tbuckley/cabot-search huggingface dataset:
Clarithromycin increases linezolid exposure in multidrug-resistant tuberculosis patients
Authors: Mathieu S. Bolhuis, Richard van Altena, Dick van Soolingen, Wiel C.M. de Lange, Donald R.A. Uges, Tjip S. van der Werf, Jos G.W. Kosterink, Jan-Willem C. Alffenaar
Journal: European Respiratory Journal (2013)

The use of linezolid for the treatment of multidrug-resistant tuberculosis is limited by dose- and time-dependent toxicity. Recently, we reported a case of pharmacokinetic drug–drug interaction between linezolid and clarithromycin that resulted in increased linezolid exposure. The aim of this prospective pharmacokinetic study is to quantify the effect of clarithromycin on the exposure of linezolid. Subjects were included in an open-label, single-centre, single-arm, fixed-order pharmacokinetic interaction study. All subjects received 300 mg linezolid twice daily during the entire study, consecutively co-administered with 250 mg and 500 mg clarithromycin once daily. Steady-state serum curves of linezolid and clarithromycin were analysed using validated methods, and differences between pharmacokinetic parameters were calculated. Linezolid exposure increased by a median (interquartile range) of 44% (23–102%, p=0.043) after co-administration of 500 mg clarithromycin (n=5) compared to baseline, whereas 250 mg clarithromycin had no statistically significant effect. Co-administration was well tolerated by most patients; none experienced severe adverse effects. One patient reported common toxicity criteria grade 2 gastrointestinal adverse events. In this study, we showed that clarithromycin significantly increased linezolid serum exposure after combining clarithromycin with linezolid in multidrug-resistant tuberculosis patients. The drug–drug interaction is possibly P-glycoprotein-mediated. Due to large interpatient variability, therapeutic drug monitoring is advisable to determine individual effect size.
Targeting lung attacks
Authors: J. M. FitzGerald
Journal: Thorax (2011)

Acute exacerbations of asthma and chronic obstructive lung disease (COPD) are significant burdens on the health care system.1 2 The economic burden is particularly high with both types of exacerbations. Unfortunately the management of these common occurrences is often haphazard and fragmented. The gaps in care relate both to the management of the specific episode in question3 and to the risk stratification of patients subsequent to the event.4 This lack of current and ongoing optimal care is disappointing, especially given the documented poor prognostic factors associated with these events. Patients hospitalised with acute asthma, and especially episodes of near fatal asthma, are associated with significantly increased future risks of intubation.5 In the case of COPD the outcomes are even more dramatic; in-hospital mortality for an acute exacerbation of COPD is at least 10% and 1-year mortality, posthospitalisation, approaches 25%. In addition to these immediate increased risks associated with exacerbations there is also a significant decline in lung function associated with both types of exacerbations.6 7 Given these data, the response of the health care system to these events is disappointing.7 This response is quite different from what occurs with a ‘heart attack’. In the case of an acute myocardial infarction initial management is much more aggressive, risk stratification is routine and patients are usually discharged on a medication bundle. In addition standard of care involves patients being enrolled in well-funded cardiac rehabilitation programmes. Similar comparisons have been drawn with the previously used term of a stroke which has in many settings been replaced with the term ‘brain attack’.

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Patient Interview Study From the Third National Cancer Survey: Overview of Problems and Potentials of These Data
Authors: Roger R. Williams, Nancy L. Stegens, John W. Horm
Journal: JNCI Journal of the National Cancer Institute (1977)

An interview requesting information on selected epidemiologic variables from the Third National Cancer Survey (TNCS) was sought for 13,179 incident cases, a random 10% sample in eight of nine geographic areas of the United States with a combined population of 21 million. An overall response of 7,518 (57%) was obtained. Nonresponse was due to refusal by physicians (14%) or patients (7%), early patient deaths (7%), no one available for Interview (5%), and tracing problems (10%). Comparison of interview respondents with all TNCS patients for age, race, sex, marital status, method of diagnosis, vital status, country of birth, and site distribution showed only small differences and no strong nonrespondent bias. These data contain information on tobacco and alcohol consumption, occupation and Industry, socioeconomic status, height, weight, obstetric and gynecologic history, and selected chronic diseases. In the absence of normal controls, two approaches to test for associations between these variables and specific cancer sites are suggested: 1) an “intercancer comparison” of patients with cancer at one site with those having cancers at other sites in the interview study, and 2) an “external comparison” of interview patients with subjects of other studies with comparable data. The need for caution with either approach is emphasized in an effort to prevent misinterpretations of these data.
Effect of sulfhydryl oxidation on ionic and gating currents associated with L-type calcium channels in isolated guinea-pig ventricular myocytes
Authors: A. Lacampagne, A. Duittoz, P. Bolanos, N. Peineau, J. A. Argibay
Journal: Cardiovascular Research (1995)

L-type calcium currents (ICa) and gating currents modification by extracellular application of the selective free sulfhydryl oxidant p-hydroxy-mercuric-phenylsulphonic acid (PHMPS) were studied.Both currents were obtained with the whole cell patch clamp technique in guinea-pig ventricular cardiocytes.The main finding was a reduction of ICa clearly differentiable from a "run down" process. This effect was protected, stopped and in some cases partially reversed by dithiothreitol, a protective reagent for -SH groups. We also found a decrease of the gating currents associated with L-type calcium channels. The calcium modulation and cAMP phosphorylation systems of ICa are unaffected by PHMPS. With barium as charge carrier the current-voltage curves of barium currents were shifted by 10 mV to the positive direction by PHMPS. The same effect was obtained with calcium currents using BAPTA as a fast calcium buffer.The results indicate that oxidation of -SH groups carried by the channel protein induces dysfunction of the calcium entry to cardiac cells by altering the gating process. A participation of thiol functions on the gating of the calcium channel is proposed.
How Do People With Diabetes Describe Their Experiences in Primary Care? Evidence From 85,760 Patients With Self-reported Diabetes From the English General Practice Patient Survey
Authors: Charlotte A.M. Paddison, Catherine L. Saunders, Gary A. Abel, Rupert A. Payne, Amanda I. Adler, Jonathan P. Graffy, Martin O. Roland
Journal: Diabetes Care (2014)

OBJECTIVE Developing primary care is an important current health policy goal in the U.S. and England. Information on patients’ experience can help to improve the care of people with diabetes. We describe the experiences of people with diabetes in primary care and examine how these experiences vary with increasing comorbidity. RESEARCH DESIGN AND METHODS Using data from 906,578 responders to the 2012 General Practice Patient Survey (England), including 85,760 with self-reported diabetes, we used logistic regressions controlling for age, sex, ethnicity, and socioeconomic status to analyze patient experience using seven items covering three domains of primary care: access, continuity, and communication. RESULTS People with diabetes were significantly more likely to report better experience on six out of seven primary care items than people without diabetes after adjusting for age, sex, ethnicity, and socioeconomic status (adjusted differences 0.88–3.20%; odds ratios [ORs] 1.07–1.18; P &amp;lt; 0.001). Those with diabetes and additional comorbid long-term conditions were more likely to report worse experiences, particularly for access to primary care appointments (patients with diabetes alone compared with patients without diabetes: OR 1.22 [95% CI 1.17–1.28] and patients with diabetes plus three or more conditions compared with patients without diabetes: OR 0.87 [95% CI 0.83–0.91]). CONCLUSIONS People with diabetes in England report primary care experiences that are at least as good as those without diabetes for most domains of care. However, improvements in primary care are needed for diabetes patients with comorbid long-term conditions, including better access to appointments and improved communication.
Infections During Left Ventricular Assist Device Support Do Not Affect Posttransplant Outcomes
Authors: P. Sinha, J. M. Chen, M. Flannery, B. E. Scully, M. C. Oz, N. M. Edwards
Journal: Circulation (2000)

Although infections acquired during ventricular assist device support may increase the risk of infection and have an impact on transplant survival, their true posttransplant consequences remain to be determined. This study evaluates the impact of an outpatient program, newer devices, and an updated infection management protocol on infection-related patient outcomes after transplant.Eighty-six patients received a left ventricular assist device (LVAD) between June 1996 and June 1999. Fifty patients transplanted during the same period, without prior device support, were used as controls; they were matched to transplanted LVAD recipients by age, sex, diagnosis, and transplant date. The nature of and actuarial freedom from peritransplant and posttransplant infections were compared at 6 months after transplant; actuarial patient survival was compared at 3 years. Infection was defined as leukocytosis or leukopenia, with a positive culture requiring either medical or surgical intervention. Forty-four patients (51%) were successfully discharged home on LVAD support, and 61 (71%) were transplanted. A high incidence of infection during device support did not have an impact on pretransplant or posttransplant mortality, posttransplant infectious rate, or overall patient survival. Active infections at transplant also did not significantly influence 6-month mortality. In comparison, LVAD recipients had a lower freedom from infection than did controls (P:<0.05); however, 3-year survival did not differ: 79% and 87% for the LVAD and control groups, respectively.Although LVADs increase the risk of infection in the early posttransplant period, this appears not to have an impact on transplantability or patient survival and likely reflects effective infection control in both inpatient and outpatient settings.
Imaging in rheumatology: Eds D A Isenberg, P Renton. (Pp 471, 125.) Oxford: Oxford University Press, 2002. ISBN 0-19-263263-9.
Authors: F W Roemer
Journal: Annals of the Rheumatic Diseases (2003)

Almost 60 contributors collaborated with the editors to produce this first edition on imaging of the rheumatic diseases. The great majority of the contributors are from the UK, with most of them working in departments of rheumatology.

The aim is to provide the rheumatologist as well as the radiologist with a comprehensive review of the currently available imaging modalities. The editors’ purpose was to outline how these methods are used to investigate rheumatic symptoms and in the long term management of patients with diverse diseases of joints, muscles, and bones.

There are three sections. The first six chapters focus on modes of imaging and provide the reader, especially the non-radiologist, with a background of knowledge of the available methods. The five chapters …
Transcriptional Profiling in Coronary Artery Disease
Authors: Thomas W. Chittenden, Jonathan A. Sherman, Fei Xiong, Amy E. Hall, Anthony A. Lanahan, Jennifer M. Taylor, Hangjun Duan, Justin D. Pearlman, Jason H. Moore, Stephen M. Schwartz, Michael Simons
Journal: Circulation (2006)

The development of collateral circulation plays an important role in protecting tissues from ischemic damage, and its stimulation has emerged as one of principal approaches to therapeutic angiogenesis. Clinical observations have documented substantial differences in the extent of collateralization among patients with coronary artery disease (CAD), with some individuals demonstrating marked abundance and others showing nearly complete absence of these vessels. Recent studies have suggested that circulating monocytes play a major role in collateral growth. The present study was undertaken to determine transcriptional profiles of circulating monocytes in CAD patients with different extents of collateral growth.Monocyte transcriptomes from CAD patients with and without collateral vessels were obtained by use of high-throughput expression profiling. Using a newly developed redundancy-based data mining method, we have identified a set of molecular markers characteristic of a "noncollateralgenic" phenotype. Moreover, we show that these transcriptional abnormalities are independent of the severity of CAD or any other known clinical parameter thought to affect collateral development and correlated with protein expression levels in monocytes and plasma.Monocyte transcription profiling identifies sets of patients with extensive versus poorly developed collateral circulation. Thus, genetic factors may heavily influence coronary collateral vessel growth in CAD and affect prognosis and response to therapeutic interventions.
Minimally Invasive Prostatic Urethral Lift: Surgical Technique and Multinational Experience
Authors: Thomas A. McNicholas, Henry H. Woo, Peter T. Chin, Damien Bolton, Manuel Fernández Arjona, Karl-Dietrich Sievert, Martin Schoenthaler, Ulrich Wetterauer, Eric J.E.J. Vrijhof, Steven Gange, Francesco Montorsi
Journal: European Urology (2013)
Alveolar macrophage immaturity in infants and young children
Authors: J Grigg, J Riedler, CF Robertson, W Boyle, S Uren
Journal: European Respiratory Journal (1999)

Very little is known about alveolar macrophage (AM) immunological function in early childhood. Using nonbronchoscopic bronchoalveolar lavage (BAL), this study sought to compare the proportion, number, and function of AM between very young and older children. BAL fluid (BALF) leukocyte parameters were determined in 63 children, and data divided into 3 age groups: group 1 (&lt;2 yrs), group 2 (&gt; or =2-&lt; or =5 yrs) and group 3 (&gt; or =6-&lt; or =17 years). In a further subgroup of children, AM function and immune receptor expression were assessed, and data categorized into two age groups: &lt;2 yrs and &gt; or =2 yrs of age. Compared to groups 2 and 3, the AM percentage in the BAL in group 1 was significantly increased (median: 98% versus 92% and 91%), as was the albumin-adjusted AM concentration. AM from children &lt;2 yrs expressed less human leukocyte antigen (HLA)-DR (versus &gt; or =2 yrs of age), were less effective in reducing nitro blue tetrazolium, and released less interleukin (IL)-1 and tumour necrosis factor on lipopolysaccharide stimulation. There was no difference in release of IL-6, expression of intercellular adhesion molecule-1 (CD54), and AM stimulation of allogeneic T-cells, between children &lt;2 yrs and &gt; or =2 yrs of age. It was concluded that the capacity of alveolar macrophage to stimulate T-cells is not enhanced in early childhood, and that immaturity of alveolar macrophage function may contribute to an increased susceptibility to respiratory infections in this age group.
The quinoxaline di-N-oxide DCQ blocks breast cancer metastasis in vitro and in vivo by targeting the hypoxia inducible factor-1 pathway
Authors: Khaled Ghattass, Sally El-Sitt, Kazem Zibara, Saide Rayes, Makhluf J Haddadin, Marwan El-Sabban, Hala Gali-Muhtasib
Journal: Molecular Cancer (2014)

Abstract Background Although tumor hypoxia poses challenges against conventional cancer treatments, it provides a therapeutic target for hypoxia-activated drugs. Here, we studied the effect of the hypoxia-activated synthetic quinoxaline di-N-oxide DCQ against breast cancer metastasis and identified the underlying mechanisms. Methods The human breast cancer cell lines MCF-7 (p53 wildtype) and MDA-MB-231 (p53 mutant) were treated with DCQ under normoxia or hypoxia. Drug toxicity on non-cancerous MCF-10A breast cells was also determined. In vitro cellular responses were investigated by flow cytometry, transfection, western blotting, ELISA and migration assays. The anti-metastatic effect of DCQ was validated in the MDA-MB-231 xenograft mouse model. Results DCQ selectively induced apoptosis in both human breast cancer cells preferentially under hypoxia without affecting the viability of non-cancerous MCF-10A. Cancer cell death was associated with an increase in reactive oxygen species (ROS) independently of p53 and was inhibited by antioxidants. DCQ-induced ROS was associated with DNA damage, the downregulation of hypoxia inducible factor-1 alpha (HIF-1α), and inhibition of vascular endothelial growth factor (VEGF) secretion. In MCF-7, HIF-1α inhibition was partially via p53-activation and was accompanied by a decrease in p-mTOR protein, suggesting interference with HIF-1α translation. In MDA-MB-231, DCQ reduced HIF-1α through proteasomal-dependent degradation mechanisms. HIF-1α inhibition by DCQ blocked VEGF secretion and invasion in MCF-7 and led to the inhibition of TWIST in MDA-MB-231. Consistently, DCQ exhibited robust antitumor activity in MDA-MB-231 breast cancer mouse xenografts, enhanced animal survival, and reduced metastatic dissemination to lungs and liver. Conclusion DCQ is the first hypoxia-activated drug showing anti-metastatic effects against breast cancer, suggesting its potential use for breast cancer therapy.
CSL–MAML-dependent Notch1 signaling controls T lineage–specific IL-7Rα gene expression in early human thymopoiesis and leukemia
Authors: Sara González-García, Marina García-Peydró, Enrique Martín-Gayo, Esteban Ballestar, Manel Esteller, Rafael Bornstein, José Luis de la Pompa, Adolfo A. Ferrando, María L. Toribio
Journal: The Journal of Experimental Medicine (2009)

Notch1 activation is essential for T-lineage specification of lymphomyeloid progenitors seeding the thymus. Progression along the T cell lineage further requires cooperative signaling provided by the interleukin 7 receptor (IL-7R), but the molecular mechanisms responsible for the dynamic and lineage-specific regulation of IL-7R during thymopoiesis are unknown. We show that active Notch1 binds to a conserved CSL-binding site in the human IL7R gene promoter and critically regulates IL7R transcription and IL-7R α chain (IL-7Rα) expression via the CSL–MAML complex. Defective Notch1 signaling selectively impaired IL-7Rα expression in T-lineage cells, but not B-lineage cells, and resulted in a compromised expansion of early human developing thymocytes, which was rescued upon ectopic IL-7Rα expression. The pathological implications of these findings are demonstrated by the regulation of IL-7Rα expression downstream of Notch1 in T cell leukemias. Thus, Notch1 controls early T cell development, in part by regulating the stage- and lineage-specific expression of IL-7Rα.
Characterization of specific leukotriene C4 binding sites on cultured human keratinocytes
Authors: A. MULLER, L. MICHEL, N. BASSET-SEGUIN, G. MODAT, L. DUBERTRET, C. BONNE
Journal: British Journal of Dermatology (1988)

Peptidoleukotriene C4 (LTC4) and leukotriene B4 (LTB4) are both suspected of being inflammatory mediators and epidermal mitogenic agents in cutaneous psoriatic lesions. In the present study an LTC4 specific binding site was characterized in membranes from cultured human keratinocytes (Kd, 8.7 nmol/1; Bmax, 1.2 pmol/mg protein). In contrast LTB4 did not show any high affinity binding which could account for its biological effects. These data suggest that LTC4, unlike LTB4, acts on epidermal cells through a receptor‐mediated mechanism.
Points from Letters: Neurology in Fiction
Authors: P. J. E. Wilson
Journal: BMJ (1974)

The European Agency for Safety and Health at Work declared, for the next decades, an increase in the proportion of ageing workers. Thus, the health and the safety at work is necessary to ensure an active ageing through the promotion of healthy lifestyles, prevention of diseases and improvement of quality of life. <h3>Methods</h3> From 09/2014 to 03/2016, a trained health visitor started a semi structural interview in a sample of 980 healthcare personnel (HCP) (mean age 46, range 18–68 years, SD ± 11.3) from five Italian hospitals. Information about dietary habits, physical activity, vaccination coverage, biological risk and exposure to biomechanical overload at work were collected. Information about health opportunities on all the variables analysed were provided for each participant during the counselling. <h3>Results</h3> The 57% of HCP ate fruit and vegetables less than 3 times/day and 33% consumed meat more than 3 times per week. The 25% practiced physical activity less than 2 days/week. The 12% of HCP was vaccinated against influenza and 72% against hepatitis B. HCP did not know their antibody coverage status against varicella, measles, rubella, mumps and related occupational risks. The 19% of HCP reported a biological injury and the 18% of them did not follow the post exposure protocols. The 37% of HCP performed manual handling of patients. Among them, 26% and 43% had not available minor and major assistive devices, respectively. <h3>Discussion</h3> The results suggest the need for a re-orientation process of services to protect ageing HCP in order to foster the adoption of healthy lifestyles and prevent occupational injuries and diseases. Ageing HCP’s well-being represent a key point also in order to improve the quality of care in healthcare settings. The study was conducted with the financial support of the Italian Ministry of Health, CCM Program 2013.
THE GROWTH OF EPITHELIUM IN TEGUMENTARY TISSUES. PART III.*.
Authors: H. LESLIE-ROBERTS
Journal: British Journal of Dermatology (1941)

Journal Article THE GROWTH OF EPITHELIUM IN TEGUMENTARY TISSUES. PART III.: THE HEALING OF CUTANEOUS WOUNDS. REGENERATION Get access H. LESLIE‐ROBERTS H. LESLIE‐ROBERTS Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 53, Issue 12, 1 December 1941, Pages 333–346, https://doi.org/10.1111/j.1365-2133.1941.tb10491.x Published: 01 December 1941
Not Only Response but Early Response to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
Authors: Jorge E. Cortes
Journal: Journal of Clinical Oncology (2011)

WhenIstartedmycareerinleukemiaresearch,interferonalfa was standard therapy for patients with chronic myeloid leukemia (CML). Interferon could induce complete cytogenetic response (CCyR; ie, 0% Philadelphia-chromosome metaphases) or partial cytogenetic response (PCyR; ie, 1% to 35%), and such responses were associated with improved survival. These responses, particularly CCyR, occurred only in a minority of patients and the time to response was not given much attention. With the introduction of tyrosine kinase inhibitors (TKIs), our goals became more ambitious,