tbuckley/cabot-search huggingface dataset:
Secretory leukocyte protease inhibitor: A pivotal mediator of anti-inflammatory responses in acetaminophen-induced acute liver failure
Authors: Charalambos Gustav Antoniades, Wafa Khamri, Robin D. Abeles, Leonie S. Taams, Evangelos Triantafyllou, Lucia A. Possamai, Christine Bernsmeier, Ragai R. Mitry, Alistair O'Brien, Derek Gilroy, Robert Goldin, Michael Heneghan, Nigel Heaton, Wayel Jassem, William Bernal, Diego Vergani, Yun Ma, Alberto Quaglia, Julia Wendon, Mark Thursz
Journal: Hepatology (2013)

Acetaminophen-induced acute liver failure (AALF) is characterized both by activation of innate immune responses and susceptibility to sepsis. Circulating monocytes and hepatic macrophages are central mediators of inflammatory responses and tissue repair processes during human AALF. Secretory leukocyte protease inhibitor (SLPI) modulates monocyte/macrophage function through inhibition of nuclear factor kappa B (NF-κB) signaling. The aims of this study were to establish the role of SLPI in AALF. Circulating levels of SLPI, monocyte cluster of differentiation 163 (CD163), human leukocyte antigen-DR (HLA-DR), and lipopolysaccharide (LPS)-stimulated levels of NF-κBp65, tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 were determined in patients with AALF, chronic liver disease, and healthy controls. Immunohistochemistry and multispectral imaging of AALF explant tissue determined the cellular sources of SLPI and hepatic macrophage phenotype. The phenotype and function of monocytes and macrophages was determined following culture with recombinant human (rh)-SLPI, liver homogenates, and plasma derived from AALF patients in the presence and absence of antihuman (α)SLPI. Hepatic and circulatory concentrations of SLPI were elevated in AALF and immunohistochemistry revealed SLPI expression in biliary epithelial cells and within hepatic macrophages (h-mψ) in areas of necrosis. H-mψ and circulating monocytes in AALF exhibited an anti-inflammatory phenotype and functional characteristics; typified by reductions in NF-κBp65, TNF-α, and IL-6 and preserved IL-10 secretion following LPS challenge. Culture of healthy monocytes with AALF liver homogenates, plasma, or rhSLPI induced monocytes with strikingly similar anti-inflammatory characteristics which were reversed by inhibiting the activity of SLPI.SLPI is a pivotal mediator of anti-inflammatory responses in AALF through modulation of monocyte/macrophage function, which may account for the susceptibility to sepsis in AALF.
Prevalence of thyroid disease in patients with obstructive sleep apnea
Authors: Ahmed BaHammam, Munir Sharif, Anwar Jammah, Salman Bahammam
Journal: European Respiratory Journal (2011)

Background: Previous studies have reported conflicting results with regard to thyroid disease in obstructive sleep apnea (OSA) patients.

Objectives: To determine the prevalence and predictors of thyroid disease in OSA patients.

Methods: Consecutive patients who were referred for an overnight polysomnography (PSG) in the study period underwent serum TSH and thyroxine (FT4) measurement within 4 weeks of PSG using the electrochemiluminescence immunoassay method. Standard definitions were used to define clinical hypothyroidism, subclinical hypothyroidism, clinical hyperthyroidism and subclinical hyperthyroidism.

Results: During the study period, 271 patients with OSA and a mean age of 48.7±14.1yr, body mass index (BMI) of 37.7±9.6 kg/m2 and apnea hypopnea index (AHI) of 55.2±37/hr and 76 non-OSA patient (control group) with a mean age of 40.8±14.9yr and BMI of 33.7±8.9kg/m2 and AHI of 3.8±3.1/hr were included. Among OSA patients, a total of 26 (9.6%) were known cases of clinical hypothyroidism. The prevalence of newly diagnosed clinical hypothyroidism was 0.4% and the prevalence of newly diagnosed subclinical hypothyroidism was 11.1% in OSA patients. In the non-OSA patients, the prevalence of newly diagnosed clinical hypothyroidism was 1.4%, and the prevalence of newly diagnosed subclinical hypothyroidism was 5%. There were no cases of clinical or subclinical hyperthyroidism in the studied group. Female gender was the only predictor of clinical hypothyroidism.

Conclusion: The prevalence of newly diagnosed clinical hypothyroidism was very low in OSA patients to warrant routine testing for thyroid function. On the other hand, subclinical hypothyroidism was common among patients with OSA.
Morphologic and Morphometric Analyses of Butyrate-Induced Alterations of Rat Glioma Cells In Vitro<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: Li-wen Ko, Adalbert Koestner
Journal: JNCI Journal of the National Cancer Institute (1980)

The effect of butyrate on cellular morphologic features and morphometric parameters was examined in vitro with clonal glioma cells of the inbred CD Fischer rat. Untreated cells were multipolar with a high nuclear:cytoplasmic ratio, contained few attenuated rough endoplasmic reticular (RER) and cytoskeletal components in the cytoplasm, and were devoid of junctional complexes. Following exposure to butyrate, the glioma cells appeared epithelioid, and each was characterized by a polygonal cell body with a substantially reduced nuclear:cytoplasmic ratio. In contrast to the coarsely clumped nuclear chromatin of untreated glioma cells, the nuclei of the butyrate-exposed cells consisted of finely dispersed chromatin. The cytoplasm of treated cells contained numerous distended RER packed with proteinaceous material and had an elaborate cyto-skeletal network. Butyrate also induced the development of junctional devices between apposed surface membranes of adjacent cells. The acquisition of these phenotypic traits more characteristic of normal glial cells makes butyrate a potent, naturally occurring reverse transformation agent.
Rapid emergence of carbapenemase-producing Enterobacteriaceae isolates in Belgium
Authors: T- D Huang, P Bogaerts, C Berhin, B Jans, A Deplano, O Denis, Y Glupczynski
Journal: Eurosurveillance (2011)

We report on the evolution and epidemiology of carbapenem non-susceptible Enterobacteriaceae (CNSE) including carbapenemase-producing Enterobacteriaceae (CPE) in Belgium between January 2007 and April 2011. Significantly higher numbers of CNSE and of CPE were detected in 2010 and 2011 compared to the years 2007 to 2009. The majority of patients carrying CPE did not have history of travel abroad. The rapid emergence of autochthonous CPE strains in Belgium since 2010 warrants strengthened epidemiological surveillance at national level.
Determinants of response to immunosuppressive therapy in idiopathic pulmonary fibrosis
Authors: K van Oortegem, B Wallaert, CH Marquette, P Ramon, T Perez, JJ Lafitte, AB Tonnel
Journal: European Respiratory Journal (1994)

Idiopathic pulmonary fibrosis (IPF) response to corticosteroids and cytotoxic medications appears to be the most important determinant of survival. The purpose of this retrospective study was to analyse the determinants of response to immunosuppressive therapy with prednisone alone, or prednisone and cyclophosphamide, in IPF. Twenty five consecutive patients were studied. Initial evaluation in untreated patients included clinical, biological and functional parameters. Sequential evaluation by pulmonary function tests (forced vital capacity (FVC) and transfer factor of the lungs for carbon monoxide (TLCO)) was performed at a 3 month interval. Response to therapy was defined as an improvement in FVC and/or TLCO of more than 10% after 12 months, with maintenance of this improvement for at least another 12 months. Twelve of the 25 patients were classified as responders. A symptomatic disease of less than 12 months duration before onset of therapy related to response. FVC was more impaired in the group of responders when the comparison was limited to patients with an FVC of less than 90%. Bronchoalveolar lavage cell counts were not significantly different between responders and non-responders. Assessment of pulmonary function after 3 months of treatment was predictive of maintenance of the response or of even further improvement. Patients with improved FVC after 3 months of therapy had a significantly shorter symptomatic disease before onset of treatment (7.6 +/- 7.1 vs 20.2 +/- 18.6 months). A beneficial effect of addition of cyclophosphamide was observed only in patients who demonstrated an early but short-lived improvement to steroids. Adverse reactions of immunosuppressive therapy were noticed in 10 patients, and required discontinuation of treatment in six of them.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of the Potentiation of Specific Tumor Immunity in Mice by Corynebacterium parvum or BCG 2
Authors: Martin T. Scott, Robert Bomford
Journal: JNCI Journal of the National Cancer Institute (1976)

Two independent studies have compared killed C. parvum (CP) vaccine with viable BCG (Pasteur) and BCG (Glaxo) vaccines, respectively, for potentiation of antitumor immunity when injected with irradiated tumor cells into B6D2F1 and CBA-T6 T6 mice. Both studies concurred that, for a given number of irradiated tumor cells, larger amounts (dry weight equivalent) of BCG than CP were required to produce similar degrees of tumor immunity. Evidence also showed that stronger and more protracted immunity was mediated by CP than by BCG.
Detection of neuroblastoma cells in blood.
Authors: T J Moss, D G Sanders
Journal: Journal of Clinical Oncology (1990)

Tumor surveillance tests are used to detect relapse and to guide the clinician in making therapeutic changes. Identification of relapse early in the course of disease may improve long-term survival. For patients with neuroblastoma, current conventional surveillance methods include radiologic testing, bone marrow analysis, physical examination, and measurement of urinary catecholamine metabolites. Immunocytologic analysis of blood for the detection of circulating tumor cells is a highly specific and sensitive method, which may prove useful in monitoring patients with neuroblastoma. In our study, circulating tumor cells were detected in seven of 10 patients with known disseminated disease at diagnosis and in six of 13 patients during therapy. In some patients, as few as two tumor cells were identified among 100,000 normal hematopoietic cells. The presence or absence of circulating neuroblasts in the 13 patients evaluated during therapy was significantly correlated with tumor relapse (P = .002). We conclude that immunocytologic analysis of blood is a sensitive method for the detection of circulating neuroblasts. We recommend that this technique be used in conjunction with other conventional methods for improved tumor detection and subsequent monitoring of neuroblastoma patients.
Abstract A21: Combined treatment increases the efficacy of chemotherapeutics by downregulating of P-glycoprotein
Authors: Nasser Samadi, Mahsa Mohseni, Parisa Ganbari, Maryam tabasinezhad, Bahman Yousefi
Journal: Clinical Cancer Research (2015)

Abstract Introduction: Understanding the mechanisms of chemoresistance is an urgent need for cancer patients. Induction of drug efflux due to overexpression of P-glycoproteins is considered as an important leading cause of multidrug resistance. In this study, we investigated the role of combination treatments of docetaxel and vinblastine in inhibition of proliferation and induction of apoptosis in H1299 cancer cells. Furthermore, the impact of P-glycoprotein activity in changing the effectiveness of the agents was studied. Methods: Cell proliferation and the percentage of apoptotic cells were assessed using MTT assay and DAPI staining, respectively. The expression of P-glycoprotein was evaluated in gene and protein levels by Real-time RT-PCR and Western blot analysis, respectively. Results: Combination treatment of the cells decreased the IC50 concentrations for both docetaxel and vinblastine from 30 nM to 15 nM and 30 nM to 5 nM, respectively (p&amp;lt;0.05). P-glycoprotein mRNA level showed a significant up-regulation in the cells incubated with docetaxel or vinblastine (p&amp;lt;0.001). Combination treatment of the cells neutralized P-glycoprotein overexpression noticeably (p&amp;lt;0.05). Adding P-glycoprotein inhibitor to the cells treated with combined docetaxel and vinblastine, enhanced the efficiency of chemotherapeutics considerably. Conclusion: Combination therapy along with down-regulation of P-glycoproteins can be considered an important strategy to improve the efficacy of therapeutics. Note: This abstract was not presented at the conference. Citation Format: Nasser Samadi, Mahsa Mohseni, Parisa Ganbari, Maryam tabasinezhad, Bahman Yousefi. Combined treatment increases the efficacy of chemotherapeutics by downregulating of P-glycoprotein. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A21.
Prevalence of Psychopathology Among Children and Adolescents
Authors: Robert E. Roberts, C. Clifford Attkisson, Abram Rosenblatt
Journal: American Journal of Psychiatry (1998)

This study was done to update and expand information given in recent reviews, provide a more systematic critique of past research, identify current research trends and issues, and explore possible strategies for future research in child psychiatric epidemiology.The authors identified and reviewed 52 studies done over the past four decades that attempted to estimate the overall prevalence of child and adolescent psychiatric disorders.About as many studies have been published since 1980 as were published before. Sample sizes ranged from 58 to 8,462; most were in the 500-1,000 range. Studies were carried out in over 20 countries, most frequently the United States and the United Kingdom. Subjects' ages ranged from 1 to 18 years. Rutter's criteria were the most frequently used for case definition; more recent studies were more likely to use DSM criteria. The most frequently used interview was the Rutter schedule. The most common time frame for calculating prevalence was the present, followed by 6 months and 1 year. Prevalence estimates of psychopathology ranged from approximately 1% to nearly 51% (mean = 15.8%). Median rates were 8% for preschoolers, 12% for preadolescents, 15% for adolescents, and 18% in studies including wider age ranges.The evidence is less informative than expected because of several problems that continue to plague research on child and adolescent disorders. These involve sampling, case ascertainment, case definition, and data analyses and presentation. Progress in understanding the epidemiology of child disorders will largely depend on whether future research successfully meets these challenges.
Obesity in COPD and the response to pulmonary rehabilitation
Authors: C.M. Nolan, J.L. Canavan, A.L. Clark, K.A. Ingram, R.P. Fowler, P. Marns, M.I. Polkey, W.D.-C. Man
Journal: European Respiratory Journal (2011)

The obesity paradox is well recognized in COPD. Obese (OB) patients with COPD may have better survival than the non-OB, yet obesity may impair lung function, increase respiratory load and dyspnea. We hypothesized that OB COPD patients referred to pulmonary rehabilitation (PR) would have reduced exercise capacity and quality of life compared with normal weight (NW) COPD patients, and would respond less well to PR.  As BMI  Despite less severe airflow obstruction in OB patients (Median IQR FEV1% predicted: NW = 40 (26, 62) vs. OB = 62 (42, 76); p  Obesity in COPD was associated with less impairment in respiratory function, but worse exercise capacity and quality of life. However OB patients respond equally well to PR as NW patients. The impairment of exercise capacity and quality of life in OB COPD patients may lead to presentation to health care professionals at an earlier stage of lung function impairment and may explain the obesity paradox.
Abstract 272: Ventilation with i-gel Supraglottic Airway Compared with Mouth-to--Pocket Mask Ventilation Reduces Interruptions in Chest Compressions During Single-Rescuer Lifeguard CPR: A Randomized Simulation Study
Authors: Bo Løfgren, Kasper Adelborg, Martin B Mortensen, Lars Henrik Nielsen, Christian Dalgas, Rozh Husain Al-Mashhadi
Journal: Circulation (2012)

Introduction: Minimizing interruptions in chest compression during cardiopulmonary resuscitation (CPR) is a crucial determinant for the outcome following cardiac arrest. The International Life Saving Federation recommends lifeguards to perform CPR using mouth-to-pocket-mask ventilation (MPV). An alternative ventilation method is supraglottic airway ventilation (SAV), however the possible benefit of SAV among lifeguards is currently unknown. The aim of this study was to compare the effect of SAV and MPV on CPR quality. Materials and methods: Surf lifeguards in active service were invited to participate. MPV (Pocket Mask™, Laerdal, Stavanger, Norway) is a mandatory part of surf lifeguard training. All participants were trained in using a supraglottic airway (i-gel, Intersurgical®, Workingham, UK). Subsequently, each surf lifeguard was randomized to perform single rescuer CPR using either SAV or MPV separated by five minutes of rest. Data were obtained from a resuscitation manikin (Ambu® Cardiac Care Trainer System, Ambu, Ballerup, Denmark) and video recordings. Results: In total, 25 surf lifeguards were included (9 female, 16, male, mean age 25.2 years). All were employed as seasonal lifeguards and none of the participants were healthcare professionals. Interruptions in chest compressions were significantly reduced by SAV (mean+/-SD: 4.8+/-1.0 sec) when compared to MPV (7.8+/-1.3 sec, p&lt;0.001). No significant difference in chest compression depth and rate were observed between groups. Time to first ventilation attempt was 1.9+/-3.0 sec faster when using MPV compared to SAV (p=0.003). No difference in effective ventilations (visible chest rise) were observed when comparing SAV (94.1%) to MPV (95.0%, p=0.96). Tidal volumes were significantly lower following MPV (0.48+/-0.19 L) compared to SAV (0.58+/-0.10 L, p=0.04). Conclusion: SAV significantly reduces interruptions in chest compressions during lifeguard CPR and is superior in delivering the recommended tidal volume compared to MPV. Our results suggest that CPR quality is improved using SAV compared to MPV among lifeguards.
Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium–Glucose Cotransporter 2 Inhibition
Authors: Anne L. Peters, Elizabeth O. Buschur, John B. Buse, Pejman Cohan, Jamie C. Diner, Irl B. Hirsch
Journal: Diabetes Care (2015)

OBJECTIVE Sodium–glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. RESEARCH DESIGN AND METHODS Cases identified incidentally are described. RESULTS We identified 13 episodes of SGLT-2 inhibitor–associated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers. CONCLUSIONS SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes.
Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes
Authors: Rena R. Wing, Paula Bolin, Frederick L. Brancati, George A. Bray, Jeanne M. Clark, Mace Coday, Richard S. Crow, Jeffrey M. Curtis, Caitlin M. Egan, Mark A. Espeland, Mary Evans, John P. Foreyt, Siran Ghazarian, Edward W. Gregg, Barbara Harrison, Helen P. Hazuda, James O. Hill, Edward S. Horton, S. Van Hubbard, John M. Jakicic, Robert W. Jeffery, Karen C. Johnson, Steven E. Kahn, Abbas E. Kitabchi, William C. Knowler, Cora E. Lewis, Barbara J. Maschak-Carey, Maria G. Montez, Anne Murillo, David M. Nathan, Jennifer Patricio, Anne Peters, Xavier Pi-Sunyer, Henry Pownall, David Reboussin, Judith G. Regensteiner, Amy D. Rickman, Donna H. Ryan, Monika Safford, Thomas A. Wadden, Lynne E. Wagenknecht, Delia S. West, David F. Williamson, Susan Z. Yanovski
Journal: New England Journal of Medicine (2013)

Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients.In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years.The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51).An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).
Follow up of asthmatic patients after admission to intensive care unit (ICU) due to an acute exacerbation
Authors: Estibaliz Perez Guzman, Nuria Marina Malanda, Ruth Diez Arnesto, Amaia Sagarna Aguirrezabala, Amaia Urrutia Gajate, Juan B. Galdiz Iturri
Journal: European Respiratory Journal (2013)

Introduction:   According to guidelines (GEMMA909) previous admissions in ICU predispose to fatal asthma. However, discharge evolution is not well known   Objetives:   To identify the characteristics of asthma patients admitted to ICU, clinical course and evolution in the follow up   Material and methods:   Data of 42 patients admitted to ICU in 2007-2011: potential triggers, % intubation, complications and functional status   Results:   Epidemiological data: 42 patients (22 [female] / 20 [male]), age 45.26 ± 16.69. Atopy: 45%; smoking habit: 57%. Control by GP (47.6% ); pulmonologist (35.7%). 33% previous admissions (11% in ICU). Functional and treatment data  ICU admission : Trigger: infection (54,8%). 33.3% intubations, with larger period in ICU (5 ± 3.74 days vs 2.29 ± 1.11). 3 patients (7,14%) died from asthma attack  Follow up : Control by pulmonologist (80%). Evolution: 61% good control, 25% readmitted, 7,5% in ICU   Conclusions:   Most of patients have a good outcome: low mortality and intubation rates.  ICU admission would not be a decisive criterion to define severity in the follow up  We found differences in treatment (IC) before and after admission in the ICU.