tbuckley/cabot-search huggingface dataset:
Pegylated interferon ? therapy in acute hepatitis C: Relation to hepatitis C virus-specific T cell response kinetics
Authors: Sanaa M. Kamal, Alaa Ismail, Camilla S. Graham, Qi He, Jens W. Rasenack, Thomas Peters, Ahmed A. Tawil, Jutta J. Fehr, Khalifa El Sayed Khalifa, Mahmoud M. Madwar, Margaret James Koziel
Journal: Hepatology (2004)

Pegylated interferon α (PEG IFN-α) improves sustained virological response rates in chronic hepatitis C, but neither its role in acute hepatitis C nor the biologic basis for its action has been defined. This prospective study assessed the efficacy of PEG IFN-α treatment in acute hepatitis C in relation to the kinetics of hepatitis C virus (HCV)-specific CD4 + T cell responses during therapy and follow-up. Forty subjects with proven acute hepatitis C who received either PEG IFN-α plus ribavirin (n = 20) or PEG IFN-α monotherapy (n = 20) for 24 weeks in addition to 14 untreated subjects with acute hepatitis C were prospectively followed. Serum HCV RNA, HCV-specific CD4 + T cell responses, and cytokine production were measured before and during therapy and at follow-up and correlated to the outcome. The sustained virological response rate was 85% with PEG IFN-α/ribavirin combination and 80% with PEG IFN-α monotherapy. Five untreated subjects had spontaneous recovery. The frequency, magnitude, and breadth of HCV-specific CD4 + T helper 1 responses were significantly higher in treated subjects compared with untreated subjects with self-limited disease or subjects with chronic evolution. The CD4 + T cell responses were maintained in subjects with sustained virological responses and self-limited disease but fluctuated in those who developed chronic infection. In conclusion , PEG IFN-α therapy in acute hepatitis induces high rates of sustained virological response and prevents choronicity, probably through efficient early stimulation of multispecific HCV-specific CD4 + T helper 1 responses. (Hepatology 2004;39:1721-1731.)
Ischaemic and hypoxic preconditioning enhance postischaemic recovery of function in the rat heart
Authors: R. D Lasley, G. M Anderson, R. M Mentzer
Journal: Cardiovascular Research (1993)

Journal Article Ischaemic and hypoxic preconditioning enhance postischaemic recovery of function in the rat heart Robert D Lasley, Robert D Lasley Division of Cardiothoracic Surgery, Department of Surgery, University of Wisconsin, H4/358 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792-0001, USA: R D Lasley, G M Anderson, R M Mentzer. Correspondence to Professor Mentzer. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gregory M Anderson, Gregory M Anderson Division of Cardiothoracic Surgery, Department of Surgery, University of Wisconsin, H4/358 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792-0001, USA: R D Lasley, G M Anderson, R M Mentzer. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert M Mentzer, Jr Robert M Mentzer, Jr Division of Cardiothoracic Surgery, Department of Surgery, University of Wisconsin, H4/358 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792-0001, USA: R D Lasley, G M Anderson, R M Mentzer. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 4, April 1993, Pages 565–570, https://doi.org/10.1093/cvr/27.4.565 Published: 01 April 1993 Article history Received: 02 September 1992 Accepted: 11 December 1992 Published: 01 April 1993
Prevalence of electrocardiographic abnormalities in West-Asian and African male athletes
Authors: M G Wilson, J C Chatard, F Carre, B Hamilton, G P Whyte, S Sharma, H Chalabi
Journal: British Journal of Sports Medicine (2011)

To evaluate the electrocardiographic (ECG) characteristics of West-Asian, black and Caucasian male athletes competing in Qatar using the 2010 recommendations for 12-lead ECG interpretation by the European Society of Cardiology (ESC).Cardiovascular screening with resting 12-lead ECG analysis of 1220 national level athletes (800 West-Asian, 300 black and 120 Caucasian) and 135 West-Asian controls was performed.Ten per cent of athletes presented with 'uncommon' ECG findings. Black African descent was an independent predictor of 'uncommon' ECG changes when compared with West-Asian and Caucasian athletes (p<0.001). Black athletes also demonstrated a significantly greater prevalence of lateral T-wave inversions than both West-Asian and Caucasian athletes (6.1% vs 1.6% and 0%, p<0.05). The rate of 'uncommon' ECG changes between West-Asian and Caucasian athletes was comparable (7.9% vs 5.8%, p>0.05). Seven athletes (0.6%) were identified with a disease associated with sudden death; this prevalence was two times higher in black athletes than in West-Asian athletes (1% vs 0.5%), and no cases were reported in Caucasian athletes and West-Asian controls. Eighteen West-Asian and black athletes were identified with repolarisation abnormalities suggestive of a cardiomyopathy, but ultimately, none were diagnosed with a cardiac disease.West-Asian and Caucasian athletes demonstrate comparable rates of ECG findings. Black African ethnicity is positively associated with increased frequencies of 'uncommon' ECG traits. Future work should examine the genetic mechanisms behind ECG and myocardial adaptations in athletes of diverse ethnicity, aiding in the clinical differentiation between physiological remodelling and potential cardiomyopathy or ion channel disorders.
Proteomic Analysis of Apoptotic Pathways Reveals Prognostic Factors in Follicular Lymphoma
Authors: Christian Gulmann, Virginia Espina, Emanuel Petricoin, Dan L. Longo, Mariarita Santi, Turid Knutsen, Mark Raffeld, Elaine S. Jaffe, Lance A. Liotta, Andrew L. Feldman
Journal: Clinical Cancer Research (2005)

Abstract Follicular lymphoma (FL) is the second most common non-Hodgkin's lymphoma and generally is incurable. Reliable prognostic markers to differentiate patients who progress rapidly from those who survive for years with indolent disease have not been established. Most cases overexpress Bcl-2, but the pathogenesis of FL remains incompletely understood. To determine whether a proteomic approach could help overcome these obstacles, we procured lymphoid follicles from 20 cases of FL and 15 cases of benign follicular hyperplasia (FH) using laser capture microdissection. Lysates were spotted on reverse-phase protein microarrays and probed with 21 antibodies to proteins in the intrinsic apoptotic pathway, including those specific for posttranslational modifications such as phosphorylation. A panel of three antibodies [phospho-Akt(Ser473), Bcl-2, and cleaved poly(ADP-ribose) polymerase] segregated most cases of FL from FH. Phospho-Akt(Ser473) and Bcl-2 were significantly increased in FL (P = 0.001 and P &amp;lt; 0.0001, respectively). Additionally, the Bcl-2/Bak ratio completely segregated FL from FH. High ratios of Bcl-2/Bak and Bcl-2/Bax were associated with early death from disease with differences in median survival times of 7.3 years (P = 0.0085) and 3.8 years (P = 0.018), respectively. Using protein microarrays, we identified candidate proteins that may signify clinically relevant molecular events in FL. This approach showed significant changes at the posttranslational level, including Akt phosphorylation, and suggested new prognostic markers, including the Bcl-2/Bak and Bcl-2/Bax ratios. Proteomic end points should be incorporated in larger, multicenter trials to validate the clinical utility of these protein microarray findings.
J.A.P. Paré
Authors: Meinhard Kneussl
Journal: European Respiratory Journal (2013)

On February 24, 2013, Jules Arthur Peter Pare MDCM, BSc, FACP, Professor Emeritus of Medicine, McGill University (Montreal, QC, Canada) died at 95 years of age in Montreal after a long and full life.

Dr Pare grew up in Montreal and received his MD degree from McGill University in 1943. He trained in Internal Medicine and Respiratory Medicine at McGill and in 1948–1949 was a postdoctoral fellow in Chest Medicine at the Massachusetts General Hospital, Harvard Medical School in Boston, MA, USA. He then returned to Montreal, where he spent the duration of his career. In 1975, he became Professor of Medicine at McGill, and between 1975 and 1983 was the combined Respiratory Division Head of all McGill teaching hospitals (Royal Victoria Hospital, Montreal General Hospital, Montreal Chest Hospital and Jewish General Hospital).



J.A.P. Pare



Professor Pare was a masterful clinician and teacher and influenced two generations of respiratory physicians at McGill and these have, in turn, affected Respiratory Medicine across all parts of the globe. With his friend, Dr Robert Fraser, a chest radiologist at McGill, he published their textbook, …
Smoking resumption after lung transplantation: standardised screening and importance for long-term outcome
Authors: David Ruttens, Stijn E. Verleden, Pieter C. Goeminne, Katrien Poels, Elly Vandermeulen, Lode Godderis, Dirk E. Van Raemdonck, Bart M. Vanaudenaerde, Jeroen Vanoirbeek, Robin Vos, Geert M. Verleden
Journal: European Respiratory Journal (2013)

coronary syndrome risk model, the Global Registry of Acute Coronary Events (GRACE), in a PE cohort, as it contains important haemodynamic variables and target organ lesion markers providing an interesting assessment of illness severity.Although the results warrant further validation in independent cohorts, the GRACE seemed to accurately capture PE severity [10].Acute PE is a complex condition with several organ-interactions, a broad clinical presentation and a wide prognosis.Currently, PE risk stratification schemes may perform satisfactorily at ruling-out illness severity and allow assessment of patient eligibility for outpatient management.The next step would be to correctly recognise truly high-risk normotensive PE cases that would benefit from early and more aggressive therapies, such as thrombolysis. @ERSpublicationsThe next step for PE risk stratification will be to correctly recognise truly high-risk normotensive PE cases http://ow.ly/nSvxM
Physiological changes during low- and high-intensity noninvasive ventilation
Authors: J. Lukácsovits, A. Carlucci, N. Hill, P. Ceriana, L. Pisani, A. Schreiber, P. Pierucci, G. Losonczy, S. Nava
Journal: European Respiratory Journal (2011)

In a physiological randomised cross-over study performed in stable hypercapnic chronic obstructive disease patients, we assessed the short-term effects of two settings of noninvasive ventilation. One setting was aimed at maximally reducing arterial carbon dioxide tension (P(a,CO(2))) (high-intensity (Hi) noninvasive positive pressure ventilation (NPPV)): mean ± SD 27.6 ± 2.1 cmH(2)O of inspiratory positive airway pressure, 4 ± 0 cmH(2)O of expiratory positive airway pressure and respiratory rate of 22 breaths · min(-1). The other was performed according to the usual parameters used in earlier studies (low-intensity (Li)-NPPV): 17.7 ± 1.6 cmH(2)O of inspiratory positive airway pressure, 4 ± 0 cmH(2)O of expiratory positive airway pressure and respiratory rate of 12 breaths · min(-1). Both modes of ventilation significantly improved gas exchange compared with spontaneous breathing (SB), but to a greater extent using Hi-NPPV (P(a,CO(2)) 59.3 ± 7.5, 55.2 ± 6.9 and 49.4 ± 7.8 mmHg for SB, Li-NPPV and Hi-NPPV, respectively). Similarly, Hi-NPPV induced a greater reduction in the pressure-time product of the diaphragm per minute from 323 ± 149 cmH(2)O · s · min(-1) during SB to 132 ± 139 cmH(2)O · s · min(-1) during Li-NPPV and 40 ± 69 cmH(2)O · s · min(-1) during Hi-NPPV, while in nine out of 15 patients, it completely abolished SB activity. Hi-NPPV also induced a marked reduction in cardiac output (CO) measured noninvasively with a Finometer PRO (Finapres Medical Systems BV, Amsterdam, the Netherlands) compared with Li-NPPV. We conclude that while Hi-NPPV is more effective than Li-NPPV in improving gas exchange and in reducing inspiratory effort, it induces a marked reduction in CO, which needs to be considered when Hi-NPPV is applied to patients with pre-existing cardiac disease.
WHO guidelines on fluid resuscitation in children: missing the FEAST data
Authors: S. Kiguli, S. O. Akech, G. Mtove, R. O. Opoka, C. Engoru, P. Olupot-Olupot, R. Nyeko, J. Evans, J. Crawley, N. Prevatt, H. Reyburn, M. Levin, E. C. George, A. South, A. G. Babiker, D. M. Gibb, K. Maitland
Journal: BMJ (2014)

The 2013 World Health Organization guidelines continue to recommend rapid fluid resuscitation for children with shock despite evidence that this can be harmful. <b>Sarah Kiguli and colleagues</b> call for WHO to think again
Self-Monitoring of Blood Glucose in Patients With Type 2 Diabetes Who Are Not Using Insulin
Authors: Nanne Kleefstra, Sebastiaan T. Houweling, Evert van Ballegooie, Henk J.G. Bilo
Journal: Diabetes Care (2005)

Response to Welschen et al.

We read the article by Welschen et al. (1) in Diabetes Care with interest. It systematically reviewed the effect of self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes who are not using insulin. This review is important and provides an answer to the extensive debate about this interesting topic.

The same …
Teaching Trainees to Negotiate Research Collaborations With Industry: A Mentorship Model
Authors: David B. Merrill, Ragy R. Girgis, Lincoln C. Bickford, Stanislav R. Vorel, Jeffrey A. Lieberman
Journal: American Journal of Psychiatry (2010)

Research collaborations with the pharmaceutical industry can offer valuable opportunities for academic psychiatrists to gain access to important resources. Such relationships, however, often produce significant conflicts of interest, and recent attention has focused on the ways in which these conflicts can compromise research integrity. Psychiatric residents generally receive little education about industry-academia interactions. The authors report their experience collaborating on a research project with representatives of a pharmaceutical company, and they propose a model for teaching psychiatric trainees responsible and productive engagement with industry investigators.
Extracellular cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide as a mediator of cytotoxicity.
Authors: C F Nathan, S C Silverstein, L H Brukner, Z A Cohn
Journal: The Journal of Experimental Medicine (1979)

When deprived of oxygen, Bacille Calmette-Guérin (BCG)-activated macrophages no longer lysed P388 lymphoma cells. Both H2O2 release and cytotoxicity by BCG-activated macrophages and by granulocytes triggered with phorbol myristate acetate (PMA) were markedly inhibited when the glucose concentration in the medium was reduced to 0.03 mM or less, or if glucose were replaced with galactose. Catalase abolished PMA-triggered cytotoxicity by both types of effector cells, whereas superoxide dismutase had no effect. Ferricytochrome C reduced the cytotoxicity of BCG-activated macrophages, an effect which was largely reversed by superoxide dismutase. 10 drugs, thought to quench singlet oxygen and/or scavenge hydroxyl radical, did not affect cytotoxicity in this system. Neither azide nor cyanide reduced cytolysis, but there was marked inhibition by lactoperoxidase and iodide. This suggested that cytotoxicity was not dependent upon myeloperoxidase, and that lactoperoxidase may have diverted H2O2 from the oxidation of target cells to oxidation of substances in serum. Mouse erythrocytes, although sensitive targets, interfered with the cytolysis of lymphoma cells, probably by competition for H2O2. Starch particles with covalently bound glucose oxidase resembled macrophages in their spatial relation to the target cells and in the flux of H2O2 they generated from their surface, but were not expected to produce any other potentially toxic products. Such particles lysed lymphoma cells, and the lysis was prevented by catalase. Neither arginase nor thymidine appeared to be involved in cytolysis by BCG-activated macrophages under the conditions used. These findings demonstrated that release of H2O2 was both necessary and sufficient for cytolysis by BCG-activated macrophages and by granulocytes when pharmacologically triggered.
Clinical and Laboratory Profile of Patients With Type 2 Diabetes With Low Glomerular Filtration Rate and Normoalbuminuria
Authors: Caroline K. Kramer, Cristiane B. Leitão, Lana C. Pinto, Sandra P. Silveiro, Jorge L. Gross, Luís H. Canani
Journal: Diabetes Care (2007)

The initial evidence of diabetic nephropathy in type 2 diabetic patients is the development of microalbuminuria (1). However, the UK Prospective Diabetes Study demonstrated that 51% of patients who progress to chronic renal failure had no preceding albuminuria (1).

Patients with low estimated glomerular filtration rate (eGFR) (<60 ml/min per 1.73 m2) and normoalbuminuria presented an increased rate of cardiovascular disease (2–4) due to unknown reasons. Aggregation of conventional cardiovascular risk factors might play a role. Therefore, the aim of this study was to analyze the clinical and laboratory features of type 2 diabetic patients with low eGFR and normoalbuminuria.

A cross-sectional study was performed in all consecutive normoalbuminuric type 2 diabetic patients attending the outpatient clinic at Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil, between 1999 and 2006 with eGFR >15 ml/min per 1.73 m2. Normoalbuminuria was defined by urinary albumin excretion (UAE) values <20 μg/min, <17 mg/l (random sample), or <30 mg in 24 h (5) on at least two occasions over the preceding 6 months while on their usual antihypertensive medication. eGFR was calculated using the Modification of Diet in Renal Disease formula: 186 × [plasma creatinine (mg/dl)−1.154 × age (years)−0.203 × (1.212 if black) × (0.742 if female)] (6). All patients answered a standard questionnaire and underwent physical examination and laboratory tests. Metabolic syndrome was defined according to …
5-Aminosalicylic acid prevents oxidant mediated damage of glyceraldehyde-3-phosphate dehydrogenase in colon epithelial cells
Authors: S M McKenzie, W F Doe, G D Buffinton
Journal: Gut (1999)

Reactive oxygen and nitrogen derived species produced by activated neutrophils have been implicated in the damage of mucosal proteins including the inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the active inflammatory lesion in patients with inflammatory bowel disease (IBD). This study investigated the efficacy of currently used IBD therapeutics to prevent injury mediated by reactive oxygen and nitrogen derived species.GAPDH activity of human colon epithelial cells was used as a sensitive indicator of injury produced by reactive oxygen and nitrogen derived species. HCT116 cells (10(6)/ml phosphate buffered saline; 37 degrees C) were incubated in the presence of 5-aminosalicylic acid (5-ASA), 6-mercaptopurine, methylprednisolone, or metronidazole before exposure to H2O2, HOCl, or NO in vitro. HCT116 cell GAPDH enzyme activity was determined by standard procedures. Cell free reactions between 5-ASA and HOCl were analysed by spectrophotometry and fluorimetry to characterise the mechanism of oxidant scavenging.GAPDH activity of HCT116 cells was inhibited by the oxidants tested: the concentration that produced 50% inhibition (IC50) was 44.5 (2.1) microM for HOCl, 379.8 (21.3) microM for H2O2, and 685.8 (103.8) microM for NO (means (SEM)). 5-ASA was the only therapeutic compound tested to show efficacy (p<0. 05) against HOCl mediated inhibition of enzyme activity; however, it was ineffective against H2O2 and NO mediated inhibition of GAPDH. Methylprednisolone, metronidazole, and the thiol-containing 6-mercaptopurine were ineffective against all oxidants. Studies at ratios of HOCl:5-ASA achievable in the mucosa showed direct scavenging to be the mechanism of protection of GAPDH activity. Mixing 5-ASA and HOCl before addition to the cells resulted in significantly greater protection of GAPDH activity than when HOCl was added to cells preincubated with 5-ASA. The addition of 5-ASA after HOCl exposure did not restore GAPDH activity.Therapies based on 5-ASA may play a direct role in scavenging the potent neutrophil oxidant HOCl, thereby protecting mucosal GAPDH from oxidative inhibition. These findings suggest that strategies for the further development of new HOCl scavenging compounds may be useful in the treatment of IBD.
SHAPING THE CONTEXT OF HEALTH: A Review of Environmental and Policy Approaches in the Prevention of Chronic Diseases
Authors: Ross C. Brownson, Debra Haire-Joshu, Douglas A. Luke
Journal: Annual Review of Public Health (2005)

Given the growing attention on how environmental and policy interventions can affect chronic disease burden, our objectives are to describe (a) effective and promising interventions to address tobacco use, physical activity, and healthy eating and (b) lessons learned from the literature and practice experience in applying environmental and policy approaches. A total of 17 interventions were reviewed, organized across 3 domains affecting the physical environment/access, economic environment, and communication environment. Many of these interventions are effective. Several lessons are important to consider, such as the need to start with environmental and policy approaches, intervene comprehensively and across multiple levels, make use of economic evaluations, make better use of existing analytic tools, understand the politics and local context, address health disparities, and conduct sound policy research.
Integrated genomic characterization of adrenocortical carcinoma
Authors: Guillaume Assié, Eric Letouzé, Martin Fassnacht, Anne Jouinot, Windy Luscap, Olivia Barreau, Hanin Omeiri, Stéphanie Rodriguez, Karine Perlemoine, Fernande René-Corail, Nabila Elarouci, Silviu Sbiera, Matthias Kroiss, Bruno Allolio, Jens Waldmann, Marcus Quinkler, Massimo Mannelli, Franco Mantero, Thomas Papathomas, Ronald De Krijger, Antoine Tabarin, Véronique Kerlan, Eric Baudin, Frédérique Tissier, Bertrand Dousset, Lionel Groussin, Laurence Amar, Eric Clauser, Xavier Bertagna, Bruno Ragazzon, Felix Beuschlein, Rossella Libé, Aurélien de Reyniès, Jérôme Bertherat
Journal: Nature Genetics (2014)
Incidence Rates of Intra- and Extrahepatic Cholangiocarcinomas in Denmark From 1978 Through 2002
Authors: P. Jepsen, H. Vilstrup, R. E. Tarone, S. Friis, H. T. Sorensen
Journal: JNCI Journal of the National Cancer Institute (2007)

Recent studies from several countries, including the United States, have indicated that the incidence rate of intrahepatic cholangiocarcinoma is increasing while that of extrahepatic cholangiocarcinoma is decreasing. We examined whether such opposing trends could be confirmed in Danish data. We computed the nationwide Danish incidence rates of intra- and extrahepatic cholangiocarcinomas from January 1, 1978, through December 31, 2002, with data from the high-quality Danish Cancer Registry. Incidence rates were standardized to the US population in 2000. The study included 1335 patients with intrahepatic cholangiocarcinoma and 1269 with extrahepatic cholangiocarcinoma. The Danish incidence rates of intra- and extrahepatic cholangiocarcinomas were nearly identical throughout the study period. From 1978 through 2002, the incidence rate of intrahepatic cholangiocarcinoma decreased from 1.27 (95% confidence interval [CI] = 0.96 to 1.58) to 0.46 (95% CI = 0.29 to 0.62) per 100000 people, and the rate of extrahepatic cholangiocarcinoma decreased from 1.05 (95% CI = 0.77 to 1.34) to 0.74 (95% CI = 0.53 to 0.95). The median age at diagnosis decreased during the study period, and the proportion of localized cancers increased. The decrease in cholangiocarcinoma incidence rates cannot be explained by time trends in known risk factors (e.g., inflammatory bowel disease, diabetes, smoking, or thorotrast), but our findings are consistent with a common etiology for intra- and extrahepatic cholangiocarcinomas.