う骨粗鬆症性楔状圧迫骨折患者の有効な治療方法と考えられた。

Objective：The efficacy of combination therapy of low−dose trichlormethiazide with conventional−dose furosemide in patients with refractory heart failure was assessed. Methods：Six patients with refractory heart failure and renal dysfunction（serum creatinine：1.7±0.8 mg／dL）under standard therapy received 40 mg furosemide daily for the first week, and additional trichlormethiazide 1 mg daily for the second week. Patients were monitored closely during hospitalization at least for these 2 weeks and then as outpatients for 6 months. Urine was collected for 24 hours during hospitalization to determine urinary volume, sodium excretion, creatinine clearance and fractional excretion of sodium. Blood laboratory examination, chest X−ray and echocardiographic measurements were performed before and 6 months after the combination therapy. Results：Combination of low−dose trichlormethiazide with conventional−dose furosemide significantly increased both urinary volume（1365±392 to 1875±402 mL／day, p＜0.05）and urinary sodium excretion（132±41 to 274±87 mmol／gCre, p＜0.01）, compared with the monotherapy of furosemide. Combination therapy also significantly enhanced fractional excretion of sodium from 1.7±0.9 to 3.7±2.5％（p＜0.05）compared with the monotherapy of furosemide, without significant changes of creatinine clearance（34±24 to 30±20mL／min）. After 6 months of combination therapy as outpatients, NYHA functional class（2.7±0.8 to 2.2±0.4, p＝0.08）and plasma BNP level（743±404 to 381±341 pg／mL, p＝0.06）tended to be improved, while clinically important hypokalemia, hyponatremia or hospitalization was not observed. Conclusions：Combination of low−dose trichlormethiazide with conventional−dose furosemide promotes natriuresis and improves conditions in patients with refractory heart failure and renal dysfunction.

Objective：This study compared renal actions of carperitide, furosemide and their combination in patients with symptomatic heart failure.Methods：Thirty nine patients were randomly allocated to 3 groups. The first group consisted of 14 patients receiving 20 mg of intravenous furosemide, the second group 10 patients receiving 25 ng／kg／min of continuous infusion of carperitide, and the third group 15 patients receiving their combined administration with the same doses of carperitide and furosemide. Urinary sodium excretion, creatinine clearance and fractional excretion of sodium for 24 hours were assessed. Results：Continuous infusion of carperitide did not cause a significant change of urinary sodium excretion（148±80 versus 139±83 mmol／gCre, p＞0.1）with a significant decrease in urine volume（903±269 versus 1266±396 mL／day, p＜0.05）, compared with intravenous furosemide. Combined administration significantly increased urine volume （1318±384 mL／day）compared with continuous infusion of carperitide alone（p＜0.05）but not with intravenous furosemide alone（p＞0.1）, and significantly promoted urinary sodium excretion（266±132 mmol／gCre）compared with either carperitide or furosemide alone（p＜0.05, respectively）. Combined administration also significantly enhanced fractional excretion of sodium from 1.3±0.7 and 1.3±0.7 to 2.1±0.9％ compared with administration of carperitide alone and furosemide alone（p＜0.05, respectively）. These effects were evident at all levels of creatinine clearance（94 to 8 with a mean of 40±22 mL／min）.Conclusions：Therefore, the combination therapy of carperitide and furosemide promotes natriuresis during treatment for heart failure in patients with various renal functions.

The mechanism by which the expenditure of oxygen to walk per unit distance at an intermediate speed is minimized, by definition optimal walking, was investigated to characterize optimal walking in humans with variations in individual walking speeds. Oxygen uptake and step rate（SR）were measured among 7 young male subjects walking at an increasing speed from 16.7 to 131.7 m min−1 with 5 m min−1 increments every 1 min on a level treadmill. Measurements of leg length（L）were also made and step length（SL）was calculated by dividing walking speed by SR. The hip joint angle（θ）was calculated as a function of both L and SL such that θ＝2sin−［1 SL（／ 2L）］ deduced from a mathematical geometrically similar model of pendulum−like legs. The minimum oxygen cost to walk per unit distance for each subject was observed over a wide range of speeds from 60 to 100 m min−1.However, the oxygen cost of walking for all the subjects was minimized during a step cycle through a hip−joint angle of about 46 deg in the astride position, regardless of L. The stifflegged model demonstrated that the pathway of the trunk during optimal walking with a swing leg angle of 46 deg was approximately maintained at an even level by the counteracting effects of the leg decline and the heel rise. These results suggest that the minimum oxygen cost of transport during optimal walking was achieved by the mechanism underlying the maximum interchange between the gravitational−potential and kinetic energy for the body with an even level of the trunk that reduces extra muscular work needed against internal and external resistance, as well as against gravity.