tbuckley/cabot-search huggingface dataset:
Acute scrotum after myocardial infarction
Authors: T. Lane, F. Myint
Journal: Journal of the Royal Society of Medicine (2003)

Mr Hamid and his colleagues (February 2003 JRSM1) report a case of intratesticular haemorrhage after use of abciximab. Such incidents have been reported previously with other anticoagulants.2 Spontaneous haemorrhage should additionally be considered in the differential diagnosis of an acute scrotum even in the absence of underlying disease or concomitant anticoagulant administration.3 Furthermore, haematoma formation may not be restricted to the testis, having been reported at other sites including the spermatic cord.4 Of particular concern when making a presumptive diagnosis of haemorrhage is the association of bleeding with testicular neoplasms, the outcome of which can be critical if associated with a metastatic extension.5 In view of the limitations of ultrasonography, follow-up imaging is desirable, to ensure the absence of an underlying neoplasm.
Bypass Surgery for Chronic Stable Angina: Predictors of Survival Benefit and Strategy for Patient Selection
Authors: Obi N. Nwasokwa, Jerome H. Koss, Gary H. Friedman, Andrew M. Grunwald, Monty M. Bodenheimer
Journal: Annals of Internal Medicine (1991)

The variable mortality risk associated with chronic stable angina calls for careful selection of patients for coronary artery bypass grafting (CABG) if the aim of management is to prolong life. The randomized and observational studies done in the last 20 years have identified the variables relevant to patient selection and thus have provided a rational basis for such clinical decisions. These studies showed that the sicker the patient, as gauged by relevant measures of coronary disease and cardiovascular morbidity, the more likely it is that CABG will prolong life. A CABG-related improvement in survival is therefore more likely to occur the worse the left ventricular function; the greater the number of diseased vessels; the more proximal the location of coronary lesions (more muscle is threatened by such lesions); the greater the severity of the lesions as determined by angiography; the more severe the angina; the more easily provocable the ischemia or the more extreme the measures of ischemia; and, within limits, the older the patient. Greater survival gain after CABG also occurs in patients with peripheral vascular disease, in patients with baseline electrocardiographic ST-segment and T-wave changes, and probably in women. Thus, patients are likely to live longer after CABG if they have left main disease; three-vessel disease with left ventricular dysfunction (ejection fraction less than 50%), class III or IV angina, provocable ischemia, or disease in the proximal left anterior descending coronary artery; two-vessel disease with proximal left anterior descending artery involvement; and two-vessel disease with class III or IV angina as well as either severe left ventricular dysfunction alone or moderate left ventricular dysfunction together with at least one proximal lesion. When the decision of whether to do CABG is less clear-cut, the presence of peripheral vascular disease, female sex, baseline electrocardiographic ST-segment and T-wave changes, or older age (over 60 but under 80 years) should weigh in favor of doing CABG. In general, patients with single-vessel disease do not seem to derive survival benefit from CABG.
Connexins Act as Tumor Suppressors in Three-dimensional Mammary Cell Organoids by Regulating Differentiation and Angiogenesis
Authors: Elizabeth McLachlan, Qing Shao, Hong-ling Wang, Stephanie Langlois, Dale W. Laird
Journal: Cancer Research (2006)

Abstract Connexins are tumor suppressors, and human breast connexin 26 (Cx26) and connexin 43 (Cx43) gap junctions are often down-regulated in breast cancer. We previously showed that Cx26 and Cx43 overexpressed in MDA-MB-231 breast cancer cells inhibited tumor growth in vivo but not in two-dimensional cultures. In the current study, we show that overexpression of Cx26 or Cx43 has tumor-suppressive properties in a three-dimensional environment such that they reduced anchorage-independent cell growth and induced partial redifferentiation of three-dimensional organoids of MDA-MB-231 cells. Importantly, the majority of exogenous connexins did not localize to the cell-cell interface or rescue gap junctional intercellular communication (GJIC) as assessed by dye transfer, providing evidence of a GJIC-independent mechanism of mammary tumor suppression. To further elucidate the mechanisms involved in connexin-induced three-dimensional redifferentiation of tumor cells, we examined whether connexin expression has a role in epithelial to mesenchymal transition (EMT). Cx26 and Cx43 reduced cell migration, increased cytokeratin 18 expression, and decreased vimentin levels, indicating a shift from a mesenchymal towards an epithelial phenotype. In addition, we examined the role of connexins in angiogenesis by probing an angiogenesis antibody array with conditioned media from three-dimensional MDA-MB-231 cultures. This revealed that connexin overexpression regulated various angiogenesis-linked proteins. Furthermore, secreted factors from connexin overexpressing cells inhibited endothelial cell tubulogenesis and migration, and xenografts of Cx43 overexpressing MDA-MB-231 cells showed reduced tumor angiogenesis. In summary, Cx26 and Cx43 inhibit the malignant properties of MDA-MB-231 cells via GJIC-independent mechanisms, including regulation of EMT and angiogenesis. (Cancer Res 2006; 66(20): 9886-94)
STUDIES ON THE PATHOGENESIS OF EXPERIMENTAL PNEUMOCOCCUS PNEUMONIA IN THE DOG
Authors: Morton Hamburger, O. H. Robertson
Journal: The Journal of Experimental Medicine (1940)

A study has been made of the mode of origin of the secondary lesions occurring spontaneously during the course of experimental pneumococcus pneumonia in the dog. It was observed that the primary lesions of dogs exhibiting interlobar spread contained much more edema fluid than did those in which the inflammatory process remained confined to a single lobe. Furthermore, the sequence of spread from lobe to lobe in relation to the anatomical arrangement of the bronchi and the prone position of the animal was such as to suggest that secondary lobe involvement arose as a result of edematous pneumonic exudate flowing into the more dependent bronchial openings. Experiments were undertaken to determine whether pneumococci are constantly being distributed throughout the lung in the experimental disease in varying degree yet produce secondary foci of consolidation only if the microorganisms reach the terminal airways and are retained there through some interference with the normal eliminatory mechanism. Attempts to produce secondary lesions in dogs with non-spreading single lobe involvement, by means of plugging a terminal bronchus of a normal lobe with starch paste or mucin were largely unsuccessful. In only three out of 19 instances did a lesion develop at the site of obstruction. An investigation was then made of the distribution of pneumococci in the lungs of dogs at the height of the pneumonia. In dogs with single lobe lesions pneumococci were recovered from the lesion itself but not from any other part of the peripheral lung tissue, whereas in animals showing spread to other lobes pneumococci were found to be distributed widely throughout the lung in both the apparently normal and the involved lobes. Some of the microscopic sections of the uninvolved parts of the lungs of dogs with metastatic lesions revealed small masses of pneumococcus-containing exudate in the smaller bronchi and terminal airways of otherwise normal tissue. This finding, in conjunction with the detection of beginning inflammatory changes in other areas normal in the gross, would seem to provide direct evidence of the manner in which pneumococci are transferred from the initial lesion to other lobes and highly presumptive evidence for the mode of origin of the secondary lesions.
Sources of cells that contribute to atherosclerotic intimal calcification: an in vivo genetic fate mapping study
Authors: Veena Naik, Elizabeth M. Leaf, Jie Hong Hu, Hsueh-Ying Yang, Ngoc B. Nguyen, Cecilia M. Giachelli, Mei Y. Speer
Journal: Cardiovascular Research (2012)

Vascular cartilaginous metaplasia and calcification are common in patients with atherosclerosis. However, sources of cells contributing to the development of this complication are currently unknown. In this study, we ascertained the origin of cells that give rise to cartilaginous and bony elements in atherosclerotic vessels.We utilized genetic fate mapping strategies to trace cells of smooth muscle (SM) origin via SM22α-Cre recombinase and Rosa26-LacZ Cre reporter alleles. In animals expressing both transgenes, co-existence within a single cell of β-galactosidase [marking cells originally derived from SM cells (SMCs)] with osteochondrogenic (Runx2/Cbfa1) or chondrocytic (Sox9, type II collagen) markers, along with simultaneous loss of SM lineage proteins, provides a strong evidence supporting reprogramming of SMCs towards osteochondrogenic or chondrocytic differentiation. Using this technique, we found that vascular SMCs accounted for ~80% of Runx2/Cbfa1-positive cells and almost all of type II collagen-positive cells (~98%) in atherosclerotic vessels of LDLr-/- and ApoE-/- mice. We also assessed contribution from bone marrow (BM)-derived cells via analysing vessels dissected from chimerical ApoE-/- mice transplanted with green fluorescence protein-expressing BM. Marrow-derived cells were found to account for ~20% of Runx2/Cbfa1-positive cells in calcified atherosclerotic vessels of ApoE-/- mice.Our results are the first to definitively identify cell sources attributable to atherosclerotic intimal calcification. SMCs were found to be a major contributor that reprogrammed its lineage towards osteochondrogenesis. Marrow-derived cells from the circulation also contributed significantly to the early osteochondrogenic differentiation in atherosclerotic vessels.
A1C and Survival in Maintenance Hemodialysis Patients
Authors: Kamyar Kalantar-Zadeh, Joel D. Kopple, Deborah L. Regidor, Jennie Jing, Christian S. Shinaberger, Jason Aronovitz, Charles J. McAllister, David Whellan, Kumar Sharma
Journal: Diabetes Care (2007)

OBJECTIVE—The optimal target for glycemic control has not been established in diabetic dialysis patients. RESEARCH DESIGN AND METHODS—To address this question, the national database of a large dialysis organization (DaVita) was analyzed via time-dependent survival models with repeated measures. RESULTS—Of 82,933 patients undergoing maintenance hemodialysis (MHD) in DaVita outpatient clinics over 3 years (July 2001 through June 2004), 23,618 diabetic MHD patients had A1C measurements at least once. Unadjusted survival analyses indicated paradoxically lower death hazard ratios (HRs) with higher A1C values. However, after adjusting for potential confounders (demographics, dialysis vintage, dose, comorbidity, anemia, and surrogates of malnutrition and inflammation), higher A1C values were incrementally associated with higher death risks. Compared with A1C in the 5–6% range, the adjusted all-cause and cardiovascular death HRs for A1C ≥10% were 1.41 (95% CI 1.25–1.60) and 1.73 (1.44–2.08), respectively (P &amp;lt; 0.001). The incremental increase in death risk for rising A1C values was monotonic and robust in nonanemic patients (hemoglobin &amp;gt;11.0 g/dl). In subgroup analyses, the association between A1C &amp;gt;6% and increased death risk was more prominent among younger patients, those who had undergone dialysis for &amp;gt;2 years, and those with higher protein intake (&amp;gt;1 g · kg−1 · day−1), blood hemoglobin (&amp;gt;11 g/dl), or serum ferritin values (&amp;gt;500 ng/ml). CONCLUSIONS—In diabetic MHD patients, the apparently counterintuitive association between poor glycemic control and greater survival is explained by such confounders as malnutrition and anemia. All things equal, higher A1C is associated with increased death risk. Lower A1C levels not related to malnutrition or anemia appear to be associated with improved survival in MHD patients.
Isolated cat trabeculae in a simulated feline heart and arterial system. Contractile basis of cardiac pump function.
Authors: G Elzinga, N Westerhof
Journal: Circulation Research (1982)

Isolated cat trabeculae were studied under conditions resembling those present for the muscle fibers in the wall of the left ventricle. To obtain such a situation experimental animals, perfusion fluid, temperature, stimulation frequency, peak stress values, contraction sequence, length, and force control were chosen with respect to that criterion. Results were compared with those described for the intact feline heart in previous studies. Special emphasis was placed on determinants of the pump function graph, i.e., the relationship between mean ventricular pressure and output. It was found that peak isometric stress values measured in the trabeculae were about twice as high as those existing on average at the base of the intact left ventricle in the circumferential direction. However, the duration of the mechanical activity, as measured in iso(volu)metric contractions, was in the isolated trabeculae (206 msec) significantly less (P less than 0.01) than found in intact right (292 msec) or intact left ventricle (344 msec). Furthermore the (maximum) output of the intact left ventricle at end-diastolic pressure could not be accounted for in a simple manner by the maximum amount of shortening found in isolated trabeculae. The points of the pump function graph obtained by varying the input impedance of the loading arterial system over a wide range of compliance and resistance values in the steady state deviated only little from the graph obtained from a series of constant pressure levels applied in a beat-to-beat fashion. Therefore, the insensitivity of the pump function graph to the nature of the arterial load is found in the intact heart as well as in isolated cardiac muscle.
Mechanotransduction in mouse inner ear hair cells requires transmembrane channel–like genes
Authors: Yoshiyuki Kawashima, Gwenaëlle S.G. Géléoc, Kiyoto Kurima, Valentina Labay, Andrea Lelli, Yukako Asai, Tomoko Makishima, Doris K. Wu, Charles C. Della Santina, Jeffrey R. Holt, Andrew J. Griffith
Journal: Journal of Clinical Investigation (2011)

Inner ear hair cells convert the mechanical stimuli of sound, gravity, and head movement into electrical signals. This mechanotransduction process is initiated by opening of cation channels near the tips of hair cell stereocilia. Since the identity of these ion channels is unknown, and mutations in the gene encoding transmembrane channel–like 1 (TMC1) cause hearing loss without vestibular dysfunction in both mice and humans, we investigated the contribution of Tmc1 and the closely related Tmc2 to mechanotransduction in mice. We found that Tmc1 and Tmc2 were expressed in mouse vestibular and cochlear hair cells and that GFP-tagged TMC proteins localized near stereocilia tips. Tmc2 expression was transient in early postnatal mouse cochlear hair cells but persisted in vestibular hair cells. While mice with a targeted deletion of Tmc1 (Tmc1Δ mice) were deaf and those with a deletion of Tmc2 (Tmc2Δ mice) were phenotypically normal, Tmc1ΔTmc2Δ mice had profound vestibular dysfunction, deafness, and structurally normal hair cells that lacked all mechanotransduction activity. Expression of either exogenous TMC1 or TMC2 rescued mechanotransduction in Tmc1ΔTmc2Δ mutant hair cells. Our results indicate that TMC1 and TMC2 are necessary for hair cell mechanotransduction and may be integral components of the mechanotransduction complex. Our data also suggest that persistent TMC2 expression in vestibular hair cells may preserve vestibular function in humans with hearing loss caused by TMC1 mutations.
Prudent use of antibiotics: acute exacerbation of COPD as an example
Authors: G. G. U. Rohde
Journal: European Respiratory Journal (2010)

This is an important year for respiratory medicine, as 2010 has been declared “Year of the Lung”. A multitude of activities have been prepared long in advance and many important initiatives are on their way or yet to come. The European Centre for Disease Prevention and Control (ECDC) has, in parallel, been campaigning for several years for a more prudent use of antibiotics 1. Last year was devoted to promoting prudent use of antibiotics to primary care prescribers and this year, a campaign promoting prudent antibiotic use to hospital prescribers is well under way 2. The majority of antibiotics are prescribed for respiratory infections and tuberculosis. The secretary of European Respiratory Society (ERS) Assembly 10 (Respiratory Infections and Tuberculosis) and members of ECDC met recently in order to organise support for European Antibiotic Awareness Day, planned for November 18, 2010. On this date, international respiratory societies also celebrate World COPD Day. This coincidence may be regarded as a signal to illustrate important common aspects of chronic obstructive pulmonary disease (COPD) management and antibiotic awareness.

Antibiotic-resistant strains of pathogenic bacteria are increasingly prevalent in hospitals and the community. Antibiotic prescriptions without clear indication contribute significantly to the increase in antibiotic resistance 3. Acute exacerbation of COPD (AE-COPD), a disease which has become a leading cause of morbidity and mortality worldwide, often results in administration of antibiotics. For example, in one study, antibiotics were found to have been prescribed in 85% of 69,820 patients admitted for AE-COPD to 360 hospitals throughout the USA 4.

The evidence for antibiotic prescription for AE-COPD is weak. Recent data suggest that ∼70% of exacerbations are infectious in origin 5. Of these, only 20–30% can be related to bacteria detected by sputum culture 5. It is difficult to prove that pathogens …
Genome-wide association identifies a susceptibility locus for coronary artery disease in the Chinese Han population
Authors: Fan Wang, Cheng-Qi Xu, Qing He, Jian-Ping Cai, Xiu-Chun Li, Dan Wang, Xin Xiong, Yu-Hua Liao, Qiu-Tang Zeng, Yan-Zong Yang, Xiang Cheng, Cong Li, Rong Yang, Chu-Chu Wang, Gang Wu, Qiu-Lun Lu, Ying Bai, Yu-Feng Huang, Dan Yin, Qing Yang, Xiao-Jing Wang, Da-Peng Dai, Rong-Feng Zhang, Jing Wan, Jiang-Hua Ren, Si-Si Li, Yuan-Yuan Zhao, Fen-Fen Fu, Yuan Huang, Qing-Xian Li, Sheng-Wei Shi, Nan Lin, Zhen-Wei Pan, Yue Li, Bo Yu, Yan-Xia Wu, Yu-He Ke, Jian Lei, Nan Wang, Chun-Yan Luo, Li-Ying Ji, Lian-Jun Gao, Lei Li, Hui Liu, Er-Wen Huang, Jin Cui, Na Jia, Xiang Ren, Hui Li, Tie Ke, Xian-Qin Zhang, Jing-Yu Liu, Mu-Gen Liu, Hao Xia, Bo Yang, Li-Song Shi, Yun-Long Xia, Xin Tu, Qing K Wang
Journal: Nature Genetics (2011)
Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β<sub>2</sub>agonist vilanterol administered once daily for 52 weeks in patients ≥12 years old with asthma: a randomised trial
Authors: William W Busse, Paul M O'Byrne, Eugene R Bleecker, Jan Lötvall, Ashley Woodcock, Leslie Andersen, Wesley Hicks, Jodie Crawford, Loretta Jacques, Ludovic Apoux, Eric D Bateman
Journal: Thorax (2013)

<h3>Background</h3> The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β<sub>2</sub> agonist vilanterol (VI) is in development for asthma and chronic obstructive pulmonary disease. <h3>Objective</h3> To assess the safety and tolerability of FF/VI over 52 weeks in patients with asthma. <h3>Methods</h3> Patients (aged ≥12 years; on inhaled corticosteroid) were randomised (2:2:1) to FF/VI 100/25 µg or FF/VI 200/25 µg once daily in the evening, or fluticasone propionate (FP) 500 µg twice daily. Safety evaluations included adverse events (AEs), non-fasting glucose, potassium, 24-h urinary cortisol excretion, ophthalmic assessments, heart rate and pulse rate. <h3>Results</h3> On-treatment AEs were similar across groups (FF/VI 66–69%; 73% FP). Oral candidiasis/oropharyngeal candidiasis was more common with FF/VI (6–7%) than FP (3%). Twelve serious AEs were reported; one (worsening hepatitis B on FP) was considered drug related. Statistically significant cortisol suppression was seen with FP compared with both FF/VI groups at Weeks 12 and 28 (ratios [95% CI] to FP ranged from 1.43 [1.11 to 1.84] to 1.67 [1.34 to 2.08]; p≤0.006), but not at Week 52 (ratios to FP were 1.05 [0.83 to 1.33] for FF/VI 100/25 µg and 1.09 [0.87 to 1.38] for FF/VI 200/25 µg). No clinically important changes in non-fasting glucose, potassium, QT interval corrected using Fridericia9s formula (QTc[F]) or ophthalmic assessments were reported. Pulse rate (10 min post dose [T<sub>max</sub>], Week 52) was significantly increased with FF/VI versus FP (3.4 bpm, 95% CI 1.3 to 5.6; p=0.002 [FF/VI 100/25 µg]; 3.4 bpm, 95% CI 1.2 to 5.6; p=0.003 [FF/VI 200/25 µg]). Mean heart rate (24-h Holter monitoring) decreased from screening values in all groups (0.2–1.1 bpm FF/VI vs 5 bpm FP; Week 52). <h3>Conclusions</h3> FF/VI (100/25 µg or 200/25 µg) administered once daily over 52 weeks was well tolerated by patients aged ≥12 years with asthma. The overall safety profile of FF/VI did not reveal any findings of significant clinical concern. <h3>ClinicalTrials.gov</h3> NCT01018186
Effects of verapamil, dibutyryl cyclic AMP, and extracellular calcium on intracellular free calcium concentrations in myocytes isolated from rat ventricles
Authors: A. M AULD, J. ASPINALL, G. J BARRITT
Journal: Cardiovascular Research (1987)

The concentration of free calcium in the myoplasm of myocytes isolated from rat ventricles was measured using quin2. Incubation of myocytes with the acetoxymethylester of quin2 (50 μmol·litre−1) for 45 min was required to give effective loading with quin2. At 1 mmol·litre−1extracellular calcium free calcium was 210(17) (n = 5) nmol·litre−1. Depolarisation of myocytes by addition of 40 mmol·litre−1 potassium caused a threefold increase in free calcium. Increases in extracellular calcium from 0.25 to 2.0 mmol·litre−1 caused a twofold increase in free calcium in polarised (resting) myocytes and a 2.5-fold increase in cells depolarised with potassium. The ability of verapamil to inhibit the electrically stimulated contraction of myocytes was dependent on the stimulation voltage. Half-maximal inhibition was given by 0.7 and 2 μmol·litre−1 verapamil at 50 and 100 V stimulation respectively. High concentrations of verapamil completely inhibited potassium induced increases in the fluorescence of quin2 loaded cells. Half-maximal inhibition was observed at 0.5 μmol·litre−1 verapamil. The calcium agonist CGP 28392 enhanced potassium induced fluorescence of quin2 loaded cells. Dibutyryl cyclic adenosine monophosphate and adrenaline increased the proportion of rod shaped cells that contracted in response to stimulation by low, but not high, voltage. Dibutyryl cyclic AMP caused a threefold increase in the potassium induced increase in free calcium. It is concluded that verapamil decreases and that calcium agonists, dibutyryl cyclic AMP, and increases in extracellular calcium increase free calcium, as monitored by intracellular quin2.
Role of galactosylation in the renal pathogenicity of murine immunoglobulin G3 monoclonal cryoglobulins
Authors: Tsuguo Mizuochi, Yves Pastore, Kohdoh Shikata, Aki Kuroki, Shuichi Kikuchi, Thierry Fulpius, Munehiro Nakata, Liliane Fossati-Jimack, Luc Reininger, Misao Matsushita, Teizo Fujita, Shozo Izui
Journal: Blood (2001)
Unraveling the Role of Hypoxia-Inducible Factor in Renal Cell Carcinoma: A Biological and Therapeutic Perspective
Authors: Sumanta Kumar Pal, Robert A. Figlin
Journal: Cancer Discovery (2011)

Abstract The genetic control of hypoxia-inducible factor (HIF) has long been associated with the pathogenesis of clear cell renal cell carcinoma. Only recently have the complex genetics and biology of relevant HIF subtypes been unraveled, leading to potential novel strategies for treating this disease. Cancer Discovery; 1(3); 198–9. © 2011 AACR. Commentary on Shen et al., p. 222.