tbuckley/cabot-search huggingface dataset:
Preventing obesity
Authors: C. M Campbell
Journal: BMJ (2003)

Preventing obesity Prevention starts in infancyEditor-Crawford in his editorial on population strategies to prevent obesity has not mentioned an important factor in the aetiology of obesity: the method by which infants are fed. 1 Von Kries et al found that a history of three to five months of exclusive breast feeding was associated with a 35% reduction in obesity at the age of 5 to 6 years, which was not accounted for by social factors, lifestyle, etc. 2 They discuss the evidence for a programming effect of breast feeding in preventing obesity and being overweight in later life.Gilman et al found that infants who were fed breast milk more than infant formula milk, or who were breast fed for longer periods, had a lower risk of being overweight during older childhood and adolescence. 3 These results are consistent with those of the DARLING study, which showed that infants who received no milk other than breast milk in the first 12 months were lighter than formula fed infants, though of similar length and head circumference. 4 This study also found that energy intake of breastfed infants was lower than that of formula fed infants, even after the introduction of solids; the authors say that comparatively low energy intakes are a function of self regulation in breastfed infants.Breastfeeding mothers also lose weight after pregnancy more effectively than those who feed artificially, an advantage seen over at least the first 12 months of breast feeding. 5 Vigorous marketing of junk food is often implicated in the obesity epidemic.What about inappropriate marketing of infant formula milk?In the United Kingdom, with its limited legal restraints, manufacturers can and do actively promote infant feeding bottles, teats, and follow-on formula milk to the public in contravention of the international code of marketing of breast milk substitutes.This recently drew comment from the UN Committee on the Convention on the Rights of the Child.In its observations of 4 October 2002 the committee recommended that the United Kingdom takes all appropriate measures to promote breast feeding and adopt the international code of marketing of breast milk substitutes in light of its low rates of breast feeding.Measures to promote and support breast feeding, including legislation and promotion of artificial feeding, seem to be a rational approach to preventing obesity.
Lesson of the Week: Minocycline and pulmonary eosinophilia
Authors: R S Dykhuizen, A M Zaidi, D J Godden, S Jegarajah, J S Legge
Journal: BMJ (1995)

as "conscientious and altruistic"; Godlee, adding insult to injury, prefers to label WHO staffas "demoralised."What is truly demoralising is the tendency of the BMJ to recycle again and again a negative image of WHO, while denying credit where it is due.This doesn't hurt just WHO staff; it hurts the people WHO is trying to help.In devoting so many thousands of words to WHO, the BM7had a real chance to reach the same high standards that it seeks of us and to enrich the debate over the future of global health.Instead, the BMJ cheapened it, and we are left to wonder why.
Abstract 19079: Specific Skipping of Exons Using Antisense Oligoribonucleotides Results in a Novel Molecule in cMyBP-C Knock-in Mouse Myocytes
Authors: Christina Gedicke, Verena Behrens-Gawlik, Patrick A Dreyfus, Thomas Eschenhagen, Lucie Carrier
Journal: Circulation (2010)

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and lacks effective treatment. It is commonly associated with mutations in the cardiac myosin-binding protein C (cMyBP...
Targeted Therapy for ETV6-RUNX1-Driven B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Roel Polak, Marc B. Bierings, Cindy S. van der Leije, Rosanna E.S. van den Dungen, Mathijs A. Sanders, Onno Roovers, Jan J. Cornelissen, João R.M. Marchante, Rob Pieters, Monique L. den Boer, Miranda Buitenhuis
Journal: Blood (2014)
Abstract 704: Cardiac Progenitor Cell Aging Is Responsible for Organ Aging
Authors: Arantxa Gonzalez, Marcello Rota, Daria Nurzynska, Yu Misao, Caroline Ojaimi, Jochen Tillmanns, Elena Padin-Iruegas, Patrick Mueller, Grazia Esposito, Claudia Bearzi, Serena Vitale, Thomas H Hintze, Mathue Baker, Buddhadeb Dawn, Roberto Bolli, Konrad Urbanek, Toru Hosoda, Jan Kajstura, Piero Anversa, Annarosa Leri
Journal: Circulation (2007)

To establish whether the aging cardiomyopathy is dictated by depletion of the cardiac progenitor cell (CPC) pool and accumulation of old myocytes, we measured first the number of CPCs in rats at 4, 12, 20 and 28 months of age. CPCs are lineage-negative cells that express the stem cell antigens c-kit, MDR-1 and/or Sca-1. Unexpectedly, from 4 to 28 months, the number of CPCs in the heart increased ~3-fold. The increase in mitotic index of CPCs in the old heart indicated enhanced activation of CPCs which resulted in an increased number of myocyte progenitors and precursors and ultimately differentiated cardiomyocytes. These observations were at variance with the concomitant accumulation of p16 INK4a -positive-myocytes and the 6-fold increased rate of myocyte apoptosis in the senescent heart pointing to defects in the CPC compartment with aging. Activation and differentiation of old CPCs may generate a myocyte progeny that rapidly reaches senescence. To evaluate the biological age of CPCs, we measured two parameters of cellular aging: the senescence-associated protein p16 INK4a and telomere length. From 4 to 28 month, p16 INK4a -positive-CPCs increased from ~6% to ~81% resulting in a sharp decrease in the number of functionally-competent CPCs. Telomere length was measured by Q-FISH in cytospin preparations of c-kit-positive-cells collected from hearts at 3 and 27 months. In old hearts, the distribution of telomere length in CPCs, myocyte progenitors-precursors and developing myocytes was shifted to the left towards shorter telomeres. Average telomere length in old CPCs, myocyte progenitors-precursors and developing myocytes was 30%, 38% and 52% shorter than in the corresponding young cell populations, respectively. Importantly, 55% of old CPCs and 15% of young CPCs had telomeres less than 8 kbp and were p16 INK4a -positive. Thus, telomere attrition in CPCs with age leads to the generation of a myocyte progeny that rapidly acquires the senescent phenotype. However, nearly 16% of the old CPC pool had telomeres greater than 14 kbp pointing to a relevant growth reserve of the senescent myocardium. In conclusion, CPC aging with reduction in telomeric length dictates the formation of a senescent progeny which conditions organ aging and failure.
Abstract 13146: The Benefit of Transferring STEMI Patients for PCI Compared with Administration of Onsite Fibrinolytic Declines as Delays Increase
Authors: Duane S Pinto, Ajay J Kirtane, Paul D Frederick, Andre Dejam, Dave P Miller, Timothy D Henry, C. Michael Gibson
Journal: Circulation (2010)

Background: Randomized trials suggest that transfer for primary percutaneous coronary intervention (X-PCI) in STEMI is superior to onsite fibrinolytic therapy (O-FT), but the time dependent effect of this benefit in a less selected population has not been described. Transport and door-to-balloon times (DB) are rapid in randomized trials, but they are often prolonged in routine practice. We hypothesized that delays due to transfer would reduce the survival advantage compared with O-FT. Methods: Patients with STEMI on initial ECG and <12 hours after onset of pain enrolled in the National Registry of Myocardial Infarction receiving either O-FT or X-PPCI were identified. Propensity score matching was performed and the effect of PCI related delay on in-hospital mortality was assessed. PCI-related delay (DB-DN) was calculated by subtracting the door-to-needle time from the DB in the matched pair. Conditional logistic regression adjusting for patient and hospital variables was utilized identifying the DB-DN wher...
Abstract 16083: Aggregate Risk Score Based on Markers of Inflammation, Immunity, and Thrombosis is an Independent Predictor of Adverse Cardiovascular Outcomes
Authors: Danny J Eapen, Pankaj Manocha, Riyaz Patel, Ravi Nanjundappa, Emir Veledar, Christina Wassel, Joe Voland, Dylan Malayter, Ibrahim Kassas, Suliman Alradawi, Heval M Kelli, Joseph C Poole, Robert B Neuman, Laurence Sperling, Arshed A Quyyumi, Stephen Epstein
Journal: Circulation (2011)

Introduction: Activation of diverse pathophysiologic processes that include inflammatory, thrombotic, and immune pathways, contribute to the development of CAD, subsequent plaque rupture and advers...
Abstract 15719: Right Ventricular Dysfunction After Transcatheter Aortic Valve Replacement (TAVR)
Authors: Saki Ito, Sorin V Pislaru, Vuyisile T Nkomo, Jae K Oh, Kevin L Greason, Verghese Mathew, David R Holmes, Charanjit S Rihal, Rakesh M Suri
Journal: Circulation (2014)

Background: Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement in patients at high surgical risk. We investigated the impact of TAVR on left (LV) and right ventricular (RV) function using conventional echocardiography parameters. Methods and results: A total of 202 consecutive patients (age 80.6±8.0 years, aortic valve area 0.80±0.16cm 2 ) who underwent TAVR at Mayo Clinic between 2008 and 2013 were included in the study. LV ejection fraction (EF) and RV systolic function including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC) and, systolic excursion velocity (S’) were compared before (median 33.5 days) and after TAVR procedure (median 30 days). Patients who underwent pacemaker implantation after TAVR were excluded. LV EF significantly improved following TAVR (55.3±12.6% pre vs 58.5±11.1% post; p&lt;0.05). In contrast, RV systolic function significantly decreased after TAVR (pre vs post; TAPSE: 18.8±6.3 mm vs 17.4±6.3 mm, FAC: 42.6±9.8% vs 37.3±8.2%; S’: 10.7±2.6 cm/s vs 10.2±2.6 cm/s; p&lt;0.05 for all). Stratifying RV functional change by TAVR approach site, patients undergoing trans-femoral TAVR (n=100) showed RV deterioration only by FAC (see Table). In contrast, RV systolic dysfunction was more prominent in trans-apical approach group (n=87) with significant decline in all parameters of RV systolic function (see Table). Conclusion: TAVR is associated with early enhancement in LV systolic function. However, there is evidence of worsening RV function in a significant number of patients. Further studies are necessary to determine whether this deterioration in RV function is related to anatomic access site or to other factors, and to evaluate its prognostic significance.
Abstract 3122: High Dose Insulin Therapy Attenuates Systemic Inflammatory Response in Patients Undergoing Elective Coronary Artery Bypass Grafting
Authors: Turki B AlBacker, George Carvalho, Thomas Schricker, Kevin Lachapelle
Journal: Circulation (2006)

Background: Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction that has been implicated in the pathogenesis of several postoperative complications. Some studies showe...
Abstract 3186: Right Ventricular Apical Pacing Impairs Left Ventricular Apical and Basal Rotation and Induces Apical-Basal Rotation Dyssynchrony
Authors: Ken Matsuoka, Masami Nishino, Masahiko Hara, Shinpei Nakatani, Akihito Hashimoto, Kiyoshi Yamagami, Hiroyasu Kato, Yasuyuki Egami, Ryu Shutta, Hitoshi Yamaguchi, Kenjiro Tanaka, Jun Tanouchi, Yoshio Yamada
Journal: Circulation (2007)

Backgrounds: Although right ventricular apical (RVA) pacing has been reported to result in asynchronous patterns of left ventricular (LV) contraction reducing the LV ejection fraction (EF), LV torsion in RVA pacing has been unknown. We hypothesized that RVA pacing impairs rotation of LV apex and base and synchrony between LV apical and basal rotation, leading to the reduction of LV torsion. Methods: We studied 30 adult patients with sick sinus syndrome who had undergone DDD pacemaker implantation. Right ventricular pacing leads were positioned at the right ventricular apex. Changing from the intrinsic AV conduction to RVA pacing, we assessed the acute effect on echocardiac parameters; LV EF, tissue Doppler imaging (TDI) derived intraventricular delay, LV rotation and torsion, and LV apical-basal rotation dyssynchrony. Results: Results were shown in a table . Changing from the intrinsic AV conduction to RVA pacing, LV EF reduced (P=0.0003) and TDI derived intraventricular delay prolonged (P&lt;0.0001). During RVA pacing, values of peak rotation in LV apex and LV base were significantly lower than those during intrinsic AV conduction (P=0.007 and 0.003, respectively). Correspondingly, LV torsion decreased significantly (P&lt;0.0001). During the intrinsic AV conduction, LV apex and base rotated at the almost same time, while, during RVA pacing, LV basal rotation was delayed as compared to LV apical rotation. Consequently, apical-basal rotation dyssynchrony during RVA pacing was significantly longer than that during the intrinsic AV conduction (P=0.02). Conclusion: RVA pacing decreases LV rotation and torsion and induces LV apical-basal rotation dyssynchrony, resulting in partially LV systolic dysfunction. Comparison between Intrinsic AV Conduction and RVA Pacing
Abstract 567: Ivabradine Improved Cardiac Function, Fibrosis And Hyperexcitability In Rat Post-myocardial Infarction Severe Heart Failure.
Authors: Paul Milliez, Johnny Nehme, Estelle Robidel, Camille Rodriguez, JaneLise Samuel, Claude Delcayre
Journal: Circulation (2007)

The selective sinus node I f current inhibitor Ivabradine (Iva) reduces heart rate (HR) without any other hemodynamic effects. We investigated in a rat model of post-MI severe heart failure, the effects of a chronic Iva administration on LV function, structure and electrical remodelling. Methods . MI was induced by coronary artery ligation in adult rats: echocardiography and Holter ECG were performed 2 months (m) after MI i.e. before randomization (n=12/group) into MI and MI+Iva (10 mg/kg/d) groups, and 3 m later. In ventricles, collagen was quantified after Sirius red staining of section and ACE and AT1-receptor mRNA expression (normalized to GAPDH) was assayed by RT-PCR. Results : 2m-post MI, all rats displayed severe decreased LVEF, and increased LVEDP compared to sham-operated (28%±3 vs 66%±5 and 32±2 vs 10±1 mmHg, respectively; p&lt;0.05). In 5m-post-MI, LVEF and LVEDP were stabilized with Iva (31±1% and 24±2 mmHg), while they were worsened in MI groups (21±3% and 38±2mmHg). Blood pressure, body and heart weights were similar in MI and MI+Iva. Iva reduced HR (RR: 201±5 vs 179±3 ms in MI; p&lt;0.05) and ventricular premature beats (514±152 vs 4717±1363/day for MI; p&lt;0.05), and improved HR variability (SDRR: 5±1.5 vs 3.9± 0.6 for MI; p&lt;0.05). There were no effects of Iva on duration (ms) of PR (45±3 vs 44±3), QRS (51±3 vs 46±3) and QT (106±7 vs 99±6, for MI and MI+Iva, respectively). The increased ventricular collagen in MI (4.0±0.1 vs 0.8±0.2 % in sham; p&lt;0.05) was markedly reduced in MI+Iva (1.8±0.1%, p&lt;0.0001 vs MI). The increases in ventricular gene expression of ACE and AT-1 receptor in MI rats (2.5 and 6 folds versus sham operated, respectively, p&lt;0.05) were completely blunted by Iva treatment. Conclusion: Iva treatment of the post-MI heart failure: 1- markedly reduced HR and ventricular excitability and without harmful effects on conduction; 2- prevented worsening of LV dysfunction and remodelling, and 3- induced a downregulation of cardiac RAAS transcripts. Thus, through its negative chronotropic effects, Iva allowed the maintenance of cardiac function below the threshold for a tissular RAAS stimulation even in severe post-MI cardiac failure. Such beneficial effects of Iva on cardiac remodelling open new perspectives for the treatment of severe heart failure
Abstract 2859: Baseline Values and Drug-induced Changes of the Ventricular Repolarization Morphology in the Electrocardiograms of Patients with a History of Drug-induced Torsades de Pointes.
Authors: J-Philippe Couderc, Sefan Kaab, Martin Hinterseer, Scott McNitt, Anthony Fossa, J Xia, Wojciech Zareba, Arthur Moss
Journal: Circulation (2007)

Background: Assessing propensity to torsades de pointes (TdP) when exposed to QT-prolonging drug is challenging because baseline QT-prolongation has limited predictive value for identifying risk of TdP. The aim of this study was to determine whether computer-based repolarization morphology parameters could identify individuals who developed drug-induced TdP. Method: Five-minute standard digital 12-lead ECGs were acquired at baseline and after a controlled sotalol challenge (2 mg/kg BW, i.v.) in 34 cardiac patients of whom 17 had a history of TdP (+TdPs) in the context of a QT prolonging drug and 17 had no history of TdP (-TdPs).Computerized ECG parameters including QT, TpTe (T peak to T end interval) and a morphological measure of the duration of the early part of the repolarization interval (ERD) were implemented. All parameters were corrected for the effect of heart rate (HR). Results: There were 9 females among the + TdP patients and 12 females in the -TdP group (p = 0.8). The drugs triggering TdPs were: antidepressant, antibiotics, antiarrhythmic and anti-migraine. They included sotalol, amiodarone, bisacodyl, erythromycin, imipramime, cipramil and sumatriptan. The table below shows the comparison of baseline values and the on-sotalol changes of the repolarization parameters after HR correction. The analysis revealed a longer QT interval duration at baseline in patient +TdPs. This prolongation was only present in the early part of the T-wave (ERD, p = 0.02). On sotalol, the patients with a history of TdPs have longer QT prolongation associated with a significant increased late part of the repolarization (TpTe, p = 0.01). Conclusion : Our results revealed that specific repolarization features are present at baseline and on sotalol challenge in patients with and without history of TdPs. These parameters could complement the role of the QT prolongation as a proarrhythmic surrogate marker. Baseline values and sotalol-induced changes in ECG parameters
Diagnosing multidrug resistant tuberculosis in Britain
Authors: F A Drobniewski
Journal: BMJ (1998)

Each year an estimated 8 million new cases of tuberculosis occur, leading to 3 million deaths; and almost a third of the world's population is infected by the causative bacterium, Mycobacterium tuberculosis. 1 2 The incidence of tuberculosis is rising in Britain too, and London has seen two recent outbreaks of multiple drug resistant tuberculosis—that is, resistance to at least isoniazid and rifampicin—in patients coinfected with HIV.3 This is one of several dramatic outbreaks of multidrug resistant tuberculosis described recently in Europe and the United States. Although overall the problem of resistance remains small in the UK, lessons from recent cases can help clinicians suspect multidrug resistant tuberculosis and enable their laboratory colleagues to identify it quickly. Updated guidelines on the management of cases of tuberculosis have recently been published.4

The UK drug resistance surveillance system MYCOBNET, coordinated by the Public Health Laboratory Service, shows that levels of multidrug resistant tuberculosis in the UK are relatively low but the incidence is higher in London than elsewhere. In 1993-6 rates of multidrug resistant tuberculosis in initial isolates rose from 0.6% to 1.7% overall; in 1993-6 1.9% of isolates from greater London were multidrug resistant compared with 0.9% outside the capital.5

As shown …
Abstract 1493: Erythropoietin Stimulates Endothelial Biosynthesis of Tetrahydrobiopterin by Activation of Phosphatidylinositol 3-kinase/Protein Kinase B Signal Transduction Pathway
Authors: Livius V d’Uscio, Anantha V Santhanam, Zvonimir S Katusic
Journal: Circulation (2007)

Erythropoietin (EPO) has been recognized as a tissue protective cytokine. Recently, it has been shown that vascular protective effects of EPO are dependent on activation of endothelial nitric oxide synthase (eNOS). Tetrahydrobiopterin (BH 4 ) is an essential cofactor required for enzymatic activity of eNOS. Therefore, our objective was to characterize the effect of EPO on biosynthesis of BH 4 in vascular wall. Incubation of isolated wild-type (C57BL/6J) mouse aortas for 18 hours at 37°C in minimal essential medium supplemented with recombinant human EPO (1–50 U/ml) caused concentration-dependent increase in intracellular levels of BH 4 as determined by HPLC analysis. Maximum biosynthesis of BH 4 was detected at therapeutic concentrations of 5 U/mL (15.8±1.3 pmol/mg protein; P&lt;0.05 vs control: 8.2±0.4 pmol/mg protein; n=6 – 8). Oxidative products of BH 4 , 7,8-dihydrobiopterin, were unaffected by EPO indicating that EPO does not affect oxidation of BH 4 . Removal of the endothelium abolished EPO-induced biosynthesis of BH 4 (P&lt;0.05; n=5) demonstrating that the vascular endothelium is a major source of BH 4 . Treatment of intact isolated wild-type mouse aortas with a selective phosphatidylinositol (PI)3-kinase inhibitor wortmannin (1 μM) significantly reduced BH 4 biosynthesis by EPO (8.4±0.6 pmol/mg protein; P&lt;0.05; n=6). Stimulatory effect of EPO on production of BH 4 in aorta was also detected in wild-type mice treated with recombinant human EPO (1000 U/kg, s.c. biweekly) for 14 days (P&lt;0.05; n=6). This vascular effect was abolished in protein kinase B (Akt) 1-deficient mice treated with EPO (P&lt;0.05; n=5). Furthermore, aortic GTP cyclohydrolase I (GTPCH I) enzymatic activity was augmented in EPO treated wild-type mice (0.48±0.12 pmol neopterin/mg protein; P&lt;0.05 vs control: 0.23±0.05 pmol neopterin/mg; n=4) but not in EPO treated Akt 1-deficient mice (0.21±0.03 pmol neopterin/mg; n=4), indicating that the selective increase in BH 4 levels was caused by de-novo biosynthesis of BH 4 via Akt/GTPCH I pathway. Our results demonstrate that EPO stimulates biosynthesis of BH 4 in vascular endothelium. This effect is most likely designed to provide optimal intracellular concentration of cofactor necessary for EPO-induced elevation of eNOS activity.
Abstract 2705: Prognostic Value of Multi-biomarker Approach Using Cystatin C, BNP and Cardiac Troponin T after Initiation of Treatment in Patients with Chronic Heart Failure
Authors: Junnichi Ishii, Shino Kan, Masanori Okumura, Tadashi Nakano, Hiroyuki Naruse, Yoshihisa Mori, Shigeru Matsui, Sadako Motoyama, Masanori Nomura, Hitoshi Hishida, Yukio Ozaki
Journal: Circulation (2007)
A lesson learnt: A view from the other side
Authors: H. Kumar
Journal: BMJ (1999)

I was 18 and had just entered medical school when I visited my aunt and uncle who lived in the same city. After an evening's shopping we returned home, and just as my uncle was getting out of the car, he broke out in sweat and went very pale. He then became so short of breath that he was unable to walk from the car to the house Realising that he was very ill, my aunt and I quickly rushed him to his local doctor in the next street. He gave him a couple of intravenous injections, whispered something to my aunt, and minutes later we were speeding along to the casualty department at my medical school. …
The lithium loading dose method in a clinical setting
Authors: G A Fava, G Molnar, B Block, J S Lee, G I Perini
Journal: American Journal of Psychiatry (1984)

The lithium loading dose method developed by Cooper and associates resulted in achievement of therapeutic concentrations in 29 of 30 psychiatric inpatients. Fewer lithium determinations were required than in 30 other inpatients treated with the traditional trial-and-error technique.
Abstract 3561: Genetic Variants Associated with Acute Myocardial Infarction Risk in Five Ethnic Groups: The INTERHEART genetics study
Authors: Sonia S Anand, Changchun Xie, Alexandre Montpetit, David Serre, Bernard Keavney, Heather Cordell, Matthew McQueen, Salim Yusuf, Thomas Hudson, James C Engert
Journal: Circulation (2007)

Background: The INTERHEART case-control study showed 9 modifiable risk factors (tobacco, diabetes, hypertension, dyslipidemia, abdominal obesity, physical inactivity, psychosocial stress, low fruit...