tbuckley/cabot-search huggingface dataset:
Effects of nutritional supplementation for HIV patients starting antiretroviral treatment: randomised controlled trial in Ethiopia
Authors: M. F. Olsen, A. Abdissa, P. Kaestel, M. Tesfaye, D. Yilma, T. Girma, J. C. K. Wells, C. Ritz, C. Molgaard, K. F. Michaelsen, D. Zerfu, S. Brage, A. B. Andersen, H. Friis
Journal: BMJ (2014)

<b>Objectives </b>To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months delay. <b>Design</b> Randomised controlled trial. <b>Setting</b> Three public ART facilities in Jimma, Oromia region, Ethiopia. <b>Participants</b> Adults with HIV eligible for ART with body mass index (BMI) &gt;16. <b>Intervention</b> Daily supplementation with 200 g (4600 kJ) of supplement containing whey or soy during either the first three or the subsequent three months of ART. <b>Outcome measures</b> Primary: lean body mass assessed with deuterium dilution, grip strength measured with dynamometers, and physical activity measured with accelerometer and heart rate monitors. Secondary: viral load and CD4 counts. Auxiliary: weight and CD3 and CD8 counts. <b>Results</b> Of 318 patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was 19.5 (SD 2.4). At three months, participants receiving the supplements containing whey or soy had increased their lean body mass by 0.85 kg (95% confidence interval 0.16 kg to 1.53 kg) and 0.97 kg (0.29 kg to 1.64 kg), respectively, more than controls. This was accompanied by an increased gain of grip strength of 0.68 kg (−0.11 kg to 1.46 kg) for the whey supplement group and 0.93 kg (0.16 kg to 1.70 kg) for the soy supplement group. There were no effects on physical activity. Total weight gain increased by 2.05 kg (1.12 kg to 2.99 kg) and 2.06 kg (1.14 kg to 2.97 kg) for the whey and soy groups, respectively. In addition, in the whey supplement group overall CD3 counts improved by 150 cells/µL (24 to 275 cells/µL), of which 112 cells/µL (15 to 209 cells/µL) were CD8 and 25 cells/µL (−2 to 53 cells/µL) were CD4. Effects of the soy containing supplement on immune recovery were not significant. The effects of the two supplements, however, were not significantly different in direct comparison. Exploratory analysis showed that relatively more lean body mass was gained by patients with undetectable viral load at three months. Patients receiving delayed supplementation had higher weight gain but lower gains in functional outcomes. <b>Conclusions</b> Lipid based nutritional supplements improved gain of weight, lean body mass, and grip strength in patients with HIV starting ART. Supplements containing whey were associated with improved immune recovery. <b>Trial registration</b> Controlled-trials.com ISRCTN32453477.
SOX Antibodies in Small-Cell Lung Cancer and Lambert-Eaton Myasthenic Syndrome: Frequency and Relation With Survival
Authors: Maarten J. Titulaer, Rinse Klooster, Marko Potman, Lidia Sabater, Francesc Graus, Ingrid M. Hegeman, Peter E. Thijssen, Paul W. Wirtz, Albert Twijnstra, Peter A.E. Sillevis Smitt, Silvère M. van der Maarel, Jan J.G.M. Verschuuren
Journal: Journal of Clinical Oncology (2009)

SOX1 antibodies are common in small-cell lung carcinoma (SCLC) with and without paraneoplastic syndrome (PNS) and can serve as serological tumor marker. Addition of other antibodies might improve its diagnostic power. We validated an enzyme-linked immunosorbent assay (ELISA) to assess the diagnostic value of serum antibodies in SCLC and Lambert-Eaton myasthenic syndrome (LEMS). Clinical outcome with respect to SOX antibodies was evaluated, as the SOX-related antitumor immune response might help to control the tumor growth.We used recombinant SOX1, SOX2, SOX3, SOX21, HuC, HuD, or HelN1 proteins in an ELISA to titrate serum samples and validated the assay by western blot. We tested 136 consecutive SCLC patients, 86 LEMS patients (43 with SCLC), 14 patients with SCLC and PNS (paraneoplastic cerebellar degeneration or Hu syndrome), 62 polyneuropathy patients, and 18 healthy controls.Our ELISA was equally reliable as western blot. Forty-three percent of SCLC patients and 67% of SCLC-LEMS patients had antibodies to one of the SOX or Hu proteins. SOX antibodies had a sensitivity of 67% and a specificity of 95% to discriminate between LEMS with SCLC and nontumor LEMS. No difference in survival was observed between SOX positive and SOX negative SCLC patients.SOX antibodies are specific serological markers for SCLC. Our assay is suitable for high throughput screening, detecting 43% of SCLC. SOX antibodies have diagnostic value in discriminating SCLC-LEMS from nontumor LEMS, but have no relation to survival in patients with SCLC.
General Knowledge and General Practice
Authors: D. L. Kerr
Journal: BMJ (1947)

<b>Background:</b> Hepatitis B infection and vaccination against it have been implicated in the potential triggering or flare of some autoimmune diseases, including rheumatoid arthritis (RA). However, the safety of hepatitis B vaccination in patients with pre-existing RA is not known. <b>Objectives:</b> To assess the safety and antibody response of immunisation with a recombinant DNA hepatitis B vaccine in patients with RA. <b>Patients and methods:</b> The study comprised 44 patients with RA, of whom 22 received three doses (the second and third dose being given after one and six months) of a recombinant DNA hepatitis B vaccine (study group) and 22 did not receive the vaccine (control group). Both groups had comparable proportions of women and similar mean age (51 years). Clinical assessment before and two and seven months after the first immunisation included evaluation of daytime pain with a 10 cm visual analogue scale, duration of morning stiffness, and number of tender and swollen joints. Erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were measured at each visit. Antibodies to hepatitis B surface antigen (HBsAg) were determined by a commercial enzyme linked immunosorbent assay (ELISA) test kit. <b>Results:</b> Hepatitis B vaccination was not associated with an appreciable deterioration in any clinical or laboratory measure of disease. The measures of disease activity of the patients and controls during the study period did not differ significantly: p=0.76 for daytime pain, p=0.1 for morning stiffness, p=0.24 and p=0.3 for tender and swollen joints respectively, p=0.08 for CRP, and p=0.12 for ESR. Fifteen of the 22 patients responded to vaccination, with an antibody level against HBsAg of 10 IU/l after seven months. Lack of response was associated with older age and higher scores of daytime pain. <b>Conclusions:</b> Hepatitis B vaccination is safe in RA and produces antibodies in 68% of the patients.
Comparing two different arginine vasopressin doses in advanced vasodilatory shock: a randomized, controlled, open-label trial
Authors: Christian Torgersen, Martin W. Dünser, Volker Wenzel, Stefan Jochberger, Viktoria Mayr, Christian A. Schmittinger, Ingo Lorenz, Stefan Schmid, Martin Westphal, Wilhelm Grander, Günter Luckner
Journal: Intensive Care Medicine (2009)
Effect of Acute and Long-term Smoking on Myocardial Blood Flow and Flow Reserve
Authors: Johannes Czernin, Karl Sun, Richard Brunken, Morten Böttcher, Michael Phelps, Heinrich Schelbert
Journal: Circulation (1995)

Background Cigarette smoking is a major preventable risk factor for coronary artery disease and sudden cardiac death. However, the effect of acute and long-term cigarette smoking on coronary vasodilatory capacity and myocardial flow reserve has not been quantified in humans. Methods and Results To examine the effect of short-term and long-term smoking, myocardial blood flow was quantified at rest and during dipyridamole-induced hyperemia (0.56 mg/kg) in 12 smokers (10 males and 2 females; mean age, 27±4 years) under baseline conditions (reflecting the effect of long-term smoking) and during short-term cigarette smoking with 13 N ammonia, positron emission tomography, and a two-compartment model. Twelve sex- and age-matched nonsmokers served as control subjects. Smoking significantly increased the rate-pressure product at rest from 7525±1290 to 9160±1125 ( P &lt;.001 versus baseline), which was paralleled by a proportional increase in myocardial blood flow at rest (0.70±0.17 versus 0.88±0.17 mL · g −1 · min −1 ; P &lt;.05 versus baseline). In contrast, hyperemic blood flow declined from 2.23±0.35 at baseline ( P =NS versus control) to 1.98±0.32 mL · g −1 · min −1 during smoking ( P &lt;.01 versus baseline). Accordingly, the myocardial flow reserve declined from 3.36±0.83 in smokers at baseline to only 2.28±0.28 during smoking ( P &lt;.0001 versus baseline). Thus, myocardial blood flow and flow reserve were similar in young, long-term smokers and young, healthy nonsmokers. Conclusions Short-term smoking increases the coronary vasomotor tone during dipyridamole-induced hyperemia and markedly reduces the myocardial flow reserve. In contrast, long-term smoking does not attenuate the coronary vasodilatory capacity in young individuals with a relatively short smoking history. It might be speculated that the short-term reduction in the coronary vasodilatory capacity during smoking could lower the ischemic threshold in smokers with coronary artery disease and contribute to the increased risk for sudden cardiac death.
Inhibition of Microsomal Triglyceride Transfer Protein in Familial Hypercholesterolemia
Authors: Marina Cuchel, LeAnne T. Bloedon, Philippe O. Szapary, Daniel M. Kolansky, Megan L. Wolfe, Antoine Sarkis, John S. Millar, Katsunori Ikewaki, Evan S. Siegelman, Richard E. Gregg, Daniel J. Rader
Journal: New England Journal of Medicine (2007)

Patients with homozygous familial hypercholesterolemia have markedly elevated cholesterol levels, which respond poorly to drug therapy, and a very high risk of premature cardiovascular disease. Inhibition of the microsomal triglyceride transfer protein may be effective in reducing cholesterol levels in these patients.
Influence of cyclosporine A on contractile function, calcium handling, and energetics in isolated human and rabbit myocardium
Authors: P Janssen
Journal: Cardiovascular Research (2000)

Objective:The immunosuppressive drug Cyclosporine A (CsA) is a key substance in pharmacological therapy following solid organ transplantation and has been suggested to prevent cardiac hypertrophy. We investigated the direct effects of CsA on myocardial function, because these are largely unknown. Methods: In multicellular cardiac muscle preparations from end-stage failing and non-failing human hearts as well as from non-failing rabbit hearts we investigated the effects of CsA on contractile performance, sarcoplasmic reticulum (SR) Ca2+-load, cytosolic calcium transients, calcium sensitivity of the myofilaments, and myocardial oxygen consumption. Results: In failing human muscle preparations there was a concentration dependent decrease in contractile force; the maximal effect amounted to 55.6±6.4% of control while EC50 was reached at 1.0±0.3 nM (n=6). These concentrations are at and even below the therapeutic plasma levels. CsA decreased the aequorin light signal in human failing trabeculae to 71.5±5.9% (n=5), indicating decreased calcium transients. Estimation of the SR calcium load via measurement of rapid cooling contractures revealed a decrease to 84.4±6.5% in failing human preparations (n=6). Measurements of both decreased SR calcium load and force development in presence of CsA were also observed in four non-failing human muscle preparations. In rabbit muscle preparations (n=8), developed force decreased to 50.2±7.7% (n=8, EC50: 1.9±0.4 nM) and rapid cooling contractures to 74.0±7.4% of control at 100 nmol/l CsA. No direct effects were observed on myofilament calcium sensitivity nor on maximal force development of permeabilized preparations from the rabbit (n=7). Oxygen consumption measurements showed that CsA decreased the economy of contraction to 76.4±7.9% in rabbit preparations (n=8). Conclusions: CsA causes a direct cardio-depressive effect at clinically relevant concentrations, most likely due to altered handling of Ca2+ by the SR.
Low-Density Lipoprotein Cholesterol and the Risk of Cancer: A Mendelian Randomization Study
Authors: Marianne Benn, Anne Tybjærg-Hansen, Stefan Stender, Ruth Frikke-Schmidt, Børge G. Nordestgaard
Journal: JNCI Journal of the National Cancer Institute (2011)

Low plasma levels of low-density lipoprotein (LDL) cholesterol are associated with an increased risk of cancer, but whether this association is causal is unclear.We studied 10 613 participants in the Copenhagen City Heart Study (CCHS) and 59 566 participants in the Copenhagen General Population Study, 6816 of whom had developed cancer by May 2009. Individuals were genotyped for PCSK9 R46L (rs11591147), ABCG8 D19H (rs11887534), and APOE R112C (rs429358) and R158C (rs7412) polymorphisms, all of which are associated with lifelong reduced plasma LDL cholesterol levels. Plasma LDL cholesterol was calculated using the Friedewald equation in samples in which the triglyceride level was less than 354 mg/dL and measured directly by colorimetry for samples with higher triglyceride levels. Risk of cancer was estimated prospectively using Cox proportional hazards regression analyses and cross-sectionally by logistic regression analyses. Causality was studied using instrumental variable analysis. All statistical tests were two-sided.In the CCHS, compared with plasma LDL cholesterol levels greater than the 66th percentile (>158 mg/dL), those lower than the 10th percentile (< 87 mg/dL) were associated with a 43% increase (95% confidence interval [CI] = 15% to 79% increase) in the risk of cancer. The polymorphisms were associated with up to a 38% reduction (95% CI = 36% to 41% reduction) in LDL cholesterol levels but not with increased risk of cancer. The causal odds ratio for cancer for a 50% reduction in plasma LDL cholesterol level due to all the genotypes in both studies combined was 0.96 (95% CI = 0.87 to 1.05), whereas the hazard ratio of cancer for a 50% reduction in plasma LDL cholesterol level in the CCHS was 1.10 (95% CI = 1.01 to 1.21) (P for causal odds ratio vs observed hazard ratio = .03).Low plasma LDL cholesterol levels were robustly associated with an increased risk of cancer, but genetically decreased LDL cholesterol was not. This finding suggests that low LDL cholesterol levels per se do not cause cancer.
Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis
Authors: Féline Kroon, Robert Landewé, Maxime Dougados, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> The aim was to compare continuous and on-demand NSAID treatment with respect to their ability to suppress radiographic progression in subgroups of patients with high/elevated CRP-levels, ESR, ASDAS-levels or BASDAI-levels in comparison to patients with normal levels. <h3>Methods</h3> Post-hoc analyses were performed in a randomized trial comparing continuous and on-demand NSAID treatment. Relevant high/elevated subgroups were created based on time-averaged (ta) CRP (&gt;5mg/L), ta-ESR (&gt;12mm/hr), ta-BASDAI (&gt;4), ta-ASDAS-CRP (&gt;2.1) and ta-ASDAS-ESR (&gt;2.1). Subgroups were further split according to NSAID-use (continuous vs. on-demand). Radiological progression was presented in probability plots. Statistical interactions were tested using multiple and logistic regression analysis. Differences in radiological progression were analysed using the Chi-square and Mann-Whitney U test. <h3>Results</h3> 150 participants randomized to either the continuous-treatment group (n=76), or the on-demand group (n=74) had complete radiographs and were included. The effect of slowing radiological progression with continuous NSAID therapy was more pronounced in patients with elevated ta-CRP-levels, elevated ta-ESR, high ta-ASDAS-CRP or high ta-ASDAS-ESR versus patients with low/normal values. No such effect was found for participants with high vs. low BASDAI. Also, in participants with elevated ta-ESR (irrespective of treatment), there appeared to be a higher rate of structural progression than in participants with normal ta-ESR. Regression analyses showed that continuous NSAID treatment neutralizes the negative effect of inflammation (high ta-ESR). <h3>Conclusions</h3> Patients with elevated acute phase reactants seem to benefit most from continuous treatment with NSAIDs. Continuous NSAID-therapy in patients with elevated acute phase reactants may lead to an improved benefit-risk-ratio of these drugs.
Phosphatidylinositol-3-Kinase as a Therapeutic Target in Melanoma
Authors: Saadia A. Aziz, Michael Davies, Elah Pick, Christopher Zito, Lucia Jilaveanu, Robert L. Camp, David L. Rimm, Yuval Kluger, Harriet M. Kluger
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Phosphatidylinositol-3 kinases (PI3K) are critical for malignant cellular processes including growth, proliferation, and survival, and are targets of drugs in clinical development. We assessed expression of PI3K in melanomas and nevi, and studied associations between PI3K pathway members and in vitro response to a PI3K inhibitor, LY294002. Experimental Design: Using Automated Quantitative Analysis, we quantified expression of p85 and p110α subunits in 540 nevi and 523 melanomas. We determined the IC50 for LY294002 for 11 melanoma cell lines and, using reverse phase protein arrays, assessed the association between levels of PI3K pathway members and sensitivity to LY294002. Results: p85 and p110α tend to be coexpressed (P &amp;lt; 0.0001); expression was higher in melanomas than nevi (P &amp;lt; 0.0001) for both subunits, and higher in metastatic than primary melanomas for p85 (P &amp;lt; 0.0001). Although phospho-Akt (pAkt) levels decreased in all cell lines treated with LY294002, sensitivity was variable. We found no association by t tests between baseline p85, p110α, and pAkt levels and sensitivity to LY294002, whereas pS6 Ser235 and Ser240 were lower in the more resistant cell lines (P = 0.01 and P = 0.004, respectively). Conclusions: Expression of p85 and p110α subunits is up-regulated in melanoma, indicating that PI3K is a good drug target. Pretreatment pS6 levels correlated with sensitivity to the PI3K inhibitor, LY294002, whereas PI3K and pAkt did not, suggesting that full activation of the PI3K pathway is needed for sensitivity to PI3K inhibition. pS6 should be evaluated as a predictor of response in melanoma patients treated with PI3K inhibitors, as these drugs enter clinical trials.
Reply to R. Steiner et al
Authors: Daniel Lenihan, Daniela Cardinale
Journal: Journal of Clinical Oncology (2013)

We graciously acknowledge the expert opinion of Steiner and Hellmann regarding statements about cardioprotection during anthracycline-based chemotherapy. In our review, we did acknowledge that dexrazoxane was a therapeutic option for cardioprotection and referenced a major review on the use of cardioprotectants. Because our review was focused on late cardiac effects of cancer treatment, we were unable to carefully detail all of the relevant studies that potentially addressed early or acute cardiotoxicity from anthracyclines, although we do agree conceptually with Steiner and Hellmann that prevention is the best strategy. Furthermore, we recognize that American Society of Clinical Oncology 2008 Clinical Practice Guideline suggests the use of dexrazoxane in specific adult patients (patients with breast cancer who have received 300 mg/m of anthracyclines) on the basis of work from Swain and others. Additionally, Lipshultz has published authoritative reports on the effective use of dexrazoxane in childhood leukemia. However, it is certainly our observation and that of others that dexrazoxane has a significantly limited use in adult patients who receive anthracyclines. This may be in part a result of attenuation of the cancer efficacy of anthracyclines or the potential concern of late effects, such as secondary leukemia. In fact, the use of dexrazoxane in children is not recommended in Europe. Conversely, angiotensinconverting enzyme inhibitors and carvedilol are ubiquitously used clinically, and their long-term safety is well established. These classic cardiac medications are known to be cardioprotective with chemotherapy, especially anthracyclines, and the ease of administering this medication(s) during chemotherapy is understood. We agree that no study has directly compared dexrazoxane cardioprotection with angiotensin-converting enzyme inhibitors or carvedilol in the context of anthracycline chemotherapy, and it seems highly unlikely that such a study will be performed.
Loss of the Mitochondrial Bioenergetic Capacity Underlies the Glucose Avidity of Carcinomas
Authors: Fernando López-Ríos, María Sánchez-Aragó, Elena García-García, Álvaro D. Ortega, José R. Berrendero, Francisco Pozo-Rodríguez, Ángel López-Encuentra, Claudio Ballestín, José M. Cuezva
Journal: Cancer Research (2007)

Abstract The down-regulation of the catalytic subunit of the mitochondrial H+-ATP synthase (β-F1-ATPase) is a hallmark of most human carcinomas. This characteristic of the cancer cell provides a proteomic signature of cellular bioenergetics that can predict the prognosis of colon, lung, and breast cancer patients. Here we show that the in vivo tumor glucose uptake of lung carcinomas, as assessed by positron emission tomography in 110 patients using 2-deoxy-2-[18F]fluoro-d-glucose as probe, inversely correlates with the bioenergetic signature determined by immunohistochemical analysis in tumor surgical specimens. Further, we show that inhibition of the activity of oxidative phosphorylation by incubation of cancer cells with oligomycin triggers a rapid increase in their rates of aerobic glycolysis. Moreover, we show that the cellular expression level of the β-F1-ATPase protein of mitochondrial oxidative phosphorylation inversely correlates (P &amp;lt; 0.001) with the rates of aerobic glycolysis in cancer cells. The results highlight the relevance of the alteration of the bioenergetic function of mitochondria for glucose capture and consumption by aerobic glycolysis in carcinomas. [Cancer Res 2007;67(19):9013–7]
No difference in skin condition between workers exposed and not exposed to glove occlusion in a semiconductor company
Authors: C.J. Apfelbacher
Journal: British Journal of Dermatology (2015)

Journal Article No difference in skin condition between workers exposed and not exposed to glove occlusion in a semiconductor company Get access C.J. Apfelbacher C.J. Apfelbacher Medical Sociology Institute of Epidemiology and Preventive Medicine University of Regensburg Dr Gessler‐Str. 17 93051 Regensburg Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 4, 1 April 2015, Pages 855–856, https://doi.org/10.1111/bjd.13652 Published: 01 April 2015