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【目 的】 紹介状なしで受診する患者の現状を調査し, 患者の大学病院に対するニーズを把握する. 【対象と方法】 1年間に群馬大学医学部附属病院を紹介状なしで初診した患者数を調査. また, 総合診療部を受診した患者について専門科受診希望の有無, 具体的な受診希望専門科, 受診前の状況等を問診表から調査した. 【結 果】 紹介状なしで大学病院を受診した患者の11.6％は専門診療科受診希望を表明せず. 専門科希望者1,104人の内, 具体的に専門科がわからない患者は64.9％であった. 総合診療部初診者2,051人の内, 48.9％は同症状で他医療機関の受診歴があった. 【結 語】 患者はかならずしも専門科希望でなくとも大学病院を受診する. 一方, 専門科希望で受診しても具体的な専門科がわからないことは多い. 受診する前に同じ症状で他の医療施設を受診している患者が相当数おり, 患者からみると紹介機能は必ずしも十分に働いていない.

Impaired lipid metabolism is an important health problem in postmenopausal women with insufficient estrogens, because dyslipidemia is a risk factor for development of atherosclerosis and the incidence of cardiovascular disease markedly increases after menopause. Pueraria mirifica (PM), a Thai herb, has been noticed as a source of phytoestrogens, estrogen-mimicking plant compounds. However, the clinical effects of PM on lipid metabolism and the underlying molecular mechanisms remain undetermined. Therefore, we examined the effects of PM on serum lipid parameters in a randomized, double-blind, placebo-controlled clinical trial. Nineteen postmenopausal women were randomly assigned to receive oral administration of PM powder or placebo. After 2 months of treatment, the PM group showed a significant increase in serum concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-1 (34% and 40%, respectively), and a significant decrease in low-density lipoprotein (LDL) cholesterol and apo B (17% and 9%, respectively), compared with baseline measurements. Moreover, significant decreases were observed in the ratios of LDL cholesterol to HDL cholesterol (37%) and apo B to apo A-1 (35%). Next, we determined the effects of PM phytoestrogens on the activation of estrogen receptor (ER)-mediated transactivation by transient expression assays of a reporter gene in cultured cells. Among PM phytoestrogens, miroestrol and coumestrol enhanced both ERalpha- and ERbeta-mediated transactivation, whereas other phytoestrogens, including daidzein and genistein, preferentially enhanced ERbeta-mediated transactivation. In conclusion, PM has a beneficial effect on lipid metabolism in postmenopausal women, which may result from the activation of gene transcription through selective binding of phytoestrogens to ERalpha and ERbeta.

Objective The objective of this study was to compare doctor-patient communications in clinical consultations via telemedicine technology to doctor-patient communications in face-to-face clinical consultations. Method Five doctors who had been practicing internal med icine for 8t o 18 years, and twenty patients were enrolled in this study; neither doctors nor patients had previous experience of telemedicine. The patients received both a telemedicine consultation and a face-to-face consultation. Three measures - video observation, medical record volume, and participants’ satisfaction - were used for the assessment. Results It was found that the time spent on the telemedicine consultation was substantially longer than the time spent on the face-to-face consultation. No statistically significant differences were found in the number of either closed or open-ended questions asked by doctors between both types of consultation. Empathyutterances, praise-utterances, and facilitation-utterances were, however, seen less in the telemedicine consultations than in the face-to-face consultations. The volume of the medical records was statistically smaller in the telemedicine consultations than in the face-to-face consultations. Patients were satisfied with the telemedicine consultation, but doctors were dissatisfied with it and felt hampered by the communication barriers. Conclusions This study suggests that new training programs are needed for doctors to develop improved communication skills and the ability to express empathy in telemedicine consultations.

Background Osteoporosis and endothelial dysfunction have been associated with atherosclerosis. The correlation between brachial arterial endothelial function and lumbar spine bone mineral density (BMD) in postmenopausal women will be investigated. Methods and Results The endothelial function in 85 postmenopausal women, including 28 women with normal spinal BMD, 27 women with osteopenia, and 30 women with osteoporosis were studied. Brachial arterial flow-mediated vasodilatation (FMD) after reactive hyperemia was assessed by ultrasonography. The BMD at the lumbar spine (lumbar 2 to 4 vertebrae) was measured by dual-energy X-ray absorptiometry. Age, years since menopause, and FMD were significantly greater in the osteoporosis group than in the normal BMD group (p

Objectives Hypertension and estrogens are both prothrombotic. We used the microchannel method to investigate whether hormone replacement therapy (HRT) with conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) affects blood flow through the microchannels in hypertensive postmenopausal women being treated with antihypertensive drugs and in normotensive postmenopausal women. Methods Sixty-two consecutive postmenopausal women were randomly assigned to a hypertensive HRT group ( n = 16), hypertensive control group ( n = 15), normotensive HRT group ( n = 16) and normotensive control group ( n = 15). Each HRT group received CEE 0.625 mg plus MPA 2.5 mg daily orally for 12 months. Both hypertensive groups were being treated with antihypertensive drugs before the study. Microvascular blood flow was assessed on the basis of blood passage time, the time required for 100 μl of whole blood to pass through a cylinder, was determined before and 12 months after the start of HRT by the microchannel method (micro channel array flow analyzer). Results CEE plus MPA therapy did not change blood passage time in any of the groups. Microscopic observation showed that the whole blood passed smoothly through the microchannels in every group. Conclusions CEE plus MPA therapy may not impair blood flow through the microchannels in hypertensive postmenopausal women receiving antihypertensive drugs or in normotensive postmenopausal women. However, administration of CEE plus MPA to postmenopausal women with hypertension warrants caution against the occurrence of thromboembolic events.

【背景・目的】 看護学生は, 短期間で幅広い専門的知識を習得しなければならず, 高い学習意欲が要求されている. 我々は実習に先立つ講義において, 試験出題部分をあらかじめ講義資料の中で明示することが, 看護学生の学習意欲に及ぼす影響を検討した. 【対象と方法】 2004年度入学の看護学科一年次の学生 (男性12名, 女性72名). 試験に出題する部分を講義資料のなかで明示し, 学習意欲について, Visual analogue scaleで定量化した. 【結 果】 試験出題部分を予告した今回の講義の方が, 予告をしない他の講義よりVisual Analogue Scaleを用いて定量した学習意欲が有意に高かった. 自由筆記の分析からは, 「実習で学習内容を実践するのが楽しみになった」など, 学習意欲に関する項目が抽出された. 【結 論】 試験出題部分の講義資料内での予告は, 看護学生の学習意欲を向上させる一手段として有用であると考えられた.

【目 的】 動脈硬化症では, 脈波速度 (PWV) は増大し, 高感度CRP (hsCRP) やインターロイキン6 (IL-6) 等の炎症マーカーも高値を示す. 本研究では, 健康な地域住民において, PWVと炎症マーカーとの関連性を検討した. 【対象と方法】 対象は, 2003年8月から2004年1月までに群馬県吉岡町の健康相談に参加した地域住民109名であった. 動脈硬化の進展度を反映する上腕―足首PWV (baPWV) を計測するとともに, hsCRP, IL-6の血中濃度を測定し, baPWVと炎症マーカーの相関関係の有無を検討した. 【結 果】 baPWVは, hsCRP及びIL-6との間に有意な正の相関を示した. また, baPWVが13.7 m/sec以上の参加者ではIL-6が有意に高値であった. 【結 語】 健常人においても血管壁の炎症が潜在的な動脈硬化を惹起する可能性が示唆された. IL-6は初期段階の動脈硬化の予知に有用と思われた.

【背景と目的】 今回我々は, 経皮エストラジオール及び経口結合型エストロゲンが閉経後女性の脈波伝播速度, 皮膚弾力性及び骨密度に与える影響を比較検討した. 【対象と方法】 経皮エストラジオールを投与する群 (経皮群, 26例), 経口結合型エストロゲンを投与する群 (経口群, 17例), 希望によりHRTを行わない群 (コントロール群, 23例) の3群に分類し, 12ヵ月間行った. 試験開始前及び12カ月後に脈波伝播速度, 皮膚弾力性, 骨密度を測定した. 【結 果】 経口群及びコントロール群の脈波伝播速度は変化しなかったが, 経皮群の脈波伝播速度は有意に減少した (p＜0.05). 皮膚弾力性及び骨密度は, 経皮群 (p＜0.05, p＜0.01), 経口群 (p＜0.01, p＜0.01) ともにそれぞれ有意に増加したが, コントロール群では皮膚弾力性は変化せず, 逆に骨密度は有意に減少した (p＜0.01). 【結 語】 閉経後女性に対する経皮エストラジオールは経口結合型エストロゲンよりも心血管系に有益であり, 両治療とも皮膚の若返りや骨の強化に有効であると思われる.

Introduction: Hypertension and estrogens are both prothrombotic. We investigated the effect of 12-month hormone replacement theraphy (HRT) on hemostatic factors in mild to moderate essential hypertensive and normotensive postmenopausal women.Materials and methods: A group of 38 hypertensive and 32 normotensive postmenopausal women received HRT (conjugated equine estogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg daily) for 12 months, and 19 hypertensive and 15 normotensive postmenopausal women did not. All hypertensive women had been administered antihypetensive drugs before the start of the study. Hemostatic factors, i.e., fibrogen, antithrombin, protein C activity, plasminogen activator inhibitor-1, D-dimer, and plasminogen, were measured in plasma of all women before, and 6 and 12 months after the start of study.Result: The antithrombin levels of the hypertensive and normotensive women who received HRT had decreased at 6 (both P

To identify risk factors of urinary tract infection (UTI) in geriatric patients, the levels of serum uric acid, serum creatinine, and urine pH were compared between pyuria-positive and -negative patients in a geriatric ward. The level of serum uric acid was higher with lower urine pH level in the pyuria-negative patients than in positive patients. The level of serum creatinine was relatively higher in the pyuria-negative patients than in the positive patients. Even after matching for serum creatinine, serum uric acid was significantly higher in the pyuria-negative male patients. The results in the present study proposed an interesting hypothesis about backgrounds for UTI in geriatric patients. The relationships among serum uric acid, serum creatinine, urine pH, and pyuria should be examined further in a larger population and in experimental studies.

Background/Aim: The cardiovascular effects of postmenopausal hormone replacement are controversially discussed. We investigated the effects of 12 months of treatment with conjugated equine estrogen and medroxyprogesterone acetate on lipoprotein(a) [Lp(a)] and other lipoproteins in Japanese postmenopausal women (PMW) with and without dyslipidemia. Methods: Forty-three normolipidemic and 17 dyslipidemic PMW [total cholesterol (TC) ≧220 mg/dl or triglyceride (TG) ≧150 mg/dl] received conjugated equine estrogen (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) daily for 12 months, and the results were compared with those of 26 normolipidemic and 14 dyslipidemic subjects declining this treatment as controls. The fasting serum levels of Lp(a), TC, TG, high-density lipoprotein cholesterol, low- density lipoprotein cholesterol, apolipoprotein (Apo) AI, Apo AII, Apo B, Apo CII, and Apo E were measured in each subject at baseline and 12 months after this treatment initiation. Results: The treatment decreased Lp(a) similarly in normolipidemic and dyslipidemic PMW and decreased TC, low-density lipoprotein cholesterol, Apo CII, and Apo E and increased high-density lipoprotein cholesterol, Apo AI, and Apo AII in both groups. The therapy also significantly increased TG in normolipidemic but not dyslipidemic subjects. In controls, the levels of Lp(a) and other lipoproteins were unaltered. Conclusions: In PMW with or without dyslipidemia, improvement in Lp(a) and other lipoproteins may represent cardiovascular benefits of hormone replacement therapy. However, an elevation of the TG levels seen with the therapy warrants caution, especially in PMW without dyslipidemia.

【背景・目的】他病院でがん診断または治療を受けているにもかかわらず, 主治医の診療情報提供書を持たず, 自らすすんで大学病院を受診した患者の動機を明らかにした.【対象と方法】総合診療部を受診したがん患者52名から受診動機を聴取し, 内容分析を行った.【結果】患者の大学病院受診の動機は, 1) 現在の診断・治療の妥当性についての相談 (30.8%), 2) 新たな症状が出現したことへの不安 (30.8%), 3) 病状が改善しないことによる不安 (19.2%), 4) 高度医療への希望・期待 (9.6%), 5) 経過観察を希望 (9.6%) の5カテゴリーにまとめられた.【結語】患者は, 現在の治療・病状に対する不安, 新たな症状が出現したことによる不安が多く, 大学病院に対し最先端の高度医療提供への期待があることが明らかになった.

Intravascular lymphomatosis (IVL) is a rare systemic disease characterized by proliferation of lymphoid cells within the lumina of small arteries, veins, and capillaries. Diagnosis requires skin, liver, lung, bone marrow, renal, meningeal, or brain vessel biopsy but is often made only when the illness has progressed or post mortem because early involvement of organs was not evident. We report a case of IVL presenting as fever of unknown origin (FUO). In this case, gallium scintigraphy and computed tomography (CT) showed no evidence of malignancy, whereas (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased FDG uptake in the sternum, left and right vertebra, humerus, femur, and especially ilium. The diagnosis was made on iliac bone marrow biopsy examination. FDG-PET was useful for the detection of spread of disease in a patient with IVL suffering from FUO.

Atherectomy specimens offer an opportunity to study the biology of coronary artery lesions. We cultured smooth muscle cells (SMCs) from specimens obtained from 24 patients with coronary restenosis after angioplasty to study the relationship between activity of SMCs (in vitro outgrowth) and the time course of restenosis. We also examined expression of a Kruppel-like zinc-finger transcription factor 5 (KLF; also known as BTEB2 and IKLF), which is markedly induced in activated SMCs, in the same specimens. SMC outgrowth was observed in 9 of 24 specimens (37.5%). Restenosis occurred sooner (p < 0.01) in patients whose specimens showed outgrowth compared to those whose specimens showed no outgrowth. Immunostaining for KLF5 was more common in specimens with outgrowth (89 vs. 20%, p < 0.01). These data suggest that the number of activated SMCs in lesions may determine in vitro outgrowth and also affect the time to restenosis.

【背景と目的】群馬大学保健学科検査技術科学専攻4年次学生が総合診療部実習で何を感じ取ったのかを, 2000年度学生と2001年度学生を比較しながら, 論述式の実習レポートから質的手法を用いて分析した.【対象と方法】2000年度学生38名, 2001年度学生38名が対象である.学生1名に外来初診患者1例を割当て, 総合診療部医師による問診と診察を見学させた.「初診患者の今後の検査計画」, 「今後の医療に対して検査技師が貢献すべき点」, 「将来に向けての抱負・夢」の3つの課題について学生が論述した実習レポート76名分を総合診療部の教員3名が独立して分析後, 結果を統合して学生の意識を評価した.【結果】「検査計画」の総合得点は両年度間で差がなかったが, 2001年度の女子は男子を+0.9点上回った(p

When the monocyte infiltrates a tissue, adhesion to the extracellular matrix provides structural anchors, and the cell may be deformed through these attachments. To test the hypothesis that human monocytes/macrophages are mechanically responsive, we studied the effects of small cyclic mechanical deformations on cultured human monocytes/macrophages. When monocytes/macrophages were subjected to 4% strain at 1 Hz for 24 hours, neither matrix metalloproteinase (MMP)-1 nor MMP-3 was induced; however, in the presence of phorbol myristate acetate, strain augmented MMP-1 expression by 5.1 ± 0.7-fold (P < 0.05) and MMP-3 expression by 1.6 ± 0.1-fold (P < 0.05). In contrast, MMP-9 expression was not changed by mechanical strain in the presence or absence of phorbol myristate acetate. Deformation rapidly induced the immediate early response genes c-fos and c-jun. In addition, mechanical deformation induced the transcription factor PU.1, an ets family member that is essential in monocyte differentiation, as well as mRNA for the M-CSF receptor. These studies demonstrate that human monocytes/macrophages respond to mechanical deformation with selective augmentation of MMPs, induction of immediate early genes, and induction of the M-CSF receptor. In addition to enhancing the proteolytic activity of macrophages within repairing tissues, cellular deformation within tissues may play a role in monocyte differentiation.

The authors report a rare case of a malignant hemangioendothelioma (MH) originating in the pericardium. In this case, a metastatic skin lesion was found first, and subsequently the existence of a primary cardiac lesion was confirmed. Generally, primary cardiac tumors grow slowly, and the prognosis of MH is relatively good. In this case, however, the patient died suddenly during the creation of a pericardial window for drainage. An autopsy showed that the MH originated from a pericardial lesion in the right atrium.

The degree of involvement of the renin-angiotensin system in endothelial dysfunction was investigated by using a one-kidney, one-clip (1K,1C) model of renal hypertension. Male Wistar rats received 0.02% enalapril, 0.02% losartan, or tap water for 1 day before and for 48 h after the induction of renal artery stenosis or sham operation. The aorta of 1K,1C rats showed increased contraction and decreased relaxation responses produced by norepinephrine and acetylcholine, respectively, vs. control responses. Exposure to 10−5 mol/l N G-monomethyl-l-arginine acetate augmented the contractile responses to norepinephrine to a greater extent in control rats than in the 1K,1C rats. The increased contraction and decreased relaxation responses to these agonists in the 1K,1C rats were normalized by enalapril or losartan. The addition of HOE-140 to the bath did not alter these normalized responses. Results suggest that angiotensin II causes endothelial dysfunction and reduces nitric oxide levels in 1K,1C rats. Such endothelial dysfunction enhanced the norepinephrine-induced contraction during the early-stage hypertension in 1K,1C rats.

本研究では, WAB失語症検査ほか当院で実施している検査指標を用い, 言語訓練中に血圧が上昇する患者と上昇しない患者の比較をした. [対象] 対象は, 沢渡温泉病院にて言語療法を受けている脳卒中患者21例である. [方法] 患者を訓練室の隣室にて30分間安静にさせ, ついで, 言語療法室に入室させ, 約30分間の訓練を開始した.その後再び患者を隣室に戻し安静にさせた.この間, 患者の上腕に血圧測定装置を装着し, 血圧・脈拍を2分間隔で測定した. [結果] WAB失語症検査の得点率を比較すると, 言語課題では流暢性を除いた全課題で血圧上昇群の得点率が非上昇群より有意に高くなった.コミュニケーションレベル評価においては, 理解系で上昇群のほうが軽症であったが, 表出系では両群の間に差がなかった. [考察] 口頭言語の流暢性にかかわらず, コミュニケーション理解能力が保たれている患者ほど言語訓練中に血圧上昇を呈しやすいことが考えられた.

Three cases of patients with cardiac myxoma who had attacks of acute myocardial infarc tion are presented. Cineangiographic study showed normal coronary arteries. Immunohistochemical and serologic examination revealed that both interleukin-6 and interleukin-8 were secreted in cardiac myxoma. The authors discuss the relation between these cytokines and myocardial infarction with normal coronary arteries.

The effect of interleukin-6 (IL-6) secreted by a human atrial myxoma in vitro was investigated in C3H female mice with acute viral myocarditis. A culture medium containing IL-6 (100 ng/ml) and IL-8 (250 ng/ml), was prepared; viral myocarditis was induced by exposure to the encephalomyocarditis virus. Mice were assigned to four groups: 1) intraperitoneal (i.p.) injection of supernatant with IL-6 and IL-8 (0.2 ml/mice) given simultaneously with virus, 500 pfu for 4 days (Group 1); 2) i.p. injection of supernatant with IL-6 starting on Day 4 for 4 days in the same manner (Group 2); 3) i.p. injection of culture medium simultaneously with the virus (Group 3); and 4) i.p. injection of PBS in the same manner (Group 4). Uninfected control mice were administered medium only (Group 5) or supernatant with IL-6 and IL-8 (Group 6) for 4 days without virus. The survival rate on Day 14 in Group 1 was 90% significantly (p < 0.01) prolonged. The ratio of heart weight-to-day weight in the Group 1 was significantly (p < 0.01) lower. Histopathological examination revealed that cardiac necrosis and cellular infiltration in Group 1 was reduced compared with Group 3. Moreover, the radio of spleen weight/body weight in Group 1 was significantly (p < 0.01) higher than that of Group 3 and of Group 4. To confirm the effect of IL-6 or IL-8, mice were treated with recombinant IL-6 to IL-8 simultaneously with virus for 4 days. IL-6 treated mice survived significantly compared with IL-8 treated mice and untreated mice. The viral titer on day 4 of IL-6 treated mice was significantly lower than IL-8 treated or untreated mice. Thus, IL-6 derived from human myxoma improved the survival of murime viral myocarditis and reduced myocardial necrosis when the myxoma-derived IL-6 was administered simultaneously with the virus, due to eliciting cellular immunity in the spleen.

Nitric oxide (NO) is present in the breath exhaled from healthy humans. The location and subtype of the NO synthase responsible for the expired NO are unknown. As dexamethasone inhibits the induction of NO synthase, we evaluated the effect of administering dexamethasone (4 mg/day for 2 days) on the amount of NO exhaled by eight healthy men. The amount of NO showed a significant linear correlation with the duration of exhalation, allowing the rate of NO release to be calculated. The rate of NO release was 0.047 +/- 0.023 nmol/s before drug administration. There was no significant change in the release rate at the end of the 2-day administration of drug or at 5 days after cessation. Serum concentrations of interferon-gamma and interleukin-1 beta were unaffected by the administration of dexamethasone. These results suggest that the NO released from the human airway under normal conditions is not generated by the action of inducible NO synthase.

Background Although the origin of cardiac myxomas is still controversial, the 2 main hypotheses are that the tumor cells originate either from multipotential mesenchymal cells or from endocardial neural tissue. Methods and Results The production of various cytokines in 2 human cardiac myxoma cell lines was examined by enzyme-linked immunosorbent assay. After 7 days of culture, extremely high concentrations of interleukin-6 were detected in the culture media from both myxoma cell lines. Increased production of CXC chemokines, interleukin-8 and growth-related oncogene-α, were observed in both myxoma cell lines. Endothelin (ET)-1 and its precursor, big ET-1, were detected in the culture media from both myxoma cell lines. The production of both ET-1 and big ET-1 by myxoma cells was higher than by human umbilical vein endothelial cells. Similar to endothelial cells, myxoma cells did not produce stem cell factor, granulocyte colony-stimulating factor, hepatocyte growth factor, or ET-3. Conclusions The similarity of the cytokine production pattern between cardiac myxoma cells and endothelial cells supports the hypothesis that the tumor cells originate from mesenchymal cells capable of endothelial differentiation. Overproduction of CXC chemokines may explain, in part, the malignant potential of histologically benign myxomas. (Circ J 2004; 68: 1230 - 1232)

Yagi A, Ichikawa S, Sakamaki T, Ono, Z, Sato K, Nakamura T, Sakamoto H, Murata K. Aldosterone response to adrenocorticotrophin and furosemide in primary aldosteronism after prolonged spironolactone treatment. Eur J Endocrinol 1994;131:215–20. ISSN 0804–4643 We evaluated the effects of prolonged spironolactone treatment on aldosterone secretion in patients with primary aldosteronism. The patients were hospitalized and underwent a furosemide test with or without dexamethasone, as well as an adrenocorticotrophin (ACTH) test. In untreated patients, neither plasma renin activity (PRA) nor plasma aldosterone showed a response in the furosemide test. In patients receiving spironolactone, furosemide increased significantly both the PRA and the plasma aldosterone concentration (from 2.6±0.8 to 7.0±2.0 μg·1−1 · h−1 (p < 0.05) and from 345.6 ± 55.8 to 492.7 ± 76.8 ng/l (p < 0.05), mean ± sem, respectively). Dexamethasone administration had no effect on the results of the furosemide test (p > 0.1). However, dexamethasone tended to decrease the basal plasma aldosterone concentration in the untreated patients, but not in the patients receiving spironolactone. In the ACTH test, the plasma aldosterone concentration increased significantly in the untreated patients (from 549.0± 69.8 to 1169.3 ± 165.5 ng/l, p 0.1). We conclude that aldosterone secretion is mainly dependent on ACTH in the untreated patients with primary aldosteronism and is more strongly regulated by the renin–angiotensin system during spironolactone treatment. Atsuko Yagi, Second Department of Internal Medicine, Gunma University School of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371, Japan

We evaluated the reliability of a new device for indirect measurement of systolic blood pressure in normal and hypertensive New Zealand White rabbits. This device consisted of an ear unit composed of an air chamber and sensitive photoelectric sensors, and was connected to an apparatus used for the tail-cuff method. Systolic blood pressure was determined by simultaneous recordings of pulse volume oscillations of the central ear artery and the chamber pressure. The blood pressure in 8 normal rabbits was 116 +/- 7/78 +/- 6 mmHg (mean +/- SEM) by direct measurement and 100 +/- 6 mmHg by indirect measurement. In a one-kidney, one-clip hypertensive model, the new device showed that blood pressure increased from 100 +/- 7 to 158 +/- 7 mmHg over 4 weeks. After nicardipine was injected, blood pressure fell from 191 +/- 10/114 +/- 10 to 117 +/- 7/72 +/- 8 mmHg as measured by the direct method, and from 158 +/- 7 to 92 +/- 6 mmHg as measured by the new device. A strong correlation (r = 0.91, p0.01) was observed between direct and indirect measurements. Our findings indicate that this device provides rapid, easy and reliable measurement of blood pressure in rabbits.

Background & Aims : Zinc (Zn) deficiency cause a variety of disorders including dermatological, neurological and immunologic abnormalities.Methods : To investigate the relation between serum levels of Zn ion and suppression of protective immunity, we measured the levels of Zn of 10 elderly patients with repeated infections (group 1), and compared with those of other 10 elderly without infections (group 2).Results and conclusions : The levels of serum Zn in group 1 were higher than those in group 2 (58.0±5.2μg/dl vs. 72.3±4.1μg/dl, P=0.0375 ; n=10, 10, respectively). Our result suggested that Zn deficiency might be a risk factor of infections in elderly.

Chronic inhibition of nitric oxide (NO) synthesis by oral administration of NG-nitro-L-arginine methyl ester (L-NAME) causes hypertension and produces arteriosclerosis in rats. Balloon injury induces upregulation of vascular endothelial growth factor (VEGF) in medial smooth muscle cells of the rat arterial wall, and NO secreted by a restored endothelium acts as the negative feedback mechanism that downregulates VEGF expression to basal levels. In this study, we tested the hypothesis that a reciprocal relation between VEGF and NO would be established in a rat model of chronic NO blockade. Male Wister rats received plain drinking water (n = 10) or L-NAME (0.5 mg/ml) in the drinking water (n = 11) for 6 weeks. After 6 weeks, the wall-to-lumen ratios and perivascular fibrosis in the coronary arteries were greater in the L-NAME group than in the control group. NO synthase-positive cells in the intima were abundantly observed in the control group, whereas no such cells were seen in the L-NAME group. In contrast, the number of VEGF-positive smooth muscle cells in the media was greater in the L-NAME group than in the control group. These findings strongly suggest a reciprocal relation between VEGF and NO even in a rat model of chronic NO blockade.

The effects of mental stress and isometric handgrip exercise on peripheral white blood cell counts and plasma active renin concentrations were studied in 20 patients with mild essential hypertension. The increases in blood pressure and pulse rate were similar for both provocations. Mental stress increased white blood cell (10.3±2.1%), platelet (2.8±1.6%), and red blood cell counts (1.7±0.3%). Isometric exercise also increased these blood cell counts (6.2±1.2%, 1.9±0. 8%, 1.0±0.3%, respectively). The increase in white blood cell counts with mental stress was significantly greater than that in response to isometric exercise. With both provocations, the increase in white blood cell counts was significantly greater than those in platelet and red blood cell counts. There was a positive correlation between the increases in white blood cell counts and systolic blood pressure with mental stress (r = 0.49, p

The beneficial effects of raloxifene, a selective estrogen receptor modulator, on cardiovascular risks and events have been investigated. Brachial arterial flow-mediated vasodilatation (FMD), carotid intima-media thickness (IMT), and pulse wave velocity (PWV) have been widely used in clinical settings as surrogate markers of atherosclerosis. This study investigated the simultaneous effects of raloxifene on brachial arterial FMD, carotid IMT, and PWV in osteoporotic postmenopausal women. A total of 31 postmenopausal women with osteoporosis or osteopenia were divided into 2 groups: a raloxifene group (n = 15; mean age +/- SD, 66.1 +/- 8.2 years) was treated with raloxifene hydrochloride (60 mg/day) orally for 12 months, and an untreated control group (n = 16; 64.1 +/- 7.8 years). Brachial arterial FMD, carotid IMT, and brachial-ankle PWV (baPWV) were measured at baseline and at 12 months after the start of the study. The brachial arterial FMD increased significantly, from 4.5 +/- 1.8% to 9.2 +/- 3.0%, in the raloxifene group (P0.01) but did not change in the control group. Nitroglycerin-induced vasodilatation did not change in either group. The carotid IMT decreased significantly, from 0.82 +/- 0.15 mm to 0.72 +/- 0.11 mm, in the raloxifene group (P0.01) but did not change in the control group. The baPWV did not change in either group. In conclusion, raloxifene may have beneficial effects on brachial arterial endothelial function and carotid wall thickness in osteoporotic postmenopausal women.

We carried out both mental stress (MS) and isometric handgrip exercise (IHG) tests in 20 mild hypertensive patients to compare responses of blood pressure, heart rate, blood cell count and pressor hormones between the two tests. Increments of blood pressure and heart rate by MS (mean±SEM, 42± 2/17±1mmHg and 8±1beats/mm) were similar to those by IHG (39 ±3/17±2mmHg and 6±1beats/ min). Packed cell volume, erythrocytes, leukocytes, and platelets significantly increased in the MS test (1.3±0.3%, 1.7±0.3%, 10.3±2.1% and 2.8±1.6%, respectively) and in the IHG test (1.3±0.3%, 1.0 ±0.3%, 6.2±1.2% and 1.9±0.8% respectively). In both tests the percent increase was significantly greater in leukocytes than in erythrocytes and platelets (p

Time-related changes in plasma levels of aldosterone, deoxycorticosterone, corticosterone, and cortisol were studied during treatment with spironolactone in 8 patients with primary aldosteronism due to adenomas. Plasma renin activity (PRA), serum sodium and serum potassium were also measured. The patients were treated with spironolactone, 75 to 225 mg daily, and blood samples were withdrawn on days 7, 14, and 21 to 28 of drug administration. Plasma aldosterone concentrations (PAC) were not altered by spironolactone; however, significant increases were observed in plasma deoxycorticosterone on days 21 to 28 and in plasma corticosterone and cortisol on days 14 and 21 to 28. The suppressed PRA values were markedly increased on days 21 to 28 and low levels of serum potassium returned to the normal range on day 7. The lack of increase in PAC, despite a remarkable rise in PRA and serum potassium, suggests biosynthetic inhibition of spironolactone at the sites of 18-hydroxylation and/or 18-oxidation, because of the elevation of deoxycorticosterone and corticosterone.

Tortuosity of the thoracic aorta on chest radiographs is characteristic of atherosclerotic disease. Aging and hypertension are associated with the tortuosity, but little is known about the influence of other atherosclerotic risk factors on this abnormality. The purpose of this study was to examine which atherosclerotic risk factors are determinants for tortuosity of the thoracic aorta. Forty-five poststroke Japanese patients (31 men and 14 women, age range 41-78 years and mean 60.5 ±8.6) were studied. The distance factor, ie, the ratio of meandering vessel length to the straight-line distance between its end points, was used to measure arterial tortuosity. The hospital records were reviewed for clinical and biochemical variables. Tortuosity of the thoracic aorta had a significant positive relationship with body mass index (BMI) ( r =0.397, p

We report a case study of a 54-year-old Japanese woman who persistently suffered from a sour-taste sensation in her mouth for 10 years, and was treated with a proton-pump inhibitor (PPI). She found sour-tasting meals irritable, and after eating such meals the sour-taste sensation worsened. She also complained of eructation and regurgitation. Upper gastrointestinal (GI) endoscopy showed duodenal erosion, superficial gastritis, and erosive oesophagitis. After 2 weeks of PPI therapy (lansoprazole, 30 mg day(-1)) the sour taste subjectively decreased to 70%, and after 6 weeks the symptoms disappeared. In addition to increased sensitivity of the mouth, gastro-oesophageal reflux might have created her obstinate sour-taste sensations. It is suggested that in such cases PPI therapy should be attempted.

Objective— Transforming growth factor-β1 (TGF-β1) controls the expression of numerous genes, including smooth muscle cell (SMC)–specific genes and extracellular matrix protein genes. Here we investigated whether c-Src plays a role in TGF-β1 signaling in mouse embryonic fibroblast C3H10T1/2 cells. Methods and Results— TGF-β1 induction of the SMC contractile protein SM22α gene expression was inhibited by PP1 (an inhibitor of Src family kinases) or by C-terminal Src kinase (a negative regulator of c-Src). Induction of SM22α by TGF-β1 was markedly attenuated in SYF cells (c-Src − , Yes − , and Fyn − ) compared with Src ++ cells (c-Src ++ , Yes − , and Fyn − ). PP1 also inhibited the TGF-β1–induced expression of serum response factor (SRF), a transcription factor regulating the SMC marker gene expression. Confocal immunofluorescence analysis showed that TGF-β1 stimulates production of hydrogen peroxide. Antioxidants such as catalase or NAD(P)H oxidase inhibitors such as apocynin inhibited the TGF-β1–induced expression of SM22α. Furthermore, we demonstrate that TGF-β1 induction of the plasminogen activator inhibitor-1 (PAI-1) gene, which is known to be dependent on Smad but not on SRF, is inhibited by PP1 and apocynin. Conclusion— Our results suggest that TGF-β1 activates c-Src and generates hydrogen peroxide through NAD(P)H oxidase, and these signaling pathways lead to the activation of specific sets of genes, including SM22α and PAI-1.

Although the origin of cardiac myxomas is still controversial, the 2 main hypotheses are that the tumor cells originate either from multipotential mesenchymal cells or from endocardial neural tissue.The production of various cytokines in 2 human cardiac myxoma cell lines was examined by enzyme-linked immunosorbent assay. After 7 days of culture, extremely high concentrations of interleukin-6 were detected in the culture media from both myxoma cell lines. Increased production of CXC chemokines, interleukin-8 and growth-related oncogene-alpha, were observed in both myxoma cell lines. Endothelin (ET)-1 and its precursor, big ET-1, were detected in the culture media from both myxoma cell lines. The production of both ET-1 and big ET-1 by myxoma cells was higher than by human umbilical vein endothelial cells. Similar to endothelial cells, myxoma cells did not produce stem cell factor, granulocyte colony-stimulating factor, hepatocyte growth factor, or ET-3.The similarity of the cytokine production pattern between cardiac myxoma cells and endothelial cells supports the hypothesis that the tumor cells originate from mesenchymal cells capable of endothelial differentiation. Overproduction of CXC chemokines may explain, in part, the malignant potential of histologically benign myxomas.

Objective : Thickened atherosclerotic plaques are prone to be hypoxic because of poor perfusion. In this study, we tested (a) whether reactive oxygen species (ROS) and c-Src play roles in hypoxic induction of HIF-1α protein and PAI-1 gene expression in the rabbit aortic smooth muscle cell line C2/2 cells and primary cultures of rat aortic smooth muscle cells, and (b) how mitochondria act on the hypoxia-induced signaling mechanism. Methods and results : Hypoxic exposure of C2/2 cells increased H2O2 generation, c-Src phosphorylation, HIF-1α protein expression, and PAI-1 gene expression. Catalase, a scavenger of H2O2, inhibited the hypoxia-induced ROS generation and PAI-1 gene expression. Src kinase inhibitors PP1 and PP2 inhibited hypoxia-induced HIF-1α protein and PAI-1 gene expression. Ablation of mitochondrial respiration by rotenone abolished hypoxia-induced ROS generation, c-Src phosphorylation, HIF-1α protein expression, and PAI-1 gene expression. Conclusion : Induction of HIF-1α protein and PAI-1 gene expression in response to hypoxia was regulated by ROS production and c-Src activation in vascular smooth muscle cells. Mitochondria linked the hypoxic signal to c-Src, which in turn led to HIF-1α protein and PAI-1 gene expression. These results provide evidence that hypoxia induces the ROS-mediated and c-Src-dependent signaling cascades which are closely associated with angiogenesis and thrombosis in atherosclerotic vasculature.

Endothelial PAS domain protein-1 (EPAS1) regulates transcription of the genes encoding erythropoietin and vascular endothelial growth factor, which are important for maintaining oxygen homeostasis. We have previously shown that plasminogen activator inhibitor-1 (PAI-1) gene expression is induced by hypoxia. In this study, we sought to determine whether PAI-1 gene expression is directly regulated by EPAS1 in cancer cells because activities of proteases and their inhibitors are tightly regulated for tumor invasion. Hypoxia increased the PAI-1 mRNA levels in human adenocarcinoma A549 cells. Overexpression of EPAS1 significantly increased the PAI-1 mRNA and protein levels. Transient transfection assays revealed that EPAS1 increased PAI-1 gene transcription through a sequence containing 5'-CACGTACA-3' located at -194 (we refer to it as site HREPAI-1) and GT-box located at -78. Electrophoretic gel mobility shift assays revealed that HREPAI-1 serves as a binding site for EPAS1, and Sp1 constitutively binds to GT-box. In conclusion, PAI-1 expression is induced by EPAS1 through HREPAI-1 and through an Sp1-binding site. These results indicate that the PAI-1 gene is a direct target of EPAS1 and suggest the role of EPAS1 and Sp1 in the hypoxic response of cancer cells.

We investigated the opinions of medical doctors and nursing staff about desirable medical treatment for terminally ill geriatric patients. The purpose of the present study is: 1) to examine the recent opinion of doctors and nurses, 2) to examine discrepancies of opinions between doctors and nurses on treatment for terminal geriatric patients. Doctors and nurses working in long-term care wards in four hospitals were enrolled. They were asked to fill in a questionnaire which asked about desirable medical treatments for a typical bedridden terminally ill geriatric patient. The difference of answers between doctors and nurses were analyzed. The most common opinion of the 18 doctors and 84 nurses were as follows: 1) for the treatment of relapsing pneumonia, they would perform oxygenation, antibiotic injections, and continuous intravenous infusion during the period of discontinuation of enteral nutrition, 2) for the treatment of relapsing urinary tract infection, they would catheterize patients for a brief period and would irrigate the bladder, and would perform antibiotics injection, 3) for chronic anemia, they would perform iron replacement, 4) for decubitus ulcer, they would treat conventionally, and 5) at the final stage just before death, they would avoid special therapy for shock after obtaining informed consent from patient's family. To most questions, the proportion of each answer was almost identical between doctors and nurses; however, there were discrepancies concerning "way of nutrition in patients with relapsing pneumonia" and "irrigation of the urinary bladder" (p = 0.0544 and 0.0531, respectively). We expect that the present study will activate a discussion of what constitutes appropriate medical treatment for terminally ill geriatric patients.

We analyzed the main disaccharide units of glycosaminoglycans synthesized by cardiac myxoma cells in vivo and in cell culture using high-performance liquid chromatography after 1-phenyl-3-methyl-5-pyrasolone labeling. Cardiac myxoma tissues contained large amounts of chondroitin-6-sulfate (46%) and hyaluronic acid (32%), along with some chondroitin-4-sulfate (13%), chondroitin (6%), and much less dermatan sulfate (3%). Cultured cardiac myxoma cells synthesized mainly chondroitin-6-sulfate. The abundant glycosaminoglycans in myxoma tissues may make up the characteristic friable gelatinous matrix which is favorable for embolism and tumor cell growth.

Objective: To delineate the clinical characteristics of post-stroke aphasic patients exhibiting the white-coat effect when a therapist is present during therapy session, 18 Japanese inpatients were studied. Design: On the basis of blood pressure assessments during two speech therapy sessions, one directed by a speech therapist and the other self-directed, patients were divided into two groups: one including the seven who exhibited the white-coat effect and the other including the 11 patients who did not. The white-coat effect was diagnosed when a pressor response was greater during a therapist-directed session than during a self-directed session. The parametric Student's t test and nonparametric Fisher's exact test were applied to clinical, laboratory, and language parameters for these two groups. Results: The groups did not differ significantly in terms of clinical or laboratory parameters. Compared with the noneffect group, the white-coat-effect group more frequently had quotients of ≥40.0 for aphasia, comprehension, and expression on the Western Aphasia Battery. The type of aphasia did not influence the prevalence of the white-coat effect. Conclusions: The white-coat effect induced by the speech therapist's presence is more common among patients with mild aphasia, without regard to the type of aphasia. Blood pressure monitoring during speech therapy should help therapists treat patients safely.

Because zinc (Zn) is an important component for cell protection against certain oxygen species, it has been suggested that Zn deficiency impairs the potent oxidant defense capacity, which is constitutively provided in the vascular system. However, the influence of dietary Zn deficiency on systemic blood pressure and vascular system is controversial and unclear. We therefore examine the effect of dietary Zn deficiency on systemic blood pressure, a potent superoxide scavenger, aortic Cu/Zn superoxide dismutase (SOD) activity, a most representative synthase of the endothelium-derived relaxing factor, and aortic endothelial nitric oxide synthase (eNOS) expression. Furthermore, the direct effects of intravenous administration of NOS inhibitor, N ω-nitro-l-arginine methyl ester (l-NAME), and a SOD mimetic compound, tempol, in normotensives were tested in Wistar-Kyoto (WKY) rats. A Zn-deficient diet (4 wk) contributed to growth retardation, the decrease in thymus weight, and the lower levels of serum Zn compared with the standard diet group. However, no significant difference in conscious systolic and diastolic blood pressure was found in the Zn-deficiency group. The administration of l-NAME caused an increase in the mean arterial pressure (MAP) levels in the two groups of rats and the involvement of the vasodilator nitric oxide (NO) in the regulation of systemic BP in the normotensive state. On the other hand, administration of the superoxide scavenger, tempol, led to a decrease in MAP levels in the two groups of rats, indicating the participation of the oxygen free radical, superoxide, in the maintenance of the systemic BP in a normotensive state. There were no significant differences between the Zn-deficient diet group and the standard diet group in the normotensive state. eNOS expression and Cu/Zn SOD activity in the aorta were also intact in Zn-deficient normotensive rats. These findings suggest that the 4 wk of Zn deficiency was inadequate to alter systemic blood pressure and focal NO signaling in the normotensive state. Long-term Zn deficiency affects the neuronal, immune, and hematopoietic systems, which contribute to systemic and/or local circulation. However, Zn deficiency alone does not cause hypertension and local vascular dysfunction in the normotensive state.

Background —Although hypertension is an important risk factor for the development of atherosclerosis, the mechanisms for this interaction are incompletely described. Previous studies have suggested that biomechanical strain regulates macrophage phenotype. We tested the hypothesis that biomechanical strain can induce expression of the class A scavenger receptor (SRA), an important lipoprotein receptor in atherogenesis. Methods and Results —Human monocyte/macrophages or THP-1 cells were cultured in a device that imposes uniform biaxial cyclic 1-Hz strains of 0%, 1%, 2%, or 3%, and SRA expression was analyzed. Mechanical strains induced SRA mRNA (3.5±0.6-fold at 3% strain for 48 hours, P P −/− mice were randomly assigned to receive standard chow, a high-cholesterol diet, or a high-cholesterol diet with hypertension induced by angiotensin II infusion for 8 weeks. Immunohistochemistry revealed that among macrophages in atherosclerotic lesions of the aorta, the proportion of macrophages with SRA expression was highest in hypertensive animals on a high-cholesterol diet (43.9±0.7%, versus 12.0±2.0% for normotensive animals on a high-cholesterol diet and 4.7±4.7% for animals on standard chow; P Conclusions —Biomechanical strain induces SRA expression by monocyte/macrophages, suggesting a novel mechanism for promotion of atherosclerosis in hypertensive patients.

Abstract —Recent studies have shown that the homeobox gene Hex plays an important role in inducing differentiation of vascular endothelial cells. In this study, we examined the expression of Hex in vascular smooth muscle cells (VSMCs) in vitro and in vivo. Immunohistochemistry showed a marked induction of Hex protein in neointimal VSMCs after balloon injury in rat aorta. Western and reverse transcriptase–polymerase chain reaction analyses demonstrated that Hex was abundantly expressed in cultured VSMCs, whereas it was undetectable in other cell types or in normal aorta. The expression pattern of Hex was similar to that of SMemb/NMHC-B, a nonmuscle isoform of myosin heavy chain that we have previously reported to be a molecular marker of dedifferentiated VSMCs. We next examined the role of Hex in SMemb gene transcription. Promoter analysis demonstrated that the sequence identical to consensus cAMP-responsive element (CRE) located at −481 of the SMemb promoter was critical for Hex responsiveness. Mutant Hex expression vector, which lacks the homeodomain, failed to stimulate SMemb gene transcription, suggesting the requirement of the homeodomain for its transactivation. Elecrophoretic mobility shift assay showed that Hex binds to a consensus binding sequence for homeobox proteins, but not to CRE. Cotransfection of protein kinase A expression vector increased the ability of Hex to stimulate SMemb promoter activity in a CRE-dependent manner. Overexpression of CRE binding protein (CREB), but not Mut-CREB which contains mutation at Ser133, strongly activated Hex-induced SMemb promoter activity. These results suggest that Hex mediates transcriptional induction of the SMemb/NMHC-B gene via its homeodomain, and Hex can function as a transcriptional modulator of CRE-dependent transcription in VSMCs.

Background —We have previously shown BTEB2, a Krüppel-like zinc finger transcription factor, to regulate expression of the SMemb/NMHC-B gene, which has been implicated in phenotypic modulation of smooth muscle cells (SMCs). The present study was done to assess the developmental and pathological expression profiles of BTEB2 and to further evaluate the clinical relevance of BTEB2 expression in human coronary artery disease. Methods and Results —Immunohistochemistry showed developmentally regulated expression of BTEB2 with abundant expression in fetal but not in adult aortic SMCs of humans and rabbits. In balloon-injured aortas, predominant expression of BTEB2 was seen in neointimal SMCs. Atherectomy specimens obtained from primary and restenotic lesions showed predominant expression of BTEB2 to stellate SMCs. The incidence of restenosis in primary lesions was significantly higher in lesions containing BTEB2-positive cells than in lesions without (55.6% versus 25.0%, P =0.01). Conclusions —The present study shows that BTEB2 expression is developmentally and pathologically regulated. BTEB2 is preferentially expressed in dedifferentiated or activated SMCs. Examination of human coronary artery specimens suggests that primary lesions containing BTEB2-positive cells are associated with higher risk of restenosis than BTEB2-negative lesions. These results suggest that BTEB2 can serve as a molecular marker for phenotypic modulation of vascular SMCs.