tbuckley/cabot-search huggingface dataset:
Sagittal Abdominal Diameter and Risk of Sudden Death in Asymptomatic Middle-Aged Men
Authors: J.P. Empana, P. Ducimetiere, M.A. Charles, X. Jouven
Journal: Circulation (2004)

Abdominal (visceral) and overall obesity are both related to coronary heart disease mortality risk; however, the relative contribution of these 2 components of fat deposit in the etiology of sudden death is unknown.We used the data from 7079 asymptomatic men of the Paris Prospective Study I who were free of ischemic heart disease and who were 43 to 52 years of age at first clinical examination between 1967 and 1972. Body mass index (BMI) and sagittal abdominal diameter (SAD) were measured at baseline and used as markers of overall and abdominal obesity. During a follow-up of 23 years, there were 118 sudden deaths and 192 fatal myocardial infarctions. After adjustment for baseline level of cardiovascular risk factors, trunk subcutaneous fat, and thoracic diameter, the ratio of the fifth over the first quintile of SAD was 2.6 (95% CI 1.0 to 6.7) and 2. 6 (95% CI 1.3 to 5.1) for sudden death and fatal myocardial infarction, respectively, and the risk of sudden death increased proportionally with SAD level. The corresponding ratios for BMI were 2.0 (95% CI 1.1 to 3.8) and 1.0 (95% CI 0.6 to 1.7), respectively. Compared with men with low SAD (first tertile) and normal BMI (<25 kg/m2), men with elevated SAD (third tertile) were at increased risk of sudden death but not of fatal myocardial infarction, whether they were of normal weight (multivariate adjusted relative risk 3. 0 [95% CI 1.3 to 6. 9]) or overweight (BMI > or =25 kg/m2; 1.9 [95% CI 1.0 to 3.9]).In asymptomatic French middle-aged men, larger SAD was associated with a particularly increased risk of sudden death, independent of BMI level and known cardiovascular risk factors.
Urinary Polycyclic Aromatic Hydrocarbon Metabolites and Th2 Immunity In Children
Authors: Kinjal M. Hew, Annett I. Walker, Arunima Kohli, Aleena Syed, Cameron McDonald-Hyman, Zheng Li, Andreas Sjodin, Kari C. Nadeau
Journal: Journal of Allergy and Clinical Immunology (2014)
Analysis of 14 Trials Comparing Sirolimus-Eluting Stents with Bare-Metal Stents
Authors: Adnan Kastrati, Julinda Mehilli, Jürgen Pache, Christoph Kaiser, Marco Valgimigli, Henning Kelbaek, Maurizio Menichelli, Manel Sabaté, Maarten J Suttorp, Dietrich Baumgart, Melchior Seyfarth, Matthias E Pfisterer, Albert Schömig
Journal: New England Journal of Medicine (2007)

The long-term effects of treatment with sirolimus-eluting stents, as compared with bare-metal stents, have not been established.We performed an analysis of individual data on 4958 patients enrolled in 14 randomized trials comparing sirolimus-eluting stents with bare-metal stents (mean follow-up interval, 12.1 to 58.9 months). The primary end point was death from any cause. Other outcomes were stent thrombosis, the composite end point of death or myocardial infarction, and the composite of death, myocardial infarction, or reintervention.The overall risk of death (hazard ratio, 1.03; 95% confidence interval [CI], 0.80 to 1.30) and the combined risk of death or myocardial infarction (hazard ratio, 0.97; 95% CI, 0.81 to 1.16) were not significantly different for patients receiving sirolimus-eluting stents versus bare-metal stents. There was a significant reduction in the combined risk of death, myocardial infarction, or reintervention (hazard ratio, 0.43; 95% CI, 0.34 to 0.54) associated with the use of sirolimus-eluting stents. There was no significant difference in the overall risk of stent thrombosis with sirolimus-eluting stents versus bare-metal stents (hazard ratio, 1.09; 95% CI, 0.64 to 1.86). However, there was evidence of a slight increase in the risk of stent thrombosis associated with sirolimus-eluting stents after the first year.The use of sirolimus-eluting stents does not have a significant effect on overall long-term survival and survival free of myocardial infarction, as compared with bare-metal stents. There is a sustained reduction in the need for reintervention after the use of sirolimus-eluting stents. The risk of stent thrombosis is at least as great as that seen with bare-metal stents.
Prevalence of anti-endothelial cell antibodies in idiopathic pulmonary arterial hypertension
Authors: S. J. Arends, J. Damoiseaux, A. Duijvestijn, L. Debrus-Palmans, K. Boomars, B. Broers, J. W. Cohen Tervaert, P. van Paassen
Journal: European Respiratory Journal (2010)

Prevalence of anti-endothelial cell antibodies in idiopathic pulmonary arterial hypertensionTo the Editors:Pulmonary arterial hypertension (PAH) is a rare disease often resulting in right-sided heart failure and premature death [1].PAH is idiopathic (IPAH), heritable, or related to conditions such as connective tissue diseases (CTD) [2].IPAH prognosis remains poor despite improved patient survival with current treatment options.Therefore, elucidating the pathophysiology of IPAH is important for the discovery of novel therapeutic approaches.Inflammation and immune reactivity have been implicated in the pathophysiology of IPAH.In 2005, TAMBY et al.[3] described the presence of anti-endothelial cell antibodies (AECA) in IPAH, pointing at the involvement of humoral immunity.AECA are a heterogeneous family of auto-antibodies capable of reacting with different endothelial cell (EC) structures [4].In PAH, pulmonary EC dysfunction is considered a key player in the initiation and progression of the disease [5].Systemic sclerosis (SSc) is a paradigm of autoimmune PAH, as 10-15% of these patients develop PAH [6].Interestingly, in SSc, immunoglobuliln (Ig)G AECA targeting cell-surface antigens have indeed been shown to induce EC dysfunction [7,8].Thus, IgG AECA-induced endothelial dysfunction may be the initiating event in IPAH.Whereas IgG auto-antibodies are considered pathogenic in various autoimmune diseases, IgM auto-antibodies have been proposed to be protective in these diseases [9].
Mechanisms of the in vivo inhibition of calcification of bioprosthetic porcine aortic valve cusps and aortic wall with triglycidylamine/mercapto bisphosphonate
Authors: H. Scott Rapoport, Jeanne M. Connolly, James Fulmer, Ning Dai, Brandon H. Murti, Robert C. Gorman, Joseph H. Gorman, Ivan Alferiev, Robert J. Levy
Journal: Biomaterials (2006)
Research 2.0: Social Networking and Direct-To-Consumer (DTC) Genomics
Authors: Sandra Soo-Jin Lee, LaVera Crawley
Journal: The American Journal of Bioethics (2009)

The convergence of increasingly efficient high throughput sequencing technology and ubiquitous Internet use by the public has fueled the proliferation of companies that provide personal genetic information (PGI) direct-to-consumers. Companies such as 23andme (Mountain View, CA) and Navigenics (Foster City, CA) are emblematic of a growing market for PGI that some argue represents a paradigm shift in how the public values this information and incorporates it into how they behave and plan for their futures. This new class of social networking business ventures that market the science of the personal genome illustrates the new trend in collaborative science. In addition to fostering a consumer empowerment movement, it promotes the trend of democratizing information--openly sharing of data with all interested parties, not just the biomedical researcher--for the purposes of pooling data (increasing statistical power) and escalating the innovation process. This target article discusses the need for new approaches to studying DTC genomics using social network analysis to identify the impact of obtaining, sharing, and using PGI. As a locus of biosociality, DTC personal genomics forges social relationships based on beliefs of common genetic susceptibility that links risk, disease, and group identity. Ethical issues related to the reframing of DTC personal genomic consumers as advocates and research subjects and the creation of new social formations around health research may be identified through social network analysis.
A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse.
Authors: A Matsuzawa, T Moriyama, T Kaneko, M Tanaka, M Kimura, H Ikeda, T Katagiri
Journal: The Journal of Experimental Medicine (1990)

Several mice with generalized lymphadenopathy were found in the CBA/KlJms (CBA) colony maintained at our institute. A new mutant strain of mice that develop massive lymphoid hyperplasia at 100% incidence within 5 mo after birth was established by crossing these diseased mice. Genetic studies on lymphadenopathy were conducted in F1, F2, and backcross populations from crosses between mutant CBA (CBA-m) and various inbred strains of mice. The results supported the control of lymphadenopathy by a single autosomal recessive gene. Since C3H/He-gld/gld (C3H-gld), MRL/MpJ-lpr/lpr (MRL-lpr), and C3H/HeJ-lpr/lpr (C3H-lpr) mice develop the same type of lymphoid hyperplasia, allelism of the mutant gene with gld or lpr was tested by investigating lymphadenopathy in F1 and backcross populations from crosses between CBA-m and C3H-gld, MRL-lpr, or C3H-lpr mice. The gene was confirmed to be allelic with lpr but not with gld. Interestingly, however, the mutant gene interacted with gld to induce less severe lymphadenopathy. Thus, the mutant gene was named lprcg, an lpr gene complementing gld in induction of lymphoproliferation. The genetic conclusion was supported by the same profile of surface markers of lymphoid cells with gld/gld, lpr/lpr, lprcg/lprcg, lprcg/lpr, and +/gld +/lprcg genotypes, as well as by massive lymph node hyperplasia and high titers of autoantibodies in the first four genotypes, but slight hyperplasia and insignificant autoantibody production in the last. The discovery of lprcg provided strong genetic evidence for the parallels between anomalous phenotypes of gld and lpr, and CBA/KlJms-lprcg/lprcg mice will contribute to elucidation of the mechanism of induction of the same abnormal differentiation and functions of lymphocytes by gld and lpr.
Infant feeding, early weight gain, and risk of type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group.
Authors: E Hyppönen, M G Kenward, S M Virtanen, A Piitulainen, P Virta-Autio, J Tuomilehto, M Knip, H K Akerblom
Journal: Diabetes Care (1999)

OBJECTIVE: To evaluate whether the increased risk of type 1 diabetes conferred by an early introduction of cow's milk supplements can be mediated by accelerated growth in formula-fed infants. RESEARCH DESIGN AND METHODS: All children &amp;lt; or = 14 years of age who were diagnosed with type 1 diabetes from September 1986 to April 1989 were invited to participate in the study. Birth date- and sex-matched control children were randomly selected from the Finnish Population Registry. At least three weight measurements from the first year of life were obtained for 435 full-term diabetic subjects and 386 control subjects from well-baby clinics and school health care units. RESULTS: Increase in body weight was greater in the diabetic girls than in the control girls, and the difference increased from 111 g (95% CI 0-218, P = 0.04) at 1 month of age to 286 g (95% CI 123-450, P = 0.0006) at 7 months. For boys, the difference in weight between the diabetic subjects and the control subjects remained stable during infancy (difference 95 g, 95% CI-2-205, P = 0.09). Increased weight was associated on average with a 1.5-fold risk of type 1 diabetes. Early introduction of formula feeding (&amp;lt; 3 vs. &amp;gt; or = 3 months) was also associated with an increased risk of type 1 diabetes after adjustment for the individual weight gain curve (adjusted odds ratio 1.53, 95% CI 1.1-2.2). No evidence for interaction was observed. CONCLUSIONS: These observations indicate that an early exposure to cow's milk formula-feeding and rapid growth in infancy are independent risk factors of childhood type 1 diabetes.
Comparison of Hemoglobin A1c With Fasting Plasma Glucose and 2-h Postchallenge Glucose for Risk Stratification Among Women With Recent Gestational Diabetes Mellitus
Authors: Catherine Kim, William H. Herman, N. Wah Cheung, Erica P. Gunderson, Caroline Richardson
Journal: Diabetes Care (2011)

OBJECTIVE Postpartum testing with a 75-g 2-h oral glucose tolerance test or fasting plasma glucose (FPG) alone is often not performed among women with histories of gestational diabetes mellitus (GDM). Use of hemoglobin A1c (A1C) might increase testing. The association between A1C and glucose has not been examined in women with histories of GDM. RESEARCH DESIGN AND METHODS We assessed the association of A1C ≥5.7% with FPG ≥100 mg/dL and 2-h glucose ≥140 mg/dL among 54 women with histories of GDM between 6 weeks and 36 months postpartum. RESULTS A1C ≥5.7% had 65% sensitivity and 68% specificity for identifying elevated FPG or 2-h glucose and 75% sensitivity and 62% specificity for elevated FPG alone. The area under the receiver operating characteristic curve for A1C was 0.76 for elevated FPG or 2-h glucose and 0.77 for elevated FPG alone. CONCLUSIONS The agreement between A1C and glucose levels is fair for detection of abnormal glucose tolerance among women with histories of GDM.
Development of Manganese-Based Nanoparticles as Contrast Probes for Magnetic Resonance Imaging
Authors: Zipeng Zhen, Jin Xie
Journal: Theranostics (2012)

MRI is one of the most important imaging tools in clinics. It interrogates nuclei of atoms in a living subject, providing detailed delineation with high spatial and temporal resolutions. To compensate the innate low sensitivity, MRI contrast probes were developed and widely used. These are typically paramagnetic or superparamagnetic materials, functioning by reducing relaxation times of nearby protons. Previously, gadolinium(Gd)-based T(1) contrast probes were dominantly used. However, it was found recently that their uses are occasionally associated with nephrogenic system fibrosis (NSF), which suggests a need of finding alternatives. Among the efforts, manganese-containing nanoparticles have attracted much attention. By careful engineering, manganese nanoparticles with comparable r(1) relaxivities can be yielded. Moreover, other functionalities, be a targeting motif, a therapeutic agent or a second imaging component, can be loaded onto these nanoparticles, resulting in multifunctional nanoplatforms.
Airway and systemic inflammation during Churg-Strauss syndrome natural course
Authors: Manuela Latorre, Chiara Baldini, Federica Novelli, Federico Dente, Stefano Bombardieri, Pier Luigi Paggiaro
Journal: European Respiratory Journal (2012)

Background  : asthma is a key feature in Churg-Strauss syndrome (CSS) but the relationship between airway and systemic manifestations over the follow-up have been scarcely investigated.    Aims  : to compare in CSS patients asthma activity/severity and systemic disease activity/damage, sputum inflammatory markers with inflammatory disease biomarkers, asthma severity and airway inflammation.    Methods  : 35 patients with CSS were enrolled. All patients were assessed for lung function and bronchial hyperreactivity. Asthma severity and control were established according to GINA guidelines and by ACT questionnaire. We measured: sputum eosinophil percentage and exhaled nitric oxide, the Birmingham Vasculitis Activity Score (BVAS) and Vasculitis Damage Index (VDI), peripheral blood eosinophils count, and serum anti-neutrophil cytoplasmic autoantibody, eosinophil cationic protein, IgE, IL2-4-5.    Results  : despite the majority of the patients presented a complete systemic remission (BVAS:14±2 diagnosis vs 2.5±2 follow-up), 80% showed a moderate/severe chronic asthma with vasculitis damage (VDI: 0 at diagnosis vs 1.7±0.8 at follow-up). A significant correlation was detected between sputum eosinophil counts and ACT (r=-0.64, p=0.014) and sputum eosinophil counts and GINA control score (p=0.008). No statistical correlation was found between peripheral eosinophil count and asthma severity, and between sputum inflammatory markers and blood inflammatory mediators.    Conclusion  : chronic asthma negatively affects the natural history of CSS. Sputum inflammatory markers might represent a complementary tool in monitoring asthma component in CSS patients, as well as blood inflammatory disease biomarkers reflect CSS systemic activity.
Intraoperative Magnetic Resonance Imaging for Radiofrequency Ablation of Hepatic Tumors
Authors: Oliver F. Bathe, Houman Mahallati
Journal: Liver Cancer (2009)

Curative resection represents the best therapeutic alternative for colorectal liver metastases and primary liver tumors (Abdalla et al., 2004; Llovet, 2005). For functioning metastatic neuroendocrine tumors, resection for the purpose of debulking is also a therapeutic consideration (Veenendaal et al., 2006). However, in some patients, resection is not feasible because of anatomic constraints, insufficient hepatic functional reserve, or other safety limitations. Radiofrequency ablation (RFA) represents an alternative therapy, but there are limitations to this treatment modality. It is best for small lesions that can be fully ablated by a single placement of the probe (Berber et al., 2005; Komorizono et al., 2003). Larger lesions require multiple probe placements to fully encompass the volume of the target lesion (Figure 7.1). Unfortunately, ultrasound does not clearly delineate the full extent of the burn and it cannot distinguish necrotic from viable tissue (Solbiati et al., 2004). In fact, bubbles occupy the general region of the heated liver and, if multiple heat applications are required, the bubbles produced by the first burns have often dissipated by the time the last burns have been completed. This further impairs the surgeon's ability to estimate the extent of tissue necrosis. Thus, RFA, while a suitable adjunct in some instances, has technical limitations that limit its use in the setting of more extensive lesions. Intraoperative magnetic resonance imaging (iMRI) represents a potential solution to the limitations of RFA. Magnetic resonance imaging provides excellent soft tissue contrast and resolution, and it provides clear visualization of vascular structures. It detects hepatic tumors with high sensitivity, and is known to be useful for following lesions after RFA (Aliberti et al., 2004; Limanond et al., 2003). In view of this, iMRI may be a useful tool for optimizing the application of RFA or other similar ablative adjuncts.
Mycophenolate Mofetil Attenuates Renal Ischemia/Reperfusion Injury
Authors: Carlucci Gualberto Ventura, Terezila Machado Coimbra, Silvia Bernardete de Campos, Isac de Castro, Luis Yu, Antonio Carlos Seguro
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Immunossupressive agents may have an impact on ischemia/reperfusion (I/R) injury. The immunossupressant mycophenolate mofetil (MMF) presents properties that can attenuate such injury. This study investigated the effects of MMF on renal I/R injury. Male Wistar rats received MMF (20 mg/kg per d) or vehicle by gavage beginning 2 d before ischemia and maintained during the entire study. Ischemic injury was induced by bilateral renal arteries occlusion for 60 min. Control rats received MMF and underwent sham operation. At days 1, 2, and 14, post-ischemia renal function was assessed and kidneys were removed for histologic and immunohistochemical studies. MMF given to nonischemic rats did not alter renal function. There was no functional protection at 24 h post-ischemia with MMF. At 2 d, post-ischemia rats pretreated with MMF presented higher inulin clearance compared with untreated rats (0.42 ± 0.04 versus 0.15 ± 0.02 ml/min per 100 g; P < 0.001) and attenuated renal blood flow decrease (5.23 ± 0.28 versus 3.24 ± 0.37 ml/min; P < 0.01). The immunostaining for intercellular adhesion molecule-1 (ICAM-1) was less intense in rats pretreated with MMF. These rats also presented an earlier decreased infiltrating macrophages/lymphocytes and cell proliferation at day 1 post-ischemia. The functional and immunohistochemical analyses performed at day 14 post-ischemia returned to values similar to controls in both groups of rats. To determine whether mycophenolic acid (MPA) could induce cytoprotection, the effects of MPA on normoxic and hypoxic/reoxygenated (H/R) isolated tubule suspensions were also investigated. MPA was not deleterious to normoxic tubules and it was not protective against H/R tubules. In conclusion, pretreatment with MMF attenuates I/R injury in rats and does not limit the recovery from ischemia. The protective effect of MMF by reducing inflammation precedes the hemodynamic changes and tubular injury. E-mail: [email protected]
Long term survivors with metastatic pancreatic adenocarcinoma treated with gemcitabine: a retrospective analysis
Authors: Bernardo HL Goulart, Jeffrey W Clark, Gregory Y Lauwers, David P Ryan, Nina Grenon, Alona Muzikansky, Andrew X Zhu
Journal: Journal of Hematology & Oncology (2009)

Abstract Background Metastatic pancreatic adenocarcinoma has a short median overall survival (OS) of 5–6 months. However, a subgroup of patients survives more than 1 year. We analyzed the survival outcomes of this subgroup and evaluated clinical and pathological factors that might affect survival durations. Methods We identified 20 patients with metastatic or recurrent pancreatic adenocarcinoma who received single-agent gemcitabine and had an OS longer than 1 year. Baseline data available after the diagnosis of metastatic or recurrent disease was categorized as: 1) clinical/demographic data (age, gender, ECOG PS, number and location of metastatic sites); 2) Laboratory data (Hematocrit, hemoglobin, glucose, LDH, renal and liver function and CA19-9); 3) Pathologic data (margins, nodal status and grade); 4) Outcomes data (OS, Time to Treatment Failure (TTF), and 2 year-OS). The lowest CA19-9 levels during treatment with gemcitabine were also recorded. We performed a univariate analysis with OS as the outcome variable. Results Baseline logarithm of CA19-9 and total bilirubin had a significant impact on OS (HR = 1.32 and 1.31, respectively). Median OS and TTF on gemcitabine were 26.9 (95% CI = 18 to 32) and 11.5 (95% CI = 9.0 to 14.3) months, respectively. Two-year OS was 56.4%, with 7 patients alive at the time of analysis. Conclusion A subgroup of patients with metastatic pancreatic cancer has prolonged survival after treatment with gemcitabine. Only bilirubin and CA 19-9 levels were predictive of longer survival in this population. Further analysis of potential prognostic and predictive markers of response to treatment and survival are needed.
What next for tobacco's legal war against regulation?
Authors: A. O'Dowd
Journal: BMJ (2014)

<h3>Abstract</h3> Cotranscriptional processing of RNA polymerase II-generated primary transcripts is a well-documented phenomenon. We recently showed that in plants, miRNA biogenesis is also a cotranscriptional event. Here, we report that Arabidopsis PRP40, the U1 snRNP auxiliary protein, positively regulates the recruitment of SE, the core component of the plant microprocessor, to miRNA genes. The association of DCL1, the microprocessor endoribonuclease, with chromatin was altered in <i>prp40ab</i> mutant plants. Impaired cotranscriptional microprocessor assembly was accompanied by RNA polymerase II accumulation at miRNA genes and retention of miRNA precursors at their transcription sites in the <i>prp40ab</i> mutant plants. We show that cotranscriptional microprocessor assembly, regulated by AtPRP40, positively affects RNAPII transcription of miRNA genes and is important to reach the correct levels of produced miRNAs.