tbuckley/cabot-search huggingface dataset:
Short- and Long-Term Mortality After Myocardial Infarction in Patients With and Without Diabetes
Authors: Sjoerd T. Nauta, Jaap W. Deckers, K. Martijn Akkerhuis, Ron T. van Domburg
Journal: Diabetes Care (2012)

To study temporal trends in short- and long-term outcome after myocardial infarction (MI) according to diabetes status.We included all 14,434 consecutive patients admitted for ST-segment elevation MI or non-ST-segment elevation MI at our center between 1985 and 2008. The study patients were compared according to prevalent diabetes. Temporal trend analyses were performed by comparing decades of admission (1985-1989 vs. 1990-1999 vs. 2000-2008).A total of 2,015 (14%) of the patients had prevalent diabetes. The risk of presenting with diabetes increased from 8 to 17% from 1985 to 2008. Diabetic patients presented with a higher prevalence of cardiovascular risk factors. With time, the use of evidence-based therapies increased in both patients with and without diabetes. Diabetes is associated with a 1.5-fold increased risk of mortality at the 20-year follow-up. Ten-year mortality decreased over time in patients with diabetes, from 53% in 1985-1989 to 39% in 2000-2008 (adjusted hazard ratio 0.56 [95% CI 0.43-0.73]), and in those without diabetes, from 38% in 1985-1989 to 29% in 2000-2008 (0.66 [0.60-0.73]; P interaction = 0.83). Patients with diabetes benefitted from a higher 30-day and 10-year absolute survival increase.Temporal mortality reductions after MI between 1985 and 2008 were at least as high in patients with diabetes compared with those without diabetes. However, long-term mortality remained higher in diabetic patients. Awareness of the high-risk profile of diabetic patients is warranted and might stimulate optimal medical care and outcome.
More toilets in India did not improve health, finds study
Authors: Z. Kmietowicz
Journal: BMJ (2014)

Increasing the number of toilets available to people in rural India did not help to reduce exposure to faecal pathogens or decrease diarrhoea, parasitic worm infections, or child malnutrition, a study has found.

Researchers from the United States, the United Kingdom, and India conducted a cluster randomised controlled trial in 100 villages in India to assess the effect of building extra toilets on health. Although systematic reviews have found that improved sanitation can reduce the prevalence of diarrhoeal disease by 22-36%, studies have been small and the evidence of a health impact is “not strong,” the study said.

Around 2.5 billion people worldwide, a third of whom live in India, lack access to basic sanitation facilities (such as a …
Diabetes and Other Disorders of Glycemia in a Rural South African Community
Authors: Ayesha A. Motala, Tonya Esterhuizen, Eleanor Gouws, Fraser J. Pirie, Mahomed A.K. Omar
Journal: Diabetes Care (2008)

The purpose of this study was to determine the prevalence of diabetes, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG), and associated risk factors in a rural South African black community.This was a cross-sectional survey conducted by random cluster sampling of adults aged >15 years. Participants had a 75-g oral glucose tolerance test using the 1998 World Health Organization criteria for disorders of glycemia.Of 1,300 subjects selected, 1,025 subjects (815 women) participated (response rate 78.9%). The overall age-adjusted prevalence of diabetes was 3.9%, IGT 4.8%, and IFG 1.5%. The prevalence was similar in men and women for diabetes (men 3.5%; women 3.9%) and IGT (men 4.6%; women 4.7%) but higher in men for IFG (men 4.0%; women 0.8%). The prevalence of diabetes and IGT increased with age both in men and women, with peak prevalence in the 55- to 64-year age-group for diabetes and in the >or=65-year age-group for IGT. Of the cases of diabetes, 84.8% were discovered during the survey. In multivariate analysis, the significant independent risk factors associated with diabetes included family history (odds ratio 3.5), alcohol ingestion (2.8), waist circumference (1.1), systolic blood pressure (1.0), serum triglycerides (2.3), and total cholesterol (1.8); hip circumference was protective (0.9).There is a moderate prevalence of diabetes and a high prevalence of total disorders of glycemia, which suggests that this community, unlike other rural communities in Africa, is well into an epidemic of glucose intolerance. There is a low proportion of known diabetes and a significant association with potentially modifiable risk factors.
DNA Replication Licensing Factors and Aneuploidy Are Linked to Tumor Cell Cycle State and Clinical Outcome in Penile Carcinoma
Authors: Oliver J. Kayes, Marco Loddo, Nimish Patel, Pranav Patel, Suks Minhas, Gareth Ambler, Alex Freeman, Alex Wollenschlaeger, David J. Ralph, Kai Stoeber, Gareth H. Williams
Journal: Clinical Cancer Research (2009)

The DNA replication licensing machinery is integral to the control of proliferation, differentiation, and maintenance of genomic stability in human cells. We have analyzed replication licensing factors (RLF), together with DNA ploidy status, to investigate their role in progression of penile squamous cell carcinoma and to assess their utility as novel prognostic tools.In a cohort of 141 patients, we linked protein expression profiles of the standard proliferation marker Ki67 and the RLFs Mcm2 and geminin to clinicopathologic variables, ploidy status, and clinical outcome.Increased Ki67, Mcm2, and geminin levels were each significantly associated with arrested tumor differentiation (P < 0.0001) and aneuploidy (P < or = 0.01). Accelerated cell cycle progression was linked to increasing tumor size, stage, and depth of invasion. Aneuploid tumors significantly correlated with tumor grade (P < 0.0001). Biomarker expression and DNA ploidy status were significant predictors of locoregional disease progression [Mcm2 (P = 0.02), geminin (P = 0.02), Ki67 (P = 0.03), and aneuploidy (P = 0.03)] in univariate analysis. Importantly, aneuploidy was a strong independent prognosticator for overall survival (hazard ratio, 4.19; 95% confidence interval, 1.17-14.95; P = 0.03). Used in conjunction with conventional pathologic information, multiparameter analysis of these variables can stratify patients into low- or high-risk groups for disease progression (Harrell's c-index = 0.88).Our findings suggest that RLFs and tumor aneuploidy may be used as an adjunct to conventional prognostic indicators, identifying men at high risk of disease progression. Our results also identify the DNA replication initiation pathway as a potentially attractive therapeutic target in penile squamous cell carcinoma.
INTRAPERITONEAL AND INTRACEREBRAL ROUTES IN SERUM PROTECTION TESTS WITH THE VIRUS OF EQUINE ENCEPHALOMYELITIS
Authors: Peter K. Olitsky, Carl G. Harford
Journal: The Journal of Experimental Medicine (1938)

Earlier experiments had shown that the sera of animals immunized with active virus have much greater protective potency when serum-virus mixtures are injected intraperitoneally into 12 to 15 day old mice than when given intracerebrally. The present work was concerned with similar tests on sera derived from guinea pigs immunized by vaccines in which the virus had been inactivated by formalin. In comparing the content of antiviral body by means of intracerebral and by intraperitoneal inoculation, it was found that both sera show about the same low degree of neutralizing capacity by the former method. By intraperitoneal inoculation, on the other hand, serum collected from guinea pigs immunized by means of active virus reveals high protective power, while that from animals receiving formolized, inactive virus exhibits lower neutralization titers which approach those obtained by the intracerebral method. The significance of this unexpected finding is discussed.
IMMUNE COMPLEX DISEASES
Authors: J. J. Cream
Journal: British Journal of Dermatology (1971)

Journal Article IMMUNE COMPLEX DISEASES Get access J. J. Cream J. J. Cream Department of Dermatology, Middlesex Hospital, London, W.l Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 85, Issue 2, 1 August 1971, Pages 189–191, https://doi.org/10.1111/j.1365-2133.1971.tb07209.x Published: 01 August 1971
Reply to B. Gyawali et al
Authors: Maiko Fujimori, Yosuke Uchitomi
Journal: Journal of Clinical Oncology (2014)

We thank Gyawali et al 1 for their questions and concerns regarding our recent report of a randomized controlled trial (RCT) on communication skills training (CST). 2 Their first comment is that the percentage of oncologists who wanted to participate in our study is lower (19.6%)than expected; they suggest as reasons for this that Japanese oncologists suffer fewer patient complaints and feel confident in communicating with their patients.As we reviewed previous RCTs on communication skills training, we found participant rates of 15% (81 of 550) for oncologists in the report by Razavi et al 3 and Delvaux et al, 4 and 18% for nurses and 55% for physician trainees in the article by Curtis et al. 5 However, in our study, 11 of 15 (73%) oncologists assigned to the control group participated in the CST workshop after the study.More than 80% of oncologists in Japan reported some perceived burden when communicating bad news to patients. 6Therefore, we disagree with the claim by Gyawali et al 1 that the participant rate is low, owing to that Japanese oncologists feel less difficulty with bad news communication.On the other hand, we agree with their claim that many Japanese oncologists may have no time to study communication skills because they are always busy and do not know what benefit CST will provide.Therefore, we believe that our study published in Journal of Clinical Oncology will contribute to the promotion of oncologists' understanding of CST.
Manipulating nucleosome disfavoring sequences allows fine-tune regulation of gene expression in yeast
Authors: Tali Raveh-Sadka, Michal Levo, Uri Shabi, Boaz Shany, Leeat Keren, Maya Lotan-Pompan, Danny Zeevi, Eilon Sharon, Adina Weinberger, Eran Segal
Journal: Nature Genetics (2012)
Exposure to nitrogen dioxide may be associated with severity of virus related asthma exacerbations
Authors: G P Currie
Journal: Thorax (2003)

▴ Chauhan AJ, Inskip HM, Linaker CH, et al . Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children. Lancet2003;361:1939–44 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Respiratory viruses are considered to be one of the main triggers of asthma exacerbations in children. Exposure to nitrogen dioxide (NO2), a common environmental pollutant, has been linked to respiratory symptoms in both children and adults. Whether high individual exposure to NO2 increases the severity … [1]: {openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DChauhan%26rft.auinit1%253DA.%2BJ.%26rft.volume%253D361%26rft.issue%253D9373%26rft.spage%253D1939%26rft.epage%253D1944%26rft.atitle%253DPersonal%2Bexposure%2Bto%2Bnitrogen%2Bdioxide%2B%2528NO2%2529%2Band%2Bthe%2Bseverity%2Bof%2Bvirus-induced%2Basthma%2Bin%2Bchildren.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252803%252913582-9%26rft_id%253Dinfo%253Apmid%252F12801737%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0140-6736(03)13582-9&link_type=DOI [3]: /lookup/external-ref?access_num=12801737&link_type=MED&atom=%2Fthoraxjnl%2F58%2F9%2F802.atom [4]: /lookup/external-ref?access_num=000183359700009&link_type=ISI
Efficient Generation of a Hepatitis B Virus Cytotoxic T Lymphocyte Epitope Requires the Structural Features of Immunoproteasomes
Authors: Alice J.A.M. Sijts, Thomas Ruppert, Barbara Rehermann, Marion Schmidt, Ulrich Koszinowski, Peter-M. Kloetzel
Journal: The Journal of Experimental Medicine (2000)

Interferon (IFN)-γ–induced cells express the proteasome subunits low molecular weight protein (LMP)2, LMP7, and MECL-1 (multicatalytic endopeptidase complex–like 1), leading to the formation of immunoproteasomes. Although these subunits are thought to optimize MHC class I antigen processing, the extent of their role and the mechanistic aspects involved remain unclear. Herein, we study the proteolytic generation of an human histocompatibility leukocyte antigen (HLA)-Aw68–restricted hepatitis B virus core antigen (HBcAg) cytotoxic T lymphocyte (CTL) epitope that is recognized by peripheral blood lymphocytes from patients with acute self-limited but not chronic hepatitis B virus (HBV). Immunological data suggest that IFN-γ–induced rather than uninduced HeLa cells process and present the HBV CTL epitope upon infection with HBcAg-expressing vaccinia viruses. Analyses of 20S proteasome digests of synthetic polypeptides covering the antigenic HBcAg peptide demonstrate that only immunoproteasomes efficiently perform the cleavages needed for the liberation of this HBV CTL epitope. Although the concerted presence of the three immunosubunits appears essential, we find that both catalytically active LMP7 and inactive LMP7 T1A support CTL epitope generation. We conclude that LMP7 influences the structural features of 20S proteasomes, thereby enhancing the activity of the LMP2 and MECL-1 catalytic sites, which provide cleavage specificity. Thus, LMP7 incorporation is of greater functional importance for the generation of an HBV CTL epitope than cleavage specificity.
Cross sectional screening of health care workers (HCW) at a regional chest clinic with an interferon gamma release assay (IGRA): First report from Sri Lanka
Authors: Dushantha Madegedara, Champa Ratnatunga, Vasanthi Thevanesam, Dhamith Nandadeva, Athula Kumara
Journal: European Respiratory Journal (2014)

Introduction :Screening of HCW for latent tuberculosis (LTBI) is not a routine practice in Sri Lanka, even in moderate risk health care settings.

Aim: To evaluate the use of a commercial IGRA (TSPOT.TB Oxford Immunotec, Abingdon, UK) for HCW screening in an intermediate burden, endemic setting.

Method: 39 HCW (70% of total) working at a regional chest clinic (outpatient treatment of over 200 smear positive TB patients per year) were screened with the IGRA. The Mantoux test had been done on 36 participants as a part of another study 6 months earlier. All participants were BCG vaccinated at birth and none had active TB.

Results: Mantoux and IGRA positivity in HCW was 47% and 16% respectively, with a significantly lower IGRA positive rate (p=0.003). Of the HCW who had valid results in both tests, 5 were both IGRA and Mantoux positive, 12 were Mantoux positive and IGRA negative, and 18 were negative with both tests. None had a negative Mantoux with a positive IGRA. Multiple logistic regression showed that working in crowded poorly ventilated areas was a significant risk factor for Mantoux positivity (p=0.020, OR(adj)=10.02) but age, gender, working in high risk areas and duration of service at the clinic were not. Though short duration of service (p=0.036) and male gender (p=0.035) were significantly associated with IGRA positivity in univariate analysis, multiple regression showed that none of the above risk factors were associated. Agreement between the two tests was fair (κ=0.3).

Conclusion: The IGRA offers more specific evidence for LTBI than the Mantoux, but positivity is not associated with known risk factors in this setting.
β1-Integrin Circumvents the Antiproliferative Effects of Trastuzumab in Human Epidermal Growth Factor Receptor-2–Positive Breast Cancer
Authors: David Lesniak, Yaoxian Xu, Jean Deschenes, Raymond Lai, John Thoms, David Murray, Sunita Gosh, John R. Mackey, Siham Sabri, Bassam Abdulkarim
Journal: Cancer Research (2009)

Abstract Resistance to trastuzumab, the monoclonal antibody targeting human epidermal growth factor receptor 2 (HER-2), is a major concern for HER-2–positive metastatic breast cancer (MBC) patients. To date, HER-2 status is the only available biomarker for selecting patients for trastuzumab-based therapy. β1-Integrin, an adhesion molecule involved in cell survival and drug resistance, shares common downstream signaling elements with HER-2, such as the phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase-1/2 (ERK1/2) pathways. The significance of β1-integrin expression in HER-2–positive breast cancer and its involvement in a patient's response to trastuzumab-based therapy are unknown. We show here that overexpression of β1-integrin is an independent negative prognostic factor for tumor progression of HER-2–positive MBC patients treated with trastuzumab-based chemotherapy. Enforced overexpression of β1-integrin, its small interfering RNA–induced knockdown or treatment with a β1-integrin–blocking antibody in HER-2–positive breast cancer cells, identified a strong inverse relationship between expression level of β1-integrin and in vitro sensitivity to trastuzumab. Notably, β1-integrin overexpression increased the phosphorylation of Akt-Ser473 and ERK1/2, thereby promoting survival and mitogenic signals to bypass the antiproliferative effects of trastuzumab. Our findings show that β1-integrin provides a novel independent prognostic biomarker of trastuzumab response in HER-2–positive MBC patients and suggest a new target to augment the antiproliferative effects of trastuzumab. [Cancer Res 2009;69(22):8620–8]
Future needs for ERCP: incidence of conditions leading to bile duct obstruction and requirements for diagnostic and therapeutic biliary procedures.
Authors: M W Gear, N A Dent, D G Colin-Jones, J H Lennard-Jones, J R Colley
Journal: Gut (1990)

Although the development of endoscopic methods of treatment for biliary obstruction has proceeded rapidly in recent years, endoscopic retrograde cholangiopancreatographic (ERCP) services are patchily distributed. A recent survey by the British Society of Gastroenterology has shown that almost half the district general hospitals questioned did not have a sphincterotomy service available locally. To assess the level of provision required, two investigations have been undertaken. Firstly, an epidemiological study of bile duct obstruction has been carried out in the South Western Region. Secondly, the actual surgical and endoscopic workload in treating obstructive jaundice has been analysed in two health districts. Using present incidence and treatment rates at least 50 ERCPs per 100,000 of the population per year are estimated to be required in the future. Surgical treatment rates can be expected to fall as the number of therapeutic ERCPs increases. The implications of this estimate in equipment and staffing terms are discussed.
Blocking the Raf/MEK/ERK Pathway Sensitizes Acute Myelogenous Leukemia Cells to Lovastatin-Induced Apoptosis
Authors: Jianghong Wu, W. Wei-Lynn Wong, Fereshteh Khosravi, Mark D. Minden, Linda Z. Penn
Journal: Cancer Research (2004)

The statin family of drugs are well-established inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase and are used clinically in the control of hypercholesterolemia. Recent evidence, from ourselves and others, shows that statins can also trigger tumor-specific apoptosis by blocking protein geranylgeranylation. We and others have proposed that statins disrupt localization and function of geranylgeranylated proteins responsible for activating signal transduction pathways essential for the growth and/or survival of transformed cells. To explore this further, we have investigated whether the mitogen-activated protein kinase (MAPK) signaling cascades play a role in regulating statin-induced apoptosis. Cells derived from acute myelogenous leukemia (AML) are used as our model system. We show that p38 and c-Jun NH2-terminal kinase/stress-activated kinase MAPK pathways are not altered during lovastatin-induced apoptosis. By contrast, exposure of primary and established AML cells to statins results in significant disruption of basal extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Addition of geranylgeranyl PPi reverses statin-induced loss of ERK1/2 phosphorylation and apoptosis. By establishing and evaluating the inducible Raf-1:ER system in AML cells, we show that constitutive activation of the Raf/MAPK kinase (MEK)/ERK pathway significantly represses but does not completely block lovastatin-induced apoptosis. Our results strongly suggest statins trigger apoptosis by regulating several signaling pathways, including the Raf/MEK/ERK pathway. Indeed, down-regulation of the Raf/MEK/ERK pathway potentiates statin-induced apoptosis because exposure to the MEK1 inhibitor PD98059 sensitizes AML cells to low, physiologically achievable concentrations of lovastatin. Our study suggests that lovastatin, alone or in combination with a MEK1 inhibitor, may represent a new and immediately available therapeutic approach to combat tumors with activated ERK1/2, such as AML.
Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group
Authors: W. Schmiegel, A. Reinacher-Schick, D. Arnold, S. Kubicka, W. Freier, G. Dietrich, M. Geißler, S. Hegewisch-Becker, A. Tannapfel, M. Pohl, A. Hinke, H.J. Schmoll, U. Graeven
Journal: Annals of Oncology (2013)
Prevalence and incidence rates of psoriatic arthritis in central Norway: data from the Nord-Trøndelag Health Study (HUNT)
Authors: Mari Hoff, Agnete Malm Gulati, Pål Richard Romundstad, Arthur Kavanaugh, Glenn Haugeberg
Journal: Annals of the Rheumatic Diseases (2013)

A wide range in the prevalence (<0.01-0.25%) and incidence (0.5-23.1/100 000) of psoriatic arthritis (PsA) is reported. The main objective of this study was to examine the prevalence and incidence of PsA in central Norway.The patients were recruited from the Nord-Trøndelag Health Study 3, a population study carried out in 2006-2008. All 94 194 inhabitants aged >20 years were invited and 50 806 (54%) responded. The study consisted of a questionnaire (Q1) and a brief medical examination. Q1 included questions if the persons suffered from psoriasis, rheumatoid arthritis (RA) or ankylosing spondylitis (AS). Patients with self-reported psoriasis further answered a specific questionnaire on psoriasis including a questionnaire concerning PsA. In order to identify patients with PsA we used the following criteria: Persons reporting they had or may have PsA; persons answering that they had psoriasis and RA; and persons answering that they had psoriasis and AS. Using this approach, 1278 patients were identified. Hospital files were evaluated by a rheumatologist according to a predefined protocol to verify the diagnosis of PsA.338 patients, 144 men and 194 women, were verified to have PsA. The prevalence of PsA was 6.7 (95% CI 5.9 to 7.4) per 1000 inhabitants >20 years with no significant difference between men and women. In the 9-year period of 2000-2008, a total of 188 patients were diagnosed with PsA, which give an incidence rate of 41.3/100 000 (35.8-47.6).The prevalence of PsA in central Norway appears to be higher than previously reported. The reason for this is unknown and may include environmental factors, life style factors and genetic differences.