tbuckley/cabot-search huggingface dataset:
Design and Results of the Antiarrhythmics vs Implantable Defibrillators (AVID) Registry
Authors: Jeffrey L. Anderson, Alfred P. Hallstrom, Andrew E. Epstein, Sergio L. Pinski, Yves Rosenberg, Matthew O. Nora, Donald Chilson, David S. Cannom, Rich Moore
Journal: Circulation (1999)

The Antiarrhythmics Versus Implantable Defibrillators (AVID) Study compared treatment with implantable cardioverter-defibrillators versus antiarrhythmic drugs in patients with life-threatening ventricular arrhythmias (VAs). AVID maintained a Registry on all patients, randomized or not, with any VA or unexplained syncope who could be considered for either of the treatment strategies. Trial-eligible arrhythmias were the categories of VF cardiac arrest, Syncopal VT, and Symptomatic VT, below.Of 5989 patients screened, 4595 were registered and 1016 were randomized. Mortality follow-up through 1996 was obtained on the 4219 Registry patients enrolled before 1997 through the National Death Index. Crude mortality rates (mean+/-SD, follow-up, 16.9+/-11.5 months) were: VF cardiac arrest, 17.0% (n=1399, 238 deaths); Syncopal VT, 21.2% (n=598, 127 deaths); Symptomatic VT, 15.8% (n=1065, 168 deaths); Stable (asymptomatic) VT, 19.7% (n=497, 98 deaths); VT/VF with transient/correctable cause, 17.8% (n=270, 48 deaths); and Unexplained syncope, 12.3% (n=390, 48 deaths).Patients with seemingly lower-risk or unknown-risk VAs (asymptomatic VT, and VT/VF associated with a transient factor) have a (high) mortality similar to that of higher-risk, AVID-eligible VAs. The similar (and poor) prognosis of most patients with VT/VF suggests the need for reevaluation of a priori risk grouping and raises the question of the appropriate arrhythmia therapy for a broad range of patients.
Doing What We Can With Advance Care Planning
Authors: Benjamin H. Levi, Michael J. Green
Journal: The American Journal of Bioethics (2010)

Click to increase image sizeClick to decrease image size Acknowledgments The project described was supported by grant 1 R21 NR008539 from National Institute of Nursing Research, National Institutes of Health. Its contents are solely the responsibility of the author and do not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. The project also received support from the American Cancer Society (grant RSGHP-08-005-01-CPHPS), and various funding from Penn State University (the Social Science Research Institute, the Woodward Endowment for Medical Science Education, and the Tobacco Settlement Fund Award). The author acknowledges the support and assistance of Dr. William Lawrence for his contribution to the MAUT model used in this program, Dr. Cheryl Dellasega for her leadership in focus-group activities, Charles Sabatino for his review of legal aspects of the program, Dr. Robert Pearlman and his collaborative team for use of the advance care planning booklet "Your Life, Your Choices," Joanne Caulfield for assistance in grant preparation and project organization, and the Instructional Media Development Center at the University of Wisconsin as well as JPL Integrated Communications for production and programming of the decision aid.
Eosinophils, neutrophils, and venular gaps in the airway mucosa at epithelial removal-restitution.
Authors: J S Erjefält, F Sundler, C G Persson
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Shedding of epithelium, increased venular permeability, and traffic of activated eosinophils and neutrophils may characterize asthmatic airways. This in vivo study involving briefly anesthetized guinea pigs examines whether epithelial denudation itself affects airway venules and granulocytes. Using an oral probe, a de-epithelialized tracheal zone (0.8 x 30 mm) was produced without bleeding or damage to the basement membrane. After 10 min, 2, 8, and 48 h, the tracheal tissue was examined by scanning and transmission electron microscopy. Silver staining revealed endothelial cell borders. Histochemistry identified neutrophils and eosinophils. Confirming previous observations, epithelial restitution started promptly and occurred speedily under a plasma exudation-derived, leukocyte-rich gel. Ten minutes after de-epithelialization, venular gaps (silver dots) were recognized as plasma exudation sites and, separately, silver rings at endothelial cell borders indicated attachment and extravasation of leukocytes. Tissue neutrophils were increased from 10 min to 48 h. Normally occurring eosinophils decreased in numbers during re-epithelialization, partly due to migration into the airway lumen and local cell death. Clusters of extracellular eosinophil granules were increased from 10 min to 8 h. Gentle removal of airway epithelium thus produced venular gaps, infiltration of neutrophils, and migration, activation, and death of eosinophils. Epithelial shedding-restitution processes may cause part of the microvascular and leukocyte changes that occur in inflammatory airway diseases.
Synovial Sarcoma: Recent Discoveries as a Roadmap to New Avenues for Therapy
Authors: Torsten O. Nielsen, Neal M. Poulin, Marc Ladanyi
Journal: Cancer Discovery (2015)

Abstract Oncogenesis in synovial sarcoma is driven by the chromosomal translocation t(X,18; p11,q11), which generates an in-frame fusion of the SWI/SNF subunit SS18 to the C-terminal repression domains of SSX1 or SSX2. Proteomic studies have identified an integral role of SS18–SSX in the SWI/SNF complex, and provide new evidence for mistargeting of polycomb repression in synovial sarcoma. Two recent in vivo studies are highlighted, providing additional support for the importance of WNT signaling in synovial sarcoma: One used a conditional mouse model in which knockout of β-catenin prevents tumor formation, and the other used a small-molecule inhibitor of β-catenin in xenograft models. Significance: Synovial sarcoma appears to arise from still poorly characterized immature mesenchymal progenitor cells through the action of its primary oncogenic driver, the SS18–SSX fusion gene, which encodes a multifaceted disruptor of epigenetic control. The effects of SS18–SSX on polycomb-mediated gene repression and SWI/SNF chromatin remodeling have recently come into focus and may offer new insights into the basic function of these processes. A central role for deregulation of WNT–β-catenin signaling in synovial sarcoma has also been strengthened by recent in vivo studies. These new insights into the the biology of synovial sarcoma are guiding novel preclinical and clinical studies in this aggressive cancer. Cancer Discov; 5(2); 124–34. ©2015 AACR.
Late-onset focal dermal elastosis: clinical and histological features
Authors: S. TAJIMA, K. SHIMIZU, T. IZUMI, S. KURIHARA, T. HARADA
Journal: British Journal of Dermatology (1995)

We describe two patients with lesions clinically resembling pseudoxanthoma elasticum and histologically exhibiting focal elastosis, with normal-appearing elastic fibres in the mid- and deep dermis. We consider that these skin lesions represent a previously undescribed entity, whose pathogenesis appears to be related to the ageing process.
Morphological Observations on the Pathogenetic Process of Transposition of the Great Arteries Induced by Retinoic Acid in Mice
Authors: Hiroshi Yasui, Makoto Nakazawa, Masae Morishima, Sachiko Miyagawa-Tomita, Kazuo Momma
Journal: Circulation (1995)

The pathogenesis of complete transposition of the great arteries (TGA) is still controversial because useful animal models have not been established. We previously reported that all-trans retinoic acid induced complete TGA at a high proportion in mice. The aim of the present study was to clarify the morphogenesis of the cardiac outflow tract in the retinoic acid-treated embryos destined to develop TGA.We first examined the morphology of TGA in mouse fetuses treated with retinoic acid to establish an animal model of TGA (experiment 1) and then examined the retinoic acid-treated embryonic hearts by means of ink injection and histology (experiment 2). All mouse fetuses and embryos showed visceroatrial situs solitus and d-ventricular loop. In experiment 1, among 45 embryos treated with retinoic acid 70 mg/kg at day 8.5 of gestation, 35 (78%) had TGA and 3 (6.7%) had a double-outlet right ventricle with a subpulmonary ventricular septal defect. In experiment 2, all hearts already exhibited d-loop at gestation day 8.5. At gestation day 9.5, conus swellings, composed of acellular cardiac jelly, where hypoplastic, and the conotruncal cavity was nonspiral or tubular. At gestation day 11.0, aberrant conus swellings located anteroposteriorly to give a straight orientation to the conotruncal cavity. At gestation day 12.0, side-by-side great arteries were transposed in that the aorta arose from the right ventricle and the pulmonary artery arose above the interventricular foramen.These results suggest that a reproducible animal model of TGA can be produced in mice by treatment with retinoic acid; that there was no loop anomaly, such as an A-loop or L-loop, in our model; and that hypoplasia of the conus swellings appears to be the primary event leading to TGA.
Wrong Drug Dispensed
Authors: Robert Ritch, Newell A. Hargett, Steven M. Podos, Jonathan Mardirossian, Michael A. Kass
Journal: JAMA (1977)

<h3>To the Editor.—</h3> We have recently reported three patients<sup>1</sup>who inadvertently received acetohexamide from the pharmacy instead of acetazolamide, which had been prescribed for treatment of glaucoma. In one case, an elderly woman suffered head trauma after ingesting the acetohexamide and, when taken semistuporous to the emergency room, was found to have a blood glucose level of 20 mg/dl. The two drugs have several characteristics in common that may cause confusion in filling the prescription: Both come as 250-mg white tablets. Both their nonproprietary names (acetazolamide, acetohexamide) and trademarks (Diamox, Dymelor) are similar. When stored generically, they may be adjacent on the pharmacy shelf. The fact that acetohexamide is not a commonly prescribed oral hypoglycemic agent when compared to tolbutamide or chlorpropamide may make it all the more easily confused. These three cases all came to our attention within a relatively short time, and it is
Predicting Later-Life Outcomes of Early-Life Exposures
Authors: Kim Boekelheide, Bruce Blumberg, Robert E. Chapin, Ila Cote, Joseph H. Graziano, Amanda Janesick, Robert Lane, Karen Lillycrop, Leslie Myatt, J. Christopher States, Kristina A. Thayer, Michael P. Waalkes, John M. Rogers
Journal: Environmental Health Perspectives (2012)

Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.Objectives: We examined the current state of understanding of later-life diseases resulting from early-life exposures in order to identify in utero and postnatal indicators of later-life diseases, develop an agenda for future research, and consider the risk assessment implications of this emerging knowledge.Methods: This review was developed based on our participation in a National Research Council workshop titled "Use of in Utero and Postnatal Indicators to Predict Health Outcomes Later in Life: State of the Science and Research Recommendations." We used a case study approach to highlight the later-life consequences of early-life malnutrition and arsenic exposure.Discussion: The environmental sensitivity of the epigenome is viewed as an adaptive mechanism by which the developing organism adjusts its metabolic and homeostatic systems to suit the anticipated extrauterine environment. Inappropriate adaptation may produce a mismatch resulting in subsequent increased susceptibility to disease. A nutritional mismatch between the prenatal and postnatal environments, or early-life obesogen exposure, may explain at least some of the recent rapid increases in the rates of obesity, type 2 diabetes, and cardiovascular diseases. Early-life arsenic exposure is also associated with later-life diseases, including cardiovascular disease and cancer.Conclusions: With mounting evidence connecting early-life exposures and later-life disease, new strategies are needed to incorporate this emerging knowledge into health protective practices.
Obstetrics and Gynecology Annual
Authors: Arthur G. King
Journal: JAMA (1975)

Unlike numerous publications that abstract or summarize articles appearing in the literature for a given year, this series analyzes in depth a selected number of subjects important in obstetrics and gynecology. The present volume discusses 16 topics, ranging from the structure and function of the amnion to urologic injuries, from fetal lipid metabolism to carcinoma of the vulva, from the sudden infant death syndrome to biostatistics in obstetrics and gynecology. Unfortunately, the collection is an effort to provide something for everybody. With 19 different contributing authors, there is a marked difference in the excellence as well as the value of the different articles. Some of the chapters might be quite incomprehensible to the average practicing obstetrician-gynecologist. Others, such as those on operative procedures and practice problems, even though summarizing recent developments in these fields, would hold little interest to the research biologist, chemist, physiologist, or statistician. Almost all the sections
Prospective Study on the Incidences of Cardiovascular-Renal Complications in Chinese Patients With Young-Onset Type 1 and Type 2 Diabetes
Authors: Andrea O.Y. Luk, Eric S.H. Lau, Wing-Yee So, Ronald C.W. Ma, Alice P.S. Kong, Risa Ozaki, Francis C.C. Chow, Juliana C.N. Chan
Journal: Diabetes Care (2013)

OBJECTIVE We examined metabolic profiles and cardiovascular-renal outcomes in a prospective cohort of Chinese patients with young-onset diabetes defined by diagnosis age &amp;lt;40 years. Patients with type 1 diabetes and normal-weight (BMI &amp;lt;23 kg/m2) and overweight (BMI ≥23 kg/m2) patients with type 2 diabetes were compared. RESEARCH DESIGN AND METHODS Between 1995 and 2004, 2,323 patients (type 1 diabetes, n = 209; normal-weight type 2 diabetes, n = 636; and overweight type 2 diabetes, n = 1,478) underwent detailed clinical assessment. Incident cardiovascular disease (CVD) including coronary heart disease, stroke, and peripheral vascular disease were identified using hospital discharge diagnoses. End-stage renal disease (ESRD) was defined by glomerular filtration rate &amp;lt;15 mL/min/1.73 m2 or dialysis. RESULTS Overweight patients with type 2 diabetes had the worst metabolic profile and highest prevalence of microvascular complications. Over a median follow-up of 9.3 years, incidences of CVD were 0.6, 5.1, and 9.6 per 1,000 person-years in patients with type 1 diabetes, normal-weight patients with type 2 diabetes, and overweight patients with type 2 diabetes. The respective figures for ESRD were 2.2, 6.4, and 8.4 per 1,000 person-years. Compared with type 1 diabetes, the overweight type 2 diabetes group had a greater hazard of progression to CVD (hazard ratio [HR] 15.3 [95% CI 2.1–112.4]) and ESRD (HR 5.4 [95% CI 1.8–15.9]), adjusted for age, sex, and disease duration. The association became nonsignificant upon additional adjustment for BMI, blood pressure, and lipid. CONCLUSIONS Young patients with type 2 diabetes had greater risks of developing cardiovascular-renal complications compared with patients with type 1 diabetes. The increased risk was driven primarily by accompanying metabolic risk factors.
Noninvasive mechanical ventilation in patients having declined tracheal intubation
Authors: Élie Azoulay, Achille Kouatchet, Samir Jaber, Jérôme Lambert, Ferhat Meziani, Matthieu Schmidt, David Schnell, Satar Mortaza, Matthieu Conseil, Xavier Tchenio, Patrick Herbecq, Pierre Andrivet, Emmanuel Guerot, Ariane Lafabrie, Sébastien Perbet, Laurent Camous, Ralf Janssen-Langenstein, François Collet, Jonathan Messika, Stéphane Legriel, Xavier Fabre, Olivier Guisset, Samia Touati, Sarah Kilani, Michael Alves, Alain Mercat, Thomas Similowski, Laurent Papazian, Anne-Pascale Meert, Sylvie Chevret, Benoît Schlemmer, Laurent Brochard, Alexandre Demoule
Journal: Intensive Care Medicine (2012)
Dipeptide absorption in man
Authors: M. D. Hellier, C. D. Holdsworth, I. McColl, D. Perrett
Journal: Gut (1972)

A quantitative perfusion method has been used to study intestinal absorption of two dipeptides-glycyl-glycine and glycyl-l-alanine-in normal subjects. In each case, the constituent amino acids were absorbed faster when presented as dipeptides than as free amino acids, suggesting intact dipeptide transport. During absorption constituent amino acids were measured within the lumen and it is suggested that these represent amino acids which have diffused back to the lumen after absorption as dipeptide. Portal blood analyses during absorption of a third dipeptide, glycyl-l-lysine, have shown that this dipeptide, known to be transported intact from the intestinal lumen, is hydrolysed to its constitutent amino acids before it reaches portal venous blood.
Nosocomial Septicemia in Patients undergoing Sclerotherapy for Variceal Hemorrhage
Authors: H.H. Gerhartz, T. Sauerbruch, M. Weinzierl, G. Ruckdeschel
Journal: Endoscopy (1984)

The data of 19 consecutive unselected patients undergoing emergency sclerotherapy who were admitted to a single intensive care unit throughout the course of one year, were analyzed retrospectively for clinical and bacteriological signs of septicemia after the first sclerotherapy session. Ten had fever and/or chills, and in six of these patients microorganisms were cultured from arterial blood or central venous catheter tips. The data show that about one-third of patients with liver cirrhosis and acute variceal hemorrhage undergoing emergency sclerotherapy may develop septic disease.
Glycemic Control and Hypoglycemia: Is the Loser the Winner?
Authors: Lawrence C. Perlmuter, Brian P. Flanagan, Parinda H. Shah, Sant P. Singh
Journal: Diabetes Care (2009)

The study by Musen et al. (1) evaluated the effect of severe hypoglycemia in intensive diabetes treatment with respect to cognitive performance in type 1 diabetic patients aged 13–19 years at entry into the Diabetes Control and Complications Trial (DCCT). The investigators concluded that …
Construction and Functional Evaluation of a Single-Chain Antibody Fusion Protein With Fibrin Targeting and Thrombin Inhibition After Activation by Factor Xa
Authors: Karlheinz Peter, Justin Graeber, Sergey Kipriyanov, Monika Zewe-Welschof, Marschall S. Runge, Wolfgang Kübler, Melvyn Little, Christoph Bode
Journal: Circulation (2000)

Background —Recombinant technology was used to produce a new anticoagulant that is preferentially localized and active at the site of the clot. Methods and Results —The variable regions of the heavy and light chains of a fibrin-specific antibody were amplified by polymerase chain reaction (PCR) with hybridoma cDNA. To obtain a functional single-chain antibody (scFv), a linker region consisting of (Gly 4 Ser) 3 was introduced by overlap PCR. After the scFv clones were ligated with DNA encoding the pIII protein of the M13 phage, high-affinity clones were selected by 10 rounds of panning on the Bβ15-22 peptide of fibrin (β-peptide). Hirudin was genetically fused to the C-terminus of the variable region of the light chain. To release the functionally essential N-terminus of hirudin at the site of a blood clot, a factor Xa recognition site was introduced between scFv 59D8 and hirudin. The fusion protein was characterized by its size on SDS-PAGE (36 kDa), by Western blotting, by its cleavage into a 29-kDa (single chain alone) and 7-kDa (hirudin) fragment, by its binding to β-peptide, and by thrombin inhibition after Xa cleavage. Finally, the fusion protein inhibited appositional growth of whole blood clots in vitro more efficiently than native hirudin. Conclusions —A fusion protein was constructed that binds to a fibrin-specific epitope and inhibits thrombin after its activation by factor Xa. This recombinant anticoagulant effectively inhibits appositional clot growth in vitro. Its efficient and fast production at low cost should facilitate a large-scale evaluation to determine whether an effective localized antithrombin activity can be achieved without systemic bleeding complications.
β-Tubulin-II Expression Strongly Predicts Outcome in Patients Receiving Induction Chemotherapy for Locally Advanced Squamous Carcinoma of the Head and Neck: A Companion Analysis of the TAX 324 Trial
Authors: Kevin J. Cullen, Lisa Schumaker, Nikolaos Nikitakis, Olga Goloubeva, Ming Tan, Nicholas J. Sarlis, Robert I. Haddad, Marshall R. Posner
Journal: Journal of Clinical Oncology (2009)

TAX 324 was a phase III trial comparing induction chemotherapy (IC) with docetaxel, cisplatin, and fluorouracil (TPF) with cisplatin and fluorouracil (PF) followed by concomitant chemoradiotherapy in locally advanced squamous cell cancer of the head and neck (LASCCHN). This study evaluates a series of tumor markers in pretreatment biopsies from that trial TAX 324 and correlates expression with survival.Pretherapy biopsy specimens were available for 265 of 501 participants. Expression of a series of six markers (p53, thymidylate synthase, glutathione s-transferase pi [GST-pi], Bcl 2, beta tubulin II [betaT-2], and HER2 neu) was evaluated by immunohistochemistry.For patients with low betaT-II expression, median overall survival (OS) was 58.6 months (95% CI, not reached [NR]), compared with 18.2 months for patients with high betaT-II expression (95% CI, 13.11 to 30.06: hazard ratio [HR], 2.39; 95% CI, 1.67 to 3.72; P < .0001). Progression-free survival in patients with low betaT-II expression was 43.2 months (95% CI, 24.4 to NR) versus 9.8 months (95% CI, 7.06 to 18.53) for high betaT-II expression, with a HR of 1.9 (95% CI, 1.43 to 2.77; P < .0001). The predictive value of betaT-II expression was greater in the TPF versus PF arm than in the PF arm.Increased tumor expression of betaT-II is strongly associated with adverse outcome in LASCCHN patients treated with IC, and our data suggest low expression of betaT-II may predict patients most likely to benefit from induction TPF therapy. Further, simple models which combine expression of betaT-II with a carefully defined set of additional immunohistochemical markers may have significant prognostic impact for patients with LASCCHN.
Talking with Patients about Dying
Authors: Thomas J. Smith, Dan L. Longo
Journal: New England Journal of Medicine (2012)

Self-deception is a valuable personal coping tool. It allows us to aspire to significance, strive for new knowledge, and yearn to make a lasting contribution to the world despite the certainty of our inevitable end. Indeed, no arduous task would ever be undertaken if we were unable to exaggerate the benefits we expect from it and underestimate the difficulty of its accomplishment. Daniel Kahneman has called this the “planning fallacy,” our tendency to overestimate benefits and underestimate costs, and thus make foolish decisions to embark on risky pathways.People have an optimistic bias. This optimism helps us cope with the . . .