tbuckley/cabot-search huggingface dataset:
Preventing premature mortality in chronic diseases for South Asians in the UK and beyond
Authors: Neeraj Bhala, M Justin S Zaman
Journal: Journal of the Royal Society of Medicine (2009)

Whathaschangedinourunderstand-ing since ethnic disparities in coronary diseasemortalitywereinitiallyhighlighted?Wegivesomepast and future pointers in this field by citingexamples in the largest ethnic minority group inthe UK – people of SouthAsian origin.Biological differences are often first sought intrying to explain ethnic differences in diseasepatterns. The higher prevalence of diabetes inSouthAsians (predominately comprising peoplefrom India, Bangladesh, Pakistan and Sri Lanka)has been long known, and was thought to be themain driver behind the higher rates of coronaryheart disease mortality seen in this populationwhen compared to the majority indigenouspopulations in the developed societies to whichSouth Asians migrate to. Theories to explainthis have historically revolved around insulinresistance.
Domestic violence affects women more than men
Authors: Jo R Richardson, Gene Feder, Jeremy Coid
Journal: BMJ (2002)

EDITOR—The letter by Horner in response to our paper on domestic violence echoed a question raised in many electronic responses to our paper: “What about the men?” 1 2

An understanding of the impact of domestic violence by men against women is crucial to justifying the attention that this issue deserves, in comparison with violence by women against men. Horner cites …
HIV-1 Vpr Induces DNA Double-Strand Breaks
Authors: Hiroaki Tachiwana, Mari Shimura, Chikako Nakai-Murakami, Kenzo Tokunaga, Yoshimasa Takizawa, Tetsutaro Sata, Hitoshi Kurumizaka, Yukihito Ishizaka
Journal: Cancer Research (2006)

Abstract Recent observations imply that HIV-1 infection induces chromosomal DNA damage responses. However, the precise molecular mechanism and biological relevance are not fully understood. Here, we report that HIV-1 infection causes double-strand breaks in chromosomal DNA. We further found that Vpr, an accessory gene product of HIV-1, is a major factor responsible for HIV-1–induced double-strand breaks. The purified Vpr protein promotes double-strand breaks when incubated with isolated nuclei, although it does not exhibit endonuclease activity in vitro. A carboxyl-terminally truncated Vpr mutant that is defective in DNA-binding activity is less capable of Vpr-dependent double-strand break formation in isolated nuclei. The data suggest that double-strand breaks induced by Vpr depend on its DNA-binding activity and that Vpr may recruit unknown nuclear factor(s) with positive endonuclease activity to chromosomal DNA. This is the first direct evidence that Vpr induces double-strand breaks in HIV-1–infected cells. We discuss the possible roles of Vpr-induced DNA damage in HIV-1 infection and the involvement of Vpr in further acquired immunodeficiency syndrome–related tumor development. (Cancer Res 2006; 66(2): 627-31)
A magic bullet for gout?
Authors: A. So, N. Busso
Journal: Annals of the Rheumatic Diseases (2009)

Do we need new treatments for gout? Hyperuricaemia, the metabolic condition underlying gouty inflammation, has attracted recent attention as new urate-lowering treatments emerge on the horizon. For an acute attack of gout, the currently available drugs—non-steroidal anti-inflammatory drugs, colchicine and corticosteroids, seem to do a pretty good job for the majority of patients in relieving the acute symptoms of inflammation. However, recent data have highlighted the epidemiological shifts in the gouty population towards a more elderly group of patients who often present multiple medical problems. This as well as clinical practice have made us aware that our current treatments of acute gout are not ideal in all situations. They may cause significant side effects in patients with poor renal and cardiac function, and practical experience indicates that quite a number of patients with chronic gout end up receiving long-term steroids, with all the side effects that such treatment engenders. Furthermore, there are abundant reports pointing out that gout is poorly managed in routine clinical practice, suggesting that we are not using all the tools at our disposition adequately. Any new treatment for gout should therefore offer distinct advantages over existing ones to justify its introduction.

With the discovery of the inflammasome as a major regulator of interleukin 1β (IL1β) processing and secretion in macrophages and dendritic cells, IL1 has once again returned to the spotlight as a mediator of acute inflammation. The identification of mutations in the NALP3 gene, a component of the inflammasome, in patients with a subset within the autoinflammatory syndromes (now called cryopyrin-associated periodic syndromes or CAPS) led to the idea of targeting IL1β in this disease. The results have been spectacular1 2 and confirmed that IL1 inhibitors can have major clinical effects if the physiopathology of the disease involves excessive IL1 production. Martinon et al …
Cellular Immunity in Breast Cancer Patients Completing Taxane Treatment
Authors: William E. Carson, Charles L. Shapiro, Timothy R. Crespin, Lisa M. Thornton, Barbara L. Andersen
Journal: Clinical Cancer Research (2004)

Abstract Purpose: A field study of postchemotherapy immune functioning relative to the use of taxanes is reported. Immune responses in breast cancer patients were analyzed as a function of whether patients received taxane as part of their adjuvant chemotherapy. Experimental Design: Immune levels of 227 stage II/III breast cancer patients were measured immediately after surgery prior to chemotherapy and again 12 months later when all chemotherapies had been completed. T-cell blastogenesis and natural killer (NK) cell lysis levels of patients receiving taxanes (n = 55) were compared with levels of patients not receiving taxanes (n = 172). Results: Regression analyses were conducted. The administration of taxane as part of combination chemotherapy predicted increased T-cell blastogenesis and NK cell cytotoxicity after the conclusion of all chemotherapies. For the Taxane group, average phytohemagglutinin-induced blastogenesis was 37% higher and NK cell cytotoxicity was 39% higher than the values for the No-Taxane group. Conclusions: Data from group comparisons with appropriate controls in a sizable clinical sample contravene traditional wisdom that taxanes suppress patients’ immune cell functions. Problems in generalizing direct-contact laboratory models to the field of cancer treatment are highlighted.
Studies in chronic allergic bronchopulmonary aspergillosis. 1. Clinical and physiological findings.
Authors: J L Malo, R Hawkins, J Pepys
Journal: Thorax (1977)

This report outlines the clinical and physiological features in 50 asthmatic patients with chronic allergic bronchopulmonary aspergillosis in whom the diagnosis was made from 2 to 25 years ago (mean duration 10-9 years). From a questionnaire and analysis of the peak expiratory flow rate measurements it was found that they were worse in the winter months, corresponding to the maximal concentrations of Aspergillus fumigatus in the atmosphere. Nineteen patients reported daily sputum production of up to an eggcupful or more, and 24 had noticed sputum 9plugs9 in the previous year. Reduction of vital capacity (VC) was found in 20 patients, of forced expiratory volume in one second (FEV1) in 38 patients, and of maximal expiratory flow at 50% VC breathing air (V50air) in 47 patients. Nine patients had significantly reduced gas transfer factor (DLCO). Significant improvement (more than 15%) in FEV1 after inhaled bronchodilator was shown by only 17 patients. There were statistically significant correlations between the degree of reduction in the physiological measurements of VC, FEV1, and V50air with the age of the patient at the time of the study and the later in life the diagnosis of aspergillosis was made, whereas the reduction in DLCO was also significantly related to the duration of aspergillosis. Prospective studies are needed for a proper assessment of any protective effect of treatment on the pathophysiological changes due to the disease over many years.
Overcrowding in Hospital Wards as a Predictor of Antidepressant Treatment Among Hospital Staff
Authors: Marianna Virtanen, Jaana Pentti, Jussi Vahtera, Jane E. Ferrie, Stephen A. Stansfeld, Hans Helenius, Marko Elovainio, Teija Honkonen, Kirsi Terho, Tuula Oksanen, Mika Kivimäki
Journal: American Journal of Psychiatry (2008)

Objective: This report assessed whether hospital ward overcrowding predicts antidepressant use among hospital staff. Method: The extent of hospital ward overcrowding was determined using administrative records of monthly bed occupancy rates between 2000 and 2004 in 203 somatic illness wards in 16 Finnish hospitals providing specialized health care. Information on job contracts for personnel was obtained from the employers' registers. Comprehensive daily data on purchased antidepressant prescriptions (World Health Organization's Anatomical Therapeutic Chemical classification code N06A) for nurses (N=6,699) and physicians (N=641) was derived from national registers. Cox proportional hazards models were used to examine the association between bed occupancy rate and subsequent antidepressant treatment. Monthly bed occupancy rates were used as a time-dependent exposure that could change in value over the course of observation. Hazard ratios were adjusted for sex, age, occupation, type and length of employment contract, hospital district, specialty, and calendar year. Results: Exposure over 6 months to an average bed occupancy rate over 10% in excess of the recommended limit was associated with new antidepressant treatment. This association followed a dose-response pattern, with increasing bed occupancy associated with an increasing likelihood of antidepressant use. There was no evidence of reverse causality; antidepressant treatment among employees did not predict subsequent excess bed occupancy. Conclusions: The increased risk of antidepressant use observed in this study suggests that overcrowding in hospital wards may have an adverse effect on the mental health of staff.
Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials
Authors: Maria Schwaederle, Melissa Zhao, J. Jack Lee, Alexander M. Eggermont, Richard L. Schilsky, John Mendelsohn, Vladimir Lazar, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2015)

Purpose The impact of a personalized cancer treatment strategy (ie, matching patients with drugs based on specific biomarkers) is still a matter of debate. Methods We reviewed phase II single-agent studies (570 studies; 32,149 patients) published between January 1, 2010, and December 31, 2012 (PubMed search). Response rate (RR), progression-free survival (PFS), and overall survival (OS) were compared for arms that used a personalized strategy versus those that did not. Results Multivariable analysis (both weighted multiple linear regression and random effects meta-regression) demonstrated that the personalized approach, compared with a nonpersonalized approach, consistently and independently correlated with higher median RR (31% v 10.5%, respectively; P &lt; .001) and prolonged median PFS (5.9 v 2.7 months, respectively; P &lt; .001) and OS (13.7 v 8.9 months, respectively; P &lt; .001). Nonpersonalized targeted arms had poorer outcomes compared with either personalized targeted therapy or cytotoxics, with median RR of 4%, 30%, and 11.9%, respectively; median PFS of 2.6, 6.9, and 3.3 months, respectively (all P &lt; .001); and median OS of 8.7, 15.9, and 9.4 months, respectively (all P &lt; .05). Personalized arms using a genomic biomarker had higher median RR and prolonged median PFS and OS (all P ≤ .05) compared with personalized arms using a protein biomarker. A personalized strategy was associated with a lower treatment-related death rate than a nonpersonalized strategy (median, 1.5% v 2.3%, respectively; P &lt; .001). Conclusion Comprehensive analysis of phase II, single-agent arms revealed that, across malignancies, a personalized strategy was an independent predictor of better outcomes and fewer toxic deaths. In addition, nonpersonalized targeted therapies were associated with significantly poorer outcomes than cytotoxic agents, which in turn were worse than personalized targeted therapy.
Functional integrity of proximal tubule cells. Effects of hypoxia and ischemia.
Authors: Y You, D J Hirsch, N S Morgunov
Journal: Journal of the American Society of Nephrology (1992)

Effects of warm hypoxia and ischemia on electrophysiologic properties of isolated perfused mouse proximal straight tubules were studied. Oxyrase (5 to 10 microliters/mL) was added to the hypoxic and ischemic solutions to lower the oxygen tension to 5 mm Hg. The ischemic solution also simulated acidosis, K+ and lactate accumulation, and substrate deprivation. Twenty-minute tubular perfusion with the hypoxic and ischemic solutions (lumen and bath) at 37 degrees C did not significantly alter basolateral membrane potential, basolateral K+ transference number, or intracellular Na+ activity from control values of -69 +/- 1 mV (N = 91), 0.71 +/- 0.01 (N = 15), and 15.2 +/- 0.8 mM (N = 12), respectively. However, the hypoxic and ischemic perfusions decreased transepithelial potential by 40% (hypoxia: -1.7 +/- 0.1 to -1.1 +/- 0.1 mV [N = 30; P < 0.001]; ischemia: -1.4 +/- 0.1 to -0.82 +/- 0.05 mV [N = 17; P < 0.001]). A similar extent of reduction in transepithelial resistance was observed (hypoxia: 14.3 +/- 1.0 to 9.2 +/- 1.1 omega.cm2 [N = 7; P < 0.005]; ischemia: 12.6 +/- 1.2 to 8.1 +/- 1.0 omega.cm2 [N = 6; P < 0.03]). In addition, neither apical (R(ap)) nor basolateral (Rbl) cell membrane resistances were significantly altered after the ischemic perfusion (control: R(ap) = 369 +/- 48 omega.cm2; Rbl = 92 +/- 11 omega.cm2 [N = 63]; reperfusion: R(ap) = 454 +/- 88 omega.cm2; Rbl = 101 +/- 16 omega.cm2 [N = 21]). It was concluded that tubular cells are able to maintain their electrogenic ionic transport after short-term exposure to hypoxic or ischemic conditions. However, cell-to-cell junctions are damaged by these insults, which could possibly increase leakage and decrease the efficiency of the active transport.
Fibromodulin, an extracellular matrix protein: characterization of its unique gene and protein expression in B-cell chronic lymphocytic leukemia and mantle cell lymphoma
Authors: Eva Mikaelsson, Amir Hossein Danesh-Manesh, Alfred Lüppert, Mahmood Jeddi-Tehrani, Mohammad-Reza Rezvany, Ramazan Ali Sharifian, Reza Safaie, Azam Roohi, Anders Österborg, Fazel Shokri, Håkan Mellstedt, Hodjattallah Rabbani
Journal: Blood (2005)
Multicenter Assessment of Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer
Authors: Homayoun Zargar, Patrick N. Espiritu, Adrian S. Fairey, Laura S. Mertens, Colin P. Dinney, Maria C. Mir, Laura-Maria Krabbe, Michael S. Cookson, Niels-Erik Jacobsen, Nilay M. Gandhi, Joshua Griffin, Jeffrey S. Montgomery, Nikhil Vasdev, Evan Y. Yu, David Youssef, Evanguelos Xylinas, Nicholas J. Campain, Wassim Kassouf, Marc A. Dall’Era, Jo-An Seah, Cesar E. Ercole, Simon Horenblas, Srikala S. Sridhar, John S. McGrath, Jonathan Aning, Shahrokh F. Shariat, Jonathan L. Wright, Andrew C. Thorpe, Todd M. Morgan, Jeff M. Holzbeierlein, Trinity J. Bivalacqua, Scott North, Daniel A. Barocas, Yair Lotan, Jorge A. Garcia, Andrew J. Stephenson, Jay B. Shah, Bas W. van Rhijn, Siamak Daneshmand, Philippe E. Spiess, Peter C. Black
Journal: European Urology (2014)
Cohabiting with domestic mites.
Authors: I H Feather, J A Warner, S T Holgate, P J Thompson, G A Stewart
Journal: Thorax (1993)

Cohabiting with domestic mitesAs lorng ago as 1662 it was realised that the inhalation of dust particles in the air could lead to symptoms now recognised as typical of an allergic reaction.John Baptista van Helmont, a Flemish physician, wrote of one of his patients (a monk): ". . .as oft as any place is swept or the wind doth otherwise on August 2,
Assessment of insulin action in insulin-dependent diabetes mellitus using [6(14)C]glucose, [3(3)H]glucose, and [2(3)H]glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used.
Authors: P M Bell, R G Firth, R A Rizza
Journal: Journal of Clinical Investigation (1986)

To determine whether [2(3)H], [3(3)H], and [6(14)C]glucose provide an equivalent assessment of glucose turnover in insulin-dependent diabetes mellitus (IDDM) and nondiabetic man, glucose utilization rates were measured using a simultaneous infusion of these isotopes before and during hyperinsulinemic euglycemic clamps. In the nondiabetic subjects, glucose turnover rates determined with [6(14)C]glucose during insulin infusion were lower (P less than 0.02) than those determined with [2(3)H]glucose and higher (P less than 0.01) than those determined with [3(3)H]glucose. In IDDM, glucose turnover rates measured with [6(14)C]glucose during insulin infusion were lower (P less than 0.05) than those determined with [2(3)H]glucose, but were not different from those determined with [3(3)H]glucose. All three isotopes indicated the presence of insulin resistance. However, using [3(3)H]glucose led to the erroneous conclusion that glucose utilization was not significantly decreased at high insulin concentrations in the diabetic patients. [6(14)C] and [3(3)H]glucose but not [2(3)H]glucose indicated impairment in insulin-induced suppression of glucose production. These results indicate that tritiated isotopes do not necessarily equally reflect the pattern of glucose metabolism in diabetic and nondiabetic man.
Contribution of oncoproteomics to cancer biomarker discovery
Authors: William CS Cho
Journal: Molecular Cancer (2007)

Oncoproteomics is the study of proteins and their interactions in a cancer cell by proteomic technologies. Proteomic research first came to the fore with the introduction of two-dimensional gel electrophoresis. At the turn of the century, proteomics has been increasingly applied to cancer research with the wide-spread introduction of mass spectrometry and proteinchip. There is an intense interest in applying proteomics to foster an improved understanding of cancer pathogenesis, develop new tumor biomarkers for diagnosis, and early detection using proteomic portrait of samples. Oncoproteomics has the potential to revolutionize clinical practice, including cancer diagnosis and screening based on proteomic platforms as a complement to histopathology, individualized selection of therapeutic combinations that target the entire cancer-specific protein network, real-time assessment of therapeutic efficacy and toxicity, and rational modulation of therapy based on changes in the cancer protein network associated with prognosis and drug resistance. Besides, oncoproteomics is also applied to the discovery of new therapeutic targets and to the study of drug effects. In pace with the successful completion of the Human Genome Project, the wave of proteomics has raised the curtain on the postgenome era. The study of oncoproteomics provides mankind with a better understanding of neoplasia. In this article, the discovery of cancer biomarkers in recent years is reviewed. The challenges ahead and perspectives of oncoproteomics for biomarkers development are also addressed. With a wealth of information that can be applied to a broad spectrum of biomarker research projects, this review serves as a reference for biomarker researchers, scientists working in proteomics and bioinformatics, oncologists, pharmaceutical scientists, biochemists, biologists, and chemists.
<i>UGT1A1</i>Promoter Genotype Correlates With SN-38 Pharmacokinetics, but Not Severe Toxicity in Patients Receiving Low-Dose Irinotecan
Authors: Clinton F. Stewart, John C. Panetta, Melinda A. O'Shaughnessy, Stacy L. Throm, Charles H. Fraga, Thandranese Owens, Tiebin Liu, Catherine Billups, Carlos Rodriguez-Galindo, Amar Gajjar, Wayne L. Furman, Lisa M. McGregor
Journal: Journal of Clinical Oncology (2007)

To study the association between UDP-glucuronosyltransferase 1A1 (UGT1A1) genotypes and severe toxicity as well as irinotecan disposition in pediatric patients with solid tumors receiving low-dose, protracted irinotecan (15 to 75 mg/m2 daily for 5 days for 2 consecutive weeks).Seventy-four patients on five institutional clinical trials received irinotecan (15 to 75 mg/m2) daily intravenously or orally for 5 days for 2 consecutive weeks. Genomic DNA was genotyped for UGT1A1*28, and patients were designated as 6/6, 6/7, or 7/7 depending on the number of TA repeats in the UGT1A1 promoter region. Patients were evaluated for gastrointestinal and hematologic toxicity, as well as baseline and maximal serum bilirubin levels. Toxicity and pharmacokinetic results were evaluated during courses 1 and 2 of irinotecan therapy.The frequencies of 6/6, 6/7, and 7/7 genotypes were 27 (36.5%), 36 (48.6%), and 9 (12.2%) of 74 patients, respectively. Patients with 7/7 genotype had a statistically greater baseline total bilirubin than patients with 6/6 or 6/7 genotype (P = .005). UGT1A1*28 genotype was not associated with grade 3 and 4 neutropenia (P = .21 for course 1; P = .23 for course 2) or diarrhea (P = .176 for course 1; P = .87 for course 2). However, patients with the 7/7 genotype tended to have higher SN-38 area under the plasma time-concentration curve (AUC) values and lower SN-38G/SN-38 AUC ratios.Severe toxicity was not increased in pediatric patients with the 7/7 genotype when treated with a low-dose protracted schedule of irinotecan. Therefore, UGT1A1 genotyping is not a useful prognostic indicator of severe toxicity for patients treated with this irinotecan dosage and schedule.
Diabetes in Employer-Sponsored Health Insurance
Authors: Pamela B. Peele, Judith R. Lave, Thomas J. Songer
Journal: Diabetes Care (2002)

OBJECTIVE—To examine medical and mental health care expenditures for large numbers of individuals with diabetes enrolled in employment-sponsored insurance plans. RESEARCH DESIGN AND METHODS—Health insurance billing data for ∼1.3 million individuals enrolled in health insurance plans sponsored by 862 large self-insured employers nationwide were used to examine employer expenditures and consumer out-of-pocket payments for 20,937 people identified with diabetes. These expenditures were compared with expenditures for individuals with other chronic illnesses. Main outcome measures were covered charges, insurance plan reimbursements, and estimated consumer out-of-pocket payments for both medical and mental health services. RESULTS—A total of 1.7% of enrollees were identified as having diabetes and ∼11% of those used at least one mental health service during 1996. Health care expenditures were three times higher for those with diabetes compared with all health care consumers in these insurance plans, but when compared with individuals with other chronic illnesses such as heart disease, HIV/AIDS, cancer, and asthma, those with diabetes were not more expensive for employers’ insurance plans. Diabetes accounts for 6.5% of total health plan expenditures. CONCLUSIONS—Diabetes is not more expensive for either consumers or their employer-sponsored insurance plans than other chronic illnesses.