tbuckley/cabot-search huggingface dataset:
Coronary artery disease and cardiovascular outcomes in patients with non-alcoholic fatty liver disease
Authors: V. W.-S. Wong, G. L.-H. Wong, G. W.-K. Yip, A. O.-S. Lo, J. Limquiaco, W. C.-W. Chu, A. M.-L. Chim, C.-M. Yu, J. Yu, F. K.-L. Chan, J. J.-Y. Sung, H. L.-Y. Chan
Journal: Gut (2011)

<h3>Objective</h3> Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is associated with cardiovascular risk. The aim of this study was to determine the role of fatty liver in predicting coronary artery disease and clinical outcomes in patients undergoing coronary angiogram. <h3>Methods</h3> This was a prospective cohort study carried out in a University hospital. Consecutive patients who underwent coronary angiogram had ultrasound screening for fatty liver. Significant cardiovascular disease was defined as ≥50% stenosis in at least one coronary artery. The primary outcome was a composite end point comprising cardiovascular deaths, non-fatal myocardial infarction and the need for further coronary intervention during prospective follow-up. <h3>Results</h3> Among 612 recruited patients, 356 (58.2%) had fatty liver by ultrasonography, 318 (52.0%) had elevated serum alanine aminotransferase and 465 (76.0%) had significant coronary artery disease. Coronary artery disease occurred in 84.6% of patients with fatty liver and 64.1% of those without fatty liver (p&lt;0.001). After adjusting for demographic and metabolic factors, fatty liver (adjusted OR 2.31; 95% CI 1.46 to 3.64) and alanine aminotransferase level (adjusted OR 1.01; 95% CI 1.00 to 1.02) remained independently associated with coronary artery disease. At a mean follow-up of 87±22 weeks, 30 (10.0%) patients with fatty liver and 18 (11.0%) patients without fatty liver reached the composite clinical end point (p=0.79). <h3>Conclusions</h3> In patients with clinical indications for coronary angiogram, fatty liver is associated with coronary artery disease independently of other metabolic factors. However, fatty liver cannot predict cardiovascular mortality and morbidity in patients with established coronary artery disease.
Wogonin Induces Eosinophil Apoptosis and Attenuates Allergic Airway Inflammation
Authors: Christopher D. Lucas, David A. Dorward, Sidharth Sharma, Jillian Rennie, Jennifer M. Felton, Ana L. Alessandri, Rodger Duffin, Jurgen Schwarze, Christopher Haslett, Adriano G. Rossi
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites.To investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate eosinophil-dominant allergic inflammation in vivo in mice.Human and mouse eosinophil apoptosis in response to wogonin was investigated by cellular morphology, flow cytometry, mitochondrial membrane permeability, and pharmacological caspase inhibition. Allergic lung inflammation was modeled in mice sensitized and challenged with ovalbumin. Bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation, mucus production, and inflammatory mediator production. Airway hyperresponsiveness to aerosolized methacholine was measured.Wogonin induced time- and concentration-dependent human and mouse eosinophil apoptosis in vitro. Wogonin-induced eosinophil apoptosis occurred with activation of caspase-3 and was inhibited by pharmacological caspase inhibition. Wogonin administration attenuated allergic airway inflammation in vivo with reductions in BAL and interstitial eosinophil numbers, increased eosinophil apoptosis, reduced airway mucus production, and attenuated airway hyperresponsiveness. This wogonin-induced reduction in allergic airway inflammation was prevented by concurrent caspase inhibition in vivo.Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans.
Standard of Anaesthetics in Britain
Authors: P. H. Venn
Journal: BMJ (1954)

<h3>Introduction</h3> An economic and demographic transition with an ageing workforce, evolving work organisation and new emerging risks is combined with a shortage of Occupational Physicians (OPs). This study aims to propose recommendations for future occupational health surveillance (OHS) and the role of OPs. <h3>Methods</h3> First, the PubMed, EU-OSHA and International Labour Organisation databases were screened for literature from 2006 to August 31, 2016, concerning OHS, return-to-work policies and risk management systems in Europe, Japan, Canada and other OECD countries. Second, a standardised mail survey was delivered to all members of the Belgian Professional Association of OPs. <h3>Results</h3> The literature review showed that European directives legally inspired countries to adapt their legislations and develop strategic OHS plans. Nevertheless, the comparison of OHS in different countries shows a varied landscape. The response rate of the survey was 54% (n=262). The results prompt a paradigm shift: Within 5 years, OPs must focus more on return–to–work (96.3%; 95% CI: 93.2% to 98.1%) and risk analyses (84.9%; 95% CI: 79.9% to 88.8%) while training occupational nurses (ONs) to execute routine occupational health examinations (46%; 95% CI: 39.8% to 52.4%). Similarly, a more standardised and multidisciplinary approach to risk assessment should be developed (74.7%; 95% CI: 68.8% to 79.8%). By 2030, OPs would be more specialised in toxicology, disability management, ionising radiation, etc. (42.2%; 95% CI: 36.2% to 48.5%), and ONs would be trained on risk assessments (74.8%; 95% CI: 68.9% to 79.9%) and health promotion (98%; 95% CI: 95.3% to 99.1%). OPs disagree that general practitioners (GPs) could solely execute occupational health examinations (81.7%; 95% CI: 76.4% to 86.1%). <h3>Discussion</h3> The role of OPs must be part of a trend toward evidence-based OHS (i.e., studying the effectiveness and efficiency of ‘fitness for the job assessments’), disability management and engagement with a wide network of stakeholders (such as ONs, GPs and health insurance organisations).
Does Percent Body Fat Predict Outcome in Anorexia Nervosa?
Authors: Laurel E.S. Mayer, Christina A. Roberto, Deborah R. Glasofer, Sarah Fischer Etu, Dympna Gallagher, Jack Wang, Steven B. Heymsfield, Richard N. Pierson, Evelyn Attia, Michael J. Devlin, B. Timothy Walsh
Journal: American Journal of Psychiatry (2007)

Objective: The goal of this study was to investigate the relationship of body composition and neuroendocrine levels with clinical outcome in women with anorexia nervosa in a relapse-prevention trial. Method: Body composition and fasting cortisol and leptin levels were assessed before random assignment in 32 weight-recovered subjects with anorexia nervosa from the New York site of the Fluoxetine to Prevent Relapse in Women With Anorexia Nervosa trial. Clinical outcome at the end of study participation was defined using modified Morgan-Russell criteria (full, good, fair, poor), then dichotomized into treatment "success" or "failure." Results: In a binary logistic regression model examining the effect of percent body fat, body mass index, anorexia nervosa subtype, waist-to-hip ratio, and serum cortisol and leptin levels on treatment outcome, only percent body fat was significantly associated with outcome. Conclusions: In recently weight-restored women with anorexia nervosa, lower percent body fat was associated with poor long-term outcome.
A Clinical Evaluation of Children with Psychotic Parents
Authors: E. JAMES ANTHONY
Journal: American Journal of Psychiatry (1969)

In a metropolitan sample the author found three groups of disturbances among children of psychotic parents: precursive disturbances—forerunners of later adult psychoses; symbiotic—directly attributable to the type of relationship between child and sick parent; and induced or parapsychotic—attributable to the environment. The latter two groups are susceptible to the effects of separation from the psychotic influence; this is less true in the first group, although there is some suggestion that specific therapeutic interventions may help avoid the development of an adult psychosis.
De novo bile salt transporter antibodies as a possible cause of recurrent graft failure after liver transplantation: A novel mechanism of cholestasis
Authors: Verena Keitel, Martin Burdelski, Zsuzsanna Vojnisek, Lutz Schmitt, Dieter Häussinger, Ralf Kubitz
Journal: Hepatology (2009)

Progressive familial intrahepatic cholestasis type 2 (PFIC-2) is caused by mutations of the bile salt export pump (BSEP [ABCB11]), an ATP-binding cassette (ABC)-transporter exclusively expressed at the canalicular membrane of hepatocytes. An absence of BSEP from the canalicular membrane causes cholestasis and leads to liver cirrhosis, which may necessitate liver transplantation in early childhood. We report on the first case of a child with PFIC-2 suffering from repeated posttransplant recurrence of progressive intrahepatic cholestasis due to autoantibodies against BSEP. These antibodies occurred after transplantation and were detected in the patient's serum and at the canalicular membrane of two consecutive liver transplants. The antibodies were reactive toward the first extracellular loop of BSEP, were of high affinity, and inhibited transport activity of BSEP, thus causing severe cholestasis. The patient had three homozygous, missense changes in the BSEP gene. Their combination resulted in the complete absence of BSEP, which explains the lack of tolerance, a prerequisite of autoantibody formation toward BSEP. The findings illustrate a novel disease mechanism due to a new class of functionally relevant autoantibodies resulting in cholestasis and subsequent liver failure. (HEPATOLOGY 2009;50:510–517.)
Vertical blockade of the IGFR- PI3K/Akt/mTOR pathway for the treatment of hepatocellular carcinoma: the role of survivin
Authors: Da-Liang Ou, Bin-Shyun Lee, Liang-In Lin, Jun-Yang Liou, Sheng-Chieh Liao, Chiun Hsu, Ann-Lii Cheng
Journal: Molecular Cancer (2014)

Abstract Background To explore whether combining inhibitors that target the insulin-like growth factor receptor (IGFR)/PI3K/Akt/mTOR signaling pathway (vertical blockade) can improve treatment efficacy for hepatocellular carcinoma (HCC). Methods HCC cell lines (including Hep3B, Huh7, and PLC5) and HUVECs (human umbilical venous endothelial cells) were tested. The molecular targeting therapy agents tested included NVP-AEW541 (IGFR kinase inhibitor), MK2206 (Akt inhibitor), BEZ235 (PI3K/mTOR inhibitor), and RAD001 (mTOR inhibitor). Potential synergistic antitumor effects were tested by median dose-effect analysis in vitro and by xenograft HCC models. Apoptosis was analyzed by flow cytometry (sub-G1 fraction analysis) and Western blotting. The activities of pertinent signaling pathways and expression of apoptosis-related proteins were measured by Western blotting. Results Vertical blockade induced a more sustained inhibition of PI3K/Akt/mTOR signaling activities in all the HCC cells and HUVEC tested. Synergistic apoptosis-inducing effects, however, varied among different cell lines and drug combinations and were most prominent when NVP-AEW541 was combined with MK2206. Using an apoptosis array, we identified survivin as a potential downstream mediator. Over-expression of survivin in HCC cells abolished the anti-tumor synergy between NVP-AEW541 and MK2206, whereas knockdown of survivin improved the anti-tumor effects of all drug combinations tested. In vivo by xenograft studies confirmed the anti-tumor synergy between NVP-AEW541 and MK2206 and exhibited acceptable toxicity profiles. Conclusions Vertical blockade of the IGFR/PI3K/Akt/mTOR pathway has promising anti-tumor activity for HCC. Survivin expression may serve as a biomarker to predict treatment efficacy.
The Heartbreak of Drug Pricing
Authors: Johnathon S. Ross
Journal: Annals of Internal Medicine (2002)

Letters4 June 2002The Heartbreak of Drug PricingJohnathon S. Ross, MD, MPHJohnathon S. Ross, MD, MPHPhysicians for a National Health Program; Toledo, OH 43606 (Ross)Note added in proof: Dr. Ross's letter was submitted in June 2001. In April 2002, the College published a proposal for achieving affordable health insurance coverage for all Americans within the next 7 years (www.acponline.org/hpp/afford_7years.pdf).Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-136-11-200206040-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Dr. Davidoff's appeal to the kind hearts of the pharmaceutical industry to restrict drug pricing (1) is fatally flawed. First, the captains of the drug industry have a fiduciary duty to their stockholders. Unlike health care professionals, they have taken no oath to place the interests of their patients before their own. This is the hallmark of our profession as compared with a corporation. The bottom line is the care of patients, not profits.Second, the idea that reducing prices will increase revenues ignores the fact that our prescriptions determine the product and quantity of drugs sold. ...Reference1. Davidoff F. The heartbreak of drug pricing [Editorial]. Ann Intern Med. 2001;134:1068-71. [PMID: 11388821] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Johnathon S. Ross, MD, MPHAffiliations: Physicians for a National Health Program; Toledo, OH 43606 (Ross)Note added in proof: Dr. Ross's letter was submitted in June 2001. In April 2002, the College published a proposal for achieving affordable health insurance coverage for all Americans within the next 7 years (www.acponline.org/hpp/afford_7years.pdf). PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Heartbreak of Drug Pricing Frank Davidoff The Heartbreak of Drug Pricing Wes Lisker The Heartbreak of Drug Pricing Frank Davidoff Metrics 4 June 2002Volume 136, Issue 11Page: 853KeywordsDrug pricesDrugsHealth careHealth insuranceHeartPrevention, policy, and public health ePublished: 4 June 2002 Issue Published: 4 June 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Reduction of Needle-Stick Injuries During Surgery: The Thimble Solution
Authors: T. Adam Kaspar
Journal: JAMA (1990)

To the Editor.—  Pate 1 recently raised concern about occupational injuries to surgeons in the operating room. Eighty-six percent of surgeons reported at least one puncture injury in the last year, with 53% of the injuries involving the index finger of the nondominant hand. 2 These data are consistent with another study that showed 56% of surgical injuries occurred to the left index finger. 3 Protecting the opposing index finger from needle-stick injuries could reduce the risk of this type of injury to surgeons. The ideal device would protect the surgeon while permitting dexterity.  We suggest the use of a thimble for the opposing index finger to protect against needle-stick injuries. This device is simple, inexpensive, effective, and widely available. Generations of sewers can vouch for its efficacy. The use of this device may potentially decrease surgical needle-stick injuries by approximately 50%.
The Influence of<i>HLA</i>Genotype on AIDS
Authors: Mary Carrington, Stephen J. O'Brien
Journal: Annual Review of Medicine (2003)

Genetic resistance to infectious diseases is likely to involve a complex array of immune-response and other genes with variants that impose subtle but significant consequences on gene expression or protein function. We have gained considerable insight into the genetic determinants of HIV-1 disease, and the HLA class I genes appear to be highly influential in this regard. Numerous reports have identified a role for HLA genotype in AIDS outcomes, implicating many HLA alleles in various aspects of HIV disease. Here we review the HLA associations with progression to AIDS that have been consistently affirmed and discuss the underlying mechanisms behind some of these associations based on functional studies of immune cell recognition.
Impact of the leucocyte immunoglobulin-like receptor A3 (<i>LILRA3</i>) on susceptibility and subphenotypes of systemic lupus erythematosus and Sjögren's syndrome
Authors: Yan Du, Yin Su, Jing He, Yue Yang, Yamei Shi, Yong Cui, Cainan Luo, Xinyu Wu, Xu Liu, Fanlei Hu, Xiaoxu Ma, Li Zheng, Jing Zhang, Xianbo Zuo, Yujun Sheng, Lijun Wu, Xuejun Zhang, Jianping Guo, Zhanguo Li
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Recently, our research group identified the non-deleted (functional) leucocyte immunoglobulin-like receptor A3 (<i>LILRA3</i>) as a new genetic risk for rheumatoid arthritis. <h3>Objectives</h3> To further investigate whether the functional <i>LILRA3</i> is a new susceptibility factor for other autoimmune diseases—for example, systemic lupus erythematosus (SLE) and primary Sjögren9s syndrome (pSS). <h3>Methods</h3> The <i>LILRA3</i> deletion polymorphism and its tagging single nucleotide polymorphism rs103294 were genotyped for 1099 patients with SLE, 403 patients with pSS and 2169 healthy controls. Association analyses were performed in whole dataset or clinical/serological subsets. The impact of <i>LILRA3</i> on SLE activity and LILRA3 expression was evaluated. <h3>Results</h3> The functional <i>LILRA3</i> conferred high susceptibility to both SLE (p=3.51×10<sup>−7</sup>, OR=2.03) and pSS (p=1.40×10<sup>−3</sup>, OR=2.32). It was associated with almost all the clinical/serological features in SLE, especially with leucopenia (p=4.09×10<sup>−7</sup>, OR=2.19) and thrombocytopenia (p=1.68×10<sup>−5</sup>, OR=1.70). In pSS, functional <i>LILRA3</i> was specifically associated with leucopenia (p=4.39×10<sup>−4</sup>, OR=3.25), anti-Ro/SSA-positive subphenotypes (p=4.54×10<sup>−3</sup>, OR=2.34) and anti-La/SSB-positive subphenotypes (p=0.012, OR=2.49). Functional <i>LILRA3</i> conferred higher disease activity in patients with SLE (p=0.044) and higher LILRA3 expression in both SLE (p=5.57×10<sup>−8</sup>) and pSS (p=1.49×10<sup>−7</sup>) than in controls. <h3>Conclusions</h3> Functional <i>LILRA3</i> is a new susceptibility factor for SLE and pSS. It highly predisposes to certain phenotypes such as leucopenia and thrombocytopenia in SLE, and may confer increased disease activity in SLE and a higher risk of leucopenia and autoantibody-positive subphenotypes in pSS.
Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection
Authors: Robert H. Cichewicz, Samir A. Kouzi
Journal: Medicinal Research Reviews (2003)

Abstract 3β‐Hydroxy‐lup‐20(29)‐en‐28‐oic acid (betulinic acid) is a pentacyclic lupane‐type triterpene that is widely distributed throughout the plant kingdom. A variety of biological activities have been ascribed to betulinic acid including anti‐inflammatory and in vitro antimalarial effects. However, betulinic acid is most highly regarded for its anti‐HIV‐1 activity and specific cytotoxicity against a variety of tumor cell lines. Interest in developing even more potent anti‐HIV agents based on betulinic acid has led to the discovery of a host of highly active derivatives exhibiting greater potencies and better therapeutic indices than some current clinical anti‐HIV agents. While its mechanism of action has not been fully determined, it has been shown that some betulinic acid analogs disrupt viral fusion to the cell in a post‐binding step through interaction with the viral glycoprotein gp41 whereas others disrupt assembly and budding of the HIV‐1 virus. With regard to its anticancer properties, betulinic acid was previously reported to exhibit selective cytotoxicity against several melanoma‐derived cell lines. However, more recent work has demonstrated that betulinic acid is cytotoxic against other non‐melanoma (neuroectodermal and malignant brain tumor) human tumor varieties. Betulinic acid appears to function by means of inducing apoptosis in cells irrespective of their p53 status. Because of its selective cytotoxicity against tumor cells and favorable therapeutic index, even at doses up to 500 mg/kg body weight, betulinic acid is a very promising new chemotherapeutic agent for the treatment of HIV infection and cancer. © 2003 Wiley Periodicals, Inc. Med Res Rev, 24, No. 1, 90–114, 2004
THE MORTALITY AND COMPLICATIONS OF DIPHTHERIA
Authors: A. K. Gordon
Journal: BMJ (1925)

<h3>Background</h3> Men who have sex with men (MSM) bear a disproportionate burden of sexually transmitted infections (STIs) including HIV. While routine STI surveillance data indicate MSM regularly access genitourinary medicine (GUM) services for their sexual health care, the extent to which MSM attend non-specialist Level 2 sexual health services is unclear. We investigated access of Level 2 services by MSM in England. <h3>Methods</h3> We used provisional data from the GUM Clinic Activity Dataset (GUMCADv2) to compare the characteristics, service usage and outcomes between MSM accessing GUM and Level 2 services who reported data in 2013. <h3>Results</h3> Of all male attendances where sexual orientation was recorded, 12.3% (6,957/57,048) of Level 2 attendances were among MSM compared to 26.3% (299,456/1,139,424) of GUM attendances (p &lt; 0.001). MSM attending Level 2 compared to GUM services, were younger (mean age: 30.5 yrs vs 38.5 yrs; p &lt; 0.001), and more likely to be of black ethnicity (6.8% vs 4.1%; p &lt; 0.001) and reside in London (49.9% vs 46.0%; p &lt; 0.001). MSM attending non-GUM services were more likely to have a full sexual health screen (41.4% vs 27.0%; p &lt; 0.001), HIV test (8.9% vs 7.1%; p &lt; 0.001), and be diagnosed with chlamydia (6.2% vs 3.0%; p &lt; 0.001), gonorrhoea (5.6% vs 4.6%: p &lt; 0.001) and first-episode genital warts (1.5% vs 1.0%: p &lt; 0.001). There was no significant difference in the proportion newly diagnosed with HIV (0.57% vs 0.69%; p = 0.268) or first-episode genital herpes (0.47% vs 0.46%; p = 0.830). <h3>Conclusion</h3> Level 2 sexual health services play an important role in the sexual health care of MSM, especially those of younger age.
ANTIMICROBIAL-RESISTANT PATHOGENS IN THE 1990s
Authors: George A. Jacoby, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Klebsiella pneumoniae have become increasingly resistant to antimicrobial agents. This chapter reviews the epidemiology of this resistance, its detection in the laboratory, the mechanisms of resistance, and the options for therapy and infection control.
Re: Eric A. Klein, Matthew R. Cooperberg, Cristina Magi-Galluzzi, et al. A 17-gene Assay to Predict Prostate Cancer Aggressiveness in the Context of Gleason Grade Heterogeneity, Tumor Multifocality, and Biopsy Undersampling. Eur Urol 2014;66:550–60
Authors: Yuri Tolkach, Markus Kuczyk, Florian Imkamp
Journal: European Urology (2014)