tbuckley/cabot-search huggingface dataset:
DAP12 (KARAP) amplifies inflammation and increases mortality from endotoxemia and septic peritonitis
Authors: Isaiah R. Turnbull, Jonathan E. McDunn, Toshiyuki Takai, R. Reid Townsend, J. Perren Cobb, Marco Colonna
Journal: The Journal of Experimental Medicine (2005)

DAP12 (KARAP) is a transmembrane signaling adaptor for a family of innate immunoreceptors that have been shown to activate granulocytes and monocytes/macrophages, amplifying production of inflammatory cytokines. Contrasting with these data, recent studies suggest that DAP12 signaling has an inhibitory role in the macrophage response to microbial products (Hamerman, J.A., N.K. Tchao, C.A. Lowell, and L.L. Lanier. 2005. Nat. Immunol. 6:579–586). To determine the in vivo role for DAP12 signaling in inflammation, we measured the response of wild-type (WT) and DAP12−/− mice to septic shock. We show that DAP12−/− mice have improved survival from both endotoxemia and cecal ligation and puncture–induced septic shock. As compared with WT mice, DAP12−/− mice have decreased plasma cytokine levels and a decreased acute phase response during sepsis, but no defect in the recruitment of cells or bacterial control. In cells isolated after sepsis and stimulated ex vivo, DAP12 signaling augments lipopolysaccharide-mediated cytokine production. These data demonstrate that, during sepsis, DAP12 signaling augments the response to microbial products, amplifying inflammation and contributing to mortality.
Air and oxygen flowmeter confusion
Authors: D W Wheeler, M Patten
Journal: Journal of the Royal Society of Medicine (2008)

We wish to report an episode of air being administered to a critically ill patient rather than oxygen, due to a mix-up with wall-mounted flowmeters. An elderly gentleman in ventricular tachycardia was anaesthetized in a resuscitation area for emergency cardioversion. Afterwards, what was thought to be high flow oxygen was administered via facemask. Mild hypoxaemia (paO2 ~8kPa) persisted, but the cause was unclear until it was noticed that the mask tubing was connected to a piped air flowmeter. Once this was corrected, hypoxaemia improved and the patient suffered no adverse consequences.

While there are standards for the design and colour of gas cylinders and pipeline outlets, there are none for flowmeters.1 In this case the error was caused by the anaesthetist (new to the hospital that week) viewing the flowmeter from the side ( Figure 1a) with another mask dangling from above obscuring the label (Figures 1b and c).



Figure 1

(A) and (B) Two flowmeters in the resuscitation room: masks are dangling down and obscuring the flowmeter below. (C) When the mask is moved away, the ‘Air’ label becomes obvious



The use of non-interchangeable connectors for anaesthetic gases has reduced the potential for administering the wrong gas, but mistakes like this are clearly happening frequently enough for the UK National Patient Safety Agency to issue guidance on the matter.2 They suggested potential solutions including capping air flowmeters, clearer labelling, and that air flowmeters should only be attached when required. Even they recognized that these are weak barriers based on human or administrative actions, which would be inadequate for the safe delivery of other drugs.3 The universal outlets of oxygen and air flowmeters – whether attached to pipeline supplies in hospitals or cylinders in surgeries and ambulances – both accept oxygen mask tubing, and while this persists we believe that this error will be made repeatedly, potentially to the detriment of many patients.
Asthma and incident cardiovascular disease: the Atherosclerosis Risk in Communities Study
Authors: J G Schanen
Journal: Thorax (2005)

<b>Background:</b> A possible association between asthma and cardiovascular disease has been described in several exploratory studies. <b>Methods:</b> The association of self-reported, doctor diagnosed asthma and incident cardiovascular disease was examined in a biracial cohort of 45–64 year old adults (N = 13501) followed over 14 years. <b>Results:</b> Compared with never having asthma, the multivariate adjusted hazard ratio (HR) of stroke (n = 438) was 1.50 (95% CI 1.04 to 2.15) for a baseline report of ever having asthma (prevalence 5.2%) and 1.55 (95% CI 0.95 to 2.52) for current asthma (prevalence 2.7%). The relative risk of stroke was 1.43 (95% CI 1.03 to 1.98) using a time dependent analysis incorporating follow up reports of asthma. Participants reporting wheeze attacks with shortness of breath also had greater risk for stroke (HR = 1.56, 95% CI 1.18 to 2.06) than participants without these symptoms. The multivariate adjusted relative risk of coronary heart disease (n = 1349) was 0.87 (95% CI 0.66 to 1.14) for ever having asthma, 0.69 (95% CI 0.46 to 1.05) for current asthma at baseline, and 0.88 (95% CI 0.69 to 1.11) using the time dependent analysis. <b>Conclusions:</b> Asthma may be an independent risk factor for incident stroke but not coronary heart disease in middle aged adults. This finding warrants replication and may motivate a search for possible mechanisms that link asthma and stroke.
Akt‐mediated foxo1 inhibition is required for liver regeneration
Authors: Montse Pauta, Noemi Rotllan, Ana Fernández‐Hernando, Cedric Langhi, Jordi Ribera, Mingjian Lu, Loreto Boix, Jordi Bruix, Wladimiro Jimenez, Yajaira Suárez, David A. Ford, Angel Baldán, Morris J. Birnbaum, Manuel Morales‐Ruiz, Carlos Fernández‐Hernando
Journal: Hepatology (2015)

Understanding the hepatic regenerative process has clinical interest as the effectiveness of many treatments for chronic liver diseases is conditioned by efficient liver regeneration. Experimental evidence points to the need for a temporal coordination between cytokines, growth factors, and metabolic signaling pathways to enable successful liver regeneration. One intracellular mediator that acts as a signal integration node for these processes is the serine-threonine kinase Akt/protein kinase B (Akt). To investigate the contribution of Akt during hepatic regeneration, we performed partial hepatectomy in mice lacking Akt1, Akt2, or both isoforms. We found that absence of Akt1 or Akt2 does not influence liver regeneration after partial hepatectomy. However, hepatic-specific Akt1 and Akt2 null mice show impaired liver regeneration and increased mortality. The major abnormal cellular events observed in total Akt-deficient livers were a marked reduction in cell proliferation, cell hypertrophy, glycogenesis, and lipid droplet formation. Most importantly, liver-specific deletion of FoxO1, a transcription factor regulated by Akt, rescued the hepatic regenerative capability in Akt1-deficient and Akt2-deficient mice and normalized the cellular events associated with liver regeneration.The Akt-FoxO1 signaling pathway plays an essential role during liver regeneration.
Developing Cystic Fibrosis Lung Transplant Referral Criteria Using Predictors of 2-Year Mortality
Authors: Nicole Mayer-Hamblett, Margaret Rosenfeld, Julia Emerson, Christopher H. Goss, Moira L. Aitken
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The first objective of our study was to develop a model identifying the best clinical predictors of 2-year mortality among patients with cystic fibrosis (CF), to assist in selection of appropriate candidates for lung transplantation. Using multivariate logistic regression, we found that age, height, FEV1, respiratory microbiology, number of hospitalizations for pulmonary exacerbations, and number of home intravenous antibiotic courses were all significant predictors of 2-year mortality among 14,572 patients in the Cystic Fibrosis Foundation National Patient Registry who were 6 years of age or older in 1996. The second objective was to compare the diagnostic accuracy of our model when used to guide referral for lung transplant with that of the widely used criterion of an FEV1 of less than 30% predicted. Surprisingly, this well-fitting model derived from the largest collection of data available on patients with CF provided no better diagnostic accuracy than the simpler FEV1 criterion. Both had high negative predictive values (98 and 97%, respectively) but only modest positive predictive values (33 and 28%, respectively). Transplant referral decisions based either on a multivariate logistic model or on the criterion of an FEV1 of less than 30% predicted are likely to result in high rates of premature referral. Better clinical predictors of short-term mortality among patients with CF are needed.
Synthesis and release of interleukin 1 by reoxygenated human mononuclear phagocytes.
Authors: S Koga, S Ogawa, K Kuwabara, J Brett, J A Leavy, J Ryan, Y Koga, J Plocinski, W Benjamin, D K Burns
Journal: Journal of Clinical Investigation (1992)

To examine the possible involvement of cytokines in reperfusion injury, we have studied production of IL-1 by human vascular cells, including smooth muscle and mononuclear phagocytes. Exposure of cells to hypoxia (pO2 approximately 14 torr) followed by reoxygenation led to significant release of IL-1 only from the mononuclear phagocytes. Elaboration of IL-1 was dependent on the oxygen tension and duration of hypoxia (optimal at lower pO2s, approximately 14-20 torr, and after 9 h), as well as the time in reoxygenation (maximal IL-1 release at 6-9 h). Although a period of hypoxia was necessary for subsequent IL-1 production during reoxygenation of either peripheral blood monocytes or cultured monocyte-derived macrophages, no IL-1 release occurred during the hypoxic exposure. IL-1 released during reoxygenation was newly synthesized, and its production was triggered by the generation of oxygen free radicals, as it could be blocked by the addition of either allopurinol or free radical scavengers to cultures and could be stimulated in part by low concentrations of hydrogen peroxide or xanthine/xanthine oxidase. The potential pathophysiological effects of IL-1-containing supernatants from reoxygenated macrophages was shown by their induction of endothelial tissue factor and enhancement of endothelial adhesiveness for neutrophils, both of which could be blocked by anti-IL-1 antibody. The relevance of IL-1 to hypoxia/reoxygenation in vivo was suggested by the presence of circulating nanogram amounts of this cytokine in the plasma of mice during the reoxygenation period following a hypoxia.
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
Authors: Benjamin F Voight, Laura J Scott, Valgerdur Steinthorsdottir, Andrew P Morris, Christian Dina, Ryan P Welch, Eleftheria Zeggini, Cornelia Huth, Yurii S Aulchenko, Gudmar Thorleifsson, Laura J McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J Willer, Soumya Raychaudhuri, Steve A McCarroll, Claudia Langenberg, Oliver M Hofmann, Josée Dupuis, Lu Qi, Ayellet V Segrè, Mandy van Hoek, Pau Navarro, Kristin Ardlie, Beverley Balkau, Rafn Benediktsson, Amanda J Bennett, Roza Blagieva, Eric Boerwinkle, Lori L Bonnycastle, Kristina Bengtsson Boström, Bert Bravenboer, Suzannah Bumpstead, Noisël P Burtt, Guillaume Charpentier, Peter S Chines, Marilyn Cornelis, David J Couper, Gabe Crawford, Alex S F Doney, Katherine S Elliott, Amanda L Elliott, Michael R Erdos, Caroline S Fox, Christopher S Franklin, Martha Ganser, Christian Gieger, Niels Grarup, Todd Green, Simon Griffin, Christopher J Groves, Candace Guiducci, Samy Hadjadj, Neelam Hassanali, Christian Herder, Bo Isomaa, Anne U Jackson, Paul R V Johnson, Torben Jørgensen, Wen H L Kao, Norman Klopp, Augustine Kong, Peter Kraft, Johanna Kuusisto, Torsten Lauritzen, Man Li, Aloysius Lieverse, Cecilia M Lindgren, Valeriya Lyssenko, Michel Marre, Thomas Meitinger, Kristian Midthjell, Mario A Morken, Narisu Narisu, Peter Nilsson, Katharine R Owen, Felicity Payne, John R B Perry, Ann-Kristin Petersen, Carl Platou, Christine Proença, Inga Prokopenko, Wolfgang Rathmann, N William Rayner, Neil R Robertson, Ghislain Rocheleau, Michael Roden, Michael J Sampson, Richa Saxena, Beverley M Shields, Peter Shrader, Gunnar Sigurdsson, Thomas Sparsø, Klaus Strassburger, Heather M Stringham, Qi Sun, Amy J Swift, Barbara Thorand, Jean Tichet, Tiinamaija Tuomi, Rob M van Dam, Timon W van Haeften, Thijs van Herpt, Jana V van Vliet-Ostaptchouk, G Bragi Walters, Michael N Weedon, Cisca Wijmenga, Jacqueline Witteman, Richard N Bergman, Stephane Cauchi, Francis S Collins, Anna L Gloyn, Ulf Gyllensten, Torben Hansen, Winston A Hide, Graham A Hitman, Albert Hofman, David J Hunter, Kristian Hveem, Markku Laakso, Karen L Mohlke, Andrew D Morris, Colin N A Palmer, Peter P Pramstaller, Igor Rudan, Eric Sijbrands, Lincoln D Stein, Jaakko Tuomilehto, Andre Uitterlinden, Mark Walker, Nicholas J Wareham, Richard M Watanabe, Gonçalo R Abecasis, Bernhard O Boehm, Harry Campbell, Mark J Daly, Andrew T Hattersley, Frank B Hu, James B Meigs, James S Pankow, Oluf Pedersen, H-Erich Wichmann, Inês Barroso, Jose C Florez, Timothy M Frayling, Leif Groop, Rob Sladek, Unnur Thorsteinsdottir, James F Wilson, Thomas Illig, Philippe Froguel, Cornelia M van Duijn, Kari Stefansson, David Altshuler, Michael Boehnke, Mark I McCarthy
Journal: Nature Genetics (2010)
Focal Infiltrations of Polymorphonuclear Leukocytes in Liver Biopsies: Traumatic Lesions?
Authors: Frederick L. Fenster, Harold O. Conn
Journal: Hepatology (1987)

A young man with chronic active hepatitis was heavily sedated during an attempted transjugular liver biopsy. The procedure was abandoned after 3 h and an immediate percutaneous liver biopsy was performed. This showed features of chronic active hepatitis but, in addition, groups of poly-morphonuclear leukocytes in the parenchyma. These were similar to the operation associated neutrophils encountered in liver biopsies taken during the course of abdominal surgery. In a review of 78 liver biopsies from patients with chronic active hepatitis, this type of infiltrate was seen in four of eight surgically resected specimens but not in 70 percutaneous biopsies. The neutrophilic infiltrate in the present case appears to be an unique occurrence in a percutaneous liver biopsy. It was probably related to hypoperfusion during the preceding prolonged sedation and illustrates the ease with which an already diseased liver can be further damaged.
Site of Primary Tumor Has a Prognostic Role in Operable Breast Cancer: The International Breast Cancer Study Group Experience
Authors: Marco Colleoni, David Zahrieh, Richard D. Gelber, Stig B. Holmberg, Jan E. Mattsson, Carl-Magnus Rudenstam, Jurij Lindtner, Darja Eržen, Raymond Snyder, John Collins, Martin F. Fey, Beat Thürlimann, Diana Crivellari, Elizabeth Murray, Caesar Mendiola, Olivia Pagani, Monica Castiglione-Gertsch, Alan S. Coates, Karen Price, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2005)

Purpose Cancer presenting at the medial site of the breast may have a worse prognosis compared with tumors located in external quadrants. For medial tumors, axillary lymph node staging may not accurately reflect the metastatic potential of the disease. Patients and Methods Eight-thousand four-hundred twenty-two patients randomly assigned to International Breast Cancer Study Group clinical trials between 1978 and 1999 were classified as medial site (1,622; 19%) or lateral, central, and other sites (6,800; 81%). Median follow-up was 11 years. Results A statistically significant difference was observed for patients with medial tumors versus those with nonmedial tumors in disease-free survival (DFS; 10-year DFS, 46% v 48%; HR, 1.10; 95% CI, 1.02 to 1.18; P = .01) and overall survival (10-year OS 59% v 61%; HR, 1.09; 1.01 to 1.19; P = .04). This difference increased after adjustment for other prognostic factors (HR, 1.22; 95% CI, 1.13 to 1.32 for DFS; and HR, 1.24; 95% CI, 1.14 to 1.35 for OS; both P = .0001). The risk of relapse for patients with medial presentation was largest for the node-negative cohort and for patients with tumors larger than 2 cm. In the subgroup of 2,931 patients with negative axillary lymph nodes, 10-year DFS was 61% v 67%, and OS was 73% v 80% for medial versus nonmedial sites, respectively (HR 1.33; 95% CI, 1.15 to 1.54; P = .0001 for DFS; and HR 1.40; 95% CI, 1.17 to 1.67; P = .0003 for OS). Conclusion Tumor site has a significant prognostic utility, especially for axillary lymph node–negative disease, that should be considered in therapeutic algorithms. New staging procedures such as biopsy of the sentinel internal mammary nodes or novel imaging methods should be further studied in patients with medial tumors.
Prospection or projection: Neurobiological basis of stimulus-independent mental traveling
Authors: Jiro Okuda
Journal: Behavioral and Brain Sciences (2007)

Abstract The number of studies concerning the neurobiology of human prospection is now rapidly exploding. Recent works suggest that prospection can be better understood in a broader context of self-projection into other times, places, or agents that can share the same cerebral basis involving medial aspects of prefrontal, parietal, and temporal cortices. Mental time travel may be extended more generally to “mental traveling,” accomplished by stimulus-independent mental processes typical of human thought.
Role of the kidneys in the metabolism of furosemide
Authors: V Pichette, P du Souich
Journal: Journal of the American Society of Nephrology (1996)

The site where furosemide is metabolized and the location where probenecid reduces furosemide metabolism remain poorly defined. The liver appears to play a minor role, and there is indirect evidence suggesting that the kidneys could be responsible for the metabolism of furosemide. To assess the role of the kidneys in the metabolism of furosemide, its intravenous kinetics have been studied in control and anephric rabbits, after the ligation of the renal pedicles. Two additional groups of rabbits, control and anephric, have received probenecid before the administration of furosemide. In the control group, the total clearance of furosemide was 18.65 +/- 1.01 mL/ min per kg; urinary and metabolic clearances of furosemide were 7.95 +/- 0.65 and 10.70 +/- 1.11 mL/min per kg, respectively. In anephric rabbits, total clearance was reduced by 85% to 2.69 +/- 0.26 mL/min per kg (P < 0.001), secondary to the abolition of furosemide renal excretion and to the reduction in metabolic clearance from 10.70 +/- 1.11 to 2.69 +/- 0.26 mL/min per kg (P < 0.001). The pretreatment with probenecid reduced the total clearance of furosemide by 80%, to 3.62 +/- 0.24 mL/min per kg (P < 0.001), because of a reduction of 90 and 75% in urinary and metabolic clearances, respectively. The administration of probenecid to anephric rabbits did not reduce further the metabolic clearance. It is concluded that the kidneys are responsible for 85% of furosemide total clearance, either via excretion (43%) or biotransformation (42%), and that probenecid inhibits both processes.
Developing patient-friendly genetic and genomic test reports: formats to promote patient engagement and understanding
Authors: Susanne B Haga, Rachel Mills, Kathryn I Pollak, Catherine Rehder, Adam H Buchanan, Isaac M Lipkus, Jennifer H Crow, Michael Datto
Journal: Genome Medicine (2014)

With the emergence of electronic medical records and patient portals, patients are increasingly able to access their health records, including laboratory reports. However, laboratory reports are usually written for clinicians rather than patients, who may not understand much of the information in the report. While several professional guidelines define the content of test reports, there are no guidelines to inform the development of a patient-friendly laboratory report. In this Opinion, we consider patient barriers to comprehension of lab results and suggest several options to reformat the lab report to promote understanding of test results and their significance to patient care, and to reduce patient anxiety and confusion. In particular, patients' health literacy, genetic literacy, e-health literacy and risk perception may influence their overall understanding of lab results and affect patient care. We propose four options to reformat lab reports: 1) inclusion of an interpretive summary section, 2) a summary letter to accompany the lab report, 3) development of a patient user guide to be provided with the report, and 4) a completely revised patient-friendly report. The complexity of genetic and genomic test reports poses a major challenge to patient understanding that warrants the development of a report more appropriate for patients.
Hyperhomocysteinemia Increases Risk of Death, Especially in Type 2 Diabetes
Authors: Ellen K. Hoogeveen, Pieter J. Kostense, Cornelis Jakobs, Jacqueline M. Dekker, Giel Nijpels, Robert J. Heine, Lex M. Bouter, Coen D. A. Stehouwer
Journal: Circulation (2000)

Background —A high serum total homocysteine (tHcy) concentration is a risk factor for death, but the strength of the relation in patients with type 2 (non–insulin-dependent) diabetes mellitus compared with nondiabetic subjects is not known. A cross-sectional study suggested that the association between tHcy and cardiovascular disease is stronger in diabetic than in nondiabetic subjects. We therefore prospectively investigated the combined effect of hyperhomocysteinemia and type 2 diabetes on mortality. Methods and Results —Between October 1, 1989, and December 31, 1991, serum was saved from 2484 men and women, 50 to 75 years of age, who were randomly selected from the town of Hoorn, The Netherlands. Fasting serum tHcy concentration was measured in 171 subjects who died (cases; 76 of cardiovascular disease) and in a stratified random sample of 640 survivors (control subjects). Mortality risks were calculated over 5 years of follow-up by means of logistic regression. The prevalence of hyperhomocysteinemia (tHcy &gt;14 μmol/L) was 25.8%. After adjustment for major cardiovascular risk factors, serum albumin, and HbA 1c , the odds ratio (95% CI) for 5-year mortality was 1.56 (1.07 to 2.30) for hyperhomocysteinemia and 1.26 (1.02 to 1.55) per 5-μmol/L increment of tHcy. The odds ratio for 5-year mortality for hyperhomocysteinemia was 1.34 (0.87 to 2.06) in nondiabetic subjects and 2.51 (1.07 to 5.91) in diabetic subjects ( P =0.08 for interaction). Conclusions —Hyperhomocysteinemia is related to 5-year mortality independent of other major risk factors and appears to be a stronger (1.9-fold) risk factor for mortality in type 2 diabetic patients than in nondiabetic subjects.
Post Mortem or Post Hoc
Authors: M. Jack Frumin
Journal: JAMA (1969)

This communication describes a rare condition, unsuspected epidural abscess, present during an otherwise uncomplicated spinal anesthesia and emphasizes the absolutely essential role of postmortem examination in establishing both the cause and nature of concurrent but not causally related complications. Without postmortem examination the actual pathological condition would have been overlooked, and the information available prior to autopsy would have incriminated the unrelated procedure of spinal anesthesia. <h3>Report of a Case.—</h3> An 87-year-old woman required amputation of her left leg for diabetic gangrene of the heel and surrounding cellulitis. The patient was a known diabetic for 35 years, treated initially with insulin and more recently with tolbutamide (Orinase). Four years earlier, the right foot had been amputated for a similar condition. There was also a history of arteriosclerotic heart disease. At the time of admission, three weeks before operation, significant findings were blood pressure, 110/70 mm Hg; temperature, 101 F (38.3