tbuckley/cabot-search huggingface dataset:
Chronic 17β-Estradiol Replacement Increases Nitric Oxide–Mediated Vasodilation of Guinea Pig Coronary Microcirculation
Authors: Loren P. Thompson, Gerard Pinkas, Carl P. Weiner
Journal: Circulation (2000)

Background —Estrogen is cardioprotective of the coronary circulation by mechanisms incompletely understood. This study determined the effect of chronic 17β-estradiol replacement on dilator responses to acetylcholine and sodium nitroprusside of the isolated coronary microcirculation. Methods and Results —Adult female guinea pigs were ovariectomized, and a 21-day-release pellet containing 0.0, 0.1, 0.25, 0.5, or 1.0 mg 17β-estradiol was implanted subcutaneously. Serum estradiol concentrations ranged from 3.9 to 74.9 pg/mL, increasing with the dose of estradiol. After 19 to 20 days, the animals were euthanized, and their hearts were removed and perfused with buffer at constant flow on an isolated heart apparatus. Both perfusion pressure and contractile force were measured in prostaglandin F 2α –constricted hearts. Vasodilation to the cumulative addition of the endothelium-dependent agonist acetylcholine (10 − 9 to 10 − 5 mol/L) and the nitric oxide (NO) donor sodium nitroprusside (10 − 9 to 10 − 5 mol/L) was measured before and after NO synthesis inhibition by nitro- l -arginine (LNA, 10 − 4 mol/L). Baseline coronary resistance was unaltered by estradiol, although LNA increased resistance in estradiol-treated hearts more than in ovariectomized controls. Chronic 17β-estradiol increased sensitivity (measured by −log EC 50 values) but not maximal response to acetylcholine compared with ovariectomized controls. Differences were abolished by LNA at all doses of estradiol. Sodium nitroprusside–induced dilation was unaffected by estradiol replacement. Conclusions —Chronic 17β-estradiol replacement, at doses producing hormone levels within the physiological range, enhances dilator sensitivity of the coronary microcirculation through enhanced NO production by the endothelium, independent of changes in NO sensitivity of the vascular smooth muscle. Thus, estradiol enhances NO production as a protective mechanism of the coronary microcirculation.
THE INFLUENCE OF AGE AND TYPE OF PATIENT UPON THE COURSE AND TREATMENT OF APPENDICITIS
Authors: W. Billington
Journal: BMJ (1912)

<b>Background:</b> Mediastinal staging in non-small cell lung cancer with endosonography (EUS-FNA plus EBUS-TBNA) followed by mediastinoscopy is more sensitive to detect nodal metastasis as compared to mediastinoscopy alone (ASTER trial, JAMA 2010;304:2245). However 11 patients need to undergo a mediastinoscopy to detect one with N2/3 missed by endosonography. We analysed if FDG-PET identifies patients in whom the mediastinoscopy can be omitted. <b>Methods:</b> In ASTER, 123 patients were randomized to endosonography followed by mediastinoscopy when the former did not show mediastinal metastasis. Sensitivity, negative predictive value (NPV) and number of mediastinoscopies needed to detect one false negative endosonography were calculated in the cases with complete data (n=120; 98%). <b>Results:</b> With PET, 77 patients had FDG-avid mediastinal nodes; the prevalence of N2/3 was 73 (62-81)%. The sensitivity and NPV of endosonography was 88 (76-94) and 75 (57-88)%. Adding mediastinoscopy increased sensitivity and NPV to 96 (88-99) and 91 (73-98)%. 43 patients did not have FDG-avid mediastinal nodes, the prevalence of N2/3 was 23 (13-38)%. The sensitivity and NPV of endosonography was 70 (40-89)% and 92 (78-97)%. Adding mediastinoscopy increased sensitivity and NPV to 80 (49-94)% and 94 (81-98)%. In patients with FDG-avid vs. FDG-cold mediastinal nodes, the number of mediastinoscopies needed to detect one false negative endosonography is 6 vs 36 (p=0.078). <b>Conclusions:</b> A negative endosonography should be followed by a mediastinoscopy if PET positive mediastinal nodes are present. In the absence of PET positive nodes, a mediastinoscopy following a negative endosonography can be omitted.
Kenneth Munro Scott
Authors: K. Mammen
Journal: BMJ (2014)

Kenneth Munro Scott was born in Tsingtao, in the German Crown Colony on Shantung Peninsula, China. He was the youngest of five children, and his parents--Charles Ernest and Clara Heywood Scott--were Presbyterian missionaries in China for 36 years. For the next 30 years, the family was buffeted by the Communist uprising and the Japanese invasion of the Chinese mainland. Ken attended schools in China, but …
Patients with long term conditions can hold health and social care budgets from 2015
Authors: G. Iacobucci
Journal: BMJ (2014)

From next year, patients in England will be able to hold combined health and social care personal budgets for the first time under a new scheme unveiled by the NHS England chief executive, Simon Stevens.

The Integrated Personal Commissioning (IPC) programme will devolve NHS and local government funding to patients, who will be able to direct how and where the money is spent. The programme—due to begin in April 2015—will enable patients to create an individual care plan with their doctor each year using funds contributed from NHS England, clinical commissioning groups, and local authorities.

Funds will initially be targeted at people with long term conditions, including frail elderly people at risk of care home admission, children with complex needs, people with learning disabilities, and …
Selective albuminuria via podocyte albumin transport in puromycin nephrotic rats is attenuated by an inhibitor of NADPH oxidase
Authors: Satoshi Kinugasa, Akihiro Tojo, Tatsuo Sakai, Harukuni Tsumura, Masafumi Takahashi, Yasunobu Hirata, Toshiro Fujita
Journal: Kidney International (2011)
AIDS cuts life expectancy insub-Saharan Africa by a quarter
Authors: D. Logie
Journal: BMJ (1999)

The spread of HIV and AIDS in subSaharan Africa has far exceeded the worst projections, according to speakers at the 11th international conference on AIDS and sexually transmitted diseases in Africa. In 13 countries the prevalence of HIV infection is more than 10% and in some it is as high as 30% At the conference in Lusaka, Zambia, last week, the epidemic was described as an unprecedented threat to the region's economic development.

At the end of 1998, 22.5 million people out of the …
RAGE Expression in Tumor-Associated Macrophages Promotes Angiogenesis in Glioma
Authors: Xuebo Chen, Leying Zhang, Ian Y. Zhang, Junling Liang, Huaqing Wang, Mao Ouyang, Shihua Wu, Anna Carolina Carvalho da Fonseca, Lihong Weng, Yasuhiko Yamamoto, Hiroshi Yamamoto, Rama Natarajan, Behnam Badie
Journal: Cancer Research (2014)

Interaction of RAGE (the receptor for advanced glycation endproducts) with its ligands can promote tumor progression, invasion, and angiogenesis. Although blocking RAGE signaling has been proposed as a potential anticancer strategy, functional contributions of RAGE expression in the tumor microenvironment (TME) have not been investigated in detail. Here, we evaluated the effect of genetic depletion of RAGE in TME on the growth of gliomas. In both invasive and noninvasive glioma models, animal survival was prolonged in RAGE knockout (Ager(-/-)) mice. However, the improvement in survival in Ager(-/-) mice was not due to changes in tumor growth rate but rather to a reduction in tumor-associated inflammation. Furthermore, RAGE ablation in the TME abrogated angiogenesis by downregulating the expression of proangiogenic factors, which prevented normal vessel formation, thereby generating a leaky vasculature. These alterations were most prominent in noninvasive gliomas, in which the expression of VEGF and proinflammatory cytokines were also lower in tumor-associated macrophages (TAM) in Ager(-/-) mice. Interestingly, reconstitution of Ager(-/-) TAM with wild-type microglia or macrophages normalized tumor vascularity. Our results establish that RAGE signaling in glioma-associated microglia and TAM drives angiogenesis, underscoring the complex role of RAGE and its ligands in gliomagenesis.
A prospective study of the causes of notably raised aspartate aminotransferase of liver origin
Authors: M W Whitehead, N D Hawkes, I Hainsworth, J G C Kingham
Journal: Gut (1999)

<h3>BACKGROUND AND AIMS</h3> To ascertain the causes of raised aspartate aminotransferase (AST) presumed to be of hepatic origin in two hospitals and the local community served by a centralised biochemistry laboratory. <h3>METHODS</h3> From June 1996 to February 1997 all patients with AST greater than 400 U/l were identified by the biochemistry laboratory; the patients’ clinical records were studied to determine the diagnosis, the clinical outcome, and whether the raised AST and its significance had been noted. <h3>RESULTS</h3> A total of 137 patients with a hepatic cause for the raised AST were found. The cause of the raised AST was hepatic ischaemia/hypoxia in 68, pancreatobiliary disease in 33, primary hepatocellular disease in 23, hepatic malignancy in five, and hepatic haematoma in one. In seven patients the diagnosis was unclear. The overall mortality was high (22%) with the highest mortality in the hepatic ischaemia group (37%). The recording and interpretation of the causes of raised AST was poor with only 48% having the correct diagnosis. In 38% the raised AST was apparently not noticed by the attending clinicians. <h3>CONCLUSIONS</h3> The commonest cause of a hepatitis like biochemical picture was hepatic hypoxia (50%) followed by pancreatobiliary disease (24%). Drug induced hepatic necrosis (8.8%) was uncommon and viral hepatitis was rare (3.6%). AST concentrations returned towards normal most rapidly in patients with hepatic hypoxia and calculous biliary obstruction. Hepatitis, viral or otherwise, is an uncommon cause of a typical hepatitic biochemical result in this community.
Lessons Learned From SARS Outbreak Prompt Rapid Response to New Coronavirus
Authors: Bridget M. Kuehn
Journal: JAMA (2013)

point, we’ve identified applications of these devices which a device sponsor may not feel is a large enough market to do their own study.” To pay for the ACC and STS study, Holmes said there should be some direct support from Edwards Lifesciences and educational grants to the societies by the valve maker, with certain conditions. “Industry has some fiduciary duties and needs some access to the data, but we need to make sure there are firewalls that mitigate any conflicts of interest,” he said.
Correlation of age, sex, body mass index and sports modality to patellar rotation in jumping athletes
Authors: L D Mendonça, N F N Bittencourt, T R T Santos, A A Silva, S T Fonseca
Journal: British Journal of Sports Medicine (2011)

Background Patellar malalignment reveals a inappropriate tendon traction and could lead to overuse injuries as patellar tendinopathy. There is two angles that describe the frontal patellar rotation: Arno (A) and McConnell (M). There is lack of evidence about the normative data, especially in jumping athletes. Objective analyse the Arno and McConnell's patellar angles profile in jumping athletes. Design observational cross-sectional. Setting all testing occurred at Minas Tênis Club and at Sports Injury Prevention and Rehabilitation Laboratory – LAPREV. Participants 171 volleyball, basketball and gymnastics athletes (41 female and 130 male) were assessed. All participants were healthy, with no current complaints of lower limb injury or pain and no history of previous lower extremity surgery. The average+SD age, height and mass of the athletes was 15.7+5.1 years, 178.2+14.5 cm, 68.3+16.5 Kg. Assessment of risk factors Age, sex, body mass index (BMI) and sports modality were the independent variables. Main outcome measurements frontal plane patellar rotation in stand position with 30° of knee flexion. Results The means for M and A angles at dominant and non-dominant limbs were −0.87 (+4.75), −4.1 (+5.2), 4.6 (+7.34) and 1.35 (+8.1) degrees respectively. Statistic significant differences were found in AD and AnD limbs at female and male group (p=0.001), in MD at modalities female volleyball and male basketball (p=0.012), in AnD at ages between &gt;19 and 7 to 10 (p=0.005), 11 to 14 (p=0.000) and 15 to 19 (p=0.006) and in AD between normal and low BMI groups. Conclusion This study shows normative data about M and A angles in jumping athletes. Some associations were found between sex, age, sports modality and BMI with A angle and modality with M angle. These variables must be considered part of athletes' preseason assessment.
The C8 Health Project: Design, Methods, and Participants
Authors: Stephanie J. Frisbee, A. Paul Brooks, Arthur Maher, Patsy Flensborg, Susan Arnold, Tony Fletcher, Kyle Steenland, Anoop Shankar, Sarah S. Knox, Cecil Pollard, Joel A. Halverson, Verónica M. Vieira, Chuanfang Jin, Kevin M. Leyden, Alan M. Ducatman
Journal: Environmental Health Perspectives (2009)

The C8 Health Project was created, authorized, and funded as part of the settlement agreement reached in the case of Jack W. Leach, et al. v. E.I. du Pont de Nemours & Company (no. 01-C-608 W.Va., Wood County Circuit Court, filed 10 April 2002). The settlement stemmed from the perfluorooctanoic acid (PFOA, or C8) contamination of drinking water in six water districts in two states near the DuPont Washington Works facility near Parkersburg, West Virginia.This study reports on the methods and results from the C8 Health Project, a population study created to gather data that would allow class members to know their own PFOA levels and permit subsequent epidemiologic investigations.Final study participation was 69,030, enrolled over a 13-month period in 2005-2006. Extensive data were collected, including demographic data, medical diagnoses (both self-report and medical records review), clinical laboratory testing, and determination of serum concentrations of 10 perfluorocarbons (PFCs). Here we describe the processes used to collect, validate, and store these health data. We also describe survey participants and their serum PFC levels.The population geometric mean for serum PFOA was 32.91 ng/mL, 500% higher than previously reported for a representative American population. Serum concentrations for perfluorohexane sulfonate and perfluorononanoic acid were elevated 39% and 73% respectively, whereas perfluorooctanesulfonate was present at levels similar to those in the U.S. population.This largest known population study of community PFC exposure permits new evaluations of associations between PFOA, in particular, and a range of health parameters. These will contribute to understanding of the biology of PFC exposure. The C8 Health Project also represents an unprecedented effort to gather basic data on an exposed population; its achievements and limitations can inform future legal settlements for populations exposed to environmental contaminants.
Reduction of morbidity and mortality from biliary complications after liver transplantation
Authors: Andrew S. Klein, Scott Savader, James F. Burdick, Jeffrey Fair, Mack Mitchell, Paul Colombani, Bruce Perler, Floyd Osterman, G. Melville Williams
Journal: Hepatology (1991)

Over a 4-yr period that began October 1, 1986, 103 orthotopic liver transplants were performed on 91 patients at the Johns Hopkins Hospital. Biliary reconstruction at the time of transplantation was performed in standard fashion by an appropriately trained member of the surgical team. Six (7%) patients developed biliary complications, which included three cases of common bile duct stricture and one case each of bile duct obstruction caused by biopsy-related hemobilia, biloma and a retained fragment of a T tube after removal. Five of the six patients were treated successfully by nonoperative interventional radiological procedures performed under local anesthesia with light intravenous sedation. Reoperative surgery (to remove the T-tube fragment from subcutaneous tissue) was required for only one patient, and no deaths (0 of 91) were attributable to biliary complications. All six patients are alive and well 6 to 33 mo after the operation with excellent liver function. Our findings would suggest that most biliary complications of orthotopic liver transplants are avoidable and that the few that do appear can usually be managed both safely and effectively by an interventional radiological approach.
Abstract 637: Antisense transcripts and R-loops caused by DNA topoisomerase I inhibition by camptothecin at human active CpG island promoters.
Authors: Jessica Marinello, Giovanni Chillemi, Susana Bueno, Stefano G. Manzo, Giovanni Capranico
Journal: Cancer Research (2013)

Abstract DNA Topoisomerase I (Top1) is specifically inhibited by camptothecin (CPT), a natural product with effective anticancer activity. CPT can stabilize a DNA-Top1 DNA cleavage complex that can lead to irreversible DNA breakage at replication forks, and transcription-dependent genome instability. The bulk of cellular Top1 activity is required at transcribing regions to modulate DNA supercoils generated by elongating RNA polymerases. However, the molecular effects of CPT inhibition of Top1 at transcriptional levels are not fully established. By next generation sequencing analyses of bisulfite-treated RNAs extracted from human HCT116 cancer cells, we here show that CPT promoted high levels of antisense tags specifically at active promoters containing CpG islands (CGI). We found several not annotated transcripts close to Refseq genes, the majority of which were promoter-associated antisense transcripts increased by CPT. We identified 256 and 84 of such transcripts in HCT116 cells and Top1-silenced HCT116-siRNATop1 cells, respectively. We validated CPT-stimulated antisense transcripts by PCR in both cell lines, and found that several of them could form R-loops at corresponding genomic regions by affinity purification with a recombinant inactive mutant RNaseH1. Drug effects were independent from replication, and required both Top1 and ongoing transcription. In addition, CPT induced an immediate burst and a subsequent rapid reduction of Top1-DNA cleavage complexes at active, but not inactive, promoters indicating a partial, time-dependent removal of Top1 from chromatin. Our findings demonstrate that Top1 activity prevents accumulation of antisense R-loops and RNAs at human active CGI promoters by relaxing negative DNA supercoils. The transcriptional CPT effects can contribute to drug therapeutic activity in cancer and other diseases. We will discuss our findings in relation to transcription regulation and genome instability caused by interference with Top1 activity. Citation Format: Jessica Marinello, Giovanni Chillemi, Susana Bueno, Stefano G. Manzo, Giovanni Capranico. Antisense transcripts and R-loops caused by DNA topoisomerase I inhibition by camptothecin at human active CpG island promoters. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 637. doi:10.1158/1538-7445.AM2013-637
Sustained Remission with Etanercept Tapering in Early Rheumatoid Arthritis
Authors: Paul Emery, Mohammed Hammoudeh, Oliver FitzGerald, Bernard Combe, Emilio Martin-Mola, Maya H. Buch, Marek Krogulec, Theresa Williams, Stefanie Gaylord, Ronald Pedersen, Jack Bukowski, Bonnie Vlahos
Journal: New England Journal of Medicine (2014)

We assessed the effects of reduction and withdrawal of treatment in patients with rheumatoid arthritis who had a remission while receiving etanercept-plus-methotrexate therapy.Patients with early active disease who had not previously received methotrexate or biologic therapy received 50 mg of etanercept plus methotrexate weekly for 52 weeks (open-label phase). We then randomly assigned patients who had qualifying responses at weeks 39 and 52 to receive 25 mg of etanercept plus methotrexate (combination-therapy group), methotrexate alone, or placebo for 39 weeks (double-blind phase). Patients who had qualifying responses at week 39 of the double-blind phase had all treatment withdrawn at that time and were followed to week 65 (treatment-withdrawal phase). The primary end point was the proportion of patients with sustained remission in the double-blind phase.Of 306 patients enrolled, 193 underwent randomization in the double-blind phase; 131 qualified for the treatment-withdrawal phase. More patients in the combination-therapy group than in the methotrexate-alone group or the placebo group met the criterion for the primary end point (40 of 63 [63%] vs. 26 of 65 [40%] and 15 of 65 [23%], respectively; P=0.009 for combination therapy vs. methotrexate alone; P<0.001 for combination therapy vs. placebo). At 65 weeks, 28 patients (44%) who had received combination therapy, 19 (29%) who had received methotrexate alone, and 15 (23%) who had received placebo were in remission (P=0.10 for combination therapy vs. methotrexate alone; P=0.02 for combination therapy vs. placebo; P=0.55 for methotrexate alone vs. placebo). No significant between-group differences were observed in radiographic progression of disease. Serious adverse events were reported in 3 patients (5%) in the combination-therapy group, 2 (3%) in the methotrexate-alone group, and 2 (3%) in the placebo group.In patients with early rheumatoid arthritis who had a remission while receiving full-dose etanercept-plus-methotrexate therapy, continuing combination therapy at a reduced dose resulted in better disease control than switching to methotrexate alone or placebo, but no significant difference was observed in radiographic progression. (Funded by Pfizer; ClinicalTrials.gov number, NCT00913458.).
An American Text-Book of Obstetrics for Practitioners and Students
Authors: James C. Cameron, Richard Cooper Norris, Dickinson, Robert Latou, b.
Journal: JAMA (1895)

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Acropustulosis of infancy
Authors: JULIA A. NEWTON, JENNIFER SALISBURY, A. MARSDEN, D. H. MCGIBBON
Journal: British Journal of Dermatology (1986)

Journal Article Acropustulosis of infancy Get access JULIA A. NEWTON, JULIA A. NEWTON The Dowling Skin Unit and the Institute of Dermatology, The United Medical and Dental Schools, St Thomas's Hospital, Tooting, London, U.K. Dr Julia A.Newton. Search for other works by this author on: Oxford Academic Google Scholar JENNIFER SALISBURY, JENNIFER SALISBURY The London Hospital, Whitechapel, Tooting, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar A. MARSDEN, A. MARSDEN St George's Hospital, Tooting, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar D. H. MCGIBBON D. H. MCGIBBON The Dowling Skin Unit and the Institute of Dermatology, The United Medical and Dental Schools, St Thomas's Hospital, Tooting, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue 6, 1 December 1986, Pages 735–739, https://doi.org/10.1111/j.1365-2133.1986.tb06657.x Published: 01 December 1986 Article history Accepted: 30 May 1986 Published: 01 December 1986