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Although both cinacalcet and etelcalcetide are calcimimetics that directly inhibit parathyroid hormone (PTH) secretion by activating the calcium (Ca)-sensing receptor (CaSR), their binding sites are different. We report a first case of a hemodialysis (HD) patient with secondary hyperparathyroidism (SHPT), in whom cinacalcet, but not etelcalcetide, could reduce serum intact PTH (i-PTH) levels. A HD patient received total parathyroidectomy (PTx) with auto-transplantation 16 years earlier. Due to SHPT relapse, cinacalcet was started at 7 years after PTx. His i-PTH levels had been controlled with both 75–100 mg of cinacalcet and 4.5 μg/week of calcitriol for a year before switching from cinacalcet to etelcalcetide. At 1 month following the switch, his serum i-PTH level increased to 716 pg/mL. The dose of etelcalcetide was gradually increased and finally reached the maximal dose of 45 mg/week. Because even the maximal dose of etelcalcetide for > 4 months did not reduce his serum i-PTH levels to

Dysregulation in total body copper causes severe complications and excess copper can be toxic. Divalent metal transporter 1, duodenal cytochrome B, and copper transporter ATPase7A are included in the many intestinal genes transactivated by HlF-α. On July X, 2022 an 80-year-old female patient on peritoneal dialysis was prescribed roxadustat 100 mg, because darbepoetin was unable to increase hemoglobin level effectively. On the same day, icodextrin 1 L was initiated to mitigate edema. Laboratory data showed hemoglobin 9.1 g/dL, transferrin saturation 77%, copper 123 μg/dL, and iron 170 μg/dL before changing to roxadustat. The patient visited us 6 days after the change because of the appetite loss. Transferrin saturation and serum copper and iron levels increased to 90%, 170 and 203 μg/dL, respectively, which were decreased or normalized after discontinuing roxadustat and icodextrin, suggesting that even short-term roxadustat administration can influence copper levels as well as iron levels. Excess copper and iron levels during roxadustat treatment do not immediately equate with toxicity, but indicate a physiological compensation or transient imbalance of metabolism especially in patients treated with ferric citrate. Further investigation for the hypoxia-inducible factor-prolyl hydroxylase inhibitors effects on iron and copper metabolisms is needed. Determining the short-term effect of roxadustat on serum copper and iron in only this case is impossible. Therefore, further accumulation of similar cases is necessary to clarify the short-term effects of roxadustat on serum copper and iron.

We present a rare case of IgA nephropathy in a patient who developed atypical hemolytic uremic syndrome (aHUS) associated with a complement factor H (CFH) gene mutation, and who was successfully treated with eculizmab. A 76-year-old man was admitted as the patients had thrombotic microangiopathies findings. The patient was treated with plasma exchange, hemodialysis and methylprednisolone. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 level was not decreased. Light microscopy findings were consistent with hemolytic uremic syndrome and immunofluorescence analysis revealed IgA and C3 were detected. Genetic analysis revealed that mutation of p.Arg1215Gln in CFH was identified. The diagnosis of aHUS was confirmed and eculizmab therapy was currently effective for 5 months.

A man in his fifties with diabetes had a past history of myocardial infarction and ventricular septal perforation. He underwent hemodialysis about a year ago and was taking amiodarone. He presented with sores and purpura on the lower limbs.-Skin biopsy showed immunofluorescence-negative leukocytoclastic vasculitis. Skin lesions were treated with ointments, which ameliorated the symptoms to some extent, but ulceration relapsed and deteriorated in both number and size. Calciphylaxis was suspected, and a second skin biopsy was performed. No calcium detection,on the arteries was observed, but leukocytoclastic vasculitis was seen. Antineutrophil cytoplasmic antibody-related vasculitis, cryoglobulin vasculitis, or anti-phospholipid syndrome were ruled out by negative findings for autoantibodies. Although he was treated with 30 mg prednisolone, his systemic condition deteriorated, and he died of disseminated intravascular coagulation. Autopsy findings showed no vasculitis in the lung, kidney or intestine, and perimyocardial patch infection was observed.Although calciphylaxis was clinically suspected, his condition was diagnosed finally as cutaneous small-vessel vasculitis.

Lanthanum carbonate is one of the new phosphate binders used for the treatment of hyperphosphatemia in patients with chronic kidney disease. It is poorly absorbed from the gastrointestinal tract, forms insoluble complexes within the lumen, and prevents the absorption of dietary phosphate. A 63-year-old female with a 7-year history of peritoneal dialysis, who was treated with lanthanum carbonate for four years, underwent endoscopic submucosal dissection for intramucosal gastric cancer. Resected specimens showed massive accumulation of macrophages containing fine, granular, brown material in the lamina propria. This was confirmed as lanthanum deposition by scanning electron microscopy with energy dispersive x-ray spectroscopy. Although lanthanum may be poorly absorbed, increased tissue accumulation of lanthanum, particularly in the liver and bone, has been reported in animals with chronic kidney disease. This report indicates enhanced gastrointestinal absorption of lanthanum in some patients or conditions, although its clinical significance awaits further studies.

Many studies have reported poor vital prognosis in hepatitis C virus (HCV)-infected dialysis patients. The rate of HCV-infected dialysis patients in Japan is as high as 9.8%, and antiviral therapy is believed to be important for improving vital prognosis. We conducted a multicenter study to examine the administration method for pegylated interferon α-2a (PEG-IFNα-2a) monotherapy in HCV-infected dialysis. We studied 56 patients: 14 with low viral loads (HCV RNA < 5.0 log IU/mL) were treated with 90 μg PEG-IFNα-2a weekly, 42 with high viral loads (HCV RNA ≥ 5.0 log IU/mL) were treated with 135 μg PEG-IFNα-2a weekly. We examined the sustained virological response (SVR), factors affecting the SVR, and treatment safety. The overall SVR rate was 39% (22/56); that for genotype 1, genotype 2, low viral loads, and high viral loads was 29%, 67%, 93%, and 21%, respectively. From receiver operating characteristic (ROC) analysis, the HCV RNA cutoff values likely to achieve SVR for genotypes 1 and 2 were

Aim: SBR759 is a calcium-free, polymeric, iron(III)-based oral phosphate binder, in development for the treatment of hyperphosphatemia. The efficacy and safety of SBR759 was compared with sevelamer hydrochloride in chronic kidney dialysis patients on hemodialysis. Methods: Japanese and Taiwanese hyperphosphatemic patients who were on hemodialysis (n = 203) received starting doses of 3.0 or 4.5 g/day SBR759 or 2.4 or 4.8 g/day sevelamer-hydrochloride (HCl) based on baseline phosphate levels. Daily doses were up-titrated every 2 weeks to reach the Kidney Disease Outcomes Quality Initiative (K/DOQI) recommended target serum phosphate concentration ≤1.7 mmol/L. The key endpoints were proportion of patients achieving target serum phosphate and the safety at week 12. Results: SBR759 showed a superior phosphate response at week 12 compared with sevelamer-HCl (83% vs 54% patients; P

A LPD seems to increase the Pi uptake by vesicles of the BBM of the renal cortex. This study was done to find if there was adaptation to a LPD in the BBM vesicles from the superficial or deep cortex in SHR, with WKY rats as control. The fractional excretion of Pi of SHR on the LPD was higher than that of WKY rats (p less than 0.01). The Vmax of Pi uptake in BBM vesicles from superficial cortex of WKY rats on the LPD was greater (p less than 0.05) than in such rats on a diet with a normal level of phosphate. Thus, the adaptation to a LPD was normal in WKY rats. However, in BBM vesicles from the superficial cortex of SHR kidneys, the difference in this Vmax depending on diet was insignificant. In BBM vesicles of the deep cortex of SHR kidneys, this Vmax was higher (p less than 0.01) on the LPD. The apparent Km was not significantly different in different groups or parts of the renal cortex. These results suggest that BBM vesicles in the superficial cortex of SHR kidneys did not adapt to the LPD. The less adaptation in SHR in vivo indicates that there may be a defect in Pi transport in BBM vesicles of the superficial cortex of SHR kidneys.

連続的携行式腹膜透析(以下PD)は自己管理を主体とした在宅の透析療法である。今回バッグ交換困難な手指変形を有する59歳女性の関節リウマチ患者に対して，SMAP法を用いたPD導入を行ない自己管理可能となった事例を経験した。事例は著明な手指関節変形を有する末期腎不全患者でUV-Fツインバッグシステムを用いた自己管理によるPDを希望した。バッグ交換は1日4回行ない1回のバッグ交換には数種類のクランプ操作を必要とするが，手指関節変形により通常のバッグ交換操作は不可能であった。既存のデバイスの活用と新たなデバイスを作製することにより自己管理によるバッグ交換が可能となった。SMAP法はPD開始までに時間的猶予があるため自己管理方法の検討と操作習得の練習期間の確保が可能であり，手指関節変形を有する関節リウマチ患者に対してSMAP法でのPD導入は有用であった。

Fertilization is an important event leading to fruit set. To determine when to isolate cDNAs for genes involved in fruit set in eggplant, pollen tube growth was observed under a fluorescence microscope. When tips of pollen tubes reached the ovules at the basal side of ovary within 48 hr after pollination, the cDNAs, preferentially expressed after/during fertilization, were isolated by suppression subtractive hybridization between cDNAs from pollinated and unpollinated fruits. Using cDNA macroarrays, 384 cDNA clones of the subtracted cDNA library were differentially screened by the probes of the cDNAs from pollinated or unpollinated fruit 2 days after anthesis. By Northern blot analyses, mRNAs corresponding to 11 cDNA clones were more concentrated in pollinated fruit than in unpollinated one. mRNAs corresponding to three cDNA clones, 1D05, 5D09 and 5E08 were specifically expressed in both pollinated and 4-chlorophenoxyacetic acid (4-CPA)-treated fruit 2 to 4 days after anthesis. The above 2 genes, except 1D05, were also expressed in N-(2-chloro-4-pyridyl)-N'-phenylurea (CPPU)-treated fruit 4 days after anthesis. These mRNAs were barely detected in the later stages of fruit development. 1D05 and 5D09 mRNAs were not found in leaves and stems, whereas 5E08 mRNA was detected at a very low level in young leaves and stems, but not in mature leaves. The deduced amino acid sequence of 1D05, 5D09 and 5E08 showed a similarity with cytochrome P450, hypothetical protein, and unknown protein, respectively. Expression patterns and putative function of genes corresponding to these cDNA clones, especially 1D05, lead us to speculate that they are possibly involved in the initiation of fruit set.

Many studies have reported poor vital prognosis in hepatitis C virus (HCV)-infected dialysis patients. The rate of HCV-infected dialysis patients in Japan is as high as 9.8%, and antiviral therapy is believed to be important for improving vital prognosis. We conducted a multicenter study to examine the administration method for pegylated interferon α-2a (PEG-IFNα-2a) monotherapy in HCV-infected dialysis. We studied 56 patients: 14 with low viral loads (HCV RNA5.0 log IU/mL) were treated with 90 μg PEG-IFNα-2a weekly, 42 with high viral loads (HCV RNA ≥ 5.0 log IU/mL) were treated with 135 μg PEG-IFNα-2a weekly. We examined the sustained virological response (SVR), factors affecting the SVR, and treatment safety. The overall SVR rate was 39% (22/56); that for genotype 1, genotype 2, low viral loads, and high viral loads was 29%, 67%, 93%, and 21%, respectively. From receiver operating characteristic (ROC) analysis, the HCV RNA cutoff values likely to achieve SVR for genotypes 1 and 2 were5.7 log IU/mL (SVR rate: 64% 9/14) and6.5 log IU/mL (SVR rate: 88% 7/8), respectively. If there was HCV RNA negativation at 4 weeks (rapid virological response), the SVR rate was 94% (16/17), whereas it was 6% (1/16) if there was HCV RNA positivity at 24 weeks. The rate of treatment discontinuation from adverse events or aggravated complications was 25% (14/56). High SVR rates can potentially be achieved with PEG-IFN monotherapy by identifying the target patients, based on virus type and viral load before initiating treatment and by modifying therapy during treatment according to responsiveness.

Lanthanum carbonate is one of the new phosphate binders used for the treatment of hyperphosphatemia in patients with chronic kidney disease. It is poorly absorbed from the gastrointestinal tract, forms insoluble complexes within the lumen, and prevents the absorption of dietary phosphate. A 63-year-old female with a 7-year history of peritoneal dialysis, who was treated with lanthanum carbonate for four years, underwent endoscopic submucosal dissection for intramucosal gastric cancer. Resected specimens showed massive accumulation of macrophages containing fine, granular, brown material in the lamina propria. This was confirmed as lanthanum deposition by scanning electron microscopy with energy dispersive x-ray spectroscopy. Although lanthanum may be poorly absorbed, increased tissue accumulation of lanthanum, particularly in the liver and bone, has been reported in animals with chronic kidney disease. This report indicates enhanced gastrointestinal absorption of lanthanum in some patients or conditions, although its clinical significance awaits further studies.

Summary To isolate genes preferentially expressed at early stages of fruits in eggplant (Solanum melongena L., var. Senryo No. 2), subtractive hybridization was used on cDNAs from pollinated fruits and poly(A)+RNA from unpollinated fruits at 3 days after anthesis. In this way, 8 cDNA clones were isolated from a cDNA library constructed from pollinated fruits at 3 days after anthesis, and were designated EEF13, 20, 22, 26, 38, 45, 48, and 53, respectively. Expression patterns of EEF genes in pollinated fruit were similar to those in 4-chlorophenoxyacetic acid (4-CPA)-treated fruit by Northern blot analyses. During development of pollinated and 4-CPA-treated fruit, the transcription patterns of EEF genes were classified into three types. EEF20 and EEF38 genes whose products are highly similar to histones, were expressed abundantly on the day of anthesis and continued to be expressed during the early stages of fruit development (Type 1). Transcription of five genes was at higher level from 2 to 4 days after anthesis (Type 2), and the encoded products of EEF22 and EEF26, showed high similarity with calreticulin and polyphenol oxidase, respectively. Another gene, EEF48 (Type 3), showed high and continuous expression from 2 to 20 days after anthesis and was almost restricted to fruits. Deduced amino acid sequence of EEF48 showed high similarity with a cell wall protein.

72歳の男性。20歳時肺結核, 24歳時に腰椎カリエス, 回盲部結核の既往あり。2ヵ月前より右胸肋部に圧痛を伴う腫脹が出現し, 初診時には鶏卵大の皮下腫瘤を形成していた。ツ反中等度陽性, 膿瘍穿刺液からガフキー1号, 結核菌培養陽性, 胸部X線像及びCT所見より胸囲結核と診断。INH 300mg/日, RFP 450mg/日, EB 750mg/日の内服を6ヵ月間行ったところ膿瘍は著明に縮小した。胸囲結核の報告は全科で年間数例と比較的稀であるが, 1975年以降1998年までの皮膚科·形成外科領域からの報告14例につき統計的観察を行った。また, 胸壁の結核性膿瘍は胸腔内病巣との連続性により分類も治療も異なるため, 他科との連携も考慮し, 「胸囲結核」の病名で統一した方が良いのではないかと考えた。

気管支樹に沿って気管支内腔を進展する比較的稀な肺腫瘍を3例経験した. 症例1は56歳男性. 職場検診で左肺上葉の異常影を指摘され来院. 気管支鏡で上区支を閉塞するポリープ状の腫瘍を認め, 左上葉切除を施行. 腫瘍は左B3の気管支内腔を圧排性に発育しており, 定型気管支カルチノイドであった. 症例2は51歳男性. 人間ドックで右肺S2の無気肺様陰影を指摘され来院.内視鏡で右B2bを閉塞するポリープ状の腫瘍を認め, 右上葉切除を行った. 右B2b内腔を鋳型に充填するように発育した腫瘍を認め, 腎癌の転移であった. 症例3は62歳男性. 血痰を主訴に来院. 胸部写真で左上区に手指状の陰影を認めた. 気管支鏡では上区支を閉塞するポリープ状の腫瘍を認めた. 切除肺では上区支からB1+2, B3の気管支内腔を発育する腫瘍で, 癌肉腫であった. 気管支樹に沿って気管支内腔を進展する肺腫瘍の種類は多く, 転移性肺腫瘍の可能性もあるため日常診療上注意が必要である.

The patient was an 80-year-old man who had an advanced non-small-cell lung cancer with complications such as COPD and dementia. Vinorelbine 20 mg/m(2) was administered intravenously from May 19, 2008. He received 2 doses weekly and rested for a week. He restarted this therapy from July 3, because his dementia was progressing. His therapy was later discontinued, so he was followed up with outpatient observation. During observation, the disease did not progress. In June, 2010, atelectasis and pleural effusion lesions disappeared, according to CT. He was alive in August, 2010.

SBR759 is a calcium-free, polymeric, iron(III)-based oral phosphate binder, in development for the treatment of hyperphosphatemia. The efficacy and safety of SBR759 was compared with sevelamer hydrochloride in chronic kidney dialysis patients on hemodialysis.Japanese and Taiwanese hyperphosphatemic patients who were on hemodialysis (n = 203) received starting doses of 3.0 or 4.5 g/day SBR759 or 2.4 or 4.8 g/day sevelamer-hydrochloride (HCl) based on baseline phosphate levels. Daily doses were up-titrated every 2 weeks to reach the Kidney Disease Outcomes Quality Initiative (K/DOQI) recommended target serum phosphate concentration ≤1.7 mmol/L. The key endpoints were proportion of patients achieving target serum phosphate and the safety at week 12.SBR759 showed a superior phosphate response at week 12 compared with sevelamer-HCl (83% vs 54% patients; P0.0001). Mean serum calcium concentrations were unaffected by either treatment. Similar incidences of adverse events and serious adverse events were seen with SBR759 and sevelamer-HCl (90.3% vs 94.1% and 5.2% vs 4.4%, respectively), but overall discontinuation rates were lower with SBR759 (11.9% vs 20.6%). The proportion of patients experiencing gastrointestinal disorders was lower in SBR759 versus sevelamer-HCl. No treatment-related serious adverse events were reported.SBR759 showed superior phosphate control with a favorable tolerability profile compared to sevelamer-HCl in hemodialysis patients.

著者らは1967年から75年までに肺癌222例中5例 (2.3%) の肺・胃重複癌を偶然経験した. これより肺・胃重複癌はもっと多いのではないかと考え, 以後の肺癌症例に胃内視鏡検査を積極的に施行してきた.その結果,(1) 1981年から85年までの肺癌358例中同時性6例 (1.7%), 異時性12例 (3.4%), 計18例 (5.0%), 1986年から90年までの肺癌352例中同時性10例 (2.8%), 異時性17例 (4.8%), 計27例 (7.7%) の肺・胃重複癌を経験した. これより肺癌に胃癌が高率に重複することと肺・胃重複癌の増加傾向が示唆された. (2) 最近5年間の肺・胃同時性重複癌の頻度は, 逐年胃内視鏡検診における初年度の胃癌発見率の3倍以上もあり非常に高率であった. (3) 最近の5年間では, 肺癌手術例, 非手術例, 肺癌全体の三者間で胃癌との重複頻度に大きな差を認めなかった. 以上から, 肺癌症例, 特に治癒の期待できる肺癌術前症例には積極的に胃内視鏡検査を施行することが大変重要であると思われた.

転移性肺腫瘍28例を対象とし, その胸部X線像と気管支内視鏡所見を比較検討した. X線像から肺野結節型, 肺野浸潤型, リンパ管症型, 無気肺型, 肺門リンパ節腫脹型の5型に, 内視鏡所見から粘膜主体型, 粘膜下主体型, 壁外型の3型に分けた. 肺野結節型の最大腫瘍径の小さい例に異常無しが, 大きい例に壁外型が多く, 肺野結節型以外は全例に異常所見を認めた. 内視鏡検査下の腫瘍細胞陽性例は28例中19例, 72%と高率であった.

持続性低血圧透析患者の臨床的特徴と看護について検討するために, 透析前収縮期血圧100mmHg以下の低血圧者10名A群と正常血圧者11名B群とについて比較した.両群の透析歴はA群11.3±6年, B群10.4±4年であり, 透析前平均血圧はA群69±7mmHg, B群では99.6±8mmHgであった.A群は合併症に2次性副甲状腺機能亢進症および手根管症候群を多数認めたが, 両群において副甲状腺ホルモン, β2-マイクログロブリン値には有意差を認めなかった, また貧血との相関関係も認められなかった. 心胸比, 体重増加率, 摂取栄養量においても両群間に差を認めなかった. A群の10例中8例においては, 循環血液量減少予防または低血圧の治療が必要であった. 血圧下降症状出現時の血圧値は各々の症例でほぼ一定であり, 透析中の血圧維持レベルを決めることにより下降防止が可能であった. また水分, 塩分摂取量の管理により適正体重を維持することが重要と考えられた.

We utilized e-Learning using example data from special support education stored in a web database as e-Learning contents. The e-Learning was conducted with teachers from various educational institutes: from primary schools to universities, in addition to special support schools. Through a collective problem solving process we were able to collect in a single web database disparate knowledge from a variety of teachers.

The patient was a 45-year-old man, weighing 50 kg, with Bartter's syndrome, who had been treated with indomethacin, a prostaglandin synthetase inhibitor, and potassium supplement for the past 10 years. He was under adequate control with this regimen, having normal serum potassium levels and slight metabolic alkalosis. He presented with sudden onset of a severe headache and was admitted to our hospital for emergency craniotomy for subarachnoid hemorrhage. Preoperative blood gas analysis revealed a pH of 7.495, Pao2 of 86.5 mmHg, Pac% of 40.8 mmHg, HCO3 of 31.4 mEq.1-1, and BE of 8.4 mEq.1-1. Serum Na +, K +, and C1levels were 139mEq.1 -~, 2.7mEq.1-1 and 95 mEq.1 -~, respectively. Plasma aldosterone and plasma renin activity were 250 pg.ml -a (10.9-62.7) and 17.0 ng.ml-~.hr -1 (0.5-2.0), respectively. Blood pressure was 140/80 mmHg and pulse rate was 110 beats per min. Oral medication was discontinued. He was pre

Size-exclusion chromatography with controlled pore glass (CPG) was used in the further purification of renal brush border membrane vesicles (BBMV) isolated by the Ca precipitation method. The BBMV obtained had an almost spherical shape and their average diameter was about 95 nm in isotonic solution. The specific activities of alkaline phosphate and leucine aminopeptidase in the BBMV preparation were increased 18- and 17-fold, respectively, over those in the crude homogenate. The uptake of d -glucose by the purified BBMV in the presence of a sodium gradient reached 8.53 nmol/mg protein at 20 s. These results indicate that CPG chromatography is a suitable procedure by which to obtain purified renal BBMV of homogenous size and with high specific marker enzyme activity for use in the study of membrane transport.

Acute parathyroidectomy (PTX) is associated with an increase in phosphate (Pi) uptake by renal cortical brush border membrane (BBM). We investigated the response to acute and chronic PTX in the renal BBM. Kinetic studies of Pi uptake were carried out in 5 groups of rats as follows; control, acute PTX (1h), chronic PTX (20h and 72h), and chronic PTX (20h) treated with 10 IU of parathyroid hormone (PTH). The Na+-dependent Pi transport in BBMV was significantly increased 1h after PTX. However, this increase was not retained 72h after PTX. The Vmax of Pi uptake was significantly increased and the apparent Km was significantly decreased in acute PTX. In chronic PTX, the Vmax and the apparent Km returned to control leyels. The treatment with PTH increased the apparent Km and decreased Vmax significantly 20h after PTX. These results suggested an adaptive response to hyperphosphatemia in chronic PTX rats.

We investigated the recognition of late potentials in patients with and without organic heart diseases and spontaneous ventricular arrhythmias. None of the normal subjects had late potentials and patients with ventricular arrhythmias but no organic heart diseases, also had no late potentials as well as patients with idiopathic ventricular tachycardias. Late potentials in patients with idiopathic cardiomyopathy were noted more frequently in the dilated type than in the hypertrophic type, especially in those with high grades of ventricular arrhythmias. Patients with old myocardial infarctions had a higher rate of late potentials recognition in cases of sudden death or ventricular tachycardias. On the other hand, we observed lower rates in patients during early stage of acute myocardial infarction in spite of the evidence of a higher rate of ventricular electrical instability. There was no association between ejection fractions, wall motion scores and late potentials. However, a higher recognition of late potentials was found in patients with inferior or posterior myocardial infarction and ventricular aneurysm. We concluded that the late potential must be evaluated in each of the different groups of organic heart diseases in order to estimate the clinical value of ventricular arrhythmias.

We evaluated long-term combined vasodilator therapy (hydralazine or ecarazine + isosorbide dinitrate) in 29 patients with chronic congestive heart failure resistant to the optimal conventional therapy. There were 24 men and 5 women, aged 28 to 76 years (mean 52 y/o). The etiology of heart failure was congestive cardiomyopathy in 24 patients, ischemic cardiomyopathy in 4 patients and advanced mitral regurgitation due to calcified mitral annulus in 1 patient. There were 21 patients in NYHA class III and 8 patients in NYHA class IV. All patients continued their previous therapeutic regimen during the period of this study. Hemodynamic measurements were performed with a triple lumen flow-directed balloon-tipped catheter in 20 patients to evaluate the effects of vasodilator therapy. In the rest of 9 patients, heart rate, blood pressure, chest X-ray examination for heart size (CTR) and M-mode echocardiograms for ejection fraction (EF) were monitored. The hemodynamic responses to the combined vasodilator therapy in 20 patients showed significant decreases in afterload and preload concomitant with an increase in cardiac output. The noninvasive evaluation of combined vasodilator therapy in 9 patients resulted in significant improvement in CTR and EF. We also noted a significant improvement in their symptoms of 29 patients. Side effects and drug toxicity were uncommon during vasodilator therapy. It is concluded that the combined vasodilator therapy is most useful adjunctive therapy in the management of severe refractory heart failure. Moreover, long-term nonparenteral vasodilators can be administered even at outpatient clinic without hemodynamic monitoring.