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Dedifferentiation programs are commonly enacted during breast cancer progression to enhance tumor cell fitness. Increased cellular plasticity within the neoplastic compartment of tumors correlates with disease aggressiveness, often culminating in greater resistance to cytotoxic therapies or the augmented ability to metastasize to distant organs. Here we report that subpopulations of dedifferentiated neoplastic breast epithelial cells express canonical leukocyte cell surface receptor proteins and have thus named this cellular program "immune mimicry." We document neoplastic cells engaging in immune mimicry within public human breast tumor single-cell RNA-seq datasets, histopathological breast tumor specimens, breast cancer cell lines, as well as in murine transgenic and cell line-derived mammary cancer models. Immune-mimicked neoplastic cells harbor hallmarks of dedifferentiation and appear enriched in treatment-resistant and high-grade breast tumors. We corroborated these observations in aggressive breast cancer cell lines where growth-arresting cytotoxic chemotherapies drove epithelial cells toward immune mimicry. Moreover, in subsequent proof-of-concept studies, we demonstrate that expression of the CD69 leukocyte activation marker by neoplastic cells confers a proliferative advantage that facilitates early tumor growth. We conclude neoplastic breast epithelial cells that upregulate leukocyte surface receptors potentiate malignancy. Moving forward, neoplastic immune mimicry should be evaluated for prognostic utility in breast cancer to determine its stratification potential for patients with increased risks of tumor recurrence, metastasis, and therapeutic resistance.

Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib. We found that ovarian cancer cell lines with high levels of endogenous Cyclin E1 expression or forced overexpression were exquisitely sensitive to azenosertib and these results extended to in vivo models of ovarian and uterine serous carcinoma. Models with high Cyclin E1 expression showed higher baseline levels of replication stress and enhanced cellular responses to azenosertib treatment. We found azenosertib synergized with different classes of chemotherapy and described distinct underlying mechanisms. Finally, we provided early evidence from an ongoing phase I study demonstrating the clinical activity of monotherapy azenosertib in patients with Cyclin E1/CDK2-activated ovarian and uterine serous carcinomas., Competing Interests: Competing interests: D. Kim is an employee and shareholder of Zentalis Pharmaceuticals. H. Chung is an employee and shareholder of Zentalis Pharmaceuticals. W. Liu is an employee and shareholder of Zentalis Pharmaceuticals. S. Kim is an employee and shareholder of Zentalis Pharmaceuticals. X. Guo is an employee and shareholder of Zentalis Pharmaceuticals. N. Jameson is an employee and shareholder of Zentalis Pharmaceuticals. P.R. de Jong is a former employee of Zentalis Pharmaceuticals. S. Yea is a former employee and shareholder of Zentalis Pharmaceuticals. L. Harford is a former employee and shareholder of Zentalis Pharmaceuticals. J. Li is a former employee of Zentalis Pharmaceuticals. D. Kim is an employee and shareholder of Zentalis Pharmaceuticals. K. Fischer is an employee and shareholder of Zentalis Pharmaceuticals. A. Samatar is a former employee of Zentalis Pharmaceuticals and shareholder in Zentalis Pharmaceuticals. A. Jubb is a former employee and shareholder of Zentalis Pharmaceuticals. K. Bunker is a former employee of Zentalis Pharmaceuticals and shareholder in Zentalis Pharmaceuticals. K. Blackwell is a former employee and shareholder of Zentalis Pharmaceuticals. F. Simpkins serves on scientific advisory boards for AstraZeneca, GSK and Zentalis Pharmaceuticals; has received institutional research funding from AstraZeneca, Repare Therapeutics, Instill Bio and Sierra Oncology. F. Meric-Bernstam is consultant for. AbbVie, Aduro BioTech Inc., Alkermes, AstraZeneca, Daiichi Sankyo Co. Ltd., Calibr (a division of Scripps Research), DebioPharm, Ecor1 Capital, eFFECTOR Therapeutics, Exelixis, F. Hoffman-La Roche Ltd., GT Apeiron, Genentech Inc., Harbinger Health, IBM Watson, Incyte, Infinity Pharmaceuticals, Jackson Laboratory, Jazz Pharmaceuticals, Kolon Life Science, LegoChem Bio, Lengo Therapeutics, Loxo Oncology, Menarini Group, OrigiMed, PACT Pharma, Parexel International, Pfizer Inc., Protai Bio Ltd, Samsung Bioepis, Seattle Genetics Inc., Tallac Therapeutics, Tyra Biosciences, Xencor, Zymeworks; Advisory Committee for Black Diamond, Biovica, Eisai, FogPharma, Immunomedics, Inflection Biosciences, Karyopharm Therapeutics, Loxo Oncology, Mersana Therapeutics, OnCusp Therapeutics, Puma Biotechnology Inc., Seattle Genetics, Sanofi, Silverback Therapeutics, Spectrum Pharmaceuticals, Theratechnologies, Zentalis; Received sponsored Research (to the institution) from Jazz Pharmaceuticals, Zymeworks, Aileron Therapeutics, Inc. AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences Inc., Curis Inc., CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., Debiopharm International, eFFECTOR Therapeutics, Genentech Inc., Guardant Health Inc., Klus Pharma, Takeda Pharmaceutical, Novartis, Puma Biotechnology Inc., Taiho Pharmaceutical Co.; Honoraria for Dava Oncology; receiving travel related funding and reimbursement from European Organization for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO), Cholangiocarcinoma Foundation, Dava Oncology. G.B. Mills is scientific advisory board/Consultant for Amphista, Astex, AstraZeneca, BlueDot, Chrysallis Biotechnology, Ellipses Pharma, GSK, ImmunoMET, Infinity, Ionis, Leapfrog Bio, Lilly, Medacorp, Nanostring, Nuvectis, PDX Pharmaceuticals, Qureator, Roche, Signalchem Lifesciences, Tarveda, Turbine, Zentalis Pharmaceuticals; Stock/Options/Financial: Bluedot, Catena Pharmaceuticals, ImmunoMet, Nuvectis, SignalChem, Tarveda, Turbine; Licensed Technology: HRD assay to Myriad Genetics, DSP patents with Nanostring; Sponsored research: AstraZeneca. O. Harismendy is an employee and shareholder of Zentalis Pharmaceuticals. J. Ma is an employee and shareholder of Zentalis Pharmaceuticals. M.R. Lackner is an employee and shareholder of Zentalis Pharmaceuticals. No disclosures were reported by the other authors., (© 2025. The Author(s).)

Introduction: We aimed to demonstrate the sensitivity of frozen section for patients with adult granulosa cell tumor (AGCT) and analyze the clinico-pathological factors that may be associated with sensitivity., Material Methods: This is a multicenter study including data of 10 Gynecological Oncology Departments. Frozen-section results of patients who had ovarian AGCT at the final pathology report were retrospectively analyzed. The relation between clinico-pathological characteristics such as age, tumor size, Ca-125 level, presence of ascites, omental metastasis, menopausal status and peritoneal cytology, and the sensitivity of frozen section in patients with AGCT were evaluated. The sensitivity of frozen section diagnosis was determined by comparing the frozen section result with the final pathological diagnosis., Results: Frozen section results of 274 patients with AGCT were obtained. The median age of the patients was 52 years (range, 17-82 years). Totally, 144 (52.7%, n = 273) patients were postmenopausal. The median tumour size was 90 mm (range, 9-700 mm). The median preoperative Ca-125 level was 23 IU/mL (range, 2-995 IU/mL). The sensitivity of frozen section for detecting AGCT was 76.3%. Any association between the sensitivity of frozen section and menopausal status, presence of ascites, positive cytology, omental metastasis, tumor size, Ca-125 level, age could not be shown., Conclusion: It is important to know the diagnosis of AGCT intraoperatively, and we demonstrated the sensitivity of frozen-section for these tumors as 76.3%., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Humoral factors and neural mechanisms play a central role in the pathogenesis of obesity and in weight loss following bariatric surgery. Although various hormones and adipokines, including ghrelin and resistin, are linked to obesity, studies analyzing the changes in fasting ghrelin and resistin levels in patients following one anastomosis gastric bypass (OAGB) are lacking., Aim: The authors aimed to investigate resistin and ghrelin levels before and after two commonly used bariatric procedures with different mechanisms of action: sleeve gastrectomy (SG) and OAGB., Patients and Methods: Fasting serum ghrelin and resistin levels were evaluated by using ELISA in a nonrandomized, prospective cohort study for the pattern of changes in the preoperative period and 1 week, 1 month, 3 months and, 12 months after surgery in age and sex-matched patients with BMI ≥40 kg/m 2 undergoing either SG ( n =40) or OAGB ( n =40). Their relationships with demographic parameters such as body weight, BMI, presence of T2DM, HbA 1 C, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index were also evaluated., Results: OAGB was superior in weight control compared to the SG group. There were significant differences in resistin and ghrelin levels between the OAGB and SG groups. Ghrelin decreased more in the SG group than the preoperative values. This change in ghrelin levels was more significant at 1 year after SG [preoperative mean (range) level of 334.2 (36.6-972.1) pg/ml decreased to 84 (9.1-227) pg/ml at 1 year] whereas in the OAGB group no significant change was observed [preoperative mean (range) level of 310 (146-548) pg/ml decreased to 264 (112-418) pg/ml at 1 year]. Resistin levels decreased in both groups, especially after 3 months and onward following both operations [the mean (range) resistin levels were 2.6 (0.87-5.4) ng/ml and decreased to 1.1 (0.5-2.4) ng/ml in the SG group vs 2.48 (0.89-6.43) ng/ml decreased to 0.72 (0.35-1.8) ng/ml in OAGB group at 1 year], which was in parallel with changes in HOMA-IR index, body weight, and BMI changes at 1st year. HOMA-IR index changes were similar, but more prominent after OAGB. OAGB was als3 three months and onward), and HOMA-IR changes., Conclusion: This is the first study to compare fasting ghrelin and resistin levels after OAGB and SG. Although similar changes were observed, ghrelin changes were more prominent after SG, whereas resistin were observed after OAGB. OAGB was superior in T2DM control, which was in parallel with weight loss, fasting resistin levels, and HOMA-IR changes suggesting a possible effect of resistin after OAGB in glucose metabolism and insulin resistance., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The main feature of adult granulosa cell tumors (AGCT) is their capacity to secrete hormones, with nearly all of them capable of synthesizing oestradiol. The primary goal of this study is to identify synchronized endometrial pathologies, particularly endometrial cancer, in AGCT patients who had undergone a hysterectomy., Materials and Methods: The study cohort comprised retrospectively of 316 AGCT patients from 10 tertiary gynecological oncology centers. AGCT surgery consisted of bilateral salpingo-oophorectomy, hysterectomy, peritoneal cytology, omentectomy, and the excision of any suspicious lesion. The median tumor size value was used to define the relationship between tumor size and endometrial cancer. The relationship between each value and endometrial cancer was evaluated., Results: Endometrial intraepithelial neoplasia, or hyperplasia with complex atypia, was detected in 7.3% of patients, and endometrial cancer in 3.1% of patients. Age, menopausal status, tumor size, International Federation of Gynecology and Obstetrics stage, ascites, and CA-125 level were not statistically significant factors to predict endometrial cancer. There was no endometrial cancer under the age of 40, and 97.8% of women diagnosed with endometrial hyperplasia were over the age of 40. During the menopausal period, the endometrial cancer risk was 4.5%. Developing endometrial cancer increased to 12.1% from 3.2% when the size of the tumor was >150 mm in menopausal patients (p = 0.036)., Conclusion: Endometrial hyperplasia, or cancer, occurs in approximately 30% of AGCT patients. Patients diagnosed with AGCT, especially those older than 40 years, should be evaluated for endometrial pathologies. There may be a relationship between tumor size and endometrial cancer, especially in menopausal patients., (© 2024 Japan Society of Obstetrics and Gynecology.)

This is the first study to have investigated the prognostic role of cytokines and soluble human leukocyte antigen-G (sHLA-G) levels in pediatric leukemia patients who have undergone allogeneic stem cell transplantation (allo-SCT). Forty-one patients with acute leukemia (n = 28, acute lymphoblastic leukemia (ALL) and n = 13, acute myeloblastic leukemia) were recruited. Patients were examined at diagnosis (n = 26), in the pre-transplantation period (PreTx) (n = 26), on the day of transplantation (Tx 0 ) (n = 41), and on post-transplantation Days 14 (PostTx 14 ) (n = 41) and 28 (PostTx 28 ) (n = 41). Serum levels of pro-inflammatory cytokines (interleukin [IL]-1, IL-2, IL-6, Tumor necrosis factor [TNF]-α), anti-inflammatory cytokines (IL-4, IL-10), and sHLA-G were measured by Enzyme-Linked ImmunoSorbent Assay. Median levels of all cytokines tested and sHLA-G were significantly higher at diagnosis and at the post-transplant time points than at PreTx (all p < 0.05). At the time of diagnosis (specifically ALL) and at PostTx 14 , elevated IL-4, IL-10, and/or sHLA-G were associated with higher post-transplant relapse rates (all p < 0.05). Elevated IL-2 and TNF-α at Tx 0 were associated with lower survival rates (both p < 0.05). Levels of serum cytokines and sHLA-G may be useful predictors of survival and relapse in pediatric leukemia patients who undergo allo-SCT., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Aims: The immune cells in tumor microenvironment release chemokines and cytokines which determine the immune phenotype of the tumor and play an important role in the prognosis. Present study evaluates the gene expression levels of IL-21 and IL-32 and their relations to clinicopathologic parameters in colorectal cancer., Patients and Methods: 31(17F) patients with colorectal cancer were included. Samples were obtained from normal and tumor tissues. After RNA isolation, IL-21 and IL-32 gene expression levels were measured. Immunohistochemistry was also carried out for CD4+, CD8+ and NKcells to measure cell density. The relations between expression levels, immune cell density and differentiation, stage, presence of vascular, perineural invasion and lymph node metastasis(MLN) were investigated., Results: IL-32 gene expression levels were increased in tumor tissues. IL-21 levels were found to be decreased in 50% of the patients. IL-32 levels were also increased with the stage however, it was decreased significantly with the increased number of the MLN. On the other hand, expression levels of IL-21 increased significantly with the presence of vascular invasion. CD4+ density was decreased with increased T-stage, vascular invasion whereas CD8+ density decreased only with the vascular invasion., Conclusions: IL-32 expressed by tumor microenvironment reveals that expression increased to control tumor growth, but levels are decreased with the increased number of MLNs which might be due to decreased CD4+ cell density. Changes on IL-21 and IL-32 together with the changes on immune cell density, indicate their role in tumor growth and invasion in colon cancer., Key Words: Colorectal Cancer, Cytokines, Immune Cell Density, Interleukin-21, Interleukin-32, Tumor Microenvironment.

Introduction: After bariatric surgery (BS), patients might suffer from nutrient maldigestion, malabsorption, and vitamin deficiencies. In this study, our aim was to assess pancreatic functions after BS using fecal elastase-1 assay (FE-1)., Material and Methods: Sixty patients (21M) undergoing BS and 20 (6M) healthy controls were included into the study. Stool samples were collected 1 year after surgery. Ten patients from one anastomosis gastric bypass (OAGB) and single anastomosis duodenal switch (SADS) groups with the lowest value of FE-1 and GIQLI scores were given pancreatic enzyme replacement therapy (PERT). After PERT, FE-1, excess weight loss (EWL), BMI, GIQLI scores, and vitamin D levels were measured., Results: Vitamin D levels were detected as 19.04 (9-46.5) pg/ml, 15.1 (8.4-23.6) pg/ml, 17.8 (5-30) pg/ml, and 21.79 (11-40.3) pg/ml after sleeve gastrectomy (SG), OAGB, SADS, and control groups, respectively (p = 0.04). GIQLI scores in the first year were found to have increased in all patients (p = 0.02). FE-1 levels were found as 642.35 (566.3-711.4) μg/g, 378.52 (183.5-561.1) μg/g, 458.88 (252.5-593, 5) μg/g, and 518.2 (351.6-691) μg/g for the SG, OAGB, SADS, and control groups, respectively. There was a strong inverse correlation between EWL and FE-1 levels at the end of the first year (Spearman's rho = - 0.688, p = 0.003). After having performed PERT for patients with the lowest FE-1 levels, the levels increased to 683.39 (615.5-720) μg/g in the OAGB and 691.5 (643.1-720) μg/g in the SADS groups (p = 0.011)., Conclusion: FE-1 measurements demonstrated that many patients suffer from malabsorption after OAGB or SADS, whereas functions remain normal after SG. PERT corrects pancreatic functions without affecting weight loss and also contributes to the normal serum level of vitamin D.

Objectives: Gastric cancer is a common malignancy worldwide. Effective treatment by interdisciplinary cooperation is important, and surgery still plays an important role., Material and Methods: In a ten-year period, 355 patients were diagnosed to have gastric cancer. One hundred and sixty-two patients with a median (range) age of 58 (23-83) years were eligible for the study. There were 107 patients in D2 and 55 patients in D2 lymphadenectomy plus para-aortic lymph node (PALN) dissection group. The two groups were compared in terms of complications, morbidity, mortality and long-term survival., Results: Length of stay was 12 (8-34) days for D2 and 14 (8-42) days for D2 plus PALND. Total number of operative mortality was 8/162 (5%), and it was not different between the groups. Twenty patients (18%) had complications in D2 group and 9 (17%) patients in D2 plus PALND group. Overall survival was also similar between the groups, but patients with T3-T4 tumors, patients with stage IIIA and IIIB disease had better survival with D2 plus PALN dissection. We found that the depth of invasion, PLN, ratio (PLN/TLN), stage and LND were all prognostic variables., Conclusion: This study showed that D2 plus PALN dissection for advanced gastric cancer can be performed as safely as a standard D2 dissection by experienced surgeons without increasing postoperative morbidity and mortality. D2 plus PALN dissection should be preferred in the advanced stage of the disease (IIIA-IIIB) as it increases the rate of survival., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest., (Copyright © 2021, Turkish Surgical Society.)

Background and objectives: Sarcoidosis is a systemic inflammatory disease of unknown etiology that involves any part of the body, mainly the lungs and thoracic lymph nodes. The clinical presentation is heterogeneous based on the degree and extent of organ involvement. The existence of variable clinical presentations and treatment responses suggest an important role of genetic predisposition. In genetic studies, sarcoidosis was found to be associated with several genes, but the strongest link was with HLA region. The aim of this study was to investigate the association of HLA class II alleles with the extent and course of disease in Turkish patients with sarcoidosis. Methods: The study included 103 patients with sarcoidosis and 100 unrelated healthy controls. HLA-DRB1 and HLA-DQB1 typing was performed by using Polymerase Chain Reaction-Sequence Specific Priming (PCR-SSP) method at low resolution level. Results: HLA-DRB1* and -DQB1* analysis revealed that while the frequency of HLA-DRB1*01 was significantly higher in the control group, HLA-DRB1*13 and -DQB1*06 alleles were more frequent in the sarcoidosis patients. When the patients were grouped based on clinical outcome as remitters and non-remitters, HLA-DRB1*10 allele was only detected in the remitters, whereas the frequency of HLA-DQB1*06 allele was significantly higher in non-remitters. Conclusions: This study supported the association of HLA alleles with sarcoidosis. In a considerably high number of patients with Turkish origin, the frequency of HLA-DRB1*13, -DRB1*10 and HLA-DQB1*06 alleles was significantly associated with increased risk and clinical outcome. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 143-149) ., (Copyright: © 2018.)

Background: Inflammatory activity originating from the epicardial adipose tissue (EAT) may have a role in coronary artery disease (CAD) pathogenesis. The relationship between macrophage infiltration, polarization in the EAT, and netrin-1 gene expression was investigated., Methods: Macrophage infiltration and polarization were examined by immunohistochemical methods and expression levels of netrin-1, Unc5b, and cytokines related with M1-macrophage subtype (IL-12 and IL-18) were determined by quantitative polymerase chain reaction in subcutaneous and epicardial adipose tissue obtained from patients undergoing coronary artery bypass grafting and non-coronary cardiac surgery., Results: CAD patients had higher CD68+ (p=0.005) and CD11c+ (p<0.001) macrophage count in EAT when compared to the controls. CD11c+/CD206+ macrophage ratio, which reflects dominancy of M1-macrophage phenotype, was significantly increased in EAT of CAD patients when compared to that of the controls (p=0.008). CAD patients had significantly higher netrin-1, Unc5b, and IL-18 gene expression in the EAT when compared to the control group (p<0.001, p<0.001, and p=0.006 respectively). Increased macrophage infiltration and polarization were associated with higher netrin-1, Unc5b, and IL-12 gene expression in EAT (p<0.05)., Conclusions: Findings suggest a link between enhanced netrin-1 expression in EAT and macrophage infiltration and polarization in patients with CAD., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Aim and Background: Obesity is a multifactorial disease in which environmental and genetic factors play an integrated role. Determining such target genes will help to elucidate the mechanisms underlying complex diseases such as obesity and diabetes which are usually seen together. Present study investigates the expression levels of STEAP4 and HIF-1α in visceral and subcutaneous adipose tissue., Patients and Methods: 30(6M) morbidly obese patients undergoing bariatric surgery were included in the study. The patients were grouped according to the BMI as Group I (BMI <50kg/m(2)) and Group II (BMI ≥50kg/m(2)). Samples from visceral (omentum) and subcutaneous adipose tissues were obtained from each patient and real-time PCR (qPCR) was carried out for STEAP4 and HIF-1α gene expressions. Correlations between expression levels and clinical parameters were analyzed., Results: Mean age of the patients recruited to the study was 37.4 (18-64) years. Mean BMI was 46 (36-60) kg/m(2). STEAP4 expression in visceral adipose tissue was significantly higher than subcutaneous tissue. Visceral STEAP4 expression was also found to be reduced with increased BMI. It was also lower in patients with HbA1C over 6. Furthermore, expression of subcutaneous and visceral HIF-1α was significantly higher in Group II. There was a significant correlation between BMI, glycosylated hemoglobin, STEAP4 and HIF-1α gene expression., Conclusions: Obesity and related disease are linked with the fact that there is a low grade inflammation in the adipose tissue of the obese individuals. Counter-regulatory processes such as STEAP4 protein family are overwhelmed by the proinflammatory stimuli. HIF-1α expression is increased due to tissue hypoxia and pro-inflammatory stimuli in the obese individuals, which results in increased visceral STEAP4 expressions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: We aimed to assess whether the type of anesthesia in cesarean section (C/S) (spinal anesthesia, SA versus general anesthesia, GA) has an effect or not on umblical vein blood gas analysis and APGAR scores of term neonates and development of transient tachypnea of the newborn (TTN)., Methods: The data of 172 procedure (85, GA versus 87, SA) were collected retrospectively. Results of umblical vein blood gas analysis, APGAR scores at first and fifth minutes and presence of TTN from in-hospital files' of neonates were examined., Results: Neonates in the SA group had significantly higher first and fifth minute APGAR scores (8, 7 versus 9, 2, p < 0.001 and 9, 3 versus 10, 2, p = 0.017, respectively). The pH value of umblical vein samples were higher (7.30 ± 0.05 versus 7.32 ± 0.05, p = 0.029) and pO2 and SaO2 levels were significantly lower in the SA group (34.8 ± 13.8 mmHg versus 27.6 ± 14.5 mmHg; p = 0.001 and 56.6% ± 18.7 versus 49.8% ± 21.4; p = 0.029, respectively) as compared to the GA group. Thirteen neonates in the GA group (15.3%) and five in the SA group (5.7%) were diagnosed as TTN (p = 0.048)., Conclusion: In our study, considerable determinants of fetal wellbeing was stated to be higher in C/S performed under SA in comparison to GA. Furthermore, our findings favor SA for avoidance of TTN.

Pancreatic cancer continues to be the fourth leading cause of death despite advancements in surgical and adjuvant therapeutic approaches. In the present review, the current cytotoxic therapeutic approaches and advanced targeted therapies are objectively discussed with consideration to the current literature.

Background: Different methods of diagnosis have been found to be inefficient in terms of screening and early diagnosis of lung cancer. Cancer cells produce proteins whose serum levels may be elevated during the early stages of cancer development. Therefore, those proteins may be recognized as potential cancer markers. The aim of this study was to differentiate healthy individuals and lung cancer cases by analyzing their serum protein profiles and evaluate the efficacy of this method in the early diagnosis of lung cancer., Materials and Methods: 170 patients with lung cancer, 53 under high risk of lung cancer, and 47 healthy people were included in our study. Proteomic analysis of the samples was performed with the SELDI-TOF-MS approach., Results: The most discriminatory peak of the high risk group was 8141. When tree classification analysis was performed between lung cancer and the healthy control group, 11547 was determined as the most discriminatory peak, with a sensitivity of 85.5%, a specificity of 89.4%, a positive predictive value (PPV) of 96.7% and a negative predictive value (NPV) of 62.7%., Conclusions: We determined three different protein peaks 11480, 11547 and 11679 were only present in the lung cancer group. The 8141 peak was found in the high-risk group, but not in the lung cancer and control groups. These peaks may prove to be markers of lung cancer which suggests that they may be used in the early diagnosis of lung cancer.

Background: Although many patients with valvular heart disease have concomitant coronary artery disease (CAD), there are limited data on the association between rheumatic valvular disease (RVD) and CAD. In this study, we aimed to investigate the prevalence of CAD in a group of patients with RVD and undergoing coronary angiography before valvular surgery., Methods: In this retrospective analysis, we enrolled a total of 1075 patients (658 women, 61.2%; mean age: 53.2 ± 9.9 years) who underwent coronary angiography for the evaluation of CAD before valvular surgery between January 2003 and May 2010., Results: The overall prevalence of significant CAD was 11.1%. Patients with significant CAD were older than patients without significant CAD (55.16 ± 10.4 vs. 51.45 ± 9.1; P<0.001). In addition, hypertension, smoking, diabetes mellitus, and dyslipidemia were more prevalent among patients with significant CAD (P<0.05). After adjustment for several risk factors, only aortic stenosis remained the predictor of significant CAD (odds ratio: 1.66; 95% confidence interval: 1.26-2.19; P<0.001). However, aortic regurgitation was inversely associated with the presence of CAD (odds ratio: 0.56; 95% confidence interval: 0.21-1.01; P<0.001)., Conclusion: The overall prevalence of CAD in our population with RVD was low. Rheumatic aortic stenosis is associated with an increased prevalence of CAD, whereas the prevalence of CAD is lower in those patients with aortic regurgitation.

Aim: To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their levels and clinicopathological parameters in gastric cancer., Methods: Tissue samples were obtained from 33 patients (8 females) with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry., Results: LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic features such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the distribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining., Conclusion: LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.

In the era of early and invasive therapeutic approaches, myocardial rupture has become an uncommon complication of myocardial infarction. We report an uncommon complication following inferior myocardial infarction with both left ventricular and right ventricular rupture and subsequent communication via a shared pseudoaneurysm., (© 2010, Wiley Periodicals, Inc.)

Objective: To evaluate the diagnostic value of mean annular velocity (MAV) and strain score index (SSI) for determination of the left ventricular systolic dysfunction in patients with first acute myocardial infarction (AMI)., Methods: Seventy-one patients (55 male, mean age: 59+/-12 years) with first acute ST-elevation myocardial infarction and 30 healthy subjects were included in this cross-sectional and observational study. Echocardiography with tissue Doppler and strain analysis was performed during initial hospital admission. Peak systolic myocardial velocities were recorded from 4 different sites on the mitral annulus. A MAV value was calculated and the peak systolic strain values of 12 segments were measured and a mean SSI was calculated. ROC curve analysis was used in order to determine cut-off values for MAV and SSI., Results: The patients with AMI had a significantly reduced MAV compared with healthy subjects (5.52+/-1.78 cm/s vs 9.80+/-1.13 cm/s, p<0.001). In ROC analysis, a cut-off value of 8.41 cm/s (AUC 0.915, 95%CI 0.887-0.952, p<0.001) for MAV differentiated AMI patients from controls with 97.2% sensitivity and 93.3% specificity. The patients with AMI have also decreased SSI (11.23+/-2.83 vs 19.11+/-2.05, p<0.001). A cut-off value of 15.35% differentiated AMI patients from controls with 94.4% sensitivity and 100% specificity (ROC AUC 0.945, 95%CI 0.901-0.972, p<0.001). There was a good correlation between left ventricular EF and MAV (r=0.73, p<0.001) and SSI (r=0.66, p<0.001)., Conclusion: The patients with first myocardial infarction have decreased mean systolic annular velocity and mean systolic strain score index.

Microvascular abnormalities caused by endothelial dysfunction seem to be responsible for the myocardial ischemia in patients with cardiac syndrome X (CSX). Nitric oxide is a key mediator of endothelial function and is synthesized by endothelial nitric oxide synthase (eNOS). We investigated if the 3 potential polymorphisms of the eNOS gene (VNTR in intron 4, T786C polymorphism in the promoter region, and G894T polymorphism in exon 7) are independent risk factors for CSX. Sixty-nine patients with CSX and 73 healthy controls were studied. Genotypes were determined through polymerase chain reaction with or without restriction endonuclease digestions. Genotype distribution was significantly different between patients with CSX and controls for intron 4aa (allele for 4 repeats of 27 bp), intron 4aa genotype frequency being 3.2% and 6.8%, respectively. The presence of intron 4a is 3.2 (odds ratio) times protective (95% confidence interval, 1.5-6.8) for the risk of CSX disease. The protective effect of intron 4a polymorphism also holds after adjustment for age and sex and when the study group is limited to those without hypertension and hyperlipidemia. No significant difference was observed in genotype distribution of G894T and T786C polymorphism between patients with CSX and controls. In conclusion, intron 4aa genotype of eNOS gene is protective for CSX. No association was found between promoter and exon 7 polymorphisms of eNOS gene and CSX.

Objective: Ventricular remodeling (VR) is a pathologic process characterized by progressive ventricular dilatation occurring after acute myocardial infarction (MI) leading to left ventricular systolic dysfunction. The purpose of the study was to evaluate the efficacy of plasma tumor necrosis factor alpha (TNF-alpha) levels to predict the left VR., Methods: This prospective observational cohort study included 72 consecutive patients with newly diagnosed MI with age ranging between 38-87 years (mean 59 +/- 12 years). Control group was consisted of 30 patients with no additional systemic disease and normal coronary arteriograms. Transthoracic echocardiography was performed to all patients and controls both in the beginning of the study and in the 6th follow-up. A coronary arteriography was also performed to all patients. Patients with an increment in the diastolic volume index more than 20% in the follow-up compared with basal values included in the VR subgroup. The patient subgroup with VR consisted of 19 patients. Statistical analyses were performed using ANOVA and Kruskal Wallis tests for comparison of variables between groups. Logistic regression and ROC analyses were used for evaluation of accuracy of TNF-alpha in prediction of VR., Results: There were no significant differences between groups according to demographic characters. The basal plasma levels of TNF-alpha were higher in the patient subgroup with VR as compared with patients without VR and controls (14.59 +/- 4.28 pg/ml vs 7.30 +/- 4.48 pg/ml, and 1.64 +/- 1.49 pg/ml, p< 0.001). In logistic regression analysis only TNF-alpha predicted the VR (OR-1.356, 95% CI 1.117-1.647). Plasma TNF-alpha levels with a cut-off > or = 10.33 pg/ml were found to have 89.5% sensitivity and 79.3% specificity to predict the development of VR., Conclusion: These results demonstrate the increment of plasma TNF-alpha levels in the acute phase of MI and the close relationship between the TNF-alpha levels and VR in the patients with first MI.

Background: Factor V (FV) [G1691A], methylenetetrahydrofolate reductase (MTHFR) [C677T] and prothrombin (PT) [G20210A] mutations are all well-recognized genetic risk factors for venous thrombosis. Although their prevalence in coronary artery disease has been established through debate, their role in patients with arterial thrombosis remains to be clarified. We investigated the prevalence rates of FV, MTHFR and PT gene mutations in patients with arterial thrombosis and in healthy controls., Methods: All subjects and controls were from Central Anatolia. Thirty (8F) patients with median (range) age of 63 (16-88) years and 90 (52F) healthy controls with median (range) age of 31 (20-73) years were studied. DNA was extracted using conventional methods (proteinase K/phenol-chloroform) followed by PCR amplification and restriction endonuclease digestion (using Hinf I and Hind III). Digested PCR products were identified using agarose gel electrophoresis and stained with ethidium bromide., Results: The prevalence rates of MTHFR and PT gene mutations were not significantly different between the groups. The prevalence rate of FV mutation was significantly higher in patients with arterial thrombosis. Coinheritance of FV and MTHFR was found in 67% of patients, which was significantly higher in arterial thrombosis, suggesting the MTHFR mutation as a synergistic risk factor for thrombosis in patients with FV mutation. PT gene mutation has no effect on arterial thrombosis., Conclusion: The increased prevalence rate and coexistence of both FV and MTHFR found in this group of patients suggest that these mutations might increase the risk of arterial thrombosis.

Evidence indicates that proteins controlling bone mineralization are also involved in the regulation of coronary calcification. The aim of the present study is to evaluate the association between plasma osteopontin (OPN) levels and coronary calcification quantified by using tomographic coronary calcium scoring. Plasma OPN levels were measured from samples of 80 intermediate-risk asymptomatic patients (56 +/- 10 years) who underwent tomographic coronary calcium scoring via multislice computed tomography for incremental risk stratification. There was no significant difference regarding OPN levels between patients with and without coronary calcification in the whole study population. Of 49 patients not receiving renin-angiotensin system inhibitors and/or statins, plasma OPN levels of patients with coronary calcification (38.7%) were significantly higher than those without coronary calcification (61.3%) (8.88 +/- 2.85 vs. 6.79 +/- 2.41, P = 0.008, respectively). On a binary logistic regression model, only age and plasma OPN level were found to be significant independent associated variables for the presence of coronary calcification in patients not receiving these medications (odds ratio for age, 1.15, P = 0.017; for plasma OPN levels, 1.63, P = 0.014). Our results indicate that plasma OPN levels may be predictive of coronary calcification, suggesting an important role of OPN in the atherosclerotic calcification pathogenesis.

Surgery is the only curative therapy for gastric cancer and controversy still exist on the extend of surgery. As the lymphatic distribution of stomach is very complex, the determination of the actual lymph node involvement is important for making the decision in order to avoid complications. Sentinel node navigation surgery has recently been introduced in gastrointestinal tract cancer. Present article reviews the detection techniques of lymph nodes and significance of lymphadenectomies in gastric cancer., ((c) 2008 Wiley-Liss, Inc.)

Background: Twelve-lead electrocardiography (ECG) is the most important source for the early diagnosis of an acute myocardial ischemia. However, its diagnostic value when the sequence of ventricular activation is altered by ventricular pacing is unknown. The aim of the study was to evaluate the ECG changes on the paced ECG during percutaneous coronary intervention (PCI) by doing temporary pacing., Methods and Results: Standard 12 lead baseline and temporary pacing ECG records were taken before the intervention in elective PCI patients. Standard 12 lead and temporary pacing ECG records were repeated during the balloon inflation. Fifteen (12 men and 3 women; age 57.2+/-9.7 years) subjects who were undergoing routine PCI were studied. Mean Delta ST deviation on the normal conduction ECG during inflation was 1.03+/-1.02 mV and mean Delta ST deviation on the paced ECG during inflation was 1.7+/-1.6 mV. The pre-inflation mean QRS duration on the paced ECG was 143.2+/-2.8 ms and during inflation mean QRS duration was 157.8+/-12.5 ms. The mean QRS prolongation was 14.6+/-13.6 ms on the paced ECG. Despite the presence of paced ECG abnormalities, significant ischemic ST segment deviations were seen after referencing the ST segment deviations to the pre-PCI. Also, there is significant QRS prolongation on the paced ECG during ischemia., Conclusions: The present study extends the correlation between normal and paced ECG during ischemia and the QRS prolongation could be a marker of myocardial ischemia on the paced electrocardiogram.

Objective: We aimed to study the comparison of strain and strain rate parameters with conventional left ventriculography derived regional function., Method: Forty patients were included in the study. The study group was selected from patients who had undergone left ventriculography and coronary angiography for clinical indications. Regional myocardial function was assessed using the centerline method via ACOM PC Quantcor LVA measurement system. Patients were also evaluated with echocardiography. Strain and strain rate Doppler echocardiographic measurements were compared with conventional left ventriculography at anterobasal, anterolateral, inferior and posterobasal segments., Results: Radiological left ventricular radial shortening was found to correlate with longitudinal strain shortening in all ventriculographic segments examined (anterobasal, r = 0.771, P < 0.0001; anterolateral, r = 0.790, P < 0.0001; posterobasal, r = 0.861, P < 0.0001; inferior, r = 0.815, P < 0.0001). Correlation was persistent both in patients with or without coronary artery disease. The sensitivity of a peak systolic longitudinal strain >12.5% for prediction of patients with radial shortening >or=20% was 75%, with a specificity of 100%. However, no relationship could be demonstrated between radiological left ventricular radial shortening and strain rate measurements., Conclusions: In our study it was shown that regional wall motion can be measured quantitatively via strain Doppler echocardiography with the left ventriculography as reference.

Cardiovascular disease is a major cause of death in patients with systemic lupus erythematosus (SLE) especially during the late phase of the disease. This study was conducted to evaluate B-type natriuretic peptide (BNP) levels in female SLE patients without cardiac symptoms and to investigate whether BNP levels correlated with echocardiographic findings. We studied 59 women with SLE and 33 healthy women. SLE patients with history of cardiac disease, diabetes mellitus, hypertension, and other inflammatory diseases were excluded from the study. All subjects had a complete history and physical examination. Overall disease activity assessment in SLE patients at the time of the study were derived by calculation of SLE disease activity index (SLEDAI). BNP levels were determined, and transthoracic echocardiography were performed in all subjects. There was no difference between SLE patients and controls in terms of age, blood pressure, smoking status, plasma glucose, creatinine levels, and lipid profiles. Nine patients had SLEDAI score greater than 5. All subjects had an EF greater than 55%. Diastolic dysfunction was more frequent in lupus patients than in controls (15 [25.4%] vs. 2 [6%]; p = 0.022). BNP levels of SLE patients were significantly higher than controls (median 17.9 range [5-211] pg/ml vs. median 14.7 range [5-39.7] pg/ml; p = 0.033). Twenty-seven of the SLE patients (46%) and seven of the controls (21%) had BNP levels greater than or equal to 20 pg/ml (p = 0.019). There were no differences in BNP levels of SLE patients with and without diastolic dysfunction (median 17.8 range [5-117] pg/ml vs. median 18.5 range [5-211] pg/mL; p = NS). BNP levels were positively correlated with left atrium diameter (r (2) = 0.39, p = 0.001). BNP levels did not correlate with erythrocyte sedimentation rate/C-reactive protein levels, SLEDAI scores, total steroid dosage used, or other echocardigraphic parameters. BNP levels were increased in female SLE patients without cardiac symptoms as compared to healthy controls. Although none of the SLE patients in our study had clinical signs of ischemic heart disease, increased levels of BNP in SLE patients might be a reflection of a ischemic myocardial tissue.

Increased QT dispersion (QTd) is a noninvasive marker of an electrophysiologic abnormality associated with high mortality in coronary artery disease. The purposes of this study were to measure changes in QTd and ST-segment changes immediately before, during and after intracoronary balloon inflation and to determine whether the coronary artery vessel involved and/or the duration of inflation affect(s) QTd. A total of 45 patients (32 men, 13 women, mean age 58 +/- 11 years) who were referred for elective percutaneous transluminal coronary angioplasty were included. The mean QT interval dispersions for all patients before the inflation, during the balloon inflation at 60 sec and after the balloon deflation at 5 min were 68 +/- 13 ms, 82 +/- 16 ms and 71 +/- 13 ms, respectively. There was no significant difference between baseline and 5 min after deflation. The increase in QTd during the balloon inflation was significant (p<0.01). There was no significant QTd change in patients with left circumflex artery (Cx) lesions during inflation and after deflation compared with baseline. The differences were statistically significant only in patients with left anterior descending (LAD) lesions and right coronary artery (RCA) lesions at 60 sec during balloon inflation (p=0.001 vs. p=0.04). Acute reversible myocardial ischemia induced by balloon inflation causes an increase in QTd limited to the LAD and RCA vessels. Therefore, when using QTd as a marker of myocardial repolarization abnormality due to acute reversible ischemia, the involved coronary artery vessel must be taken into account.

Acute physical exertion may trigger an acute coronary syndrome. Furthermore, acute physical exercise may influence hemostatic markers in healthy individuals. However, the effect of acute exercise on blood fibrinolysis and coagulation in patients with coronary artery disease (CAD) is still not well understood. Nineteen untrained patients with angiographically proven CAD (age, 58 +/- 9 years, 12 males), and 25 age- and sex-matched controls without CAD (age, 56 +/- 6 years, 16 males) underwent a treadmill exercise test. Global fibrinolytic capacity (GFC) and prothrombin fragment 1 + 2 (F 1 + 2) levels were measured before exercise, at peak exercise, and 2 hours after recovery. There were no differences between the groups with respect to left ventricular ejection fraction, history of hypertension, body mass index, and serum lipids. Before exercise, GFC was significantly lower in patients with CAD when compared with controls (1.40 +/- 0.43 versus 3.28 +/- 1.19 microg/mL, respectively; P < 0.001). In patients with CAD, F 1 + 2 levels were significantly higher than those of controls (1.15 +/- 0.43 versus 0.79 +/- 0.10 nmol/L, respectively; P = 0.002). In both study groups, GFC levels increased significantly at peak exercise and decreased to baseline values 2 hours after recovery. At peak exercise, F 1 + 2 levels significantly increased in both study groups. However, while F 1 + 2 levels of controls decreased to baseline values 2 hours after recovery (0.79 +/- 0.10 versus 0.80 +/- 0.10 nmol/L; P > 0.05), F 1 + 2 levels of patients with CAD were still significantly elevated (1.15 +/- 0.43 versus 1.84 +/- 0.06 nmol/L; P = 0.002). Acute exercise increases coagulation and fibrinolysis both in untrained subjects with and without CAD. However, in patients with CAD, the equilibrium between fibrinolysis and coagulation during peak exercise is disturbed in favor of coagulation after recovery.

Although autopsy studies have documented that heart is affected in most of systemic lupus erythematosus (SLE) patients, clinical manifestations occur in less than 10%. QT dispersion, a new parameter that can be used to assess homogeneity of cardiac repolarization and autonomic function, has not been studied in SLE patients. The aim of our study was to evaluate the QT dispersion (QTd) in SLE patients without overt cardiac involvement. Eighty-three patients with a diagnosis of SLE (mean age 41+/-13) and age- and sex-matched 77 healthy control subjects (mean age 43+/-10) were enrolled in the study. All subjects had their complete history taken, laboratory examination, and transthoracic echocardiography (ECG). Patients with cardiac disease, hypertension, diabetes, or taking medications that may effect QTd or any ECG abnormalities were excluded. Resting 12-lead ECG were recorded for measurement of QTd. None of the patients and control subjects had overt cardiac involvement. The mean SLE duration was 86.5+/-15.4 months. QT dispersion was significantly greater in SLE patients than incontrol subjects (55.2+/-24.7 vs 20.7+/-5.3 ms, respectively; p<0.001). There was no correlation between QTd and duration of SLE, SLEDAI-K score, corticosteroid usage, and presence of anti SS-A antibody. QT dispersion is significantly increased in SLE patients without overt cardiac involvement. Our result suggests that prolonged QT dispersion can be a useful noninvasive and simple method for early detection of cardiac involvement in SLE patients.

Background: The regions of ruptured atherosclerotic plaques have numerous macrophages. Osteopontin that modulates macrophage function has been shown in atherosclerotic plaques. We aimed to study the plasma levels of osteopontin in patients with unstable angina or non-ST-seg ment elevation myocardial infarction (NSTEMI) and the rela tionship between osteopontin and the extent of the coronary artery disease (CAD)., Methods: We studied 65 patients with unstable angina or NSTEMI, 25 patients with stable angina and 18 patients as the control group. The extent of coronary artery stenosis was determined by the number of vessels with >50% stenosis. Plasma osteopontin concentrations were measured from the blood samples that were drawn immediately after admission to the emergency department in unstable angina/NSTEMI patients and before the coronary angiograph in the stable angina and control groups., Results: The plasma osteopontin concentration was (495 118 ng/ml) significantly higher in the patients with unstable angina/NSTEMI compared to the stable angina group (319 106 ng/ml) and control group (125+/-54 ng/ml) (p=0.0001 The plasma osteopontin levels were lower in the patients with stable angina pectoris who had one-vessel disease compared to those with two-vessel disease (p=0.01). How ever, in the unstable angina/NSTEMI group, the plasma osteopontin levels were statistically not different among the patients with one-vessel, and two-vessel and three-vessel disease (p=NS). There was no correlation between the plasma osteopontin levels and the extent of coronary stenosis., Conclusions: The plasma osteopontin levels are elevatedin patients with unstable angina/NSTEMI, but there appears to be no correlation with the extent of CAD. These results ma suggest that osteopontin may have a role in the pathobiology of ACS.

Although the severity of valvular calcification is an important prognostic indicator, the cellular mechanisms of the calcification process are unknown. Osteopontin modulates inflammation and biomineralization, and increased osteopontin expression has been demonstrated in calcified degenerative or rheumatic cardiac valves. The present study evaluated soluble plasma osteopontin in 32 patients with echocardiographically determined rheumatic mitral stenosis and compared the results to those of a control group of 22 healthy patients. Patients were evaluated with routine echocardiographic techniques, Wilkins scoring, and 2-dimensional echocardiographic calcium scoring. Patients with rheumatic involvement other than in the mitral valve were excluded. Plasma osteopontin and high-sensitivity C-reactive protein levels in patients with mitral stenosis were significantly higher those of the control group (p = 0.006 and p = 0.0001, respectively). A significant correlation was found between plasma osteopontin levels and the severity of mitral valve calcification (p = 0.003) and also between high-sensitivity C-reactive protein levels and Wilkins score (p = 0.009). There was a stepwise and statistically significant increase in soluble plasma osteopontin levels in association with the severity of mitral valve calcification. In conclusion, increased osteopontin levels were correlated with the severity of mitral valve calcification in patients with rheumatic mitral stenosis, suggesting an important role of osteopontin in the modulation of valvular calcification. Elevated levels of high-sensitivity C-reactive protein concentrations suggest the presence of ongoing inflammation in those patients.

Pseudoexfoliation syndrome (PEX) is the most common clinical precursor of open-angle glaucoma. Recent studies have shown that pseudoexfoliative material is widely distributed throughout the body, including blood vessels. The aim of our study was to evaluate endothelial function in the brachial artery of patients with pseudoexfoliation syndrome. We prospectively examined 23 patients with PEX (mean age, 70 +/- 8 years) and 20 healthy age- and sex-matched individuals (mean age, 68 +/- 9 years) as a control group. Brachial artery endothelial function was assessed by vascular response to reactive hyperemia (flow-mediated dilation (FMD) and sublingual nitroglycerin (NTG-mediated dilation) using high-resolution ultrasound. Flow-mediated and NTG-induced dilation were expressed as the percent change in diameter after reactive hyperemia and after NTG administration relative to the baseline value, respectively. Patients with cardiovascular disease and other conditions associated with endothelial dysfunction were excluded. When compared with controls, patients with PEX had significantly lower flow-mediated dilation (4.5 +/- 2.8 versus 8.2 +/- 3.7, P = 0.01) and NTG-mediated dilation (10.9 +/- 3.1 versus 15.8 +/- 3.8, P = 0.0001). Flow-mediated dilation and NTG-mediated dilation were similar in PEX patients with glaucoma (n = 11) and without glaucoma (n = 12). Flow-mediated and NTG-mediated dilation did not correlate with any measured parameter in any patient or control subject. The findings indicate that systemic endothelial function is impaired in PEX syndrome patients.

Objective: The aim of our study was to: (1) measure atrial electromechanical delay in patients with mitral stenosis (MS) and in a control group; (2) find the echocardiographic parameters that affect atrial electromechanical delay; and (3) examine the correlation between atrial electromechanical delay and P-wave dispersion (PWD)., Methods: A total of 25 patients with pure MS (age 43 +/- 10 years; 18 women, 7 men) and 16 control subjects (age 41 +/- 8 years; 9 women, 7 men) were studied. Interatrial and intra-atrial electromechanical delay was measured with Doppler tissue echocardiography. From the 12-lead electrocardiograms, PWD was calculated., Results: Interatrial electromechanical delay was 71.2 +/- 33 in the MS group and 40.5 +/- 21.0 in the control group (P = .01). In the MS group, PWD was 50 +/- 7 and in the control group it was 29 +/- 5 (P = .03). A positive correlation was detected between interatrial electromechanical delay and PWD (r = 0.6, P = .03)., Conclusion: This study shows that interatrial electromechanical delay gets longer in MS and is correlated with PWD. Atrial electromechanical delay is related with left atrial size but not with severity of MS.

Platelet hyperactivity is important in the pathobiology of acute coronary syndromes. Glycoprotein V (GPV) is an integral membrane protein of platelets in the function of the GPIb-V-IX receptor for vWf/shear-dependent platelet adhesion in arteries. Soluble GPV is a novel marker of platelet activation. The aim of this study is to assess circulating soluble GPV levels in unstable angina pectoris (UA). Twenty-one patients (15 men, six women, aged 52+/-7 years) with UA pectoris were studied. The inclusion criteria were angina at rest lasting >20 min during the preceding 6 h, with transient ST segment depression and/or T wave inversion and no evidence of myocardial infarction detected with the use of cardiac troponin-T. Coronary artery stenosis was angiographically confirmed in all patients. Twenty age- and sex-matched healthy adults (14 men, six women, aged 48+/-7 years) served as controls. There were no significant differences among the studied groups with respect to age, sex, obesity, smoking, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride and platelet counts. Plasma-soluble GPV concentrations were higher in the UA patient group (126+/-46 ng/ml) than those in the healthy controls (82+/-15 ng/ml) (P=0.001). There was a significant correlation only between plasma-soluble GPV levels and smoking (r=0.526, P=0.0001). Smoker UA patients had higher levels of soluble GPV than the non-smoker patients (139+/-40 vs. 113+/-50 ng/ml, respectively, P=0.02). However, soluble GPV levels were similar in smoker and non-smoker healthy controls (P=0.2). It is concluded that soluble GPV concentrations are significantly increased during the acute clinical course of unstable angina pectoris, indicating that soluble GPV may be useful marker of platelet activation in those patients. The level of the molecule is significantly affected from smoking in those patients.

Intravenous leiomyomatosis with a cardiac extension is an extremely rare condition. In this report, a case of a 43-year-old female patient is described: she was operated for right atrial mass protruding into the inferior vena cava, which was later diagnosed as leiomyoma. After a 3-year symptom-free period, recurrence of the extension through the inferior vena cava was observed. After abdominal ultrasonographic examination, which revealed bilateral ovarian and retroperitoneal mass, bilateral oopherectomy, retroperitoneal, and right atrial mass excision was done. The retroperitoneal and right atrial mass was reported as leiomyoma. On her last admission, she had complaints of dizziness, abdominal pain, and bilateral leg edema; and right atrial mass extending through the common iliac vein was noted, but the patient did not accept any further treatment modality.

Background: Statins promptly lower rates of adverse cardiovascular events in patients with acute coronary syndromes (ACS). These therapeutic properties may be mediated by the effects of statins on key hemostatic factors. This study examined the immediate effects of fluvastatin on plasma free tissue factor pathway inhibitor (fTFPI) and soluble endothelial protein C receptor (sEPCR) concentrations in patients with unstable angina or non-ST segment elevation myocardial infarction., Methods: We studied 57 patients consecutively admitted to our emergency department and randomly assigned to placebo (n = 29) versus fluvastatin, 80 mg, p.o. (n = 28). All patients were treated with aspirin and metoprolol p.o., nitroglycerin i.v., and subcutaneous enoxaparin. Venous blood was sampled as soon as possible upon admission, before and 6 h after administration of study drug and standard anti-ischemic therapy., Results: Mean sEPCR concentrations decreased significantly in patients treated with fluvastatin (-8.1 +/- 6.7% from baseline) and was unchanged in the placebo group (-2.3 +/- 14.4%, P = 0.007 vs. fluvastatin). Though fTFPI increased significantly after the administration of both fluvastatin and placebo, the mean increase after fluvastatin (450+/-436%) was significantly greater than after placebo (155+/-141%, P = 0.001)., Conclusions: Treatment with fluvastatin significantly modified key hemostatic factors toward an antithrombotic effect within 6 h. These properties may, in part, explain the early salutary effects of fluvastatin in patients with ACS.

Behcet's disease is known as a chronic systemic vasculitic syndrome, the hallmark of which is recurrent oral aphthous and genital ulcerations and uveitis. Vascular involvement, mainly thrombosis, reportedly affects as many as one-third of patients. Cardiac involvement, however, is very rare. We present in this report a young female patient developing right ventricular thrombus while being treated medically.

Left ventricular long-axis function evaluated by M-mode or tissue Doppler echocardiography has been shown to be useful indexes of left ventricular systolic function; however it has not been evaluated in patients with mitral stenosis. We examined the left ventricular long-axis function of the patients with pure mitral stenosis and normal global systolic function as assessed by fractional shortening of the left ventricle (LV). Fifty-two patients with pure mitral stenosis and twenty-two healthy controls were evaluated by echocardiography. Although there was no statistically significant difference in global systolic function, M-mode derived systolic motion of the septal side and (12 +/- 3 vs 14.4 +/- 1.5 mm, P = 0.016) the lateral side of mitral annulus (13.2 +/- 3 vs 16.8 +/- 2 mm, P = 0.001) were both significantly lower in the patients with mitral stenosis than control subjects. Similarly tissue Doppler systolic velocity of the septal annulus (7.6 +/- 1.1 vs 10.4 +/- 3.2 cm/s, P = 0.03) and lateral mitral annulus (7.6 +/- 1.1 vs 10.4 +/- 3.2 cm/s, P = 0.003) were also significantly lower in patients with mitral stenosis than in controls. There was a statistically significant correlation between septal annular motion and annular velocity (r = 0.643, P = 0.002). Septal annular motion and annular velocity were also correlated with left atrial ejection fraction (r = 0.338, P = 0.005 and r = 0.676, P = 0.001, respectively). Thus, patients with mitral stenosis had significantly impaired long-axis function evaluated by M-mode or tissue Doppler echocardiography despite normal global systolic function.

It is well known that chronic atrial fibrillation (CAF) and paroxysmal atrial fibrillation (PAF) are associated with hypercoagulable state. However, pathological hemostatic changes during the paroxysmal supraventricular tachycardia (PSVT) have not yet been elucidated. To determine platelet activity in patients with PSVT, PAF and CAF, we examined the levels of beta-thromboglobulin (BTG) and platelet factor 4 (PF4) during tachyarrhythmia attacks. We measured the levels of BTG and PF4, as an index of platelet activation in 15 patients with PAF (9 men, mean age 45+/-11), and 14 patients with PSVT (8 men, mean age 40+/-10). Levels were compared to 22 age and sex matched healthy controls in sinus rhythm and with 25 patients with CAF (16 men, mean age 51+/-12). Blood samples were taken during arrhythmia and 24 hours after conversion to sinus rhythm. Patients taking medications or have clinical conditions that may affect the BTG and PF4 levels were excluded. In patients with PAF, BTG and PF4 levels were significantly higher than in controls (p<0.009, and p=0.002, respectively), and in patients with PSVT (p<0.004, and p=0.009, respectively), however, BTG and PF4 levels were significantly lower than CAF patients (p=0.002, and p=0.02, respectively). Moreover, BTG and PF4 levels were significantly decreased 24 hours after conversion to sinus rhythm (p<0.0001), and p=0.004, respectively). Although BTG and PF4 levels in patients with PSVT were significantly lower than in patients with PAF (p=0.04, and p=0.009, respectively) and CAF (p=0.0001, and p=0.0001, respectively), BTG and PF4 levels were similar to controls and did not change significantly after recovery to sinus rhythm (p=NS for all). These results indicate that there was no platelet activation in patients with PSVT during tachyarrhythmia but significantly increased platelet activity in PAF and CAF patients. There was a significant decrement of the platelet activity to a level of control subjects twenty-four hours after cardioversion of PAF.

Background: Paroxysmal atrial fibrillation (PAF) in hypertrophic cardiomyopathy (HCM) is associated with poor prognosis. Previous studies have shown good correlation between P-wave dispersion (Pd) and occurrence of PAF. However, Pd in patients with HCM for predicting PAF has not been studied., Hypothesis: The aim of the study was to determine whether Pd could identify patients with HCM who are likely to suffer from PAF., Methods: Twenty-two patients with HCM with a history of PAF (Group 1) and 26 patients with HCM without a history of PAF (Group 2) were studied. Maximum (Pmax) and minimum (Pmin) P-wave durations, as well as P-wave dispersion (Pd = Pmax - Pmin) were calculated from 12-lead surface electrocardiograms (ECG)., Results: P-wave dispersion was significantly different between the groups (Group 1: 55 +/- 6 ms vs. Group 2: 37 +/- 8 ms; p<0.001), while Pmax (Group 1: 134 +/- 11 ms vs. Group 2: 128 +/- 13 ms; p = 0.06) and Pmin (Group 1: 78 +/- 9 ms vs. Group 2: 81 +/- 7 ms; p = 0.07) was not significantly different. Patients with a history of PAF had higher left atrial diameter than the patients without PAF (Group 1: 52 +/- 8 mm vs. Group 2: 48 +/- 10 mm; p = 0.02). A cut-off value of 46 ms for Pd had a sensitivity of 76% and a specificity of 82% in discriminating between patients with and without PAF., Conclusion: This study suggests that P-wave dispersion could identify patients with HCM who are likely to develop PAF.

This study is designed to assess the value of heart rate turbulence (HRT) in the acute phase of MI for prediction of long-term mortality risk. The study included 128 consecutive acute MI patients with 24-hour Holter recordings to evaluate HRT (turbulence onset and slope), SDNN, mean RR interval, and ventricular premature beat frequency. LVEF was evaluated by two-dimensional echocardiography. Data from 117 patients (mean age 58 +/- 11 years) were available for further analysis. Twelve patients died during follow-up (mean 312 +/- 78 days). Although SDNN < 70 ms was the most powerful predictor of mortality among all presumed risk factors (hazard ratio 20 [95% CI 2.6-158]; P = 0.004) in univariate Cox regression analysis, in multivariate analysis LVEF < or = 0.40 and turbulence slope < or = 2.5 ms/RR interval were the only independent predictors of mortality (hazard ratio 6.9 [95% CI 1.8-26]; P = 0.006, hazard ratio 7.3 [95% CI 1.4-37]; P = 0.016, respectively). Addition of HRT parameters for LVEF increased remarkably the positive predictive value (60%) without any decrease in the negative predictive value (92%). Blunted HRT reaction within the first 24 hours of acute MI is an independent predictor of long-term mortality. Furthermore, its predictive power is comparable and also additive to that of LVEF.

There is substantial evidence that platelet production and release take place in the lungs. Thrombopoietin (Tpo) stimulation can cause platelet release in the pulmonary vasculature. On the other hand, myelofibrosis can occur in Tpo-overexpressing transgenic mice models, and there is unexplained pulmonary hypertension in chronic myeloproliferative disorders including primary myelofibrosis. In this study, we aimed to assess local Tpo concentrations inside the pulmonary artery and associated vessels in humans. We measured Tpo concentrations in plasma samples taken concurrently from the right ventricle, the pulmonary artery, and the left ventricle during cardiac catheterization in patients with and without pulmonary hypertension. The study group comprised 10 patients with normal pulmonary arterial pressure (Group A, male/female 4/6, mean age 48 +/- 19) and 14 patients with pulmonary hypertension (Group B, male/female 9/5, mean age 57 +/- 16). The Tpo levels inside the right ventricle, the pulmonary artery and the left ventricle were 33.3 +/- 15.6, 47.2 +/- 33.9, and 34.4 +/- 18.6 pg/ml, respectively, in Group A; and 85.0 +/- 39.8, 128.4 +/- 50.4, and 81.5 +/- 35.5 pg/ml, respectively, in Group B. Levels of the Tpo were significantly higher in all three localizations in Group B compared to Group A. Moreover, the Tpo concentration inside the pulmonary artery is significantly higher than the Tpo concentrations in the right and left ventricles in Group B patients. There were positive correlations between the Tpo levels and pulmonary artery systolic pressure over the whole patient group. In conclusion, there could be an association between pulmonary hypertension and Tpo level. Moreover, lung vasculature holding the major regulatory thrombopoietic hormone, Tpo, may be an important place for megakaryocytopoiesis.

Background: The beneficial effects of HMG-CoA reductase inhibitors (statins) in patients with coronary artery disease (CAD) appear to be attributable not only to their lipid-lowering properties, but also to their therapeutic effects on the coagulation system, and anti-inflammatory effect. Furthermore, statins mitigate the apoptosis of vascular smooth muscle cells (VSMC) and macrophages in atherosclerotic plaques., Hypothesis: The purpose of this study was to evaluate the effects of short-term atorvastatin treatment on the fibrinolytic system and systemic inflammatory status, and on apoptosis in hyperlipidemic patients with CAD., Methods: The study population consisted of 36 hyperlipidemic patients (14 women and 22 men, mean age 53+/-9 years) with stable CAD, untreated with lipid-lowering medications. Serum lipoproteins, fibrinogen levels, sFas and sL-selectin, and global fibrinolytic capacity (GFC) were measured at baseline and after 12 weeks of treatment with atorvastatin, 10 mg/day., Results: Atorvastatin treatment decreased serum low-density lipoprotein (-39%, P=0.0001), total cholesterol (-32%, P=0.0001), and triglycerides (-22%, P=0.0001), and increased high-density lipoprotein (+13%, P=0.0001) at 12 weeks compared to baseline. These effects were associated with a decrease in plasma fibrinogen from 331+/-73 to 298+/-58 mg/dl (P=0.0001), and sL-selectin levels from 666+/-201 to 584+/-162 ng/ml (P=0.0001). sFas levels and GFC increased from 3754+/-1264 to 4873+/-1835 pg/ml and from 3.5+/-2.4 to 5.6+/-2.9 microg/ml, respectively (both P=0.0001)., Conclusions: These results suggest that lipid lowering with atorvastatin therapy significantly increases GFC, decreases fibrinogen levels, and causes leukocyte deactivation. Our findings also suggest that atorvastatin treatment mitigates apoptosis of VSMC in the atherosclerotic plaque. These effects of atorvastatin may, in part, explain the early decrease in cardiovascular events observed in clinical trials of statins.

Chronic atrial fibrillation (AF) has often been associated with systemic embolization, and patients with mitral stenosis (MS) have the highest thromboembolic risk. Increased risk of thromboembolism could be in part due to impaired fibrinolytic function. Global fibrinolytic capacity (GFC) is an innovative technique for evaluating the entire fibrinolytic system. The aim of our study was to evaluate fibrinolytic activity in patients with rheumatic and nonrheumatic chronic AE To investigate fibrinolytic activity, we assessed GFC in peripheral blood samples of 32 patients with nonrheumatic AF (14 women; mean age, 56 +/- 1 years), 30 patients with rheumatic MS and AF (23 women; mean age, 35 +/- 9 years), and 32 patients with rheumatic MS and sinus rhythm (24 women; mean age, 36 +/- 8 years). The control group comprised 30 healthy adult subjects in normal sinus rhythm. Patients with chronic AF (rheumatic and nonrheumatic) had lower GFC than did the controls (P = .0001). The rheumatic AF group also showed decreased levels of GFC compared with the nonrheumatic AF group, with the rheumatic MS and sinus rhythm group, and with controls (P = .03, P = .02, P = .0001, respectively). GFC was lower in patients with rheumatic MS and sinus rhythm than in controls (P = .003). Although there were correlations between GFC and mitral valve area, transmitral mean gradient, left atrial diameter, and mitral calcification in patients with rheumatic MS, multivariate analysis showed only transmitral gradient as an independent factor affecting GFC. Patients with AF have decreased GFC, a finding that suggests the presence of a hypofibrinolytic state. Fibrinolytic dysfunction was more pronounced in rheumatic MS patients with AF than in those with nonrheumatic AF. Moreover, patients with rheumatic MS and sinus rhythm had decreased global fibrinolytic activity. Hypofibrinolysis documented by decreased GFC can be one of the important causes of increased risk of embolism in patients with AF and rheumatic MS.

Although mitral valve prolapse (MVP) has shown to be associated with thromboembolic complications, the cause of thromboembolic events in those patients is still unknown. The purpose of this study was to evaluate the fibrinolytic activity in MVP patients. The study included 35 consecutive patients (25 women, mean age 25+/-11 years) with echocardiographically documented MVP and 25 age- and sex-matched subjects as a control group. Four of MVP patients have a history of transient ischemic attack (TIA). Global fibrinolytic capacity (GFC), a new technique that examines the effectiveness of the entire fibrinolytic system, was measured. Global fibrinolytic capacity was found to be nonsignificantly increased in MVP patients (3.14+/-1.42 microg/mL) compared to those in control subjects (2.36+/-1.33 microg/mL) (p>0.05). However, in four of these MVP patients who had a history of transient ischemic attack, the GFC level was significantly lower than in patients who have no history of transient ischemic attack (1.67+/-0.6 microg/mL vs 3.27+/-1.46 (microg/mL, p=0.003). Furthermore, the GFC levels of these four patients were less than those of controls (p=0.04). These results showed that global fibrinolytic activity was similar in MVP patients without a history of TIA and control subjects. However, MVP patients with a history of TIA had significantly decreased global fibrinolytic activity compared to controls and as well as MVP patients without a history of TIA.