Coffee consumption is inversely associated with depressive status in Japanese patients with type 2 diabetes.

Depression has been reported to be more prevalent among diabetic patients than non-diabetic individuals. Although depression and diabetes are causally and bi-directionally related, the influence of food intake frequency on depressive symptoms in diabetic patients has not been fully evaluated. This cross-sectional study analyzed data obtained from 89 patients with type 2 diabetes who completed self-administered questionnaires regarding food intake frequency, diabetic variables, physical activity and depressive states. The prevalence of a "definite" depressive state was 16.9%. The duration of diabetes, hemoglobin A1c levels, diabetic microvascular complications and physical activity levels were similar between depressed and non-depressed patients. Daily intakes of total lipids, n-6 polyunsaturated fatty acids and lipid energy ratios were significantly lower, and the carbohydrate energy ratio was significantly higher in depressed than in non-depressed patients. Coffee consumption was inversely associated with depressive symptoms, but no significant association was found between tea or green tea consumption and depressive symptoms. The logistic regression analysis showed that coffee consumption was an independent predictor of non-depressed status in diabetic patients. This might be due to biologically active compounds containing in coffee other than caffeine.

Atorvastatin induces associated reductions in platelet P-selectin, oxidized low-density lipoprotein, and interleukin-6 in patients with coronary artery diseases.

The development and progression of atherosclerosis comprises various processes, such as endothelial dysfunction, chronic inflammation, thrombus formation, and lipid profile modification. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that have pleiotropic effects in addition to cholesterol-lowering properties. However, the mechanisms of these effects are not completely understood. Here, we investigated whether atorvastatin affects the levels of malondialdehyde-modified low-density lipoprotein (MDALDL), an oxidized LDL, the proinflammatory cytokine interleukin-6 (IL-6), or platelet P-selectin, a marker of platelet activation, relative to that of LDL cholesterol (LDL-C). Forty-eight patients with coronary artery disease and hyperlipidemia were separated into two groups that were administered with (atorvastatin group) or without (control group) atorvastatin. The baseline MDA-LDL level in all participants significantly correlated with LDL-C (r = 0.71, P < 0.01) and apolipoprotein B levels (r = 0.66, P < 0.01). Atorvastatin (10 mg/day) significantly reduced the LDL-C level within 4 weeks and persisted for a further 8 weeks of administration. Atorvastatin also reduced the MDA-LDL level within 4 weeks and further reduced it over the next 8 weeks. Platelet P-selectin expression did not change until 4 weeks of administration and then significantly decreased at 12 weeks, whereas the IL-6 level was gradually, but not significantly, reduced at 12 weeks. In contrast, none of these parameters significantly changed in the control group within these time frames. The reduction (%) in IL-6 between 4 and 12 weeks after atorvastatin administration significantly correlated with that of MDALDL and of platelet P-selectin (r = 0.65, P < 0.05 and r = 0.70, P < 0.05, respectively). These results suggested that the positive effects of atorvastatin on the LDL-C oxidation, platelet activation and inflammation that are involved in atherosclerotic processes are exerted in concert after lowering LDL-C.

The echocardiographic Tei-index reflects early myocardial damage induced by anthracyclines in patients with hematological malignancies.

Anthracyclines are antineoplastic agents that are effective against solid tumors and hematological malignancies. However, drug-induced cardiotoxicity imposes dose limitations. Myocardial damage due to anthracyclines has been assessed by measuring left ventricular ejection fraction (LVEF) or fraction shortening (FS) by echocardiography and criteria for discontinuing treatment have been established based on these indexes. However, cardiotoxicity is already irreversible when either LVEF or FS fulfills these criteria. The Tei-index has recently been established to assess combined systolic and diastolic myocardial function during echocardiography. It can also detect small changes in cardiac function. We therefore surmised that the Tei-index would reflect early myocardial damage induced by anthracyclines. We treated 23 patients with the anthracycline, doxorubicin (DXR), and examined them at least twice during the treatment. An additional dose of DXR significantly correlated with a change in the Tei-index (DeltaTei-index). In contrast, a change in LVEF did not correlate with increased doses of DXR. The DeltaTei-index did not correlate with either LVEF or the Tei-index before treatment. These results suggested that the DeltaTei-index is a more sensitive indicator of early cardiotoxicity induced by anthracyclines than LVEF regardless of its value before treatment.

Acute pulmonary embolism after an earthquake in Japan.

There have been no reports on acute pulmonary embolism (APE) after earthquakes. Our aim was to clarify the actual the occurrence of APE following the 2004 Mid Niigata Prefecture earthquake in Japan, and to assess the risk factors for APE after the event. We sent questionnaires to 122 hospitals in the Niigata Prefecture after the earthquake. Cities, towns, and villages in the prefecture were classified into two areas (high evacuee rate area, and low evacuee rate area) due to the mean ratio of evacuees to the overall population during 1 week immediately after the earthquake. A rate of 5% and higher was encountered for the high evacuee rate area and a rate of < 5% was encountered for the low evacuee rate area. Ten out-of-hospital cases of APE (seven in the high evacuee rate area and three in the low evacuee rate area) were diagnosed within the first month after the earthquake. The relative risk of APE was high in the high evacuee rate area (13.09; P = 0.0002) and also higher in women (8.55; P = 0.04). All patients in the high evacuee rate area had stayed in their automobiles for long periods of time, but none had done so in the low evacuee rate area ( P = 0.008).

[Case of bronchial asthma complicated with Takotsubo cardiomyopathy after frequent epinephrine medication].

A 62-year-old man with non-topic severe persistent asthma and chronic obstructive disease suffered severe asthma exacerbation. Epinephrine was repeatedly injected subcutaneously (0.3mg x 8 times in four hours) in addition to intravenous methylprednisolone for his severe asthma. Despite these treatments, his symptoms steadily deteriorated and thus he was transferred to our hospital. He did not have chest pain or a sensation of compression, while ECG on admission demonstrated ST elevation, loss of R-wave progression, negative T waves and QT interval prolongation, suggesting ischemic heart disease. Nonetheless creatine kinase and its MB isozyme were within normal range and myosin light chain I and troponin T were only mildly elevated. Echocardiography demonstrated apical dyskinesia and hypersystole in the basal region of the heart. Finally this case was diagnosed as Takotsubo cardiomyopathy, probably due to catecholamine-mediated myocardial stunning by overuse of epinephrine for acute severe asthma exacerbation. Abnormal findings of ECG and echocardiography became normal without any specific treatments for the heart.

Diagnostic and therapeutic strategy for acute pulmonary thromboembolism.

BACKGROUND: The diagnostic and therapeutic strategy for acute pulmonary thromboembolism (APTE) was published by the Japanese Circulation Society. But in Japan, there has been no report on how to improve the pre-test probability in APTE-suspected cases, to determine a practically available diagnostic strategy, nor has been a report that compares diagnostic methods and therapies for APTE by decision analysis. METHODS AND RESULTS: APTE was found in 66.7% before using diagnostic imaging techniques. Compared with the absence of APTE, prolonged immobilization, cancer, tachycardia, unilateral leg swelling and inverted T-wave in V(1-3) were found more often in the presence of APTE. The rate of obtaining the result on the day of ordering the examination test was 100% with arterial blood gas analysis, trans-thoracic echocardiography and computed tomography (CT), 78.2% in D-dimer, 85.5% in pulmonary angiography, and 54.5% in perfusion lung scan. Decision analysis showed that the highest expected utility was anticoagulant over 0.51 in pre-test probability, with CT between 0.13 and 0.51. CONCLUSIONS: The pre-test probability of APTE has already been high before using specific diagnostic imaging techniques in Japan. Our results showed that the diagnostic strategy for APTE made by the Japanese Circulation Society was available in most hospitals in Japan.

A case of asymptomatic fusiform aneurysm of the superior vena cava detected by magnetic resonance imaging.

A rare case of fusiform aneurysm of the superior vena cava (SVC) in a 65-year-old Japanese woman is presented herein. Aneurysm of the SVC was detected incidentally as widening of the upper mediastinum on chest radiography and was further defined using magnetic resonance imaging, venography and chest computed tomography. Based on previous reports, conservative management was planned with anticoagulation therapy as prophylaxis against thrombotic complications rather than surgical resection for aneurysm.

[A case of multiple pulmonary arteriovenous fistulae associated with hereditary hemorrhagic telangiectasia that deteriorated during pregnancy].

A 29-year-old woman was admitted to our hospital because of persistent breathlessness on exertion after the delivery of her second child. Although at the age of 26 she had been given a diagnosis of multiple pulmonary arteriovenous fistula (PAVF), treatment was not done because of the absence of symptoms. An intrauterine growth retardation (IUGR) due to hypoxemia occurred during the second pregnancy, and then she delivered a 1,283g baby by cesarean section in the 36th gestation week. Her symptoms and hypoxemia improved after transcatheter embolization. Hereditary hemorrhagic telangiectasia was diagnosed on the basis of recurrent epistaxis since her childhood, pulmonary and hepatic vascular abnormality (PAVF and hepatic arterioportal shunt) and telangiectasis of the buccal mucosa and tongue. We should consider an early treatment of PAVF for young female because pregnancy may induce increase of arteriovenous shunt, fatal hemoptysis, infertility, miscarriage and IUGR.

Risk factors of acute pulmonary thromboembolism in Japanese patients hospitalized for medical illness: results of a multicenter registry in the Japanese society of pulmonary embolism research.

BACKGROUND: Although the prophylaxis of acute pulmonary thromboembolism (APTE) in hospitalized patients has been improving in Japan, there is no report concerning APTE of Japanese medical patients. Therefore, the present study was designed to investigate the characteristics of APTE in Japanese patients hospitalized for medical illness, through a retrospective study. METHODS: In a total of 1,438 registry patients with pulmonary thromboembolism for recent 10 years, 1,027 patients with APTE were analyzed with respect to underlying diseases or predisposing factors, and clinical course. RESULTS: A hundred thirty three patients hospitalized for medical illness developed APTE, among 433 in-hospital APTE patients. The prevalence of APTE in women was more than in men. The mean age of the patients at diagnosis was 61 +/- 17 years. Main risk factors were a prolonged immobilization, stroke, cancer, indwelling central venous catheter. Fifty-four patients had 3 or more risk factors. In-hospital mortality rate was 23%. CONCLUSIONS: Japanese patients in this registry had almost the same findings as in western patients, except for some points that had the possibility of demonstrating a difference between westerners and Japanese in the development of APTE. Our results will be available for establishing the prevention of APTE in medical patients in Japan.

Intimal sarcoma of the pulmonary artery: report of an autopsy case.

Primary pulmonary artery sarcomas (PASs) are rare and lethal tumors. They are easily misdiagnosed as chronic pulmonary embolism, mediastinal mass or tumor emboli, which delay a proper treatment. Although the advanced technologies are now increasingly being used, their diagnosis is usually hard to establish preoperatively at the present time. We report here a case of a 68-year-old female with PAS with lung metastases, who firstly presented with symptoms of common cold and anemia. Although a PAS had been suspected, the final diagnosis of pulmonary intimal sarcoma was made only postoperatively by histological and immunohistochemical examination. The patient died 8 months after the operation because of tumor growth progression, despite adjuvant chemotherapy and radiation therapy. Although pulmonary intimal sarcomas are usually of poorly differentiated mesenchymal malignancy, most reported cases are immunohistochemically positive for vimentin, alpha-smooth muscle actin (SMA), and/or desmin, therefore resembling leiomyosarcomas. However, the diagnosis of leiomyosarcoma should not be made on the basis of immunostains in the absence of typical morphologic features, and PAS, like the present case, should be more appropriately classified as intimal sarcoma according to the new WHO Classification of Tumours of Soft Tissue and Bone published in 2002.

Clinical characteristics, diagnosis and management of patients with pulmonary thromboembolism who are not diagnosed in the acute phase and not classified as chronic thromboembolic pulmonary hypertension.

BACKGROUND: There have been many cases of pulmonary thromboembolism (PTE) that were not diagnosed in the acute phase and not classified as chronic thromboembolic pulmonary hypertension (CTEPH). The aim of the present study was clarify the clinical characteristics of chronic PTE. METHODS AND RESULTS: The study subjects were 601 patients (chronic PTE = 92, acute PTE = 456, CTEPH = 53) who were clinically diagnosed before their death. Dyspnea and chest pain, which are frequently found in acute PTE, were found less frequently in chronic PTE. The diagnosis of chronic PTE is often delayed in cases of mild to moderate severity with atypical onset. Chronic heart failure and chronic respiratory failure were most frequent in chronic PTE, and cerebrovascular disease was present in approximately 15% of the cases of chronic PTE. Pulmonary angiography and ventilation lung scan were used least frequently in acute PTE. Heparin and thrombolysis were used most frequently in acute PTE. CONCLUSIONS: Besides the atypical onset and reduced severity, the presence of preexisting diseases may be one of the reasons why the diagnosis for chronic PTE is delayed. The diagnostic and management techniques differ according to the type of PTE.

Chest pain and ST segment depression caused by expansion of gastric tube used for esophageal reconstruction.

We describe a 76-year-old man in whom a gastric tube was used for esophageal reconstruction via the anterior mediastinum after esophagectomy for esophageal cancer. Stenosis of the tube resulted in fluid accumulation, which directly compressed the heart and caused angina-like chest pain associated with ST-segment depression in lead V(2-3) on the electrocardiogram (ECG). Coronary angiography revealed no stenosis. Drainage of the fluid in the gastric tube resulted in immediate relief of symptoms and normalization of ECG. Angina-like chest pain associated with ST segment changes were caused by expansion of the gastric tube and compression of the heart.

Effectiveness and safety of the thrombolytic therapy for acute pulmonary thromboembolism: results of a multicenter registry in the Japanese Society of Pulmonary Embolism Research.

OBJECTIVE: To assess the effectiveness and safety of thrombolytic treatment for acute pulmonary thromboembolism (APTE), especially in the hemodynamically stable patients with right ventricular afterload stress. METHODS AND RESULTS: In a total of 221 patients with APTE, the association between thrombolytic treatment and the clinical outcomes were investigated. Thrombolysis was given to 121 patients (Thrombolytic Group), and the remaining 100 patients were treated with anticoagulation alone (Anticoagulation Group). In both patients with prolonged shock and patients who were hemodynamically stable without right ventricular afterload stress, the rate of death and recurrence of APTE in Anticoagulation Group were similar to those in Thrombolytic Group. In patients with right ventricular afterload stress, better outcomes were observed in Thrombolytic Group than in Anticoagulation Group, although the difference did not reach statistical significance. There was no significant difference in the rate of major bleeding episode between these two groups. CONCLUSION: Our results suggested that performing thrombolytic treatment in APTE patients with right ventricular afterload stress should be considered even in Japan.

Evaluation of venous thromboembolism and coagulation-fibrinolysis markers in Japanese patients with inflammatory bowel disease.

BACKGROUND: Arterial or venous thromboembolism is rarely encountered clinically as an extradigestive tract complication in inflammatory bowel disease (IBD). However, it is one of the important prognostic factors for IBD patients. The present study was designed to evaluate the relationship between pulmonary embolism (PE) and deep vein thrombosis (DVT) with coagulation-fibrinolysis markers in patients with active IBD. METHODS: In 47 consecutive cases hospitalized due to active IBD [26 with Crohn's disease (CD) and 21 with ulcerative colitis (UC)], we evaluated the disease severity, blood tests, pulmonary ventilation-perfusion scan (V/Q scan), and magnetic resonance venography (MRV) or conventional venography. RESULTS: PE was diagnosed by V/Q scan in 5 (2 with CD and 3 with UC; 10.6%). DVT was diagnosed in 5 (2 with CD and 3 with UC; 10.6%). Of the 47 patients, 8 (17.0%) had venous thromboembolism (either PE or DVT), and 2 of them (4.3%) had both conditions. In UC patients, the thrombosis group was in more severe stages based on endoscopic grading than the nonthrombosis group. In all patients, the thrombosis group were older (50.3 +/- 14.3 years) than the nonthrombosis group (29.2 +/- 11.7 years). Furthermore, the thrombosis group had higher thrombin-antithrombin III complex (13.1 +/- 17.7 ng/ml) and d-dimer (964 +/- 1402 ng/ml) values than the nonthrombosis group (5.3 +/- 5.5 ng/ml, P=0.0245, and 207 +/- 192 ng/ml, P=0.0016, respectively). There were no significant differences in leukocyte and platelet counts, C-reactive protein, and fibrinogen between the two groups. CONCLUSIONS: A high incidence of venous thromboembolism was suggested in Japanese patients with active IBD. We should be careful with thrombosis in treatment of IBD patients, especially those who are of older age and in more severe stages.

Antiapoptotic activity of Akt is down-regulated by Ca2+ in myocardiac H9c2 cells. Evidence of Ca(2+)-dependent regulation of protein phosphatase 2Ac.

Cell survival signaling of the Akt/protein kinase B pathway was influenced by a change in the cytoplasmic free calcium concentration ([Ca2+]i) for over 2 h via the regulation of a Ser/Thr phosphatase, protein phosphatase 2Ac (PP2Ac), in rat myocardiac H9c2 cells. Akt was down-regulated when [Ca2+]i was elevated by thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, but was up-regulated when it was suppressed by 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA-AM), a cell permeable Ca2+ chelator. The inactivation of Akt was well correlated with the susceptibility to oxidant-induced apoptosis in H9c2 cells. To investigate the mechanism of the Ca(2+)-dependent regulation of Akt via the regulation of PP2A, we examined the transcriptional regulation of PP2Acalpha in H9c2 cells with Ca2+ modulators. Transcription of the PP2Acalpha gene was increased by thapsigargin but decreased by BAPTA-AM. The promoter activity was examined and the cAMP response element (CRE) was found responsible for the Ca(2+)-dependent regulation of PP2Acalpha. Furthermore, phosphorylation of CRE-binding protein increased with thapsigargin but decreased with BAPTA-AM. A long term change of [Ca2+]i regulates PP2Acalpha gene transcription via CRE, resulting in a change in the activation status of Akt leading to an altered susceptibility to apoptosis.

Inferior vena cava filter is a new additional therapeutic option to reduce mortality from acute pulmonary embolism.

BACKGROUND: There are few reports that examine the current imaging and management techniques according to the severity of acute pulmonary embolism (APE) or that clarify whether the management strategy ameliorated the mortality from APE. METHODS AND RESULTS: The study group were 456 patients with APE who were clinically diagnosed before their death. The severity at diagnosis, and the imaging and management techniques were analyzed. Mortality from APE was 0.8% in patients without shock nor right ventricular overload, 2.7% in patients with right ventricular overload without shock, 15.6% in patients with shock, and 52.4% in patients with cardiopulmonary arrest (p<0.0001). In the more severe cases, pulmonary angiography and trans-thoracic echocardiography were used more frequently, whereas both ventilation and perfusion lung scans were used less frequently. Computed tomography was used widely, regardless of the severity. Thrombolytic therapy and catheter therapy were used more frequently in the more severe cases, but an inferior vena cava filter was the only management strategy that reduced the mortality from APE. CONCLUSIONS: The severity of APE at diagnosis affected the selection of both the diagnostic techniques and the type of management. Implantation of inferior vena cava filters reduced the mortality from APE.

The use of a hydrophilic-coated catheter during transradial cardiac catheterization is associated with a low incidence of radial artery spasm.

BACKGROUND: Radial artery spasm (RAS) is a common complication of transradial approach (TRA) to percutaneous coronary angiography (CAG) and coronary intervention. Lower friction resistance between catheter and RA wall may reduce RAS upon insertion, manipulation, and withdrawal of the catheter. The aim of this study was to investigate whether the use of a hydrophilic-coated (HC) catheter, which has lower friction coefficient, could reduce the incidence of RAS compared with a non-hydrophilic-coated (NHC) catheter. METHODS: A total 250 patients attempted diagnostic CAG using 5-French catheters via the TRA between September 2000 and April 2002. Two hundred thirty-four (93.6%) patients who achieved successful coronary cannulation were selected for the study. NHC catheters were used in 149 patients (63.7%), and HC catheters were used in 85 patients (36.3%). We compared the incidence of RAS between NHC and HC catheters. RESULTS: RAS occurred in 17 (7%) patients totally. RAS was less likely to occur in HC group (one patient, 1%) than in the NHC group (16 patients, 11%, P = 0.007). CONCLUSIONS: We conclude that the use of HC catheters can reduce RAS upon insertion, manipulation, and withdrawal of the catheter compared with NHC catheters.

Chronic visceral hypersensitivity renders defecation more susceptible to stress via a serotonergic pathway in rats.

Visceral hypersensitivity, intestinal dysmotility, and stress play major roles in irritable bowel syndrome. However, the significance of visceral hypersensitivity in stress-induced changes of colorectal motor function is not conclusive. A rat model of chronic visceral hypersensitivity was induced by mechanical colorectal irritation during postnatal development. Defecation and colonic transit time were not different between the visceral hypersensitivity and the control groups at baseline. Stress and a 5-hydroxytryptamine (5-HT) agonist both resulted in a significant increase in defecation in the visceral hypersensitivity group compared with the controls. Prior administration of granisetron, a 5-HT3 receptor antagonist, inhibited stress-induced changes in defecation in the visceral hypersensitivity group as well as the controls. Stress-induced acceleration of colonic transit was not significantly different between the two groups. Our results indicate that chronic visceral hypersensitivity can modulate the effect of stress on defecation via a serotonergic pathway and suggest that visceral hypersensitivity may be related to the susceptibility of the defecative response to stressful events in patients with irritable bowel syndrome.