[Successful Conservative Management of Bronchopleural Fistula after Intraoperative Bronchial Injury].

A 64-year-old woman diagnosed as primary lung cancer was admitted for surgery. Right lower lobectomy and ND2a-1 nodal dissection was performed under video-assisted thoracic surgery( VATS). The membranous portion of intermediate bronchus was injured about length of 5 mm while dissecting subcarinal lymph nodes. The fistula was closed by knotted suture using 4-0 polydioxanone (PDS) and covered with pericardial fat pad. Although the postoperative course was uneventful and discharged at postoperative day (POD) nine, bloody sputum appeared and right pneumothorax developed at POD 11. Bronchoscopy revealed a slit-like bronchopleural fistula at intermediate bronchus. By continuous thoracic drainage, the fistula successfully closed at POD 13.

Long-term efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 5-year extension of a phase 3 study (reSURFACE 1).

The three part, double-blind, randomized, controlled reSURFACE 1 trial and extension study (NCT01722331) evaluated efficacy and safety of tildrakizumab in adults with moderate to severe plaque psoriasis. Patients with ≥50% improvement from baseline in Psoriasis Area and Severity Index (PASI 50) following treatment with tildrakizumab 100 mg (TIL100) or 200 mg (TIL200) could enter the optional long-term extension study and continue treatment at the same dose for an additional 192 weeks. This subgroup analysis assessed the long-term efficacy and safety of tildrakizumab treatment for Japanese patients enrolled in reSURFACE 1 for up to 5 years of treatment. The primary efficacy outcomes were the proportions of patients who maintained PASI 75 and Physician Global Assessment (PGA) clear or minimal with ≥2-grade reduction from baseline (PGA 0/1) from base study week 64 to extension week 192. Secondary outcomes were the proportion of patients who maintained PASI 90/100 from base study week 64 to extension week 192. Adverse events (AEs) were monitored throughout the study and for up to 20 weeks after the last study visit. Of the 120 Japanese patients who entered the reSURFACE 1 extension study, 43 (79.6%) patients receiving tildrakizumab 100 mg and 58 (87.9%) patients receiving tildrakizumab 200 mg completed the extension study. Of all Japanese patients with PASI 75/90/100 and PGA 0/1 at week 64, 85%/88% receiving TIL100/TIL200 maintained PASI 75, 70%/96% maintained PASI 90, 63%/67% maintained PASI 100, and 68%/72% maintained PGA 0/1 at extension week 192. AEs led to discontinuation in 1.7 patients per 100 patient-years (P100PY) receiving tildrakizumab 100 mg and 0.8 P100PY receiving tildrakizumab 200 mg. Incidences of severe infections, malignancies, confirmed major adverse cardiac events, and hypersensitivity reactions were low in both treatment groups. Through 5 years of treatment, tildrakizumab maintained efficacy and was well tolerated with low rates of AEs of special interest.

Randomized, double-blind, placebo-controlled, phase I study of the safety and pharmacokinetics of namilumab in healthy Japanese and Caucasian men
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OBJECTIVE: Namilumab is an investigational human monoclonal antibody to human granulocyte-macrophage colony-stimulating factor (GM-CSF). A phase I study of repeated namilumab dosing (150 or 300 mg subcutaneously) in non-Japanese patients with rheumatoid arthritis reported no safety concerns. The objective of this study was to report the safety (primary endpoint) and pharmacokinetic/pharmacodynamic effects of namilumab in healthy Japanese and Caucasian men aged 20 - 45 years (NCT02354599). MATERIALS AND METHODS: 24 Japanese subjects were randomized to a single dose of namilumab (80, 150, or 300 mg; n = 6/group) or placebo (n = 6; 2 subjects randomized/matched dose); 8 Caucasian subjects received namilumab 150 mg (n = 6) or placebo (n = 2). RESULTS: Overall, 29 subjects completed the study (2 withdrew voluntarily; 1 due to a serious adverse event (AE) unrelated to treatment). Baseline demographics were similar across treatment groups; mean age and weight were higher in Caucasians. Namilumab was well tolerated, with no notable safety concerns or pharmacokinetic/pharmacodynamic differences between Japanese and Caucasian subjects. AEs were mild to moderate, with no dose-proportional increase in Japanese subjects. Area under the serum concentration-time curve from zero to infinity (AUC0-∞) and maximum serum concentration (Cmax) increased in a dose-proportional manner in Japanese subjects. AUC0-∞ was similar in Japanese (575.2 µg×day/mL) and Caucasian (559.7 µg×day/mL) 150-mg groups. Cmax was ~ 40% higher in Japanese subjects. Mean plasma total GM-CSF concentration-time profiles were similar in the Japanese and Caucasian 150-mg groups. Namilumab induced no clinically-relevant antibody response. CONCLUSION: Namilumab was well tolerated in Japanese and Caucasian subjects; namilumab 150 mg had similar pharmacokinetics in both populations, supporting further clinical development of this dose.
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[Esophageal Achalasia after Surgery for Lung Cancer].

A 61-year-old man was admitted to our hospital for an abnormal chest shadow. Computed tomography (CT) showed a pulmonary nodular shadow in the right middle lobe. He was diagnosed with stage cT2aN0M0 (IB) pulmonary adenocarcinoma and was treated with surgery of right middle lobectomy and mediastinal lymph node dissection. On 2nd day after surgery, he got aspiration pneumonia. CT showed consolidation of left lower lobe, stenosis of lower esophagus with dilation of the oral side and stagnation of residual foods. Esophagogram showed stenosis of the lower esophagus and stagnation of the contrast medium. He was diagnosed with esophageal achalasia. Balloon dilation was performed and the obstruction was improved. He has been well without recurrence of achalasia.

[Hemothorax due to Idiopathic Rupture of Pulmonary Artery with Defect of Tunica Media].

A 47-years-old man with hemodynamic shock was refered to our hospital by an ambulance. Chest computed tomography(CT)showed left hemothorax and the extravasation of contrast media in his left lung. Emergency operation was done. A lot of intrathoracic hematoma and pulsating bleeding from the lung was found, and lingular segmentectomy was performed. Pathologically, the rupture of pulmonary artery of 2.2 mm in diameter was found without the finding of imflammation nor degeneration due to any basal diseases. Around the lesion, some artery of 0.3~3.0 mm in diameter showed defect of tunica media. This vascular anomaly was considered to lead his hemothorax.

Impact of renal function on the underlying pathophysiology of coronary plaque composition in patients with type 2 diabetes mellitus.

BACKGROUND: Both the progression of diabetic kidney disease and increased glycemic variability play important roles in the pathogenesis of coronary plaque formation via inflammatory pathways in patients with type 2 diabetes mellitus (T2DM). Therefore we evaluated the role of renal function in the contributory effects of blood glucose fluctuations and blood levels of inflammatory cytokine concentrations on the tissue characteristics of coronary plaques in patients with T2DM. METHODS: We prospectively enrolled 71 T2DM patients (mean age: 68 ± 9, male 79%) with 153 coronary artery lesions. Patients were divided into 2 groups according to their estimated glomerular filtration rate (eGFR) levels: Group 1 (≥ 60 mL/min/1.73 m2, n = 40) and Group 2 (< 60 mL/min/1.73 m2, n = 31). All patients underwent continuous glucose monitoring (CGM) for 120 h and the mean amplitude of glycemic excursions (MAGE) was calculated. Serum tumor necrosis factor (TNF)-α was also measured. In addition, gray-scale coronary intravascular ultrasound (IVUS) and iMap-IVUS were performed in the coronary lesions with < 50% luminal reduction. RESULTS: In Group 1, MAGE correlated with percent lipidic volume (%LV) (r = 0.477, p = 0.002). In this group, stepwise multivariate linear regression analyses showed that only MAGE was independently associated with %LV (ß = 0.477, p = 0.002). In contrast, in Group 2, only serum TNF-α correlated with percent fibrotic volume (%FV) (r = - 0.471, p = 0.007), %LV (r = 0.496, p = 0.005) and percent necrotic volume (%NV) (r = 0.426, p = 0.017). In this group, stepwise multivariate linear regression analyses showed that only serum TNF-α was independently associated with each tissue characteristic (%FV ß = - 0.471 and p = 0.007, %LV ß = 0.496 and p = 0.005, %NV: ß = 0.426 and p = 0.017). CONCLUSIONS: In T2DM patients, the tissue characteristics of coronary plaques were associated with MAGE in patients with eGFR ≥ 60 mL/min/1.73 m2 and with serum TNF-α in those with eGFR < 60 mL/min/1.73 m2.

[Mucosa-associated Lymphoid Tissue Lymphoma in the Thymus;Report of a Case].

A 64-years-old woman with chronic thyroiditis was refered to our hospital because of anterior mediastinum tumors identified by chest computed tomography (CT). The lesions with increased fluoro-2-deoxy-D-glucose (FDG) uptake was noted by CT and positron emission tomography (PET). Extended thymo-thymectomy was performed, and the tumors was completely resected. Pathologically, the tumors were diagnosed as mucosa-associated lymphoid tissue( MALT) lymphoma of the thymus. Postoperative chemotherapy was not performed and the patient has been well for 4 years without recurrence. But she has developed the symptoms of Sjögren syndrome 3 years after operation.

Excess APP O-glycosylation by GalNAc-T6 decreases Aß production.

Alterations of the structure and/or amount of glycans present on proteins are associated with many diseases. We previously demonstrated that changes in N-glycans alter Aß production. In the present study, we focused on the relationship between Alzheimer's disease (AD) and O-glycan, another type of glycan. The UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family functions in the first step of mucin-type O-glycan synthesis. Analysis of the expression of GalNAc-Ts in the human brain using real-time PCR revealed that the expression of several GalNAc-Ts was altered with sporadic AD progression. Three of these GalNAc-Ts (GalNAc-T1, GalNAc-T4 and GalNAc-T6) were transfected into HEK293T cells to examine their impact on Aß production. Transfection of GalNAc-T6 significantly reduced both Aß1-40 and Aß1-42 generation, but GalNAc-T1 and GalNAc-T4 only reduced Aß1-40 generation. Although these three GalNAc-Ts exhibited enzymatic activities on soluble amyloid precursor protein (APP), the GalNAc transferase activity of GalNAc-T6 to APP was most prominent. The expression of α-secretase and ß-secretase was slightly altered in the transfected cells, but the activities of α-secretase and ß-secretase were not significantly altered. These data suggest that excess O-glycosylation on APP by GalNAc-T6 inhibits Aß production.

Chronic Inflammatory Disease Is an Independent Risk Factor for Coronary Flow Velocity Reserve Impairment Unrelated to the Processes of Coronary Artery Calcium Deposition.

BACKGROUND: Chronic inflammatory disease (CID) is a complex multisystem disease characterized by chronic inflammation, which can lead to coronary microvascular dysfunction (CMD) and can also predispose to coronary artery calcium deposition, even in the absence of obstructive coronary artery disease. METHODS: Twenty-one patients with systemic lupus erythematosus (SLE; mean age, 60 ± 11 years), 21 patients with systemic sclerosis (SSc; mean age, 66 ± 11 years), 32 patients with rheumatoid arthritis (RA; mean age, 65 ± 9 years), and 23 control subjects with comparable traditional risk factors for coronary artery disease (mean age, 65 ± 10 years) were prospectively enrolled in the outpatient clinic. All study participants underwent transthoracic Doppler-derived echocardiography for coronary flow velocity reserve (CFVR) measurement in the left anterior descending coronary artery; CFVR < 2.5 defined CMD. Coronary artery calcium score in the left anterior descending coronary artery was also assessed by computed tomography. RESULTS: None of study participants had obstructive coronary artery disease. The prevalence of CMD was 26% in the control group, 67% in the SLE group, 76% in the SSc group, and 63% in the RA group (P < .05, CID groups vs control group). CFVR was significantly lower in all three CID groups than in the control group (control group, 3.01 ± 0.72; SLE group, 2.23 ± 0.71; SSc group, 2.14 ± 0.54; RA group, 2.33 ± 0.62; P < .05, CID groups vs control group). In contrast, coronary artery calcium scores were similar in the four groups and had no relation to CMD. The odds ratios for CMD in patients with SLE, SSc, and RA were 16.70, 25.78, and 8.44 (P < .05) after adjusting for age, body mass index, the presence or absence of anemia, and hemoglobin level. Multiple linear regression analysis showed that only the presence of CID was independently associated with reduced CFVR among all study participants. CONCLUSIONS: CID strongly contributes to CMD identified by qualitative evaluation of CFVR independently of traditional coronary risk factors of atherosclerosis but does not predispose to coronary artery calcification.

Comparison of neointimal coverage between everolimus-eluting stents and sirolimus-eluting stents: an optical coherence tomography substudy of the RESET (Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial).

AIMS: The aim of the present study was to compare vascular healing response between the first-generation sirolimus-eluting stent (SES) and the second-generation everolimus-eluting stent (EES) by using optical coherence tomography (OCT). METHODS AND RESULTS: The RESET was a prospective, multicentre, randomised, open-label trial comparing EES and SES. Of the 3,197 patients enrolled in the RESET, nine-month follow-up OCT after stent implantation was performed in 100 patients (48 EES-treated lesions in 44 patients and 62 SES-treated lesions in 56 patients), thus constituting the OCT substudy population. The percentage of uncovered struts per lesion (8±15% vs. 14±19%, p=0.031) and cross-sections with >30% uncovered struts per lesion (6±14% vs. 18±29%, p=0.009) was significantly lower in EES compared with SES. The frequency of DES-treated lesions with incomplete stent apposition (8 [17%] vs. 29 [47%], p<0.001) was significantly lower in EES compared with SES. Intra-stent thrombus was comparably observed between EES and SES (1 [2%] vs. 5 [8%], p=0.229). CONCLUSIONS: Compared with SES, EES was associated with a favourable vascular response at nine months after stent implantation.

Detection of coronary artery disease using coronary flow velocity reserve by transthoracic Doppler echocardiography versus multidetector computed tomography coronary angiography: influence of calcium score.

BACKGROUND: There have been no clinical data specifying the degree of calcium deposition at which coronary flow velocity reserve (CFVR) measurement using transthoracic Doppler echocardiography surpasses 320-row multidetector computed tomographic coronary angiography (CTCA) in detecting obstructive coronary artery disease. METHODS: One hundred seventy patients who underwent invasive coronary angiography, transthoracic Doppler echocardiography, and CTCA were prospectively enrolled. Coronary artery stenosis was defined as percentage diameter stenosis ≥ 50% on invasive coronary angiography. CFVR < 2.0 and narrowing ≥ 50% measured with CTCA were the thresholds indicating the presence of coronary artery stenosis. The degree of coronary artery calcification was also assessed using the Agatston calcium score method by computed tomography. RESULTS: The majority of patients (89%) were classified as having either high or intermediate pretest probability of coronary artery disease. Significant coronary artery stenoses by invasive coronary angiography were found in 71 patients and 104 vessels. Although the overall diagnostic performance of CTCA was comparable with that of CFVR measurement for detecting coronary artery stenosis, only the diagnostic performance of CTCA was negatively affected by the extent of a patient's coronary artery calcification. Receiver operating characteristic curve analysis indicated that only CFVR measurement is diagnostically accurate when calcium scores are >319 in the patient-based assessment, 189 for the left anterior descending coronary artery, 98 for the left circumflex coronary artery and 282 for the right coronary artery. CONCLUSIONS: Transthoracic Doppler echocardiography and 320-row multidetector CTCA successfully diagnosed significant coronary artery stenosis with high feasibility and accuracy. However, only the diagnostic performance of CTCA was negatively affected by the extent of a patient's coronary artery calcification, and therefore the diagnostic performance of CFVR measurement for detecting coronary artery stenosis surpassed that of CTCA when the calcium score exceeded specified cutoff values.

The prognostic significance of eukaryotic elongation factor 1 alpha-2 in non-small cell lung cancer.

BACKGROUND: Eukaryotic elongation factor 1 alpha-2 (eEF1A2) has been recently shown to be a putative oncogene of lung cancer. MATERIALS AND METHODS: We analyzed the expression and prognostic significance of eEF1A2 in 69 primary non-small cell lung cancer (NSCLC) cases. We also suppressed eEF1A2 expression using RNA interference and then analyzed cell proliferation, migration and invasion of five adenocarcinoma cell lines. RESULTS: eEF1A2 protein expression was positive in 84.1%. Negative immunostaining for eEF1A2 was shown to be an independent prognostic factor and significantly correlated with lymph node metastasis. There was no significant correlation between eEF1A2 protein and mRNA expression levels. Among the five examined cell lines, transfection of eEF1A2 siRNA inhibited cell migration in only one cell line while it did not change cell proliferation and invasion. CONCLUSION: Negative immunostaining of eEF1A2 predicted for poor prognosis of NSCLC. The mechanism of this result could not be elucidated by cell proliferation, migration and invasion assays.

[Clinicopathological features of peripheral small-sized (2 cm or less in diameter) non-small cell lung cancer].

Ninety-three patients with completely resected peripheral non-small cell lung cancer, clinically diagnosed 2 cm or less in diameter, were retrospectively reviewed. Their preoperative computed tomography (CT) and positron emission tomography (PET) findings, carcinoembryonic antigen (CEA) values, clinico-pathological features and postoperative outcomes were analysed. Ground-glass opacity (GGO) ratio( soft tissue density area of the tumor/maximum area of the tumor in diameter) was measured. The overall survival rate at 3 years was 93.3% and the relapse-free survival rate at 3 years was 89.4% with a median follow-up period of 38.5 months. Patients with GGO ratio 0.25 or less had no lymph node (LN) involvement nor lymph vascular invasion. Only 2 of them (8%) had vascular invasion. Fisher's exact probability test revealed CEA ≥ 5 ng/ ml as risk factor for LN involvement( p=0.0400). Multiple logistic regression analysis showed that solid adenocarcinoma and squamous cell carcinoma recurred more frequently than adenocarcinoma with GGO (p=0.0619, odds ratio 4.969, 95%CI 0.9242~37.67).

String-sign in left internal thoracic artery is associated with regression in left main trunk stenosis after coronary artery bypass.

The left internal thoracic artery (LITA) is the conduit of choice for coronary artery bypass (CABG) due to favorable long-term patency. Uncommonly, diffuse narrowing like a string without significant stenosis of an anastomosis is observed in the LITA graft (called "string sign"). Isolated left main trunk (LMT) diseases were reported to regress in some cases. However, the relationship between "string sign" and the regression of solitary LMT disease remains unknown.We retrospectively studied 40 consecutive patients with isolated LMT stenosis who underwent CABG using LITA and who underwent angiography before and after operation (31 males, 9 females, mean age, 65.0 years). The patients were divided into 2 groups according to the postoperative angiographic outcomes of the LITA graft: one group included patients with "string sign" (6 patients), the other group consisted of patients with a patent LITA graft (34 patients).There were no significant differences in clinical backgrounds between the two groups. The 2 groups showed similar quantitative % coronary artery stenosis of the LMT before operation (77.5% versus 76.8%) and the observation period was similar in both groups. Coronary angiography after CABG revealed that % stenosis of the LMT in patients with "string sign" was significantly less than that in patients with a patent LITA graft (41.7 ± 26% versus 82.5 ± 11%, P < 0.001). Regression in LMT was significantly more frequently observed in the "string sign group". Furthermore, ostial stenosis was more frequent in patients with "string sign". "String phenomenon" of the LITA graft is one of the signs related to the regression of LMT stenosis, and especially in ostial stenosis of the LMT.

[A case of castration-refractory prostate cancer showing marked decrease of serum PSA level after zoledronic acid treatment with estramustine phosphate and prednisolone].

A 66-year-old man was referred to our outpatient clinic for an elevated serum prostatic-specific antigen (PSA 4,319 ng/ mL). Magnetic resonance imaging (MRI) showed multiple metastatic lesions in the bones. The patient had received androgen deprivation therapy, but six months after treatment, he was diagnosed as having prostate cancer refractory to hormones. Combined treatment with docetaxel (DOC 30 mg/m²/week )and estramustine phosphate (EMP 560 mg/day) was initiated as first-line chemotherapy, but the treatment was discontinued because of side effects. Then, treatment with zoledronic acid was started(4 mg/4 weeks)and the PSA level decreased dramatically from 457.2 ng/mL to 5.5 ng/mL. Seven months after the diagnosis of CRPC, MRI showed a decrease ofbone metastases, and the PSA levels continued to decrease, eventually reaching 0.3 ng/mL. Zoledronic acid appears to not only show efficacy in preventing skeletal-related events, but has a potential antitumor effect in patients with metastatic CRPC.

[The fluorodeoxyglucose-positron emission tomography (FDG-PET) findings and surgical strategy for pulmonary sclerosing hemangioma].

The pulmonary sclerosing hemangioma is a comparatively rare lung tumor. We operated on 7 patients of the pulmonary sclerosing hemangioma during January, 2009 from December, 2001. We collected the information such as preoperative image findings, surgical methods, and the postoperative course. FDG-PET was performed in 4 patients preoperatively, and there was FDG uptake in 2 patients, and no FDG uptake in 2 patients. In 2 cases with FDG uptake, there was a tendency to increase the tumor diameter during preoperative follow-up. Among 7 patients, 1 patient underwent tumor enucleation, 2 patients underwent partial resection, and 2 patients underwent thoracoscopic lobectomy. Lung biopsy was performed in remaining 2 cases. Because a tumor was located in pulmonary hilum in 1 case, we underwent lung needle biopsy under thoracoscopy. Because another case was a multiple case, and the resection of all lesions was impossibile, we performed lung biopsy (partial resection). In all cases, the recurrence or exacerbation of the tumor was not detected postoperatively. We thought that the findings of FDG-PET reflected proliferation potency of the pulmonary sclerosing hemangioma. The clinical features of the pulmonary sclerosing hemangioma are various. Therefore, the surgical treatment should be determined in each case carefully while considering the FDG-PET findings.

[Female case of successful engraftment after PBSCT from her HLA-haploidentical son for severe aplastic anemia during maintenance peritoneal dialysis].

A 51-year-old woman developed very severe aplastic anemia complicated by chronic renal failure. She underwent ATG therapy, resulting in a transient effect. Thereafter, renal insufficiency progressed, followed by the induction of CAPD therapy. Although rabbit ATG (rATG) was administered as the next immunotherapy for aplastic anemia, pancytopenia persisted and she experienced repeated episodes of severe infection including MRSA and fungal infections. She was transplanted with peripheral blood stem cells from her HLA-haploidentical son after a reduced-intensity conditioning regimen that included cyclophosphamide (three days of 30 mg/kg), fludarabine (two days of 20 mg/m(2)) and rATG (three days of 2.5 mg/kg). FK506 (0.03 mg/kg/24H) was administered for the prophylaxis of GVHD. Prompt trilineage engraftment occurred, resulting in the improvement of infections. Three months after grafting, she succumbed to cerebrovascular disease, although there was no apparent GVHD and she had remained well with stable hematopoiesis.

Synergistic effect of a factor Xa inhibitor, TAK-442, and antiplatelet agents on whole blood coagulation and arterial thrombosis in rats.

INTRODUCTION: Activated platelets facilitate blood coagulation by providing factor V and a procoagulant surface for prothrombinase. Here, we investigated the potential synergy of a potent factor Xa/prothrombinase inhibitor, TAK-442, plus aspirin or clopidogrel in preventing arterial thrombosis and whole blood coagulation. METHODS: Thrombus formation was initiated by FeCl(3)-induced rat carotid injury. Bleeding time was evaluated with the rat tail transection model. Whole blood coagulation was assessed by thromboelastographic examination (TEG) for which blood obtained from control, aspirin-, or clopidogrel-treated rats was transferred to a TEG analyzer containing, collagen or adenosine diphosphate (ADP), and TAK-442 or vehicle. RESULTS: TAK-442 (3mg/kg, po), aspirin (100mg/kg, po) or clopidogrel (3mg/kg, po) alone had no significant effect on thrombus formation, whereas the combination of TAK-442 with aspirin and clopidogrel remarkably prolonged the time to thrombus formation without additional significant prolongation of bleeding time. TEG demonstrated that the onset of collagen-induced blood coagulation were slightly longer in aspirin-treated rats than control; however, when the blood from aspirin-treated rats was subsequently treated in vitro with 100 nM TAK-442, the onset of clotting was significantly prolonged. In contrast, only marginal prolongation was observed with TAK-442 treatment of blood from control animals. The onset time of ADP-induced blood coagulation was slightly longer in clopidogrel-treated rats compared with control, and it was further extended by TAK-442 treatment. CONCLUSION: These results demonstrate that blood coagulation can be markedly delayed by the addition of TAK-442 to antiplatelets treatment which could contribute to synergistic antithrombotic efficacy in these settings.

Delayed Cell Cycle Progression and Apoptosis Induced by Hemicellulase-Treated Agaricus blazei.

We examined the effects of hemicellulase-treated Agaricus blazei (AB fraction H, ABH) on growth of several tumor cell lines. ABH inhibited the proliferation of some cell lines without cytotoxic effects. It markedly prolonged the S phase of the cell cycle. ABH also induced mitochondria-mediated apoptosis in different cell lines. However, it had no impact on the growth of other cell lines. ABH induced strong activation of p38 mitogen-activated protein kinase (MAPK) in the cells in which it evoked apoptosis. On the other hand, ABH showed only a weak p38 activation effect in those cell lines in which it delayed cell cycle progression with little induction of apoptosis. However, p38 MAPK-specific inhibitor inhibited both ABH-induced effects, and ABH also caused apoptosis in the latter cells under conditions of high p38 MAPK activity induced by combined treatment with TNF-alpha. These results indicate that the responsiveness of p38 MAPK to ABH, which differs between cell lines, determines subsequent cellular responses on cell growth.

Long-term (11-year) statin therapy following percutaneous coronary intervention improves clinical outcome and is not associated with increased malignancy.

BACKGROUND: Statins have been proven to reduce cardiac events and mortality. However, there are few studies dealing with the long-term efficacy of statin therapy following percutaneous coronary intervention (PCI). METHODS: We collected data from 575 consecutive patients who underwent PCI between 1987 and 1992. The baseline data, mortality and incidence of cardiovascular events of patients given statins and those not given statins at the time of PCI were compared. RESULTS: There were 243 patients in the statin group and 332 patients in the non-statin group. During follow-up (11.0+/-3.0 years), 68 patients died. At about 10 years, statin use was significantly associated with lower all-cause mortality (8.2% versus 14.5%, P=0.023) and cardiac death (2.5% versus 6.9%, P=0.017). After adjusting for variables, statin use was found to be an independent predictor of death from all causes (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.29-0.99, P=0.048) and cardiac death (HR 0.24, 95% CI 0.07-0.80, P=0.02). CONCLUSION: Statin use at the time of PCI was associated with a significantly reduced risk of death from all causes and cardiac death. Furthermore, this study provides evidence of a clinical benefit at about 10 years of statin use in patients who underwent PCI.