tbuckley/cabot-search huggingface dataset:
Abstract P395: Statin Use in Late Life Does Not Impact Risk of Dementia or Cognitive Change in the Next Few Years: Results of a Systematic Review and Methodological Commentary
Authors: Melinda C Power, Jennifer Weuve, A. R Sharrett, Deborah Blacker, Rebecca F Gottesman
Journal: Circulation (2015)

Introduction: The recently published American College of Cardiology and American Heart Association guidelines on the management of cholesterol expanded the population recommended to receive statins by approximately 13 million United States adults. Statins are hypothesized to reduce risk of dementia through treatment of hyperlipidemia, through anti-oxidant and anti-inflammatory effects, or through influence on brain amyloid-beta or tau metabolism. However, firm conclusions about whether statin use impacts cognitive decline and dementia remain elusive. Existing reviews have focused solely on trials, did not systematically discuss study quality, or discussed and meta-analyzed all observational studies as a group, which may be inappropriate when differences in study design or analyses yield non-comparable effect estimates. Hypothesis: The purpose of this systematic review is to summarize findings from randomized controlled trials and observational cohort studies, study designs that are most useful for evaluating the putative causal effect of statin use on cognition. We hypothesized that the literature would support a protective effect of statin use on cognitive decline and dementia. METHODS: Following a systematic literature search, we grouped eligible reports by study design and statistical approach, and provide specific commentary on findings, as well as the potential for and direction of bias. RESULTS AND CONCLUSIONS: While observational studies of statin use at or near the time of dementia diagnosis suggest a protective effect, these findings may be attributable to reverse causation. Randomized controlled trials and well-conducted observational studies of baseline statin use and subsequent cognition do not support a causal preventive effect of statin use in late-life on cognitive decline or dementia. This of course does not undermine existing recommendations regarding statin use for preventing cardiovascular disease. Important questions remain unanswered, including questions about the impact of midlife or long-term statin use. Much future human research on statins and cognition will be observational; careful study design and analysis will be required to avoid common sources of bias. We advocate continuing systematic review with attention to study quality and the likelihood of bias; the AlzRisk database entry on this topic, which is currently limited to studies reporting on Alzheimer’s disease, will be available shortly and will be updated over time (see www.alzrisk.org for reviews of 11 other potential non-genetic risk factors for Alzheimer’s disease).
A novel, orally active, small molecule Hsp90 inhibitor.
Authors: Patrick Fadden, Amy Barabasz, Tom Barta, Jeron Eaves, Briana Foley, Lifeng Geng, Steven Hall, Gunnar Hanson, He Huang, James Otto, Bert Pronk, John Rice, James Veal
Journal: Cancer Research (2006)

5548   The molecular chaperone Hsp90 plays a central role in maintaining the functional competency of a number of signaling transducers involved in cell growth, survival and oncogenesis. For this reason Hsp90 has become an exciting therapeutic target for the treatment of cancer. Derivatives of the natural product geldanamycin, 17-AAG and 17-DMAG, inhibit Hsp90 by competing with ATP binding and are currently under clinical investigation. We present here the discovery and characterization of SNX-5542 as a novel, water soluble, orally active small molecule inhibitor of Hsp90 that is structurally unrelated to any of the current published Hsp90 inhibitors. In vitro and in vivo evidence, presented herein, demonstrate that SNX-5542 acts as a highly selective Hsp90 inhibitor with activity and efficacy equivalent to or better than published Hsp90 inhibitors. These data include: 1) competitive displacement of ATP from Hsp90, 2) Hsp90 client degradation that is time dependent in cells treated with compound, 3) compound dependent upregulation of Hsp70 and 4) broad, potent antiproliferative response in human cancer cells treated with SNX-5542. SNX-5542 exhibits low nanomolar potency in each of the in vitro cellular assays tested. The in vivo efficacy of orally dosed SNX-5542 was demonstrated in human xenograft models of colon and breast cancer. Additionally, pharmacodynamic evidence of Hsp90 inhibition was characterized in tumor tissue samples from these experiments. Initial preclinical toxicity studies are favorable indicating that SNX-5542 has the potential to be clinically beneficial in the treatment of a wide range of cancers. SNX-5542 also represents a new tool for addressing Hsp90 biology and physiology.
Cytomegalovirus Antibody Level and Mortality Among Community-Dwelling Older Adults With Stable Cardiovascular Disease
Authors: Timo E Strandberg, Kaisu H Pitkala, Reijo S Tilvis
Journal: JAMA (2009)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Racial/ethnic disparities in medical care
Authors: Drew Altman, Marsha Lillie-Blanton
Journal: BMJ (2003)

Engaging physicians in the dialogue 

From BMJ USA 2003;June:300 

Last year, the Institute of Medicine (IOM) released the report Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care , which concluded, based on an extensive review of the literature, that racial and ethnic disparities in patient care occur among similarly insured groups.1 One study of Medicare beneficiaries, for example, found that black patients with early stage lung cancer were nearly half as likely as whites to undergo surgery and had lower five-year survival rates.2 Another study found that Latino patients who had undergone diagnostic angiography were 40% less likely than whites to undergo coronary bypass surgery.3 A study that identified patients considered appropriate candidates for renal transplantation found that the procedure occurred among 17% of black patients and 52% of white patients.4 While the evidence varies for specific conditions and racial/ethnic minority groups, the data sufficiently compel us to begin undertaking actions to systematically and aggressively eliminate disparities in needed medical care.

This …
Diagnostic and Therapeutic Approaches in Respiratory Endoscopy
Authors: R. Peric, M. de, N. van, J.G. Aerts
Journal: Endoscopy (2013)

The field of respiratory endoscopy has developed over the last decade. Endoscopy is now used for early detection, diagnostic procedures, endoscopic ultrasound and endobronchial inter‐ ventions. Bronchoscopy is a standard procedure for endoscopists but recently new techniques like autofluoresence bronchoscopy have been introduced. It is not known how these techni‐ ques should be incorporated in standard clinical care. Autofluorescence bronchoscopy can be used for detection of premalignant lesions but it is known that the used histological classifi‐ cation does not correlate to biological behaviour. Premalignant lesions may regress or very early abnormal lesions may progress into tumor. Therefore the work up of these lesions is not known. To overcome this problem new techniques are introduced like optical coherence tomography or incorporation of spectroscopy. The value of these techniques for daily practice and research will be reviewed. We will discuss all the presently available techniques and there indications.
Characterization of Mast Cell-Committed Progenitors Present in Human Umbilical Cord Blood
Authors: Duraisamy Kempuraj, Hirohisa Saito, Azusa Kaneko, Kazumi Fukagawa, Masaharu Nakayama, Hano Toru, Morimitsu Tomikawa, Hiroshi Tachimoto, Motohiro Ebisawa, Akira Akasawa, Toko Miyagi, Hiromitsu Kimura, Toshiharu Nakajima, Kohichiro Tsuji, Tatsutoshi Nakahata
Journal: Blood (1999)
Baby bred to provide stem cells for sister
Authors: Deborah Josefson
Journal: BMJ (2000)

A couple in Colorado, United States, has used in vitro fertilisation and preimplantation genetics to produce embryos and screen them for a child who could be a stem cell and bone marrow donor for their daughter.

The case, which has provoked widespread discussion about the ethical issues involved, is believed to be the first known instance where preimplantation genetics was used both to screen for a disease and to ensure a tissue donor match in a sibling.

The couple's daughter, 6 year old Molly Nash, was born with Fanconi's anaemia. Fanconi's anaemia is a rare, autosomal recessive disease characterised by aplastic anaemia (bone marrow failure of all marrow lineages), brittle chromosomes, and the variable presence of skeletal, cardiac, and renal anomalies.

Additionally, affected persons may have mental retardation, small facies, gastrointestinal disorders, “cafe au lait” …
Abstract 83: Comparison of surface-directed and classic androgen receptor antagonists
Authors: Ji Ho Suh, Arundhati Chattopadhyay, Douglas H. Sieglaff, Cheryl L. Storer, Marc B. Cox, Paul Webb
Journal: Cancer Research (2015)

Abstract Background: The androgen receptor (AR) surface-directed antagonist MJC13 inhibits AR function and proliferation of prostate cancer (PC) cells and these effects are related to arrest of an AR/chaperone complex in the cytoplasm. Here, we compared activities of MJC13 and the classic AR antagonist flutamide. Method and Results: MJC13 and flutamide inhibit all dihydrotestosterone (DHT)-dependent genes in LNCaP PC cells and both compounds are equally effective. Control ChIP assays confirm that MJC13 inhibits AR binding to the prostate specific antigen (PSA) promoter more strongly than flutamide, consistent with different mechanisms of action. Examination of efficacy of MJC13 in conditions that reflect aspects of castrate resistant prostate cancer (CRPC) reveals that it inhibits a flutamide-dependent AR mutant (ART877A), but displays greatly restricted gene-specific activity in 22Rv1 cells that express a constitutively active truncated AR and is inactive against glucocorticoid receptor (GR), which can co-opt androgen-dependent signaling networks in CRPC. While flutamide inhibits AR interactions with the coactivator SRC2, it does not affect β-catenin binding. In contrast, MJC13 inhibits AR interactions with both coregulators and, unlike flutamide, strongly inhibits amplification of AR activity obtained with SRC2 and β-catenin. MJC13 also preferentially inhibits β-catenin-enhanced cell division in LNCaP cells relative to flutamide. Conclusion: Our findings suggest that a surface-directed antagonist can block AR activity in some conditions in which a classic antagonist fails and may display utility in some forms of CRPC. Citation Format: Ji Ho Suh, Arundhati Chattopadhyay, Douglas H. Sieglaff, Cheryl L. Storer, Marc B. Cox, Paul Webb. Comparison of surface-directed and classic androgen receptor antagonists. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 83. doi:10.1158/1538-7445.AM2015-83
The Risks of Staying in London: A Review of Overseas Visitors Admitted to a London Hospital
Authors: G N Fuller, S F Journeaux, K Corner, A F Lant
Journal: Journal of the Royal Society of Medicine (1988)

A retrospective review of 103 acute admissions of overseas visitors to a central London hospital was performed. Admissions were most commonly due to infection (43 admissions) and to recurrence of preexisting disease (40 admissions). Patients over 60 years were frequently admitted with new diagnoses. Groups at risk of admission were identified and strategies to reduce admissions discussed.
Family history and risk of venous thromboembolism with oral contraception
Authors: J. P Vandenbroucke, F. J M van der Meer, F. M Helmerhorst, F. R Rosendaal, B. Cosmi
Journal: BMJ (2001)

Editor—Cosmi et al in their article claim that family history has poor diagnostic test qualities to detect prothrombotic mutations.1 They also indicate that overall population screening is not cost effective. Although it always was obvious that family history would never make a perfect test (of families with many cases of venous thrombosis, up to 40 or 50% have factor V Leiden2), the finding of an equal predictive value for a positive and a negative family history by Cosmi et al is surprising and might be due to the small numbers included or the type of history that was considered “positive.”

Even if family history is far from perfect as a diagnostic test for one or two mutations, the question is whether one should refrain from using it. In our original publication, we tried to emphasise the meaning of family history for the prescription of oral contraceptives, and not really as a clue for the detection of mutations.3 Apart from any prothrombotic mutation, a strongly positive family history might point to a tendency for venous thrombosis that might be taken into account clinically in the decision whether or not to use oral contraceptives.

Moreover, even the meaning of a mutation is different in the context of a positive family history: the age at first venous thrombosis with factor V Leiden is about 10 years younger in persons with a positive family history than in consecutive patients.4 The most important information that one would like to obtain from a family history is not a proxy test for factor V Leiden or any other mutation, but the likelihood that a woman will develop thrombosis if she uses oral contraceptives. Whether or not family history would be valuable for that purpose is the ultimate test.
Human respiratory epithelial cells acquire a long-lasting antiviral condition when exposed to interferon beta
Authors: Giel Gaajetaan, Gert Grauls, Catrien Bruggeman, Frank Stassen
Journal: European Respiratory Journal (2011)

Type I interferons (IFNs) induce strong antiviral effects and are therefore attractive to prevent seasonal respiratory infections or reduce the incidence of virus-mediated exacerbation in COPD patients. Yet, clinical application of type I IFNs is hindered due to significant side effects observed during repetitive use. In this study we investigate the duration of protection, mediated by prophylactic IFNbeta, against a human rhinovirus (HRV) infection.  Human respiratory epithelial (A549) cells were exposed for 18 hours to various concentrations (31-500 IU/ml) of IFNbeta. Then, IFNbeta was either removed or maintained in the supernatant for the rest of the experiment. Next, cells were infected with HRV-1B (MOI 0.1) at t = 0, 24, 48, 72 or 168 hours after the initial exposure to IFNbeta. At 48 hours post infection, the protective effect of IFNbeta on HRV-induced cell death was determined by a colorimetric assay. RT-qPCR and plaque assay were used to determine HRV infection.  In the continuous presence of IFNbeta, 90-100% of A549 cells were protected against HRV-induced cell death at every time point and at all IFNbeta concentrations. This strong protective effect was confirmed by RT-qPCR and plaque assay. Alternatively, when IFNbeta was removed, cell death increased with time and in dose-dependent way. Nevertheless, at 168h post IFNbeta stimulation (500IU/ml), still 75% of all cells were viable.  These data show that IFNbeta has not only a strong, but also long-lasting protective effect against HRV-1B. This opens new opportunities for prophylactic treatment of viral respiratory infections without the risk of side effects often seen after repetitive and systemic use.
Infertility. A Practical Guide for the Physician.
Authors: Mary G. Hammond, Luther M. Talbert
Journal: Annals of Internal Medicine (1981)

Overview of the diagnostic evaluation the physician and the infertile couple - helping in perspective infertility in the male therapeutic donor insemination the cervix in infertility antisperm antibodies - diagnosis and treatment uterine factor in infertility and pregnancy wastage tubal disease endometriosis and infertility management of ovulatory dysfunction nutritional aspects of infertility hyperprolactinaemia and infertility empiric therapy for unexplained infertility habitual abortion the role of the office nurse in general infertility care assisted reproduction technologies nursing administration in an ART programme frontiers in reproductive technology how to evaluate reports on infertility treatment.
Unicef reports progress in reducing vertical transmission of HIV
Authors: John Zarocostas
Journal: BMJ (2008)

UK paediatricians will debate a motion of no confidence in the General Medical Council's handling of disciplinary cases involving child protection work, at their professional association's forthcoming meeting.The motion has been put forward by 32 members of the Royal College of Paediatrics and Child Health and will be tabled at the college's annual spring meeting, to be held at York University from 14 April.Many but not all of the motion's signatories are members of Professionals Against Child Abuse, a group formed last year in response to high profile GMC cases against paediatricians.The motion argues that paediatricians are more harshly treated than other specialties, citing cases in which other doctors escaped removal from the register after convictions for assaulting children and viewing child pornography.The motion also accuses the GMC of giving too much weight to serial and vexatious complaints by campaigners and of failing to consider previous investigations that have exonerated paediatricians when starting proceedings against them.This constitutes double jeopardy, the paediatricians argue.Paul Davis, a consultant paediatrician in Cardiff and one of the signatories, said the fear of being struck off was a "powerful deterrent" in discouraging professionals from giving expert testimony and from making child protection referrals."The numbers on the child protection register have declined sharply," he said.A spokesperson for the GMC said, "It is extremely rare for a paediatrician to appear before a panel in connection with child protection work.Since 2004 panels have considered more than 600 cases.Only two could reasonably be said to have been about paediatricians involved in child protection work.Our critics are trying to create the impression that the GMC is intent on unfairly persecuting paediatricians involved in child protection work.Nothing could be further from the truth." Paediatricians debate a motion of no confidence in GMCUK NEWS Review shows growing trend for trials of new cancer drugs to stop early, p 793 WoRld NEWS Germany "has two tier health service" p 796 bmj.comCompany's decision to lengthen lipid lowering trial causes controversy
Low-dose 5-fluorouracil induces cell cycle G2 arrest and apoptosis in keloid fibroblasts
Authors: L. Huang, Y.P. Wong, Y.J. Cai, I. Lung, C.S. Leung, A. Burd
Journal: British Journal of Dermatology (2010)

Intralesional injection of low-dose 5-fluorouracil (5-FU) has recently been used as an experimental modality for treating keloid scarring and has shown promising efficacy in improving scar appearance and preventing recurrence of the keloid.We sought to explore the cellular- and molecular-based evidence for the observed clinical benefits.Primary cell lines of keloid fibroblasts were treated with 5-FU at a range of lower doses (∼10 mg mL(-1) ) in monolayer culture and subjected to examination for cell viability, proliferative potential, apoptosis, cell cycle and associated proteins involved in cell cycle control.5-FU significantly inhibited cell proliferation of keloid fibroblasts in the full dose range used in this study. The DNA synthesis was completely inhibited by 5-FU at 72 h, and significant cell apoptosis was observed at concentrations ≥ 1 mg mL(-1) for a period over 72 h. 5-FU caused a significant delay in cell cycle progression and the G2/M phase arrest. 5-FU induced p53 and p21 accumulation together with a decrease in cyclin B1 and Bcl-2 levels in treated keloid fibroblasts.Our data indicate that low-dose 5-FU (as low as 1 mg mL(-1) ) induces significant inhibition of proliferation, G2/M cell cycle arrest and apoptosis but not immediate cell death of keloid fibroblasts. The lack of tissue necrosis is a particular benefit as further scarring is likely to be prevented. These results support the use of low-dose 5-FU as a potential modality for treating keloid scars.
Comparison of PCR detection of mecA with agar dilution and Etest for oxacillin susceptibility testing in clinical isolates of coagulase-negative staphylococci
Authors: Y. Tveten, A. Jenkins, A. Digranes, K.K. Melby, A.G. Allum, B.-E. Kristiansen
Journal: Clinical Microbiology and Infection (2004)
Sustained high-level expression of full-length human factor VIII and restoration of clotting activity in hemophilic mice using a minimal adenovirus vector
Authors: Cristina Balagué, Jiemin Zhou, Yifan Dai, Ramón Alemany, Steven F. Josephs, Grai Andreason, Mangala Hariharan, Erica Sethi, Elena Prokopenko, Hsing-yi Jan, Yan-Chun Lou, Debbie Hubert-Leslie, Lulio Ruiz, Wei-Wei Zhang
Journal: Blood (2000)