tbuckley/cabot-search huggingface dataset:
Prevalence of asthma symptoms in video and written questionnaires among children in four regions of Finland
Authors: J Pekkanen, ST Remes, T Husman, M Lindberg, M Kajosaari, A Koivikko, L Soininen
Journal: European Respiratory Journal (1997)

The aim of this study was to determine whether there are regional differences in the prevalence of childhood asthma in Finland. A secondary objective was to assess the concordance between a written and a video questionnaire on asthma symptoms. In 1994-1995, the self-reported prevalence of asthma symptoms in four regions of Finland was studied among 11,607 schoolchildren aged 13-14 yrs, as part of the International Study of Asthma and Allergies in Childhood (ISAAC). The ISAAC written and video (AVQ 3,0) questionnaires were administered in the school setting. The prevalences of any wheezing during the previous 12 months in the ISAAC video questionnaire were 10% in East Finland (Kuopio County, n=2,821), 12% in South Finland (Helsinki area, n=2,771), 12% in Southwest Finland (Turku and Pori County, n=2,983), and 11% in North Finland (Lapland, n=3,032). The prevalences in the ISAAC written questionnaire were 13, 20, 15, and 16%, respectively. The surveys were performed during winter, except in Helsinki where the survey was carried out mainly during the spring pollen season. During autumn, the prevalence in the written questionnaire in Helsinki was 16%. In multivariate analysis, boys had a lower prevalence than girls, and smokers a threefold higher prevalence than nonsmokers. In conclusion, the prevalence of childhood asthma is lower in Finland than in other European countries, and may be even lower in the eastern part of the country. In contrast to the results from some other European countries, prevalences were lower in the video than in the written questionnaire, which suggests that translating the word "wheezing" into other languages, including Finnish, may produce results that cannot be compared. The strong association of smoking with wheeze both in the video and written questionnaires should be considered in further analysis of the ISAAC study.
Why We Must Leave Our Organs to Others
Authors: D. Micah Hester
Journal: The American Journal of Bioethics (2006)

Organ procurement presents several ethical concerns (from what constitutes acceptable criteria for death to issues involved in specifically designating to whom an organ can be given), but none is more central than the concern for what are appropriate means for acquiring organs. The following discussion attempts a different perspective on the issue of organ procurement by arguing that, rather than appealing to our charitable consciences or our pocketbooks, relinquishing our organs after death in this day and age is, in fact, obligatory for most people. Each of us is pressed by the growing demand for our organs should we die "rightly," and that desperate need has risen to such a level that not to release our organs for transplantation would constitute a serious moral wrong.
Outcome of Acute Promyelocytic Leukemia (APL) in Children and Adolescents: An Analysis in Two Consecutive Trials of the European APL Group
Authors: Cecile Bally, Jehane Fadlallah, Guy Leverger, Yves Bertrand, Alain Robert, Andre Baruchel, Agnes Guerci, Christian Recher, Emmanuel Raffoux, Xavier Thomas, Thierry Leblanc, Nadia Idres, Bruno Cassinat, Norbert Vey, Christine Chomienne, Herve Dombret, Miguel Sanz, Pierre Fenaux, Lionel Adès
Journal: Journal of Clinical Oncology (2012)

Acute promyelocytic leukemia (APL) is rare in children. All-trans-retinoic acid (ATRA) combined with chemotherapy, the reference treatment of APL, is generally considered to produce similar results in children and adults. However, previously published childhood APL studies have generally analyzed all patients age < 18 years as a group, without further dividing according to age.We compared disease characteristics and outcomes of children (age ≤ 12 years), adolescents (13 to 18 years), and adults (> 18 years) included in two multicenter APL clinical trials (APL 93 and 2000 trials).Of the 833 patients age ≤ 60 years included in the two trials, 26 (3%), 58 (7%), and 749 (90%) were children, adolescents, and adults, respectively. Children had significantly higher baseline WBC counts (P < .001). The complete remission (CR) rate (92%, 100%, and 94.5%, respectively) and 5-year cumulative incidence of relapse (CIR; 28%, 20%, and 23%, respectively) did not differ between children, adolescents, and adults, whereas adolescents had significantly better overall survival (OS; 5-year OS, 93.6% v 80.4% in adults and 80.4% in children; P = .03). However, in children age ≤ 4 years, the 5-year CIR was 52%, compared with 17.6% in children age 5 to 12 years (P = .006), although most of the younger children who relapsed experienced durable salvage with autologous or allogeneic stem-cell transplantation.Adolescents and children age > 4 years with APL treated with ATRA and chemotherapy have outcomes at least as favorable as those of adults. Younger children seem to experience more relapses and may require reinforcement of first-line treatment.
Reducing TNF Receptor 2+ Regulatory T Cells via the Combined Action of Azacitidine and the HDAC Inhibitor, Panobinostat for Clinical Benefit in Acute Myeloid Leukemia Patients
Authors: Chindu Govindaraj, Peter Tan, Patricia Walker, Andrew Wei, Andrew Spencer, Magdalena Plebanski
Journal: Clinical Cancer Research (2013)

Acute myeloid leukemia (AML) provides an environment that enables immune suppression, resulting in functionally defective effector T cells; regulatory T cells (Treg) are significant contributors to the impaired antitumor immune response. As TNF is present at high levels in AML and TNF receptor-2 (TNFR2)-expressing Tregs identify highly functional Tregs, we examine the hypothesis that TNFR2(+) Tregs are a relevant Treg subset in this cancer. We also determine the effect of the novel combinatorial therapy of the demethylating agent, azacitidine with the histone deacetylase inhibitor, panobinostat on Tregs, particularly TNFR2(+) Tregs.Thirty healthy donors and 14 patients with AML were enrolled in this study. Patients were treated with azacitidine and panobinostat for 28-day cycles. The frequency and functional relevance of TNFR2(+) Tregs were analyzed subsequently.We report that TNFR2(+) Tregs are increased in AML and have a high migration potential toward the bone marrow. Furthermore, we demonstrate that the level of TNFR2(+) Tregs in the peripheral blood and the bone marrow of patients are decreased in vivo after exposure to panobinostat and azacitidine. Reductions in TNFR2(+) Tregs were associated with increases in Interferon (IFN)-γ and interleukin (IL)-2 production by effector T cells within the bone marrow and beneficial clinical responses. In vitro mechanistic studies indicated panobinostat as the primary driver for the reduction of Tregs.Our study provides for the first time, in vivo validation of the ability of panobinostat in combination with azacitidine to suppress prevalent TNFR2(+) Tregs, resulting in clinical benefits within patients with AML.
Impact of Clinical Syndrome Acuity on the Differential Response to 2 Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Coronary Stenting
Authors: Gregg W. Stone, David J. Moliterno, Michel Bertrand, Franz-Josef Neumann, Howard C. Herrmann, Eric R. Powers, Cindy L. Grines, Jeffrey W. Moses, David J. Cohen, Eric A. Cohen, Marc Cohen, Kathy Wolski, Peter M. DiBattiste, Eric J. Topol
Journal: Circulation (2002)

Background — Although glycoprotein IIb/IIIa inhibitors have been shown to reduce periprocedural and late ischemic events in patients undergoing stent implantation, the relative safety and efficacy of different agents in this class is less established. Also unknown is whether the acuity of the presenting clinical syndrome, which may affect the degree of platelet inhibition required or achieved, influences the response to different antiplatelet agents. Methods and Results — A prospective, multicenter, double-blind, randomized trial was performed in which 4809 patients undergoing planned stenting were randomized to receive abciximab or tirofiban. In patients with acute coronary syndromes (ACS; n=3025), abciximab resulted in lower rates of myocardial infarction at 30 days (5.8% versus 8.5%; P =0.004) and 6 months (7.2% versus 9.8%; P =0.013), although 6-month mortality rates were identical (1.39% in both groups; P =0.99). Conversely, in patients without ACS (n=1784), myocardial infarction rates were not significantly lower with tirofiban, survival was similar, and target vessel revascularization was reduced, which translated into a trend toward enhanced 6-month event-free survival with tirofiban (89.7% versus 86.6%; P =0.056). Conclusions — In patients with ACS undergoing stent implantation, abciximab use compared with tirofiban results in greater suppression of periprocedural myonecrosis, although a survival benefit has not been demonstrated. Patients with stable coronary syndromes may have equivalent or better outcomes with tirofiban relative to abciximab, with fewer adverse hematologic and hemorrhagic events. These data raise important issues regarding the relative pharmacodynamic inhibition of platelet function required in varying clinical scenarios and have important implications for the cost-effective utilization of glycoprotein IIb/IIIa inhibitors.
Disappearance of bone marrow B cell clonal expansion in patients with type II hepatitis C virus-related cryoglobulinemic glomerulonephritis after clinical efficient rituximab therapy
Authors: L Quartuccio, S Salvin, M Fabris, S Sacco, S De Vita
Journal: Annals of the Rheumatic Diseases (2008)

Preliminary data provided encouraging results on efficacy and safety of B cell depletion with rituximab in active glomerulonephritis in the course of mixed cryoglobulinemia (MC).1 2

B cell oligomonoclonal expansion in peripheral blood and in bone marrow (BM) seems to be a key pathological and molecular feature in MC.3 4 Recently, renal involvement in MC has been associated with B cell clonal expansion in the BM.5 We report new data on the possible relationship between clinical efficacy of rituximab in MC nephritis and the disappearance of BM B cell clonal expansion after (month +6) rituximab administration demonstrated by molecular studies (fig 1).4



Figure 1 Bone marrow (BM) B cell expansion before and after rituximab. Bone marrow B cell expansion was evaluated in BM needle aspiration samples by semi-nested PCR using an upstream primer directed to the third framework variable (V) region of the IgH genes and downstream primers directed to the joining (J) region, as described previously.5 Samples were tested in duplicate, and the results were confirmed in repeated experiments. PCR products were analysed on 10% polyacrylamide gels stained with ethidium bromide. A clonal B cell expansion was defined by the presence of discrete, reproducible narrow band(s) within the predicted size range, while a polyclonal pattern by a ladder of bands with similar intensities or by the presence of weakly dominant bands, not become reproducible in repeated amplification. A monoclonal pattern of B cell expansion is shown at baseline in patients 1 and 2, and an oligoclonal pattern in patient 3. At 6 months after rituximab therapy the molecular pattern of B cell expansion had changed in all the three cases from clonal to polyclonal.

Three patients, two females and one male, aged 58, 62 …
Risk Adjustment for Outcomes After Carotid Endarterectomy
Authors: Christopher J Abularrage
Journal: JAMA Surgery (2013)

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Chemokine and Chemokine Receptor Expression during Initiation and Resolution of Immune Complex Glomerulonephritis
Authors: HANS-JOACHIM ANDERS, VOLKER VIELHAUER, MATTHIAS KRETZLER, CLEMENS D. COHEN, STEPHAN SEGERER, BRUNO LUCKOW, LARS WELLER, HERMANN-JOSEF GRÖNE, DETLEF SCHLÖNDORFF
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Chemokines participate in leukocyte infiltration, which plays a major role in glomerular injury during immune complex glomerulonephritis (IC-GN). Because target cell expression of chemokine receptors (CCR) is thought to mediate leukocyte migration, the expression pattern of chemokines and CCR in a model of IC-GN was examined. The transient course and predominant glomerular pathology of this model allows the examination of both the induction and resolution phases of IC-GN. GN was induced in mice by daily apoferritin injection for 2 wk. Urine samples and kidneys were obtained at 1, 2, and 4 wk. Albuminuria was noted at 2 wk, but resolved after 4 wk. This was associated with glomerular IC deposits and mesangial proliferation. Glomerular macrophage infiltration was prominent at 1 and 2 wk, which resolved at 4 wk. Expression of monocyte chemoattractant protein-1 (MCP-1) and RANTES mRNA was upregulated at week 1 and decreased to control levels at weeks 2 and 4. The expression was localized to glomeruli by in situ hybridization and immunohistochemistry. The mRNA of CCR1, CCR2, and CCR5 but not CCR3 or CCR4 were upregulated at week 1 and decreased at weeks 2 and 4. Expression of CCR5 was located to the glomerulus by in situ hybridization and quantitative reverse transcription-PCR of isolated glomeruli. In summary, in a model of transient IC-GN, MCP-1 and RANTES and their receptors CCR1, CCR2, and CCR5 are expressed early and are already downregulated at the peak of proteinuria and leukocyte infiltration. Resolution of glomerulonephritis is associated with a return to baseline of chemokine and CCR expression. Therefore, it is concluded that glomerular MCP-1 and RANTES production directs circulating leukocytes that express CCR1, CCR2, and CCR5 into the glomerulus. After initiating GN, MCP-1 and RANTES and their receptors are readily downregulated.
Masking MALT1: the paracaspase's potential for cancer therapy
Authors: Domagoj Vucic, Vishva M. Dixit
Journal: The Journal of Experimental Medicine (2009)

A key feature of aggressive B cell lymphomas is constitutive NF-κB activation, which requires signals from the CARD11–BCL-10–MALT1 (CMB) complex. The unique enzymatic activity of MALT1 degrades one of its binding partners, BCL-10, as well as the NF-κB inhibitor A20. New data shows that targeting MALT1 protease activity may be a promising therapeutic strategy for treating aggressive B cell lymphomas.
A New Target for Therapy in Squamous Cell Carcinoma of the Lung
Authors: Kadoaki Ohashi, William Pao
Journal: Cancer Discovery (2011)

Investigators report the identification of novel somatic mutations in the DDR2 kinase gene in squamous cell carcinoma of the lung. Cellular, biochemical, and human data suggest that tumor cells harboring DDR2 mutations have increased sensitivity to existing tyrosine kinase inhibitors, providing rationale for clinical trials of agents that inhibit DDR2 kinase in the disease.
Strategies for hepatitis B infection.
Authors: P J Wismans, J van Hattum
Journal: Gut (1993)

ment in only eight patients (2%).Three have already died within 6 months, of unrelated causes, and five remain well, so far.We strive not to leave stents in on a permanent basis, believing that most patients can be managed effectively by expert endo- scopy, radiology, and surgery, including adjuvant techniques such as shock wave lithotripsy.Stenting is useful for a few weeks or months during which the patient's health and options can be reviewed.The King's group are rightly cautious in their recommendations.Stentinghas not yet been shown to be a good permanent method for managing difficult stones, and should be used very sparingly.
Parkinsonism in a ham-seller
Authors: R. Price
Journal: Journal of the Royal Society of Medicine (2005)

Dr Budrys (April 2005 JRSM1) recognizes features of parkinsonism in Mr Kulik the ham-seller as portrayed by Isidore Weiss in 1814. From his name Weiss is Jewish, and probably Kulik also—in which case Kulik's affliction could be the artist's ironic comment on the penalties of selling unclean meat.
Systemic effects of formoterol and salmeterol: a dose-response comparison in healthy subjects
Authors: A R Guhan
Journal: Thorax (2000)

<h3>BACKGROUND</h3> The main adverse effects of inhaled long acting β<sub>2</sub> agonists relate to their systemic activity. The systemic effects seen over eight hours after inhalation of three doses of salmeterol and formoterol were therefore compared in normal subjects. <h3>METHODS</h3> A double blind, randomised, crossover study was carried out in 16 healthy subjects who inhaled formoterol 24, 48 and 96 μg (via Turbuhaler<sup>®</sup>), salmeterol 100, 200 and 400 μg (via Diskhaler<sup>®</sup>), or placebo on separate days. Heart rate, systolic and diastolic blood pressure, and plasma potassium and glucose concentrations were measured for eight hours following each drug and mean values were used to plot the time course of change after each dose. Mean maximum (or minimum) absolute values were used to construct dose-response curves to calculate the relative dose potency of the two drugs. Lunch was taken after the four hour readings and, since this caused additional changes to the main outcome measures, data from the first four hours are also presented in a post hoc analysis. <h3>RESULTS</h3> Both salmeterol and formoterol caused an early dose dependent increase in heart rate and glucose concentrations and a fall in diastolic blood pressure and plasma potassium concentration; formoterol also caused an early increase in systolic blood pressure. The cardiovascular effects occurred more rapidly than the metabolic effects and the response to formoterol was faster than that of salmeterol, apart from the glycaemic response. The effects of salmeterol were slightly more prolonged than those of formoterol, although some dose related effects were apparent at eight hours with both drugs. The relative dose potency for formoterol compared with salmeterol at four and eight hours for the different end points excluding systolic blood pressure ranged from 1.6 to 7.0 after adjusting for baseline values. Relative dose potencies (95% CI) for maximum heart rate and plasma potassium concentrations were 4.1 (3.0 to 5.6) and 5.8 (4.1 to 8.6) over four hours and 2.4 (1.2 to 3.8) and 3.0 (1.2 to 5.7) over eight hours. <h3>CONCLUSIONS</h3> Formoterol and salmeterol cause dose related changes in heart rate, diastolic blood pressure, and plasma glucose and potassium concentrations. Formoterol has a more rapid onset for most end points whereas salmeterol has slightly more prolonged activity. Both drugs have a relatively modest therapeutic window. The relative dose potencies of the two drugs for the main end points were similar to the fourfold difference in recommended doses. Some differences in the pharmacological profile of the two drugs emerged and are as yet unexplained.
Guns and suicide: possible effects of some specific legislation
Authors: C L Rich, J G Young, R C Fowler, J Wagner, N A Black
Journal: American Journal of Psychiatry (1990)

The authors describe suicide rates in Toronto and Ontario and methods used for suicide in Toronto for 5 years before and after enactment of Canadian gun control legislation in 1978. They also present data from San Diego, Calif., where state laws attempt to limit access to guns by certain psychiatric patients. Both sets of data indicate that gun control legislation may have led to decreased use of guns by suicidal men, but the difference was apparently offset by an increase in suicide by leaping. In the case of men using guns for suicide, these data support a hypothesis of substitution of suicide method.
Ten years EULAR Scleroderma Research and Trials (EUSTAR): what has been achieved?
Authors: Ulf Müller-Ladner, Alan Tyndall, Laszlo Czirjak, Christopher Denton, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

Ten years ago a group of researchers interested in and dedicated to the field of systemic sclerosis started a unique experiment called European League Against Rheumatism (EULAR) Scleroderma Trials And Research (EUSTAR) that was designed to establish a large-scale database in a rare disease to facilitate the exact characterisation of this debilitating disease, spread the knowledge even beyond the borders of Europe and stimulate innovative research targeting the major problems of the affected patients. This EUSTAR experiment, with all its facets, including the creation of a large-scale database, the initiation of more than 40 investigator-driven clinical and basic science projects, the teaching of more than 400 young clinicians in the field of systemic sclerosis and the realisation of multicenter EU grants, which were all facilitated by an initial research grant from EULAR, is outlined and commented upon by the members of the steering committee in this viewpoint article on behalf of the now more than 150 contributing centres and the international systemic sclerosis patients' association, the Federation of European Scleroderma Associations.
Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of cerebrospinal fluid
Authors: Amanda M. Saratsis, Sridevi Yadavilli, Suresh Magge, Brian R. Rood, Jennifer Perez, D. Ashley Hill, Eugene Hwang, Lindsay Kilburn, Roger J. Packer, Javad Nazarian
Journal: Neuro-Oncology (2012)

Diffuse intrinsic pontine glioma (DIPG) is a leading cause of brain tumor–related death in children. DIPG is not surgically resectable, resulting in a paucity of tissue available for molecular studies. As such, tumor biology is poorly understood, and, currently, there are no effective treatments. In the absence of frozen tumor specimens, body fluids—such as cerebrospinal fluid (CSF), serum, and urine—can serve as more readily accessible vehicles for detecting tumor-secreted proteins. We analyzed a total of 76 specimens, including CSF, serum, urine, and normal and tumor brainstem tissue. Protein profiling of CSF from patients with DIPG was generated by mass spectrometry using an LTQ-Orbitrap-XL and database search using the Sequest algorithm. Quantitative and statistical analyses were performed with ProteoIQ and Partek Genomics Suite. A total of 528 unique proteins were identified, 71% of which are known secreted proteins. CSF proteomic analysis revealed selective upregulation of Cyclophillin A (CypA) and dimethylarginase 1 (DDAH1) in DIPG (n = 10), compared with controls (n = 4). Protein expression was further validated with Western blot analysis and immunohistochemical assays using CSF, brain tissue, serum, and urine from DIPG and control specimens. Immunohistochemical staining showed selective upregulation of secreted but not cytosolic CypA and DDAH1 in patients with DIPG. In this study, we present the first comprehensive protein profile of CSF specimens from patients with DIPG to demonstrate selective expression of tumor proteins potentially involved in brainstem gliomagenesis. Detection of secreted CypA and DDAH1 in serum and urine has potential clinical application, with implications for assessing treatment response and detecting tumor recurrence in patients with DIPG.