tbuckley/cabot-search huggingface dataset:
The influence of aging and aortic stiffness on permanent dilation and breaking stress of the thoracic descending aorta
Authors: M Groenink
Journal: Cardiovascular Research (1999)

Objective: To assess the influence of aging and aortic stiffness on the extent of irreversible deformation and breaking stress of the human thoracic aorta. Methods: From 14 human heart valve donors without aortic disease (mean age 35 years, range 8–59 years), 14 intact segments of the thoracic descending aorta were studied within 48 h after cardiac arrest. In an experimental setup, the segments were submitted to increasing hydrostatic pressure loads, both statically and dynamically, while radius and wall thickness were monitored echocardiographically. Pressure–radius curves were constructed. Radius and wall thickness were determined at a pressure of 100 mmHg. Radius at elastin resting length and collagen recruitment pressure (Pcol, mmHg) were derived from the pressure–radius relationship and stress–strain curves were constructed to yield Young's moduli of elastin and collagen. Distensibility (D, mmHg−1) was determined while loading the segment with a sinusoidal pressure wave of 120/50 mmHg at both 0.5 and 1 Hz. Subsequently increasing static pressure loads of 400, 800, 1200 and 1600 mmHg were applied. After each pressure load, the increase in aortic radius at a pressure of 100 mmHg (Rinc) was determined. The experiment continued until rupture occurred and breaking stress (σbreak, N m−2) was calculated. donor age and aortic stiffness were correlated with Rinc and σbreak of the aortic segments. Results: Mean breaking stress of the 14 segments was 2.7×106 N m−2. Breaking stress was negatively correlated with age (r2=0.66) and positively with D (r2=0.44) and with Pcol (r2=0.18). Seven segments survived a pressure load of 800 mmHg, in these vessels, the extent of irreversible dilation was positively correlated with age (r2=0.42) and negatively with D (r2=0.40) and Pcol (r2=0.40). Conclusion: Permanent deformation and rupture of the human thoracic aorta following pressure overload are influenced by age, distensibility and collagen recruitment pressure.
Reversing motor vehicle injuries: a preventable tragedy
Authors: Thirupathirajan Thinakararajan, Neil Buxton
Journal: Journal of the Royal Society of Medicine (2008)

In this letter to the editor, the authors review the problem of driveway motor vehicle injuries. They report their experience of treating two children within a short period of six months, both of whom had experienced major head trauma by an automobile being backed up in a home driveway. The authors briefly report the injuries sustained, including the first child's injuries that resulted in his death. They offer suggestions for preventive strategies, including fencing driveways off, adding sensor systems for when the automobile is in reverse, and using rear observing cameras. The authors propose that all new vehicles, not just those in the luxury class, be equipped with these reversing sensor systems, alarms, or cameras. The letter includes computed tomography (CT) brain scans of the two injured children.
Coagulation Factor Xa Induces Endothelium-Dependent Relaxations in Rat Aorta
Authors: Paul Schaeffer, Anne-Marie Mares, Frédérique Dol, Françoise Bono, Jean-Marc Herbert
Journal: Circulation Research (1997)

Abstract The relaxing effect of coagulation factor Xa on phenylephrine-contracted rat aortic rings was compared with the effect of thrombin and trypsin. All three proteases induced a dose-dependent relaxation in the presence of an intact endothelium. EC 50 values were 3±1, 24±9, and 16±1 nmol/L for thrombin, trypsin, and factor Xa, respectively. Whereas thrombin induced rapid relaxations followed by partial recontraction, trypsin and factor Xa induced slower sustained effects. Factor Xa–induced relaxations were not affected by hirudin at high concentrations (1 μmol/L) but were abolished by DX9065A, a specific inhibitor of the catalytic activity of factor Xa. Furthermore, no relaxations to factor Xa could be elicited in the presence of the NO synthase inhibitor N ω -nitro- l -arginine methyl ester (100 μmol/L), whereas relaxations were not altered in the presence of the inactive enantiomer N ω -nitro- d -arginine methyl ester (100 μmol/L). Addition of factor Xa together with thrombin induced relaxations that were larger than those induced by thrombin alone, whereas factor Xa had no additional effects on trypsin-induced relaxations. Furthermore, factor Xa relaxed thrombin-desensitized aortic rings but was ineffective in trypsin-desensitized tissues. These data suggest that factor Xa acts on a cleavable endothelial receptor that induces NO release, resulting in the relaxation of precontracted rat aortic rings. Factor Xa does not act through endothelial thrombin receptors but may activate another cleavable trypsin-sensitive receptor.
One Hundred Years After “Carcinoid”: Epidemiology of and Prognostic Factors for Neuroendocrine Tumors in 35,825 Cases in the United States
Authors: James C. Yao, Manal Hassan, Alexandria Phan, Cecile Dagohoy, Colleen Leary, Jeannette E. Mares, Eddie K. Abdalla, Jason B. Fleming, Jean-Nicolas Vauthey, Asif Rashid, Douglas B. Evans
Journal: Journal of Clinical Oncology (2008)

Purpose Neuroendocrine tumors (NETs) are considered rare tumors and can produce a variety of hormones. In this study, we examined the epidemiology of and prognostic factors for NETs, because a thorough examination of neither had previously been performed. Methods The Surveillance, Epidemiology, and End Results (SEER) Program registries were searched to identify NET cases from 1973 to 2004. Associated population data were used for incidence and prevalence analyses. Results We identified 35,618 patients with NETs. We observed a significant increase in the reported annual age-adjusted incidence of NETs from 1973 (1.09/100,000) to 2004 (5.25/100,000). Using the SEER 9 registry data, we estimated the 29-year limited-duration prevalence of NETs on January 1, 2004, to be 9,263. Also, the estimated 29-year limited-duration prevalence in the United States on that date was 103,312 cases (35/100,000). The most common primary tumor site varied by race, with the lung being the most common in white patients, and the rectum being the most common in Asian/Pacific Islander, American Indian/Alaskan Native, and African American patients. Additionally, survival duration varied by histologic grade. In multivariate analysis of patients with well-differentiated to moderately differentiated NETs, disease stage, primary tumor site, histologic grade, sex, race, age, and year of diagnosis were predictors of outcome (P &lt; .001). Conclusion We observed increased reported incidence of NETs and increased survival durations over time, suggesting that NETs are more prevalent than previously reported. Clinicians need to be become familiar with the natural history and patterns of disease progression, which are characteristic of these tumors.
Decreased haem oxygenase-1 and increased inducible nitric oxide synthase in the lung of severe COPD patients
Authors: P. Maestrelli, C. Páska, M. Saetta, G. Turato, Y. Nowicki, S. Monti, B. Formichi, M. Miniati, L.M. Fabbri
Journal: European Respiratory Journal (2003)

Oxidant/antioxidant imbalance is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). The current study examined the expression of antioxidant and pro-oxidant enzymes, haem oxygenases (HO) and inducible nitric oxide synthase (iNOS) respectively, in patients with severe COPD and control smokers without lung function impairment. Immunoreactivity for HO-1, HO-2, iNOS and nitric oxide-derived oxidants expressed as nitrotyrosine (N-Tyr) was quantified in peripheral lung. HO-1+ alveolar macrophages were decreased in severe COPD compared to control smokers, whereas no difference was observed in iNOS+ macrophages. In contrast, severe patients had significantly higher numbers of iNOS+ cells in alveolar walls. These iNOS+ cells were identified as type 2 pneumocytes and their number was inversely related to HO-1+ macrophages. There were no significant differences in N-Tyr immunostaining between the two groups. However, the rate of protein nitration in lungtissue was directly related to iNOS expression and associated with lower valuesofforced expiratory volume in one second/forced vital capacity. HO-2 was constitutively expressed by type 2 pneumocytes and these cells were increased in severe COPD. In conclusion, the results suggest that the enzymes involved in the oxidative stressresponse may have a different role in the lung defence and that imbalance betweenhaemoxygenase-1 and inducible nitric oxide synthase may be associated withthe development of severe impairment in chronic obstructive pulmonary disease patients.
Role of L-Type Calcium Channels in Pacing-Induced Short-Term and Long-Term Cardiac Memory in Canine Heart
Authors: Alexei N. Plotnikov, Hangang Yu, J. Christoph Geller, Ravil Z. Gainullin, Parag Chandra, Kornelis W. Patberg, Steven Friezema, Peter Danilo, Ira S. Cohen, Steven J. Feinmark, Michael R. Rosen
Journal: Circulation (2003)

Background— We tested the hypothesis that I Ca,L is important to the development of cardiac memory. Methods and Results— The effects of L-type Ca 2+ channel blockade and β-blockade were tested on acutely anesthetized and on chronically instrumented, conscious dogs. Short-term memory (STM) was induced by 2 hours of ventricular pacing and long-term memory (LTM) by ventricular pacing for 21 days. STM dogs received placebo, nifedipine, or propranolol, and LTM dogs received placebo, atenolol, or amlodipine. AT 1 receptor blockade (candesartan) and ACE inhibition (trandolapril) were also tested in LTM. Microelectrodes were used to record transmembrane potentials from isolated epicardial and endocardial slabs using a protocol simulating STM in intact animals. Left ventricular epicardial myocytes from LTM or sham control dogs were dissociated, and I Ca,L was recorded (whole-cell patch-clamp technique). Evolution of STM and LTM was attenuated by I Ca,L blockers but not β-blockers. Neither AT 1 receptor blockade nor ACE inhibition suppressed LTM. In microelectrode experiments, pacing induced an epicardial-endocardial gradient change mimicking STM that was suppressed by nifedipine. In patch-clamp experiments, peak I Ca,L density in LTM and control were equivalent, but activation was more positive and time constants of inactivation longer in LTM ( P &lt;0.05). Conclusions— I Ca,L blockade but not β-adrenergic blockade suppresses cardiac memory. LTM evolution is unaffected by angiotensin II blockade and is associated with altered I Ca,L kinetics.
Reduced insulin secretion in offspring of African type 2 diabetic parents.
Authors: J C Mbanya, L N Pani, D N Mbanya, E Sobngwi, J Ngogang
Journal: Diabetes Care (2000)

To determine the early biochemical predictors of increased susceptibility to develop diabetes in offspring of African type 2 diabetic parents.A total of 69 offspring (case subjects) of 26 families in Cameroon with at least one type 2 diabetic parent were studied, and 62 offspring (control subjects) from 25 families in Cameroon with no parent with type 2 diabetes underwent an oral glucose tolerance test. Early insulin secretion was calculated using the ratio of the 0- to 30-min incremental insulin values to the 0- to 30-min incremental glucose. Anthropometric parameters were also measured.Of the case subjects, 23% were glucose intolerant (4% with diabetes and 19% with impaired glucose tolerance [IGT]) compared with 6.5% (all with IGT) of control subjects (P = 0.02). There was also an increasing prevalence of glucose intolerance, especially IGT with increasing number of glucose-intolerant parents. Fasting serum insulin levels were not different in the two groups; however, at 30 min, the case subjects had lower insulin levels than the control subjects (P < 0.006). Case subjects with IGT had lower 30-min insulin concentration, early insulin secretion, and 2-h insulin levels than those with normal glucose tolerance (NGT) (F = 4.1, P < 0.05; F = 4.1, P < 0.04; and F = 5.1, P < 0.03, respectively). Furthermore, case subjects with NGT and IGT had lower early insulin secretion than control subjects (F = 4. 1, P < 0.03). These differences remained after adjustment for BMI and regardless of the status of parental diabetes. Two-hour insulin concentration showed a positive association (odds ratio = 0.95 CI 0.90-0.99, P = 0.039) with IGT in the case subjects.Diabetes and IGT are more prevalent in the offspring of African type 2 diabetic parents, and this may be due to an underlying degree of beta-cell impairment marked by reduced early-phase insulin secretion.
Endothelium and myocardial protecting actions of taprostene, a stable prostacyclin analogue, after acute myocardial ischemia and reperfusion in cats.
Authors: G Johnson, L E Furlan, N Aoki, A M Lefer
Journal: Circulation Research (1990)

The effects of taprostene, a synthetic prostacyclin analogue, were investigated in a 6-hour model of myocardial ischemia (MI) with reperfusion in anesthetized cats. Taprostene (100 ng/kg/min) was infused intravenously starting 30 minutes postocclusion of the left anterior descending coronary artery followed by reperfusion 1 hour later, and the cats were observed for an additional 4.5 hours. Taprostene infusion resulted in significantly lower plasma creatine phosphokinase activities at every time from 3 to 6 hours for the MI + taprostene group compared with the MI + vehicle group and were not significantly different when compared with sham MI controls. The areas at risk, expressed as a percentage of the total left ventricular weights, were not significantly different between the MI groups. However, the necrotic area expressed as a percentage of the myocardial area at risk was significantly lower in the taprostene-treated cats compared with the untreated MI group (p less than 0.01). Cardiac myeloperoxidase activities indicated that significantly fewer neutrophils were attracted to the area at risk and to the ischemic zone of the MI + taprostene cats when compared with the MI cats given only the vehicle. Data from isolated left anterior descending coronary artery ring preparations removed from hearts after 6 hours of ischemia indicated that the endothelium was damaged by ischemia-reperfusion injury in the untreated cats. However, endothelial dysfunction was not observed in circumflex coronary arteries of ischemic cats or in coronary rings isolated from MI + taprostene cats. Thus, taprostene exerted a significant cardioprotection in cats subjected to ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Rifaximin Therapy for Patients with Irritable Bowel Syndrome without Constipation
Authors: Mark Pimentel, Anthony Lembo, William D. Chey, Salam Zakko, Yehuda Ringel, Jing Yu, Shadreck M. Mareya, Audrey L. Shaw, Enoch Bortey, William P. Forbes
Journal: New England Journal of Medicine (2011)

Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome (IBS). We evaluated rifaximin, a minimally absorbed antibiotic, as treatment for IBS.In two identically designed, phase 3, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2), patients who had IBS without constipation were randomly assigned to either rifaximin at a dose of 550 mg or placebo, three times daily for 2 weeks, and were followed for an additional 10 weeks. The primary end point, the proportion of patients who had adequate relief of global IBS symptoms, and the key secondary end point, the proportion of patients who had adequate relief of IBS-related bloating, were assessed weekly. Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study.Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P=0.01, in TARGET 1; 40.6% vs. 32.2%, P=0.03, in TARGET 2; 40.7% vs. 31.7%, P<0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P=0.005, in TARGET 1; 41.0% vs. 31.9%, P=0.02, in TARGET 2; 40.2% vs. 30.3%, P<0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups.Among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms, bloating, abdominal pain, and loose or watery stools. (Funded by Salix Pharmaceuticals; ClinicalTrials.gov numbers, NCT00731679 and NCT00724126.).
Paediatrician found guilty of manslaughter after boy’s death from septic shock
Authors: Clare Dyer
Journal: BMJ (2015)

<h3>BACKGROUND AND PURPOSE:</h3> The ubiquitous use of the Internet by the public in an attempt to better understand their health care requires the on-line resources written at an appropriate level to maximize comprehension for the average user. The National Institutes of Health and the American Medical Association recommend on-line patient education resources written at a third-to-seventh grade level. We evaluated the readability of the patient education resources provided on the Web site of the American Society of Neuroradiology (http://www.asnr.org/patientinfo/). <h3>MATERIALS AND METHODS:</h3> All patient education material from the ASNR Web site and the Society of Neurointerventional Surgery Web site were downloaded and evaluated with the computer software, Readability Studio Professional Edition, by using 10 quantitative readability scales: the Flesch Reading Ease, Flesch-Kincaid Grade Level, Simple Measure of Gobbledygook, Coleman-Liau Index, Gunning Fog Index, New Dale-Chall, FORCAST Formula, Fry Graph, Raygor Reading Estimate, and New Fog Count. An unpaired <i>t</i> test was used to compare the readability level of resources available on the American Society of Neuroradiology and the Society of Neurointerventional Surgery Web sites. <h3>RESULTS:</h3> The 20 individual patient education articles were written at a 13.9 ± 1.4 grade level with only 5% written at &lt;11th grade level. There was no statistical difference between the level of readability of the resources on the American Society of Neuroradiology and Society of Neurointerventional Surgery Web sites. <h3>CONCLUSIONS:</h3> The patient education resources on these Web sites fail to meet the guidelines of the National Institutes of Health and American Medical Association. Members of the public may fail to fully understand these resources and would benefit from revisions that result in more comprehensible information cast in simpler language.
UNDERSTANDING PRESENTATION OF VIRAL ANTIGENS TO CD8<sup>+</sup>T CELLS IN VIVO: The Key to Rational Vaccine Design
Authors: Jonathan W. Yewdell, S.M. Mansour Haeryfar
Journal: Annual Review of Immunology (2004)

CD8+ T cells play a critical role in antiviral immunity by exerting direct antiviral activity against infected cells. Because of their ability to recognize all types of viral proteins, they offer the promise of providing broad immunity to viruses that evade humoral immunity by varying their surface proteins. Consequently, there is considerable interest in developing vaccines that elicit effective antiviral T(CD8+) responses. Generating optimal vaccines ultimately requires rational design based on detailed knowledge of how T(CD8+) are activated in vivo under natural circumstances. Here we review recent progress obtained largely by in vivo studies in mice to understand the mechanistic basis for activation of naive T(CD8+) in virus infections. These studies point the way to detailed understanding and provide some key information for vaccine development, although much remains to be learned to enable truly rational vaccine design.
NORMATIVE DATA FOR MUSCLE FLEXIBILITY IN MALE SOCCER PLAYERS
Authors: N Bittencourt, J Ocarino, F Sorrentino, F Jales, S Gabriel, L Mendonça, S Fonseca
Journal: British Journal of Sports Medicine (2014)

Background Muscular tightness is frequently postulated as an intrinsic risk factor for a muscle injury in soccer. Further, hamstring, iliopsoas and quadriceps flexibility measurements are of clinical relevance for monitoring recovery after such injury. Objective Describe normative data of flexibility for the hamstring, iliopsoas and quadriceps. Design Cross-sectional study. Setting The modified Thomas test was used to measure flexibility for iliopsoas and quadriceps. The passive knee extension test was used to determine the hamstring flexibility. The ICC of these tests range from 0.97 to 0.99. All these measurements were performed at Sports Injuries Prevention and Rehabilitation Laboratory. Participants 182 elite male soccer players participated in this study; the means for age were of 18.3±3.6 years, body mass of 73.3±8.5 kg and height of 1.78±10.6 m. Assessment of risk factors Hamstring, iliopsoas and quadriceps flexibility. Results For the iliopsoas and quadriceps flexibility the means were -6.76°± 5.7 and 55.2°±8.35 in the dominant leg (DL) and –7.6°±5.1 and 53.1°±8.2 in the non-dominant leg (NDL), respectively. The hamstring means were 134°±8.5 in the DL and 134.7°±8.3 in the NDL. The DL were significantly less flexible than the NDL for iliopsoas (P&lt;.0001) and for the quadriceps the NDL were less flexible (P&lt;.0001). Conclusions The study has provided normative data for a clinical test measuring flexibility of the hamstring, iliopsoas and quadriceps. The athletes had asymmetries between limbs for the MTT and had hamstring flexibility values similar to injured soccer players. Therefore, the flexibility assessment should be performed in preseason to guide preventive interventions and provide baseline values to rehabilitation parameters after a muscle strain.
Expression profiling in APP23 mouse brain: inhibition of Aβ amyloidosis and inflammation in response to LXR agonist treatment
Authors: Iliya Lefterov, Angie Bookout, Zhu Wang, Matthias Staufenbiel, David Mangelsdorf, Radosveta Koldamova
Journal: Molecular Neurodegeneration (2007)

Recent studies demonstrate that in addition to its modulatory effect on APP processing, in vivo application of Liver X Receptor agonist T0901317 (T0) to APP transgenic and non-transgenic mice decreases the level of Aβ42. Moreover, in young Tg2576 mice T0 completely reversed contextual memory deficits. Compared to other tissues, the regulatory functions of LXRs in brain remain largely unexplored and our knowledge so far is limited to the cholesterol transporters and apoE. In this study we applied T0 to APP23 mice for various times and examined gene and protein expression. We also performed a series of experiments with primary brain cells derived from wild type and LXR knockout mice subjected to various LXR agonist treatments and inflammatory stimuli. We demonstrate an upregulation of genes related to lipid metabolism/transport, metabolism of xenobiotics and detoxification. Downregulated genes are involved in immune response and inflammation, cell death and apoptosis. Additional treatment experiments demonstrated an increase of soluble apolipoproteins E and A-I and a decrease of insoluble Aβ. In primary LXRwt but not in LXRα-/-β-/- microglia and astrocytes LXR agonists suppressed the inflammatory response induced by LPS or fibrillar Aβ. The results show that LXR agonists could alleviate AD pathology by acting on amyloid deposition and brain inflammation. An increased understanding of the LXR controlled regulation of Aβ aggregation and clearance systems will lead to the development of more specific and powerful agonists targeting LXR for the treatment of AD.