tbuckley/cabot-search huggingface dataset:
Cutting Edge: Flow Cytometry in Myelodysplastic Syndromes
Authors: Arjan A. van de Loosdrecht, Theresia M. Westers
Journal: Journal of the National Comprehensive Cancer Network (2013)

Flow cytometry (FC) is recognized as one of the important tools in the diagnosis of myelodysplastic syndromes (MDS), especially when cytomorphology and cytogenetics are inconclusive. Minimal requirements to analyze dysplasia using FC have been proposed by the International Workshops from the European LeukemiaNet on Standardization of FC in MDS. These should enable a categorization of FC results in cytopenic patients as “normal,” “suggestive of,” or “indicative of” MDS. Notably, FC should be considered as part of an integrated diagnosis, rather than as a separate technique. This article highlights tools to implement FC in the diagnostic workup of MDS. Current advances in FC for diagnosis and prognosis of MDS are also introduced.
Re-evaluation of link between interpregnancy interval and adverse birth outcomes: retrospective cohort study matching two intervals per mother
Authors: S. J. Ball, G. Pereira, P. Jacoby, N. de Klerk, F. J. Stanley
Journal: BMJ (2014)

<b>Objective</b> To re-evaluate the causal effect of interpregnancy interval on adverse birth outcomes, on the basis that previous studies relying on between mother comparisons may have inadequately adjusted for confounding by maternal risk factors. <b>Design</b> Retrospective cohort study using conditional logistic regression (matching two intervals per mother so each mother acts as her own control) to model the incidence of adverse birth outcomes as a function of interpregnancy interval; additional unconditional logistic regression with adjustment for confounders enabled comparison with the unmatched design of previous studies. <b>Setting</b> Perth, Western Australia, 1980-2010. <b>Participants</b> 40 441 mothers who each delivered three liveborn singleton neonates. <b>Main outcome measures</b> Preterm birth (&lt;37 weeks), small for gestational age birth (&lt;10th centile of birth weight by sex and gestational age), and low birth weight (&lt;2500 g). <b>Results</b> Within mother analysis of interpregnancy intervals indicated a much weaker effect of short intervals on the odds of preterm birth and low birth weight compared with estimates generated using a traditional between mother analysis. The traditional unmatched design estimated an adjusted odds ratio for an interpregnancy interval of 0-5 months (relative to the reference category of 18-23 months) of 1.41 (95% confidence interval 1.31 to 1.51) for preterm birth, 1.26 (1.15 to 1.37) for low birth weight, and 0.98 (0.92 to 1.06) for small for gestational age birth. In comparison, the matched design showed a much weaker effect of short interpregnancy interval on preterm birth (odds ratio 1.07, 0.86 to 1.34) and low birth weight (1.03, 0.79 to 1.34), and the effect for small for gestational age birth remained small (1.08, 0.87 to 1.34). Both the unmatched and matched models estimated a high odds of small for gestational age birth and low birth weight for long interpregnancy intervals (longer than 59 months), but the estimated effect of long interpregnancy intervals on the odds of preterm birth was much weaker in the matched model than in the unmatched model. <b>Conclusion</b> This study questions the causal effect of short interpregnancy intervals on adverse birth outcomes and points to the possibility of unmeasured or inadequately specified maternal factors in previous studies.
The need for the integrated care for advanced COPD patients in the northern Poland (Pomerania)
Authors: Iwona Damps-Konstanska, Lidia Werachowska, Amelia Szymanowska-Narloch, Piotr Krakowiak, Malgorzata Kaczmarek, Ewa Jassem
Journal: European Respiratory Journal (2012)

COPD is one of the most prevalent chronic disease, significantly increasing morbidity and mortality in developed countries. Symptom control and preventing risk of exacerbation is the main goal in the management of COPD. Poor compliance and insufficient self-management, especially in the more advanced patients are recognized causes of increased exacerbation rate. Currently, in the Northern Poland the model of integrated care for advanced COPD patients is to be introduced. However little is known about the need and acceptance for such a care among patients and their relatives. Thus, the aim of this initial study was to assess the QoL (using SGRQ) in 30 consecutive advanced COPD patients living one of the small towns in Pomerania and their acceptance for continuing support (two times a week during one month) delivered in their homes (assessed by specially constructed questionnaire). Home intervention included two-hours meeting (structured as follows: 30 min of education including assessment of the proper use of inhalators and medications intake, 30 min of physical activity, 30 min of small-talk focused on the subject proposed by patient, and 30 min of the assessment of symptoms, pulsoximetry and PEF measurement) with medical caregiver. Results demonstrated poor QoL in the study group during the stable period of the disease (total score of SGRQ – mean: 71; range: from 24 to 91) and the full acceptance for the home support (28 patients were very satisfied, 2 were satisfied). These findings confirmed the need for integrated care in Pomerania and chance for realization of the program.
Herpesvirus saimiri strain 11 immortalizes a restricted marmoset T8 lymphocyte subpopulation in vitro.
Authors: M Kiyotaki, R C Desrosiers, N L Letvin
Journal: The Journal of Experimental Medicine (1986)

Herpesvirus saimiri induces a fatal lymphoproliferative syndrome in a variety of New World primate species. We now show that cell lines derived from PBL of the common marmoset by in vitro-immortalization with H. saimiri strain 11 represent a remarkably restricted lymphocyte population. These cell lines have NK cell function, phenotypically express both suppressor/cytotoxic (T8) and NK cell (NKH1)-associated antigens, and express a T cell receptor. This subpopulation of lymphocytes is a very minor population of cells in the peripheral blood of common marmosets (less than or equal to 3%). The specificity in the interaction between H. saimiri strain 11 and a subpopulation of common marmoset lymphocytes represents an example of a restricted viral lymphotropism and may have important implications for the disease induced by this virus in New World monkeys.
Should asthma management be guided by airway inflammatory markers instead of symptoms?
Authors: A Bhowmik
Journal: Thorax (2003)

<h3>Background and Objectives</h3> Refractory status epilepticus (RSE) bears significant morbidity and mortality. Therapy escalation and in some cases intubation are recommended. Most existing studies are retrospective and focus on intensive care units. We aimed to describe routine-care management and analyze determinants of RSE development and outcomes in a large multicenter cohort. <h3>Methods</h3> We performed post hoc analysis of an observational, cohort study, which prospectively registered all consecutive adults with SE at 9 centers from 3 central European countries. Only incident episodes were included. Ongoing SE despite 2 antiseizure medications was defined as RSE. Patients intubated during first-line or second-line treatments were excluded. Variables investigated included demographics, severity (Status Epilepticus Severity Score), etiology, and guideline-compliant treatment (defined as fixed minimum doses). Outcome parameters included survival and mRS at baseline, and discharge (good: 0–2, or absence of worsening compared with prehospitalization). <h3>Results</h3> Among 1,179 SE episodes from 1,049 adults, 996 patients were eligible (median age: 70 years, 52% female), of which 545 (54.7%) developed RSE. RSE was associated with higher baseline mRS (<i>p</i> &lt; 0.001) and treatment deviation from guidelines (<i>p</i> &lt; 0.001, OR 0.09; 95% CI 0.06–0.1). Good outcomes were observed in 52.7% of refractory patients, correlating with lower status epilepticus severity (<i>p</i> &lt; 0.001), absence of acute etiology (<i>p</i> &lt; 0.001, OR 0.5; 95% CI 0.3–0.7), adequate first-line benzodiazepine dose (<i>p</i> &lt; 0.001, OR 2.5; 95% CI 1.6–4.0), shorter durations of SE and hospitalization (both <i>p</i> &lt; 0.001), and lack of intubation (<i>p</i> &lt; 0.001, OR 0.4; 95% CI 0.3–0.6). Most (71.7%) refractory patients were not intubated. Intubation was associated with younger age (<i>p</i> = 0.006), more severe consciousness disturbances (<i>p</i> &lt; 0.001, OR 3.2; 95% CI 2.1–4.8), more severe SE types (<i>p</i> &lt; 0.001), higher severity score (<i>p</i> = 0.009), acute etiologies (<i>p</i> = 0.01, OR 1.6; 95% CI 1.1–2.4), more antiseizure medications (<i>p</i> &lt; 0.001), initial treatment after shorter latency (<i>p</i> = 0.01), worse outcomes (<i>p</i> &lt; 0.001, OR 0.4; 95% CI 0.4–0.6), and longer hospitalizations (<i>p</i> &lt; 0.001). <h3>Discussion</h3> Variables associated with RSE were identified, some potentially preventable. More than 70% of RSE were treated without intubation, suggesting that focal RSE without deep impairment of consciousness, in older patients, may be successfully treated outside ICUs. <h3>Trial Registration Information</h3> Original cohort study registered at the German Clinical Trials Register (DRKS00000725).
Guidelines for clinical use of cardiac radionuclide imaging report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on Radionuclide Imaging), developed in collaboration with the American Society of Nuclear Cardiology
Authors: James L. Ritchie, Timothy M. Bateman, Robert O. Bonow, Michael H. Crawford, Raymond J. Gibbons, Robert J. Hall, Robert A. O'Rourke, Alfred F. Parisi, Mario S. Verani, Melvin D. Cheitlin, Arthur Garson, Richard P. Lewis, Thomas J. Ryan, Robert C. Schlant, William L. Winters
Journal: Journal of the American College of Cardiology (1995)
ET-45 * KNOCKDOWN OF TNFSF13B INDUCES GLIOMA STEM CELL APOPTOSIS
Authors: Y. Piao, C. Thomas, L. Holmes, V. Henry, J. de Groot
Journal: Neuro-Oncology (2014)

Tumor Necrosis Factor (Ligand) Super Family member 13B (TNFSF13B; BAFF) is primarily produced by myeloid lineage cells, activated T cells and dendritic cells, and up-regulates anti-apoptotic Bcl-2 family proteins. Approximately 20% of glioblastoma overexpress TNFSF13B, which may account for treatment resistance. A Kaplan-Meier curve from a query of The Cancer Genome Atlas (TCGA) showed that glioblastoma patients with increased expression (EXP > 2) of TNFSF13B have a significantly shorter overall survival (P = 0.025). By immunoblotting, TNFSF13B expression was differentially expressed in a panel of glioma stem cells (GSCs). GFP-tagged TNFSF13B shRNA lentivirus was used to knock down TNFSF13B in multiple cell lines. Erlotinib or lapatinib inhibited cell viability to a greater extent in shTNFSF13B cells compared to scramble control. After 1 µM erlotinib treatment for 3 days, cell viability was suppressed by 34% in shTNFSF13B GSC11 cells compared to scramble control cells. Lapatinib (0.1 µM for 3 days) reduced cell viability by 40% in shTNFSF13B GSC11 cells compared to controls. Apoptosis, assessed by Annexin V-based flow cytometry, revealed a 30% increase in Annexin V staining after erlotinib treatment (1 µM for 3 days) in shTNFSF13B GSC11 cells compared with controls. The level of anti-apopototic proteins BCL-XL and Bid markedly decreased which was concomitant with an increase in cleaved caspase 9 in shTNFSF13B cells treated with EGFR inhibitors. Using an apoptosis protein array, we observed that anti-apoptotic proteins Bcl-2, survivin, claspin and HIF-1α significantly decreased in shTNFSF13B cells compared with scramble cells after treatment of 1 µM erlotinib. Ongoing in vivo studies are validating the impact of targeting TNFSF13B in a glioma xenograft model. Our studies identified TNFSF13B as a potentially important mediator of glioma stem cell survival in vitro and suggest that TNFSF13B may be a potential therapeutic target to enhance the efficacy of anti-EGFR therapy.
THE PROPHYLAXIS OF CARDIAC COMPLICATIONS IN ELECTROSHOCK THERAPY
Authors: MAX HAYMAN
Journal: American Journal of Psychiatry (1945)

The cases cited suggest that premedication in patients with cardiac disease is an effective prophylaxis for the development of cardiac complications. Often where cardiac complications occur they are preceded by various arrhythmias and these may be controlled with quinidine sulfate. Vasodilator drugs may be useful in preventing cardiac complications of vascular origin but there was no opportunity to test this. No mention in the literature of such premedication has come to attention and the writer has had no opportunity in recent years of developing this work. A wider trial and close observation of such premedication by workers now engaged in this field may enable more patients in the older age group with psychiatric conditions to obtain the benefit of electroshock treatment.
Left ventricular function after repair of tetralogy of fallot and its relationship to age at surgery.
Authors: K M Borow, L H Green, A R Castaneda, J F Keane
Journal: Circulation (1980)

Left ventricular (LV) work-function curves were used to assess LV performance in eight postoperative tetralogy of Fallot (TOF) patients who underwent repair before 2 years of age (group 1) and 12 patients who underwent repair after 2 years of age (group 2). All patients were without significant residual shunts or pulmonary stenosis. Results were compared with those in seven control patients. Left- and right-heart hemodynamics were measured at various levels of afterload induced by methoxamine while heart rate was maintained constant. Cardiac output was serially measured. The slope (m) for each patient's LV end-diastolic pressure (EDP) vs LV minute-work index (MWI) relationship was determined. There were no significant differences in resting cardiac index, LV systolic pressure, LVEDP, aortic oxygen saturation or MWI among the groups. However, with afterload stress, group 2 patients had abnormal work-function curves with depressed slopes (m = 0.21 +/- 0.04) compared with the values for group 1 patients (m = 0.89 +/- 0.13, p less than 0.001) or the control group (m = 1.13 +/- 0.12, p less than 0.001). Thus, LV dysfunction unmasked by an afterload stress was present in the older TOF patients but not in the patients repaired during infancy. These findings raise the possibility that early, definitive repair of TOF may help preserve postoperative LV function.
Comparison of the distribution of intramyocardial pressure across the canine left ventricular wall in the beating heart during diastole and in the arrested heart. Evidence of epicardial muscle tone during diastole.
Authors: P D Stein, H N Sabbah, M Marzilli, E F Blick
Journal: Circulation Research (1980)

Computations of compliance of the left ventricle (LV) during diastole assume passive tissue characteristics. To evaluate this assumption, we measured diastolic LV intramyocardial pressure simultaneously in the subepicardium and subendocardium in 18 open-chest dogs, using 1-mm in diameter micromanometers. Subepicardial pressure, 26 +/- 1 mm Hg (mean +/- SEM) exceeded subendocardial pressure, 14 +/- 1 mm Hg (P less than 0.001), and it exceeded left ventricular end-diastolic pressure (LVEDP) (9 +/- 1 mm Hg) (P less than 0.001). After an infusion of dextran-40 (10 dogs), subepicardial diastolic pressure increased to 42 +/- 4 mm Hg which was higher than diastolic subendocardial pressure, 26 +/- 2 mm Hg (P less than 0.001) and LVEDP, 24 +/- 2 mm Hg (P less than 0.001). Following cardiac arrest (12 dogs) with the intramyocardial probes unchanged in position, LV intracavitary pressure, 9 +/- 1 mm Hg, and subendocardial pressure, 13 +/- 3 mm Hg, did not differ significantly from the pressures in the beating heart. Subepicardial pressure, 9 +/- 1 mm Hg, was lower than in the beating heart (P less than 0.001). Following distention of the arrested LV (12 dogs), subepicardial pressure, 31 +/- 7 mm Hg, was lower than both subendocardial pressure, 58 +/- 12 mm Hg (P less than 0.001) and LV intracavitary pressure, 54 +/- 11 mm Hg (P less than 0.001). These observations indicate that tone is maintained by the subepicardium during diastole. Furthermore, the LV wall does not appear to behave as a passive shell during ventricular filling.
Comparative Metabolomics Reveals Endogenous Ligands of DAF-12, a Nuclear Hormone Receptor, Regulating C. elegans Development and Lifespan
Authors: Parag Mahanti, Neelanjan Bose, Axel Bethke, Joshua C. Judkins, Joshua Wollam, Kathleen J. Dumas, Anna M. Zimmerman, Sydney L. Campbell, Patrick J. Hu, Adam Antebi, Frank C. Schroeder
Journal: Cell Metabolism (2014)
Is intrapulmonary arteriovenous shunting and hypoxemia a contraindication for liver transplantation?
Authors: Siw L. Eriksson
Journal: Hepatology (1991)

A 12-year-old boy with Wilson’s disease developed exertional dyspnea, cyanosis, and finger clubbing 10 months after diagnosis. The hypoxemia was caused by arteriovenous shunting, demonstrated by radionuclide scanning and pulmonary arteriography. Orthotopic liver transplantation was performed after the development of severe hypoxemia. There was no apparent reversal of the intrapulmonary arteriovenous shunting and he died 10 days posttransplantation of multiple organ failure secondary to hypoxemia. Monitoring arterial oxygen saturation in children with cirrhosis is warranted since the presence of significant arteriovenous shunting may influence prognosis and decisions regarding liver transplantation.
Successful treatment of hydroxyethyl starch-induced pruritus with topical capsaicin
Authors: R.-M. SZEIMIES, W. STOLZ, U. WLOTZKE, H.C. KORTING, M. LANDTHALER
Journal: British Journal of Dermatology (1994)

We report a case of recalcitrant pruritus after infusion therapy with hydroxyethyl starch (HES) for sudden deafness. The diagnosis was confirmed by detection of typical HES storage vacuoles within dermal macrophages and perineural cells. Treatment with antihistamines and antipruritic agents, UVB irradiation, and neuroleptic drugs, was ineffective. Topical capsaicin (0.05%) twice daily produced excellent symptomatic relief, without side‐effects.
Alcohol and mortality in Russia: prospective observational study of 151 000 adults
Authors: David Zaridze, Sarah Lewington, Alexander Boroda, Ghislaine Scélo, Rostislav Karpov, Alexander Lazarev, Irina Konobeevskaya, Vladimir Igitov, Tatiyana Terechova, Paolo Boffetta, Paul Sherliker, Xiangling Kong, Gary Whitlock, Jillian Boreham, Paul Brennan, Richard Peto
Journal: The Lancet (2014)

Russian adults have extraordinarily high rates of premature death. Retrospective enquiries to the families of about 50,000 deceased Russians had found excess vodka use among those dying from external causes (accident, suicide, violence) and eight particular disease groupings. We now seek prospective evidence of these associations.
A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD
Authors: Peter K Davidsen, John M Herbert, Philipp Antczak, Kim Clarke, Elisabet Ferrer, Victor I Peinado, Constancio Gonzalez, Josep Roca, Stuart Egginton, Joan A Barberá, Francesco Falciani
Journal: Genome Medicine (2014)

A relatively large percentage of patients with chronic obstructive pulmonary disease (COPD) develop systemic co-morbidities that affect prognosis, among which muscle wasting is particularly debilitating. Despite significant research effort, the pathophysiology of this important extrapulmonary manifestation is still unclear. A key question that remains unanswered is to what extent systemic inflammatory mediators might play a role in this pathology. Cigarette smoke (CS) is the main risk factor for developing COPD and therefore animal models chronically exposed to CS have been proposed for mechanistic studies and biomarker discovery. Although mice have been successfully used as a pre-clinical in vivo model to study the pulmonary effects of acute and chronic CS exposure, data suggest that they may be inadequate models for studying the effects of CS on peripheral muscle function. In contrast, recent findings indicate that the guinea pig model (Cavia porcellus) may better mimic muscle wasting.We have used a systems biology approach to compare the transcriptional profile of hindlimb skeletal muscles from a Guinea pig rodent model exposed to CS and/or chronic hypoxia to COPD patients with muscle wasting.We show that guinea pigs exposed to long-term CS accurately reflect most of the transcriptional changes observed in dysfunctional limb muscle of severe COPD patients when compared to matched controls. Using network inference, we could then show that the expression profile in whole lung of genes encoding for soluble inflammatory mediators is informative of the molecular state of skeletal muscles in the guinea pig smoking model. Finally, we show that CXCL10 and CXCL9, two of the candidate systemic cytokines identified using this pre-clinical model, are indeed detected at significantly higher levels in serum of COPD patients, and that their serum protein level is inversely correlated with the expression of aerobic energy metabolism genes in skeletal muscle.We conclude that CXCL10 and CXCL9 are promising candidate inflammatory signals linked to the regulation of central metabolism genes in skeletal muscles. On a methodological level, our work also shows that a system level analysis of animal models of diseases can be very effective to generate clinically relevant hypothesis.
Increased inflammatory activity parallels increased basal nitric oxide production and blunted response to nitric oxide in vivo in rheumatoid arthritis
Authors: H Yki-Jarvinen
Journal: Annals of the Rheumatic Diseases (2003)

<b>Background:</b> Endothelial dysfunction, defined as loss of bioactivity of NO in the vessel wall, is thought to precede atherosclerosis. <b>Objective:</b> To determine whether endothelial dysfunction characterises patients with RA and whether these patients have increased inducible nitric oxide synthase (iNOS) dependent NO production in vivo. <b>Methods and results:</b> Twenty patients with RA and 33 normal subjects received intrabrachial artery infusions of endothelium dependent (acetylcholine (ACh)) and independent (sodium nitroprusside (SNP)) vasodilators to determine arterial responsiveness to NO. Basal flow and its percentage decrease by NG-monomethyl-l-arginine (l-NMMA), an inhibitor of both iNOS and endothelium dependent NOS (eNOS), was used to determine the contribution of iNOS and eNOS dependent NO to basal flow. Both SNP (p&lt;0.01) and ACh (p&lt;0.05) increased blood flow significantly less in patients with RA than normal subjects. Serum concentrations of TNFα were, within the RA group, inversely correlated with blood flow responses to both SNP (<i>r</i>=−0.67, p=0.002) and ACh (<i>r</i>=−0.64, p&lt;0.005). Basal flow was significantly increased in RA and correlated within this group with serum CRP (<i>r</i>=0.48, p&lt;0.05), TNFα (<i>r</i>=0.61, p&lt;0.01) concentrations, and ESR (<i>r</i>=0.68, p&lt;0.002). l-NMMA decreased basal flow significantly more (-34±2%) in the patients with RA than the normal subjects (-24±3%, p&lt;0.02), suggesting in view of the blunted response to ACh, increased iNOS activity. <b>Conclusions:</b> Patients with RA have a dual abnormality in NO dependent vascular function. Basal blood flow is increased in proportion to inflammatory activity and more inhibited by l-NMMA, suggesting increased iNOS activity, and responsiveness to NO is reduced.