tbuckley/cabot-search huggingface dataset:
Prospective evaluation of a sequential pacing and high-energy bidirectional shock algorithm for transvenous cardioversion in patients with ventricular tachycardia.
Authors: B D Lindsay, S Saksena, S T Rothbart, N Wasty, D Pantopoulos
Journal: Circulation (1987)

Rapid ventricular pacing alone or in combination with low- or intermediate-energy shocks has limited efficacy in cardioverting rapid ventricular tachycardia (VT) when delivered through two transvenous catheter electrodes. This prospective study determined the efficacy and safety of an algorithm that used a sequence of rapid ventricular pacing (RVP) and intermediate-energy (5 and 15 J) and high-energy (25J) single, bidirectional shocks delivered by two transvenous catheter electrodes in conjunction with a cutaneous electrode in patients with sustained VT. The bidirectional shock was simultaneously delivered over two electrical vectors via a common right ventricular apical cathode and tow anodes consisting of the superior vena caval catheter electrode and cutaneous patch. The electrical therapy delivered was determined by the cycle length of VT. Slow VT (cycle length greater than 300 msec) was sequentially treated by RVP followed by incremental bidirectional shocks of 5, 15, and 25 J. Rapid VT (cycle length less than 300 msec) was treated with no incremental bidirectional shocks of 15 and 25 J. VT was reinduced to determine reproducibility of the algorithm for episodes that were successfully terminated. For patients in whom the primary algorithm failed, a second algorithm was used that excluded 5 and 15 J shocks and went directly to a 25 J shock. VT was reinduced twice and the secondary algorithm was evaluated. Thus, reproducibility of termination of VT with the primary and secondary algorithm was examined. Fifty episodes of slow VT and 40 episodes of rapid VT were induced in 22 patients (mean left ventricular ejection fraction 31 +/- 14%). Six patients had rapid VT, nine patients had slow VT, and seven patients had both.(ABSTRACT TRUNCATED AT 250 WORDS)
The search for size: a doping risk factor in adolescent rugby?
Authors: Kevin Till, Ben Jones, Jim McKenna, Lisa Whitaker, Susan H Backhouse
Journal: British Journal of Sports Medicine (2015)

Rugby Union is currently under the spotlight with 18 individuals from the UK currently banned from the sport for committing an anti-doping rule violation(s). Notably, the vast majority of these cases arise from the amateur and/or schoolboy game.1 Beyond the UK, 12 of 52 South African schoolboy rugby players recently returned positive tests for using anabolic androgenic steroids (AAS).2 The drive for players becoming bigger, stronger and faster may be a powerful determinant of these worrisome developments. With this motivation in mind, is it entirely coincidental that such concerns accompany evidence of increased doping that yields these biological changes?

The emphasis on physical attributes within rugby tracks its evolution. For example, the match demands (eg, number of collisions) have increased since professionalisation of the game in the 1990s, accompanied by progressive increases in the size and physical attributes of players.3 A French study4 highlighted the importance of body size (height and body mass) in discriminating between successful and less successful teams in the rugby union World …
CX3CR1+ CD115+ CD135+ common macrophage/DC precursors and the role of CX3CR1 in their response to inflammation
Authors: Cedric Auffray, Darin K. Fogg, Emilie Narni-Mancinelli, Brigitte Senechal, Celine Trouillet, Noah Saederup, Julia Leemput, Karine Bigot, Laura Campisi, Marc Abitbol, Thierry Molina, Israel Charo, David A. Hume, Ana Cumano, Gregoire Lauvau, Frederic Geissmann
Journal: The Journal of Experimental Medicine (2009)

CX3CR1 expression is associated with the commitment of CSF-1R+ myeloid precursors to the macrophage/dendritic cell (DC) lineage. However, the relationship of the CSF-1R+ CX3CR1+ macrophage/DC precursor (MDP) with other DC precursors and the role of CX3CR1 in macrophage and DC development remain unclear. We show that MDPs give rise to conventional DCs (cDCs), plasmacytoid DCs (PDCs), and monocytes, including Gr1+ inflammatory monocytes that differentiate into TipDCs during infection. CX3CR1 deficiency selectively impairs the recruitment of blood Gr1+ monocytes in the spleen after transfer and during acute Listeria monocytogenes infection but does not affect the development of monocytes, cDCs, and PDCs.
A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer
Authors: Y.S. Hong, S.Y. Song, S.I. Lee, H.C. Chung, S.H. Choi, S.H. Noh, J.N. Park, J.Y. Han, J.H. Kang, K.S. Lee, J.Y. Cho
Journal: Annals of Oncology (2004)
Clinical Significance of Differentiation of <i>Mycobacterium massiliense</i> from <i>Mycobacterium abscessus</i>
Authors: Won-Jung Koh, Kyeongman Jeon, Nam Yong Lee, Bum-Joon Kim, Yoon-Hoh Kook, Seung-Heon Lee, Young Kil Park, Chang Ki Kim, Sung Jae Shin, Gwen A. Huitt, Charles L. Daley, O. Jung Kwon
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Mycobacterium massiliense has been recognized as a separate species from Mycobacterium abscessus; however, little is known regarding the clinical impact of this differentiation.Objectives: To compare clinical features and treatment outcomes between patients with M. abscessus lung disease and those with M. massiliense lung disease.Methods: We performed molecular identification of stored clinical isolates of M. abscessus complex and compared clinical characteristics and treatment outcomes between 64 patients with M. abscessus lung disease and 81 patients with M. massiliense lung disease.Measurements and Main Results: The clinical and radiographic manifestations of disease caused by each species were similar. Standardized combination antibiotic therapy, including a clarithromycin-containing regimen in combination with an initial 4-week course of cefoxitin and amikacin, was given to 57 patients (24 with M. abscessus and 33 with M. massiliense) for more than 12 months. The proportion of patients with sputum conversion and maintenance of negative sputum cultures was higher in patients with M. massiliense infection (88%) than in those with M. abscessus infection (25%; P < 0.001). Inducible resistance to clarithromycin (minimal inhibitory concentrations ≥ 32 μg/ml) was found in all tested M. abscessus isolates (n = 19), but in none of the M. massiliense isolates (n = 28).Conclusions: Treatment response rates to combination antibiotic therapy including clarithromycin were much higher in patients with M. massiliense lung disease than in those with M. abscessus lung disease. The inducible resistance to clarithromycin could explain the lack of efficacy of clarithromycin-containing antibiotic therapy against M. abscessus lung disease.
Phase I Safety, Pharmacokinetics, and Clinical Activity Study of Lapatinib (GW572016), a Reversible Dual Inhibitor of Epidermal Growth Factor Receptor Tyrosine Kinases, in Heavily Pretreated Patients With Metastatic Carcinomas
Authors: Howard A. Burris, Herbert I. Hurwitz, E. Claire Dees, Afshin Dowlati, Kimberly L. Blackwell, Bert O'Neil, Paul K. Marcom, Matthew J. Ellis, Beth Overmoyer, Suzanne F. Jones, Jennifer L. Harris, Deborah A. Smith, Kevin M. Koch, Andrew Stead, Steve Mangum, Neil L. Spector
Journal: Journal of Clinical Oncology (2005)

This study (EGF10004) assessed the safety/tolerability, pharmacokinetics, and clinical activity of daily oral dosing with lapatinib (GW572016) in patients with ErbB1-expressing and/or ErbB2-overexpressing advanced-stage refractory solid tumors.Heavily pretreated patients with ErbB1-expressing and/or ErbB2-overexpressing metastatic cancers were randomly assigned to one of five dose cohorts of lapatinib administered once daily. Pharmacokinetic samples were obtained on days 1 and 20. Clinical response was assessed every 8 weeks.Sixty-seven patients with metastatic solid tumors were treated with lapatinib. The most frequently reported drug-related adverse events were diarrhea (42%) and rash (31%). No grade 4 drug-related adverse events were reported. Five grade 3 drug-related toxicities (gastrointestinal events and rash) were experienced by four patients. Drug-related interstitial pneumonitis or cardiac dysfunction associated with other ErbB-targeted therapies was not reported. Four patients with trastuzumab-resistant metastatic breast cancer-two of whom were classified as having inflammatory breast cancer-had partial responses (PRs). Twenty-four patients with various other carcinomas experienced stable disease, of whom 10 received lapatinib for > or = 6 months. The relationships between lapatinib dose or serum concentration and clinical response could not be adequately characterized due to the limited response data. The incidence of diarrhea increased with increasing dose, whereas the incidence of rash was not related to dose.Lapatinib was well tolerated at doses ranging from 500 to 1,600 mg once daily. Clinical activity was observed in heavily pretreated patients with ErbB1-expressing and/or ErbB2-overexpressing metastatic cancers, including four PRs in patients with trastuzumab-resistant breast cancers and prolonged stable disease in 10 patients.
Isolation and Characterization of an Immortal Neoplastic Cell Line (KS Y-1) From AIDS-Associated Kaposi's Sarcoma
Authors: Y. Lunardi-Iskandar, P. Gill, V. H. Lam, R. A. Zeman, F. Michaels, D. L. Mann, M. S. Reitz, M. Kaplan, Z. N. Berneman, D. Carter, J. L. Bryant, R. C. Gallo
Journal: JNCI Journal of the National Cancer Institute (1995)

Background: Acquired immunodeficiency syndrome (AIDS) is associated with the occurrence of tumors such as Kaposi's sarcoma (KS) and B-cell lymphoma. However, no evidence exists yet that human immunodeficiency virus type 1, the causative agent of AIDS, is directly responsible for cell transformation. It is also not clear whether KS lesions, which are of complex cellularity, contain tumor cells derived from a true monoclonal malignancy (originating from a single malignant cell) or whether the lesions are just polyclonally hyperplastic in nature (containing increased numbers of normal cells). In fact, the presence of malignant KS cells has never been unequivocally shown in AIDS-associated KS, and previously isolated KS cell cultures were not immortal or malignant. Purpose: Our purpose was to ( a ) utilize technology that could facilitate isolation and enrichment of tumor cells from AIDS-associated KS lesions, ( b ) establish and characterize an immortalized KS cell line, and ( c ) test the malignant potential of such a cell line in animal models. Methods: Mononuclear cells were isolated from 2.5 L of pleural effusion from an AIDS-associated KS patient. T-lymphocytes, B-lymphocytes, monocytes/macrophages, and fibroblasts were removed by a cytotoxicity method, using monoclonal antibodies specific for cell surface markers and baby rabbit complement. KS cells were cultured in the absence of exogenous growth factors in an effort to select for transformed cells capable of self-sustained growth. The karyotype abnormalities were detected by G-banded marker studies, and phenotypic markers were determined by indirect immunofluorescence and immunocytochemical methods. Beige nude XID and severe combined immunodeficient mice were used to evaluate the tumorigenic, angiogenic, and metastatic potentials of cells. Results: An immortalized cell line, named KS Y-l, was isolated. Its phenotype is similar to that of endothelial cells with positive CD34 and CD31 markers. Tetraploid chromosomal abnormalities were found in primary fresh KS tissue and in vitro passages of KS Y-l cells. These cells promoted tumorigenesis, angiogenesis, and metastasis in immunodeficient mice. Tumors produced at the site of injection, as well as metastases in the lung, spleen, pancreas, gastrointestinal tract, and skin showed a human tetraploid karyotype. KS Y-1 cells show high plating efficiency. Conclusion: The KS Y-l cell line could be the first evidence of AIDS-associated KS cells that may develop clones with an indisputable malignant cell phenotype. Implications: KS Y-l cells in the in vivo mouse model can be used to study the effects of therapeutic compounds in advanced KS. [J Natl Cancer Inst 87:974–981, 1995]
Vascular endothelial growth factor receptor 2–mediated angiogenesis is essential for gonadotropin-dependent follicle development
Authors: Ralf C. Zimmermann, Tipton Hartman, Suzanne Kavic, Samuel A. Pauli, Peter Bohlen, Mark V. Sauer, Jan Kitajewski
Journal: Journal of Clinical Investigation (2003)

Gonadotropins induce ovarian follicle growth that is coincident with increased follicular vasculature, suggesting a role of angiogenesis in follicle development. Functional studies performed in nonhuman primates show that administration of substances that inactivate VEGF block the development and function of preovulatory follicles as demonstrated by histological analysis or hormone measurements. Blockage of function of VEGF receptor 2 (VEGFR-2) alters follicular hormone secretion, suggesting that the intraovarian effect of VEGF might be mediated by this receptor. The specific mechanism by which follicular development was blocked in these previous studies remains unclear, however. Here we characterize the intraovarian role of VEGFR-2 activity on follicular development by choosing a model in which active feedback is absent, the prepuberally hypophysectomized mouse. Hypophysectomy prevents advanced follicle growth and maturation; however, follicle development to the preovulatory stage can be stimulated by administration of gonadotropins. We report that exogenously administered gonadotropins are unable to drive follicle development to the preovulatory stage in the presence of antiangiogenic agent, VEGFR-2–neutralizing Ab’s. This inhibition of follicular development is caused by arrests to both angiogenesis and antrum formation. We conclude that the intraovarian VEGF/VEGFR-2 pathway is critical for gonadotropin-dependent angiogenesis and follicular development.
Effects of Autonomic Nerves and Their Mediators on the Coronary Circulation and Myocardial Contraction
Authors: ADAM B. DENISON, HAROLD D. GREEN, Earl B. Dawson, Thomas W. Kitchen
Journal: Circulation Research (1958)

Mean and phasic coronary flows were recorded simultaneously by an electromagnetic meter, and peripheral coronary pressure was recorded distally from the temporarily occluded descending branch of the left coronary artery. From the results of these studies we conclude that: 1. The sympathetic cardiac nerves, as does levarterenol, increase myocardial contraction, (indicated by a shorter, more abrupt systole and more rapid isometric relaxation), and cause a slight degree of coronary arteriolar dilation. 2. Parasympathetic fibers exert no significant effect, although acetylcholine diminishes coronary arteriolar tone and may slightly diminish ventricular contraction. 3. That measurements of mean coronary flow and resistance are relatively satisfactory for indicating changes in coronary arteriolar tone, but are of relatively little value in evaluating myocardial contraction.
Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation.
Authors: W Luo, I L Grupp, J Harrer, S Ponniah, G Grupp, J J Duffy, T Doetschman, E G Kranias
Journal: Circulation Research (1994)

Phospholamban is the regulator of the Ca(2+)-ATPase in cardiac sarcoplasmic reticulum (SR), and it has been suggested to be an important determinant in the inotropic responses of the heart to beta-adrenergic stimulation. To determine the role of phospholamban in vivo, the gene coding for this protein was targeted in murine embryonic stem cells, and mice deficient in phospholamban were generated. The phospholamban-deficient mice showed no gross developmental abnormalities but exhibited enhanced myocardial performance without changes in heart rate. The time to peak pressure and the time to half-relaxation were significantly shorter in phospholamban-deficient mice compared with their wild-type homozygous littermates as assessed in work-performing mouse heart preparations under identical venous returns, afterloads, and heart rates. The first derivatives of intraventricular pressure (+/- dP/dt) were also significantly elevated, and this was associated with an increase in the affinity of the SR Ca(2+)-ATPase for Ca2+ in the phospholamban-deficient hearts. Baseline levels of these parameters in the phospholamban-deficient hearts were equal to those observed in hearts of wild-type littermates maximally stimulated with the beta-agonist isoproterenol. These findings indicate that phospholamban acts as a critical repressor of basal myocardial contractility and may be the key phosphoprotein in mediating the heart's contractile responses to beta-adrenergic agonists.
Bronchial CD8 Cell Infiltrate and Lung Function Decline in Asthma
Authors: Elizabeth L. J. van Rensen, Jacob K. Sont, Christine E. Evertse, Luuk N. A. Willems, Thais Mauad, Pieter S. Hiemstra, Peter J. Sterk
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Patients with asthma have an accelerated decline in lung function, which can lead to irreversible airway obstruction. It is generally assumed that this is related to specific aspects of airway inflammation and/or remodeling.Objective: We investigated the prognostic significance of bronchial eosinophil and CD8+ cell counts and subepithelial reticular layer thickness for the subsequent decline in lung function in patients with asthma after 7.5 years of follow-up.Methods: In a prospective study, pre- and post-bronchodilator lung function (FEV1) was measured at baseline, and after 2 years and 7.5 years in 32 patients with asthma. Annual decline in lung function after 7.5 years of follow-up was related to type and severity of airway inflammation and remodeling in bronchial biopsies, which were taken at baseline and at Year 2.Results: Annual decline in post-bronchodilator FEV1 (mean [SD], 46.6 [53.4] ml/year) was significantly larger than the decline in prebronchodilator FEV1 (mean [SD], 27.5 [62.5] ml/year), indicating loss in reversibility. Although annual fall in post-bronchodilator FEV1 was not related to thickness of the reticular layer or to eosinophil counts in bronchial biopsies, there was a significant correlation with CD8+ T cells (r = −0.39, p = 0.032). Analyzing the biopsies taken at Year 2, the significant association between annual fall in post-bronchodilator FEV1 and CD8 cells could independently be confirmed (r = −0.39, p = 0.036).Conclusion: The outcome of asthma, as determined by the annual decline in FEV1, can be predicted by the bronchial CD8+ cell infiltrate. This suggests that the inflammatory phenotype in asthma has prognostic relevance, which may require phenotype-specific therapeutic strategies.
Effect of bronchial thermoplasty on airway distensibility
Authors: R. H. Brown
Journal: European Respiratory Journal (2005)

Recent studies have reported that the application of thermal energy delivered through a bronchoscope (bronchial thermoplasty) impairs the ability of airways to narrow in response to methacholine. How such altered smooth muscle affects the response of airways to lung inflation may have important clinical implications, particularly as it relates to the abnormal response of asthmatic subjects to lung inflation and deep inspiration. The aim of this study was to examine whether bronchial thermoplasty affected airway distension with lung inflation in relaxed and contracted airways. A total of 230 airways were studied, ranging 2.5-15 mm, in six dogs. These airways were divided into two groups: an untreated (control) population and a bronchial thermoplasty-treated population. Prior to treatment, the airway pressure-area curves in the two groups of airways were identical. In contrast, the relaxed and contracted airway pressure-area curves in treated airways were shifted upward at all points, showing increased airway area at both 3 and 5 weeks post-treatment. In conclusion, these results show that reducing that amount of functional smooth muscle with bronchial thermoplasty leads to increased airway size in both relaxed and contracted states over a normal range of inflation pressures.
Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: population based cohort study
Authors: N. Roos, H. Kieler, L. Sahlin, G. Ekman-Ordeberg, H. Falconer, O. Stephansson
Journal: BMJ (2011)

To study the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome, taking into account maternal characteristics and assisted reproductive technology.Population based cohort study.Singleton births registered in the Swedish medical birth register between 1995 and 2007.By linkage with the Swedish patient register, 3787 births among women with a diagnosis of polycystic ovary syndrome and 1,191,336 births among women without such a diagnosis.Risk of adverse pregnancy outcomes (gestational diabetes, pre-eclampsia, preterm birth, stillbirth, neonatal death, low Apgar score (<7 at five minutes), meconium aspiration, large for gestational age, macrosomia, small for gestational age), adjusted for maternal characteristics (body mass index, age), socioeconomic factors (educational level, and cohabitating with infant's father), and assisted reproductive technology.Women with polycystic ovary syndrome were more often obese and more commonly used assisted reproductive technology than women without such a diagnosis (60.6% v 34.8% and 13.7% v 1.5%). Polycystic ovary syndrome was strongly associated with pre-eclampsia (adjusted odds ratio 1.45, 95% confidence interval 1.24 to 1.69) and very preterm birth (2.21, 1.69 to 2.90) and the risk of gestational diabetes was more than doubled (2.32, 1.88 to 2.88). Infants born to mothers with polycystic ovary syndrome were more prone to be large for gestational age (1.39, 1.19 to 1.62) and were at increased risk of meconium aspiration (2.02, 1.13 to 3.61) and having a low Apgar score (<7) at five minutes (1.41, 1.09 to 1.83).Women with polycystic ovary syndrome are at increased risk of adverse pregnancy and birth outcomes that cannot be explained by assisted reproductive technology. These women may need increased surveillance during pregnancy and parturition.