tbuckley/cabot-search huggingface dataset:
Effect of Pravastatin on Cardiovascular Events in Older Patients with Myocardial Infarction and Cholesterol Levels in the Average Range: Results of the Cholesterol and Recurrent Events (CARE) Trial
Authors: Sandra J. Lewis
Journal: Annals of Internal Medicine (1998)

Background: A majority of all myocardial infarctions occur in patients who are 65 years of age or older and have average cholesterol levels, but little information is available on whether cholesterol lowering in such patients reduces the rate of recurrent cardiovascular disease. Objective: To determine whether pravastatin reduces the rate of recurrent cardiovascular events in older patients. Design: Subset analysis of a randomized, controlled trial. Setting: 80 hospitals and affiliates in the United States and Canada. Patients: 1283 patients aged 65 to 75 years who had had myocardial infarction and had a plasma total cholesterol level less than 6.2 mmol/L (240 mg/dL) and a low-density lipoprotein cholesterol level of 3.0 to 4.5 mmol/L (115 to 174 mg/dL). Intervention: Pravastatin, 40 mg/d, or placebo. Measurements: Five-year event rates of major coronary events (coronary death, nonfatal myocardial infarction, angioplasty, or bypass surgery) and stroke. Results: Major coronary events occurred in 28.1% of placebo recipients and 19.7% of pravastatin recipients (difference, 9.0 percentage points [95% CI, 4 to 13 percentage points]; relative risk reduction, 32%; P < 0.001). Coronary death occurred in 10.3% of the placebo group and in 5.8% of the pravastatin group (difference, 4.6 percentage points [CI, 1.9 to 6.5 percentage points]; relative risk reduction, 45%; P = 0.004). Stroke incidence was 7.3% in the placebo group and 4.5% in the pravastatin group (absolute reduction, 2.9 percentage points [CI, 0.3 to 4.5 percentage points]; relative reduction, 40%; P = 0.03). The numbers of older patients needed to treat for 5 years were 11 (CI, 8 to 24) to prevent a major coronary event and 22 (CI, 15 to 53) to prevent a coronary death. For every 1000 older patients treated, 225 cardiovascular hospitalizations would be prevented compared with 121 hospitalizations in 1000 younger patients. Conclusions: In older patients with myocardial infarction and cholesterol levels in the average range, pravastatin is associated with a clinically important reduction in risk for major coronary events and stroke. Given the high cardiovascular event rate in older patients, the potential for absolute benefit in this age group is substantial.
Initial Clinical Results Using Intracardiac Electrogram Monitoring to Detect and Alert Patients During Coronary Plaque Rupture and Ischemia
Authors: Tim A. Fischell, David R. Fischell, Alvaro Avezum, M. Sasha John, David Holmes, Malcolm Foster, Richard Kovach, Paulo Medeiros, Leopoldo Piegas, Helio Guimaraes, C. Michael Gibson
Journal: Journal of the American College of Cardiology (2010)
Five good reasons to read (and cite) the ERJ
Authors: K. F. Rabe, P. J. Sterk
Journal: European Respiratory Journal (2007)

Now 5 years into the job and with 1 more year to go, your Editors are pleased to update you once again through an editorial that has developed into a regular column summarising the state of your Journal, our reflections on the job and the current developments. The leadership of the European Respiratory Society (ERS) has clearly recognised the relevance and impact of the European Respiratory Journal ( ERJ ) and the other allied society publications, which has resulted in the formulation of the first publication strategy around what we believe is the flagship publication, the ERJ . This has also helped us, as Editors, to critically review the current status of the ERJ and has allowed us to formulate our own mission and aims for the coming years.

To make a long story short: we believe the ERJ is doing very well indeed at the moment, but as our readers and critical audience, you obviously deserve to know why we are so untypically confident in this statement. At least five good reasons come to mind when we think about recent developments within the ERJ that have contributed to its wider acceptance amongst those of you who search for novel scientific information, to use it for your research and cite the papers presented, and those of you who “simply” read the ERJ to keep up to date with a rapidly evolving clinical field.

The first and probably most straightforward …
Computer Derived Global Judgments in Psychiatry
Authors: CHARLES F. STROEBEL, BERNARD C. GLUECK
Journal: American Journal of Psychiatry (1970)

The authors describe a system in which factor scores obtained on a routine daily basis for each patient from computer scored nursing notes are subjected to sequential analysis to yield computer global decisions of "significantly better," "worse," or "unchanged" without special research techniques. The system's simplicity, objectivity, and enhanced reliability should make computer derived global decisions an attractive and extensively applicable technique in a wide variety of clinical and research settings.
Elastic Tension for Fractured Femur
Authors: W. R. Wilson
Journal: BMJ (1940)

The following observations are based mainly on ambu- lance study and practice at a first-aid post.It is hoped that they will prove at least interesting to others who have or may have the care of accident cases.-Concerning the application of traction to a limb for the correction of overriding of broken fragments of bone, both the methods in common use for the femur have defects inherent in them which seem to call for remedy.The more simple one, as done in ambulance work, consisting of a bandage around the ankle, pulled tight to the lower end of a Thomas splint, falls short of the ideal in the smallness of its range of action.No sooner have the muscles begun to
Association of genetic variants of methionine metabolism with methotrexate-induced CNS white matter changes in patients with primary CNS lymphoma
Authors: Michael Linnebank, Susanna Moskau, Annika Jürgens, Matthias Simon, Alexander Semmler, Katjana Orlopp, Axel Glasmacher, Christopher Bangard, Marlies Vogt-Schaden, Horst Urbach, Ingo G.H. Schmidt-Wolf, Hendrik Pels, Uwe Schlegel
Journal: Neuro-Oncology (2008)

Methotrexate (MTX) is an important anticancer drug and the most efficient chemotherapy component in primary CNS lymphoma (PCNSL). A typical side effect of intravenous high-dose MTX is the occurrence of confluent CNS white matter changes (WMC). Because MTX directly interferes with methionine metabolism, we analyzed the impact of genetic variants of methionine metabolism on the occurrence of WMC as a model of MTX toxicity. In a retrospective analysis of 68 PCNSL patients treated with MTX-based polychemotherapy with (n = 42) or without (n = 26) intraventricular treatment, 10 genetic variants influencing methionine metabolism were analyzed. Pearson's χ2 test and multinominal regression analysis were used to define the relevance of these genetic variants for the occurrence of WMC. In this patient sample, the occurrence of WMC was significantly predicted by the TT genotype of methylenetetrahydrofolate reductase c.677C>T (χ2 = 8.67; p = 0.013; df = 2), the AA genotype of methylenetetrahydrofolate reductase c.1298A>C (χ2 = 13.5; p = 0.001; df = 2), and the GG genotype of transcobalamin 2 c.776C>G (χ2 = 19.73; p < 0.001), in addition to male gender (χ2 = 11.95; p = 0.001). These data strengthen the hypothesis that MTX effects are influenced by methionine metabolism, which may offer new strategies to improve MTX-based therapies.
Changes in intraepithelial lymphocyte subpopulations in coeliac disease and enteropathy associated T cell lymphoma (malignant histiocytosis of the intestine).
Authors: J Spencer, T T MacDonald, T C Diss, J A Walker-Smith, P J Ciclitira, P G Isaacson
Journal: Gut (1989)

Studies of the morphologic and phenotypic diversity of intraepithelial T cells in human small intestine have shown them to be heterogeneous, yet distinct from most extra intestinal T cells. In this study sequential immunoenzymatic staining was used to define new intraepithelial lymphocyte subpopulations in man. In normal human jejunum approximately 6% of the intraepithelial T cells expressing CD3 (an antigen associated with the T cell receptor) do not express the T cell subset antigens CD4 or CD8. Approximately 20% of CD7+ cells (T cells and null cells) do not express CD4 or CD8 and 14% of the CD7+ cells do not express CD3 and are therefore not T cells. The CD7+, CD3+/-, CD4-, CD8- population is concentrated in the tips of the villi. In coeliac disease, the ratios of the subsets change significantly. The percentage of CD3+, 4-, 8- cells increases to 28%, the proportion of CD7+, 4-, 8- cells remains unchanged and the CD7+, CD3- (non-T cell) population is reduced to 1.4% of the CD7+ cells. In contrast, in patients with villous atrophy of uncertain aetiology, all CD4-, CD8- lymphocyte subsets are decreased compared with normal biopsies. Finally, in enteropathy associated T cell lymphoma (malignant histiocytosis of the intestine) in which the 'uninvolved mucosa' is histologically similar to untreated coeliac disease, the changes in the intraepithelial T cell sub-sets are indistinguishable from those in coeliac disease, suggesting that the lymphoma is a complication of coeliac disease.
Plasmacytoma-Like Post-Transplantation Lymphoproliferative Disease Occurring in a Cardiac Allograft: A Case Report and Review of the Literature
Authors: Tzu-Fei Wang, Jonathan L. Klein, Pamela K. Woodard, Anjum Hassan, Susan M. Joseph, Gregory A. Ewald, Geoffrey L. Uy
Journal: Journal of Clinical Oncology (2012)

A 33-year-old woman with a history of an orthotopic heart transplantation in 2006 for a left anterior descending artery dissection presented 5 years post-transplantation with intermittent palpitations and light headedness for 2 months.The patient had multiple episodes of acute and chronic rejection since her transplantation, and her immunosuppression consisted of prednisone 5 mg per day, mycophenolate mofetil, tacrolimus, and rapamune at the time of presentation.Telemetry monitoring revealed a new onset of sinus pauses.An echocardiogram showed normal biventricular function with left ventricular hypertrophy and biatrial enlargement.Myocardial magnetic resonance imaging of the heart demonstrated patchy areas of delayed contrast enhancement that mostly involved the left ventricular infe-
A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome
Authors: E.M.E.W. Heijnen, M.J.C. Eijkemans, E.G. Hughes, J.S.E. Laven, N.S. Macklon, B.C.J.M. Fauser
Journal: Human Reproduction Update (2005)

This meta-analysis was conducted to compare outcomes of conventional IVF in women presenting with polycystic ovary syndrome (PCOS) and non-PCOS patients. Studies in which PCOS patients undergoing IVF were compared with a matched—no male factor—control group were considered for this review. A definition consistent with the Rotterdam consensus criteria of PCOS was required, and all patients within a given study had to be treated with the same ovarian stimulation protocol. Information regarding patient characteristics and pregnancy outcome was also required. Nine out of 290 identified studies reporting data on 458 PCOS patients (793 cycles) and 694 matched controls (1116 cycles) fulfilled these inclusion criteria. PCOS patients demonstrated a significantly reduced chance of oocyte retrieval per started cycle, odds ratio (OR) = 0.5 [95% confidence interval (CI) = 0.2–1.0]. However, no difference was observed in chance of embryo transfer per oocyte retrieval between the groups (OR = 0.7, 95% CI = 0.4–1.3). Significantly more oocytes per retrieval were obtained in PCOS patients compared with controls [random effects estimate 3.4 [95% (CI) = 1.7–5.1)]. The number of oocytes fertilized did not differ significantly between PCOS patients and controls, weighted mean difference (WMD) 0.1 oocytes (95% CI = 21.4–1.6). No significant difference was observed in the clinical pregnancy rates per started cycle, OR = 1.0 (95% CI = 0.8–1.3). The incidence of ovarian hyperstimulation syndrome (OHSS) after oocyte retrieval was rarely reported. This meta-analysis demonstrates an increased cancellation rate, but more oocytes retrieved per retrieval and a lower fertilization rate in PCOS undergoing IVF. Overall, PCOS and control patients achieved similar pregnancy and live birth rates per cycle.
Operator-Independent Isotropic Three-Dimensional Magnetic Resonance Imaging for Morphology in Congenital Heart Disease
Authors: Thomas Sangild Sørensen, Hermann Körperich, Gerald F. Greil, Joachim Eichhorn, Peter Barth, Hans Meyer, Erik Morre Pedersen, Philipp Beerbaum
Journal: Circulation (2004)

Background— Operator-independent isotropic 3D MRI may greatly simplify the assessment of complex morphology in congenital heart disease. We sought to evaluate the reliability of this new approach. Methods and Results— In 31 adolescent and adult patients (age, 6 to 42 years; median, 16 years) with congenital heart disease, cardiac morphology was determined with free-breathing (navigator-gated), isotropic, 3D steady-state free-precession (3D SSFP) MRI and independently evaluated by 2 observers. Cardiac diagnoses and multiple distance measurements were compared with conventional MR reference sequences (ie, spin-echo, cine gradient-echo, contrast-enhanced MR angiography) and with echocardiography/cine cardioangiography or surgery. Of the 31 patients, 24 had native congenital heart defects or residual defects after repair that warranted immediate treatment. None of these defects was missed by 3D SSFP. Novel diagnostic issues were discovered in 4 of 31 patients (coronary anomalies, n=3; left juxtaposition of the right atrial appendage in double-outlet right ventricle and transposition of the great arteries, 1). For sizes of valves and vessels, we found minor mean differences of −1.1 to 1.6 mm, with SD ranging from 1.2 to 2.9 mm, demonstrating overall good agreement with standard MRI (Bland-Altman analysis). Interobserver variability of 3D SSFP distance measures was low; mean differences ranged from −1.5 to 1.0 mm, and SD ranged from 0.8 to 2.5 mm. Scatter was lower for extracardiac than intracardiac measures. Conclusions— In adolescents and adults, isotropic 3D SSFP MRI allows reliable assessment of complex cardiac morphology. Distance measurements are accurate and reproducible. Thus, a single operator-independent acquisition may substitute for conventional 2D MRI sequences to accelerate and simplify MR scanning in congenital heart disease.
Chronic thromboembolic pulmonary hypertension and vascular transformation of the lymph node sinuses
Authors: M Meysman, M Diltoer, HD Raeve, I Monsieur, L Huyghens
Journal: European Respiratory Journal (1997)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease often not recognized until it is far advanced. Medical management does not reverse the effects of the disease, nor does it prevent its progression. Pulmonary thromboendarterectomy is the preferred treatment. We present the case of a patient in whom CTEPH was mistaken for an interstitial lung disease with mediastinal lymph node enlargement. The mediastinal lymph node enlargement was due to vascular transformation of the lymph node sinuses (VTS). This is an unusual case of chronic thromboembolic pulmonary hypertension with vascular transformation of the lymph node sinuses.
Differential Role of an NF-κB Transcriptional Response Element in Endothelial Versus Intimal Cell VCAM-1 Expression
Authors: David S. Milstone, Motoi Ilyama, Mian Chen, Peter O’Donnell, Vannessa M. Davis, Jorge Plutzky, Jonathan D. Brown, Saptarsi M. Haldar, Allan Siu, Andrew C. Lau, Su-Ning Zhu, Mayada F. Basheer, Tucker Collins, Jenny Jongstra-Bilen, Myron I. Cybulsky
Journal: Circulation Research (2015)

Human and murine Vcam1 promoters contain 2 adjacent nuclear factor-κB (NF-κB)-binding elements. Both are essential for cytokine-induced transcription of transiently transfected promoter-reporter constructs. However, the relevance of these insights to regulation of the endogenous Vcam1 gene and to pathophysiological processes in vivo remained unknown.Determine the role of the 5' NF-κB-binding element in expression of the endogenous Vcam1 gene.Homologous recombination in embryonic stem cells was used to inactivate the 5' NF-κB element in the Vcam1 promoter and alter 3 nucleotides in the 5' untranslated region to allow direct comparison of wild-type versus mutant allele RNA expression and chromatin configuration in heterozygous mice. Systemic treatment with inflammatory cytokines or endotoxin (lipopolysaccharide) induced lower expression of the mutant allele relative to wild-type by endothelial cells in the aorta, heart, and lungs. The mutant allele also showed lower endothelial expression in 2-week atherosclerotic lesions in Vcam1 heterozygous/low-density lipoprotein receptor-deficient mice fed a cholesterol-rich diet. In vivo chromatin immunoprecipitation assays of heart showed diminished lipopolysaccharide-induced association of RNA polymerase 2 and NF-κB p65 with the mutant promoter. In contrast, expression of mutant and wild-type alleles was comparable in intimal cells of wire-injured carotid artery and 4- to 12-week atherosclerotic lesions.This study highlights differences between in vivo and in vitro promoter analyses, and reveals a differential role for a NF-κB transcriptional response element in endothelial vascular cell adhesion molecule-1 expression induced by inflammatory cytokines or a cholesterol-rich diet versus intimal cell expression in atherosclerotic lesions and injured arteries.
Cyclin D1 Degradation Is Sufficient to Induce G1 Cell Cycle Arrest despite Constitutive Expression of Cyclin E2 in Ovarian Cancer Cells
Authors: Chioniso Patience Masamha, Doris Mangiaracina Benbrook
Journal: Cancer Research (2009)

D- and E-type cyclins mediate G(1)-S phase cell cycle progression through activation of specific cyclin-dependent kinases (cdk) that phosphorylate the retinoblastoma protein (pRb), thereby alleviating repression of E2F-DP transactivation of S-phase genes. Cyclin D1 is often overexpressed in a variety of cancers and is associated with tumorigenesis and metastasis. Loss of cyclin D can cause G(1) arrest in some cells, but in other cellular contexts, the downstream cyclin E protein can substitute for cyclin D and facilitate G(1)-S progression. The objective of this study was to determine if a flexible heteroarotinoid anticancer compound, SHetA2, regulates cell cycle proteins and cell cycle progression in ovarian cancer cells. SHetA2 induced cyclin D1 phosphorylation, ubiquitination, and proteasomal degradation, causing G(1) arrest in ovarian cancer cells despite continued cyclin E2 expression and independently of p53 and glycogen synthase kinase-3beta. Cyclin D1 loss inhibited pRb S780 phosphorylation by cyclin D1-cdk4/6 and released p21 from cyclin D1-cdk4/6-p21 protein complexes to form cyclin E2-cdk2-p21 complexes, which repressed phosphorylation of pRb S612 by cyclin E2-cdk2 and ultimately E2F-DP transcriptional activity. G(1) arrest was prevented by overexpression or preventing degradation of cyclin D1 but not by restoration of pRb S612 phosphorylation through p21 knockdown. In conclusion, we show that loss of cyclin D1 in ovarian cancer cells treated with SHetA2 is sufficient to induce G(1) cell cycle arrest and this strategy is not impeded by the presence of cyclin E2. Therefore, cyclin D1 is a sufficient therapeutic target in ovarian cancer cells.
Metabolic Mapping of MCF10A Human Breast Cells via Multiphoton Fluorescence Lifetime Imaging of the Coenzyme NADH
Authors: Damian K. Bird, Long Yan, Kristin M. Vrotsos, Kevin W. Eliceiri, Emily M. Vaughan, Patricia J. Keely, John G. White, Nirmala Ramanujam
Journal: Cancer Research (2005)

Biochemical estimation of NADH concentration is a useful method for monitoring cellular metabolism, because the NADH/NAD+ reduction-oxidation pair is crucial for electron transfer in the mitochondrial electron chain. In this article, we present a novel method for deriving functional maps of intracellular reduction-oxidation ratio in vivo via measurement of the fluorescence lifetimes and the ratio of free and protein-bound NADH using two-photon fluorescence lifetime imaging (FLIM). Through systematic analysis of FLIM data from the control cells, it was observed that there is a statistically significant decrease in the fluorescence lifetime of both free and protein-bound NADH and the contribution of protein-bound NADH as cells progress from an early to logarithmic to confluent phase. Potassium cyanide (KCN) treatment and serum starvation of cells yielded similar changes. There was a statistically significant decrease in the fluorescence lifetime of protein-bound and free NADH at the early and logarithmic phase of the growth curve and a statistically significant decrease in the contribution of protein-bound NADH relative to that observed in the control cells at all three phases of the growth curve. The imposed perturbations (confluence, serum starvation, and KCN treatment) are all expected to result in an increase in the ratio of NADH/NAD+. Our studies suggest that the fluorescence lifetime of both the free and the protein-bound components of NADH and the ratio of free to protein-bound NADH is related to changes in the NADH/NAD+ ratio.
Enhanced PMN response in chronic bronchitis and community-acquired pneumonia
Authors: A. Strassburg, D. Droemann, G. van Zandbergen, H. Kothe, K. Dalhoff
Journal: European Respiratory Journal (2004)

Chronic bronchitis is a frequent underlying disease in community-acquired pneumonia (CAP). It is unclear to what extent an impaired or exaggerated innate immune response contributes to disease manifestations and severity. To assess the role of neutrophil activation and recruitment during acute pneumonic episodes, peripheral polymorphonulcear neutrophil (PMN) activation, chemotactic activity, interleukin-8 (CXCL-8) and CXCL-8 receptor (CXCR) expression and apoptosis rate were evaluated in CAP patients with and without chronic bronchitis. In addition, the expression of CXCRs and CXCL-8 was assessed on pulmonary neutrophils in chronic bronchitis patients to compare the activation of the chemokine system in different compartments. CAP severity was assessed by the simplified acute physiology score II and the prognosis of disease was assessed by the pneumonia severity index (PSI). An increased chemotactic activity of PMN from chronic bronchitis patients with CAP was found, which was not related to the expression of CXCRs. In addition, a decreased apoptosis rate of PMN was observed. Chemotactic activity was related to the PSI. Comparison of peripheral and pulmonary PMN revealed enhanced CXCL-8 levels and a decreased CXCR expression in the lung. In conclusion, neutrophil function in patients with chronic bronchitis and community-acquired pneumonia is characterised by an increased chemotactic activity combined with a decreased apoptosis rate. The downregulation of interleukin-8 receptors in the pulmonary compartment deserves further investigation.