tbuckley/cabot-search huggingface dataset:
Spectrophotometric determination of oxygen saturation of blood independent of the presence of indocyanine green
Authors: G. A. MOOK, A. BUURSMA, A. GERDlNG, G. KWANT, W. G. ZIJLSTRA
Journal: Cardiovascular Research (1979)

The strong absorbance of indocyanine green in a broad band around lambda = 800 nm invalidates the usual spectrophotometric two-wavelength methods for measuring oxygen saturation operating in the red and near infrared region. By proper wavelength selection, however, the effect of the dye can be eliminated. With the two-wavelength method utilising lambda = 660 and 860 nm oxygen saturation is measured virtually independent of the presence of indocyanine green.
Exercise stress echocardiography for the study of the pulmonary circulation
Authors: P. Argiento, N. Chesler, M. Mulè, M. D'Alto, E. Bossone, P. Unger, R. Naeije
Journal: European Respiratory Journal (2009)

Exercise stress tests have been used for the diagnosis of pulmonary hypertension, but with variable protocols and uncertain limits of normal. The pulmonary haemodynamic response to progressively increased workload and recovery was investigated by Doppler echocardiography in 25 healthy volunteers aged 19–62 yrs (mean 36 yrs). Mean pulmonary artery pressure ( P̄ pa ) was estimated from the maximum velocity of tricuspid regurgitation. Cardiac output (Q) was calculated from the aortic velocity-time integral. Slopes and extrapolated pressure intercepts of P̄ pa –Q plots were calculated after using the adjustment of Poon for individual variability. A pulmonary vascular distensibility α was calculated from each P̄ pa –Q plot to estimate compliance. P̄ pa increased from 14±3 mmHg to 30±7 mmHg, and decreased to 19±4 mmHg after 5 min recovery. The slope of P̄ pa –Q was 1.37±0.65 mmHg·min −1 ·L −1 with an extrapolated pressure intercept of 8.2±3.6 mmHg and an α of 0.017±0.018 mmHg −1 . These results agree with those of previous invasive studies. Multipoint P̄ pa –Q plots were well described by a linear approximation, from which resistance can be calulated. We conclude that exercise echocardiography of the pulmonary circulation is feasible and provides realistic resistance and compliance estimations. Measurements during recovery are unreliable because of rapid return to baseline.
Ubiquitin Proteasome Dysfunction in Human Hypertrophic and Dilated Cardiomyopathies
Authors: Jaime M. Predmore, Ping Wang, Frank Davis, Sarah Bartolone, Margaret V. Westfall, David B. Dyke, Francis Pagani, Saul R. Powell, Sharlene M. Day
Journal: Circulation (2010)

Background— The ubiquitin proteasome system maintains a dynamic equilibrium of proteins and prevents accumulation of damaged and misfolded proteins, yet its role in human cardiac dysfunction is not well understood. The present study evaluated ubiquitin proteasome system function in human heart failure and hypertrophic cardiomyopathy (HCM). Methods and Results— Proteasome function was studied in human nonfailing donor hearts, explanted failing hearts, and myectomy samples from patients with HCM. Proteasome proteolytic activities were markedly reduced in failing and HCM hearts compared with nonfailing hearts ( P &lt;0.01). This activity was partially restored after mechanical unloading in failing hearts ( P &lt;0.01) and was significantly lower in HCM hearts with pathogenic sarcomere mutations than in those lacking these mutations ( P &lt;0.05). There were no changes in the protein content of ubiquitin proteasome system subunits (ie, 11S, 20S, and 19S) or in active-site labeling of the 20S proteolytic subunit β-5 among groups to explain decreased ubiquitin proteasome system activity in HCM and failing hearts. Examination of protein oxidation revealed that total protein carbonyls, 4-hydroxynonenylated proteins, and oxidative modification to 19S ATPase subunit Rpt 5 were increased in failing compared with nonfailing hearts. Conclusions— Proteasome activity in HCM and failing human hearts is impaired in the absence of changes in proteasome protein content or availability of proteolytic active sites. These data provide strong evidence that posttranslational modifications to the proteasome may account for defective protein degradation in human cardiomyopathies.
THE BACTERICIDAL ACTION OF HUMAN SERUM ON HEMOLYTIC STREPTOCOCCI
Authors: William S. Tillett
Journal: The Journal of Experimental Medicine (1937)

Although sera derived from patients at the time of acute, active infection were found to be capable of destroying hemolytic streptococci under aerobic conditions, the organisms retained viability when the tests were performed in the environment of anaerobiosis afforded by a vaseline seal or an anaerobic jar. Within the limitations of the experimental procedures which were employed, the aerobic or anaerobic effect was found to be a reversible reaction. Heating sera at 60 degrees C. for 1 hour inactivated the streptococcidal element in most instances, but not in every case; heating at 56 degrees C. for 1 hour impaired the killing power of half of the specimens which were tested. Sera retained the capacity to destroy hemolytic streptococci when kept in the ice box for 3 weeks; a slight diminution in killing power was noted after 4 weeks. By the methods which were employed, the streptococcidal property of sera could not be correlated with either true antibacterial agglutination or with pseudo-agglutination. The significance of the findings as a basis for analyzing the mechanism of the streptococcidal phenomenon is discussed.
Insulin-like Growth Factor Receptor as a Therapeutic Target in Head and Neck Cancer
Authors: Christopher J. Barnes, Kazufumi Ohshiro, Suresh K. Rayala, Adel K. El-Naggar, Rakesh Kumar
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Insulin-like growth factor type I receptor (IGF-IR) plays critical roles in epithelial cancer cell development, proliferation, motility, and survival, and new therapeutic agents targeting IGF-IR are in development. Another receptor tyrosine kinase, the epidermal growth factor receptor (EGFR), is an established therapeutic target in head and neck cancer and IGF-IR/EGFR heterodimerization has been reported in other epithelial cancers. The present study was undertaken to determine the effects of anti–IGF-IR therapeutic targeting on cell signaling and cancer cell phenotypes in squamous cell carcinomas of the head and neck (SCCHN). Experimental Design: The therapeutic efficacy of the human anti–IGF-IR antibody IMC-A12 alone and in combination with the EGFR blocking antibody cetuximab (C225) was tested in SCCHN cell lines and in tumor xenografts. Results: IGF-IR was overexpressed in human head and neck cancer cell lines and tumors. Pretreatment of serum-starved 183A or TU159 SCCHN cell lines with A12 (10 μg/mL) blocked IGF-stimulated activation of IGF-IR, insulin receptor substrate (IRS)-1 and IRS-2, mitogen-activated protein kinase, and phosphatidylinositol 3-kinase. A12 induced G0-G1 cell cycle arrest and blocked cell growth, motility, and anchorage-independent growth. Stimulation of head and neck cancer cells with either IGF or EGF resulted in IGF-IR and EGFR heterodimerization, but only IGF caused activating phosphorylation of both receptors. Combined treatment with A12 and the EGFR blocking antibody C225 was more effective at reducing cell proliferation and migration than either agent alone. Finally, TU159 tongue cancer cell xenografts grown in athymic nude mice were treated thrice weekly for 4 weeks with vehicle, A12 (40 mg/kg i.p.), C225 (40 mg/kg i.p.), or both agents (n = 8 mice per group; 2 tumors per mouse). Linear regression slope analysis showed significant differences in median tumor volume over time between all three treatment groups and the control group. Complete regression was seen in 31% (A12), 31% (C225), and 44% (A12 + C225) of tumors. Conclusion: Here we found the overexpression of IGF-IR, the functional heterodimerization of IGF-IR and EGFR, and effective therapeutic targeting of these receptors in human head and neck cancer xenografts.
A comparison of systematic stenting and conventional balloon angioplasty during primary percutaneous transluminal coronary angioplasty for acute myocardial infarction
Authors: Luc Maillard, Philippe Raynaud, Martial Hamon, Jean-Pierre Monassier, Khalife Khalife, Philippe Gabriel Steg, Patrick Serruys, Farzin Beygui, Jean-Leon Guermonprez, Christian M. Spaulding, Jean-Marc Boulenc, Janusz Lipiecki, Antoine Lafont, Philippe Brunel, Gilles Grollier, Rene Koning, Pierre Coste, Xavier Favereau, Bernard Lancelin, Eric Van Belle
Journal: Journal of the American College of Cardiology (2000)
A simple consensus approach improves somatic mutation prediction accuracy
Authors: David L Goode, Sally M Hunter, Maria A Doyle, Tao Ma, Simone M Rowley, David Choong, Georgina L Ryland, Ian G Campbell
Journal: Genome Medicine (2013)

Differentiating true somatic mutations from artifacts in massively parallel sequencing data is an immense challenge. To develop methods for optimal somatic mutation detection and to identify factors influencing somatic mutation prediction accuracy, we validated predictions from three somatic mutation detection algorithms, MuTect, JointSNVMix2 and SomaticSniper, by Sanger sequencing. Full consensus predictions had a validation rate of >98%, but some partial consensus predictions validated too. In cases of partial consensus, read depth and mapping quality data, along with additional prediction methods, aided in removing inaccurate predictions. Our consensus approach is fast, flexible and provides a high-confidence list of putative somatic mutations.
Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United States: retrospective analysis of effectiveness and safety
Authors: J. Poeran, R. Rasul, S. Suzuki, T. Danninger, M. Mazumdar, M. Opperer, F. Boettner, S. G. Memtsoudis
Journal: BMJ (2014)

<b>Objective</b> To determine the effectiveness and safety of perioperative tranexamic acid use in patients undergoing total hip or knee arthroplasty in the United States. <b>Design</b> Retrospective cohort study; multilevel multivariable logistic regression models measured the association between tranexamic acid use in the perioperative period and outcomes. <b>Setting</b> 510 US hospitals from the claims based Premier Perspective database for 2006-12. <b>Participants</b> 872&nbsp;416 patients who had total hip or knee arthroplasty. <b>Intervention</b> Perioperative intravenous tranexamic acid use by dose categories (none, ≤1000 mg, 2000 mg, and ≥3000 mg). <b>Main outcome measures</b> Allogeneic or autologous transfusion, thromboembolic complications (pulmonary embolism, deep venous thrombosis), acute renal failure, and combined complications (thromboembolic complications, acute renal failure, cerebrovascular events, myocardial infarction, in-hospital mortality). <b>Results</b> While comparable regarding average age and comorbidity index, patients receiving tranexamic acid (versus those who did not) showed lower rates of allogeneic or autologous transfusion (7.7% <i>v</i> 20.1%), thromboembolic complications (0.6% <i>v</i> 0.8%), acute renal failure (1.2% <i>v</i> 1.6%), and combined complications (1.9% <i>v</i> 2.6%); all P&lt;0.01. In the multilevel models, tranexamic acid dose categories (versus no tranexamic acid use) were associated with significantly (P&lt;0.001) decreased odds for allogeneic or autologous blood transfusions (odds ratio 0.31 to 0.38 by dose category) and no significantly increased risk for complications: thromboembolic complications (odds ratio 0.85 to 1.02), acute renal failure (0.70 to 1.11), and combined complications (0.75 to 0.98). <b>Conclusions</b> Tranexamic acid was effective in reducing the need for blood transfusions while not increasing the risk of complications, including thromboembolic events and renal failure. Thus our data provide incremental evidence of the potential effectiveness and safety of tranexamic acid in patients requiring orthopedic surgery.
Studies back minimum pricing on alcohol to save lives
Authors: A. O'Dowd
Journal: BMJ (2009)

A 50 pence (€0.56; $0.76) minimum unit price for alcohol in the United Kingdom could save as many as 3400 lives a year, researchers have told MPs.

A minimum price for alcohol units has the potential to reduce deaths and hospital admissions by encouraging less drinking, said witnesses at the latest evidence session of the parliamentary health select committee’s inquiry into alcohol.

The lead researchers of two studies into the subject said that minimum pricing would mean fewer alcohol related deaths and disease.

Petra Meier, senior lecturer in public health at the University of Sheffield, giving evidence, spoke of the study she led, funded by the Department of Health, published in December last year.

That study looked for evidence to link the price of alcohol …
Degradation of leucine zipper-positive isoform of MYPT1 may contribute to development of nitrate tolerance
Authors: D. Dou, H. Ma, X. Zheng, L. Ying, Y. Guo, X. Yu, Y. Gao
Journal: Cardiovascular Research (2009)

AimsA depressed cGMP-dependent protein kinase (PKG) activity is implicated in nitrate tolerance. The present study determines whether the leucine zipper-positive (LZ+) isoform of myosin phosphatase target subunit 1 (MYPT1), a key target protein for PKG actions, is involved in the development of nitrate tolerance.
Effect of Diuretic-Based Antihypertensive Treatment on Cardiovascular Disease Risk in Older Diabetic Patients With Isolated Systolic Hypertension
Authors: J. David Curb, Sara L. Pressel, Jeffrey A. Cutler, Peter J. Savage, William B. Applegate, Henry Black, Greta Camel, Barry R. Davis, Phillip H. Frost, Nelly Gonzalez, Gordon Guthrie, Albert Oberman, Gail H. Rutan, Jeremiah Stamler
Journal: JAMA (1996)

To assess the effect of low-dose, diuretic-based antihypertensive treatment on major cardiovascular disease (CVD) event rates in older, non-insulin-treated diabetic patients with isolated systolic hypertension (ISH), compared with nondiabetic patients.Double-blind, randomized, placebo-controlled trial: the Systolic Hypertension in the Elderly Program (SHEP).Multiple clinical and support centers in the United States.A total of 4736 men and women aged 60 years and older at baseline with ISH (systolic blood pressure [BP], > or = 160 mm Hg; diastolic BP, <90 mm Hg) at baseline, 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients (4 additional patients not so classifiable were randomized but not included in these analyses). Diabetes mellitus defined as physician diagnosis, taking oral hypoglycemic drugs, fasting glucose level of 7.8 mmol/L or more (> or = 140 mg/dL), or any combination of these characteristics.The active treatment group received a low dose of chlorthalidone (12.5-25.0 mg/d) with a step-up to atenolol (25.0-50.0 mg/d) or reserpine (0.05-0.10 mg/d) if needed. The placebo group received placebo and any active antihypertensive drugs prescribed by patient's private physician for persistently high BP.The 5-year rates of major CVD events, nonfatal plus fatal stroke, nonfatal myocardial infarction (MI) and fatal coronary heart disease (CHD), major CHD events, and all-cause mortality.The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients, with few adverse effects. For both diabetic and nondiabetic patients, all outcome rates were lower for participants randomized to the active treatment group than for those randomized to the placebo group. Thus, 5-year major CVD rate was lower by 34% for active treatment compared with placebo, both for diabetic patients (95% confidence interval [CI], 6%-54%) and nondiabetic patients (95% CI, 21%-45%). Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients (101/1000 vs 51/1000 randomized participants at the 5-year follow-up), reflecting the higher risk of diabetic patients.Low-dose diuretic-based (chlorthalidone) treatment is effective in preventing major CVD events, cerebral and cardiac, in both non-insulin-treated diabetic and nondiabetic older patients with ISH.
Gene Expression Profiles of Serous, Endometrioid, and Clear Cell Subtypes of Ovarian and Endometrial Cancer
Authors: Kristin K. Zorn, Tomas Bonome, Lisa Gangi, Gadisetti V.R. Chandramouli, Christopher S. Awtrey, Ginger J. Gardner, J. Carl Barrett, Jeff Boyd, Michael J. Birrer
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. Experimental Design: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. Results: Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. Conclusions: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished.
OXYGEN TENSION OF TISSUES BY THE POLAROGRAPHIC METHOD. VI. EFFECT OF CHANGES IN POSITION ON OXYGEN TENSION OF THE SKIN OF TOES 1
Authors: Phyllis G. Williams, Hugh Montgomery, Orville Horwitz
Journal: Journal of Clinical Investigation (1953)

peripheral arterial occlusion is aggravated by raising the limb and relieved somewhat by lowering the limb. Patients with this condition often complain of foot pain while in bed. This is relieved by getting out of bed. If the head of the bed is raised or special devices are used to lower the leg (1) the pain of the foot is often relieved and the color of the foot improved. Conversely, a case recently came to our attention in which the foot of a patient, who had been confined to bed for a year because of a cerebrovascular accident, became gangrenous only two days after being elevated on two pillows. Elevation of a normal limb decreases the arterial pressure within it, whereas dependency increases the pressure. Measurements of intra-arterial pressure show that the pressure varies directly with the vertical distance from the right atrium to the point of measurement (2). Such changes might be ex
A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study
Authors: A. DeCensi, B. Bonanni, P. Maisonneuve, D. Serrano, U. Omodei, C. Varricchio, M. Cazzaniga, M. Lazzeroni, N. Rotmensz, B. Santillo, M. Sideri, E. Cassano, C. Belloni, M. Muraca, N. Segnan, P. Masullo, A. Costa, N. Monti, A. Vella, L. Bisanti, G. D'Aiuto, U. Veronesi
Journal: Annals of Oncology (2013)
Enhanced Pharmacodynamic and Antitumor Properties of a Histone Deacetylase Inhibitor Encapsulated in Liposomes or ErbB2-Targeted Immunoliposomes
Authors: Daryl C. Drummond, Corina Marx, Zexiong Guo, Gary Scott, Charles Noble, Donghui Wang, Maria Pallavicini, John W. Park, Dmitri B. Kirpotin, Christopher C. Benz
Journal: Clinical Cancer Research (2005)

Abstract ErbB2-overexpressing human cancers represent potentially sensitive targets for therapy by candidate histone deacetylase (HDAC) inhibitors as we have shown that HDAC inhibitors can selectively reduce ErbB2 expression by repressing the ErbB2 promoter and accelerating the decay of cytoplasmic ErbB2 transcripts. To extend these in vitro findings and enhance the in vivo pharmacodynamic properties of HDAC inhibitors, we stably encapsulated a potent hydroxamate-based HDAC inhibitor (LAQ824) within long-circulating liposomes (Ls-LAQ824) and immunoliposomes (ILs-LAQ824) bearing &amp;gt;10,000 LAQ824 molecules per nanovesicle. Liposomal LAQ824 exhibits prolonged in vivo stability and, unlike free LAQ824, circulates with a half-life of 10.8 hours following a single i.v. injection. Three weekly i.v. injections of 20 to 25 mg/kg Ls-LAQ824 in nude mice with ErbB2 overexpressing BT-474 breast tumor xenografts significantly impairs tumor growth, and administration of ErbB2-targeted ILs-LAQ824 may further improve this antitumor activity. Studies of tumor-bearing mice 24 hours after single treatment indicate that: (a) &amp;gt;10% of injected liposomal LAQ824 is still circulating (whereas free LAQ824 is undetectable in the blood after 15 minutes); and (b) tumor uptake of Ls-LAQ824 and ILs-LAQ824 is &amp;gt;3% injected drug per gram of tumor, producing levels of acetylated tumor histones that are 5- to 10-fold increased over those following free LAQ824 or saline treatments and resulting in concordantly reduced levels of tumor ErbB2 mRNA. These preclinical results support the clinical evaluation of HDAC inhibitors against ErbB2-overexpressing malignancies, and further indicate that encapsulation into targeted and nontargeted liposomes substantially improves the in vivo pharmacokinetics, tumor uptake, and antitumor properties of hydroxamate-based HDAC inhibitors.
Hematopoietic engraftment following transplantation of bone marrow cells carrying a Philadelphia (Ph′)‐like chromosome
Authors: Peter Graze, Robert Sparkes, Ronald Como, Robert P. Gale
Journal: American Journal of Hematology (1977)

Abstract A phenotypically normal donor for bone marrow transplantation was found to have a previously unreported karyotype, 46, XY, t(18q+; 22q‐), resulting in a Ph′‐like chromosome. Identification of the Ph′‐like chromosome in cultures of skin fibroblasts, phytohemaglutinin‐stimulated peripheral blood cells, and bone marrow cells from the marrow donor, but not in cell cultures from siblings or parents, indicated that it represented an acquired somatic mutation. Demonstration of the Ph′‐like chromosome in the marrow graft recipient's blood and bone marrow cells after transplantation provided a unique and definitive marker of engraftment. Hematopoiesis appeared normal in both the donor and recipient after transplantation. This study indicates that a mutation creating a Ph′‐like chromosome in hematopoietic cells need not produce hematologic abnormality. Presence of this translocation did not appear to interfere with normal hematopoietic or lymphoid differentiation and replication in the transplant setting.