tbuckley/cabot-search huggingface dataset:
Intermediate- and Long-Term Cognitive Outcomes After Cardiovascular Procedures in Older Adults
Authors: Howard A. Fink, Laura S. Hemmy, Roderick MacDonald, Maureen H. Carlyle, Carin M. Olson, Maurice W. Dysken, J. Riley McCarten, Robert L. Kane, Santiago A. Garcia, Indulis R. Rutks, Jeannine Ouellette, Timothy J. Wilt
Journal: Annals of Internal Medicine (2015)

Background: Risks for intermediate- and long-term cognitive impairment after cardiovascular procedures in older adults are poorly understood. Purpose: To summarize evidence about cognitive outcomes in adults aged 65 years or older at least 3 months after coronary or carotid revascularization, cardiac valve procedures, or ablation for atrial fibrillation. Data Sources: MEDLINE, Cochrane, and Scopus databases from 1990 to January 2015; ClinicalTrials.gov; and bibliographies of reviews and eligible studies. Study Selection: English-language trials and prospective cohort studies. Data Extraction: One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and strength of evidence (SOE). Data Synthesis: 17 trials and 4 cohort studies were included; 80% of patients were men, and mean age was 68 years. Cognitive function did not differ after the procedure between on- and off-pump coronary artery bypass grafting (CABG) (n = 6; low SOE), hypothermic and normothermic CABG (n = 3; moderate to low SOE), or CABG and medical management (n = 1; insufficient SOE). One trial reported lower risk for incident cognitive impairment with minimal versus conventional extracorporeal CABG (risk ratio, 0.34 [95% CI, 0.16 to 0.73]; low SOE). Two trials found no difference between surgical carotid revascularization and carotid stenting or angioplasty (low and insufficient SOE, respectively). One cohort study reported increased cognitive decline after transcatheter versus surgical aortic valve replacement but had large selection and outcome measurement biases (insufficient SOE). Limitations: Mostly low to insufficient SOE; no pertinent data for ablation; limited generalizability to the most elderly patients, women, and persons with substantial baseline cognitive impairment; and possible selective reporting and publication bias. Conclusion: Intermediate- and long-term cognitive impairment in older adults attributable to the studied cardiovascular procedures may be uncommon. Nevertheless, clinicians counseling patients before these procedures should discuss the uncertainty in their risk for adverse cognitive outcomes. Primary Funding Source: Agency for Healthcare Research and Quality.
LIVER DISEASE AMONG HOMOSEXUAL MALES
Authors: W.R. Ellis, IainM. Murray-Lyon, J.C. Coleman, B.A. Evans, J.L. Fluker, J. Bull, P.W.N. Keeling, P.D. Simmons, J.E. Banatvala, J.R. Willcox, R.P.H. Thompson
Journal: The Lancet (1979)
Emotional Aspects of Never Events
Authors: Jarek Kobiela, Paulina Kobiela
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Closed-Loop Systems: Diversity and Natural Selection
Authors: Stuart A. Weinzimer
Journal: Diabetes Care (2012)

When Charles Darwin sailed the HMS Beagle to the Galapagos Islands in 1835, he was moved and inspired by the incredible diversity in the species of finches and tortoises, leading ultimately to the formulation of his ideas on the origin of species and natural selection. One might have been similarly moved during a recent meeting of the Juvenile Diabetes Research Foundation (JDRF) Artificial Pancreas Project Consortium, held during the annual Scientific Sessions of the American Diabetes Association—in a somewhat less exotic location in downtown Philadelphia. In the relative absence of selective pressure (i.e., with the generous financial support of the JDRF and the National Institute of Diabetes and Digestive and Kidney Diseases), an incredibly rich and varied bio(engineering) diversity has been allowed to flourish in the environment of closed-loop artificial pancreas research. Multiple species of glucose sensors, insulin pumps, and particularly algorithm and controller designs, combined in various permutations to populate the display tables and research presentations during the meeting. This open environment is appropriate and conducive for the early stages of system development; allowing broad creative and engineering latitude should maximize the likelihood of the generation of successful closed-loop devices. However, now that the first “in-human” feasibility studies are rolling out and researchers, funders, and regulatory agencies are evaluating their early results, the first waves of selective pressures are starting to be felt. Each group has its favorite sensor or pump; …
Systemic Actinomyces infection. A potential complication of intrauterine contraceptive devices
Authors: S. M. de la Monte
Journal: JAMA (1982)

Infections caused by Actinomyces organisms have been demonstrated to occur in association with IUD use. Uterine actinomycosis infection is usually superficial, but it is potentially invasive. It may prove fatal. When Actinomyces is detected in a vaginal Papanicolaou smear, establishment of the correct diagnosis followed by IUD removal and appropriate antibiotic therapy are recommended. A case history is presented of a 28 year old woman who had been using an IUD and who had systemic Actinomyces infection and a brain abscess develop several years after removal of her uterus and fallopian tubes. The woman was referred to the Johns Hopkins Hospital in Baltimore in 1977 for evaluation of headaches and grand mal seizures. 4 years earlier, in 1973, she had been seen at another hospital with a recent weight loss of 18 kg. She was found to have a tubo-ovarian abscess, for which she underwent a hysterectomy, bilateral salpingectomy, and unilateral oophorectomy. At the time of surgery, an IUD was in place. A histopathological diagnosis of botryomycosis tubo-ovarian abscess was made on submitted tissues. She received no antibiotic therapy. In 1975, pulmonary infiltrates developed that were attributed to bronchopneumonia. She was treated with a short course of tetracycline hydrochloride. Later that year she was thought to have sarcoidosis and was treated for 1 year with several doses of prednisone. Clinically, her condition remained stable until March 1977, when a pyogenic subcostal abscess was drained. In July 1977, she had headache, dizziness, generalized seizures, and an incomplete right homonymous hemianopsia develop. A craniotomy for excision and drainage of an abscess was performed. The presence of Actinomyces israelii in brain tissue was confirmed by direct immunoflourescence using specific antiserum. It was confirmed that Actinomyces had been present at the time of her 1st surgical procedure. She was treated with high doses of intravenous penicillin G potassium for the first 4 weeks, followed by lower doses of oral penicillin V potassium for an additional 15 months. She recovered completely, except for a persistent right homonymous hemianopsia. The case illustrates that systemic dissemination and potentially life threatening complications of uterine actinomycosis can occur if the infection is unrecognized and/or inadequately treated.
Targeting the Transposase Domain of the DNA Repair Component Metnase to Enhance Chemotherapy
Authors: Elizabeth A. Williamson, Leah Damiani, Andrei Leitao, Chelin Hu, Helen Hathaway, Tudor Oprea, Larry Sklar, Montaser Shaheen, Julie Bauman, Wei Wang, Jac A. Nickoloff, Suk-Hee Lee, Robert Hromas
Journal: Cancer Research (2012)

Abstract Previous studies have shown that the DNA repair component Metnase (SETMAR) mediates resistance to DNA damaging cancer chemotherapy. Metnase has a nuclease domain that shares homology with the Transposase family. We therefore virtually screened the tertiary Metnase structure against the 550,000 compound ChemDiv library to identify small molecules that might dock in the active site of the transposase nuclease domain of Metnase. We identified eight compounds as possible Metnase inhibitors. Interestingly, among these candidate inhibitors were quinolone antibiotics and HIV integrase inhibitors, which share common structural features. Previous reports have described possible activity of quinolones as antineoplastic agents. Therefore, we chose the quinolone ciprofloxacin for further study, based on its wide clinical availability and low toxicity. We found that ciprofloxacin inhibits the ability of Metnase to cleave DNA and inhibits Metnase-dependent DNA repair. Ciprofloxacin on its own did not induce DNA damage, but it did reduce repair of chemotherapy-induced DNA damage. Ciprofloxacin increased the sensitivity of cancer cell lines and a xenograft tumor model to clinically relevant chemotherapy. These studies provide a mechanism for the previously postulated antineoplastic activity of quinolones, and suggest that ciprofloxacin might be a simple yet effective adjunct to cancer chemotherapy. Cancer Res; 72(23); 6200–8. ©2012 AACR.
Aims and Content of the Medical Curriculum
Authors: A. M. Jones
Journal: BMJ (1956)

Committee on Medical Education of the British Medical Association listed its own suggestions in the report already referred to (British Medical Journal, 1956), and this article may end with a glance at them.The main theme is the continuation of medical education throughout life, undergraduate education being regarded as a preparation for this.Translation of this ideal into practice involves innumerable problems over the whole range of medical work.First, there are the problems common to all doctors, such as methods of study, keeping up to date, travel, writing, and facilities such as libraries and technical aids of all kinds.Second, there are the problems of training men for the very numerous medical careers.Obviously a judicious selection of topics for discussion will be necessary.The task of planning is in most capable hands, and there can be no doubt that the Second World Conference will be as stimulating and helpful as the first. SummaryThe First World Conference on Medical Education reaffirmed the professional ideal of medicine, and the papers as a whole deal with the translation of this ideal into practice.The best preparation for medicine is a balanced education in both arts and science up to the end of schooldays.Medical faculties should not impose special admission requirements, official or unofficial.No subject should be studied at school because of its potential technical value in medicine.For medical pur- poses chemistry, physics, and biology are best studied at the university.English grammar could with advantage be taught both historically and comparatively.English literature should include works from each century, including the twentieth, and also current newspapers.Since the medical course is a preparation for post- graduate study, less should be taught, and taught better.The Second World Conference on Medical Education, due in 1959, is on postgraduate medical education, and may well present medicine as a lifelong study.
How does tibial cartilage volume relate to symptoms in subjects with knee osteoarthritis?
Authors: A E Wluka
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> No consistent relationship between the severity of symptoms of knee osteoarthritis (OA) and radiographic change has been demonstrated. <b>Objectives:</b> To determine the relationship between symptoms of knee OA and tibial cartilage volume, whether pain predicts loss of cartilage in knee OA, and whether change in cartilage volume over time relates to change in symptoms over the same period. <b>Method:</b> 132 subjects with symptomatic, early (mild to moderate) knee OA were studied. At baseline and 2 years later, participants had MRI scans of their knee and completed questionnaires quantifying symptoms of knee OA (knee-specific WOMAC: pain, stiffness, function) and general physical and mental health (SF-36). Tibial cartilage volume was determined from the MRI images. <b>Results:</b> Complete data were available for 117 (89%) subjects. A weak association was found between tibial cartilage volume and symptoms at baseline. The severity of the symptoms of knee OA at baseline did not predict subsequent tibial cartilage loss. However, weak associations were seen between worsening of symptoms of OA and increased cartilage loss: pain (<i>r</i><sub>s</sub> = 0.28, p = 0.002), stiffness (<i>r</i><sub>s</sub> = 0.17, p = 0.07), and deterioration in function (<i>r</i><sub>s</sub> = 0.21, p = 0.02). <b>Conclusion:</b> Tibial cartilage volume is weakly associated with symptoms in knee OA. There is a weak association between loss of tibial cartilage and worsening of symptoms. This suggests that although cartilage is not a major determinant of symptoms in knee OA, it does relate to symptoms.
Immunomodulatory role of proteinase-activated receptor-2
Authors: Anne Crilly, Helen Palmer, Mohammad B Nickdel, Lynette Dunning, John C Lockhart, Robin Plevin, Iain B Mcinnes, William R Ferrell
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> Proteinase-activated receptor-2 (PAR<sub>2</sub>) has been implicated in inflammatory articular pathology. Using the collagen-induced arthritis model (CIA) the authors have explored the capacity of PAR<sub>2</sub> to regulate adaptive immune pathways that could promote autoimmune mediated articular damage. <h3>Methods</h3> Using PAR<sub>2</sub> gene deletion and other approaches to inhibit or prevent PAR<sub>2</sub> activation, the development and progression of CIA were assessed via clinical and histological scores together with ex vivo immune analyses. <h3>Results</h3> The progression of CIA, assessed by arthritic score and histological assessment of joint damage, was significantly (p&lt;0.0001) abrogated in PAR<sub>2</sub> deficient mice or in wild-type mice administered either a PAR<sub>2</sub> antagonist (ENMD-1068) or a PAR<sub>2</sub> neutralising antibody (SAM11). Lymph node derived cell suspensions from PAR<sub>2</sub> deficient mice were found to produce significantly less interleukin (IL)-17 and IFNγ in ex vivo recall collagen stimulation assays compared with wild-type littermates. In addition, substantial inhibition of TNFα, IL-6, IL-1β and IL-12 along with GM-CSF and MIP-1α was observed. However, spleen and lymph node histology did not differ between groups nor was any difference detected in draining lymph node cell subsets. Anticollagen antibody titres were significantly lower in PAR<sub>2</sub> deficient mice. <h3>Conclusion</h3> These data support an important role for PAR<sub>2</sub> in the pathogenesis of CIA and suggest an immunomodulatory role for this receptor in an adaptive model of inflammatory arthritis. PAR<sub>2</sub> antagonism may offer future potential for the management of inflammatory arthritides in which a proteinase rich environment prevails.
Phase II Trial of Bevacizumab in Combination with Weekly Docetaxel in Metastatic Breast Cancer Patients
Authors: Bhuvaneswari Ramaswamy, Anthony D. Elias, Nicole T. Kelbick, Angela Dodley, Mark Morrow, Marsha Hauger, Joan Allen, Chris Rhoades, Kari Kendra, Helen X. Chen, S. Gail Eckhardt, Charles L. Shapiro
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To evaluate the safety and efficacy of bevacizumab and weekly docetaxel as first- or second-line therapy in patients with metastatic breast cancer (MBC). Patients and Methods: Twenty-seven MBC patients received i.v. bevacizumab at 10 mg/kg on days 1 and 15 in combination with i.v. docetaxel 35 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Primary end points were to assess toxicity, overall response rate, and progression-free survival. A secondary end point was to assess the relationship between plasma endothelial and cell adhesion markers and clinical outcomes. Results: One-hundred fifty-eight treatment cycles were administered with a median of six cycles (range 1-15 cycles) per patient. The most common grade 4 toxicities per patient were as follows: 2 (7%)—pulmonary embolus, 1 (4%)—febrile neutropenia, and 1 (4%)—infection; grade 3 toxicities were 4 (15%)—neutropenia, 4 (15%)—fatigue, 2 (7%)—neuropathy, 2 (7%)—athralgias, 2 (7%)—stomatitis, 1 (7%)—pleural effusion, and 1 (4%)—hypertension. The overall response rate was 52% [95% confidence interval (95% CI), 32-71%], median response duration was 6.0 months (95% CI, 4.6-6.5 months), and the median progression-free survival was 7.5 months (95% CI, 6.2-8.3 months). In hypothesis-generating univariate and limited multivariate analyses, E-selectin was statistically significantly associated with response to the combination. Conclusion: Bevazicumab in combination with weekly docetaxel is active with acceptable toxicities in MBC. Additional studies evaluating E-selectin as a marker of response to bevacizumab-containing chemotherapy are warranted.
Increased Endothelial Exocytosis and Generation of Endothelin-1 Contributes to Constriction of Aged Arteries
Authors: Aditya Goel, Baogen Su, Sheila Flavahan, Charles J. Lowenstein, Dan E. Berkowitz, Nicholas A. Flavahan
Journal: Circulation Research (2010)

Circulating levels of endothelin (ET)-1 and endogenous ET(A)-mediated constriction are increased in human aging. The mechanisms responsible are not known.Investigate the storage, release, and activity of ET-1 system in arteries from young and aged Fischer-344 rats.After NO synthase inhibition (L-NAME), thrombin contracted aged arteries, which was inhibited by endothelial denudation, ET(A) receptor antagonism (BQ123), and ECE inhibition (phosphoramidon, SM19712) or by inhibiting exocytosis (TAT-NSF, N-ethylmaleimide-sensitive factor inhibitor). Thrombin did not cause endothelium-dependent contraction of young arteries. In aged but not young arteries, thrombin rapidly increased ET-1 release, which was abolished by endothelium denudation or TAT-NSF. L-NAME did not affect ET-1 release. ET-1 immunofluorescent staining was punctate and distinct from von Willebrand factor (VWF). VWF and ET-1 immunofluorescent intensity was similar in young and aged quiescent arteries. Thrombin rapidly increased ET-1 staining and decreased VWF staining in aged but had no effect in young aortas. After L-NAME, thrombin decreased VWF staining in young aortas. NO donor DEA-NONOate (1 to 100 nmol/L) reversed thrombin-induced exocytosis in young (VWF) but not aged L-NAME-treated aortas (VWF, ET-1). Expression of preproET-1 mRNA and ECE-1 mRNA were increased in aged compared to young endothelium. BigET-1 levels and contraction to exogenous BigET-1 (but not ET-1) were also increased in aged compared to young arteries.The stimulated exocytotic release of ET-1 is dramatically increased in aged endothelium. This reflects increased reactivity of exocytosis, increased expression and storage of ET-1 precursor peptides, and increased expression of ECE-1. Altered endothelial exocytosis of ET-1 and other mediators may contribute to cardiovascular pathology in aging.
Long-term outcome in polymyositis and dermatomyositis
Authors: I M Bronner, M F G van der Meulen, M de Visser, S Kalmijn, W J van Venrooij, A E Voskuyl, H J Dinant, W H J P Linssen, J H J Wokke, J E Hoogendijk
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Although polymyositis and dermatomyositis are regarded as treatable disorders, prognosis is not well known, as in the literature long-term outcome and prognostic factors vary widely. <b>Aim:</b> To analyse the prognostic outcome factors in polymyositis and adult dermatomyositis. <b>Methods:</b> We determined mortality, clinical outcome (muscle strength, disability, persistent use of drugs and quality of life) and disease course and analysed prognostic outcome factors. <b>Results:</b> Disease-related death occurred in at least 10% of the patients, mainly because of associated cancer and pulmonary complications. Re-examination of 110 patients after a median follow-up of 5 years showed that 20% remained in remission and were off drugs, whereas 80% had a polycyclic or chronic continuous course. The cumulative risk of incident connective tissue disorder in patients with myositis was significantly increased. 65% of the patients had normal strength at follow-up, 34% had no or slight disability, and 16% had normal physical sickness impact profile scores. Muscle weakness was associated with higher age (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3 to 10.3). Disability was associated with male sex (OR 3.1; 95% CI 1.2 to 7.9). 41% of the patients with a favourable clinical outcome were still using drugs. Jo-1 antibodies predicted the persistent use of drugs (OR 4.4, 95% CI 1.3 to 15.0). <b>Conclusions:</b> Dermatomyositis and polymyositis are serious diseases with a disease-related mortality of at least 10%. In the long term, myositis has a major effect on perceived disability and quality of life, despite the regained muscle strength.
Molecular Pathways: Sterols and Receptor Signaling in Cancer
Authors: Linara Gabitova, Andrey Gorin, Igor Astsaturov
Journal: Clinical Cancer Research (2013)

Abstract Accelerated cholesterol and lipid metabolism are the hallmarks of cancer and contribute to malignant transformation due to the obligatory requirement for cholesterol for the function of eukaryotic membranes. To build new membranes and maintain active signaling, cancer cells depend on high intensity of endogenous cholesterol biosynthesis and uptake of lipid particles. This metabolic dependency of cancer cells on cholesterol and other lipids is tightly regulated by the cholesterol homeostasis network, including (i) sterol response element–binding proteins (SREBP), master transcriptional regulators of cholesterol and fatty acid pathway genes; (ii) nuclear sterol receptors (liver X receptors, LXR), which coordinate growth with the availability of cholesterol; and (iii) lipid particle receptors, such as low-density lipid particle (LDL) receptor, providing exogenous sterol and lipids to cancer cells. In addition, activity of oncogenic receptors, such as MUC1 or EGFR, accelerates sterol uptake and biosynthesis. Therefore, a general strategy of reducing the cholesterol pool in cancer cells is challenged by the highly efficient feedback loops compensating for a blockade at a single point in the cholesterol homeostatic network. Besides the well-established structural role of cholesterol in membranes, recent studies have uncovered potent biologic activities of certain cholesterol metabolic precursors and its oxidized derivatives, oxysterols. The former, meiosis-activating sterols, exert effects on trafficking and signaling of oncogenic EGF receptor (EGFR). Cholesterol epoxides, the highly active products of cholesterol oxidation, are being neutralized by the distal sterol pathway enzymes, emopamyl-binding protein (EBP) and dehydrocholesterol-7 reductase (DHCR7). These recently discovered “moonlighting” activities of the cholesterol pathway genes and metabolites expand our understanding of the uniquely conserved roles these sterol molecules play in the regulation of cellular proliferation and in cancer. Clin Cancer Res; 20(1); 28–34. ©2013 AACR.