tbuckley/cabot-search huggingface dataset:
A Framework for Health Care Organizations to Develop and Evaluate a Safety Scorecard
Authors: Peter J. Pronovost, Sean M. Berenholtz, Dale M. Needham
Journal: JAMA (2007)

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GLIOMAS PROMOTE INDUCTION OF B7-H1/PD-L1 EXPRESSION ON MONOCYTES: CLINICAL EVIDENCE OF AN IMMUNOSUPPRESSIVE MECHANISM THAT CAN BE TARGETED WITH ANTIBODY BLOCKADE
Authors: A. T. Parsa, O. Bloch, C. Crane, R. Kaur, M. Safae
Journal: Neuro-Oncology (2014)

BACKGROUND: Gliomas are known to induce local and systemic immunosuppression, inhibiting T-cell-mediated cytotoxic responses to tumor growth. Tumor-associated macrophages are a significant component of the immune infiltrate in gliomas and may express immunosuppressive surface ligands, such as B7-H1. METHODS: Tumor and peripheral blood samples from patients with glioblastoma (GBM) were analyzed by flow cytometry to evaluate the expression of B7-H1 in circulating and tumor-infiltrating macrophages. Human monocytes from healthy patients were stimulated with conditioned media from glioma cells to evaluate B7-H1 expression. Production of interleukin (IL)-10 by stimulated monocytes was measured by ELISA, and stimulation with IL-10 alone was evaluated for the ability to induce B7-H1 expression. The effect of inhibiting IL-10 and its receptor on glioma-induced B7-H1 expression in monocytes was evaluated. RESULTS: Circulating monocytes in patients with GBM had significantly increased expression of B7-H1 compared with healthy control patients. Tumor-associated macrophages from matched GBM tissue had even greater B7-H1 expression. Treatment of normal monocytes with glioma-conditioned media could significantly increase B7-H1 expression. Stimulation of monocytes with conditioned media resulted in substantial production of IL-10 and upregulation of the IL-10 receptor. Stimulation of monocytes with IL-10 alone could significantly increase B7-H1 expression, sufficient to induce T-cell apoptosis when cocultured with stimulated monocytes. Inhibition of IL-10 and the IL-10 receptor could knock down the effect of glioma media on B7-H1 by more than 50%. CONCLUSIONS: Gliomas can upregulate B7-H1 expression in circulating monocytes and tumor-infiltrative macrophages through modulation of autocrine/paracrine IL-10 signaling, resulting in an immunosuppressive phenotype. These data describe a novel mechanism of immunosuppression that can be targeted with antibody blockade. SECONDARY CATEGORY: Tumor Biology.
Starting in Immunology by Way of Immunopathology
Authors: Emil R. Unanue
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

This article comments on my trajectory first from Havana as a medical student, to Pittsburgh as a pathology intern, then to La Jolla. It reviews my initial experience in immunology research at the Scripps Research Institute in the early 1960s. Under Frank Dixon, my work examined how antibodies to the glomerular basement membrane (GBM) cause disease. I present these studies in the broader context of immunological renal injury. The early studies by Dixon and his group examining the models of acute or chronic serum sickness were major for our understanding of renal and vascular pathology. I review them because of their historical importance in immunopathology and also cover facets of Dixon's overall contributions to immunology. The studies in serum sickness and anti-GBM nephritis led to an understanding of autoimmune glomerulonephritides, the first proven autoantibody-induced diseases.
A Duty to Treat During a Pandemic? The Time for Talk is Now
Authors: Tracey M. Bailey, Rhonda J. Rosychuk, Olive Yonge, Thomas J. Marrie
Journal: The American Journal of Bioethics (2008)

Future pandemics, and in particular, an influenza pandemic, will create demands on our healthcare systems that will not have been faced by healthcare professionals (HCPs) in recent decades. The dem...
Acute pancreatitis in peritoneal dialysis and haemodialysis: risk, clinical course, outcome, and possible aetiology
Authors: M J Bruno
Journal: Gut (2000)

It has been suggested that the incidence of acute pancreatitis in patients with end stage renal failure is increased.To assess the risk of acute pancreatitis in patients on long term peritoneal dialysis and long term haemodialysis compared with the general population, to evaluate its clinical course and outcome, and to identify possible aetiological factors.All patients who were maintained on long term peritoneal dialysis and/or haemodialysis (total dialysis time more than six weeks) from January 1989 to March 1998 in a large general hospital in The Netherlands.Retrospective cohort study. Standardised ratios (as an approximate relative risk) between the incidence of acute pancreatitis in haemodialysis or peritoneal dialysis and the general population were calculated. Possible risk factors were identified. Patients with and without acute pancreatitis were compared.In 269 patients on haemodialysis (total of 614 person years), one patient developed an attack of acute pancreatitis. Patients on haemodialysis did not show an increased risk for acute pancreatitis compared with the general population (standardised ratio 11; 95% confidence interval (CI) 0.275 to 60.5). In 128 patients on peritoneal dialysis (total of 241 person years), seven patients had nine attacks of acute pancreatitis. Patients on peritoneal dialysis had a significantly and highly increased risk for acute pancreatitis (standardised ratio 249; 95% CI 114 to 473). Mortality in this series of nine attacks was 11%. No single aetiological risk factor could be identified.The risk of acute pancreatitis in patients on long term peritoneal dialysis is significantly and highly increased compared with the general population. The underlying causal mechanisms remain to be elucidated.
aHIF: a Natural Antisense Transcript Overexpressed in Human Renal Cancer and During Hypoxia
Authors: C. A. Thrash-Bingham, K. D. Tartof
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Nonpapillary renal carcinoma is the predominant form of human kidney cancer and represents a distinct disease entity, morphologically and molecularly, from papillary renal carcinoma. We have discovered a natural antisense transcript that is complementary to the 3′ untranslated region of hypoxia inducible factor α (HIF1α) messenger RNA (mRNA) and is strikingly overexpressed specifically in nonpapillary kidney cancer. HIF1α encodes a protein that is known to have two important functions: 1) to act as a transcription factor for hypoxia inducible genes and 2) to stabilize p53 protein during hypoxia. Because of the importance of HIF1α, we have characterized this natural antisense transcript, which we have named "aHIF." METHODS: Differential display, reverse transcription-polymerase chain reaction, ribonuclease protection, and DNA-sequencing methods were used in our analysis. RESULTS AND CONCLUSIONS: We show the following: 1) aHIF is a natural antisense transcript derived from HIF1α gene sequences encoding the 3′ untranslated region of HIF1α mRNA; 2) aHIF is specifically overexpressed in all nonpapillary clear-cell renal carcinomas examined, but not in the papillary renal carcinomas examined; 3) aHIF is overexpressed in an established nonpapillary renal carcinoma cell line under both normoxic (i.e., normal aerobic) and hypoxic conditions; and 4) although aHIF is not further induced by hypoxia in nonpapillary disease, it can be induced in lymphocytes where there is a concomitant decrease in HIF1α mRNA. To our knowledge, this is the first case of overexpression of a natural antisense transcript exclusively associated with a specific human malignant disease.
Indications, Complications, and Management of Inferior Vena Cava Filters
Authors: Shayna Sarosiek, Mark Crowther, J. Mark Sloan
Journal: JAMA Internal Medicine (2013)

Retrievable inferior vena cava (IVC) filters were designed to provide temporary protection from pulmonary embolism, sparing patients from long-term complications of permanent filters. However, many retrievable IVC filters are left in place indefinitely.To review the medical records of patients with IVC filters to determine patient demographics and date of and indication for IVC filter placement, as well as complications, follow-up data, date of IVC filter retrieval, and use of anticoagulant therapy.A retrospective review of IVC filter use between August 1, 2003, and February 28, 2011, was conducted at Boston Medical Center, a tertiary referral center with the largest trauma center in New England.In total, 978 patients. Twenty six patients were excluded from the study because of incomplete medical records.Placement of retrievable IVC filter.In total, 952 medical records were included in the analysis.Of 679 retrievable IVC filters that were placed, 58 (8.5%) were successfully removed. Unsuccessful retrieval attempts were made in 13 patients (18.3% of attempts). Seventy-four venous thrombotic events (7.8% of 952 patients included in the study) occurred after IVC filter placement, including 25 pulmonary emboli, all of which occurred with the IVC filter in place. Forty-eight percent of venous thrombotic events were in patients without venous thromboembolism at the time of IVC filter placement, and 89.4% occurred in patients not receiving anticoagulants. Many IVC filters placed after trauma were inserted when the highest bleeding risk had subsided, and anticoagulant therapy may have been appropriate. While many of these filters were placed because of a perceived contraindication to anticoagulants, 237 patients (24.9%) were discharged on a regimen of anticoagulant therapy.Our research suggests that the use of IVC filters for prophylaxis and treatment of venous thrombotic events, combined with a low retrieval rate and inconsistent use of anticoagulant therapy, results in suboptimal outcomes due to high rates of venous thromboembolism.
Origin and Evolution of Laminin Gene Family Diversity
Authors: B. Fahey, B. M. Degnan
Journal: Molecular Biology and Evolution (2012)

Laminins are a family of multidomain glycoproteins that are important contributors to the structure of metazoan extracellular matrices. To investigate the origin and evolution of the laminin family, we characterized the full complement of laminin-related genes in the genome of the sponge, Amphimedon queenslandica. As a representative of the Demospongiae, a group consistently placed within the earliest diverging branch of animals by molecular phylogenies, Amphimedon is uniquely placed to provide insight into early steps in the evolution of metazoan gene families. Five Amphimedon laminin-related genes possess the conserved molecular features, and most of the domains found in bilaterian laminins, but all display domain architectures distinct from those of the canonical laminin chain types known from model bilaterians. This finding prompted us to perform a comparative genomic analysis of laminins and related genes from a choanoflagellate and diverse metazoans and to conduct phylogenetic analyses using the conserved Laminin N-terminal domain in order to explore the relationships between genes with distinct architectures. Laminin-like genes appear to have originated in the holozoan lineage (choanoflagellates + metazoans + several other unicellular opisthokont taxa), with several laminin domains originating later and appearing only in metazoan (animal) or eumetazoan (placozoans + ctenophores + cnidarians + bilaterians) laminins. Typical bilaterian α, β, and γ laminin chain forms arose in the eumetazoan stem and another chain type that is conserved in Amphimedon, the cnidarian, Nematostella vectensis, and the echinoderm, Strongylocentrotus purpuratus, appears to have been lost independently from the placozoan, Trichoplax adhaerens, and from multiple bilaterians. Phylogenetic analysis did not clearly reconstruct relationships between the distinct laminin chain types (with the exception of the α chains) but did reveal how several members of the netrin family were generated independently from within the laminin family by duplication and domain shuffling and by domain loss. Together, our results suggest that gene duplication and loss and domain shuffling and loss all played a role in the evolution of the laminin family and contributed to the generation of lineage-specific diversity in the laminin gene complements of extant metazoans.
Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes
Authors: Geltrude Mingrone, Simona Panunzi, Andrea De Gaetano, Caterina Guidone, Amerigo Iaconelli, Laura Leccesi, Giuseppe Nanni, Alfons Pomp, Marco Castagneto, Giovanni Ghirlanda, Francesco Rubino
Journal: New England Journal of Medicine (2012)

Roux-en-Y gastric bypass and biliopancreatic diversion can markedly ameliorate diabetes in morbidly obese patients, often resulting in disease remission. Prospective, randomized trials comparing these procedures with medical therapy for the treatment of diabetes are needed.In this single-center, nonblinded, randomized, controlled trial, 60 patients between the ages of 30 and 60 years with a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 35 or more, a history of at least 5 years of diabetes, and a glycated hemoglobin level of 7.0% or more were randomly assigned to receive conventional medical therapy or undergo either gastric bypass or biliopancreatic diversion. The primary end point was the rate of diabetes remission at 2 years (defined as a fasting glucose level of <100 mg per deciliter [5.6 mmol per liter] and a glycated hemoglobin level of <6.5% in the absence of pharmacologic therapy).At 2 years, diabetes remission had occurred in no patients in the medical-therapy group versus 75% in the gastric-bypass group and 95% in the biliopancreatic-diversion group (P<0.001 for both comparisons). Age, sex, baseline BMI, duration of diabetes, and weight changes were not significant predictors of diabetes remission at 2 years or of improvement in glycemia at 1 and 3 months. At 2 years, the average baseline glycated hemoglobin level (8.65±1.45%) had decreased in all groups, but patients in the two surgical groups had the greatest degree of improvement (average glycated hemoglobin levels, 7.69±0.57% in the medical-therapy group, 6.35±1.42% in the gastric-bypass group, and 4.95±0.49% in the biliopancreatic-diversion group).In severely obese patients with type 2 diabetes, bariatric surgery resulted in better glucose control than did medical therapy. Preoperative BMI and weight loss did not predict the improvement in hyperglycemia after these procedures. (Funded by Catholic University of Rome; ClinicalTrials.gov number, NCT00888836.).
Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and clinical and MRI measures of disease activity in a 1-year follow-up study of patients with axial spondyloarthritis treated with tumour necrosis factor α inhibitors
Authors: Susanne Juhl Pedersen, Inge Juul Sørensen, Kay-Geert A Hermann, Ole Rintek Madsen, Niels Tvede, Michael Sejer Hansen, Gorm Thamsborg, Lis Smedegaard Andersen, Ole Majgaard, Anne Gitte Loft, Jon Erlendsson, Karsten Asmussen, Julia S Johansen, Anne Grethe Jurik, Jakob Møller, Maria Hasselquist, Dorrit Mikkelsen, Thomas Skjødt, Annette Hansen, Mikkel Østergaard
Journal: Annals of the Rheumatic Diseases (2009)

To investigate construct validity and responsiveness of the novel ankylosing spondylitis (AS) disease activity score (ASDAS) in patients with spondyloarthritis (SpA).In a 46-week prospective longitudinal multicentre study of 60 patients with SpA (80% men, median age 40 years (range 21-62)) treated with tumour necrosis factor alpha (TNFalpha) inhibitors (infliximab, n=41; etanercept, n=13; adalimumab, n=6), the responsiveness of ASDAS, conventional clinical measures of disease activity and treatment response and the Berlin MRI sacroiliac joint (SIJ) and lumbar spine inflammation scores were compared.After 22 weeks, 58.3% of the patients were clinical responders (50% or 20 mm reduction in the Bath AS Disease Activity Index (BASDAI)). At baseline, clinical responders had significantly higher median (range) ASDAS than non-responders (4.15 (1.98-6.04) vs 2.99 (2.05-6.19), p=0.008). Changes in ASDAS correlated with changes in clinical measures of disease activity (including BASDAI (rho=0.76) and C-reactive protein (CRP) (0.79)), MRI SIJ inflammation (0.46) and MRI total inflammation scores (0.34). Patients with higher BASDAI or Assessment of SpondyloArthritis International Society (ASAS) responses obtained more profound reductions in ASDAS. ASDAS had the highest responsiveness with an effect size of 2.04 and a standardised response mean of 1.45, whereas BASDAI (effect size 1.86; standardised response mean 1.36) and CRP (effect size 0.63; standardised response mean 0.70) were less responsive. Linear regression showed that a change in BASDAI of 20 mm or 50% corresponded to a change in ASDAS of 1.38 and 1.95, respectively.ASDAS demonstrates construct validity and high responsiveness during treatment with TNFalpha inhibitors in patients with SpA. The proposed thresholds for disease activity and treatment response need further validation. Trial registration number NCT00133315.
Epigenetic modifications of chronic hypoxia-mediated neurodegeneration in Alzheimer’s disease
Authors: Hui Liu, Weidong Le
Journal: Translational Neurodegeneration (2014)

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting the elderly people. AD is characterized by progressive and gradual decline in cognitive function and memory loss. While familial early-onset AD is usually associated with gene mutations, the etiology of sporadic late-onset form of AD is largely unknown. It has been reported that environmental factors and epigenetic alterations significantly contribute to the process of AD. Our previous studies have documented that chronic hypoxia is one of the environmental factors that may trigger the AD development and aggravate the disease progression. In this review, we will summarize the pathological effects of chronic hypoxia on the onset and development of AD and put forward the possible molecule mechanisms underlying the chronic hypoxia mediated AD pathogenesis. Finally, we propose that epigenetic regulations may represent new opportunity for the therapeutic intervention of this disease.
A Case of Extra-Uterine Gestation Cured by Abdominal Section Two Hours and a Half after Rupture
Authors: G. E. Herman
Journal: BMJ (1888)

Again she improved in health'; but left the hospital still amnmic, still jaundiced, and with a large spleen, on August 26th.That the last two cases were of the same nature there can scarcely be a doubt; and that they presented many characters ia common with the first two is also obvious.The identity between the last two is implied by the association in both of chronic en- largement of the spleen, chronic yellowness of conjunctiva and skin, simulating hlepatic jaundice, and deterioration in the quality of the blood.It is true that in one of the patients there was a loud cardiac murmur, venous bruits, and marked bloodlessness, with such changes in the blood as are found in advanced pernicious an.emia; and that in the other the heart's sounds were healthy, no venous hlums were observed, the anuemia was scarcely noticeable, and the microscopic changes in the blood were only slight.But I confess I have a suspicion that the cardiac murmur was hemic, and, at any rate, all the other differences just enumerated are only such as might be explained by the different stages of anaemia the cases had severally attained.The resemblances between the last two cases and the quoted cases of pernicious anaemia were mainly the presence, in both series, of jaundice without discoverable disease of the liver, altera- tion in the quality of the blood with loss, or tendency to loss, of red corpuscles, and the kind of weakness which attends progressive antmia.Indeed, it might, I think, be argued that they were all four cases of pernicious anmmia, or, at any rate, of the same form of disease; inasmuch as, in addition to the resemblances above enumerated, enlargement of the spleen was present in all.It will be recollected that in my first case, although enlargement of the spleen was not observed clinically, the organ weighed a pound at the necropsy; and that, in the second case, some en- larg,ment both of the liver and of the spleen was detected during life.But, on the other hand, the long duration of the last two cases, and the fact that the patients were both girls, of an age at which ordinary chlorosis is common, pernicious anmemia rare if not unheard of, render this view of their nature improbable.I believe, although I do not pretend to adduce adequate proof of the correctness of my belief, that the first two and last two cases really belonged to different categories.
Injuries kill over 20000 children a year in developed countries
Authors: J. O'N. Roach
Journal: BMJ (2001)

Injury accounts for almost 40% of annual deaths in children aged 1 to 14 in the world's most developed nations, says a new report by Unicef released this week.

Traffic accidents, intentional injuries, drowning, falls, fires, poisonings, and other hazards kill more than 20000 children aged under 15 every year. This makes preventable injuries the principal cause of child death in developed nations.

Peter Adamson, one of the report's authors, said: “Over 500 children, anonymous to most of us, died from accidents this year [in the United …