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This study is a prospective multicenter study designed to investigate the effects of lipid-lowering therapy with pitavastatin on atherosclerotic plaque in patients with coronary heart disease, and to determine which factor is more closely associated with plaque regression. Participants (n = 63) were treated with pitavastatin for 12 months, and the carotid intima-media thickness (IMT) was measured by ultrasound before and after treatment. Mean IMT slightly but significantly decreased (from 0.99 ± 0.33 to 0.94 ± 0.28 mm for overall, P = 0.01) regardless of the presence of pretreatment with other statins. There were no significant relations with hs-CRP, malondialdehyde-LDL, LDL cholesterol, and smaller LDL cholesterol levels despite their decrease by pitavastatin. Decreases in mean IMT were observed significantly more frequently in subjects with high on-treatment HDL cholesterol levels than with low HDL cholesterol levels (P = 0.017). The change in mean IMT tended to be inversely correlated with increments in HDL cholesterol and apolipoprotein A-I. The IMT regression was more often observed in the absence of diabetes and metabolic syndrome. In conclusion, we demonstrated that treatment with pitavastatin attenuated atherosclerotic plaque. This effect was associated with the level of HDL cholesterol, and was stronger in the absence of diabetes and metabolic syndrome in our ischemic heart disease patients.

Trousseau syndrome is most commonly defined as a hypercoagulability syndrome associated with mucin-producing adenocarcinoma. We report here a rare case of Trousseau syndrome presenting as pulmonary arterial hypertension. The patient complained of cough and increasing exertional dyspnea. Rapidly progressive symptom development of pulmonary arterial hypertension accompanied by right heart failure was observed, and the patient died on hospital day 2. An autopsy revealed Krukenberg tumors on both ovaries and a signet-ring cell gastric carcinoma. In the lungs there was tumor embolism with signet-ring cells to some extent, but the peripheral pulmonary arteries were occupied primarily by pulmonary embolism with platelets, fibroblasts, and fibrotic organized thrombi.

Since distinct cholesterol and triglyceride concentrations in major lipoproteins and their subclasses may be related to atherosclerosis, we investigated the relationship of cholesterol and triglyceride concentrations in lipoprotein subclasses and the severity of carotid intima-media thickness (IMT), a surrogate marker of subclinical atherosclerosis. We studied 116 apparently healthy Japanese men (53 ± 9 years) without a history of cardiovascular diseases who were not taking any medication. Carotid IMT was measured by means of high-resolution vascular ultrasound. Plasma cholesterol and triglyceride concentrations in major lipoproteins and their subclasses were determined by HPLC with gel permeation columns. By univariate analyses, carotid IMT was the most closely related to age (r = 0.528, P < 0.001), followed by smoking habit expressed as pack-year cigarette consumption (r = 0.409, P < 0.001). In addition to total cholesterol and LDL cholesterol, carotid IMT was significantly associated with cholesterol and triglyceride concentrations in several LDL and VLDL subclasses. Stepwise multiple linear regression analysis revealed that age (β = 0.436, P < 0.001), smoking (pack-years) (β = 0.225, P = 0.007), and large LDL cholesterol (β = 0.175, P = 0.023) were independent predictors of determining carotid IMT (adjusted R(2) = 0.347, P < 0.001). These results indicate that large LDL cholesterol is an important, independent determinant of carotid IMT in healthy men.

Blood folate concentration is decreased by tobacco smoking and presumably secondhand smoke. Because low folate concentration is associated with hyperhomocysteinemia, both are emerging as important and independent risk factors for atherosclerosis as well as prediction of early coronary artery disease. The primary cause of low folate concentration in smokers might be related to lifestyle and dietary habits. Smokers tend to consume fewer folate-rich fruits and vegetables vs non-smokers. Adverse cardiovascular health is generally attributed to toxic gases, particulates, and tars generated from tobacco smoking. Although low folate concentration and hyperhomocysteinemia are typically found in smokers, their role in this pathophysiologic process remains controversial. In fact, several studies failed to demonstrate a beneficial effect of daily folic acid supplementation as a homocysteine-lowering therapy on cardiovascular outcome even in smokers. In this review, we investigate the relationship between folate status and smoking.

症例は40歳,女性. 20年前より,左腋窩の皮膚変化に気づいていたが副乳腺だと思い放置. 1年前より腫瘤状となり, 1カ月前から増大し受診した.左腋窩に8×7.5cmの硬い腫瘤を認めた.マンモグラフィー,超音波検査,胸部CT検査で左腋窩部に大きな充実性腫瘍を認めた.穿刺細胞診はclass IIIbで,異所性乳癌を疑い腫瘍摘出術,腋窩リンパ節郭清施行.腫瘍は境界明瞭,黄白色,充実性,分葉状であった.病理組織学的検査ではstoriform pattern (花むしろ模様)を示す隆起性皮膚線維肉腫が主体で,細胞密度が増し,紡錘形細胞が束状増殖(herringbone pattern)する線維肉腫領域も伴っていた.免疫組織化学検査でCD34が隆起性皮膚線維肉腫領域で陽性,線維肉腫領域でも部分的に陽性であった. 3年半無再発であるが,本症は再発率が高いとされており,厳重な経過観察が必要である.

Cardiogenic shock developed in a 72-year-old Japanese woman during combination therapy with verapamil and atenolol for recurrent supraventricular arrhythmia. She had coronary atherosclerosis, liver cirrhosis and brady-cardia-tachycardia syndrome. Despite of the high-dose catecholamines and counterpulsation, she progressively deteriorated. Bolus administration of intravenous calcium chloride (CaCl2) immediately resolved her hemodynamic collapse.

BACKGROUND Recent studies on the role of bcl-2 in malignant tumors have suggested its prognostic significance. The goals of the current study were to determine any correlation between bcl-2 expression in esophageal squamous cell carcinoma and histopathology, lymph node metastasis, and clinical variables, and to assess its applicability as a parameter for prognosis. METHODS Immunohistochemical staining for bcl-2 (clone 124) was performed on archival material from 105 esophageal squamous cell carcinomas. The results were compared among patient subgroups. RESULTS bcl-2 was expressed in 58% of esophageal carcinomas, demonstrating positive correlations with a lack of keratinization and an early stage of disease. Lymph node metastasis was significantly less frequently observed in the subset of early stage carcinomas with bcl-2 staining. Univariate analysis revealed significantly longer disease free survival in patients with bcl-2 positive carcinomas than in those bcl-2 negative. bcl-2 expression did not have independent prognostic value in a multivariate survival analysis. CONCLUSIONS bcl-2 is frequently expressed in esophageal carcinomas, and this expression is positively associated with nonkeratinization and an early stage, whereas it is negatively linked with lymph node metastasis and may indicate a favorable prognosis. Cancer 1997; 79:1287-93. © 1997 American Cancer Society.

保存的治療が奏効した特発性食道破裂の1例を報告した.症例は59歳の男性で, 嘔吐した直後の心窩部痛で発症した.発症から約7時間で来院し, 全身状態も安定していたが保存的治療を行った.来院時胸部単純X線写真やCTでは縦隔気腫と少量の胸水を認めたのみで気胸はなく, 同日の上部消化管X線検査 (以下, UGI) で造影剤の管外漏出を認めなかった.第3病日のUGIで下部食道から造影剤の管外漏出を認めたが, これは縦隔内に留まり胸腔内に流入しなかったため, 保存的治療を続行した.UGIと内視鏡で破裂部の治癒傾向を確認したうえで第64病日に食事を開始し, 第78病日に退院した.従来の特発性食道破裂に対する保存的治療報告例は, ほとんどが診断遅延例や, 全身状態不良例であったが, 発症後早期でも食道からの内容物の漏出が縦隔内の小範囲に留まり, 縦隔膿瘍や膿胸の合併がなければ, 本症に対する保存的治療が可能な症例もあると考えた.

In order to clarify the cell kinetics of colorectal villous tumors (VT), 21 villous adenomatous areas and 12 carcinomatous areas within villous adenomas were investigated for proliferative activity and apoptosis and compared with a series of 41 tubular tumors (TT), demonstrating elements of intramucosal carcinomas as well as tubular adenomas (so-called carcinoma in tubular adenoma). Proliferation was estimated in terms of Ki-67 labeling indices and mitotic indices, and apoptosis was assessed by DNA nick-end labeling to give apoptotic indices. Apoptotic indices of villous adenomatous and carcinomatous regions were significantly lower than the values for their tubular counterparts. Ki-67 labeling indices were also significantly lower for adenoma components. Apoptotic indices, Ki-67 labeling indices and mitotic indices increased with atypia raised in tubular adenoma components. Correlations of mitotic indices with apoptotic indices, Ki-67 labeling indices with apoptotic indices and mitotic indices with Ki-67 labeling indices were found for each villous tumor group and tubular tumor group, and the apoptosis and proliferation ratios for villous tumors were relatively low, suggesting a tendency for greater growth due to less cell deletion. Although this is only one of the biological features of villous tumor groups, it might play a major role in generation of malignancy.

Our present study was conducted by cooperation between Departments of Internal Medicine and surgery of a hospital, which was highly significant because the results were comprehensive without a bias toward either department. The present report describes whether or not emergency operations have decreased because of progress in various conservative hemostatic methods for hemorrhagic ulcer and short-term and long-term prognoses after conservative therapy. Compared with the first 8-year period, the number of patients treated by conservative therapy increased with a definite decrease in that of emergency operations in the latter 8-year period. As for the results of conservative treatment, the rate of short-term prognostic hemostasis was 81.3%. Of the long-term prognostic cases, ulcers recurred in 50%, accompanied by recurrent bleeding in 34.8%. These patients were again treated by conservative therapy, and hemostasis was successful in 95.7%. The mortality rate following conservative therapy was 13.7% in the first period and 11.0% in the latter period. The surgical mortality rate was 6.0% in the first period and 5.4% in the latter period. There was no surgical death among the patients undergoing palliative operation. Our therapeutic policy for hemorrhagic ulcer will be described based on these findings.

Serum creatine kinase (CK) MM isoforms were determined by chromatofocusing in 22 patients with acute myocardial infarction undergoing intracoronary thrombolysis. In 13 patients with successful coronary recanalization within 3.6 +/- 1.0 (SD) h after onset, time to peak CK activity occurred 13 +/- 3 h after onset which was significantly shorter (p less than 0.01) than that in 9 patients without coronary recanalization (20 +/- 4 h). The proportion of CK MM-A, the myocardial isoform, in serum in the reperfused group at 6, 10, and 14 h after onset (53 +/- 9, 38 +/- 5, and 27 +/- 4%, respectively) was always significantly lower (p less than 0.01) than that in the nonreperfused group (69 +/- 7, 59 +/- 8, and 43 +/- 4%). During the same period, the proportions of CK MM-B and CK MM-C, the converted isoforms derived intravascularly from MM-A by circulating carboxypeptidase, in the reperfused group were always significantly higher (p less than 0.01) than those in the nonreperfused group. The ratios of MM-A% to MM-B% and MM-A% to MM-C% amplified the differences between the two groups. At 10 h after onset, these ratios clearly differentiated the reperfused and the nonreperfused group at the values of 1.0 (MM-A/MM-B) and 3.0 (MM-A/MM-C) with the diagnostic sensitivity of 85% and 92%, respectively. Thus, myocardial reperfusion was detectable noninvasively by analysis of serum CK MM isoforms during the early stage of acute myocardial infarction.

Sixteen dogs were subjected to acute, permanent coronary occlusion to assess the relationship between latency for the rise of serum creatine kinase (CK) activity and infarct size. Serum CK activity was measured every 30 min from 0 h to 6 h and serially afterwards until 72 h after coronary occlusion. The serum CK activity immediately before coronary occlusion (0 h) was 61 +/- 18 (SD, n = 16) (range 37-95) IU/l. It exceeded the normal threshold value (100 IU/l) at 3.7 +/- 1.4 (range 1.5-6) h, increased at a maximal rate at 7.0 +/- 1.2 h and reached a peak value of 1700 +/- 1308 (range 304-5109) IU/l at 11.0 +/- 1.8 h after coronary occlusion. The cumulative CK release (CKr) was 6556 +/- 5984 (range 454-21580) IU/l, indicating that various sizes of infarction were produced. In 7 dogs, the infarct size was determined anatomically with an enzyme staining technique. The latency of the CK rise was significantly (p less than 0.01, n = 16) and inversely correlated with the max dE/dt (r = -0.692), peak CK (r = -0.716) and CKr (r = -0.691). The CKr was correlated well (p less than 0.001, n = 16) with max dE/dt (r = 0.946), peak CK (r = 0.984) and the infarct size (r = 0.912, p less than 0.005, n = 7). Thus, the latency of the rise of serum CK activity was inversely correlated with myocardial infarct size.

十二指腸潰瘍緊急手術例111例 (穿孔101例, 出血10例) の手術術式を中心に検討を行った. 術式の内訳は広範囲胃切除術 (以下広範胃切) が75例と多く, 選択的迷走神経切離術兼幽門洞切除術 (selective vagotomy+antrectomy以下SV+A) を主体とする迷切付加手術は32例であった. 術式の年次別推移をみると, 1980年までは広範胃切が大部分でSV+Aの症例はなかったが, 1980年までに広範胃切を行った56例中2例 (3.6%) に吻合部潰瘍の発生をみたことから, 1981年以降は緊急手術においても迷切付加手術が望ましいと考えてSV+Aを基本術式とし, SV+Aが55%と過半数を占めるようになった.

Subforms of creatine kinase MM isoenzyme (isoforms, pI: MMA = 7.95, MMB = 7.76, MMC = 7.54) in human myocardium and serum were quantified by chromatofocusing. Creatine kinase MMA was a dominant isoform (greater than 94% of MM) in normal (n = 3) and in both infarcted and non-infarcted myocardium (n = 2). To investigate isoform conversion in vitro partially purified MMA was incubated with human plasma at 37 degrees C for 24 h (n = 5). Creatine kinase MMB (0%, 47%, 44% of MM at 0, 12, 24 h respectively) and MMC (0%, 22%, 42%) sequentially appeared in incubation media whereas MMA (100%, 31%, 14%) disappeared rapidly with a mean disappearance rate of -0.00169(0.00021)(SD) min-1. Individual differences in conversion velocity were small (SD less than 5%). To investigate isoform conversion in vivo serum isoforms were analysed in patients with acute myocardial infarction (n = 7). MMA was first dominant (A:B:C = 54:34:12%) in the early stage (6-9 h after the onset of chest pain) followed by MMB dominant (19:42:39%) in the middle stage (24-35 h), and MMC dominant (6:22:72%) in the late stage (54-60 h). Changes in isoform proportion were time dependent regardless of serum creatine kinase activity. These findings are consistent with canine isoform conversion reported previously except that in man the velocity of conversion was slower than in the dog. Thus analysis of serum creatine kinase MM isoforms may allow the onset of acute myocardial infarction to be precisely dated. Moreover, determination of MMA, the isoform native to myocardium with a short serum half life, may be useful in the prompt diagnosis of myocardial infarction.

Recent investigations have shown that cardiac isoenzymes change with mechanical overload and possibly with myocardial ischaemia. This complicates the interpretation of serum enzyme changes in acute myocardial infarction. We have therefore investigated the rate of release of isoenzymes from necrosing myocardium and the effect of ischaemia per se. Discrete myocardial infarction was produced in 35 male Wistar rats by ligation of left coronary artery. Six (n = 7), 12 (n = 6), 24 (n = 9), 72 (n = 7) h and 3 weeks (n = 6) after surgery, total and isoenzyme activities of creatine kinase (CK), lactate dehydrogenase (LD) and aspartate aminotransferase (AST) were measured in the infarcted myocardium. Untreated rats (n = 12) were used as the control (time 0). Sham operation was performed in 36 rats. During the early period (0 to 12 or 24 h) of infarction, each (iso)enzyme disappeared monoexponentially from the myocardium (mean r = 0.88) with different disappearance rates. Cytosolic isoenzyme fractions decreased more rapidly than mitochondrial fractions. CK MB and the LD-H subunit decreased faster than CK MM and the LD-M subunit. Such differences in the disappearance rate may be related to subcellular localisation of each isoenzyme. In the late period (72 h and 3 weeks), CK BB and the LD-M subunit showed significant reaccumulation in the infarcted myocardium. Although inflammatory cells can be responsible for the reaccumulation of LD-M subunit, the origin of CK BB is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)