tbuckley/cabot-search huggingface dataset:
Energy Loss Index in Aortic Stenosis
Authors: Philippe Pibarot, Damien Garcia, Jean G. Dumesnil
Journal: Circulation (2013)

Cardiology and European Society of Cardiology-European Association for Cardio-Thoracic Surgery guidelines, 1,2 aortic valve replacement (AVR) is considered a class I indication in patients with aortic stenosis (AS) if the stenosis is severe and the patient has symptoms or left ventricular ejection fraction <50%.Hence, accurate assessment of the hemodynamic severity of the valvular stenosis is crucial for clinical decision making.The stenosis severity is generally determined by measuring the transvalvular pressure gradient or the aortic valve effective orifice area (AVA); however, these conventional parameters do not account for the extent of pressure recovery that may occur downstream of the stenosis.In an article published in 2000 in Circulation, 3 we proposed a new Doppler echocardiographic parameter based on the energy loss concept to adjust the AVA for pressure recovery, and we postulated that this energy loss index (ELI) would improve assessment of stenosis severity and risk stratification in AS.Thirteen years later, Bahlmann and colleagues 4 publish in this issue of Circulation the first prospective study to demonstrate that ELI provides independent and incremental prognostic information to that derived from conventional measures of AS severity.In this elegant substudy of the SEAS (Simvastatin Ezetimibe in Aortic Stenosis) trial, the authors report that a 1 cm²/m² reduction in baseline ELI predicts a 2-fold increase in the risk of aortic valve events and of the composite of mortality and heart failure hospitalization after adjustment for peak aortic jet velocity or mean gradient.
Leukocyte-Derived Microparticles in Vascular Homeostasis
Authors: Anne Angelillo-Scherrer
Journal: Circulation Research (2012)

Leukocyte-derived microparticles (LMPs) may originate from neutrophils, monocytes/macrophages, and lymphocytes. They express markers from their parental cells and harbor membrane and cytoplasmic proteins as well as bioactive lipids implicated in a variety of mechanisms, maintaining or disrupting vascular homeostasis. When they carry tissue factor or coagulation inhibitors, they participate in hemostasis and pathological thrombosis. Both proinflammatory and anti-inflammatory processes can be affected by LMPs, thus ensuring an appropriate inflammatory response. LMPs also play a dual role in the endothelium by either improving the endothelial function or inducing an endothelial dysfunction. LMPs are implicated in all stages of atherosclerosis. They circulate at a high level in the bloodstream of patients with high atherothrombotic risk, such as smokers, diabetics, and subjects with obstructive sleep apnea, where their prolonged contact with the vessel wall may contribute to its overall deterioration. Numbering microparticles, including LMPs, might be useful in predicting cardiovascular events. LMPs modify the endothelial function and promote the recruitment of inflammatory cells in the vascular wall, necessary processes for the progression of the atherosclerotic lesion. In addition, LMPs favor the neovascularization within the vulnerable plaque and, in the ruptured plaque, they take part in coagulation and platelet activation. Finally, LMPs participate in angiogenesis. They might represent a novel therapeutic tool to reset the angiogenic switch in pathologies with altered angiogenesis. Additional studies are needed to further investigate the role of LMPs in cardiovascular diseases. However, large-scale studies are currently difficult to set up because microparticle measurement still requires elaborate techniques which lack standardization.
Hormonal characteristics of the human menstrual cycle throughout reproductive life.
Authors: B M Sherman, S G Korenman
Journal: Journal of Clinical Investigation (1975)

The changes in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FHS), estradiol, and progesterone that occur both early and late in reproductive life were characterized and compared with findings in young, normal women and in patients with certain menstrual disorders. A total of 50 complete menstrual cycles in 37 were examined. Five distinct patterns of hormonal regulation were found, three of which are reported here: (a) A long follicular phase and delayed follicular maturation in young women with long, unpredictable intermenstrual intervals from menarche; (b) a short follicular phase with increasing age and in short cycles in perimenopausal women; and (c) true anovulatory vaginal bleeding in long cycles in perimenopausal women. The short cycles before and during the menopausal transition were found to have lower E2 levels and high FSH concentrations throughout, while LH remained in the normal range. During long cycles in perimenopausal women, concentrations of LH and FSH were in the menopausal range. However, follicular maturation was observed months after high levels of gonadotropins were attained. These studies permit the characterization of the menstrual history of the normal woman in terms of the hormonal changes that occur and provide a basis for the definition of several disorders of follicular maturation.
Prescribing Tai Chi for Fibromyalgia — Are We There Yet?
Authors: Gloria Y. Yeh, Ted J. Kaptchuk, Robert H. Shmerling
Journal: New England Journal of Medicine (2010)

Fibromyalgia is a common and poorly understood pain disorder that afflicts an estimated 200 million or more people worldwide.1 The lack of objective abnormalities detected on physical examination and standard blood and imaging tests has led many physicians to question the existence of this disorder.2 However, for those experiencing the pain and other associated symptoms (including fatigue, stiffness, and nonrestorative sleep), there is little doubt that the condition is real — and so is the need for relief. Studies over the past decade suggest that fibromyalgia may be due, at least in part, to an alteration in pain sensitivity in . . .
THE ORGANOTROPIC, BACTERIOTROPIC, AND LEUCOCYTOTROPIC ACTIONS OF CERTAIN ORGANIC CHEMICALS
Authors: Lloyd D. Felton, Katharine M. Dougherty
Journal: The Journal of Experimental Medicine (1922)

We are dealing, as the results show, with groups of chemicals, all of which, whether bacteriotropic or not, greatly inhibit the engulfing of Staphylococcus aureus by leucocytes. Not a sufficiently large number of experiments was performed in attempt to cure experimental staphylococcus infections to warrant any condusion in regard to possible therapeutic activity against this organism. How-ever, as will appear in another paper, the only group out of the seven which definitely possessed an in vivo bactericidal action against pneumococcus is that of the cinchona derivatives. Certain members of the other chemical groups studied, although bactericidal in a very high dilution, -chemicals in which the concentration of a non-lethal dose was many times greater than that required to kill multiple minimal lethal doses of organisms in vitro, -had no certain effect when bacteria and drug were injected simultaneously into the peritoneal cavity of a mouse. In fact, the treated mouse often died before the controls. If we may assume,-leaving out of consideration the practical significance of in vivo chemical destruction and excretion following the injection of the drug into the animal,-that the failure of these chemicals to exhibit a benign influence on a systemic infection in cases in which the drug can be used in a bactericidal dilution, is due to their antiphagocytic property, only one step has been taken in analysis of the factors vital for the defense of the animal against a specific microorganism. Why do these chemicals inhibit leucocytic activity? Is it because of their influence upon complement, opsonin, or the leucocyte itself, or some special one function that determines the ability to ingest bacteria? Only further work can definitely settle this question and also determine whether or not such an analysis would be of practical importance in a rational development of chemotherapy. The ideal chemotherapeutic agent may be one that has an in vivo bactericidal potency and a negligible or stimulatory phagocytic action in doses non-lethal for the experimental animal. However difficult such a drug may be to find, it seems unlikely that the ultimate success in chemotherapy will be so simple. Again, it is conceivable that a secondary action of a drug, although leucocytotropic and not bacteriotropic, may bring about conditions in the animal body that will enable it to throw off the invading organism. Or finally, a drug compatible with the forces necessary to the host's defense and possessing in vivo bactericidal action to a greater or less degree may be the chemical sought for, the goal toward which we should strive, to achieve a rational chemotherapy for infectious diseases.
A case of erythema elevatum diutinum associated with B-cell lymphoma: a rare distribution involving palms, soles and nails
Authors: Y. Futei, I. Konohana
Journal: British Journal of Dermatology (2000)

We report a case of erythema elevatum diutinum (EED) in association with malignant B‐cell lymphoma. A 62‐year‐old man developed EED with an unusual distribution involving the palms, soles and nails. Treatment with dapsone was effective for his skin and nails until he developed generalized lymphadenopathy which turned out to be malignant lymphoma. Many haematological diseases, e.g. IgA paraproteinaemia and myeloma, have been reported in association with EED, but not malignant lymphoma. Even though it may just be a coincidence, we would like to add malignant lymphoma as one of the diseases associated with EED because the activity of EED and malignant lymphoma fluctuated in parallel.
OC-025 Survival Of Patients With Palliative Inoperable Gastrointestinal Obstruction Due To Malignancy Treated With Home Parenteral Nutrition
Authors: M Naghibi, M Stroud, TR Smith, M Elia
Journal: Gut (2014)

<h3>Introduction</h3> There is controversy about the indications for home parenteral nutrition (HPN) during the palliative phase of malignancy causing inoperable gastrointestinal obstruction (IBO). This is partly due to uncertainty about the survival of patients. This study aimed to establish the survival characteristics of these patients in order to inform decisions about the use of HPN. <h3>Methods</h3> A systematic review with meta-analyses were carried out in accordance with the Cochrane protocol for adult patients (&gt;18 years) with a confirmed diagnosis of malignancy causing IBO (in at least 80% of the patients) being treated with palliative HPN. A literature search was carried out in April 2013 using Medline, EMBASE, CINALH and Web of knowledge. Whenever possible, individual patient data were extracted to allow meta-analyses. <h3>Results</h3> 11 studies involving 420 patients, met the inclusion criteria. 3 studies reported individual patient data, 4 studies represented this using Kaplan Meier, one study using scatter plot and 3 studies only reported averages for survival length. The extraction procedure which gathered individual information on 220 patients from 8 studies, allowed a random effects model meta-analysis to be carried out. The mean age of patients within individual studies ranged between 45–61 years. 64% of patients were female. The underlying primary malignancy was gastrointestinal (53%), gynaecological (25%) (accounting for the female predominance), and others (22%). Four studies reported use of palliative chemoradiotherapy with 39–100% of the patients under going at least one cycle of treatment. Figure 1 shows the survival at monthly intervals for six months. The overall median survival is 83 days. 24% were still alive at 6 months but only about 2% at year. <h3>Conclusion</h3> This is first systematic review showing the survival in patients with malignant inoperable bowel obstruction receiving HPN during the palliative phase of care. We show, using the largest published cohort to date, that the median survival is only 83 days. The described variability in survival length between studies and between patients can be substantial. This information can help inform clinician decisions about the use of HPN in such patients. <h3>Disclosure of Interest</h3> None Declared.
Cep63 Recruits Cdk1 to the Centrosome: Implications for Regulation of Mitotic Entry, Centrosome Amplification, and Genome Maintenance
Authors: Harald Löffler, Anne Fechter, Marc Matuszewska, Rainer Saffrich, Martin Mistrik, Joachim Marhold, Christin Hornung, Frank Westermann, Jiri Bartek, Alwin Krämer
Journal: Cancer Research (2011)

Abstract Centrosomes are central regulators of mitosis that are often amplified in cancer cells. Centrosomes function both as organizers of the mitotic spindle and as reaction centers to trigger activation of Cdk1 and G2/M transition in the cell cycle, but their functional organization remains incomplete. Recent proteomic studies have identified novel components of the human centrosome including Cep63, a protein of unknown function that Xenopus studies have implicated in mitotic spindle assembly and spindle inactivation after DNA damage. Here, we report that human Cep63 binds to and recruits Cdk1 to centrosomes, and thereby regulates mitotic entry. RNAi-mediated Cep63 depletion in U2OS cancer cells induced polyploidization through mitotic skipping. Elicitation of this phenotype was associated with downregulation of centrosomal Cdk1, mimicking the phenotype induced by direct depletion of Cdk1. In contrast, Cep63 overexpression induced de novo centrosome amplification during cell-cycle interphase. Induction of this phenotype was suppressible by cell treatment with the Cdk inhibitor roscovitine. In a survey of 244 neuroblastoma cases, Cep63 mRNA overexpression was associated with MYCN oncogene amplification and poor prognosis. In cultured cells, Cep63 overexpression was associated with an enhancement in replication-induced DNA breakage. Together, our findings define human Cep63 as a centrosomal recruitment factor for Cdk1 that is essential for mitotic entry, providing a physical link between the centrosome and the cell-cycle machinery. Cancer Res; 71(6); 2129–39. ©2011 AACR.
Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer
Authors: José Baselga, Javier Cortés, Sung-Bae Kim, Seock-Ah Im, Roberto Hegg, Young-Hyuck Im, Laslo Roman, José Luiz Pedrini, Tadeusz Pienkowski, Adam Knott, Emma Clark, Mark C. Benyunes, Graham Ross, Sandra M. Swain
Journal: New England Journal of Medicine (2011)

The anti–human epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody trastuzumab improves the outcome in patients with HER2-positive metastatic breast cancer. However, most cases of advanced disease eventually progress. Pertuzumab, an anti-HER2 humanized monoclonal antibody that inhibits receptor dimerization, has a mechanism of action that is complementary to that of trastuzumab, and combination therapy with the two antibodies has shown promising activity and an acceptable safety profile in phase 2 studies involving patients with HER2-positive breast cancer.
Rho kinase inhibitors for pulmonary hypertension: waiting for clinical evidence
Authors: P. Pacaud, G. Loirand
Journal: European Respiratory Journal (2010)

Pulmonary arterial hypertension (PAH) is a rare disease characterised by a progressive increase of pulmonary vascular resistance (PVR) and pulmonary arterial pressure ( P pa), leading to right ventricle hypertrophy and death 1, 2. Although major advances in the understanding of disease development and treatment have been achieved over the past two decades, the pathogenesis of PAH is still not clearly understood. Idiopathic, familial and connective tissue disease-associated forms of PAH display similar pathological changes and are considered to share common pathogenic mechanisms, which involve endothelial dysfunction, endothelial and smooth muscle cell proliferation, increased vasoconstriction and in situ thrombosis 2. The consequence of this process is right ventricular ischaemia, remodelling, dilation, dysfunction and failure 3. Accordingly, current therapies are based on the use of drugs that improve endothelial function. Pharmacological agents targeting the endothelin (ET)-1 (ET-1 receptor antagonists, such as bosentan or sitaxentan), the nitric oxide (sildenafil, type 5 phosphodiesterase inhibitor), or the prostacyclin (epoprostenol, iloprost) pathways have shown benefits for patients with PAH 4. However, these treatments failed to improve the long-term survival and their use is hampered by either side-effects or inconvenient drug administration routes 5. Indeed, none of the currently available therapies is curative, so the search for new targets for novel therapeutic strategies continues.

Among promising targets recently identified is the serine-threonine kinase Rho kinase. Two isoforms of Rho kinase, Rock-1 and Rock-2, have been identified and found to be expressed in arteries. Rho kinase regulates a variety of cellular functions including motility, proliferation, apoptosis, contraction and gene expression 6. Rho kinase is considered to be a major determinant of arterial tone, through its essential role in the regulation of the Ca2+ sensitivity of smooth muscle cell contraction. Furthermore, Rho kinase negatively controls endothelial nitric oxide synthase expression and …
Anti-argonaute 2 (Ago2/Su) and -Ro antibodies are the common autoantibody specificities in primary anti-phospholipid syndrome (PAPS)
Authors: A Ceribelli, I Cavazzana, F Franceschini, A Tincani, B A Pauley, J Y F Chan, E K L Chan, M Satoh
Journal: Annals of the Rheumatic Diseases (2010)

Purpose Primary antiphospholipid syndrome (PAPS) is defi ned as patients with anti-phospholipid antibodies and thrombotic or obstetric symptoms, without systemic lupus erythematous (SLE) or other systemic rheumatic diseases.PAPS patients can have incomplete SLE-like features and some can evolve into SLE during follow-up.However, few studies systematically examined lupus autoantibodies and their clinical signifi cance in PAPS.The aim of our study is to characterise lupus autoantibodies in PAPS to analyse their clinical and laboratory correlations and their predictive role for the evolution of PAPS into SLE.Methods Sera from 52 PAPS patients were screened by indirect immunofl uorescence (IIF) antinuclear antibodies (ANA), immunoprecipitation (IP) of 35S-labeled K562 cell extract and ELISA (anti-argonaute 2 (Ago2, Su), 60kRo, 52kRo, La, dsDNA)).Anti-Ago2/Su positive sera were also tested for anti-GW body (GWBs) by IIF double staining using rabbit anti-GWBs serum.Results ANA were positive in 56% of PAPS patients.Anti-Ago2/Su antibodies were found in 13% (7/52) and anti-Ro/SSA in 10% (5/52) by IP.Interestingly, 79% (41/52) were negative by IP, thus anti-Ago2/Su and anti-Ro/SSA were the only identifiable specifi cities by IP in PAPS patients.No other lupus-related autoantibody was detected.Positive samples had a single specifi city except one case that had both.No particular association with clinical features of anti-phospholipid syndrome was found, except that IgG anti-β2glycoproteinI (β2GPI) antibodies were less frequent in anti-Ago2/Su positive patients (p=0.02).Although 2/7 anti-Ago2/Su positive patients had malar rash, there was no signifi cant association between the presence of anti-Ago2/Su or Ro/SSA and SLE-like features in PAPS.None of anti-Ago2/Su or -Ro positive patients developed SLE during follow-up.Although Ago2 is a key component of GWBs and
Periodontal Disease and Incident Type 2 Diabetes
Authors: Ryan T. Demmer, David R. Jacobs, Moïse Desvarieux
Journal: Diabetes Care (2008)

Type 2 diabetes and periodontal disease are known to be associated, but the temporality of this relationship has not been firmly established. We investigated whether baseline periodontal disease independently predicts incident diabetes over two decades of follow-up.A total of 9,296 nondiabetic male and female National Health and Nutrition Examination Survey (NHANES I) participants aged 25-74 years who completed a baseline dental examination (1971-1976) and had at least one follow-up evaluation (1982-1992) were studied. We defined six categories of baseline periodontal disease using the periodontal index. Of 7,168 dentate participants, 47% had periodontal index = 0 (periodontally healthy); the remaining were classified into periodontal index quintiles. Incident diabetes was defined by 1) death certificate (ICD-9 code 250), 2) self-report of diabetes requiring pharmacological treatment, or 3) health care facility stay with diabetes discharge code. Multivariable logistic regression models assessed incident diabetes odds across increasing levels of periodontal index in comparison with periodontally healthy participants.The adjusted odds ratios (ORs) for incident diabetes in periodontal index categories 1 and 2 were not elevated, whereas the ORs in periodontal index categories 3 through 5 were 2.26 (95% CI 1.56-3.27), 1.71 (1.0-2.69), and 1.50 (0.99-2.27), respectively. The OR in edentulous participants was 1.30 (1.00-1.70). Dentate participants with advanced tooth loss had an OR of 1.70 (P < 0.05) relative to those with minimal tooth loss.Baseline periodontal disease is an independent predictor of incident diabetes in the nationally representative sample of NHANES I.
Mechanistic Insights into Vascular Calcification in CKD
Authors: Rukshana Shroff, David A. Long, Catherine Shanahan
Journal: Journal of the American Society of Nephrology (2012)

Cardiovascular disease begins early in the course of renal decline and is a life-limiting problem in patients with CKD. The increased burden of cardiovascular disease is due, at least in part, to calcification of the vessel wall. The uremic milieu provides a perfect storm of risk factors for accelerated calcification, but elevated calcium and phosphate levels remain key to the initiation and progression of vascular smooth muscle cell calcification in CKD. Vascular calcification is a highly regulated process that involves a complex interplay between promoters and inhibitors of calcification and has many similarities to bone ossification. Here, we discuss current understanding of the process of vascular calcification, focusing specifically on the discrete and synergistic effects of calcium and phosphate in mediating vascular smooth muscle cell apoptosis, osteochondrocytic differentiation, vesicle release, calcification inhibitor expression, senescence, and death. Using our model of intact human vessels, factors initiating vascular calcification in vivo and the role of calcium and phosphate in driving accelerated calcification ex vivo are described. This work allows us to link clinical and basic research into a working theoretical model to explain the pathway of development of vascular calcification in CKD.