tbuckley/cabot-search huggingface dataset:
Effect of dietary supplementation with ω-3 fatty acids on progression of atherosclerosis in carotid arteries
Authors: P Angerer
Journal: Cardiovascular Research (2002)

Objective: Omega-3 polyunsaturated fatty acids (ω-3 PUFA) from fish oil slow atherosclerosis progression in coronary arteries, as we showed in a randomized double-blind placebo-controlled clinical trial. Embedded in this trial, the present study examined the influence of 2 years of dietary supplementation with 1.65 g ω-3 PUFA per day on progression of carotid atherosclerosis in 223 patients with coronary artery disease. Methods: Coronary angiography, a comprehensive clinical examination, and intima-media thickness measurement by B-mode ultrasound of the carotid arteries (common, internal and bifurcation), were performed at the study start and study end. An expert panel visually evaluated the global change of carotid atherosclerosis on a semiquantitative scale. A second outcome measure was the change of overall mean maximum intima-media thickness. Results: One hundred and seventy-one patients completed the study. In the global change score, 38% of the patients in the fish oil group and 35% in the placebo group showed progression. Global change was not different between intervention groups. Mean maximum intima-media thickness increased by 0.07±0.13 mm and 0.05±0.11 mm in the fish oil and placebo group, respectively (mean±S.D., P=0.24). No correlation was found between the change in carotid and coronary arteries. Conclusions: In this group of selected patients with documented coronary artery disease ω-3 PUFA given for 2 years did not demonstrate an effect on slowing progression of atherosclerosis in carotid arteries as measured by ultrasound.
CTLA-4Ig suppresses liver injury by inhibiting acquired immune responses in a mouse model of fulminant hepatitis
Authors: Yasuhiro Nakayama, Yukihiro Shimizu, Katsuharu Hirano, Kazumi Ebata, Masami Minemura, Akiharu Watanabe, Toshiro Sugiyama
Journal: Hepatology (2005)

Abstract Expression of costimulatory molecules is significantly upregulated in various organs in an animal model of severe hepatitis induced by injection of Propionibacterium acnes ( P. acnes ) and lipopolysaccharide (LPS). In the present study, we examined whether blockade of costimulatory signals by CTLA-4Ig can suppress the liver injury in this model. We injected an adenovirus encoding CTLA-4Ig (AdCTLA-4Ig) into mice 7 days before, on the same day, or 3 days after P. acnes priming. The virus was found to infect the liver preferentially, and CTLA-4Ig was detected in the serum as early as 2 days after viral injection. After injection of LPS, liver injury and survival rates were examined. Most of the mice not injected with AdCTLA-4Ig died within 12 hours after injection of LPS. In contrast, all the AdCTLA-4Ig–injected mice survived when the virus was injected 7 days before or on the same day as P. acnes priming. Importantly, hemorrhagic liver injury and serum alanine aminotransferase levels were significantly reduced after LPS injection even when AdCTLA-4Ig was injected 3 days after P. acnes priming. Immunological analyses showed that CTLA-4Ig inhibited the activation and expansion of P. acnes –specific CD4+ T cells in the hepatic lymph nodes, leading to a reduction in the recruitment of the cells to the liver. The total amounts of interferon-γ, interleukin-12, and various chemokines in the liver were then decreased, resulting in inhibition of the secondary recruitment of not only T cells but also macrophages. In conclusion , CTLA-4Ig could be useful for treatment of severe liver injury. Supplementary material for this article can be found on the Hepatology website ( http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html ). (Hepatology 2005;42:915–924.)
Complex Interactions Between the Sinoatrial Node and Atrium During Reentrant Arrhythmias in the Canine Heart
Authors: Vadim V. Fedorov, Roger Chang, Alexey V. Glukhov, Geran Kostecki, Deborah Janks, Richard B. Schuessler, Igor R. Efimov
Journal: Circulation (2010)

Background— Numerous studies implicate the sinoatrial node (SAN) as a participant in atrial arrhythmias, including atrial flutter (AFL) and atrial fibrillation (AF). However, the direct role of the SAN has never been described. Methods and Results— The SAN was optically mapped in coronary perfused preparations from normal canine hearts (n=17). Optical action potentials were recorded during spontaneous rhythm, overdrive atrial pacing, and AF/AFL induced by acetylcholine (ACh; 0.3 to 3 μmol/L) and/or isoproterenol (Iso; 0.2 to 1 μmol/L). An optical action potential multiple component algorithm and dominant frequency analysis were used to reconstruct SAN activation and to identify specialized sinoatrial conduction pathways. Both ACh and Iso facilitated pacing-induced AF/AFL by shortening atrial repolarization. The entire SAN structure created a substrate for macroreentry with 9.6±1.7 Hz (69 episodes in all preparations). Atrial excitation waves could enter the SAN through the sinoatrial conduction pathways and overdrive suppress the node. The sinoatrial conduction pathways acted as a filter for atrial waves by slowing conduction and creating entrance block. ACh/Iso modulated filtering properties of the sinoatrial conduction pathways by increasing/decreasing the degree of the entrance block, respectively. Thus, the SAN could beat independently from AF/AFL reentrant activity during ACh (49±39%) and ACh/Iso (62±25%) ( P =0.38). Without ACh, the AF/AFL waves captured the SAN and overdrive suppressed it. Spontaneous SAN activity could terminate or convert AFL to AF during cholinergic withdrawal. Conclusions— The specialized structure of the SAN can be a substrate for AF/AFL. Cholinergic stimulation not only can slow sinus rhythm and facilitate AF/AFL but also protects the intrinsic SAN function from the fast AF/AFL rhythm.
The History of Cryosurgery
Authors: S M Cooper, R P R Dawber
Journal: Journal of the Royal Society of Medicine (2001)

The controlled destruction of tissue by freezing is today widely practised in medicine. Terms for it include cryotherapy, cryocautery, cryocongelation and cryogenic surgery, but cryosurgery (literally, cold handiwork) seems most appropriate. Cryosurgery is a cheap, easy, and safe treatment suitable for both hospital and office based practice. Its major advantage is excellent cosmetic results with minimal scarring.

The benefits of cold have been appreciated for many thousands of years. The ancient Egyptians, and later Hippocrates, were aware of the analgesic and anti-inflammatory properties of cold. Over the past 200 years cold treatment has evolved from generalized application such as hydrotherapy (Figure 1) to specific, focal destruction of tissue—today's cryosurgery.



Figure 1

A man self-administering hydrotherapy. Wellcome Library, London
Macrophage-lymphocyte interaction. II. Antigen-mediated physical interactions between immune guinea pig lymph node lymphocytes and syngeneic macrophages.
Authors: P E Lipsky, A S Rosenthal
Journal: The Journal of Experimental Medicine (1975)

The effect of specific antigen on the development of physical interactions between lymph node lymphocytes (LNL) obtained from animals which had been immunized to that antigen and macrophages was examined. We found that the presence of antigen, either limited to the macrophage () or free in the medium, profoundly increased the degree of ) or free in the medium, profoundly increased the degree of Mphi-LNL interaction observed. This enhanced interaction was dependent on the coincidence in the cultures of Mphi bearing antigen and LNL from animals specifically immunized to that antigen. Although antigen-independent interactions developed equally well between syngeneic and allogeneic combinations of lymphocytes and macrophages, antigen mediated interactions required that macrophages and lymphocytes be syngeneic. Prolongation of antigen-mediated Mphi-LNL interactions resulted in the induction of LNL DNA synthesis, initially involving those lymphocytes physically associated with antigen-bearing Mphi. These studies are interpreted to indicate that physical interaction between immune lymphocytes and antigen-bearing Mphi represents a morphological correlate of the functional activation of immune lymphocytes. Further, it is suggested that the physical events involved in lymphocyte proliferation may proceed sequentially from antigen-independent reversible binding of lymphocytes by macrophages to prolonged antigen-stabilized interaction eventuating in the triggering of specifically immune lymphocytes.
Heterogeneity of Altered Cytokine Levels Across the Clinical Spectrum of Diabetes in China
Authors: Yufei Xiang, Pengcheng Zhou, Xiaojue Li, Gan Huang, Zhenqi Liu, Aimin Xu, R. David Leslie, Zhiguang Zhou
Journal: Diabetes Care (2011)

To determine the relationship between selected cytokines and diabetes in Chinese subjects.Adult patients with recent-onset type 1 diabetes (n=53), latent autoimmune diabetes in adults (LADA) (n=250), and type 2 diabetes (n=285) from multiple centers were compared with normal subjects (n=196). We centrally tested serum GAD antibodies (GADAs), interleukin-6 (IL-6), lipocalin 2 (LCN2), high-sensitivity C-reactive protein (hs-CRP), and adiponectin.After adjustment for age, sex, and BMI, all diabetes types had increased IL-6 and LCN2 (P<0.01), and all four cytokines were increased in LADA (P<0.01). In type 1 diabetes, adiponectin but not hs-CRP was increased (P<0.01), whereas in type 2 diabetes, hs-CRP but not adiponectin was increased (P<0.01). Adiponectin was correlated positively with GADA titer and negatively with hs-CRP (P<0.01 for both).In China, inflammatory markers are increased in all three major types of diabetes, but probably for different reasons, even in autoimmune diabetes.
Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness
Authors: Sylvia Kaaya, Eddy Eustache, Ilana Lapidos-Salaiz, Seggane Musisi, Christina Psaros, Lawrence Wissow
Journal: PLoS Medicine (2013)

In the fourth article of a five-part series providing a global perspective on integrating mental health, Sylvia Kaaya and colleagues discuss the importance of integrating mental health interventions into HIV prevention and treatment platforms. Please see later in the article for the Editors' Summary
Risk of peanut allergy can be reduced by 80% by including peanuts in infant diets, study finds
Authors: Z. Kmietowicz
Journal: BMJ (2015)

Children at risk of food allergies can be prevented from developing a peanut allergy by including peanuts in their diet from about 7 months of age, findings from a randomised trial have shown.1

Experts described the results as “compelling” and said that the study “makes it clear that we can do something now to reverse the increasing prevalence of peanut allergy.” They added that guidelines, which in the past have advised parents to avoid giving peanuts to children at risk of atopic disease, should be rewritten. In the meantime they have given guidance on how to introduce peanuts into the diets of children at risk of food allergies.

The prevalence of peanut allergy among children in developed countries has doubled in the past 10 years and stands at …
Users Fear that Lymphoma Drugs Will Disappear
Authors: K. Garber
Journal: JNCI Journal of the National Cancer Institute (2007)

Y-labeled ibritumomab) at a San Francisco investors’ conference. The U.S. Food and Drug Admi nistration had recently approved Zevalin for the treatment of relapsed non-Hodgkin lymphoma (NHL), the fi fth most common cancer in the country. Initial Zevalin sales were low, but Rastetter expected the drug to take off just like another slow starter, rituximab, approved 5 years earlier. “We will see the same pattern with Zevalin,” Rastetter said, “as this new technology is also tried and then adopted.” But Rastetter was wrong. Over the last 4 years, sales of Zevalin, a radiolabeled antibody, improved little and are now declining. A second lymphoma radiopharmaceutical, Bexxar ( 131 I-labeled tositu
Oncogenic Function of a Novel WD-Domain Protein, STRAP, in Human Carcinogenesis
Authors: Sunil K. Halder, Govindaraj Anumanthan, Ramakoti Maddula, Jason Mann, Anna Chytil, Adriana L. Gonzalez, M. Key Washington, Harold L. Moses, R. Daniel Beauchamp, Pran K. Datta
Journal: Cancer Research (2006)

Abstract The development and progression of malignancies is a complex multistage process that involves the contribution of a number of genes giving growth advantage to cells when transformed. The role of transforming growth factor-β (TGF-β) in carcinogenesis is complex with tumor-suppressor or prooncogenic activities depending on the cell type and the stage of the disease. We have previously reported the identification of a novel WD-domain protein, STRAP, that associates with both TGF-β receptors and that synergizes with the inhibitory Smad, Smad7, in the negative regulation of TGF-β–induced transcription. Here, we show that STRAP is ubiquitously expressed and is localized in both cytoplasm and nucleus. STRAP is up-regulated in 60% colon and in 78% lung carcinomas. Stable expression of STRAP results in activation of mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and in down-regulation of the cyclin-dependent kinase inhibitor p21Cip1, which results in retinoblastoma protein hyperphosphorylation. In addition, we have observed that Smad2/3 phosphorylation, TGF-β–mediated transcription, and growth inhibition are induced in STRAP-knockout mouse embryonic fibroblasts compared with wild-type cells. Ectopic expression of STRAP in A549 lung adenocarcinoma cell line inhibits TGF-β–induced growth inhibition and enhances anchorage-independent growth of these cells. Moreover, overexpression of STRAP increases tumorigenicity in athymic nude mice. Knockdown of endogenous STRAP by small interfering RNA increases TGF-β signaling, reduces ERK activity, increases p21Cip1 expression, and decreases tumorigenicity. Taken together, these results suggest that up-regulation of STRAP in human cancers may provide growth advantage to tumor cells via TGF-β–dependent and TGF-β–independent mechanisms, thus demonstrating the oncogenic function of STRAP. (Cancer Res 2006; 66(12): 6156-66)
Differences in disease severity between combination treatments in a Swedish population
Authors: Linda Ekerljung, Anders Bjerg, Jan Lötvall, Bo Lundbäck
Journal: European Respiratory Journal (2014)

Background: The prevalence of obstructive lung diseases in Sweden approximates that in other Westernized countries. Nonetheless, the distribution of users of [Symbicort (Symb)] and [Seretide (Ser)] is different from comparable countries. The study compares clinical data on morbidity in asthma and COPD between users of [Symb] and [Ser] in a representative population sample.  Methods: From responders (n 18 087) to a postal questionnaire on asthma, performed in a random population sample (16-75y), a random sample of 2000 was invited to clinical examinations and, in addition, all subjects reporting asthma (n=1524) were invited. Of the 2006 participants, 744 had current asthma and 372 fulfilled the GOLD spirometric criteria for COPD  Results: Of the 744 subjects with asthma, 17% used [Symb] while 8% used [Ser]. Uncontrolled asthma according to GINA was present in 20% and 33% respectively (p=0.05). Use of rescue medication ≥3 times per week was 14% and 28%, respectively (p=0.03). Categorized as BDP equipotent doses, 26% of [Symb] users and 6.5% of [Ser] users had ≤500 µg BDP daily, while 3.7% vs. 27.4% had > 600 µg BDP daily (both p  Conclusion: In this large well-characterized population sample, subjects with obstructive airway disease who used [Seretide] had more severe disease compared to [Symbicort] users. This suggests that [Symbicort] is considered a first-line treatment for obstructive airway disease in Sweden, while [Seretide] is reserved for more severe disease.
Impact of noninvasive ventilation on exercise tolerance in subjects with heart failure: Randomized and controlled clinical trial
Authors: Larissa Andrade, Jasiel Nascimento-Junior, Daniella Brandão, Shirley Campos, Ines Remigio, Raquel Britto, Taina Vidal, Wilson Oliveira, Silvia Martins, Armele Dornelas de Andrade
Journal: European Respiratory Journal (2014)

Introduction: Dyspnea and fatigue determine exercise intolerance in heart failure (HF) subjects, hampering performance in activities of daily living. In this context, noninvasive ventilation (NIV) has been used to minimize such impairment, increasing functional capacity Aim: To evaluate the impact of NIV on exercise performance in HF individuals. Methods: A randomized crossover clinical trial with allocation concealment consisted of two experimental phases: NIV and control, 7 days apart of each other. During NIV phase, 30 minutes of bi-level ventilation was performed. Any type of ventilator support was offered during control phase. Functional capacity was assessed by cardiopulmonary exercise test on a treadmill. Results: 24 subjects, 7 (24%) females were evaluated, with a mean ejection fraction of 36.04+8.46%, and mean age of 51.83+10.23 years. NIV determined an increase of maximal oxygen consumption (VO2max) (control: 18.35+4.44 ml/kg/min X NIV: 20.61+4.90 ml/kg/min, p ≤ 0.01); in heart rate (HR) (control: 127.33 +20.96 bpm X NIV: 134.78 +19.53 bpm, p ≤ 0.04) and in heart rate variation (Δ HR) (control: 63.35 +19.34% X NIV : 69.76 +16.66 %, p ≤ 0.02). Also, differences between cardiopulmonary exercise time (CPX-T) (control: 444.50 + 90.53s X NIV 501.05 +103.05s, p =0.01) and recovery time of oxygen consumption (T1/2/VO2) (control: 171,33 + 61.04s X NIV : 144.91 + 49.26s , p= 0.01) were found. Conclusion: NIV promotes a beneficial effect in HF patients by increasing exercise tolerance, optimizing time recovery and improving chronotropic and respiratory reserve.
Joint sepsis: a chance for cure
Authors: D. J. McCarthy
Journal: JAMA (1982)

Most types of joint inflammation can be controlled with empirical therapies, but only in septic joint inflammation is there an opportunity for cure. The retrospective analysis of 32 culture-proved cases of hematogenous septic arthritis in men by Ho and Su in this issue ofThe Journal(p 797) shows a strong direct correlation between duration of symptoms before treatment and the time needed to sterilize the joint fluid after treatment has begun. Time to sterilize the fluid correlated exceedingly well with treatment outcome, whereas the duration of symptoms did not. These findings are similar to those reported in a prospective study of septic bursitis by the same authors. It is generally accepted that the outcome of joint infection in a previously healthy person will be good if appropriate therapy is given within one week from the onset of symptoms. Delay in treatment beyond one week or the presence of serious
Sox9 and programming of liver and pancreatic progenitors
Authors: Yoshiya Kawaguchi
Journal: Journal of Clinical Investigation (2013)

Recent advances in developmental biology have greatly expanded our understanding of progenitor cell programming and the fundamental roles that Sox9 plays in liver and pancreas organogenesis. In the last 2 years, several studies have dissected the behavior of the Sox9+ duct cells in adult organs, but conflicting results have left unanswered the long-standing question of whether physiologically functioning progenitors exist in adult liver and pancreas. On the other hand, increasing evidence suggests that duct cells function as progenitors in the tissue restoration process after injury, during which embryonic programs are sometimes reactivated. This article discusses the role of Sox9 in programming liver and pancreatic progenitors as well as controversies in the field.
Retrovirus-mediated gene transfer in primary T lymphocytes impairs their anti–Epstein-Barr virus potential through both culture-dependent and selection process–dependent mechanisms
Authors: Delphine Sauce, Marie Bodinier, Marina Garin, Bruno Petracca, Nicolas Tonnelier, Anne Duperrier, Junia V. Melo, Jane F. Apperley, Christophe Ferrand, Patrick Hervé, François Lang, Pierre Tiberghien, Eric Robinet
Journal: Blood (2002)
Determination of the Upper Limit of Vulnerability Using Implantable Cardioverter-Defibrillator Electrograms
Authors: Charles Swerdlow, Kalyanam Shivkumar, Jianxin Zhang
Journal: Circulation (2003)

The upper limit of vulnerability (ULV) correlates with the defibrillation threshold and can be determined with 1 episode of ventricular fibrillation (VF). To automate the ULV in an implantable cardioverter-defibrillator (ICD), the most vulnerable intervals must be identified from an ICD electrogram rather than the latest-peaking surface T wave (Tpeak). We hypothesized that the recovery time (TR), defined as the maximum derivative (dV/dt) of the T wave of the shock electrogram, correlates with the most vulnerable intervals.We determined ULV, defibrillation threshold, and the most vulnerable intervals in 25 patients at ICD implantation. The ULV was the weakest T-wave shock that did not induce VF. The most vulnerable intervals were the ones associated with the strongest shocks that induced VF. Telemetered shock electrograms were stored on digital tape and differentiated offline to measure TR. Tpeak and TR were highly correlated (Tpeak-TR=-2+/-11 ms; rho=0.80, P<0.001). At least 1 most vulnerable interval timed between -20 ms and +20 ms relative to Tpeak in all patients and between -40 ms and +20 ms relative to TR in 96% of patients.The recovery time of shock electrograms provides accurate information about global repolarization. TR closely approximates Tpeak. The ULV method may be automated in an ICD by timing T-wave shocks relative to TR.
Comment on: Kromhout et al. n-3 Fatty Acids, Ventricular Arrhythmia–Related Events, and Fatal Myocardial Infarction in Postmyocardial Infarction Patients With Diabetes. Diabetes Care 2011;34:2515–2520
Authors: Ilaria Giordani, Fabiana Picconi, Ilaria Malandrucco, Simona Frontoni
Journal: Diabetes Care (2012)

We read the article by Kromhout et al. (1) with interest. The authors clearly suggest that low-dose supplementation of the n-3 fatty acids eicosapentaenoic acid, docosahexaenoic acid, and α-linolenic acid significantly reduces ventricular arrhythmia–related events in postmyocardial infarction patients with diabetes.

An abnormal cardiac repolarization, due to an imbalance of the autonomic nervous system, could link diabetes and cardiac arrhythmias, as an association was shown between autonomic neuropathy (AN) and abnormalities in sympathovagal balance and QT interval prolongation (2) in diabetic patients.

The sympathovagal balance, expressed as low frequency:high frequency (LF:HF) ratio, represents the most accurate measure of sympathovagal balance (2).

We have previously shown that acute hyperglycemia …