tbuckley/cabot-search huggingface dataset:
Characteristics and outcome of patients with active pulmonary tuberculosis requiring intensive care
Authors: R. Erbes, K. Oettel, M. Raffenberg, H. Mauch, M. Schmidt-Ioanas, H. Lode
Journal: European Respiratory Journal (2006)

Severe tuberculosis (TB) requiring intensive care unit (ICU) care is rare but commonly known to be of markedly bad prognosis. The present study aimed to describe this condition and to determine the mortality rate and risk factors associated with mortality. Patients with confirmed TB admitted to ICU between 1990 and 2001 were retrospectively identified and enrolled. Clinical, radiological and bacteriological data at admission and during hospital stay were recorded. A multivariate analysis was performed to identify the predictive factors for mortality. A total of 58 TB patients (12 females, mean age 48 yrs) admitted to ICU were included. Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score at admission was 13.1+/-5.6 and 22 of 58 (37.9%) patients required mechanical ventilation. The in-hospital mortality was 15 of 58 (25.9%); 13 (22.4%) patients died in the ICU. The mean survival of patients who died was 53.6 days (range 1-229), with 50% of the patients dying within the first 32 days. The factors independently associated with mortality were: acute renal failure, need for mechanical ventilation, chronic pancreatitis, sepsis, acute respiratory distress syndrome, and nosocomial pneumonia. These data indicate a high mortality of patients with tuberculosis requiring intensive care unit care and identifies new independently associated risk factors.
Non-steroidal anti-inflammatory use in the XV Pan-American Games (2007)
Authors: E R Da Silva, E H De Rose, J P Ribeiro, L B R Sampedro, D V Devos, A O Ferreira, L F M Kruel
Journal: British Journal of Sports Medicine (2009)

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used in sports medicine to reduce time of incapacity. Objective To describe the frequency of NSAIDs use by athletes in the XV Pan-American Games. Methods All athletes who were tested by the anti-doping control filled a form. The voluntarily declared medications were recorded and categorised according to sport modality, sex, region and control situation according to the World Anti-Doping Agency. Results Among the 1261 athletes tested (231 out-competition (OC) and 1030 in-competition (IC); 733 men and 528 women), 63% reported use of drugs, NSAIDs being the most frequently (64% of users) used medications. The use of medications was not significantly different between sexes or among different regions of the world. The number of users of only one type of NSAID was higher than those who used more than one type of NSAIDs or a combination with analgesics (335 vs 168 cases). IC reports presented higher use of NSAIDs than OC. Conclusion Athletes tested by the anti-doping control of the XV Pan-American Games reported a high frequency of NSAIDs use. The frequent utilisation in competition suggests that these medications might be used as ergogenic aid.
The Effects of Biological Sex and Diet on the Development of Heart Failure
Authors: John P. Konhilas, Leslie A. Leinwand
Journal: Circulation (2007)

B iological sex and gender 1 * have emerged as prominent players in cardiovascular health.It is widely appreciated that male and female hearts are different both at baseline and in response to numerous stimuli (for a recent review see Llamas et al 2 ).In general, male hearts respond less well to pressure or volume overload, to myocardial infarction (MI), and to aging.In considering the mechanisms that underlie sexually dimorphic cardiac traits, estrogen is an obvious candidate.However, data in the literature conflict on this point.The findings that cardiovascular risk increases when estrogen production ceases and that ovariectomy prevents the more beneficial outcome of volume overload or aging in females argues in favor of a protective role of estrogen. 3,4In contrast, the finding that estradiol-treated female rodents have a greater post-MI rate of death argues against a protective role. 5,6Recent human studies on hormone replacement therapy similarly question the cardioprotective role of estrogen. 7,8learly, the role of estrogen in cardiovascular disease (CVD) is complex, and further study is necessary.More significantly, it seems unlikely that the male/female dimorphisms in CVD can be attributed to a single factor such as estrogen.This review will consider the impact of estrogen, estrogen receptors (ERs), and diet on heart disease.The relationship between diet and CVD has traditionally focused on the consumption of fat and its impact on blood triglycerides and cholesterol. 9 -11 This review will not focus on these well-studied nutritional factors but will focus instead on a group of nutritional factors, phytoestrogens, that can mimic the actions of endogenous estrogens and seem likely to have profound effects on CVD in a sex-specific manner. Clinical Impact of Sex and CongestiveHeart Failure *It is generally accepted that biological sex is defined as being chromosomally male or female, whereas gender is a function of biological sex, culture, behavior, and environment.For simplicity, we have decided to use the term sex in this review.
Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice
Authors: Hormuzd A Katki, Walter K Kinney, Barbara Fetterman, Thomas Lorey, Nancy E Poitras, Li Cheung, Franklin Demuth, Mark Schiffman, Sholom Wacholder, Philip E Castle
Journal: The Lancet Oncology (2011)
Molecular determinants of cardiac specification
Authors: C. Lopez-Sanchez, V. Garcia-Martinez
Journal: Cardiovascular Research (2011)

In this review, we report and analyse the molecular factors involved in cardiogenesis from the earliest stages of development, using mainly the chick embryo as a model. The first part of the review demonstrates the areas where cardiogenic cells are located from gastrula stages, analysing a brief summary of the fate map of cardiogenic cells, from the epiblast through to the primitive heart tube. The next part analyses the commitment of pre-cardiac cells in cardiogenesis before, during, and after ingression through the primitive streak. Throughout the different journeys of the pre-cardiac cells, from the origin on the epiblast level up to the constitution of the tubular heart in the mid-line, the genes involved in the different stages of the process of cardiogenesis are very numerous. These have a greater or lesser importance depending on their specificity and the order in which they appear, bearing in mind that they become more valuable as the developmental process advances and the precursor cells start acquiring the commitment of pre-cardiac cells. Next, we show some box-filled diagrams to illustrate the dynamic gene expression pattern throughout the early stages of heart development, grouping the genes by their chronological significance. Finally, we discuss the implications that this temporal genomic expression could have in the induction and specification of the different types of cells and regions of the heart.
von Hippel–Lindau mutation in mice recapitulates Chuvash polycythemia via hypoxia-inducible factor-2α signaling and splenic erythropoiesis
Authors: Michele M. Hickey, Jennifer C. Lam, Natalie A. Bezman, W. Kimryn Rathmell, M. Celeste Simon
Journal: Journal of Clinical Investigation (2007)

The R200W mutation in the von Hippel–Lindau (VHL) tumor suppressor protein (pVHL) is unique in that it is not associated with tumor development, but rather with Chuvash polycythemia, a heritable disease characterized by elevated hematocrit and increased serum levels of erythropoietin and VEGF. Previous studies have implicated hypoxia-inducible factor–1α (HIF-1α) signaling in this disorder, although the effects of this mutation on pVHL function are not fully understood. In order to explore the mechanisms underlying the development of this polycythemia, we generated mice homozygous for the R200W mutation (VhlR/R). VhlR/R mice developed polycythemia highly similar to the human disease. The activity of HIF proteins, specifically the HIF-2α isoform, was upregulated in ES cells and tissues from VhlR/R mice. Furthermore, we observed a striking phenotype in VhlR/R spleens, with greater numbers of erythroid progenitors and megakaryocytes and increased erythroid differentiation of VhlR/R splenic cells in vitro. These findings suggest that enhanced expression of key HIF-2α genes promotes splenic erythropoiesis, resulting in the development of polycythemia in VhlR/R mice. This mouse model is a faithful recapitulation of this VHL-associated syndrome and represents a useful tool for studying polycythemias and investigating potential therapeutics.
Fever and increasing cANCA titre after kidney and autologous stem cell transplantation for Wegener's granulomatosis
Authors: T Daikeler, C Erley, M Mohren, C Amberger, H Einsele, L Kanz, I Kötter
Journal: Annals of the Rheumatic Diseases (2005)

In conclusion, infliximab can be used safely in daily clinical practice, but both doctors and patients should be aware of the (infection) risks, especially in patients receiving a higher dose (.3 mg/kg) of infliximab, in order to anticipate and minimise these risks.
Presentation of Exogenous Antigens on Major Histocompatibility Complex (MHC) Class I and MHC Class II Molecules Is Differentially Regulated during Dendritic Cell Maturation
Authors: Lélia Delamarre, Hilda Holcombe, Ira Mellman
Journal: The Journal of Experimental Medicine (2003)

During maturation, dendritic cells (DCs) regulate their capacity to process and present major histocompatibility complex (MHC) II–restricted antigens. Here we show that presentation of exogenous antigens by MHC I is also subject to developmental control, but in a fashion strikingly distinct from MHC II. Immature mouse bone marrow–derived DCs internalize soluble ovalbumin and sequester the antigen intracellularly until they receive an appropriate signal that induces cross presentation. At that time, peptides are generated in a proteasome-dependent fashion and used to form peptide–MHC I complexes that appear at the plasma membrane. Unlike MHC II, these events do not involve a marked redistribution of preexisting MHC I molecules from intracellular compartments to the DC surface. Moreover, out of nine stimuli well known to induce the phenotypic maturation of DCs and to promote MHC II presentation, only two (CD40 ligation, disruption of cell–cell contacts) activated cross presentation on MHC I. In contrast, formation of peptide–MHC I complexes from endogenous cytosolic antigens occurs even in unstimulated, immature DCs. Thus, the MHC I and MHC II pathways of antigen presentation are differentially regulated during DC maturation.
Successful Use of a Sucrose-Containing Enteral Formula in Diabetic Nursing Home Elderly
Authors: Yaakov Levinson, Aviva Epstein, Bella Adler, Leon Epstein, Tzvi Dwolatzky
Journal: Diabetes Care (2006)

The prevalence of diabetes among the elderly is high (1), and many elderly diabetic patients require formula feeding for nutritional support. Traditionally, sucrose-containing formulas are seldom administered to diabetic patients, since it is assumed that the high content of simple sugars will lead to a rapid elevation in blood glucose levels. However, sucrose actually has a moderate glycemic index (2), and there is no evidence that carbohydrate from sugars is more rapidly absorbed than from starch (3). Also, a high-sucrose diet did not adversely affect glycemia in subjects with type 2 diabetes (4). Finally, the position statement of the American Diabetes Association in 2002 (5) states that the intake of sucrose-containing foods by diabetic individuals need not be restricted.

The prevalence of diabetes among residents of long-term care institutions is ∼18% (6), and patients may require prolonged formula feeding. The use of high-fat, low-carbohydrate commercial formulas for diabetic patients is controversial (7), and their usefulness in prolonged nutritional support may be limited.

The purpose of our study was to examine the effect of a sucrose-containing high-calorie, high-protein, in-house formula on the nutritional state and glycemic control of elderly diabetic patients in a long-term care institution.

We performed a prospective observational study assessing the nutritional outcome and glycemic control …
Loaded Shortening, Power Output, and Rate of Force Redevelopment Are Increased With Knockout of Cardiac Myosin Binding Protein-C
Authors: F. Steven Korte, Kerry S. McDonald, Samantha P. Harris, Richard L. Moss
Journal: Circulation Research (2003)

Myosin binding protein-C (MyBP-C) is localized to the thick filaments of striated muscle where it appears to have both structural and regulatory functions. Importantly, mutations in the cardiac MyBP-C gene are associated with familial hypertrophic cardiomyopathy. The purpose of this study was to examine the role that MyBP-C plays in regulating force, power output, and force development rates in cardiac myocytes. Skinned cardiac myocytes from wild-type (WT) and MyBP-C knockout (MyBP-C-/-) mice were attached between a force transducer and position motor. Force, loaded shortening velocities, and rates of force redevelopment were measured during both maximal and half-maximal Ca2+ activations. Isometric force was not different between the two groups with force being 17.0+/-7.2 and 20.5+/-3.1 kN/m2 in wild-type and MyBP-C-/- myocytes, respectively. Peak normalized power output was significantly increased by 26% in MyBP-C-/- myocytes (0.15+/-0.01 versus 0.19+/-0.03 P/Po x ML/sec) during maximal Ca2+ activations. Interestingly, peak power output in MyBP-C-/- myocytes was increased to an even greater extent (46%, 0.09+/-0.03 versus 0.14+/-0.02 P/Po x ML/sec) during half-maximal Ca2+ activations. There was also an effect on the rate constant of force redevelopment (ktr) during half-maximal Ca2+ activations, with ktr being significantly greater in MyBP-C-/- myocytes (WT=5.8+/-0.9 s(-1) versus MyBP-C-/-=7.7+/-1.7 s(-1)). These results suggest that cMyBP-C is an important regulator of myocardial work capacity whereby MyBP-C acts to limit power output.
Simvastatin Attenuates Oxidant-Induced Mitochondrial Dysfunction in Cardiac Myocytes
Authors: Steven P. Jones, Yasushi Teshima, Masaharu Akao, Eduardo Marbán
Journal: Circulation Research (2003)

3-Hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase inhibitors (statins) can exert beneficial effects independently of serum cholesterol reduction by increasing the bioavailability of nitric oxide. However, it is unclear whether statins can exert such effects directly on cardiac myocytes and whether mitochondria are potential targets. Neonatal rat cardiac myocytes were cultured and subjected to oxidant stress (1 hour of 100 μmol/L H 2 O 2 ). Mitochondrial membrane potential, a key determinant of cardiomyocyte viability, was assessed by flow cytometric analysis of tetramethylrhodamine ethyl ester (TMRE)–loaded cells. Hydrogen peroxide significantly reduced mitochondrial membrane potential. Incubation of the cardiac myocytes in simvastatin (≥1 μmol/L) 1 hour before peroxide exposure significantly attenuated the loss of TMRE fluorescence. This effect was inhibited by the nitric oxide synthase inhibitor N G -nitro- l -arginine methyl ester (L-NAME) or the ATP-sensitive mitochondrial potassium channel (mitoK ATP ) blocker 5-hydroxydecanoate. Simvastatin attenuates mitochondrial membrane depolarization after exposure to oxidant stress. These findings provide primary evidence that myocytes can act as triggers and effectors in the cardioprotective cascade of simvastatin therapy. These results bear implications of statin therapy as a potential clinical application of pharmacological preconditioning.
A Phase I Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of Deforolimus in Patients with Advanced Malignancies
Authors: Christine M. Hartford, Apurva A. Desai, Linda Janisch, Theodore Karrison, Victor M. Rivera, Lori Berk, John W. Loewy, Hedy Kindler, Walter M. Stadler, Heather L. Knowles, Camille Bedrosian, Mark J. Ratain
Journal: Clinical Cancer Research (2009)

Abstract Purpose: This was a phase I trial to determine the maximum tolerated dose and toxicity of deforolimus (AP23573, MK-8669), an inhibitor of mammalian target of rapamycin (mTOR). The pharmacokinetics, pharmacodynamics, and antineoplastic effects were also studied. Experimental Design: Deforolimus was administered intravenously over 30 min every 7 days according to a flat dosing schedule. Dose was escalated according to an accelerated titration design. Patients remained on study until disease progression as long as they tolerated the drug without significant toxicities. Results: Forty-six patients were enrolled on the study. Common side effects included fatigue, anorexia, and mucositis. The maximum tolerated dose was 75 mg and mucositis was the dose-limiting toxicity. Similar to other mTOR inhibitors, deforolimus exhibited nonlinear pharmacokinetics and a prolonged half-life. Among 34 patients evaluable for response, 1 patient had a partial response, 21 patients had stable disease, and 12 had progressed. Percent change in tumor size was significantly associated with AUC (P = 0.015). A significant association was also detected for maximum change in cholesterol within the first two cycles of therapy and change in tumor size (r = −0.38; P = 0.029). Conclusions: Deforolimus was well tolerated on the schedule tested in this trial with toxicity and pharmacokinetic profiles that were similar to that of other mTOR inhibitors. Additional phase II studies are needed to determine if deforolimus is superior to other mTOR inhibitors in terms of efficacy. The change in serum cholesterol as a potential biomarker of activity should be studied further.
Defining the sports medicine specialist in the United Kingdom: a Delphi study
Authors: B Thompson, D MacAuley, O McNally, S O’Neill
Journal: British Journal of Sports Medicine (2004)

To define the role and responsibilities of the sports medicine specialist using a recognised research technique.A Delphi technique was employed using anonymous postal questionnaires sent to a random sample of 300 members of the British Association of Sport and Exercise Medicine. The questionnaire of 300 putative attributes was developed in a pilot study and the Delphi technique used allowed participants to modify their responses according to the responses of other participants.There was a 53% response to both rounds of the study with 75.6% of the respondents being male, 39% having a higher qualification in sports medicine, and 45.6% being general practitioners. Some 86.3% strongly agreed that sport and exercise medicine should be a recognised speciality and 90% strongly agreed that it should be available on the National Health Service (NHS). The most important specialist attributes were orthopaedic and soft tissue medicine (83.6% strongly agreed) and emergency medical management (79.7% strongly agreed). More than 75% of respondents did not agree that either research or personal playing experience were relevant.Sports and exercise medicine is an evolving speciality in the United Kingdom. We believe this is the first systematic attempt to define the role and responsibilities of the sports medicine specialist and the findings are of relevance to the future development of a career pathway.
Subspecific origin and haplotype diversity in the laboratory mouse
Authors: Hyuna Yang, Jeremy R Wang, John P Didion, Ryan J Buus, Timothy A Bell, Catherine E Welsh, François Bonhomme, Alex Hon-Tsen Yu, Michael W Nachman, Jaroslav Pialek, Priscilla Tucker, Pierre Boursot, Leonard McMillan, Gary A Churchill, Fernando Pardo-Manuel de Villena
Journal: Nature Genetics (2011)
PROBABLE INFLUENCE OF THE MODERN SMALL ARM PROJECTILE ON MILITARY SURGERY.
Authors: G. F. LYDSTON
Journal: JAMA (1898)

The modern small arm is destined to be the chief factor in modifying military surgical practice. It is as yet untried upon a sufficiently large scale in actual warfare to determine its practical merits. Certain things, however, have been fairly well established, and multitudinous and varied views have been expressed as to its utility. As the small arm was designed as a superior instrument for the infliction of physical injury, its merits and demerits are perhaps of more interest to military surgery than to any other branch of the service. The first point for consideration is the question of the relative danger experienced by non-combatants of the present day, and by the surgeon more particularly, as compared with the past. Until the invention of the modern rapid-fire, extremely long range rifle, it was comparatively easy for the hospital department to put itself in a position which was not only safe,
Origin and Evolution of Eukaryotic Chaperonins: Phylogenetic Evidence for Ancient Duplications in CCT Genes
Authors: John M. Archibald, John M. Logsdon Jr., W. Ford Doolittle
Journal: Molecular Biology and Evolution (2000)

Chaperonins are oligomeric protein-folding complexes which are divided into two distantly related structural classes. Group I chaperonins (called GroEL/cpn60/hsp60) are found in bacteria and eukaryotic organelles, while group II chaperonins are present in archaea and the cytoplasm of eukaryotes (called CCT/TriC). While archaea possess one to three chaperonin subunit–encoding genes, eight distinct CCT gene families (paralogs) have been characterized in eukaryotes. We are interested in determining when during eukaryotic evolution the multiple gene duplications producing the CCT subunits occurred. We describe the sequence and phylogenetic analysis of five CCT genes from Trichomonas vaginalis and seven from Giardia lamblia, representatives of amitochondriate protist lineages thought to have diverged early from other eukaryotes. Our data show that the gene duplications producing the eight CCT paralogs took place prior to the organismal divergence of Trichomonas and Giardia from other eukaryotes. Thus, these divergent protists likely possess completely hetero-oligomeric CCT complexes like those in yeast and mammalian cells. No close phylogenetic relationship between the archaeal chaperonins and specific CCT subunits was observed, suggesting that none of the CCT gene duplications predate the divergence of archaea and eukaryotes. The duplications producing the CCTδ and CCTϵ subunits, as well as CCTα, CCTβ, and CCTη, are the most recent in the CCT gene family. Our analyses show significant differences in the rates of evolution of archaeal chaperonins compared with the eukaryotic CCTs, as well as among the different CCT subunits themselves. We discuss these results in light of current views on the origin, evolution, and function of CCT complexes.