tbuckley/cabot-search huggingface dataset:
A History of the Heart and the Circulation
Authors: F. A. Willius, T. J. Dry
Journal: JAMA (1949)

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Type II Diabetes Mellitus Presenting as the Charles Bonnet Syndrome
Authors: Marion Gray, Ian R Jones
Journal: Journal of the Royal Society of Medicine (1997)

In Charles Bonnet syndrome an individual with impaired vision experiences visual hallucinations, often of a complex nature. The syndrome is named after the 18th century naturalist and philosopher who described these symptoms in his grandfather. In 1936 Morsier proposed including under the label those visual hallucinations occurring in the elderly who had preservation of intellectual function and thus insight into the nature of the visions1. Since then many cases have been described in association with established eye disease; here we describe a case in which Charles Bonnet syndrome was the presenting feature of type II diabetes mellitus.
Abstract 3492: Increased Late I <sub>Na</sub> in Left Atrial Myocytes of Left Ventricular Hypertrophy Rabbits and its Role in Genesis of Atrial Early Afterdepolarizations
Authors: Donglin Guo, Zhen Jiao, Binu Malhottra, Chinmay Patel, Peter R Kowey, Gan-Xin Yan
Journal: Circulation (2008)

Atrial fibrillation is the most common sustained arrhythmia affecting more than 2 million people annually in USA. Previous studies have shown that left ventricular hypertrophy (LVH) results in an increase in the late I Na that plays an important role in genesis of ventricular arrhythmias. We tested the hypothesis that LVH, which is associated with elevated pressure in the left atrium, could enhance the late I Na in left atrial (LA) myocytes, leading to increased trigger activities. Rabbit LVH, which exhibited a significantly greater left ventricle to body mass ratio, was induced using the renovascular hypertension model. Interestingly, early afterdepolarizations (EADs) at action potential phase 2 and 3 occurred in 6 of 10 LA myocytes isolated from 5 LVH rabbits at a pacing cycle length of 2000 ms, whereas EADs were elicited in none of 10 cells isolated from 5 control rabbits ( p &lt;0.01). Spontaneously activities (SA) were observed in 6 of 10 LA myocytes from five LVH rabbits at the pacing rate of 8000 ms. The density of the late I Na was significantly larger in LA myocytes of LVH rabbits than that recorded in control rabbits (0.59±0.02 pA/pF in LVH versus 0.42±0.05 pA/pF in control, n=6, p &lt;0.01). Ranolazine, a late I Na blocker, exerted a concentration-dependent blocking effect on the late I Na in LA myocytes of the rabbits (IC 50 =15.7±0.6 μM) and abolished all of atrial EADs and SA of the LVH rabbits at 30 μM. Our results demonstrate that LVH results in a significant increase in the late I Na in the LA myocytes that may render these cells susceptible to genesis of EADs. The late I Na is a potentially useful ionic target by antiarrhythmic drugs for the treatment of atrial fibrillation in the setting of LVH. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Website of the Week: Learning from one another to bridge the “know-do gap”
Authors: Neil Pakenham-Walsh
Journal: BMJ (2004)

The “know-do gap” is a new term to describe an old problem: the gap between what we know and what we do in practice. But the term can mean many different things, not least depending on who the “we” refers to—a farmer in Nepal, doctor in Nairobi, health educator in New York, the World Health Organization, the biomedical community, the Catholic Church, or the President of South Africa. Gaps also exist between what a profession as a whole knows and what individual professionals know to be relevant to their practice and between people's awareness of health risks and their actual behaviour.

The main approach to bridge these gaps continues to be to push information out, whether to “get health information to developing countries,” to “translate research into practice,” or just to “get our message across.” This approach has limited success. It is not only the “target population” that needs information, communication, and education (ICE); we all do. All of us who are involved in the creation, exchange, and use of health knowledge—healthcare providers, researchers, publishers, information professionals, policy makers—have unique ICE needs ourselves. These needs are currently unmet. Consequently our effectiveness in preventing and managing disease is severely compromised.

This issue of the BMJ reminds us that much can be learnt from developing countries. Anyone who has worked in development will know that to be true. What matters most is ensuring that everyone has the same opportunity to keep informed, to benefit from continuing professional development and education, and to communicate with others who share common interests.

Information and communication tools, and especially email, provide unprecedented opportunities for learning across geographical and professional boundaries. An example is HIF-net at WHO (Health Information Forum), an email forum to support dialogue among health professionals and others who are committed to improving access to relevant and reliable information for healthcare workers in developing countries (www.inasp.info/health/hif-net.html). The list has over 1500 members from over 130 countries, and two thirds of the members are from the developing world. Similar examples are the electronic conference of the African networks for health research and development (AFRO-NETS, at www.afronets.org) and the aid workers network (www.aidworkers.net).

What is important is not so much that “we” learn from developing countries but that we learn together and that we apply this learning to achieve shared goals for world health.
Catheter Ablation of Long-Standing Persistent Atrial Fibrillation
Authors: Roland Richard Tilz, Andreas Rillig, Anna-Maria Thum, Anita Arya, Peter Wohlmuth, Andreas Metzner, Shibu Mathew, Yasuhiro Yoshiga, Erik Wissner, Karl-Heinz Kuck, Feifan Ouyang
Journal: Journal of the American College of Cardiology (2012)
Abstract 9328: Living Alone and Cardiovascular Events in Stable Outpatients at Risk of or with Atherothrombosis: Insight From the REACH Registry
Authors: Jacob A Udell, Ph. G Steg, Benjamin M Scirica, Sidney C Smith, E. M Ohman, Kim A Eagle, Shinya Goto, Jang Ik Cho, Deepak L Bhatt, None REACH Registry Investigators
Journal: Circulation (2011)

Background: Living alone (LA), a proxy for social support, has been inconsistently linked with CVD. Methods: Outpatients from 29 countries at risk of, or with, atherothrombosis were enrolled in the REACH registry and followed for 4 years. Event rates for mortality, vascular events (CV death, MI, or stroke), CHF, bleeding, and vascular procedures were examined by living arrangement with sequential risk adjustment for age, gender, CV risk factors, therapy, degree of preexisting atherothrombosis, and sociodemographic factors. Effect modification was tested by age, gender, geography, ethnicity, education, and employment. Results: Among the 44,617 REACH patients with reported living arrangements, 8,605 (19%) were living alone. LA strongly correlated with 4-year mortality (11.4% vs. 9.3%, crude HR, 1.16 [95% CI 1.08-1.24]; p&lt;0.001), risk of vascular events (12.9% vs. 11.9%, crude HR, 1.27 [1.18-1.37]; p&lt;0.001) along with CV death, hospitalization for CHF, bleeding, and vascular procedures. However, after multivariable adjustment the effect of LA on mortality (adjusted HR 1.17 [0.99-1.25] and risk of vascular events (adjusted HR 1.08 [0.98-1.18]) was attenuated. LA remained associated with increased risks of CHF (HR 1.09 [1.00-1.18]), vascular procedures (HR 1.44 [1.21-1.72]), PCI (HR 1.33 [1.04-1.69]), and limb amputation (HR 3.32 [95% CI 1.89-5.82]). There was effect modification by age and employment status, with an inverse correlation between LA and mortality in those older than 80 years or retired. Conclusion: In the REACH population, age, current risk factors, and past CV events accounted for most of the association between LA and increased mortality or risk of major vascular events. However, LA was associated with several serious CV events such as risk of CHF, PCI and limb amputation. Elderly retired individuals who live alone may have more favorable prognosis from CVD than others living alone.
Abstract 3148: Development of Heart Failure is a Risk Factor for Incident New Onset Diabetes in the Community
Authors: Ankit Rathod, Apurva O Badheka, Mohammad A Kizilbash, Neha Garg, Vikas Veerana, Tamam Mohamad, Sony Jacob, Luis Afonso
Journal: Circulation (2009)

Introduction: Although Diabetes Mellitus (DM) is a well known risk factor for development of congestive heart failure (CHF), the converse relationship is less clear. CHF is a state of increased sym...
Abstract 5436: Generation of Induced Pluripotent Stem Cells From Peripheral Blood of Coronary Artery Disease Patients
Authors: Sinae Kim, Changwon Park, Ji Woong Han, Sung-Whan Kim, Hyongbum Kim, Yong Jin Choi, Eugine Lee, Riyaz Patel, In-Hyun Park, George Q. Daley, Arshed Quyyumi, Young-sup Yoon
Journal: Circulation (2009)

Background. Studies have demonstrated that ectopic expression of defined transcription factors can reprogram somatic cells into induced pluripotent stem cells (iPS). However, the sources of patient-derived iPS cells are limited to fibroblasts or mesenchymal cells, which require invasive procedures and long-term manipulation. Accordingly, in this study we aimed to generate human iPS cells from peripheral blood mononuclear cells (PB-MNCs) of coronary artery disease (CAD) patients. Methods and Results. We recruited one healthy volunteer and three male patients aged 58, 62, and 77, respectively, who have CADs confirmed by coronary angiography. PB-MNCs obtained by density gradient centrifugation were cultured in an adherent fashion. The adherent cells were infected with the lentiviral supernatant for the four transcription factors of OCT4, SOX2, KLF4 or c-MYC. We used third generation lentiviral vectors which do not have infectivity. At 10 days post-infection, colonies showing hES cell-like morphology were selected and transferred to feeder layers for expansion. After 3 to 4 passages, we observed tightly packed and flat colonies of cells characterized by large nuclei and scant cytoplasm, highly suggesting successful generation of iPS cells from PB-MNCs of all the patients (HiPS-ECP1, HiPS-ECP2 and HiPS-ECP3) and a healthy volunteer (HiPS-ENB). A series of assays including cytochemistry, real-time RT-PCR and teratoma formation assay revealed identical pluripotency of these iPS cells to human ES cells (H1). Bisulfite sequencing of the OCT4 and NANOG promoters in the iPS cells showed profound demethylation similar to hES cells. We next examined the differentiation capacity of the iPS cells. The iPS cells readily form EBs at 10 days in suspension culture. Upon further cultivation of EBs for another 10 days, these iPS cells spontaneously differentiated into cell types of all 3 embryonic germ layers. In conclusion. This study provides the first evidence that iPS cells can be successfully generated from PB of CAD patients, which have almost identical characteristics to iPS cells derived from healthy volunteers or human ES cells. This advance will facilitate the use of iPS cells for autologous cell therapy for ischemic cardiovascular diseases.
Abstract 2900: Periodontal Disease and Presence of Coronary Artery Disease in Patients Undergoing Coronary Angiography
Authors: Johann Auer, Thomas Weber, Gernot Szuesz, Robert Berent, Gudrun Lamm, Gerald Krennmair, Bernd Eber
Journal: Circulation (2006)

BACKGROUND: Periodontitis has been linked to coronary artery disease (CAD) risk, possibly through providing a systemic inflammatory burden. Few studies have evaluated periodontal disease and angiog...
Experimental Studies in Metal Cancerigenesis. VI. Tissue Reactions in Rats and Rabbits After Parenteral Introduction of Suspensions of Arsenic, Beryllium, or Asbestos in Lanolin
Authors: Hueper Wc
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Experimental Studies in Metal Cancerigenesis. VI. Tissue Reactions in Rats and Rabbits After Parenteral Introduction of Suspensions of Arsenic, Beryllium, or Asbestos in Lanolin Get access W. C. Hueper W. C. Hueper National Cancer Institute,2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 1, August 1954, Pages 113–129, https://doi.org/10.1093/jnci/15.1.113 Published: 01 August 1954 Article history Received: 23 March 1954 Published: 01 August 1954
Correction of Cobalamin Malabsorption in Pancreatic Insufficiency with a Cobalamin Analogue that Binds with High Affinity to R Protein but not to Intrinsic Factor
Authors: Robert H. Allen, Bellur Seetharam, Nancy C. Allen, Elaine R. Podell, David H. Alpers
Journal: Journal of Clinical Investigation (1978)

In vitro studies indicate that [57Co]cobalamin (Cbl) is preferentially bound to salivary R protein as opposed to intrinsic factor (IF) and that [57Co]Cbl bound to R protein is not transferred to IF at either pH 2 or pH 8. Incubation of R protein-[57Co]Cbl with pancreatic proteases causes a partial degradation of the R protein moiety and a rapid transfer of [57Co]Cbl to IF. We have postulated that the etiology of Cbl malabsorption in pancreatic insufficiency is an inability to partially degrade R protein because of a lack of pancreatic proteases. We have tested this hypothesis by determining the ability of a nonradioactive Cbl analogue, bound with high affinity by R protein but not by IF, to correct the malabsorption of [57Co]Cbl in patients with pancreatic insufficiency.
Report calls for $2bn global fund to kickstart antibiotic development
Authors: J. Wise
Journal: BMJ (2015)

A review on antimicrobial resistance commissioned by the UK prime minister has called for the establishment of a global innovation fund of around $2bn over five years to boost funding for “blue sky” research into drugs and diagnostics.

Its report said that there was a need to kickstart drug development to tackle the growing global problem of drug resistant infections.1 This was the economist Jim O’Neill’s third paper on the challenges of antimicrobial resistance.2

Another recommendation is for a global organisation to make lump sum payments to drug companies to incentivise the development of the most needed antibiotics. Payment would be set against selective criteria agreed in advance. The report said that this approach would “de-link” the profitability of a drug from volume of sales. It would get rid of the commercial imperative for drug companies to sell large quantities of new antibiotics, which had contributed to the spread of resistance.

The report, which David Cameron commissioned in July 2014, also called for innovative partnerships between academia …
Abstract 3547: Hydrogen Sulfide Therapy Attenuates Left Ventricular Dysfunction and Reduces Mortality in a Murine Model of Heart Failure
Authors: John W Calvert, Susheel Gundewar, Saurabh Jha, John W Elrod, David J Lefer
Journal: Circulation (2008)

Hydrogen sulfide (H2S) is an endogenous signaling molecule with potent cytoprotective effects. In vivo evidence regarding its use in the treatment of heart failure (HF) is lacking. Therefore, we ev...
Spirituality and clinical care
Authors: D. R Nethercott
Journal: BMJ (2003)

Editor—I agree with Culliford that knowing your patients better makes for a better therapeutic relationship.1 Often—for example, in terminal care or when physical measures do not have an impact on any disease—being able to relate in “wider” terms can increase the potential for healing. But I disagree with Culliford on the question of methodology.

Most religions and other arenas of spirituality use ritualised gestures, incantations, prayers, symbolism, and rites. Unless you believe that these processes have effects through a perceived extracorporeal being, power, or energy, the effect is presumed to come from within patients themselves. But the placebo effect is inherently based on its own camouflage. Once you know you're taking placebo then the magic is lost.

The entire effect is dependent on your “faith” in the procedure. Although I might deliberately use the placebo effect in my pharmacological treatment of patients, is it not an unethical deceit for me to portray a facade of spirituality for their benefit when I don't believe it myself? If that is true then what is Culliford suggesting? Might it be that my deficiencies as a non-believer translate into deficiencies as a doctor? Perhaps I don't really want an answer to that.
Abstract MP40: A Steps/Day Translation of the Moderate-to-Vigorous Physical Activity Guideline for Children and Adolescents
Authors: Marc A Adams, William D Johnson, Catrine Tudor-Locke
Journal: Circulation (2013)

Background: An evidence-based steps/day translation of U.S. federal guidelines for youth to engage in ≥60 minutes/day of moderate-to-vigorous physical activity (MVPA) would help health researchers, medical practitioners, and lay professionals charged with increasing youth’s physical activity (PA). The purpose of this study was to determine the number of free-living steps/day (both raw and adjusted to a pedometer scale) that correctly classified children (6-11 years) and adolescents (12-17 years) as meeting the 60-minute MVPA guideline using the 2005-2006 National Health and Nutrition Examination Survey (NHANES) accelerometer data, and to evaluate the 12,000 steps/day recommendation recently adopted by the President’s Challenge Physical Activity and Fitness Awards Program. Methods: NHANES children (n=915) and adolescents (n= 1,302) were included in this analysis. Receiver Operating Characteristic (ROC) curve plots and classification statistics (i.e., false positive and negatives, positive and negative predictive values) revealed candidate steps/day cut points that discriminated meeting/not meeting the MVPA threshold by age group, gender and different accelerometer activity cut points. The Evenson cut point and two Freedson age-specific (3 and 4 METs) cut points were used to define minimum MVPA, and optimal steps/day were examined for raw steps and adjusted to a pedometer-scale to facilitate translation to lay populations. Results: For boys and girls (6-11 years) with ≥ 60 minutes/day of MVPA, a range of 11,500-13,500 raw steps/day for children was the optimal range that balanced classification errors. For adolescent boys and girls (12-17) with ≥60 minutes/day of MVPA, 11,500-14,000 raw steps/day was optimal. Translation to a pedometer-scaling reduced these minimum values by 2,500 step/day to 9,000 steps/day. Area under the curve was ≥84% in all analyses. Conclusions: A persistent question in the physical activity literature has been “How many steps/day are enough?” No single study has definitively identified a precise and unyielding steps/day value for youth. Considering the other evidence to date, we propose a reasonable ‘rule of thumb’ value of ≥ 11,500 steps/day for both children and adolescents (and both genders), accepting that more MVPA is better. For practical applications, 9,000 steps/day appears to be a more pedometer-friendly value. These steps/day values provide a marker that medical practitioners and lay professionals can use in clinical settings to estimate and increase youth’s moderate-to-vigorous physical activity.
Anti-CXCL12/SDF-1 Spiegelmer® Nox-A12 Alone and In Combination With Bendamustine and Rituximab In Patients With Relapsed Chronic Lymphocytic Leukemia (CLL): Results From A Phase IIa Study
Authors: Marco Gobbi, Michael Steurer, Federico Caligaris-Cappio, Marco Montillo, Ann Janssens, Livio Trentin, Thomas Dümmler, Stefan Zöllner, Stefan Zeitler, Kai Riecke, Anna Kruschinski
Journal: Blood (2013)
Abstract P054: Rare Variants in and Near IRS1 are Associated with Fasting Insulin in CHARGE-S Cohorts
Authors: Belinda K Cornes, Jennifer Brody, Alanna C Morrison, David Siscovick, James B Meigs
Journal: Circulation (2013)

Introduction: Common variants in the gene encoding insulin receptor substrate 1 ( IRS1 ) and nearby on 2q36.3 have been associated with levels of fasting insulin (FI). We hypothesized that a greater burden of rare variants in these regions is associated with higher FI. Methods: CHARGE-S sequenced (average coverage &gt;60x) the IRS1 and 2q36.6 regions (totaling 185 kb) in 3,539 individuals on the SOLiD platform. FI information among non-diabetics was available in 3 studies: Framingham Heart Study ( N =811), Cardiovascular Heart Study ( N =967) and Atherosclerosis Risk in Communities Study ( N =1761). We analyzed rare variants (MAF &lt; 1%) using a weighted sum test, similar to Madsen-Browning (powerful to detect an association if effects of casual rare variants are in the same direction), and the SKAT test (preferred method if variant effects are in opposite directions). Meta-analyses of weighted rare variants results used the inverse-variance method while SKAT results used a similar approach. For multi-variant tests, the threshold for significance was considered to be α = 0.05. Coding annotation predictions were obtained from the dbNSFP database which includes functional predictions from SIFT, MutationTaster, Polyphen-2, Phylo-P and LRT. Non-coding annotation information (protein binding regions, transcription factor binding sites, DNase hypersensitivity sites, conservation scores) was obtained from ENCODE and ORegAnno databases. From these annotations, we grouped different types of variants together (possible loss of function; possibly regulatory) in order to determine specific variants contributing most to the effect. Results: Sequencing found 4,534 variants in two regions, 86.7% of which were rare and novel, not seen in 1000 genomes or dbSNP. Approximately 20% of variants had annotation information available; of these, 34 variants were possibly damaging. We found suggestive association with FI ( p =0.03) for all rare variants in the meta-analysis of weighted-sum tests at 2q36.3 but not at IRS1 . At IRS1 (but not at 2q36.3), SKAT meta-analysis tests showed evidence for all rare variants associated with FI ( p =0.03). SKAT tests restricted to N =365 possibly damaging variants at IRS1 suggested an association with FI in coding ( p =0.06) and in non-coding ( p =0.02) variants. Conclusion: Large scale deep sequencing in the IRS1 and 2q36.3 regions found very large numbers of new, rare variants. Multi-variant tests suggest that rare variation in these regions influence FI levels, with individuals with more and rarer variants having higher FI. Further investigation is warranted to address why weighted sum and SKAT tests provide different levels of evidence for association in the two regions. Also, conditional analyses will test whether new rare variants at IRS1 or 2q36 explain observed GWAS associations.