tbuckley/cabot-search huggingface dataset:
Update in Chronic Obstructive Pulmonary Disease in 2010
Authors: MeiLan K. Han
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

The year 2010 marked several milestones for chronic obstructive pulmonary disease (COPD). Unfortunately, COPD moved from fourth leading cause of death in the United States to third. On the other hand, the United States also celebrated the 1-year anniversary of the Family Smoking Prevention and Tobacco Control Act (FSPTCA), which led to increased regulation of tobacco marketing, and the implementation of public health strategies to reduce tobacco-related morbidity and mortality (1). Also in 2010, the editorial team of the Journal published an article entitled “What the Journal Would Like to Publish on Chronic Obstructive Pulmonary Disease” (2). This article challenged the scientific community to focus on issues such as understanding disease susceptibility, the mechanism of inflammation persistence after smoking exposure is withdrawn, and the multicomponent nature of the disease. The review that follows is an overview of key publications on COPD in the last year. So I invite you to be the judge: Have we risen to the challenge? The obstacles we face in understanding and treating COPD are great, but not unique. The year 2010 also marked the 5-year anniversary for the Bill & Melinda Gates Foundation Grand Challenges in Global Health initiative. In reviewing the past 5 years, Bill Gates reflected, “We were naive when we began.” The rate of discovery in medical research may seem slow relative to the exponential pace of advance in fields such as computing. Yet we are making progress. The articles that follow demonstrate progress in our understanding of host susceptibility and the inflammatory response in COPD, and also the mechanisms of currently available therapies and how biomarkers may help us better target therapies in the future.
EORTC Elderly Task Force and Lung Cancer Group and International Society for Geriatric Oncology (SIOG) experts’ opinion for the treatment of non-small-cell lung cancer in an elderly population
Authors: A.G. Pallis, C. Gridelli, J.P. van Meerbeeck, L. Greillier, U. Wedding, D. Lacombe, J. Welch, C.P. Belani, M. Aapro
Journal: Annals of Oncology (2009)
Cellular fine structure in the invasive nodules of different histogenetic types of malignant melanoma
Authors: J.A.A. HUNTER, S. ZAYNOUN, W.D. PATERSON, S.S. BLEEHEN, RONA MACKIE, A.J. COCHRAN
Journal: British Journal of Dermatology (1978)

Ultrastructural studies were carried out on the invasive nodule of forty malignant melanomas. The findings support the concept that the fine structure of lentigo maligna melanoma is often characteristic, and differs from that of superficial spreading and nodular melanoma. The melanosomes in lentigo maligna melanoma are usually ellipsoidal and resemble those of normal melanocytes, whereas the melanosomes in superficial spreading and nodular melanoma are most often spheroidal and abnormal in appearance. Superficial spreading and nodular melanomas cannot be distinguished reliably by their ultrastructure. Melanosomal appearances could not be related to the presence of a pre-existing naevus or the depth of invasion of the tumour nodule.
Surplus of 2.2bn will help NHS meet future challenges
Authors: A. O'Dowd
Journal: BMJ (2008)

The NHS has performed better than expected financially and has achieved an overall official surplus of £2.2bn (€2.5bn; $3.4bn) for 2007-8, the finalised official figures show.

The report published jointly this week by the spending watchdogs the Audit Commission and the National Audit Office show that the NHS’s recorded surplus is significantly higher than the original forecast of £916m and more than three times that recorded in 2006-7 (£515m).

Their report says that NHS organisations are starting to perform better in financial terms, with only 11 of 340 NHS organisations (3%) reporting a deficit, down from 22% of organisations in 2006-7.

More than a …
Histocompatibility Genes (the H-2 Complex) and Susceptibility to Mammary Tumor Virus in Mice2
Authors: O. Mühlbock, Anna Dux
Journal: JNCI Journal of the National Cancer Institute (1974)

Congenic strains of C57BL/10ScSn (H-2b) mice with the haplotypes H-2a, H-2d, H-2f, H-2i, H-2k, H-2m, H-2r, and H-2pa received mammary tumor virus (MTV) by foster-nursing on (C3H × 020)F1 females. After force breeding of mice, the mammary tumor incidence showed remarkable differences among strains. Relatively resistant were the strains with the haplotypes H-2b and H-2m highly susceptible, those with H-2f, H-2i, H-2d, and H-2a. The others showed intermediate susceptibility. Comparison of the results, especially with the recombinant strains, indicated that genes in or near the D end of the H-2 locus determined the susceptibility to MTV: The subloci 2Db and 2Da determined resistance, and 2Dd and 20f, high susceptibility.
The role of CCL21 in recruitment of T-precursor cells to fetal thymi
Authors: Cunlan Liu, Tomoo Ueno, Sachiyo Kuse, Fumi Saito, Takeshi Nitta, Luca Piali, Hideki Nakano, Terutaka Kakiuchi, Martin Lipp, Georg A. Hollander, Yousuke Takahama
Journal: Blood (2004)
Biobehavioral Influences on Matrix Metalloproteinase Expression in Ovarian Carcinoma
Authors: Susan K. Lutgendorf, Donald M. Lamkin, Nicholas B. Jennings, Jesusa M.G. Arevalo, Frank Penedo, Koen DeGeest, Robert R. Langley, Joseph A. Lucci, Steve W. Cole, David M. Lubaroff, Anil K. Sood
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Stromal cells in the tumor microenvironment, such as macrophages, play an active role in tumor growth and angiogenesis. However, little is known about relationships of biobehavioral factors with angiogenic cytokines and matrix metalloproteinases (MMP) produced by stromal cells. This study examined distress, MMPs, and angiogenic cytokines in ovarian cancer patients and in vitro. Experimental Design: Patients suspected of ovarian cancer completed preoperative questionnaires. At surgery, 56 were confirmed to have epithelial ovarian cancer. Tumor samples were analyzed for macrophage (CD68+) and tumor cell levels of MMP-2, MMP-9, and vascular endothelial growth factor. In vitro stimulation of isolated macrophage cells by the stress hormones norepinephrine and cortisol was done to assess effects on MMP-9. Results: Depressed patients showed significant elevations of MMP-9 in CD68+ cells, adjusting for stage (P &amp;lt; 0.0001). Patients with higher levels of current stress (P = 0.01), life stress over the last 6 months (P = 0.004), and general negative affect (P = 0.007) also showed significantly greater MMP-9 in CD68+ cells. In contrast, higher social support was associated with lower levels of MMP-9 (P = 0.023) and vascular endothelial growth factor (P = 0.036) in tumor cells. In vitro analyses showed that macrophage MMP-9 production could be directly enhanced (up to a 2-fold increase) by the stress hormones norepinephrine and cortisol. Conclusions: Ovarian cancer patients with elevated depressive symptoms, chronic stress, and low social support showed elevations in MMP-9 in tumor-associated macrophages. Direct in vitro enhancement of stromal MMP-9 production by stress hormones was also shown. These findings may have implications for patient outcomes in ovarian cancer.
Treatment of HIV-related Tuberculosis in the Era of Effective Antiretroviral Therapy
Authors: WILLIAM J. BURMAN, BRENDA E. JONES
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Section:ChooseTop of pageAbstract <<INTRODUCTIONOVERLAPPING TOXICITY PROF...PHARMACOKINETIC ISSUES IN...PARADOXICAL REACTIONS (IM...RECOMMENDATIONS FOR THE U...ReferencesCITING ARTICLES
Combining gemcitabine, cisplatin, and ifosfamide (GIP) is active in patients with relapsed metastatic germ-cell tumors (GCT): a prospective multicenter GETUG phase II trial
Authors: K. Fizazi, G. Gravis, A. Flechon, L. Geoffrois, C. Chevreau, B. Laguerre, R. Delva, J.C. Eymard, F. Rolland, N. Houede, A. Laplanche, D. Burcoveanu, S. Culine
Journal: Annals of Oncology (2014)
Identification of a Novel Role of T Cells in Postnatal Vasculogenesis
Authors: Jin Hur, Han-Mo Yang, Chang-Hwan Yoon, Choon-Soo Lee, Kyung-Woo Park, Ji-Hyun Kim, Tae-Youn Kim, Ju-Young Kim, Hyun-Jae Kang, In-Ho Chae, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2007)

The colony number of early endothelial progenitor cells (EPCs) has been used as a quantitative indicator of the number of EPCs in the blood or as a biological marker of cardiovascular diseases. In the present study, we found a subset of T cells that were localized at the center of the EPC colony and played a pivotal role in colony formation and differentiation of early EPCs.We found that CD3+ CD31+ CXCR4+ T cells (referred to as angiogenic T cells in the present study) constituted the center of EPC colonies during cultures of human peripheral blood mononuclear cells. These angiogenic T cells were required for colony formation and differentiation of early EPCs. They secreted high levels of angiogenic cytokines such as vascular endothelial growth factor, interleukin-8, and matrix metalloproteinases. Angiogenic T cells showed superior angiogenic potential to the other subset of T cells in the experiments with regard to Matrigel tube formation, adhesion, transendothelial migration, and collagen invasion assay, mainly through the stromal cell-derived factor 1/CXCR-4 axis. Furthermore, angiogenic T cells enhanced endothelial cell proliferation and function. In vivo study showed that angiogenic T cells play an important role in the process of vessel formation. Clinical study showed that the level of angiogenic T cells in the peripheral blood was well correlated with EPC colony numbers and had inverse relationships with age and the number of risk factors for coronary artery disease.These findings suggest that angiogenic T cells could be a potential therapeutic target for ischemic cardiovascular diseases.
Hydrogen Peroxide Activates Mitogen-Activated Protein Kinases and Na <sup>+</sup> -H <sup>+</sup> Exchange in Neonatal Rat Cardiac Myocytes
Authors: Abdelkarim Sabri, Kenneth L. Byron, Allen M. Samarel, Jeremy Bell, Pamela A. Lucchesi
Journal: Circulation Research (1998)

Abstract —Reperfusion of cardiac tissue after an ischemic episode is associated with metabolic and contractile dysfunction, including reduced tension development and activation of the Na + -H + exchanger (NHE). Oxygen-derived free radicals are key mediators of reperfusion abnormalities, although the cellular mechanisms involved have not been fully defined. In the present study, the effects of free radicals on mitogen-activated protein (MAP) kinase function were investigated using cultured neonatal rat ventricular myocytes. Acute exposure of spontaneously beating myocytes to 50 μmol/L hydrogen peroxide (H 2 O 2 ) caused a sustained decrease in contraction amplitude (80% of control). MAP kinase activity was measured by in-gel kinase assays and Western blot analysis. Acute exposure to H 2 O 2 (100 μmol/L, 5 minutes) resulted in sustained MAP kinase activation that persisted for 60 minutes. Catalase, but not superoxide dismutase, completely inhibited MAP kinase activation by H 2 O 2 . Pretreatment with chelerythrine (10 μmol/L, 45 minutes), a protein kinase C inhibitor, or genistein (75 μmol/L, 45 minutes) or herbimycin A (3 μmol/L, 45 minutes), tyrosine kinase inhibitors, caused significant inhibition of H 2 O 2 -stimulated MAP kinase activity (51%, 78%, and 45%, respectively, at 20 minutes). Brief exposure to H 2 O 2 also stimulated NHE activity. This effect was completely abolished by pretreatment with the MAP kinase kinase inhibitor PD 98059 (30 μmol/L, 60 minutes). These results suggest that low doses of H 2 O 2 induce MAP kinase–dependent pathways that regulate NHE activity during reperfusion injury.
Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus
Authors: James Bentham, David L Morris, Deborah S Cunninghame Graham, Christopher L Pinder, Philip Tombleson, Timothy W Behrens, Javier Martín, Benjamin P Fairfax, Julian C Knight, Lingyan Chen, Joseph Replogle, Ann-Christine Syvänen, Lars Rönnblom, Robert R Graham, Joan E Wither, John D Rioux, Marta E Alarcón-Riquelme, Timothy J Vyse
Journal: Nature Genetics (2015)
Reversible depression in myocardial performance in dogs with experimental phosphorus deficiency.
Authors: T J Fuller, W W Nichols, B J Brenner, J C Peterson
Journal: Journal of Clinical Investigation (1978)

The effects of phosphorus depletion on cardiac muscle function in six awake dogs were evaluated with surgically implanted transducers to serially measure ascending aortic root blood flow and high fidelity left ventricular pressure. After the animals recovered from surgery, phosphorus depletion was induced by feeding them a synthetic phosphorus-deficient diet plus aluminum carbonate gel for 35 days, followed by the same diet with phosphorus supplementation for 21 days. In addition to the cardiac studies, sequential measurements of phosphorus content in skeletal muscle and phosphorus in serum were obtained to ascertain the level of phosphorus depletion. Serum inorganic phosphorus concentration (mg/100 ml) decreased from 5.1 +/- 0.1 on day 0 to 0.9 +/- 0.1 on day 35 (P less than 0.01), and total muscle phosphorus (content mmul/100 g fat-free dry weight) decreased from 28.0 +/- on day 0 to 22.6 +/- 0.5 on day 35 (P less than 0.01). During the period of phosphorus depletion, there was no significant change in heart rate; however, stroke volume (milliliter) and peak blood flow velocity (centimeter per second) declined from 24 +/- 2 to 17 +/- 2 (P less than 0.01) and 121 +/- 12 to 98 +/- 7 (P less than 0.01), respectively. Maximum ascending aortic blood flow acceleration (centimeter per second square) and maximum left ventricular time rate of change of pressure (mm Hg per second) also decreased from 4,630 +/- 313 to 3,817 +/0 346 (P less than 0.01) and 2,582 +/- 347 to 2,120 +/- 297 (P less than 0.01) during phosphorus depletion. After repletion all values returned to control values. These results indicate that moderate diet-induced phosphorus depletion can depress myocardial performance. With repletion of phosphorus, myocardial performance improves.
Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial
Authors: Nir Lipsman, D Blake Woodside, Peter Giacobbe, Clement Hamani, Jacqueline C Carter, Sarah Jane Norwood, Kalam Sutandar, Randy Staab, Gavin Elias, Christopher H Lyman, Gwenn S Smith, Andres M Lozano
Journal: The Lancet (2013)
Back pain--whose responsibility?
Authors: J. K Paterson
Journal: Journal of the Royal Society of Medicine (2002)

Emergency ambulance triageMr Thakore and colleagues (March 2002 JRSM 1 ) conclude that 55% of calls for emergency ambulances did not merit an immediate response.As they acknowledge, the design of the study was not ideal.The initial reason for the request was determined from ambulance crew and accident and emergency (A&E) data after the patient had been seen.This will almost inevitably introduce bias when applying the triage criteria, and the assessment should have been blinded.Also, it is much easier to make such determinations in hindsight, with additional time and clinical information, than when faced with a real call when one has to consider the consequences of the decision reached.It is surprising that this paper makes no reference to priority-based dispatch systems, such as the Advanced Medical Priority Dispatch System (AMPDS), as these are currently used by most ambulance services in the UK.These systems have been shown to have a low risk of serious under-prioritization of life-threatening episodes 2 .However, work that we have undertaken in Nottingham suggests that they may not be very effective in predicting low-priority 999 calls 3 .The NHS Executive has stressed the importance of developing telephone prioritization systems that will free ambulance services from having to respond to `patients who dialled 999 but who do not need emergency care' 4 .We believe this may be dif®cult to achieve.Appropriate and effective telephone triage on non-emergency 999 calls requires a greater understanding of the relationship between the initial telephone assessment by ambulance control and the subsequent outcome of the individual call.Without these data we will not be able to ensure that such a system could operate safely and we endorse the authors' views that prospective studies are essential to assess the feasibility of accurately identifying lower priority calls.
Dissociation of Sarcoglycans and the Dystrophin Carboxyl Terminus From the Sarcolemma in Enteroviral Cardiomyopathy
Authors: Gil-Hwan Lee, Cornel Badorff, Kirk U. Knowlton
Journal: Circulation Research (2000)

Enteroviral infection can cause an acquired form of dilated cardiomyopathy. We recently reported that dystrophin is cleaved, functionally impaired, and morphologically disrupted in vitro as well as in vivo during infection with coxsackievirus B3. Genetic dystrophin truncations lead to a marked decrease in dystrophin-associated glycoproteins, whereas expression of only the naturally occurring dystrophin carboxyl terminus, Dp-71, restores the sarcolemmal association of the dystrophin-associated glycoproteins. We sought to determine whether acute cleavage of dystrophin leads to a dissociation of the carboxyl-terminal dystrophin fragment and of the sarcoglycans from the sarcolemma during coxsackievirus B3 infection. We found that in cultured cardiac myocytes and murine hearts infected with coxsackievirus B3, the sarcolemmal localization of the dystrophin carboxyl terminus is lost. The dystrophin-associated glycoproteins alpha-, beta-, gamma-, and delta-sarcoglycan and beta-dystroglycan were markedly decreased in the membrane fraction of infected cells in culture, and the typical sarcolemmal localization for each of these proteins was lost in coxsackievirus-B3-infected cardiomyocytes in vivo. Furthermore, sucrose gradient ultracentrifugation demonstrated that delta-sarcoglycan was physically dissociated from dystrophin within the membrane fraction. In vivo, the sarcolemmal integrity was functionally impaired with Evans blue dye uptake even though there was no generalized disruption of the sarcolemma of infected myocytes evidenced by intact wheat germ agglutinin staining. In analogy to hereditary sarcoglycanopathies, this disintegration of the sarcoglycan complex may, in addition to the dystrophin cleavage, play an important role in the pathogenesis of enterovirus-induced cardiomyopathy. These results imply a potential role for disruption of the sarcoglycans in an acquired form of heart failure.
Knee osteoarthritis. Efficacy of a new method of contrast-enhanced musculoskeletal ultrasonography in detection of synovitis in patients with knee osteoarthritis in comparison with magnetic resonance imaging
Authors: I H Song, G R Burmester, M Backhaus, C E Althoff, K G Hermann, A K Scheel, C Werner, T Knetsch, M Schoenharting
Journal: Annals of the Rheumatic Diseases (2007)

To develop a new method of digital synovial vascularisation quantification by using contrast-enhanced musculoskeletal ultrasonography (MUS) in detecting synovitis in patients with knee osteoarthritis (OA) compared with healthy subjects and MRI.Evaluation of 41 patients with painful knee OA and 6 healthy subjects. The severity of knee pain was evaluated. All patients and all 6 healthy subjects underwent contrast medium-enhanced (CE)-MUS with SonoVue, and 36 patients additionally underwent CEMRI with Magnevist. Joint effusion, synovial thickening and pain were assessed and compared with B-mode and Power Doppler sonography (PDS) as well as contrast medium enhancement.Pain evaluated by the visual analogue scale(VAS) hardly correlated with other markers of disease activity measured by ultrasound (US) in B-mode or MRI. US of the superior recess revealed an effusion or synovial thickening in 58%. PDS findings were positive in 63%, and CE-MUS in the superior knee recess was positive in 95%. MRI showed effusion in the superior recess in 61% and showed positive findings in 82% when using contrast medium. The kappa value was 0.48 between US and MRI with regard to the effusion in the superior recess, and 0.53 between PD signal in the superior recess and effusion in the superior recess by US. Using MRI as the reference standard, there was a sensitivity of 72% for assessing effusion in the superior recess and 81% for assessing effusion in the lateral recess.Assessment of disease activity (synovitis) in knee OA by VAS is not sufficient. US PDS was more sensitive than B-mode, and CE-MUS was more sensitive than PDS and CE-MRI in detecting synovitis in patients with painful knee OA. Also, CE-MRI was more sensitive in detecting inflammatory changes in the superior recess than without contrast medium. Using CE-MUS and performing time/intensity analysis has shown to be a good model for evaluation of an inflammatory process in the setting of knee OA in the superior recess.
Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Authors: Sharon H. Giordano, Sarah Temin, Jeffrey J. Kirshner, Sarat Chandarlapaty, Jennie R. Crews, Nancy E. Davidson, Francisco J. Esteva, Ana M. Gonzalez-Angulo, Ian Krop, Jennifer Levinson, Nancy U. Lin, Shanu Modi, Debra A. Patt, Edith A. Perez, Jane Perlmutter, Naren Ramakrishna, Eric P. Winer
Journal: Journal of Clinical Oncology (2014)

To provide evidence-based recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.The American Society of Clinical Oncology convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic literature review from January 2009 to October 2012. Outcomes of interest included overall survival, progression-free survival (PFS), and adverse events.A total of 16 trials met the systematic review criteria. The CLEOPATRA trial found survival and PFS benefits for docetaxel, trastuzumab, and pertuzumab in first-line treatment, and the EMILIA trial found survival and PFS benefits for trastuzumab emtansine (T-DM1) in second-line treatment. T-DM1 also showed a third-line PFS benefit. One trial reported on duration of HER2-targeted therapy, and three others reported on endocrine therapy for patients with HER-positive advanced breast cancer.HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and T-DM1 for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations or T-DM1 (if not previously administered) and may offer pertuzumab, if the patient has not previously received it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive/progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone.