tbuckley/cabot-search huggingface dataset:
Abstract 8403: High Mobility Group Box-1 Stimulates Vascular Smooth Muscle Cells Migration via TLR4-dependent PI3K/Akt Pathway Activation
Authors: Jian Yang, Jun Yang, Jia-Wang Ding, Song Li, Wu-Song Dong
Journal: Circulation (2011)

Background: Migration of vascular smooth muscle cells (VSMCs) is a key event in neointimal formation and atherosclerosis. High mobility group box-1 (HMGB1), a highly conserved nuclear protein, can also act as an extracellular chemotactic cytokine for VSMCs. However, the role of HMGB1 receptors and details of signaling in VSMCs migration are largely unexplored. Toll-like receptor 4 (TLR4), a member of HMGB1 cell-surface receptors, is widely distributed in the vasculature. Moreover, TLR4 and its downstream PI3K/Akt pathway have been reported to regulate cell differentiation, proliferation and migration. Therefore, we determined whether TLR4 signaling and PI3K/Akt pathway activation occur in HMGB1-induced VSMCs migration. Methods and results: VSMCs from rat thoracic aorta were studied. We found that HMGB1 stimulated VSMCs migration in a dose-dependent manner, with the highest value (about 3.5-fold increase). In addition, incubation of VSMCs with HMGB1 (100 ng/ml) caused a rapid increase in PI3K activity and Akt phosphorylation ( P both&lt;0.05). Silencing of TLR4 with siRNA significantly inhibited the HMGB1-induced migration of VSMCs by 49.7±6.3%, in comparison to Control siRNA-transfected VSMCs (Figure 1, P &lt;0.05). We also observed that pretreated cells with TLR4 siRNA or the PI3K inhibitor LY294002 could markedly block PI3K/Akt pathway activation and VSMCs migration mediated by HMGB1 ( P both&lt;0.05). Conclusion: These data provide the first evidence that HMGB1-induced VSMCs migration is mediated through a TLR4-dependent PI3K/Akt signaling pathway, which suggest a possible molecular mechanism for HMGB1 may contribute to neointima formation after vascular damage.
Abstract P53: Four Electrocardiogram Waveform Measures Quantify Differences between Electrically Induced and Ischemically Induced Ventricular Fibrillation
Authors: Lawrence D Sherman, James T Niemann, John P Rosborough, James J Menegazzi
Journal: Circulation (2008)

Background: Analysis of the ECG has been shown to be useful to estimate the duration of VF in swine and the probability of successful defibrillation in animals and in patients. We use four methods to analyze the waveform: the logarithm of the absolute correlations (LAC): the median slope (MS): the angular velocity (AV): the amplitude spectrum area (AMSA). We hypothesized that VF produced by ischemia differs from electrically induced VF when analyzed by these measures. Methods: Electrical VF (EVF) was induced in 10 anesthetized and instrumented swine using electrical stimulation of the endocardium. Ischemic VF (IVF) was induced in 10 animals by occlusion of the LAD. After 7 min of VF, chest compressions were performed for 1 min followed by defibrillation. The response to shock was recorded as ROSC if a BP of 60 mmHg was present. LAC, MS, AV and AMSA were calculated on sequential 5 second epochs of VF for 7 minutes. VF was analyzed in segments from1 to 3 minutes, 3 to 4 minutes, and 4 to 7 minutes using the generalized estimating equations method in SAS. Probability of ROSC at first shock was also evaluated for IVF and EVF groups. Results: Differences in curves for all four measures were significant for minutes 1–3 and 4 –7. Curves are shown in Figure . No measure was significant for minute 3– 4. Probability of ROSC at first shock was 50% in the electric VF group and 10% in the ischemic VF group (p=0.039 for mean LAC prior to shock). Conclusions: EVF differs significantly from IVF for all measures both in early VF from 1–3 minutes and late VF from 4 –7 minute. All methods may be valid in predicting “down time” and choosing CPR first or Shock first.
Uptake of breast screening
Authors: K. Boomla, K. Moser, J. Naish
Journal: BMJ (1995)

recommend, as S Field and colleagues do in their editorial,2 that two views should be taken instead of one and that the screening interval should be reduced from three to two years, without even considering the possible adverse effects of repeated exposure to low doses of ionising radiation,3 strikes me as foolhardy.
Lesson of the Week: Pulmonary hypoplasia presenting as persistent tachypnoea in the first few months of life
Authors: N R Aiton, G F Fox, S Hannam, C M M Stern, A D Milner
Journal: BMJ (1996)

Over the past two years four infants with persistent tachypnoea have been referred to this hospital. All were subsequently found to have pulmonary hypoplasia. Two (cases 1 and 2) were self referred from the local population. The third had been admitted under the care of a general paediatrician in this hospital (CMMS), and the fourth case was discovered by chance. All the infants had been born in this hospital, for which the delivery rate is about 3500 a year.

### CASE 1

This boy was born by normal delivery at 39 weeks' gestation after an uneventful pregnancy; he weighed 2960 g. He was seen on the postnatal ward at 12 hours of age for grunting and poor feeding. A chest x ray taken at the time was consistent with transient tachypnoea of the newborn. He was discharged at 5 days of age but remained tachypnoeic. At 3 weeks of age he was admitted with fever and coryzal symptoms, pronounced tachypnoea, and poor feeding. Examination was unremarkable apart from a respiratory rate of 70/minute with mild intercostal recession.

The coryzal illness resolved but he continued to be tachypnoeic. An electrocardiogram and an echocardiogram did not disclose any abnormalities. He was referred for lung function testing at the age of 4 months because of parental anxiety. His functional residual capacity measured by whole body plethysmography was 16.9 ml/kg indicating pulmonary hypoplasia. In our laboratory the normal mean is 29.8 ml/kg (range 17.6-42 ml/kg). Over the first year his respiratory rate gradually settled to 30-35/minute at rest. A repeat measurement at 12 months of age was 20 ml/kg, showing “catch up” lung growth.

### CASE 2

Born …
Phase I/II trial of capecitabine and gefitinib in patients with advanced colorectal cancer after failure of first-line therapy
Authors: A. Jimeno, I. Sevilla, C. Gravalos, M. E. Vega, P. Escudero, E. Torre, F. Rivera, M. L. Garcia de Paredes, R. Colomer, H. Cortes-Funes
Journal: Journal of Clinical Oncology (2005)

3176 Background: Capecitabine is active in advanced colorectal cancer (ACC) and appears to have synergistic activity with gefitinib (IRESSA) in vitro (Magne et al, Clin Cancer Res 2003;9:4735–42). The study aimed to evaluate the safety and efficacy of gefitinib in combination with capecitabine in patients (pts) with ACC. Methods: A multicenter Phase I/II trial recruited pts aged ≥18 years with WHO performance status (PS) ≤2, adequate organ function, and measurable disease. The Phase I study combines gefitinib 250 mg/day with 2 escalating capecitabine doses (1000 and 1250 mg/m2 twice daily on Days 1–14 of a 21-day cycle). The recommended dose of capecitabine (based on the safety and tolerability results from the Phase I study) will then be evaluated in combination with gefitinib in a Phase II trial. Tumor status is assessed every 9 weeks using RECIST. Tumor biomarkers (epidermal growth factor receptor [EGFR], HER2, and thymidylate phosphorylase expression, and the serum levels of EGFR-extracellular domain [ECD], HER2-ECD, and vascular endothelial growth factor) are assessed before and after treatment. Results: To date, 10 pts have been enrolled at doses of 250/1000 (n=6) and 250/1250 (n=4): median age, 62 years (range 47–71); male/female, 9/1; PS 0/≥1, 7/3. The most common adverse drug reactions (NCI-CTC) during the first 2 treatment cycles were: diarrhea (Grade [G] 1, n=5; G2, n=1 for 3 weeks [dose-limiting toxicity]), asthenia (G1, n=2; G2, n=3), rash (G1, n=4; G2, n=1), elevated transaminases (G1, n=1; G3, n=1), anemia (G1, n=3) and leukopenia (G1, n=1). Two treatment interruptions were required, without associated dose reduction. Response assessment (10 pts): stable disease (5), disease progression (1), too early for evaluation (4). Nine pts remain on therapy after 2–7 cycles. Tumor biomarker data will be presented. Conclusions: The combination of gefitinib and capecitabine in ACC appears to have a manageable tolerability profile. IRESSA is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Surveillance of listeria infections in Europe
Authors: H de Valk, C Jacquet, V Goulet, V Vaillant, A Perra, F Simon, J C Desenclos, P Martin
Journal: Eurosurveillance (2005)

In addition to the economic consequences and threats associated with outbreaks, listeriosis remains of great public health concern, as it has one of the highest case fatality rates of all the foodborne infections (20%-30%), and has common source epidemic potential. Changes in the way food is produced, distributed and stored have created the potential for diffuse and widespread outbreaks involving many countries. In 2002, a survey was carried out to assess the need for and the feasibility of a European network on listeria infections in humans. Data on surveillance systems and laboratory methods were collected through two postal surveys sent to the national Centres for communicable disease surveillance and to the listeria reference laboratories. Surveillance systems for listeria infections were in operation in 16 out of the 17 countries surveyed, and 16 countries had a national reference laboratory (NRL). All countries based their case definition of listeriosis on the isolation of Listeria monocytogenes. Fourteen NRLs performed at least one typing method on human strains. At least 13 countries already carried out or expressed willingness to carry out characterisation of isolates by pulsed field gel electrophoresis (PFGE) of L. monocytogenes strains isolated from human cases following a standard protocol. The participants concluded that there was a clear added value to having a European surveillance network for listeria infections, particularly for outbreak detection and investigation, and that a surveillance network based on the existing national surveillance systems was feasible.
Therapy of Molecular Relapse in Acute Promyelocytic Leukemia
Authors: Francesco Lo Coco, Daniela Diverio, Giuseppe Avvisati, Maria C. Petti, Giovanna Meloni, Enrico M. Pogliani, Andrea Biondi, Giuseppe Rossi, Carmelo Carlo-Stella, Carmine Selleri, Bruno Martino, Giorgina Specchia, Franco Mandelli
Journal: Blood (1999)
Fortnightly Review: Glomerulonephritis: diagnosis and treatment
Authors: P D Mason, C D Pusey
Journal: BMJ (1994)

points * Glomerulonephritis presents in many different ways and an accurate diagnosis cannot be made clinically * Dipstix testing of urine is a sensitive way of detecting occult glomerulonephritis once infection has been excluded * Early referral of patients for assessment and renal biopsy is essential to detect treatable conditions * Early treatment is more likely to result in preservation of or improvement in renal function * Patients with glomerular disease of whatever type and severity require long term follow up while urinary abnormalities persist * Assiduous blood pressure control (aiming for < 145/90 mm Hg) is vital to minimise the rate ofprogression of renal failure * Consider antithrombotic and anti-infection prophylaxis in patients with severe and refractory nephrotic syndrome * Specific treatment may be indicated depend- ing on the disease Box 1-Manifestations ofglomerular disease * Asymptomatic proteinuria * Asymptomatic haematuria * The nephrotic syndrome * The nephritic syndrome * Acute/rapidly progressive renal failure * End stage chronic renal failure * Hypertension
Endemic hepatitis E in two Nordic countries
Authors: H Norder, L Sundqvist, L Magnusson, S Østergaard Breum, M Löfdahl, L E Larsen, C K Hjulsager, L Magnius, B  E Böttiger, F Widén
Journal: Eurosurveillance (2009)

Antibodies against hepatitis E virus (anti-HEV) were found in 248 Swedish and Danish patients between 1993 and 2007. Most patients were symptomatic and tested for anti-HEV due to travel abroad. Among patients with known country of infection, most were infected in Asia, mainly on the Indian subcontinent. However, 29 patients were infected in Europe, nine of these had HEV IgM and/or HEV RNA in serum. In sera from 65 of 141 tested patients HEV RNA could be detected, and 63 strains could be typed by limited sequencing within ORF2. HEV RNA was found in sera from 71% of the patients with HEV IgM and IgG and in 18% of the patients with only detectable HEV IgG. It was also found up to three weeks after the onset of disease in 67% of the patients with known date of onset. Patients infected in Europe were infected by genotype 3, and were older than those infected by genotype 1 (mean age 55.3 vs 30 years, p&lt;0.001). Since it is known that genotype 3 can infect domestic pigs, HEV strains from 18 piglets in 17 herds in Sweden and Denmark were sequenced. Phylogenetic analyses of the genotype 3 strains showed geographical clades and high similarity between strains from patients and pigs from the same area. There are thus autochthonous hepatitis E cases in Scandinavia, and there are probably many undiagnosed ones. Patients with hepatitis of unknown etiology should therefore be investigated for anti-HEV even if they have not been outside Europe, since infections acquired from pigs or other animals should be taken into consideration.
Abstract 9177: Mitral Valve Adaptation in Chronic Aortic Regurgitation with Preserved Systolic Function: A Three-Dimensional Echocardiographic Study
Authors: Jonathan Beaudoin, Mark D Handschumacher, Judy Hung, Robert A Levine, Ehud Schwammenthal
Journal: Circulation (2011)

Introduction: Chronic aortic regurgitation (AR) causes left ventricular (LV) remodeling and ultimately heart failure. This creates the potential for functional mitral regurgitation (MR) caused by papillary muscle displacement and mitral valve tethering. However, MR is typically absent during the compensated stage of AR despite substantial LV dilatation. Increased mitral leaflet area has been identified in ischemic and non-ischemic heart failure. It is unknown whether increased mitral valve size could represent a compensatory mechanism capable of preventing MR in patients with LV dilatation due to chronic AR. Hypothesis: Chronic AR is associated with mitral valve enlargement and this can prevent functional MR in patients with LV dilatation. Our objective is to compare mitral valve leaflet area in patients with chronic AR and preserved systolic function to that of normal patients using 3D-echocardiography. Methods: From January to April 2011, we prospectively enrolled 44 patients (22 with at least moderate aortic regurgitation and 22 controls). 3D echocardiograms were performed to assess mitral valve geometry including total diastolic leaflet area measured by a previously validated method. Results: Both groups had normal ejection fraction (60 ± 7 % in AR vs 63 ± 7 % in normals, p=0.17). Only 1 AR patient had significant (more than mild) functional MR. LV volume by 3D echocardiography was significantly larger in the AR group (LV end-diastolic volume index: 80 ± 23 cm3/m2 vs 49 ± 12 cm3/m2, p&lt;0.01). The mitral valve leaflet area indexed for body surface area was significantly increased in the AR group (8.9 ± 1.7 cm2/m2 vs 7.4 ± 1.2 cm2/m2, p&lt;0.01). Patients with AR also had increased mitral leaflet thickness (2.3 ± 0.3 mm vs 2.0 ± 0.3 mm, p&lt;0.01) regardless of AR jet impact on the valve. Mitral valve leaflet area significantly correlated with LV end-diastolic LV volume (p&lt;0.01). Conclusion: Mitral valve leaflet area and thickness are significantly increased in patients with chronic AR and preserved ejection fraction. Area enlargement is proportional to LV volume, and can potentially explain why functional MR is uncommon in this population. Understanding the mechanisms underlying this adaptation could lead to new therapeutic interventions for functional MR.
Effectiveness of combined triazolam-behavioral therapy for primary insomnia
Authors: J B Milby, V Williams, J N Hall, S Khuder, T McGill, V Wooten
Journal: American Journal of Psychiatry (1993)

The authors examined sleep improvement in subjects with primary insomnia who received triazolam plus behavioral therapy (N = 8) or triazolam plus sleep-related information (N = 7). At follow-up, total sleep and restedness in the morning showed greater improvement with combined triazolam-behavioral therapy and returned toward baseline in the control subjects.
Abstract 3961: Macrophage Catalase Overexpression Inhibits Atherosclerosis and Vascular Inflammation
Authors: Juan C Velasquez, Daiana Weiss, Giji Joseph, Natalia Landazuri, W. Robert Taylor
Journal: Circulation (2008)

Previous studies have supported a linkage between hydrogen peroxide (H2O2), intracellular signaling cascades, vascular inflammation, and atherosclerosis. However, the precise role and relevance of macrophage-derived H2O2 in these processes has not been determined. To address this question, we developed transgenic mice on an apoE−/− background with overexpression of catalase in macrophages driven by the lysozyme promoter (Tgcat-mac). Overexpression of the human catalase gene in macrophages was confirmed by immunostaining, and increased enzymatic activity using an Amplex Red-based fluorometric assay on cells obtained from a peritoneal lavage. Tgcat-mac mice were normotensive at baseline and exhibited a hypertensive response to 0.75 mg/kg/day of angiotensin II that did not differ from that of controls. Atherosclerotic lesion surface area was analyzed using en-face preparations of the descending aorta. Tgcat-mac mice were almost completely protected against atherosclerosis that occurred in response to treatme...
Clinical Study Comparing Bleeding and Nonbleeding Rectal Varices
Authors: R. Shudo, Y. Yazaki, S. Sakurai, H. Uenishi, H. Yamada, K. Sugawara
Journal: Endoscopy (2002)

Although rectal varices constitute an important cause of lower digestive tract bleeding in patients with portal hypertension, the etiology and pathology of rectal varices remains controversial, and adequate treatment for rectal varices has yet to be established. In this study, we evaluated rectal varices to identify any common characteristics of varices which are susceptible to hemorrhage.The patients included 40 individuals with rectal varices among 425 patients with portal hypertension who had been treated in our institution. We retrospectively examined patient data regarding underlying hepatic diseases, hepatic function and endoscopic findings with regard to varices.Bleeding from rectal varices occurred in 15 of the 40 patients. Although the prevalence of hemorrhage tended to increase with exacerbation of hepatic dysfunction, no significant differences were found. Similarly, although the incidence of hemorrhage tended to be somewhat higher in patients who had undergone any treatment for complicated esophageal varices than in patients who had not, no significant difference was found. The prevalence of hemorrhage from rectal varices significantly increased in rectal varices of more advanced form, and the prevalence was significantly higher in patients with positive "red color" sign.The prevalence of hemorrhage from rectal varices was significantly higher in patients with rectal varices of advanced form and/or with a positive "red color" sign.
Abstract 21265: Relation of Epicardial Fat Volume Corrected With Body Surface Area to Vulnerable Coronary Plaques Assessed by Multislice Computed Tomography in Patients Without Coronary Artery Calcium
Authors: Kenji Harada, Takashi Yamamoto, Naho Terada, Ayumi Okada, Masahito Shigekiyo, Hiroyoshi Yoshikawa, Shingo Hashimoto, Akira Hirono, Katsuya Tamura, Hiroyuki Fujinaga
Journal: Circulation (2010)

Background: Recent data demonstrated multislice computed tomography (MSCT) have suggested that epicardial adipose tissue (EAT) is related to coronary artery disease (CAD). However, it is unknown th...
The initial encounter: what to do first?
Authors: A Margulies, L L Havens
Journal: American Journal of Psychiatry (1981)

The first interview presents dilemmas to the psychiatric practitioner. Is he or she to concentrate in objective-descriptive fashion, observing symptoms and signs, seeking the likely syndrome or disease concept? Is he or she to work associatively, toward unconscious themes as developed by the psychoanalytic schools? Would an existential approach be best, an attempt to understand the patient's life purposes and difficulties empathically? Alternatively, should the therapist grasp the patient's situation in interpersonal terms? The authors suggest that these decisions are less central than the need to establish a working relationship in order to continue the investigation or treatment and to uncover as much as possible of the relevant data, and that the newer schools of existential and interpersonal psychiatry offer the critical keys to achieving this.
Abstract 3292: AZD6140 Exerts Greater Inhibition of Platelet Aggregation than Clopidogrel in Patients with Stable Atherosclerotic Disease or Unstable Coronary Disease
Authors: Robert F Storey, Christopher P Cannon, Robert A Harrington, Per Morten Sandset, Stanley Heptinstall, Mark Wickens, Gary Peters, Hakan Emanuelsson, Deborah Price, Steen Husted
Journal: Circulation (2006)
Abstract 3116: Subclinical Coronary Atherosclerosis Detected by Coronary CT Angiography in Asymptomatic Population with and without Mild Renal Insufficiency
Authors: Iksung Cho, Hee-Suk Min, Byung-Hee Oh, Young-Bae Park, Sang-Hyun Kim, Sang Il Choi, EunJu Chun, Jung-Won Suh, Dong-Ju Choi, Chul-Ho Kim, Hyuk-Jae Chang
Journal: Circulation (2008)

BACKGROUND The prevalence of coronary artery disease (CAD) increased in patients with moderate to severe renal insufficiency. The impact of renal insufficiency on the development of CAD may increase as renal function continues to deteriorate, however, there is no data available in mild renal insufficiency. The purpose of this study was to explore the association between mild renal insufficiency and coronary atherosclerosis, using coronary CT angiography (CCTA). METHODS We consecutively enrolled 4984 asymptomatic subjects (mean age 49 ± 10 years, 61% male), who underwent CCTA (64-slice MDCT) as part of a general health evaluation. We categorized subjects based on their estimate of renal function (estimated glomerular filtration rate (eGFR), using MDRD equation: ≥ 60 vs. 45 to 59 ml/min/1.73 m 2 ). Patients with eGFR less than 45 ml/min/1.73 m 2 were excluded. Coronary artery calcium score (CACS), presence of plaque, and significant stenosis (≥ 50% lumen diameter) were compared between 2 groups. Regression analysis was performed to assess the correlation between CAD and mild renal insufficiency. RESULTS Three hundreds forty-two subjects (7%) had mild renal insufficiency (eGFR: 45 to 59) and 4642 (93%) had normal renal function (eGFR: ≥ 60 ml/min/1.73 m 2 ). Subjects with mild renal insufficiency showed higher incidence of CAD (124 (36%) vs. 1039 (22%), p&lt;0.001) and significant stenosis (31 (9%) vs. 147 (3%), p&lt;0.001). However, after adjusting conventional risk factors, mild renal insufficiency was no longer an independent risk factor for the presence of CAD and significant stenosis. Furthermore, after age and sex-matching, there was no significant difference in incidence of moderate to severe (≥ 100) CACS (44 (13%) vs. 39 (12%), p=0.64), CAD (122 (36%) vs. 114 (34%), p = 0.57), and significant stenosis (11 (9%) vs. 9 (6%), p = 0.19) between 2 groups. CONCLUSIONS The higher incidence of CAD and significant stenosis in subjects with mild renal insufficiency was observed, however, which are primarily attributed to the effect of other conventional risk factors. Mild renal insufficiency may not act as an independent risk factor for coronary atherosclerosis.