tbuckley/cabot-search huggingface dataset:
Ventricular beats induce variations in cycle length of rapid (type II) atrial flutter in humans. Evidence of leading circle reentry.
Authors: F Ravelli, M Disertori, F Cozzi, R Antolini, M A Allessie
Journal: Circulation (1994)

Slight variation in cycle lengths of common and rapid atrial flutter in humans is an established phenomenon, but its mechanisms have not been completely clarified. In a previous study, we demonstrated that in common atrial flutter the variations in atrial cycle length were due to atrial stretch affecting the revolution time of a reentrant circuit. In the present study, we investigate the nature of atrial cycle length variations in the rapid type of human atrial flutter.Atrial interval variations of 17 episodes of rapid atrial flutter in 14 patients were investigated by measuring the sequence of atrial intervals from intraesophageal or intra-atrial leads and the onset of QRS complexes from a surface lead (V1). To study whether interval variation in flutter cycle was related to ventricular activity, a phase plot was constructed in which the flutter cycle length was plotted against the time after the previous QRS complex. This showed that the interval fluctuations were strictly coupled to the moment of ventricular activation. After the onset of the QRS complex, the rapid atrial flutter interval gradually decreased by an average of 4.1% (P < .001) and reached a minimum value after 300 to 600 milliseconds. Thereafter, the intervals increased again until the next ventricular beat occurred. In 10 patients developing both common and rapid atrial flutter, two different phase relations were found. Whereas during common atrial flutter the atrial interval increased after the QRS complex, it decreased during rapid atrial flutter. In three patients, intra-atrial pressure was recorded together with the electrical activity during both common and rapid atrial flutter episodes. This showed that variations in atrial flutter cycle length were associated with the rise of atrial pressure during ventricular contraction.These findings indicate a role of contraction-excitation feedback caused by atrial stretch after a ventricular activation. The shortening of the atrial interval after the onset of the QRS complex as found in patients during rapid atrial flutter can be explained by stretch-induced shortening of atrial refractoriness and consequent shortening of the revolution time of a functionally determined intra-atrial circuit.
Patients' refusal to consent to storage and use of samples in Swedish biobanks: cross sectional study
Authors: L. Johnsson, M. G Hansson, S. Eriksson, G. Helgesson
Journal: BMJ (2008)

<b>Objectives</b> To estimate how many people object to storage of biological samples collected in health care in Sweden and to their use in research and how many withdraw previous consent. <b>Design</b> Cross sectional study of register data. <b>Setting</b> Biobanks used in Swedish health care, 2005-6. <b>Population</b> Data on refusal to consent were obtained for 1.4 million biobank samples per year from 20 of 21 counties. <b>Main outcome measures</b> Rates of preliminary refusal to consent, confirmed refusal, and withdrawal of consent. <b>Results</b> Patients refused consent to either storage or use of their samples in about 1 in 690 cases; about 1 in 1600 confirmed their decision by completing a dissent form. Rather than having the samples destroyed, about 1 in 6200 patients wanted to restrict their use. Of those who had previously consented, about 1 in 19 000 withdrew their consent. <b>Conclusions</b> Refusal to consent to biobank research in Sweden is rare, and the interests of individuals and research interests need not be at odds. The Swedish healthcare organisation is currently obliged to obtain either consent or refusal to each potential use of each sample taken, and lack of consent to research is used as the default position. A system of presumed consent with straightforward opt out would correspond with people’s attitudes, as expressed in their actions, towards biobank research.
Persistent abnormal liver fibrosis after weaning off parenteral nutrition in pediatric intestinal failure
Authors: Annika Mutanen, Jouko Lohi, Päivi Heikkilä, Antti I. Koivusalo, Risto J. Rintala, Mikko P. Pakarinen
Journal: Hepatology (2013)

The aim of this study was to evaluate the long-term effects of pediatric intestinal failure (IF) on liver histology. Altogether, 38 IF patients (median age: 7.2 years; range, 0.2-27) underwent liver biopsy, gastroscopy, abdominal ultrasound, and laboratory tests. Sixteen patients were on parenteral nutrition (PN) after 74 PN months (range, 2.5-204). Twenty-two had weaned off PN 8.8 years (range, 0.3-27) earlier, after 35 PN months (range, 0.7-250). Fifteen transplant donor livers served as controls. Abnormal liver histology was found in 94% of patients on PN and 77% of patients weaned off PN ( P = 0.370). During PN, liver histology weighted with cholestasis (38% of patients on PN versus 0% of patients weaned off PN; P = 0.003) and portal inflammation (38% versus 9%; P = 0.050) were found. Fibrosis (88% versus 64%; P = 0.143; Metavir stage: 1.6 [range, 0-4] versus 1.1 [range, 0-2]; P = 0.089) and steatosis (50% versus 45%; P = 1.000) were equally common during and after weaning off PN. Plasma alanine aminotransferase (78 U/L [range, 19-204] versus 34 [range, 9-129]; P = 0.009) and conjugated bilirubin (43 μmol/L [range, 1-215] versus 4 [range, 1-23]; P = 0.037) were significantly higher during than after weaning off PN. Esophageal varices were encountered in 1 patient after weaning off PN. Metavir stage was associated with small bowel length ( r = −0.486; P = 0.002) and number of septic episodes ( r = 0.480; P = 0.002). In a multivariate analysis, age-adjusted small bowel length (ß = −0.533; P = 0.001), portal inflammation (ß = 0.291; P = 0.030), and absence of an ileocecal valve (ß = 0.267; P = 0.048) were predictive for fibrosis stage. Conclusion : Despite resolution of cholestasis and portal inflammation, significant liver fibrosis and steatosis persist after weaning off PN. Extensive small intestinal resection was the major predictor for liver fibrosis stage. (Hepatology 2013;58:729–738)
It's unethical for general practitioners to be commissioners
Authors: M. Sheehan
Journal: BMJ (2011)

The government wants to liberate the English National Health Service. By this they seem to mean to liberate the NHS from managers. The idea is that managing can be done by those who are already doing another job—general practitioners. It may be that the NHS is currently top-heavy, and it may not be as good as it might be. However, I have several ethical concerns about devolving commissioning responsibility to GPs.

There are two ways to ask how we should allocate NHS resources. Should we fund cheaper, less effective drugs, or better, more expensive ones? Here, the relevant considerations involve population level calculations—evidence of effectiveness, evidence of cost effectiveness, incidence, and projected demand. Alternatively, we might ask whether Mr Jones’s GP should decide to prescribe the drug that is less effective but cheaper, or the better, more expensive drug? Here, features of Mr Jones’s circumstances matter. Does he live alone? Can he cope with a few more headaches? Mr Jones’s GP can answer these questions because he knows him and his situation. The answers to these questions, given on the …
Improvements In Health-Related Quality Of Life From Asteria I &amp; II: Phase III Studies To Evaluate The Efficacy and Safety Of Omalizumab In Patients With Chronic Idiopathic/Spontaneous Urticaria Who Remain Symptomatic Despite H1 Antihistamine Treatment
Authors: Karina Raimundo, James Zazzali, Benjamin Trzaskoma, Karin Rosen
Journal: Journal of Allergy and Clinical Immunology (2014)
Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations
Authors: Desirée Schubert, Claudia Bode, Rupert Kenefeck, Tie Zheng Hou, James B Wing, Alan Kennedy, Alla Bulashevska, Britt-Sabina Petersen, Alejandro A Schäffer, Björn A Grüning, Susanne Unger, Natalie Frede, Ulrich Baumann, Torsten Witte, Reinhold E Schmidt, Gregor Dueckers, Tim Niehues, Suranjith Seneviratne, Maria Kanariou, Carsten Speckmann, Stephan Ehl, Anne Rensing-Ehl, Klaus Warnatz, Mirzokhid Rakhmanov, Robert Thimme, Peter Hasselblatt, Florian Emmerich, Toni Cathomen, Rolf Backofen, Paul Fisch, Maximilian Seidl, Annette May, Annette Schmitt-Graeff, Shinji Ikemizu, Ulrich Salzer, Andre Franke, Shimon Sakaguchi, Lucy S K Walker, David M Sansom, Bodo Grimbacher
Journal: Nature Medicine (2014)
Abstract 2860: A critical role of bone marrow-derived cells for hedgehog-mediated carcinogenesis.
Authors: Jingwu Xie, Eric Qipeng Fan, Dongsheng Gu, Hailan Liu, Xiaoli Zhang, Mark Kaplan, Merv Yoder
Journal: Cancer Research (2013)

Abstract Amounting evidence indicate that the tissue microenvironment in a developing tumor is created by the tumor to orchestrates molecular and cellular interactions. As a major pathway involved in tumorigenesis, Hedgehog (Hh) signaling is known to regulate tumor microenvironment, but the underlying molecular mechanisms in hedgehog-driven tumors remain unclear. Here we show that smoothened (SMO)-mediated tumor development is accompanied by TGFβ activation in a variety of cell types of the tumor microenvironment, such as keratinocytes, fibroblasts and myeloid-derived suppressor cells. To determine the role of TGFβ signaling for SMO-mediated tumor development, we generated cell type specific TGFβR2flp/flp mice in which SmoM2 expression is accompanied by TGFβR2 knocking out. We found that while K14cre-mediated TGFβRII knockout promoted tumor development, Mx-1cre-mediated TGFβRII knockout suppressed tumor development, indicating a tumor promoting effect of stromal TGFβ signaling. Using EGFP expressing mice for bone marrow transplantation, we determined that most stromal cells with TGFβ signaling activation are derived from bone marrow. To further determine the role of stromal TGFβ signaling for hedgehog signaling-mediated tumor development, we performed bone marrow transplantation experiments in mice that can be induced to develop basal cell carcinomas (BCC). We found that bone marrow cells with TGFβR2 knockout, but not the wild type cells, inhibited tumor development and reduced the size of developed tumors. Reduction of tumor development was associated with decreased expression of multiple inflammation stimulatory cytokines as well as the number of myeloid-derived suppressor cells (MDSCs). The tumor promoting effect of TGFβ signaling is not limited to BCC because tumor growth of B16-F10 cells was also affected by TGFβRII elimination in bone marrow-derived cells. Our data indicate that TGFβ signaling in the tumor microenvironment, not in the keratinocytes, is critical for maintaining the tumor microenvironment to foster tumor development and growth. Citation Format: Jingwu Xie, Eric Qipeng Fan, Dongsheng Gu, Hailan Liu, Xiaoli Zhang, Mark Kaplan, Merv Yoder. A critical role of bone marrow-derived cells for hedgehog-mediated carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2860. doi:10.1158/1538-7445.AM2013-2860
Education in Anesthesiology
Authors: Leonard F. Walts
Journal: JAMA (1968)

In the spring of 1967, the Josiah Macy Foundation sponsored a twoday meeting on the subject of anesthesia education. The papers read at this meeting make up the substance of this book.  Participants were, for the most part, professors of anesthesia at leading universities in the United States and abroad. They considered all phases of anesthesia education from the instruction of first- and second-year medical students to the continuing education of the practicing anesthesiologist.  Since these men represent university programs, some of their innovations were not totally unexpected. Ideas expressed by individuals at the conferences included clinical research training for medical students, university type training for all anesthesiologists, and the formation of specialized postgraduate training centers. The latter would give indepth training in such subspecialties as pain therapy, respirology, and cardiovascular anesthesia and would require four to five years of study. All of these suggestions have been made to correct
Anti‐cAngptl4 Ab‐Conjugated N‐TiO<sub>2</sub>/NaYF<sub>4</sub>:Yb,Tm Nanocomposite for Near Infrared‐Triggered Drug Release and Enhanced Targeted Cancer Cell Ablation
Authors: Qing Chi Xu, Yan Zhang, Ming Jie Tan, Yang Liu, Shaojun Yuan, Cleo Choong, Nguan Soon Tan, Timothy Thatt Yang Tan
Journal: Advanced Healthcare Materials (2012)

Nanomedicine: NIR-active N-TiO2/NaYF4:Yb,Tm nanocomposites (NCs) were synthesized for the first time and its potential applications in drug release and targeted cancer cell ablation are explored. Upon 980 nm laser irradiation, the anti-cAngptl4 Ab-conjugated N-TiO2/NaYF4:Yb,Tm NCs shows a significant increase in apoptotic A-5RT3 cells when compared with that of the unconjugated NCs. The mechanisms for NIR-induced photocatalysis, drug release and targeted cancer cell killing are proposed.
An Outbreak of Post-operative Sepsis
Authors: E. J. K. Penikett, R. Knox, J. Liddell
Journal: BMJ (1958)

CONTRACTION OF DUCTUS ARTERIOSUS.~~~~~~~~~(DA lungs and dissecting away the pericardium, leaving the aorta and pulmonary trunk undisturbed except for cutting them across just above the valves.When this has been done the ductus can be seen to cross the descending aorta from right to left at a very acute angle and enter it, as described, on its antero-lateral aspect.When the vessels are removed from the body their elasticity abolishes this relationship. SummaryPost-mortem observations show that the ductus arteriosus may be contracted or uncontracted.In most infants that have lived independently it is contracted, while in most stillborn infants it is uncontracted.These observations are taken to support the idea that active contraction of the ductus is associated with the onset of respiration.Most of the stillborn infants were mature, and most of the neonatal deaths were of premature infants.In both stillbirth and neonatal death there were more examples of uncontracted ductus among mature infants than among premature infants.The questions inherent in these findings require further study.I am indebted to Dr. K. W. Cross for help with statistics, and to Mr. C. Johnstone for help with photography.
The Federated Council of Internal Medicine's Resource Guide for Residency Education: An Instrument for Curricular Change
Authors: Jack Ende
Journal: Annals of Internal Medicine (1997)

The Federated Council of Internal Medicine has developed a resource guide to help internal medicine residency programs produce internists who are prepared for today's practice of internal medicine and the challenges of practice in the future.The guide situates general internal medicine as the primary care profession that focuses on preventive, short-term, and long-term care of adult patients. It assumes that a single pathway is sufficient for educating general internists and subspecialty-bound trainees. It identifies the learning experiences that should be part of general internal medicine residency training, lists the clinical competencies that are important for primary care practice, and describes the role of the integrative disciplines that should inform the care of every patient. It also describes a process that program directors and local program committees can use to develop competency-based curricula.
Abstract 5182: Real-time molecular imaging of αv-integrin GFP-expression in osteosarcoma cells <i>in vitro</i> and <i>in vivo</i>
Authors: Yasunori Tome, Naotoshi Sugimoto, Shuya Yano, Masashi Momiyama, Hiroki Maehara, Katsuro Tomita, Hiroyuki Tsuchiya, Fuminori Kanaya, Robert M. Hoffman
Journal: Cancer Research (2012)

Abstract We describe here real-time imaging of αv integrin-GFP expression in osteosarcoma cells (143B) in vitro and in vivo. 143B cells were stably transfected with an αv integrin-GFP vector. Confocal microscopy demonstrated that αv integrin immunofluorescent staining colocalized with αv integrin-GFP fluorescence. In vitro, when αv integrin-GFP osteosarcoma cells were seeded on a dish coated with fibronectin, which bonds αv integrin. αv integrin adhesion plaques were observed by confocal microscopy using the Olympus FV1000. When αv integrin-GFP-expressing 143B cells (1×106) were transplanted in the tibia or injected subcutaneously in nude mice, the cells aligned along collagen orthotopic fibers. In the orthotopic model, osteosarcoma cells punctate expression of αv integrin-GFP was imaged in the osteosarcoma cells as they invaded muscular tissue. In the subcutaneous model, osteosarcoma cells, strongly expressing αv integrin-GFP, were observed around the blood vessels in the tumor. These results show that αv integrin-GFP allows the real-time imaging of the role of αv integrin during cancer cell invasion allowing the further understanding of its role in the process. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5182. doi:1538-7445.AM2012-5182
Development of Type 1 Diabetes despite Severe Hereditary B-Cell Deficiency
Authors: Stephan Martin, Dorothea Wolf-Eichbaum, Gaby Duinkerken, Werner A. Scherbaum, Hubert Kolb, Jeroen G. Noordzij, Bart O. Roep
Journal: New England Journal of Medicine (2001)

Type 1 diabetes results from an immune-mediated destruction of pancreatic beta cells. The disease can be transmitted by bone marrow transplantation in humans1 and animals.2,3 Furthermore, T cells that are reactive to several islet autoantigens have been identified in both mice and humans.4,5 Although it is generally accepted that T cells have a role during the disease process, the possible role of B cells and autoantibodies in type 1 diabetes in humans has not been fully resolved. When they are activated, B cells can produce autoantibodies to pancreatic beta-cell antigens — such as glutamic acid decarboxylase 65 (GAD65), . . .
How it strikes a historian.
Authors: I Loudon
Journal: BMJ (1984)

<h3>Abstract</h3> Strong phenological shifts in response to changes in climatic conditions have been reported for many species, including amphibians, which are expected to breed earlier. Phenological shifts in breeding are observed in a wide number of amphibian populations, but less is known about populations living at high elevations, which are predicted to be more sensitive to climate change than lowland populations. The goal of this study is to assess the main factors determining the timing of breeding in an alpine population of the common toad (<i>Bufo bufo</i>) and to describe the observed shifts in its breeding phenology. We modelled the effect of environmental variables on the start and peak dates of the breeding season using 39 years of individual-based data. In addition, we investigated the effect of the lunar cycle, as well as the individual variation in breeding phenology. Finally, to understand the role of the genetic component of the breeding phenology we calculated the repeatability of the timing of arrival at the breeding site. Breeding advanced to earlier dates in the first years of the study but the trend continued only until the mid 1990s, and stabilised afterwards. Overall, toads are now breeding on average around 30 days earlier than at the start of the study period. High temperatures and low snow cover in winter and spring, as well as reduced spring precipitation were all associated with earlier breeding. Additionally, we found evidence of males arriving on average before females at the breeding site but no clear and strong effect of the lunar cycle. We only found weak evidence of among-individual variation in shifts in the breeding phenology, as well as a low repeatability of arrival timing. Our findings show that the observed changes in breeding phenology are strongly associated with the environmental conditions. These results contribute to filling a knowledge gap on the effects of climate change on alpine amphibian populations. Moreover, we show that changes in phenology, especially in the mountains, can be hard to predict as local microclimatic conditions do not necessarily reflect the observed global climatic trends.
First seizures in adults
Authors: H. Angus-Leppan
Journal: BMJ (2014)

#### Summary points

A seizure is a clinical manifestation of presumed or proved abnormal electrical activity in the brain. A first seizure can range from a fleeting subjective experience such as deja vu or a twitch (myoclonic jerk) through to a tonic-clonic convulsion. Some seizure manifestations overlap with normal phenomena. A single seizure may be provoked (with an acute precipitant that may or may not recur) or unprovoked (idiopathic or of unknown cause). Epilepsy is defined as more than one seizure.

#### Sources and selection criteria

I consulted my personal archive of references and searched Medline and the Cochrane Collaboration and Clinical Evidence databases, using “seizure”, “first seizure”, and specific topics. I also consulted the National Institute for Health and Care Excellence’s guidelines. I carefully examined randomised controlled trials, systematic reviews, and meta-analyses. Ranges of results are used in preference to averages, because pooling results from methodologically diverse studies is not accurate

This article focuses on the diagnosis of first seizures and differentiation from their “mimics” in adults. The …
Fatigue in psoriasis: a phenomenon to be explored
Authors: I.M. Skoie, T. Ternowitz, G. Jonsson, K. Norheim, R. Omdal
Journal: British Journal of Dermatology (2014)

Fatigue is a prevalent and substantial phenomenon in many patients with chronic inflammatory diseases, often rated by patients as the most troublesome symptom and aspect of their disease. It frequently interferes with physical and social functions and may lead to social withdrawal, long-standing sick leave and disability. Although psychological and somatic factors such as depression, sleep disorders, pain and anaemia influence fatigue, the underlying pathophysiological mechanisms by which fatigue is generated and regulated are largely unknown. Increasing evidence points towards a genetic and molecular basis for fatigue as part of the innate immune system and cellular stress responses. Few studies have focused on fatigue in dermatological diseases. Most of these studies describe fatigue as a phenomenon related to psoriatic arthritis and describe the beneficial effects of biological agents on fatigue observed in clinical studies. It is therefore possible that this problem has been underestimated and deserves more attention in the dermatological community. In this review, we provide a definition and explanation for chronic fatigue, describe some commonly used instruments for measuring fatigue, and present hypothetical biological mechanisms with an emphasis on activation of the innate immune system and oxidative stress. An overview of relevant clinical studies covering the theme 'psoriasis and fatigue' is given.