tbuckley/cabot-search huggingface dataset:
Occupational Exposure to Environmental Tobacco Smoke
Authors: S K Hammond, G Sorensen, R Youngstrom, J K Ockene
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The article by Dr Hammond and colleagues,<sup>1</sup>reporting high measured levels of nicotine in occupational settings without smoking restrictions, even exceeding those from some household studies, underscores concerns about the health risks associated with workplace exposure to ETS. To the degree that nicotine serves as a marker of ETS, these data are consistent with the finding that point estimates for the relative risks associated with workplace sources of exposure were somewhat higher than those associated with adult exposures from a spouse or other household members in our study of ETS and lung cancer among women who were lifetime never-smokers.<sup>2</sup> The evidence offered by Hammond et al regarding the potentially high historical levels of exposure to important constituents of ETS among nonsmoking workers in various settings without smoking restrictions prompted us to examine more closely the effect of workplace ETS exposure on risk of lung cancer
Side effects of atypical antipsychotics: a brief overview
Authors: ALP ÜÇOK, WOLFGANG GAEBEL
Journal: World Psychiatry (2008)

This paper reviews the available evidence concerning the side effects of atypical antipsychotics, including weight gain, type II diabetes mellitus, hyperlipidemia, QTc interval prolongation, myocarditis, sexual side effects, extrapyramidal side effects and cataract. Some recommendations about how to prevent and manage these side effects are also provided. It is concluded that atypical antipsychotics do not represent a homogeneous class, and that differences in side effects should be taken into account by clinicians when choosing an antipsychotic for an individual patient.
Statistical analysis of exacerbation rates in COPD: TRISTAN and ISOLDE revisited
Authors: O. N. Keene, P. M. A. Calverley, P. W. Jones, J. Vestbo, J. A. Anderson
Journal: European Respiratory Journal (2008)

Various statistical methods have been used to measure the impact of treatment on chronic obstructive pulmonary disease (COPD) exacerbations. Poisson regression has recently been recommended as the appropriate method but the model does not satisfactorily account for variability between patients. In contrast, use of a negative binomial model, which corresponds to assuming a separate Poisson parameter for each patient, offers a more appealing approach. The present paper reviews analysis methods, with particular focus on the negative binomial model. To illustrate the differences that arise from using different analysis methods, we have reanalysed data from two large studies which, among other objectives, investigated the effectiveness of inhaled corticosteroids in reducing COPD exacerbation rates. Using the negative binomial model to reanalyse data from the TRISTAN and ISOLDE studies, the overall estimates of exacerbation rates on each treatment arm are higher and the confidence intervals for comparisons between treatments are wider, but the overall conclusions of TRISTAN and ISOLDE regarding reduction of exacerbations remain unchanged. The negative binomial approach appears to provide a better fit to the distribution of the data than earlier methods and is currently the method of choice. Research needs to continue on further methods to improve the analysis of exacerbation data.
Electrophysiologic actions of O-demethyl encainide: an active metabolite.
Authors: H J Duff, A K Dawson, D M Roden, J A Oates, R F Smith, R L Woosley
Journal: Circulation (1983)

Differences between the electrophysiologic actions of the antiarrhythmic agent encainide have been reported after short-term intravenous and oral administration. Only prolongation of the HV interval and QRS duration have been described immediately after short-term intravenous administration of encainide in dogs and man. However, during oral therapy or more prolonged infusions, prolongation of the AH interval and atrial and ventricular effective refractory periods have also occurred. In most patients receiving encainide therapy, metabolites (O-demethyl encainide and 3-methoxy-O-demethyl encainide) accumulate during prolonged therapy to concentrations greater than those of the parent drug. We compared the electrophysiologic action of O-demethyl encainide with that of saline in anesthetized dogs to determine if this metabolite has pharmacologic activity and whether its electrophysiologic effects could account for the disparities noted between effects of intravenous and oral encainide therapy. An initial pharmacokinetic evaluation allowed design of a series of loading and maintenance infusions that produced plasma concentrations similar to those seen during encainide therapy in man (concentration after first maintenance dose, 149 +/- 27 ng/ml [+/- SE] and after second maintenance dose, 230 +/- 45 ng/ml). Significant increases in atrial effective refractory period and ventricular refractoriness, and prolongation of AH interval and HV conduction time were observed. These effects are similar to those reported after prolonged oral encainide therapy but are substantially different from those seen after short-term infusions of encainide. These findings indicate that the difference between the electrophysiologic actions of intravenous and oral encainide may be due to pharmacologic effects of at least one encainide metabolite, O-demethyl encainide.
Book: Biomarkers of Disease: An Evidence-Based Approach
Authors: D. O'Reilly
Journal: BMJ (2002)

Eds Andrew K Trull, Laurence M Demers, David W Holt, Atholl Johnston, J Michael Tredger, Christopher P Price Cambridge University Press, £80, pp 516 ISBN 0 521 81102 3 Rating:![Graphic][1]</img> Reading the history of one's subject can be an illuminating and humbling experience. In the 1960s when the use of biochemical measurements in the diagnosis and monitoring of disease was still very much in its infancy, clinical biochemists were to the fore in advocating that we abandon the concept of the normal range in favour … [1]: /embed/inline-graphic-1.gif
Novel mechanism of regulation of fibrosis in kidney tumor with tuberous sclerosis
Authors: Sitai Liang, Gabriela Cuevas, Shaza Tizani, Tiffanie Salas, Huijuan Liu, Baojie Li, Samy L Habib
Journal: Molecular Cancer (2013)

Abstract Background Deficiency in tuberin results in activation the mTOR pathway and leads to accumulation of cell matrix proteins. The mechanisms by which tuberin regulates fibrosis in kidney angiomyolipomas (AMLs) of tuberous sclerosis patients are not fully known. Method In the present study, we investigated the potential role of tuberin/mTOR pathway in the regulation of cell fibrosis in AML cells and kidney tumor tissue from tuberous sclerosis complex (TSC) patients. Results AML cells treated with rapamycin shows a significant decrease in mRNA and protein expression as well as in promoter transcriptional activity of alpha-smooth muscle actin (α-SMA) compared to untreated cells. In addition, cells treated with rapamycin significantly decreased the protein expression of the transcription factor YY1. Rapamycin treatment also results in the redistribution of YY1 from the nucleus to cytoplasm in AML cells. Moreover, cells treated with rapamycin resulted in a significant reduce of binding of YY1 to the αSMA promoter element in nuclear extracts of AML cells. Kidney angiomyolipoma tissues from TSC patients showed lower levels of tuberin and higher levels of phospho-p70S6K that resulted in higher levels of mRNA and protein of αSMA expression compared to control kidney tissues. In addition, most of the α-SMA staining was identified in the smooth muscle cells of AML tissues. YY1 was also significantly increased in tumor tissue of AMLs compared to control kidney tissue suggesting that YY1 plays a major role in the regulation of αSMA. Conclusions These data comprise the first report to provide one mechanism whereby rapamycin might inhibit the cell fibrosis in kidney tumor of TSC patients.
Increased risk of cirrhosis and its decompensation in chronic hepatitis C patients with new-onset diabetes: A nationwide cohort study
Authors: Yi-Wen Huang, Sien-Sing Yang, Szu-Chieh Fu, Ting-Chuan Wang, Cheng-Kai Hsu, Ding-Shinn Chen, Jui-Ting Hu, Jia-Horng Kao
Journal: Hepatology (2014)

The effect of diabetes on cirrhosis, its decompensation, and their time relationship in chronic hepatitis C (CHC) patients remains unclear. We conducted a nation-wide cohort study by using the Taiwanese National Health Insurance Research Database, which is comprised of data from &gt;99% of the entire population. Among having randomly sampled 1 million enrollees, 6,251 adult CHC patients were identified from 1997 to 2009. Diabetes was defined as new onset in CHC patients who were given the diagnosis in the years 1999-2003, but not in 1997-1998. The cohorts of CHC with new-onset diabetes (n = 424) and nondiabetes (n = 1,708) were followed up from inception point in diabetes and from year 1999 in the nondiabetes cohort until development of cirrhosis or its decompensation, withdrawal from insurance, or December 2009. Kaplan-Meier's survival analysis showed a significantly higher cumulative incidence of cirrhosis (relative risk [RR] = 1.53; 95% confidence interval [CI] = 1.11-2.11; log-rank test; P &lt; 0.001) and decompensated cirrhosis (RR = 2.01; 95% CI = 1.07-3.79; log-rank test; P &lt; 0.001) among patients with new-onset diabetes, as compared to those without. After adjustment for age, gender, CHC treatment, diabetes treatment, hepatocellular carcinoma, comorbidity index, hypertension, hyperlipidemia, and obesity by Cox's proportional hazard model, diabetes was still an independent predictor for cirrhosis (hazard ratio [HR] = 2.505; 95% CI = 1.609-3.897; P &lt; 0.001) and its decompensation (HR = 3.560; 95% CI = 1.526-8.307; P = 0.003). Conclusion : CHC patients who develop diabetes are at an increased risk of liver cirrhosis and its decompensation over time. (Hepatology 2014;60:807–814)
Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death.
Authors: M J Davies, A C Thomas, P A Knapman, J R Hangartner
Journal: Circulation (1986)

A specific search for intramyocardial platelet aggregates was made in 90 patients who died suddenly of ischemic heart disease. Platelet aggregates in small intramyocardial vessels were found in 27 (30%). There was a significant difference (p less than .05) in the incidence of platelet aggregates in patients with chest pain of recent onset (unstable angina) before death (16/36, 44.4%) and that in those without it (11/54, 20.4%). Multifocal microscopic necrosis with involvement of the full thickness of the ventricular wall, including the subpericardial zone, was significantly more common (p = less than .005) in the patients with platelet emboli (55.6% vs 12.7%). With one exception, aggregates were confined to the segment of myocardium immediately downstream of a major epicardial coronary artery containing an atheromatous plaque that had undergone fissuring and on which mural thrombus had developed. The results support the view that platelet aggregates in the myocardium represent an embolic phenomenon and are a potential cause of unstable angina. The association of myocardial necrosis with such emboli could precipitate sudden death from ventricular fibrillation.
The monoclonal antibody Zt/f2 targeting RON receptor tyrosine kinase as potential therapeutics against tumor growth-mediated by colon cancer cells
Authors: Hang-Ping Yao, Yong-Qing Zhou, Qi Ma, Sunny Guin, Snehal S Padhye, Rui-Wen Zhang, Ming-Hai Wang
Journal: Molecular Cancer (2011)

Abstract Background Overexpression of the RON receptor tyrosine kinase contributes to epithelial cell transformation, malignant progression, and acquired drug resistance. RON also has been considered as a potential target for therapeutic intervention. This study determines biochemical features and inhibitory activity of a mouse monoclonal antibody (mAb) Zt/f2 in experimental cancer therapy. Results Zt/f2 is a mouse IgG2a mAb that is highly specific and sensitive to human RON and its oncogenic variants such as RON160 (ED 50 = 2.3 nmol/L). Receptor binding studies revealed that Zt/f2 interacts with an epitope(s) located in a 49 amino acid sequence coded by exon 11 in the RON β-chain extracellular sequences. This sequence is critical in regulating RON maturation and phosphorylation. Zt/f2 did not compete with ligand macrophage-stimulating protein for binding to RON; however, its engagement effectively induced RON internalization, which diminishes RON expression and impairs downstream signaling activation. These biochemical features provide the cellular basis for the use of Zt/f2 to inhibit tumor growth in animal model. Repeated administration of Zt/f2 as a single agent into Balb/c mice results in partial inhibition of tumor growth caused by transformed NIH-3T3 cells expressing oncogenic RON160. Colon cancer HT-29 cell-mediated tumor growth in athymic nude mice also was attenuated following Zt/f2 treatment. In both cases, ~50% inhibition of tumor growth as measured by tumor volume was achieved. Moreover, Zt/f2 in combination with 5-fluorouracil showed an enhanced inhibition effect of ~80% on HT-29 cell-mediated tumor growth in vivo . Conclusions Zt/f2 is a potential therapeutic mAb capable of inhibiting RON-mediated oncogenesis by colon cancer cells in animal models. The inhibitory effect of Zt/f2 in vivo in combination with chemoagent 5-fluorouracil could represent a novel strategy for future colon cancer therapy.
A Randomized Trial of Two Methods to Disclose Prognosis to Surrogate Decision Makers in Intensive Care Units
Authors: Susan J. Lee Char, Leah R. Evans, Grace L. Malvar, Douglas B. White
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Surrogate decision makers and clinicians often have discordant perceptions about a patient's prognosis. There is a paucity of empirical data to guide communication about prognosis.To assess: (1) whether numeric or qualitative statements more reliably convey prognostic estimates; and (2) whether surrogates believe physicians' prognostic estimates.A total of 169 surrogate decision makers for intensive care unit patients were randomized to view 1 of 2 versions of a video portraying a simulated family conference involving a hypothetical patient. The videos varied only by whether prognosis was conveyed in numeric terms ("10% chance of surviving") or qualitative terms ("very unlikely" to survive).We assessed: (1) surrogates' personal estimates of the patient's prognosis; and (2) surrogates' understanding of the physician's prognostic estimate. Neither surrogates' personal estimates nor their understanding of the physician's prognostication differed when prognosis was conveyed numerically versus qualitatively (surrogates' estimate, 22 ± 23% chance of survival versus 26 ± 24%, P = 0.26; understanding of physician's estimate, 17 ± 22% chance of survival versus 16 ± 17%, P = 0.62). One in five surrogates estimated the patient's prognosis was greater than 20% more optimistic than the physician's prognostication. Less trust in physicians was associated with larger discrepancies between surrogates' personal estimates and their understanding of the physician's estimate.Neither numeric nor qualitative statements reliably convey news of a poor prognosis to surrogates in intensive care units. Many surrogates do not view physicians' prognostications as absolutely accurate. Factors other than ineffective communication may contribute to physician-surrogate discordance about prognosis.
Reducing Rate of Fertility Multiples Requires Policy Changes
Authors: Josephine Johnston, Michael K. Gusmano, Pasquale Patrizio
Journal: JAMA Pediatrics (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Efficacy and safety of adalimumab in Chinese adults with active ankylosing spondylitis: results of a randomised, controlled trial
Authors: Feng Huang, Jieruo Gu, Ping Zhu, Chunde Bao, Jianhua Xu, Huji Xu, Huaxiang Wu, Guochun Wang, Qun Shi, Nupun Andhivarothai, Jaclyn Anderson, Aileen L Pangan
Journal: Annals of the Rheumatic Diseases (2013)

Efficacy of adalimumab for ankylosing spondylitis (AS) has been established for Western populations but not in the Chinese population. This study is the first to evaluate the efficacy and safety of adalimumab in Chinese patients with AS.Chinese adults with active AS who had an inadequate response or were intolerant to ≥1 non-steroidal anti-inflammatory drugs were randomised to adalimumab 40 mg (N=229) or matching placebo (N=115) subcutaneously every other week (EOW) for 12 weeks, followed by a 12-week open-label adalimumab 40 mg EOW phase. The primary efficacy endpoint was the percentage of patients meeting the Assessment in Spondyloarthritis International Society (ASAS20) response criteria at week 12. The recently developed AS Disease Activity Score (ASDAS), as well as efficacy measures of spinal mobility, disease activity, physical function and quality of life were evaluated.At week 12, adalimumab treatment resulted in a significantly greater percentage of ASAS20 responders than placebo (67.2% versus 30.4%, respectively; p<0.001). Differences in ASAS20 were observed as early as week 2 (42.8% vs 6.1%, respectively; p<0.001). The percentages of patients achieving ASAS40, ASAS 5/6 and ASDAS inactive disease were significantly greater with adalimumab than placebo at week 12 (all p<0.001). Tuberculosis was reported in one patient. No cases of malignancy, lymphoma, demyelinating disease or lupus-like syndrome were reported during the study.Adalimumab significantly reduced the signs and symptoms, improved physical function and quality of life of Chinese patients with active AS, and was generally safe and well tolerated in this population.
Macrophage expression of interleukin-10 is a prognostic factor in nonsmall cell lung cancer
Authors: E. Zeni, L. Mazzetti, D. Miotto, N. Lo Cascio, P. Maestrelli, P. Querzoli, M. Pedriali, E. De Rosa, L. M. Fabbri, C. E. Mapp, P. Boschetto
Journal: European Respiratory Journal (2007)

Interleukin (IL)-10 is expressed in many solid tumours and plays an ambiguous role in controlling cancer growth and metastasis. In order to determine whether IL-10 is involved in tumour progression and prognosis in nonsmall cell lung cancer (NSCLC), IL-10 expression in tumour cells and tumour-associated macrophages (TAMs) and its associations, if any, with clinicopathological features were investigated. Paraffin-embedded sections of surgical specimens obtained from 50 patients who had undergone surgery for NSCLC were immunostained with an antibody directed against IL-10. TAMs and tumour cells positive for IL-10 were subsequently quantified. IL-10-positive TAM percentage was higher in patients with stage II, III and IV NSCLC, and in those with lymph node metastases compared with patients with stage I NSCLC. High IL-10 expression by TAMs was a significant independent predictor of advanced tumour stage, and thus was associated with worse overall survival. Conversely, IL-10 expression by tumour cells did not differ between stages II, III and IV and stage I NSCLC. In conclusion, interleukin-10 expression by tumour-associated macrophages, but not by tumour cells, may play a role in the progression and prognosis of nonsmall cell lung cancer. These results may be useful in the development of novel approaches for anticancer treatments.
B cell differentiation and isotype switching is related to division cycle number.
Authors: P D Hodgkin, J H Lee, A B Lyons
Journal: The Journal of Experimental Medicine (1996)

The mature, resting immunoglobulin (Ig) M, IgD+ B lymphocyte can be induced by T cells to proliferate, switch isotype, and differentiate into Ig-secreting or memory cells. Furthermore, B cell activation results in the de novo expression or loss of a number of cell surface molecules that function in cell recirculation or further interaction with T cells. Here, a novel fluorescent technique reveals that T-dependent B cell activation induces cell surface changes that correlate with division cycle number. Furthermore, striking stepwise changes are often centered on a single round of cell division. Particularly marked was the consistent increase in IgG1+ B cells after the second division cycle, from an initial level of < 3% IgG1+ to a plateau of approximately 40% after six cell divisions. The relationship between the percentage of IgG1+ B cells and division number was independent of time after stimulation, indicating a requirement for cell division in isotype switching. IgD expression became negative after four divisions, and a number of changes centered on the sixth division, including the loss of IgM, CD23, and B220. The techniques used here should prove useful for tracking other differentiation pathways and for future analysis of the molecular events associated with stepwise differentiation at the single cell level.
Glycemic Variability and Diabetes Complications: Does It Matter? Of Course It Does!
Authors: Irl B. Hirsch
Journal: Diabetes Care (2015)

There is no argument that improving mean levels of glycemic control as judged by assays for glycated hemoglobin (HbA(1c)) reduces the risks of microvascular complications and cardiovascular disease events in patients with type 1 and type 2 diabetes. However, observations in some trials have suggested that targeting HbA(1c) to suggested targets may not always result in improved outcomes for people with long-standing type 2 diabetes. The reasons why the glycemic control strategies that primarily use HbA(1c) in these studies did not have predicted outcomes are not clear. Thus, controversy remains as to whether there are glycemic metrics beyond HbA(1c) that can be defined as effective measures that can be used in addition to HbA(1c) to help in assessing the risk of an individual developing diabetes complications. In this regard, the concept of "glycemic variability" (GV) is one metric that has attracted a lot of attention. GV can be simply defined as the degree to which a patient's blood glucose level fluctuates between high (peaks) and low (nadir) levels. The best and most precise way to assess GV is also one that is still debated. Thus, while there is universal agreement that HbA(1c) is the current gold standard for the primary clinical target, there is no consensus as to whether other proposed glycemic metrics hold promise to provide additional clinical data or whether there should be additional targets beyond HbA(1c). Therefore, given the current controversy, we provide a Point-Counterpoint debate on this issue. In the point narrative below, Dr. Hirsch provides his argument that fluctuations in blood glucose as assessed by GV metrics are deleterious and control of GV should be a primary treatment target. In the following counterpoint narrative, Dr. Bergenstal argues that there are better markers to assess the risk of diabetes than GV and provides his consideration of other concepts.