tbuckley/cabot-search huggingface dataset:
Cutaneous lymphomatoid granulomatosis: a rare cause of recurrent skin ulceration
Authors: M.L. WOOD, C.I. HARRINGTON, D.N. SLATER, N. ROONEY, A. CLARK
Journal: British Journal of Dermatology (2006)

We report the case of a 34-year-old male who presented with recurrent skin ulceration due to lymphomatoid granulomatosis. Monoclonal antibody studies showed a high T helper (T4):T suppressor (T8) cell ratio in both the lesions and the peripheral blood. Plasma cells in the infiltrate showed IgA lambda staining but as yet no monoclonal immunoglobulin has been identified in the blood or urine. Lymphocytes bearing markers of immature cells (T10) were observed in the tissue and blood.
Hemodynamics of Intestinal Circulation
Authors: EWALD E. SELKURT, MARIO P. SCIBETTA, THEODORE E. CULL
Journal: Circulation Research (1958)

The pressure-flow relationship was studied in isolated denervated intestinal loops of the dog in a range of pressure varying from 0 to 240 mm. Hg. The relationship was curvilinear, convex to the pressure axis. Flow started at a minimal pressure of 16 mm. Hg, then increased more rapidly than pressure up to 240 mm. Hg. Critical closure, passive expansion of vessels with rising intraluminal pressure, and anomalous viscosity of blood appeared to be the important factors influencing vascular resistance and flow in the present studies.
AT-26 * CLINICAL MANAGEMENT AND OUTCOME OF HISTOLOGICALLY VERIFIED ADULT BRAINSTEM GLIOMAS IN SWITZERLAND: A RETROSPECTIVE ANALYSIS OF 21 PATIENTS
Authors: T. Hundsberger, M. Tonder, A. Hottinger, D. Brugge, U. Roelcke, M. Putora, R. Stupp, M. Weller
Journal: Neuro-Oncology (2014)

BACKGROUND: Because of low incidence, mixed study populations and paucity of clinical and histological data, the management of adult brainstem gliomas remains non-standardized. We here describe characteristics, treatment and outcome of patients with exclusively histologically confirmed adult brainstem gliomas. METHODS: A retrospective chart review of adults (> age 18 years) was conducted. Brainstem glioma was defined as a glial tumor located in the midbrain, pons or medulla. Characteristics, management and outcome were analyzed. RESULTS: 21 patients (17 males; median age 41 years) were diagnosed between 2004 and 2012 by biopsy (n = 15), partial (n = 4) or complete resection (n = 2). Diagnoses were glioblastoma (WHO grade IV, n = 6), anaplastic astrocytoma (WHO grade III, n = 7), diffuse astrocytoma (WHO grade II, n = 6) and pilocytic astrocytoma (WHO grade I, n = 2). Diffuse gliomas were mainly located in the pons and frequently showed MRI contrast enhancement. Endophytic growth was common (16 versus 5). Postoperative therapy in low-grade (WHO grade I/II) and high-grade gliomas (WHO grade III/IV) consisted of radiotherapy alone (3 in each group), radiochemotherapy (2 versus 6), chemotherapy alone (0 versus 2) or no postoperative therapy (3 versus 1). Median PFS (24.1 versus 5.8 months; log-rank, p = 0.009) and mOS (30.5 versus 11.5 months; log-rank, p = 0.028) was significantly better in WHO grade II than in WHO grade III/IV tumors. Second-line therapy considerably varied. CONCLUSIONS: Histologically verification of adult brainstem glioma is feasible and has an impact on postoperative treatment. Low-grade gliomas can simple be followed or treated with radiotherapy alone. Radiochemotherapy with temozolomide can safely be prescribed for high-grade gliomas without additional CNS toxicities.
Origin of Type 2 Helper T Cells
Authors: A.B. Kay
Journal: New England Journal of Medicine (1994)

The concept of a subdivision of CD4+ helper T cells based on their cytokine profile was first proposed by Mosmann and Coffman in 19871. Type 2 helper T cells preferentially transcribe and translate messenger RNA (mRNA) for interleukin-4 and interleukin-5 and predominate in blood and tissues involved in atopic allergy and helminthic infections. Interleukin-4 is an essential cofactor for the production of IgE by B cells, and interleukin-5, together with granulocyte-macrophage colony-stimulating factor and interleukin-3, promotes eosinophil maturation, activation, and survival. The counterpart of the type 2 subgroup is the type 1 subgroup. Through the elaboration of interferon gamma . . .
TB screening and anti-TNF treatment
Authors: G Provenzano
Journal: Thorax (2005)

Reactivation of tuberculosis (TB) is a major concern during treatment with TNF inhibitors.1 Different guidelines to detect active and latent TB have been recommended in various countries before starting treatment with these drugs. There is evidence that their application has led to a significant reduction in the number of cases of TB,2 but we do not know which is the most cost effective strategy.

In our department 69 consecutive patients with rheumatoid arthritis (n = 53), ankylosing spondylitis (n = 10), and psoriatic arthritis (n = 6) considered for treatment with TNF inhibitors …
Diagnostic accuracy of pleural fluid NTpro-BNP for pleural effusions of cardiac origin
Authors: Juan Antonio Mazzei, Juan Bourbotte, Marcelo Melero, Daniel Piñeiro, Griselda Pargament, Marcela Catro
Journal: European Respiratory Journal (2012)

INTRODUCTION  The most frequent cause of a pleural effusion is heart failure. The diagnosis is based on clinical findings and biochemical parameters.  RATIONALE  The existence of a specific heart biomarker could avoid unnecessary studies for the diagnosis of cardiac origin of pleural fluids.  OBJECTIVE  The purpose of our study was to evaluate the diagnostic accuracy of pleural fluid aminoterminal fragment N-terminal pro-brain natriuretico peptide (NTpro-BNP) for pleural effusions of cardiac origin compared with Framingham criteria.  MATERIAL AND METHODS  We studied 32 consecutive patients admitted at the work site. Pleural and blood samples were simultaneously obtained  NTpro-BNP was measured in blood and pleural fluids (Bio Merieux® Enzyme-Linked Fluorescent Assay). Light criteria and serum-pleural albumin gradient was used to discriminate transudates from exudates.  RESULTS  The cut-off value of pleural fluid NTpro-BNP level to discriminate between pleural effusions due to heart failure was ≥1.791 pg/mL. The sensitivity and specificity was 75.0%(95%CI 47.6-92.6) and 81.2%(95%CI 54.4-95.7) respectively; with a positive predictive value of 80.0%(95%CI 51.9-96.0), negative predictive value 81.8%(95%CI 50.1-93.2), positive likelihood ratio 4.0(95%CI 20.8-5.8) and negative likelihood ratio 0.3(95%CI 0.1-1.2).  CONCLUSIONS  Pleural fluid NTpro-BNP is a very useful biomarker with high diagnostic accuracy for distinguishing pleural effusions of cardiac origin.
Estrogen receptor-α signaling in osteoblast progenitors stimulates cortical bone accrual
Authors: Maria Almeida, Srividhya Iyer, Marta Martin-Millan, Shoshana M. Bartell, Li Han, Elena Ambrogini, Melda Onal, Jinhu Xiong, Robert S. Weinstein, Robert L. Jilka, Charles A. O’Brien, Stavros C. Manolagas
Journal: Journal of Clinical Investigation (2012)

The detection of estrogen receptor-α (ERα) in osteoblasts and osteoclasts over 20 years ago suggested that direct effects of estrogens on both of these cell types are responsible for their beneficial effects on the skeleton, but the role of ERα in osteoblast lineage cells has remained elusive. In addition, estrogen activation of ERα in osteoclasts can only account for the protective effect of estrogens on the cancellous, but not the cortical, bone compartment that represents 80% of the entire skeleton. Here, we deleted ERα at different stages of differentiation in murine osteoblast lineage cells. We found that ERα in osteoblast progenitors expressing Osterix1 (Osx1) potentiates Wnt/β-catenin signaling, thereby increasing proliferation and differentiation of periosteal cells. Further, this signaling pathway was required for optimal cortical bone accrual at the periosteum in mice. Notably, this function did not require estrogens. The osteoblast progenitor ERα mediated a protective effect of estrogens against endocortical, but not cancellous, bone resorption. ERα in mature osteoblasts or osteocytes did not influence cancellous or cortical bone mass. Hence, the ERα in both osteoblast progenitors and osteoclasts functions to optimize bone mass but at distinct bone compartments and in response to different cues.
Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans
Authors: Eva Efsen, Cecilia Grappone, Raffaella M.S DeFranco, Stefano Milani, Roberto G Romanelli, Andrea Bonacchi, Alessandra Caligiuri, Paola Failli, Francesco Annunziato, Gabriella Pagliai, Massimo Pinzani, Giacomo Laffi, Paolo Gentilini, Fabio Marra
Journal: Journal of Hepatology (2002)
Reply to J.R. Anderson et al
Authors: Daniel Williamson, Edoardo Missiaglia, Aurélien de Reyniès, Gaëlle Pierron, Benedicte Thuille, Gilles Palenzuela, Khin Thway, Daniel Orbach, Marick Laé, Paul Fréneaux, Kathy Pritchard-Jones, Odile Oberlin, Janet Shipley, Olivier Delattre
Journal: Journal of Clinical Oncology (2010)
Group B <i>Streptococcus</i> suppression of phagocyte functions by protein-mediated engagement of human Siglec-5
Authors: Aaron F. Carlin, Yung-Chi Chang, Thomas Areschoug, Gunnar Lindahl, Nancy Hurtado-Ziola, Charles C. King, Ajit Varki, Victor Nizet
Journal: The Journal of Experimental Medicine (2009)

Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections in human newborns. A key GBS virulence factor is its capsular polysaccharide (CPS), displaying terminal sialic acid (Sia) residues which block deposition and activation of complement on the bacterial surface. We recently demonstrated that GBS Sia can bind human CD33-related Sia-recognizing immunoglobulin (Ig) superfamily lectins (hCD33rSiglecs), a family of inhibitory receptors expressed on the surface of leukocytes. We report the unexpected discovery that certain GBS strains may bind one such receptor, hSiglec-5, in a Sia-independent manner, via the cell wall–anchored β protein, resulting in recruitment of SHP protein tyrosine phosphatases. Using a panel of WT and mutant GBS strains together with Siglec-expressing cells and soluble Siglec-Fc chimeras, we show that GBS β protein binding to Siglec-5 functions to impair human leukocyte phagocytosis, oxidative burst, and extracellular trap production, promoting bacterial survival. We conclude that protein-mediated functional engagement of an inhibitory host lectin receptor promotes bacterial innate immune evasion.
Plasma trough levels of mycophenolic acid do not correlate with efficacy and safety of mycophenolate mofetil in psoriasis
Authors: E. Dauden, C. Sanchez-Peinado, D. Ruiz-Genao, M. Garcia-F-Villalta, M.J. Onate, A. Garcia-Diez
Journal: British Journal of Dermatology (2004)

Mycophenolate mofetil (MMF) has been shown to be effective for systemic treatment of psoriasis. MMF is the prodrug of mycophenolic acid (MPA), the pharmacologically active compound. The measurement of plasma MPA levels could be useful for optimizing therapeutic management using MMF.To investigate whether plasma trough levels of MPA correlate with the efficacy and safety of oral MMF in the treatment of patients with psoriasis.Six patients (four women and two men, mean age 58 years) with severe chronic plaque-type psoriasis were treated with oral MMF 1 g twice daily. The Psoriasis Area and Severity Index (PASI), routine laboratory examinations and plasma MPA trough levels, measured by an enzyme-multiplied immunoassay (EMIT), were determined at 2 weeks and 1, 3, 5 and 7 months.All the patients experienced a marked improvement within the first 15 days and continued to do so for 5-7 months. Two patients achieved complete remission. MMF was well tolerated. MPA levels showed a wide intra- and interindividual variability. There was no significant correlation between MPA trough levels and the reduction of the PASI or the presence of adverse effects, but a good correlation with therapeutic compliance.The monitoring of MPA trough levels with EMIT appears to be a poor predictor of efficacy or toxicity. In contrast, it is a useful tool to evaluate the degree of therapeutic compliance.
Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population: Inter99 randomised trial
Authors: T. Jorgensen, R. K. Jacobsen, U. Toft, M. Aadahl, C. Glumer, C. Pisinger
Journal: BMJ (2014)

<b>Objective</b> To investigate the effect of systematic screening for risk factors for ischaemic heart disease followed by repeated lifestyle counselling on the 10 year development of ischaemic heart disease at a population level. <b>Design</b> Randomised controlled community based trial. <b>Setting</b> Suburbs of Copenhagen, Denmark <b>Participants</b> 59 616 people aged 30-60 years randomised with different age and sex randomisation ratios to an intervention group (n=11 629) and a control group (n=47 987). <b>Intervention</b> The intervention group was invited for screening, risk assessment, and lifestyle counselling up to four times over a five year period. All participants with an unhealthy lifestyle had individually tailored lifestyle counselling at all visits (at baseline and after one and three years); those at high risk of ischaemic heart disease, according to predefined criteria, were furthermore offered six sessions of group based lifestyle counselling on smoking cessation, diet, and physical activity. After five years all were invited for a final counselling session. Participants were referred to their general practitioner for medical treatment, if relevant. The control group was not invited for screening. <b>Main outcome measures</b> The primary outcome measure was incidence of ischaemic heart disease in the intervention group compared with the control group. Secondary outcome measures were stroke, combined events (ischaemic heart disease, stroke, or both), and mortality. <b>Results</b> 6091 (52.4%) people in the intervention group participated at baseline. Among 5978 people eligible at five year follow-up (59 died and 54 emigrated), 4028 (67.4%) attended. A total of 3163 people died in the 10 year follow-up period. Among 58 308 without a history of ischaemic heart disease at baseline, 2782 developed ischaemic heart disease. Among 58 940 without a history of stroke at baseline, 1726 developed stroke. No significant difference was seen between the intervention and control groups in the primary end point (hazard ratio for ischaemic heart disease 1.03, 95% confidence interval 0.94 to 1.13) or in the secondary endpoints (stroke 0.98, 0.87 to 1.11; combined endpoint 1.01, 0.93 to 1.09; total mortality 1.00, 0.91 to 1.09). <b>Conclusion</b> A community based, individually tailored intervention programme with screening for risk of ischaemic heart disease and repeated lifestyle intervention over five years had no effect on ischaemic heart disease, stroke, or mortality at the population level after 10 years. <b>Trial registration</b> Clinical trials NCT00289237.
Are there clinical benefits associated with treatment of mild chemotherapy-induced anemia (CIA)? A systematic review
Authors: G. Rossi, J. Glaspy, G. Lyman
Journal: Journal of Clinical Oncology (2005)

8194 Background: American Society of Hematology [ASH]/American Society of Clinical Oncology [ASCO] clinical practice guidelines for the management of CIA recommend initiating erythropoietic therapy at hemoglobin (Hb) ≤ 10 g/dL. However, there is increasing debate regarding the benefits of initiating erythropoietic therapy in patients with mild anemia. We conducted a systematic review to determine if there are clinical benefits associated with initiating erythropoietic therapy in cancer patients with Hb ≥ 10 g/dL. Methods: Medline database and conference proceedings (ASH and ASCO) were searched to identify randomized controlled trials that evaluated the effect of early erythropoietic intervention on transfusion incidence, Hb concentration, and/or patient-reported outcomes relative to control and to late intervention (Hb < 10 g/dL). Data were extracted from studies that met prespecified eligibility criteria. For outcome measures not associated with significant heterogeneity, summary measures of relative risk associated with early erythropoietic intervention were estimated using the method of Mantel and Haenszel. Results: Eleven studies (5 papers, 6 abstracts) were identified and included in this analysis. Erythropoietic treatment of mild anemia effectively decreased transfusion incidence and the proportion of patients with Hb < 10 g/dL compared with no treatment, with relative risk reductions of 0.47 (95% CL:0.38, 0.57; 6 studies, P < .001) and 0.48 (95% CL: 0.25, 0.89; 4 studies, P = .195), respectively. The findings from studies in which early and late intervention were compared also indicated a reduction in the relative risk of transfusions and Hb < 10 g/dL following early intervention (0.55 [95% CL: 0.42, 0.73; 5 studies, P < .001) and 0.42 (95% CL: 0.32, 0.56; 2 studies, P < .001), respectively. Conclusions: These findings suggest that optimal clinical benefits from erythropoietic treatment of CIA may be achieved with initiation at Hb levels of 10–12 g/dL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen Amgen
Differential expression of miR-17∼92 identifies BCL2 as a therapeutic target in BCR-ABL-positive B-lineage acute lymphoblastic leukemia
Authors: M Scherr, A Elder, K Battmer, D Barzan, S Bomken, M Ricke-Hoch, A Schröder, L Venturini, H J Blair, J Vormoor, O Ottmann, A Ganser, A Pich, D Hilfiker-Kleiner, O Heidenreich, M Eder
Journal: Leukemia (2013)

Despite advances in allogeneic stem cell transplantation, BCR-ABL-positive acute lymphoblastic leukaemia (ALL) remains a high-risk disease, necessitating the development of novel treatment strategies. As the known oncomir, miR-17∼92, is regulated by BCR-ABL fusion in chronic myeloid leukaemia, we investigated its role in BCR-ABL translocated ALL. miR-17∼92-encoded miRNAs were significantly less abundant in BCR-ABL-positive as compared to -negative ALL-cells and overexpression of miR-17∼19b triggered apoptosis in a BCR-ABL-dependent manner. Stable isotope labelling of amino acids in culture (SILAC) followed by liquid chromatography and mass spectroscopy (LC-MS) identified several apoptosis-related proteins including Bcl2 as potential targets of miR-17∼19b. We validated Bcl2 as a direct target of this miRNA cluster in mice and humans, and, similar to miR-17∼19b overexpression, Bcl2-specific RNAi strongly induced apoptosis in BCR-ABL-positive cells. Furthermore, BCR-ABL-positive human ALL cell lines were more sensitive to pharmacological BCL2 inhibition than negative ones. Finally, in a xenograft model using patient-derived leukaemic blasts, real-time, in vivo imaging confirmed pharmacological inhibition of BCL2 as a new therapeutic strategy in BCR-ABL-positive ALL. These data demonstrate the role of miR-17∼92 in regulation of apoptosis, and identify BCL2 as a therapeutic target of particular relevance in BCR-ABL-positive ALL.
A Life-Saving Maneuver to Prevent Food-Choking
Authors: Henry J. Heimlich
Journal: JAMA (1975)

EACH year, 3,900 healthy individuals in the United States strangle because of food stuck in their throats (<i>New York Times Magazine</i>, June 16, 1974, p 10). The actual incidence is probably much higher, as indicated by a report of unsuspected food-choking found at postmortem examinations of three patients thought to have died from myocardial infarction in one nursing home last year.<sup>1</sup>Food-choking is the sixth leading cause of accidental death—its victims number more than those accidentally killed by firearms or in airplane accidents. This article describes experimental studies and the clinical evaluation of a simple maneuver that prevents these food-choking fatalities. Food-choking can be recognized easily. The victim cannot speak or breathe; he becomes pale, then deeply cyanotic, and collapses. Because death is sudden (occurring in four to five minutes), the episode is sometimes confused with a myocardial infarction, although the signs and symptoms of the two are different. The
Seroprevalence, correlates, and characteristics of undetected coeliac disease in England
Authors: J West
Journal: Gut (2003)

<b>Objective:</b> To examine the seroprevalence, correlates, and characteristics of undetected coeliac disease in a large adult population sample in Cambridge, UK. <b>Methods:</b> The Cambridge General Practice Health Study invited individuals from 12 general practices, aged 45–76 years, to attend for a health survey that included a bone density measurement, between 1990 and 1995. A total of 7550 participants’ serum samples were tested for antiendomysial antibody (EMA). Seroprevalence of undetected coeliac disease was based on EMA positivity. Differences between EMA positive and negative participants of various physiological correlates and reported characteristics were estimated by multivariate logistic and linear regression and adjusted for age, sex, social class, and smoking behaviour. <b>Results:</b> The seroprevalence of undetected coeliac disease in this general population sample aged 45–76 was 1.2% (95% confidence interval (CI) 0.9–1.4). EMA positive participants (n=87) were on average slightly lighter by 2.2 kg (p=0.08), were more likely to have reported their general health as being “good or excellent” (odds ratio (OR) 1.76 (95% CI 0.90–3.46)), and were less likely to report being a current smoker (OR for current versus never 0.36 (95% CI 0.14–0.90)) than EMA negative participants. EMA positivity was associated with an 8% reduction in mean serum cholesterol (0.5 mmol/l; p&lt;0.01) and reductions in mean haemoglobin (0.3 g/dl; p&lt;0.01), total protein (1.0 g/l; p&lt;0.05), and corrected serum calcium (0.02 mmol/l; p&lt;0.05). There was an increased risk of osteoporosis in EMA positive participants (OR 3.1 (95% CI 1.3–7.2)) and of mild anaemia (OR 4.6 (95% CI 2.5–8.2)) compared with EMA negative participants. <b>Conclusions:</b> Undetected coeliac disease is likely to affect approximately 1% of the population of England aged 45–76 years, a value similar to several other countries. Those affected report “better health” but they do have an increased risk of osteoporosis and mild anaemia. In contrast, they have a favourable cardiovascular risk profile that may afford protection from ischaemic heart disease and stroke.