tbuckley/cabot-search huggingface dataset:
Abstract 1716: Calcium Channel Blockers Reduce the Antiplatelet Effect of Clopidogrel
Authors: Jolanta Siller-Matula, Irene Lang, Guenter Christ, Bernd Jilma
Journal: Circulation (2008)

Due to the known CYP3A4 inhibition by calcium channel blockers, we hypothesized that there might be a pharmacodynamic interaction between clopidogrel and dihydropyridines in patients with coronary artery disease (CAD). Clopidogrel is activated by CYP3A4 which also metabolizes calcium channel blockers of the dihydropyridine class. Methods: Responsiveness to clopidogrel was assessed by the vasodilator stimulated phosphoprotein (VASP) phosphorylation assay and aggregometry in 200 patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). The platelet reactivity index (PRI in the VASP assay, normal range 69–100%) was higher in patients on both clopidogrel and calcium channel blockers (61%) as compared to patients on clopidogrel without calcium channel blockers (48%). The absolute difference was 13% (95%CI: 6 –20%; p = 0.001) and the relative difference approached 21%. A high post-treatment platelet reactivity (PRI &gt; 69%) was seen in 40% of patients with concomitant calcium channel blocker treatment compared to 20% without (X2-test: p = 0.008). Intake of calcium channel blocker remained an independent predictor of high platelet reactivity after adjustment for cardiovascular risk factors. This corresponded to an increased platelet aggregation of similar magnitude (p &lt; 0.05). In vitro incubation with calcium channel blockers (nimodipine, verapamil, amlodipine and diltiazem) did not alter the PRI or the ADP-induced platelet aggregation of patients on clopidogrel, indicating that the interaction occurs in vivo, conceivably at the level of the CYP3A4 cytochrome. Co-administration of calcium channel blockers is associated with a decreased platelet inhibition by clopidogrel.
Contribution of molecular diagnosis to the management of cutaneous leishmaniasis in travellers
Authors: R.A. Lavergne, X. Iriart, G. Martin-Blondel, P. Chauvin, S. Menard, J. Fillaux, S. Cassaing, C. Roques-Malecaze, S. Arnaud, A. Valentin, J.F. Magnaval, B. Marchou, A. Berry
Journal: Clinical Microbiology and Infection (2013)
A memorable patient: What a rotten job you've got
Authors: E. Davies
Journal: BMJ (1999)

He was a large man with gynaecomastia and he was covered in bruises. The day before his general practitioner had sent him up to hospital for a full blood count. The phlebotomist he saw had taken enough blood for a clotting screen and this had revealed disseminated intravascular coagulation. He had been admitted urgently to the ward on which I was house officer. There my efforts to obtain more blood were failing as each vein I tried ballooned and bled into his skin. I sweated, he contained his irritation, and finally there were a few more millilitres.

With some relief I stood near the door, talking in general terms about further tests. “What do you think's the cause of this blood not clotting then?” he asked. He had been diagnosed 17 years before with …
On the Preparations of the Indian Hemp, or gunjah: Cannabis Indica Their Effects on the Animal System in Health, and their Utility in the Treatment of Tetanus and other Convulsive Diseases
Authors: W. B. O'Shaughnessy
Journal: BMJ (1843)

This pamphlet contains a detail of facts of a very important kind, which, we doubt not, will cause a great sensation among the members of the profession throughout the world.We feel it, therefore, to be a duty to give as full an account of its contents as our space will permit.It will appear clearly from what we shall state that Dr. O'Shaughnessy has the merit of having added to our materia medica a drug of great and un- equivocal powers, and, probably, a remedy of marked efficacy in diseases hitherto the most unmanageable.For the sake of accuracy, in a matter of so much consequence, we shall avail ourselves, as much as possible, of the author's own words, and endeavour to communicate all the more important facts in a series of extracts from his pamphlet."The narcotic effects of hemp are popularly known in the south of Africa, South America, Turkey, Egypt, Asia Minor, India, and the adjacent territories of the Malays, Burmese, and Siamese.In all these countries hemp is used in various forms, by the dissipated and depraved, as the ready agent of a pleasing intoxication.In the popular medicine of these nations we find it extensively employed for a multitude of affections.But in western Europe its use either as a stimulant or as a remedy is equally unknown Much difference of VOL.X.
İleri Evre Küçük Hücreli Dışı Akciğer Kanserinde Sık Kullanılan Birinci Basamak Rejimler İle Histolojinin Rolü- Üç Kollu Randomize Bir Çalışmanın Retrospektif Analizinin Kısa Bir Raporu
Authors: Giorgio V. Scagliotti, Filippo De Marinis, Massimo Rinaldi, Lucio Crinò, Cesare Gridelli, Sergio Ricci, Yan D. Zhao, Astra M. Liepa, PharmD, Patrick Peterson, Maurizio Tonato
Journal: Journal of Thoracic Oncology (2010)
Altered hepatic gene expression in nonalcoholic fatty liver disease is associated with lower hepatic n‐3 and n‐6 polyunsaturated fatty acids
Authors: Bianca M. Arendt, Elena M. Comelli, David W.L. Ma, Wendy Lou, Anastasia Teterina, TaeHyung Kim, Scott K. Fung, David K.H. Wong, Ian McGilvray, Sandra E. Fischer, Johane P. Allard
Journal: Hepatology (2015)

In nonalcoholic fatty liver disease, hepatic gene expression and fatty acid (FA) composition have been reported independently, but a comprehensive gene expression profiling in relation to FA composition is lacking. The aim was to assess this relationship. In a cross-sectional study, hepatic gene expression (Illumina Microarray) was first compared among 20 patients with simple steatosis (SS), 19 with nonalcoholic steatohepatitis (NASH), and 24 healthy controls. The FA composition in hepatic total lipids was compared between SS and NASH, and associations between gene expression and FAs were examined. Gene expression differed mainly between healthy controls and patients (SS and NASH), including genes related to unsaturated FA metabolism. Twenty-two genes were differentially expressed between NASH and SS; most of them correlated with disease severity and related more to cancer progression than to lipid metabolism. Biologically active long-chain polyunsaturated FAs (PUFAs; eicosapentaenoic acid + docosahexaenoic acid, arachidonic acid) in hepatic total lipids were lower in NASH than in SS. This may be related to overexpression of FADS1, FADS2, and PNPLA3. The degree and direction of correlations between PUFAs and gene expression were different among SS and NASH, which may suggest that low PUFA content in NASH modulates gene expression in a different way compared with SS or, alternatively, that gene expression influences PUFA content differently depending on disease severity (SS versus NASH).Well-defined subjects with either healthy liver, SS, or NASH showed distinct hepatic gene expression profiles including genes involved in unsaturated FA metabolism. In patients with NASH, hepatic PUFAs were lower and associations with gene expression were different compared to SS.
Abstract 20549: First in Man Experience with a Dedicated Coronary Re-Entry Device for Revascularization of Chronic Total Occlusion
Authors: Kamran I Muhammad, William L Lombardi, Etsuo Tsuchikane, Craig A Thompson, Patrick L Whitlow
Journal: Circulation (2010)

Background: Successful percutaneous coronary intervention (PCI) for chronic total coronary occlusion (CTO) has been shown to improve outcomes in patients with ischemia. Despite newer dedicated guid...
Abstract 18655: Lack of Accuracy of Chest Radiography in Predicting Left Ventricular Lead Position when Compared to Chest Computed Tomography: Potential Implications for Cardiac Resynchronization Therapy
Authors: Christopher Ingelmo, John Rickard, Richard A Grimm, Bruce L Wilkoff, Paul Schoenhagen, Patrick Tchou, Milind Y Desai
Journal: Circulation (2010)

Background: While cardiac resynchronization therapy (CRT) improves outcomes in patients with systolic heart failure and prolonged QRS duration, up to 33% of patients do not respond clinically. Inap...
Calcification in the apocrine glands of naevus sebaceus
Authors: S.W. Choi, H.J. Woo, K-Y. Rho, S.J. Kang, S. Yi, H.O. Kim
Journal: British Journal of Dermatology (2000)

S IR, Naevus sebaceus is a hamartomatous lesion composed predominantly of sebaceous glands, 1 with ectopic apocrine glands being present in about two‐thirds of patients. 2 We describe a patient with naevus sebaceus and calcified apocrine glands; to our knowledge, this condition has not previously been reported in the literature A 40‐year‐old Korean man presented with an asymptomatic, 3 × 3 cm, verrucous, yellowish, alopecic plaque on the occipital scalp. At the edge of the lesion, a filiform warty component and many tiny dark brown puncta were present ( Fig. 1a). It had been present since birth, but flatter and skin‐coloured, becoming more verrucous and yellowish after adolescence. Laboratory findings were all within normal limits, including serum calcium and phosphate levels, and he had no other dermatological problem. Clinically, it was diagnosed as naevus sebaceus, and complete excision was performed. Histological examination revealed papillomatous changes, acanthosis of the epithelium and marked proliferation of the sebaceous glands. Some immature hair follicles were seen in adjacent sebaceous glands. In the mid‐dermis, there was a proliferation of numerous apocrine sweat gland structures ( Fig. 1b). In the lumina of the apocrine glands, decapitation secretion was apparent and eosinophilic secretion materials were seen in the innermost region. Some of the apocrine tubular structures contained calcified material, and parts of the epithelium showed a clear foamy cytoplasm. The clear cells were also seen in the lumina of some apocrine glands (Fig. 1c). Apocrine glands were connected to the adjacent sebaceous glands with long ducts. Calcification of secretion material was confirmed indirectly by von Kossa stain. Areas of dark brown puncta in a small part of the lesion showed dilated follicular epithelium with keratin plugging, but there was no direct correlation with calcification in the apocrine glands.
Mood's state, illness behaviour and quality of life in COPD and CHF patients with comparable functional status
Authors: Chiara Fante, Panagiota Tzani, Marina Aiello, Chiara Scelfo, Tareq Khourieh, Emilio Marangio, Carlo Pruneti, Alfredo Chetta
Journal: European Respiratory Journal (2014)

Introduction:  People may widely differ in their emotional responses to illness. We hypothesized that patients with chronic disabling pulmonary or cardiac disease, but with comparable functional status may have similar emotional responses to the underlying disease. Accordingly, we assessed mood9s state, illness behaviour and quality of life in COPD and CHF patients with comparable exercise tolerance.   Methods:  19 COPD (FEV 1   1 /VC  2 ) and 21 CHF (Ejection fraction  2 ) patients were assessed by cardiopulmonary exercise test (CPET) and by the Profile of Mood States (POMS), Illness Behaviour Questionnaire (IBQ) and Short Form-36 health survey (SF-36) to evaluate respectively mood9s state, illness behaviour and quality of life.   Results:  VO 2  peak values were 17.8 mL/kg/min ±5 and 16.6 mL/kg/min ±5 in COPD and CHF patients, respectively ( p=ns ). No significant differences were found in POMS, IBQ and SF-36 scores between the two groups. In all patients, VO 2  peak was significantly and directly related to SF-36 physical activity and general health subscales and to IBQ dysphoria subscale ( p  for all comparisons).   Conclusions:  Our pilot study shows that patients with chronic pulmonary or cardiac disabling disease, but with comparable functional status do not differ in mood9s state, illness behaviour and quality of life. Maximal exercise capacity was also related to illness behaviour and quality of life, but not to mood9s state.
Abstract 15228: Chronic Thromboembolic Pulmonary Hypertension (CTEPH): A Pig Model
Authors: Sandra Voss, Holger M Nef, Andreas Rolf, Sebastian Szardien, Lena Greim, Christian Troidl, Jedrzej Hoffmann, Matthias Willmer, Robert Voswinckel, Ardeschir Ghofrani, Christian W Hamm, Helge Mollmann
Journal: Circulation (2012)
Abstract 3790: Artesunate inhibits multiple proinflammatory transcription factors leading to the suppression of growth and induction of apoptosis in prostate cancer cells
Authors: Alamelu Nachiyappan, Muthu K Shanmugam, Feng Li, Alan Prem Kumar, Gautam Sethi
Journal: Cancer Research (2014)

Abstract Prostate cancer (PCa) is common and a frequent cause of cancer death among men worldwide. Moreover, PCa rates have risen quite significantly in the last decade in Singapore men and although some of the increase can be attributed to enhanced detection, much of the increased incidence is associated with genetic alterations and life-style related factors. Current therapies for metastatic prostate cancer are only marginally effective, and hence new treatment modalities are urgently needed. Considerable evidence suggests that chronic inflammation plays a pivotal role in the development and progression of PCa. Thus, the agents that can suppress inflammatory mediators have a potential in treatment of PCa. One way to expedite drug development is to find new uses for drugs already in clinical use. Hence we propose to investigate the role of artesunate, (a drug approved for the treatment of multidrug-resistant malaria) in PCa using diverse prostate cancer cell lines. In this study, we investigated the effect of artesunate (ART) primarily on signal transducer and activator of transcription 3(STAT3) signaling pathway in both androgen independent (DU145) and androgen dependent (LNCaP) PCa cell lines and also prospectively tested the hypothesis of NF-κB and STAT3 inhibition using a virtual predictive functional proteomics tumor pathway technology platform. We found that ART inhibited constitutive and IL-6-induced activation of STAT3 in DU145 and LNCaP cells in a dose and time dependent manner. We observed that STAT3 suppression by ART was mediated through the inhibition of activation of upstream kinases such as (c-Src, JAK1, and JAK2) and generation of reactive oxygen species (ROS) was also involved in this process. Our preliminary findings further indicate that ART also suppressed constitutive NF-κB activation in PCa cells. ART exhibited significant anti-proliferative effects and abrogated the migratory/invasive potential of PCa cells. Moreover, ART down-regulated the expression of various NF-κB and STAT3 regulated gene products involved in proliferation, survival and angiogenesis, also induced apoptosis in PCa cells lines as evident by DNA fragmentation and Annexin V staining. Overall our preliminary results from experimental and predictive studies indicate that ART mediates its anti-tumor effects through suppression of NF-κB and STAT3 pathways in PCa. Citation Format: Alamelu Nachiyappan, Muthu K Shanmugam, Feng Li, Alan Prem Kumar, Gautam Sethi. Artesunate inhibits multiple proinflammatory transcription factors leading to the suppression of growth and induction of apoptosis in prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3790. doi:10.1158/1538-7445.AM2014-3790
Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice
Authors: Xianzheng Wang, Aihua Dong, Jingjing Xiao, Xingjun Zhou, Haili Mi, Hanqian Xu, Jiming Zhang, Bin Wang
Journal: Cellular and Molecular Immunology (2015)
Abstract 16336: “Use-Dependent” Block of Ryanodine Receptor Calcium Channels by Flecainide and R-Propafenone Determines Their Potency for Calcium Wave Annihilation in Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Eleonora Savio Galimberti, Bjorn C Knollmann
Journal: Circulation (2011)

Background- Myocytes lacking calsequestrin (casq2-/-) exhibit frequent spontaneous RyR2 channel openings and Ca2+ waves that can trigger delayed afterdepolarizations and ventricular arrhythmias. We...
Abstract 18739: Acute Effect of the Na+/ca2+ Exchanger (ncx) Inhibitor Sea0400 on Diastolic Function in vivo and in vitro in a Model of Heart Failure With Preserved Ejection Fraction
Authors: Uwe Primessnig, Burkert Pieske, Frank Heinzel
Journal: Circulation (2014)

Background: Heart failure with preserved ejection fraction (HFPEF) is increasingly common but underlying cellular mechanisms are not well understood. We investigated cardiomyocyte function and the role of SEA0400, in vivo and in vitro in a rat model of diastolic heart failure. Methods: Young male Wistar rats were subjected to subtotal nephrectomy (NXT) or sham operation (SOP). After 24 weeks in vivo (pressure-volume loops) and in vitro characterization (cardiomyocyte function (Ca2+ transients, sarcoplasmic reticulum (SR) diastolic Ca2+ leak (Ca2+ sparks) and SR Ca2+ content)) as well as NCX function (caffeine-induced Ca2+ transient, TAU) and protein expression) were determined without an with the NCX inhibitor SEA0400 (in vivo: 1 mg/kgKG for 30 minutes/ in vitro: 300nM for 5 minutes incubation). Results: NXT rats showed stable compensated renal impairment and signs and symptoms of HFPEF (hypertrophied left ventricle (LV), left- and upward shift of end diastolic pressure (EDP) volume relationship, increased lung weight/body weight ratio indicating pulmonary congestion and preserved LV systolic function (EF, dP/dt)). In LV cardiomyocytes from NXT Ca2+ transient amplitude was unchanged but time for early (50%) decay was significantly prolonged at 24 weeks and correlated with diastolic dysfunction (EDP) in vivo. TAU of the caffeine transient was significantly prolonged at 24 weeks indicating reduced NCX forward mode activity, while NCX protein expression was up-regulated, suggesting increased NCX reverse mode activity. Ca2+ spark frequency was increased and SR Ca2+ content was decreased in NXT (p&lt;0.05). SEA0400 significantly accelerated Ca2+ transient decay and reduced Ca2+ spark frequency in NXT. Acute in vivo treatment with SEA0400 significantly enhanced active relaxation (isovolumetric relaxation constant) of the LV in NXT. Conclusion: This model of HFPEF is associated with prolonged cytosolic Ca2+ decay and increased diastolic Ca2+ leak in LV cardiomyocytes. Acute treatment with NCX inhibitor SEA0400 normalized cytosolic Ca2+ transients, improved net transsarcolemmal Ca2+ export and decreased SR Ca2+ leak in NXT, in line with a role for reverse mode NCX activity in HFPEF. In vivo active relaxation was improved after acute SEA0400 treatment.
Abstract 17226: Vascular Smooth Muscle Responsiveness to a Nitric Oxide Donor is Impaired in Healthy Adults with Increased Adiposity
Authors: Demetra D Christou, Gary L Pierce, Douglas R Seals
Journal: Circulation (2011)

Background- Vascular smooth muscle responsiveness to an exogenous nitric oxide donor (i.e., nitroglycerin-induced dilation; NID) is impaired in cardiovascular disease and in adults at risk for atherosclerosis. Although adiposity is associated with increased risk of atherosclerosis, its relation to NID is poorly defined. We sought to examine the relation of NID to total and abdominal adiposity in a healthy group of men and women varying widely in adiposity levels and age. Methods and Results- In 224 carefully screened adults (age:18-79 yrs, body mass index (BMI): 16.4-42.2 kg/m 2 ), we measured NID, total body adiposity (BMI and % body fat (%BF); dual-energy x-ray absorptiometry) and indices of abdominal adiposity (waist circumference (WC) and waist to hip ratio (WHR)). In a subgroup of 74 subjects, we also measured total abdominal (TAF), abdominal visceral (AVF) and subcutaneous fat (ASF) using CT scans. NID was determined as the vasodilator response (brachial ultrasonography) to 0.4 mg sublingual nitroglycerin. Based on multiple linear regression analyses, NID was negatively related to BMI (part correlation coefficient (r part )=-0.19, P=0.004) and not related with total %BF (r part =-0.12, P=0.07), whereas it was consistently negatively related with abdominal adiposity (WC, r part =-0.22; WHR, r part =-0.19; TAF, r part =-0.36; AVF, r part =-0.36; and ASF, r part =-0.30, all P≤0.009), independent of sex. Accounting for systolic blood pressure, high density lipoprotein (HDL) cholesterol and fasting blood glucose reduced all of the sex-independent relations between NID and adiposity by 3 to 42%, but overall the relations remained significant (P≤0.05). NID was 35% lower in a subgroup of subjects with the highest compared to the lowest quintile of abdominal visceral fat (P=0.003). This difference in NID was abolished after accounting for systolic blood pressure (P=0.2) and HDL cholesterol (P=0.1) but was not changed after accounting for fasting glucose (P=0.002). Conclusions- Total adiposity is modestly (BMI) or not related (% body fat) with NID, whereas abdominal adiposity is more consistently and strongly related with NID. Adiposity may influence NID in part via modulation of blood pressure, HDL cholesterol and/or fasting glucose.
Abstract P1-07-35: Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer
Authors: Catherine A Powell, Mohd W Nasser, Jacob C Wochna, Konstantin Shilo, Xiaoli Zhang, Ramesh K Ganju
Journal: Cancer Research (2015)

Abstract Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has a poor prognosis for patients, not only due to its aggressive nature, but also due to the lack of effective therapeutic strategies. High mortality is associated with metastasis of the primary TNBC. We analyzed the role of fatty acid binding protein 5 (FABP5), an intracellular fatty acid transport protein, in aggressive breast cancers, especially TNBC. FABP5 expression was analyzed in a tumor microarray (TMA) containing 423 breast cancer patient samples and found that FABP5 expression is associated with tumor grade, triple negative status, and disease-free survival. Next, a mechanistic approach was taken and found that FABP5 knockdown TNBC cell lines express lesser EGFR protein compared to control, and upon EGFR activation express less phospho-FAK and phospho-Pyk2. We found that EGFR was not down regulated at the transcriptional level in FABP5 knockout cells. Further analysis indicated the role for Cbl, an E3 ubiquitin-protein ligase, as a potential mechanistic target for the down-regulation of EGFR protein in FABP5 knockdown cell lines. EGFR is over-expressed in aggressive breast cancers, especially TNBC. Though EGFR is highly expressed in aggressive subtypes of breast cancer, targeted therapeutic strategies have not been successful in clinic. EGFR has been shown to be involved in distant metastasis in aggressive breast cancers. We found a correlation between FABP5 and EGFR expression and metastasis-free survival using publically available datasets from The Cancer Genome Atlas. We next studied the functional consequence of FABP5 knockdown in TNBC cell lines. We showed that EGF-induced FABP5 knockdown cells migrated less compared to control. Additionally, FABP5 knockdown cells were significantly less able to migrate into a wound in response to EGF stimulation. EGF-induced cell attachment of FABP5 knockdown cells is significantly decreased compared to control. Our findings suggest FABP5 modulates metastatic potential of TNBC through alterations in EGFR expression and downstream migratory signaling molecules. Citation Format: Catherine A Powell, Mohd W Nasser, Jacob C Wochna, Konstantin Shilo, Xiaoli Zhang, Ramesh K Ganju. Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-35.