tbuckley/cabot-search huggingface dataset:
What a stroke
Authors: Umair Ansari, James Crampton
Journal: BMJ (2005)

the analysis and the writing, editing, and final review of the manuscript.KD is the guarantor.All authors are members of a collaborative health systems development research programme that has used maternal health as one possible probe to understand health systems functioning in several low and middle income countries.These findings result from both literature review and dataset analysis in Russia.Statistical information was derived from the State Statistical Committee from the Ministry of Health annual statistical publications, and from the Tula Oblast Statistics Office.Relevant information from empirical studies conducted by the authors in 2002-3 has also been reported, including a study of maternal care provision in Tula and analysis of a dataset including all births in Tula in 2000.Competing interests: None declared.
VIRAL HEPATITIS ASSOCIATED WITH TRANSPLANTABLE MOUSE LEUKEMIA
Authors: Herbert Braunsteiner, Charlotte Friend
Journal: The Journal of Experimental Medicine (1954)

An hepatic disease caused by a filterable agent carried in leukemic mice is described. Ordinarily the virus remains latent and asymptomatic. If, however, the mice are treated with urethane or methylformamide before and after virus inoculation, the disease becomes manifest and is characterized by extremely marked liver necrosis. Infant mice, a large percentage of weanlings, and adult Bagg albino mice are killed when injected with a filtrate from organs of diseased animals. Adult F1 and Swiss mice show signs of the disease but generally recover. They succumb, however, when simultaneously treated with urethane or methylformamide. By continuing the treatment of consecutive transfer generations an acute disease can be induced which finally kills all adult F1 mice without the treatment. At this stage the original leukemia may be lost. Mice which have recovered from the subacute disease are resistant to the acute disease, and mice injected with the latent form of the agent are immune to the subacute disease. However, even immunized animals lose their resistance if they are treated with urethane. The acute or subacute disease can be reduced to the latent stage by passing the agent through several generations of immunized animals. The relationship of this hepatitis virus of mice to viruses causing similar diseases is discussed, as is the possibility that these agents are closely related, if not identical.
Use of Over-the-Counter Nicotine Patch for Smoking Cessation: Prudent or Premature?
Authors: S. E. McNagny, J. S. Ahluwalia
Journal: JAMA (1996)

<h3>To the Editor.</h3> —In a well-designed and thoughtful analysis, Drs Fiscella and Franks<sup>1</sup>determine the incremental costeffectiveness of the transdermal nicotine patch for smoking cessation as an adjunct to physician counseling. The authors conclude that their findings support both the use of the nicotine patch and health insurance coverage of patch therapy. We heartily endorse these conclusions. The authors also conclude that their analysis does not support over-the-counter (OTC) use of the patch since their model was insensitive to incremental changes in physician time. We respectfully question this conclusion. The only costs considered in the authors' analysis, those of patch and physician counseling, would be nil with OTC use for anyone obtaining patches without physician counseling. Thus, from the perspective of the medical payer used in their model, patch use would become highly costeffective, even if patch effectiveness were found to be significantly lower with OTC use. The key
Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice
Authors: Rusty L. Montgomery, Matthew J. Potthoff, Michael Haberland, Xiaoxia Qi, Satoshi Matsuzaki, Kenneth M. Humphries, James A. Richardson, Rhonda Bassel-Duby, Eric N. Olson
Journal: Journal of Clinical Investigation (2008)

Histone deacetylase (HDAC) inhibitors show remarkable therapeutic potential for a variety of disorders, including cancer, neurological disease, and cardiac hypertrophy. However, the specific HDAC isoforms that mediate their actions are unclear, as are the physiological and pathological functions of individual HDACs in vivo. To explore the role of Hdac3 in the heart, we generated mice with a conditional Hdac3 null allele. Although global deletion of Hdac3 resulted in lethality by E9.5, mice with a cardiac-specific deletion of Hdac3 survived until 3-4 months of age. At this time, they showed massive cardiac hypertrophy and upregulation of genes associated with fatty acid uptake, fatty acid oxidation, and electron transport/oxidative phosphorylation accompanied by fatty acid-induced myocardial lipid accumulation and elevated triglyceride levels. These abnormalities in cardiac metabolism can be attributed to excessive activity of the nuclear receptor PPARalpha. The phenotype associated with cardiac-specific Hdac3 gene deletion differs from that of all other Hdac gene mutations. These findings reveal a unique role for Hdac3 in maintenance of cardiac function and regulation of myocardial energy metabolism.
Family Medicine: Principles and Practice
Authors: Theodore G. Ganiats
Journal: JAMA (1994)

To create a specialty textbook the editor must somehow come up with a single work that summarizes the essence of the specialty. In any specialty this is difficult, but in many ways the specialty of family practice, because of its breadth, makes this effort all the more challenging. In its fourth edition, Taylor's<i>Family Medicine: Principles and Practice</i>clearly rises to the challenge. A textbook like this should be judged on its readability, including organization, comprehensiveness, and timeliness. A key element would be the quality of the authors and how well the book comes together as a unit despite having multiple authors. Dr Taylor has assembled a veritable<i>Who's Who</i>in family medicine with about 200 authors. However, the book maintains the feel of the work of a smaller group and is exquisite in its organization and presentation. The text is divided into three parts. The first discusses the specialty
Abstract 454: <i>TET2</i> alterations facilitate progression of metastatic prostate cancer
Authors: Michael L. Nickerson, Sudipto Das, Hong Lou, Hongchuan Li, Sevilay Turan, Kate Im, Stephen Anderson, Thorkell Andresson, Michael Dean
Journal: Cancer Research (2014)

Abstract Metastatic prostate cancer (mPCa) is a highly lethal disease and molecular markers identifying disease subtypes and/or therapeutic targets are needed. We sequenced the exomes of five metastatic tumors and healthy kidney tissue from an index patient with castration resistant mPCa to identify lesions associated with disease progression and metastasis. A somatic missense TET2 alteration predicted to be deleterious to the protein was observed at the metastatic stage of disease. We sequenced TET2 in additional mPCa tumors and PCa cell lines and detected somatic missense alterations, frequent LOH, and a frameshift truncation in PCa cell line, DU-145, derived from a mPCa brain tumor. We also observed complex combinations of frequent and rare germline missense SNPs, which may contribute to a previously described association of TET2 with PCa risk by GWAS. In this study, we confirm transcription factor binding to TET2 alleles associated with disease by GWAS. We examine TET2 binding partners in prostate cells by affinity purification, mass spectrometry, and forward and reverse immunoprecipitation. We confirmed a protein complex containing TET2, OGT, and two transcriptional co-activators/splicing factors implicated in receptor-mediated gene expression. Functional analysis shows TET2 loss alters expression of a unique set of genes, increases cell proliferation, and therefore is a driver of PCa. TET2 loss may facilitate progression to castration resistant mPCa and appears to define a subset of cases with metastatic disease. Citation Format: Michael L. Nickerson, Sudipto Das, Hong Lou, Hongchuan Li, Sevilay Turan, Kate Im, Stephen Anderson, Thorkell Andresson, Michael Dean. TET2 alterations facilitate progression of metastatic prostate cancer. [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 454. doi:10.1158/1538-7445.AM2014-454
Alpha1 antitrypsin deficiency and pulmonary emphysema
Authors: M. C. Jones, G. O. Thomas
Journal: Thorax (1971)

An association between a genetically determined deficiency of the serum enzyme α<sub>1</sub> antitrypsin and pulmonary emphysema is now well established. Serum antitryptic activity was measured in 103 patients suspected of having emphysema. Eighty-seven fulfilled the diagnostic criteria for emphysema and, of these, 16 had deficient levels, 5 had intermediate levels, and 66 had normal levels. The results of clinical, radiographic, and physiological studies in each group were then compared. Characteristic features noted in the deficient group included onset of dyspnoea during the third or fourth decades and uniformly symmetrical radiographic lower zone involvement. Other factors such as sex distribution, cigarette smoking, and chronic bronchitis are discussed. Sixty-eight relatives of the 16 patients with deficient levels were also studied. The findings in these are compatible with an autosomal recessive mode of inheritance although difficulties in identifying the heterozygous state were encountered. Six relatives had deficient levels and of these three had emphysema.
Congenital dysfibrinogenemia: fibrinogen detroit
Authors: Eberhard F. Mammen, Ananda S. Prasad, Marion I. Barnhart, Chi C. Au
Journal: Journal of Clinical Investigation (1969)

A 17 yr old female with a congenital bleeding disorder was found to suffer from dysfibrinogenemia. Whole blood and plasma coagulation times were delayed and thrombelastograms were grossly abnormal. Clottability of plasma fibrinogen by addition of thrombin was not demonstrated during the 30 min test period. Fibrinogen was revealed by turbidometric and immunologic techniques. Other coagulation factors were present in normal amounts and prothrombin activation was normal. Patient's plasma inhibited thrombin clotting times of normal plasma and purified normal fibrinogen. Fibrinolysis was not detected. The plasma fibrinogen migrated normally on paper and cellulose acetate electrophoresis, but on immunoelectrophoresis it displayed a faster mobility than normal fibrinogen. On immunodiffusion the antigenic determinants were similar to those of normal fibrinogen. The patient's fibrinogen-antifibrinogen precipitins required longer to appear and the resultant precipitin was broader and hazier than those elicited with normal fibrinogen. These findings suggest the presence of two discrete populations of fibrinogen molecules. Investigation of the family of the patient suggested that the defect has an autosomal dominant pattern of heredity. Immunologic comparisons of our patient's plasma and of her relatives with plasma of patients with "Fibrinogen Baltimore" and "Fibrinogen Cleveland" revealed certain differences in immunoelectrophoretic mobility as well as in immunodiffusion. In keeping with the nomenclatures of abnormal fibrinogens in the literature, we propose the term "Fibrinogen Detroit" for this fibrinogen.Physicochemical properties of "Fibrinogen Detroit" were investigated also and compared with those of normal fibrinogen. Purified normal fibrinogen (clottability 96.7%) and "Fibrinogen Detroit" revealed homogeneity when studied by ultracentrifugation and immunoelectrophoresis. Native and cleaved "Fibrinogen Detroit" had the same sedimentation constants and molecular weights as the normal. In fresh samples. 3 moles of free SH groups/mole of fibrinogen were titrated in both. Determination of the amino acid composition revealed a decreased content of lysine, glucosamine, and galactosamine in abnormal fibrinogen. Total carbohydrates, protein-bound hexoses, sialic acid, and hexosamine were decreased in the abnormal fibrinogen. In an investigation with Doctors Blombäck a specific molecular defect was revealed in the N-terminal disulfide knot of the alpha (A) chain in which the arginine at the 19th position was replaced by serine. It is believed that the substitution of a strongly basic amino acid with a neutral hydroxy acid may result in considerable conformational changes in the N-terminal disulfide knot of fibrinogen which might affect the "active site" for polymerization. The lower carbohydrate content observed in "Fibrinogen Detroit" may have been the result of a change in primary and tertiary structure of the protein.
Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir
Authors: Eric F. Donaldson, Patrick R. Harrington, Julian J. O'Rear, Lisa K. Naeger
Journal: Hepatology (2014)

Sofosbuvir (Sovaldi, SOF) is a nucleotide analog prodrug that targets the hepatitis C virus (HCV) nonstructural protein 5B (NS5B) polymerase and inhibits viral replication. High sustained virological response rates are achieved when SOF is used in combination with ribavirin with or without pegylated interferon in subjects with chronic HCV infection. Potential mechanisms of HCV resistance to SOF and other nucleos(t)ide analog NS5B polymerase inhibitors are not well understood. SOF was the first U.S. Food and Drug Administration (FDA)‐approved antiviral drug for which genotypic resistance analyses were based almost entirely on next‐generation sequencing (NGS), an emerging technology that lacks a standard data analysis pipeline. The FDA Division of Antiviral Products developed an NGS analysis pipeline and performed independent analyses of NGS data from five SOF clinical trials. Additionally, structural bioinformatics approaches were used to characterize potential resistance‐associated substitutions. Using protocols we developed, independent analyses of the NGS data reproduced results that were comparable to those reported by Gilead Sciences, Inc. Low‐frequency, treatment‐emergent substitutions occurring at conserved NS5B amino acid positions in subjects who experienced virological failure were also noted and further evaluated. The NS5B substitutions, L159F (sometimes in combination with L320F or C316N) and V321A, emerged in 2.2%‐4.4% of subjects who failed SOF treatment across clinical trials. Moreover, baseline polymorphisms at position 316 were potentially associated with reduced response rates in HCV genotype 1b subjects. Analyses of these variants modeled in NS5B crystal structures indicated that all four substitutions could feasibly affect SOF anti‐HCV activity. Conclusion : SOF has a high barrier to resistance; however, low‐frequency NS5B substitutions associated with treatment failure were identified that may contribute to resistance of this important drug for chronic HCV infection. (H epatology 2015;61:56–65)
Internal cardioversion of atrial fibrillation using standard ventricular implantable cardioverter-defibrillators
Authors: M.K. Chung, M.J. Niebauer, B.L. Witkoll, F.J. Jaeger, G.A. Kidwell, V.A. Morant, P.J. Tehou
Journal: Journal of the American College of Cardiology (1998)
Spironolactone Prevents the Heart Againts Anthracycline Cardiotoxicity
Authors: Mahmut Akpek, Ibrahim Ozdogru, Omer Sahin, Mevlude Inanc, Ali Dogan, Cevat Yazici, Veli Berk, Halit Karaca, Nihat Kalay, Abdurrahman Oguzhan
Journal: Journal of the American College of Cardiology (2013)
Barrier-Spermicide Use and Bacteriuria-Reply
Authors: Thomas M. Hooton, Sharon Hillier, Walter E. Stamm
Journal: JAMA (1991)

In Reply.—  Dr Dratman is correct in pointing out, as does our article, that we demonstrated an association of spermicide or diaphragm-spermicide use with bacteriuria and vaginal colonization with Escherichia coli rather than with urinary tract infection (UTI). Given our study design, we did not expect to find an association with infection. However, a strong association between diaphragm-spermicide use and UTI has been established previously 1-3 and is widely accepted among investigators in the field. Whether an association exists between spermicide use alone and UTI remains to be established.  The mechanisms underlying the findings reported in our study are not known. It seems unlikely that any significant alterations in vaginal flora are due to the latex in condoms because condoms are in relatively brief contact with vaginal flora. We are aware of no data that demonstrate that the latex used in diaphragms has antibacterial effects. It is certainly possible that
Quantifying the fraction of cirrhosis attributable to alcohol among chronic hepatitis C virus patients: Implications for treatment cost-effectiveness
Authors: Hamish A. Innes, Sharon J. Hutchinson, Stephen Barclay, Elaine Cadzow, John F. Dillon, Andrew Fraser, David J. Goldberg, Peter R. Mills, Scott A. McDonald, Judith Morris, Adrian Stanley, Peter Hayes
Journal: Hepatology (2012)

A substantial baseline risk of liver cirrhosis exists for patients with chronic hepatitis C virus (HCV) infection. However, the extent to which this could be driven by heavy alcohol use is unclear. Therefore, our principal aim was to determine the fraction of cirrhosis attributable to heavy alcohol use among chronic HCV patients attending a liver clinic. The study population comprised chronic HCV patients who had attended one of five liver clinics in Scotland during 1996-2010 and had (1) remained in follow-up for at least 6 months, (2) acquired HCV through either injecting drugs or blood transfusion, and (3) an estimated date of acquiring infection. Predictors of cirrhosis were determined from multivariate logistic regression. Regression parameters were used to determine the fraction of cirrhosis attributable to heavy alcohol use. Among 1,620 patients, 9% were diagnosed with cirrhosis, and 34% had ever engaged in heavy alcohol use (&gt;50 units/week for a sustained period). Significant predictors of cirrhosis were age, duration of infection, and ever heavy alcohol use. The fraction of cirrhosis attributable to ever heavy alcohol use was 36.1% (95% confidence interval [CI]: 24.4-47.4). Moreover, among patients who had ever engaged in heavy alcohol use specifically, this attributable fraction exceeded 50% (61.6%; 95% CI: 47.0-72.2). Conclusions: A substantial proportion of patients with chronic HCV develop liver cirrhosis as a consequence of heavy alcohol use. This has not been adequately acknowledged by cost utility analyses (CUAs). As such, estimates of cost-effectiveness may be exaggerated. Thus, these data are important to guide forthcoming CUAs in terms of taking better account of the factors leading to cirrhosis among patients with chronic HCV.
Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients
Authors: Zoe E. Athanassa, Sophia L. Markantonis, Marina-Zoe F. Fousteri, Pavlos M. Myrianthefs, Eleni G. Boutzouka, Athanassios Tsakris, George J. Baltopoulos
Journal: Intensive Care Medicine (2012)
Is Intravenous Administration of Branched Chain Amino Acids Effective in the Treatment of Hepatic Encephalopathy? A Multicenter Study
Authors: John Wahren, Jacques Denis, Philippe Desurmont, Ljusk S. Eriksson, Jean-Marc Escoffier, André P. Gauthier, Lars Hagenfeldt, Henri Michel, Pierre Opolon, Jean-Claude Paris, Michel Veyrac
Journal: Hepatology (1983)

The influence of intravenous infusion of branched-chain amino acids (BCAAs) on brain function in patients with liver cirrhosis and acute hepatic encephalopathy was examined using a double-blind, randomized study design. Five medical centers in France and Sweden participated, and 50 patients were studied. The patients received either BCAAs (40 gm per day) in 5% glucose or 5% glucose alone (placebo) for 5 days or until "wake up". Nutritional support was provided with equal proportions of carbohydrate and fat. During BCAA administration, plasma concentrations of aromatic amino acids and methionine fell (20 to 40%, p less than 0.05 to 0.01), and the ratio of BCAAs to aromatic amino acid concentrations increased significantly. Clinical improvement was seen in 14 of 25 BCAA-treated patients and in 12 of 25 patients receiving placebo (N.S.). EEG responses were similar in the two groups during treatment. In the BCAA group, 10 of 25 patients died in the course of the study, compared to 5 of 25 in the placebo group (N.S.); six patients died from encephalopathy in the BCAA group as compared to three among placebo-treated patients. It is concluded that BCAA administration, in the dose and composition employed in the present study, reduces the concentrations of aromatic amino acids but neither improves cerebral function nor decreases mortality in patients with hepatic encephalopathy.
Aggregation-related association of lipid with the cytoskeleton of rabbit and human platelets prelabeled with [3H]palmitic acid. Similar effects of adenosine diphosphate- and thrombin-induced aggregation.
Authors: A Livne, M A Packham, M A Guccione, J F Mustard
Journal: Journal of Clinical Investigation (1988)

To investigate the association of lipid with the cytoskeleton of platelets during aggregation, rabbit and human platelets were isolated and labeled with [3H]palmitic acid; lipid extraction showed approximately 80% in phospholipid. Limited aggregation was induced with ADP or thrombin, and the cytoskeleton was isolated after lysis with 1% Triton X-100, 5 mM EGTA. Cytoskeleton from unactivated platelets had approximately 0.03% of the total label in the platelets, but after aggregation with ADP (2 microM) or thrombin (0.1 U/ml) for 20-30 s, 1.5-8% of the label was with the cytoskeleton. Fibrinogen enhanced aggregation and the association of label with the cytoskeleton; incorporation of label increased exponentially as aggregation proceeded, decreased exponentially during deaggregation, and appeared to be related to the number of sites of contact. Inhibitors that increase cyclic AMP inhibited aggregation and cytoskeletal labeling, but aspirin had no effect. Some experiments were done with DNase I and Ca2+ in the Triton X-100 lysis medium to cause actin depolymerization, under conditions in which the Ca2+-dependent protease activity was inhibited. This greatly reduced the association of label with the cytoskeleton at early time points, but when aggregation had proceeded further, a large proportion of the label was not dissociated by this treatment. These findings, electron microscopy, and the enrichment of the cytoskeleton of aggregated platelets with only some of the membrane proteins that were labeled by the 125I-lactoperoxidase method, indicated that with limited aggregation, the 3H-labeled lipid was mainly associated with the cytoskeleton and not with trapped membrane fragments resulting from incomplete lysis. Since the pattern of cytoskeleton labeling ([3H]palmitate) and the selective association of some membrane proteins with the cytoskeleton/lipid complex was the same with ADP and thrombin, the reactions must be dependent on aggregation and not on events associated with the release of granule contents.
1041-92 Calmodulin kinase inhibition improves cardiac function after myocardial infarction
Authors: Michelle S Khoo, Rong Zhang, Chad E Grueter, Gemin Ni, Corrie Painter, Mesut Eren, Linda Gleaves, Edward Price, Jinying Yang, Ernest C Madu, Douglas E Vaughan, Mark E Anderson
Journal: Journal of the American College of Cardiology (2004)