tbuckley/cabot-search huggingface dataset:
ABL001, a Potent Allosteric Inhibitor of BCR-ABL, Prevents Emergence of Resistant Disease When Administered in Combination with Nilotinib in an in Vivo Murine Model of Chronic Myeloid Leukemia
Authors: Andrew Wylie, Joseph Schoepfer, Giuliano Berellini, Hongbo Cai, Giorgio Caravatti, Simona Cotesta, Stephanie Dodd, Jerry Donovan, Bernhard Erb, Pascal Furet, Geeti Gangal, Robert Grotzfeld, Quamrul Hassan, Tami Hood, Varsha Iyer, Sandra Jacob, Wolfgang Jahnke, Franco Lombardo, Alice Loo, Paul W. Manley, Andreas Marzinzik, Michael Palmer, Xavier Pelle, Bahaa Salem, Sreenath Sharma, Sanjeev Thohan, Suzanne Zhu, Nicholas Keen, Lilli Petruzzelli, K. Gary Vanasse, William R Sellers
Journal: Blood (2014)
Distribution of rpoB mutations among multidrug-resistant Mycobacterium tuberculosis (MDRTB) strains from Thailand and development of a rapid method for mutation detection
Authors: T. Prammananan, W. Cheunoy, D. Taechamahapun, J. Yorsangsukkamol, S. Phunpruch, P. Phdarat, M. Leechawengwong, A. Chaiprasert
Journal: Clinical Microbiology and Infection (2008)
Racial/Ethnic Variation in All‐Cause Mortality Among United States Medicaid Recipients With Systemic Lupus Erythematosus: A Hispanic and Asian Paradox
Authors: José A. Gómez‐Puerta, Medha Barbhaiya, Hongshu Guan, Candace H. Feldman, Graciela S. Alarcón, Karen H. Costenbader
Journal: Arthritis & Rheumatology (2015)

The incidence of systemic lupus erythematosus (SLE) is disproportionately high in nonwhite patients compared with white patients. However, variation in mortality according to race/ethnicity has not been well studied. The aim of this study was to examine all-cause mortality according to race/ethnicity among SLE patients enrolled in Medicaid.We used Medicaid Analytic eXtract data, with billing claims from 47 US states and Washington, DC, to identify individuals ages 18-65 years who were enrolled in Medicaid for ≥3 months in 2000-2006. Individuals were classified as having SLE if they had ≥3 visits ≥30 days apart with an International Classification of Diseases, Ninth Revision (ICD-9) code for SLE (710.0). Among the individuals with SLE, those with lupus nephritis (LN) were identified by the presence of ≥2 ICD-9 claims for glomerulonephritis, proteinuria, or renal failure. We calculated mortality rates per 1,000 person-years, with 95% confidence intervals (95% CIs), according to race/ethnicity. Multivariable Cox proportional hazards regression models were used to estimate mortality risks, adjusting for age, sex, demographics, and comorbidities.Among 42,221 prevalent cases of SLE, 8,191 prevalent cases of LN were identified. Blacks represented 40.1%, whites 38.4%, and Hispanics 15.3%. Overall SLE mortality rates per 1,000 person-years were highest among Native American (27.52), white (20.17), and black (24.13) patients and were lower among Hispanic (7.12) or Asian (5.18) patients. After multivariable adjustment, Hispanic and Asian patients had lower mortality risks (hazard ratio [HR] 0.48 [95% CI 0.40-0.59] and 0.59 [95% CI 0.40-0.86], respectively) compared with whites. Conversely, the risk of death was significantly higher among Native American (HR 1.40 [95% CI 1.04-1.90]) and black (HR 1.21 [95% CI 1.10-1.33]) patients compared with white patients. Among patients with LN, mortality risks were lower in Hispanic and Asian patients compared with white patients.After accounting for demographic and clinical factors, mortality among Asian and Hispanic Medicaid patients with SLE was lower than that among black, white, or Native American patients.
Minimally Differentiated Acute Myeloid Leukemia (AML-M0): Comparison of 25 Cases With Other French-American-British Subtypes
Authors: Adriano Venditti, Giovanni Del Poeta, Francesco Buccisano, Anna Tamburini, M. Christina Cox, Roberto Stasi, Antonio Bruno, Germano Aronica, Laura Maffei, Giovanna Suppo, Maria Domenica Simone, Laura Forte, Valeria Cordero, Massimiliano Postorino, Vincenza Tufilli, Giancarlo Isacchi, Mario Masi, Giuseppe Papa, Sergio Amadori
Journal: Blood (1997)
Clinical significance of hemosiderin-laden macrophages in bronchoalveolar lavage fluid of patients with idiopathic interstitial pneumonias
Authors: Tomoko Kagawa, Toru Arai, Chikatoshi Sugimoto, Kazunobu Tachibana, Taisuke Tsuji, Yoshinobu Matsuda, Yumiko Sasaki, Reiko Sugawara, Yasusi Inoue, Yoshio Fujita, Tomoaki Teramoto, Masanori Kitaichi, Seiji Hayashi, Yoshikazu Inoue
Journal: European Respiratory Journal (2013)

Introduction: Hemosiderin-laden macrophages (HLMs) in bronchoalveolar lavage(BAL) fluid (BALF) has been quantified for the diagnose of diffuse alveolar hemorrhage (DAH). However, the role of HLMs is not uncertain in patients with idiopathic interstitial pneumonias (IIPs).

Aim: To know the role including prognostic significance of HLMs in bronchoalveolar lavage (BALF) in IIPs.

Subjects: 265 patients were diagnosed as IIPs between January 2005 and February 2009 and HLMs were detected in 33 cases. 25 patients with assessable data were retrospectively analyzed.

Methods: BAL was performed with three 50-ml-aliquots of saline. Prussian blue stain was used to detect HLMs. HLMs in BALF were quantified by modified hemosiderin score (HS), which was originally described by Golde (BMJ 1975). IIPs were classified with pathological and/or radiological findings into idiopathic pulmonary fibrosis (IPF) and non-IPF.

Results: The median age was 65 yrs (range 42-85). Follow-up period of 25 patients (male 22, female 3) was 1554 days (median, range 9-2826). The 15 patients were diagnosed with IPF, and 10 patients were diagnosed with non-IPF. Modified HS in severe IIPs were larger than that in mild IIPs (p<0.10). IIPs with acute exacerbation (AE) during follow-up period after BAL showed significantly larger modified HS than those without AE (p=0.001). Other clinical findings were not associated with modified HS.

Conclusion: The number of HLMs in BALF may reflect clinical severity, AE and prognosis of IPF.

Grant from National Ministry of Health, Labour, and Welfare, and National Hospital Organization.
Temporal association of CD40 antigen expression with discrete stages of human B-cell ontogeny and the efficacy of anti-CD40 immunotoxins against clonogenic B-lineage acute lymphoblastic leukemia as well as B- lineage non-Hodgkin's lymphoma cells
Authors: FM Uckun, K Gajl-Peczalska, DE Myers, W Jaszcz, S Haissig, JA Ledbetter
Journal: Blood (1990)
Everolimus improves exercise capacity and pulmonary vascular resistance in patients with advanced pulmonary hypertension – A pilot study
Authors: Hans-Juergen Seyfarth, Stefan Hammerschmidt, Michael Halank, Petra Neuhaus, Hubert Wirtz
Journal: European Respiratory Journal (2011)

Background:  In recent years, pulmonary arterial hypertension (PAH) has been recognized to be a predominantly proliferative process. The inhibitor of the mammalian target of rapamycin (mTOR) everolimus inhibits cellular protein synthesis and growth in cells of the vascular wall.   Methods:  Ten patients with PAH (n=8) or chronic thromboembolic pulmonary hypertension (CTEPH) and progressive disease despite therapy with at least two vasodilating drugs were included in a prospective open label pilot study. All patients were treated additionally with everolimus. Safety and tolerability were observed. Pulmonary vascular resistance (PVR) and 6-minute walking distance (6MWD) were considered as primary endpoints.   Results:  In two patients study medication was stopped prematurely due to an adverse event. The remaining 8 patients exhibited a significant improvement in PVR (1049±438 vs. 689±235 dyn*sec*cm -5 ; p=0.004) and 6MWD (246±105 vs. 313±127m; p=0.04) after 6 months of therapy with everolimus.   Conclusion:  Antiproliferative with everolimus therapy was tolerated in ten patients in this pilot study. The observed improvements in PVR and in 6MWD may stimulate further consideration of mTOR inhibition in pulmonary hypertension.
Abstract 55: Opposing Roles Of Distinct Macrophage Lineages In Heart Failure And Cardiac Recovery
Authors: Kory J Lavine, Slava Epelman, Keita Uchida, Kassandra J Weber, Joel D Schilling, Colin G Nichols, Gwendalyn J Randolph, Douglas L Mann
Journal: Circulation Research (2014)

Why inflammation is simultaneously deleterious following injury and essential for tissue repair continues to be fundamentally important and debated question. Recently, a new paradigm has emerged in the macrophage field: that organs are replete with resident macrophages of embryonic origin, distinct from monocyte-derived macrophages. This added complexity raises the question of whether distinct immune cells drive inflammatory and reparative activities following injury. Previous work has demonstrated that the neonatal heart has a remarkable capacity for tissue repair compared to the adult, offering an ideal context to examine these concepts. We hypothesized that unrecognized differences in macrophage composition in the neonatal and adult heart represents a key determinant of cardiac recovery. To test this hypothesis, we generated a novel cardiomyocyte ablation model and demonstrated that following injury neonatal mice expand a population of resident cardiac macrophages derived from embryonic lineages, which generate minimal inflammation and are necessary and sufficient for cardiac recovery through promotion of cardiomyocyte proliferation and angiogenesis. During homeostasis the adult heart also contained embryonic-derived macrophages with similar properties. However, following injury these cells disappeared, and instead, the adult heart recruited pro-inflammatory monocytes and monocyte-derived macrophages that lacked reparative activities. Inhibition of monocyte recruitment into the injured adult heart preserved embryonic-derived macrophage subsets, reduced inflammatory cytokine and chemokine production, and enhanced tissue repair. Together, these findings indicate that embryonic-derived macrophages, rather than monocyte-derived macrophages, are key mediators of cardiac recovery. Therapeutics targeting distinct macrophage and monocyte lineages may serve as novel treatments for heart failure.
Mechanistical differences of chronic lung allograft dysfunction phenotypes in lung transplantation
Authors: Monika I. Suwara, Bart M. Vanaudenaerde, Stijn E. Verleden, Lee A. Borthwick, Robin Vos, Nicola J. Green, Chris Ward, Dirk E. Van Raemdonck, Paul A. Corris, Derek A. Mann, Geert M. Verleden, Andrew J. Fisher
Journal: European Respiratory Journal (2012)

Purpose:  The neomacrolide azithromycin, is now widely used in the treatment of Bronchiolitis Oblierans Syndrome after lung transplantation. However, only a proportion of patients respond by improving their lung function. This study aimed to evaluate differences in airway microenvironment between azithromycin responsive (>10% improvement in FEV 1 ) and azithromycin resistant BOS patients.   Methods:  Bronchoalveolar lavage (BAL) from recipients identified as stable n=10 (control), azithromycin responsive n=10 and azithromycin resistant n=10 were evaluated for cell differential, IL-1α, IL-1β, IL-6, IL-8, TNF-α proteins. BAL was then added to primary bronchial epithelial cells (PBEC) and tested for viability by XTT assay.   Results:  BAL neutrophilia (%) was increased in responders (56% p   Conclusions:  Unlike in responders, where azithromycin blocks IL-17 T cell mediated neutrophilia, azithromycin resistant phenotype is associated with epithelial damage, inducing IL-1α, TNFα and IL-1β release. This suggests anti-IL-1/TNFα therapies could be considered for BOS patients who develop an azithromycin resistant phenotype.
Role of Troponin I Proteolysis in the Pathogenesis of Stunned Myocardium
Authors: Wei Dong Gao, Dan Atar, Yongge Liu, Nestor Gustavo Perez, Anne M. Murphy, Eduardo Marban
Journal: Circulation Research (1997)

Myocardial stunning is characterized by decreased myofilament Ca2+ responsiveness. To investigate the molecular basis of stunned myocardium, we performed PAGE and Western immunoblot analysis of the contractile proteins. Isolated rat hearts were retrogradely perfused at 37 degrees C for either 50 minutes (control group) or for 10 minutes, followed by 20-minute global ischemia and 20-minute reperfusion (stunned group), or for 20-minute ischemia without reflow. Another group consisted of hearts subjected to 20-minute ischemia in which stunning was mitigated by 10-minute reperfusion with low Ca2+/low pH solution. Myocardial tissue samples subjected to PAGE revealed no obvious differences among groups. Western immunoblots for actin, tropomyosin, troponin C, troponin T, myosin light chain-1, and myosin light chain-2 showed highly selective recognition of the appropriate full-length molecular weight bands in all groups. Troponin I (TnI) Western blots revealed an additional band (approximately 26 kD, compared with 32 kD for the full-length protein) in stunned myocardial samples only. In parallel experiments, skinned trabeculae were treated with calpain I for 20 minutes; Western blots showed a TnI degradation pattern similar to that observed in stunned myocardium. Such TnI degradation was prevented by calpastatin, a naturally occurring calpain inhibitor. The results show that (1) TnI is partially and selectively degraded in stunned myocardium; (2) this degradation could be prevented by low Ca2+/low pH reperfusion, which also prevented the contractile dysfunction of stunning; and (3) calpain I could similarly degrade TnI, supporting the idea that Ca(2+)-dependent myofilament proteolysis underlies myocardial stunning.
Molecular Biology of the Ewing’s Sarcoma/Primitive Neuroectodermal Tumor Family
Authors: Enrique de Alava, William L. Gerald
Journal: Journal of Clinical Oncology (2000)

ABSTRACT: Ewing’s sarcoma (ES) and primitive neuroectodermal tumor (PNET) are members of a tumor family consistently associated with chromosomal translocation and functional fusion of the EWS gene to any of several structurally related transcription factor genes. Similar gene fusion events occur in other mesenchymal and hematopoietic tumors and are tumor-specific. The resulting novel transcription factor–like chimeric proteins are believed to contribute to tumor biology by aberrant regulation of gene expression altering critical controls of cell proliferation and differentiation. These tumor-specific molecular rearrangements are useful for primary diagnosis, may provide prognostic information, and present potential therapeutic targets. The recent advances in our understanding of the molecular biology of ES and PNET represent a paradigm for the application of the basic biology of neoplasia to clinical management of patients.
Fenspiride as complementary anti-inflammatory agent in therapy of patients with chronic obstructive pulmonary disease
Authors: Tetyana Pertseva, Olena Myronenko, Natalya Klimenko
Journal: European Respiratory Journal (2011)

The aim of our study was to study the efficacy of fenspiride (F) in the complex therapy of patients with chronic obstructive pulmonary disease (COPD).   Study population:  COPD pts with I-II stages (n=20) were observed on an extent 6-month treatment period. Among them were 13 males (65%). Mild age 49,02±11,32 year, duration of COPD 13,03±4,76. 1st gr. (10 pts) – combined therapy with F (160 mg/day) and fenoteroly/ipratropium bromide (F+I) (200+80 mcg dayly). 2nd gr. (10 pts) – monotherapy with F+I.   Methods:  Spirometry and pneumotonometry were performed on days 1, 90 and 180 by means MasterScreen Body/Diff (“Jaeger”, German). Functional status was accessed by six-minute walk distance (6MWD) test and Borg dyspnea scale. The St. George9s Respiratory Questionnaire (SGRQ) data were determined before and after treatment period.   Results : Significant increase in all of the SGRQ domains in pts of 1st gr (p 0.05).   Conclusion:  The study demonstrated greater efficacy of long-term complex therapy with fenspiride and fenoterol/ipratropium bromide compared with fenoterol/ipratropium bromide alone in patients with COPD. This combination regimen can be recommended for the reduction of inflammation and prevention of disease progression in COPD patients.
A Comparison of the Attitudes Shown by General Practitioners, Hospital Doctors and Medical Students towards Alternative Medicine
Authors: Michael R Perkin, Richard M Pearcy, Jocelyn S Fraser
Journal: Journal of the Royal Society of Medicine (1994)

The aim of this study was to compare and contrast the views of general practitioners (GPs), hospital doctors and medical students to alternative medicine. A questionnaire was sent to a random sample of 100 GPs and 100 hospital doctors in the South West Thames Regional Health Authority (SWTRHA). A convenience sample of 237 pre-clinical medical students at St George's Hospital Medical School was also given a questionnaire. Eighty-seven GPs and 81 hospital doctors replied. Five therapies were investigated: acupuncture; chiropractice; homeopathy; naturopathy; and osteopathy. All respondents were asked about their attitude towards and knowledge of these therapies. Doctors were asked how often they referred patients for such treatment and whether they practised it themselves. GPs and hospital doctors had similar levels of knowledge of the therapies. Medical students were the least informed but the most enthusiastic respondents. Seventy per cent of hospital doctors and 93% of GPs had, on at least one occasion, suggested a referral for alternative treatment. GPs were making these referrals more frequently and earlier. Twelve per cent of hospital doctors and 20% of GPs were practising alternative medicine. The majority of the respondents felt that alternative medicine should be available on the National Health Service (NHS) and that medical students should receive some tuition about alternative therapies. A considerable proportion of those doctors referring patients to alternative practitioners were ignorant of their official qualifications.
Increasing prevalence of complicated pneumonia and pneumococcal related hemolytic uremic syndrome despite territory-wide program of pneumococcal conjugated vaccination (PCV-7) program in children
Authors: Gary Wong, Tony Nelson, Grace Chiang, Ting Fan Leung, Paul Chan, Margaret Ip
Journal: European Respiratory Journal (2014)

Background: US studies suggested that use of PCV-7 may be associated with increased incidence of complicated pneumonia. From September 2009 PCV7 was included in Hong Kong9s publicly funded immunization schedule.  Methods: We performed a retrospective study using data from the central computerized database of all public hospitals in Hong Kong for children 18 yrs or below to determine rates of hospitalization pre- and post-PCV7 vaccination by retrieving all cases with a discharge diagnosis of pneumonia, complicated pneumonia, invasive pneumococcal diseases, pneumococcal bacteremia from Jan 2005 to Dec 2013. Records from one tertiary university hospital were conducted to evaluate the types of invasive pneumococcal diseases.  Results: From 2005 to 2013, annual incidence rates of pneumococcal bacteremia decreased by 40 to 50%. However, the adjusted incidence rates of complicated pneumonia for children under 18 years and under 5 years have increased from 6.9 (2005 to 2008) to 13.6/100,000/yr (2010 to 2013) (P  Conclusion:We documented a significant increase of complicated pneumonia shortly after PCV7 vaccination was started in Hong Kong. Severe cases were caused by serotypes not covered by PCV7 or 10. PCV-13 booster may reduce severe infections due to serotypes 3 and 19A.
Evaluation of symptom checkers for self diagnosis and triage: audit study
Authors: Hannah L Semigran, Jeffrey A Linder, Courtney Gidengil, Ateev Mehrotra
Journal: BMJ (2015)

<b>Objective</b> To determine the diagnostic and triage accuracy of online symptom checkers (tools that use computer algorithms to help patients with self diagnosis or self triage). <b>Design</b> Audit study. <b>Setting</b> Publicly available, free symptom checkers. <b>Participants</b> 23 symptom checkers that were in English and provided advice across a range of conditions. 45 standardized patient vignettes were compiled and equally divided into three categories of triage urgency: emergent care required (for example, pulmonary embolism), non-emergent care reasonable (for example, otitis media), and self care reasonable (for example, viral upper respiratory tract infection). <b>Main outcome measures</b> For symptom checkers that provided a diagnosis, our main outcomes were whether the symptom checker listed the correct diagnosis first or within the first 20 potential diagnoses (n=770 standardized patient evaluations). For symptom checkers that provided a triage recommendation, our main outcomes were whether the symptom checker correctly recommended emergent care, non-emergent care, or self care (n=532 standardized patient evaluations). <b>Results</b> The 23 symptom checkers provided the correct diagnosis first in 34% (95% confidence interval 31% to 37%) of standardized patient evaluations, listed the correct diagnosis within the top 20 diagnoses given in 58% (55% to 62%) of standardized patient evaluations, and provided the appropriate triage advice in 57% (52% to 61%) of standardized patient evaluations. Triage performance varied by urgency of condition, with appropriate triage advice provided in 80% (95% confidence interval 75% to 86%) of emergent cases, 55% (47% to 63%) of non-emergent cases, and 33% (26% to 40%) of self care cases (P&lt;0.001). Performance on appropriate triage advice across the 23 individual symptom checkers ranged from 33% (95% confidence interval 19% to 48%) to 78% (64% to 91%) of standardized patient evaluations. <b>Conclusions</b> Symptom checkers had deficits in both triage and diagnosis. Triage advice from symptom checkers is generally risk averse, encouraging users to seek care for conditions where self care is reasonable.
Hypercalcemia during pulse vitamin D3 therapy in CAPD patients treated with low calcium dialysate
Authors: A Chagnac, Y Ori, T Weinstein, D Zevin, A Korzets, J Hirsh, S Edelstein, U Gafter
Journal: Journal of the American Society of Nephrology (1997)

Oral pulse therapy with vitamin D is effective in suppressing parathyroid hormone (PTH) secretion in continuous ambulatory peritoneal dialysis patients with secondary hyperparathyroidism (2'hpt). However, this treatment often leads to hypercalcemia. The goals of the study were: (1) to examine whether the incidence of hypercalcemia decreases when dialysate calcium is reduced from 1.25 to 1.0 mmol/L; (2) to determine the relative role of the factors involved in the pathogenesis of hypercalcemia; and (3) to study the efficacy of a low oral pulse dose of alfacalcidol in preventing the recurrence of 2'hpt. Fourteen continuous ambulatory peritoneal dialysis patients with 2'hpt were treated with pulse oral alfacalcidol and calcium carbonate and dialyzed with a 1.0-mmol (n = 7) or a 1.25-mmol (n = 7) dialysate calcium. The response rate (87%) and the incidence (71%) and severity of hypercalcemia were similar in both groups. In the early response stage, PTH decreased by 70% in both groups, and serum ionized calcium (iCa) increased from 1.18 +/- 0.02 to 1.27 +/- 0.04 mmol/L (P < 0.005) in the 1.0 group and from 1.19 +/- 0.02 to 1.29 +/- 0.02 mmol/L in the 1.25 group (P < 0.005). Nine of the 12 responders had a further decrease in serum PTH, which was associated with an additional increase in iCa from 1.28 +/- 0.02 to 1.47 +/- 0.04 (P < 0.005). Multivariate analysis showed that the early increase in iCa was positively correlated with alfacalcidol dosage (r = 0.69). In contrast, the late increase in iCa was mostly accounted for by the decrease in serum PTH (r = -0.93). This occurred while calcium carbonate, alfacalcidol dosage, and serum 1,25 hydroxy D3 remained unchanged compared with the early response stage. Finally, an alfacalcidol dose of 1 microg twice weekly was unable to maintain serum PTH at an adequate level in the long term. These data show that a reduction in dialysate calcium from 1.25 to 1.0 mmol does not reduce the occurrence of hypercalcemia and suggest that lowering serum PTH reduces the ability of the bone to handle a calcium load within a few weeks, thus causing hypercalcemia.