tbuckley/cabot-search huggingface dataset:
Clinical Lectures: DELIVERED IN ST. BARTHOLOMEW'S HOSPITAL, LONDON
Authors: F. C. Skey
Journal: BMJ (1856)

OX ABDOMINAL TUXOURS AND INTESTINAL PARALYSIS.GuTwrXElx,-In large institutions like this hospital, we have a series of instructive cases always collecting on our hands; and what is instructive and interesting to us surgeons must be interesting also to you as pupils.I therefore pur- pose to-day, though the summer session may be said to be now entirely at an end, and the class may be rather weary of lectures, except on that attractive subject, botany, to go over the details of two or three surgical cases.There is an advantage, also, while the salient features of cases or of pog mortem examinations are flitting through the memory, in fixing the disease or pathological accident, as the case may be, well in the mind.We have always, indeed, in this hospital, as they used to say some time ago, un embarras d richesses-such a crowding of good cases, as they are called, that we must utilise them for your advantage, and keep up with the newest facts both of science aud clinical experience.We are all learners, in fact-all students-all going along in the same groove.The first case to which I wish to draw your attention to- day is that of a young woman with a tumour of the abdo- men or abdominal walls.I will read the heads of the case.This young woman was admitted October 5th, with a large swelling of the abdomen, very particular in appear- ance, and remarkable altogether, as it was so unlike many of the growths we find in this locality.It extended along the rectus muscles to the ensiform cartilage, branching off in its outline, as it struck me at the time of first seeiDg her, something in the shape of the fornix in the brain.It was large and nodulated, and reached into the hypochondrium, as you can imagine a body shaped like the fornix would do.Many surgeons saw the case, and looked, I must confess, very unfavourably at it as to the probable issue.There was no pain, nor did the patient complain of any pain on defecation or micturition.The tumour had been two and a half years in existence; this was also remarkable, taking
Physiological Changes from Maturity Through Senescence
Authors: Richard B. Stoughton
Journal: JAMA (1962)

LET US admit that our knowledge of the physiology of aging is sparse. It is a most entertaining subject to the philosopher and a most elusive subject to the laboratory investigator, nor is it a new subject to the investigator or to the philosopher. Direct measurement of the physiologic functions of primitive and complex organisms during different stages of life has defined physiologic aging in terms of quantitative and occasionally qualitative differences noted with increasing age. This approach is simple and useful, but it has not given much insight to mechanisms.  Some general concepts of the aging process are presented in recent reviews. In brief, some of these concepts are as follows: It is generally agreed that if any single aging process exists, it is unknown at this time. In lower animals the life span can be elongated by either decreasing the basal metabolism rate or the environmental temperature or
DNA adducts as a dosimeter for risk estimation.
Authors: S A Belinsky, C M White, T R Devereux, M W Anderson
Journal: Environmental Health Perspectives (1987)

The dose response for O6-methylguanine (O6MG) formation and cytotoxicity was determined in lung and nasal mucosa from Fischer 344 rats during multiple dose administration of the tobacco-specific nitrosamine-4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK). O6MG accumulated in the lung following treatment for 12 days with doses of NNK from 0.3 to 100 mg/kg/day. The dose response for NNK was nonlinear; the O6MG-to-dose ratio, an index of alkylation efficiency, increased dramatically as the dose of carcinogen decreased. These data suggest that low- and high-Km pathways may exist for activation of NNK to a methylating agent. Marked differences in O6MG concentration were observed in specific lung cell populations. The Clara cell, one of the suggested progenitor cells for nitrosamine-induced neoplasia, was found to possess the greatest concentration of O6MG. Moreover, as the dose of NNK was decreased from 100 to 0.3 mg/kg, the alkylation efficiency in this cell population increased 38-fold. The presence of a high-affinity pathway in the Clara cell for activation of NNK may contribute to the potent carcinogenicity observed following low-dose exposure to this tobacco-specific carcinogen. The dose response for O6MG formation differed considerably between the respiratory and olfactory mucosa from the nasal passages of the rat. The dose response was nonlinear in respiratory mucosa but linear in olfactory mucosa. The alkylation efficiency increased dramatically only in the respiratory mucosa as the dose of NNK was decreased. These studies suggest that a low Km pathway for NNK activation is also present in the nose and that this pathway is localized predominantly in the respiratory region.(ABSTRACT TRUNCATED AT 250 WORDS)
Transformative mutation specific pharmacotherapy for cystic fibrosis
Authors: D. B. Sanders, P. M. Farrell
Journal: BMJ (2012)

Has shown remarkable promise in clinical trials, and could revolutionise treatment

Ever since the discovery of the cystic fibrosis transmembrane conductance regulator gene ( CFTR) in 1989 explained the genetics and pathophysiology of cystic fibrosis,1 healthcare providers, patients, and parents have hoped that a CFTR based treatment would be discovered. The study by Ramsey and colleagues published in November 2011 is a crucial step towards fulfilling that hope.2

In conjunction with Vertex Pharmaceuticals, the Therapeutic Drug Network (TDN) of the US Cystic Fibrosis Foundation (CFF), and the European Cystic Fibrosis Society Clinical Trials Network, 63 cystic fibrosis centres conducted a phase III randomised double blind placebo controlled trial to evaluate the CFTR potentiator developed as VX-770 and then named ivacaftor.3 4 Over 48 weeks, the study assessed 161 patients with cystic fibrosis and at least one specific CFTR mutation (G551D) that decreases CFTR channel function at the cell surface. Ivacaftor is a small molecule that increases the time that activated CFTR channels are open to transmit chloride ions.3 Patients who received ivacaftor had no adverse effects but had a 10.6% absolute increase from baseline in pulmonary function (forced expiratory volume in one second; FEV1)—the study’s primary end point, were 55% less likely to have a pulmonary exacerbation, scored better on the respiratory symptoms domain of the quality of life instrument, gained 2.7 kg more …
A178: Development of Tools to Facilitate Shared Decision Making about Medications for Juvenile Idiopathic Arthritis—A Project of the Pediatric Rheumatology Care and Outcomes Improvement Network
Authors: Esi Morgan DeWitt, Ellen A. Lipstein, Katie Staun, Linda Scherer, Janalee Taylor, Carole M. Lannon, William B. Brinkman
Journal: Arthritis & Rheumatology (2014)

Background/Purpose: Medication options for juvenile idiopathic arthritis (JIA) are increasing. Medications differ on a variety of attributes, including mechanisms of action, dosing intervals, modes of administration, safety profiles, and cost. Some parents of children with JIA are left with questions and concerns about medications suggesting a need for improved clinician‐parent communication. Decisions like this, with multiple reasonable options that differ in ways that matter to families, are conducive to “Shared Decision Making” (SDM). SDM is a process whereby clinicians share information about the options and patients/parents share information about their goals and preferences. Together, a treatment plan is developed that is the best fit for the individual patient and their family. We conducted a project to develop tools to facilitate SDM within the Pediatric Rheumatology Care and Outcomes Improvement Network (PR‐COIN). PR‐COIN is a learning network designed to improve outcomes of JIA care using quality improvement (QI) approaches. Methods: Development of issue cards to facilitate SDM involved multiple steps including qualitative interviews with clinicians and care providers, direct observation of clinical encounters, and an iterative design process involving a graphic designer and a stakeholder panel of clinicians, allied health professionals and parents. We introduced the prototype issue cards for use in clinics using Plan‐Do‐Study‐Act (PDSA) cycles. We elicited feedback to guide card revisions from PR‐COIN members via weekly electronic surveys and discussions during monthly webinars and following direct observation of encounters using the cards. Results: We identified the medication attributes deemed most important to discuss by our stakeholders, including “How Soon” will therapies take effect, “How Often” are they given, “Side Effects”, “Cost”, “How Long” will need to stay on the medication, and “Other Considerations.” We used these attributes to organize the issue cards and symbols to convey key concepts (see Figure). Intended use of the cards involves clinicians showing the cards to patient and parent and asking which card they would like to discuss first. By selecting a card, the family reveals what is important to them. After 18 revisions, PR‐COIN stakeholders at 6 sites found the issue cards to be acceptable for regular use. image Conclusion: PR‐COIN issue cards are well accepted by clinicians and families within network sites. PDSA cycles continue as we seek to implement the issue cards in routine clinical care to facilitate SDM across the network. Our ultimate goal is to drive improvement in child JIA outcomes by reliably engaging patients/parents in SDM to select a medication that is a good fit.
Health Security for All: Dreams of Universal Health Care in America
Authors: Ronald T. Ackermann
Journal: Annals of Internal Medicine (2005)

Medical Writings: Book Notes2 August 2005Health Security for All: Dreams of Universal Health Care in AmericaRonald T. Ackermann, MD, MPHRonald T. Ackermann, MD, MPHFrom Indiana University School of Medicine, Indianapolis, Indiana.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-3-200508020-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Derickson A. 240 pages. Baltimore, MD: Johns Hopkins Univ Pr; 2005. ISBN 0801880815. Order at www.press.jhu.edu.Field of medicine: Health policy, public health, and health care reform.Format: Hardcover book.Audience: Students of health policy, public health, and history of medicine and professionals or activists interested in health care reform.Purpose: To provide an overview of efforts during the past century to achieve universal access to health care in the United States and to educate students of health care reform about the pitfalls and successes of these past efforts in the unique landscape of U.S. politics.Content: This treatise is ... Author, Article, and Disclosure InformationAffiliations: From Indiana University School of Medicine, Indianapolis, Indiana. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 2 August 2005Volume 143, Issue 3Page: 240KeywordsForecastingHealth careHealth care policyHealth information technologyHistory of medicineLiteracyMedical servicesPrevention, policy, and public healthPublic policySoftware tools ePublished: 2 August 2005 Issue Published: 2 August 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Myocardial protection during coronary angioplasty with an autoperfusion balloon catheter in humans.
Authors: P J Quigley, T Hinohara, H R Phillips, R H Peter, V S Behar, Y Kong, C A Simonton, J A Perez, R S Stack
Journal: Circulation (1988)

An autoperfusion balloon catheter was developed to allow passive myocardial perfusion during inflation through a central lumen and multiple side holes in the shaft proximal and distal to the balloon. We report its safety and efficacy in 11 patients undergoing elective angioplasty to a single coronary lesion. Each lesion was dilated three times with the autoperfusion inflation bracketed between two inflations by standard angioplasty catheters. Chest pain score, 12-lead electrocardiogram, heart rate, and mean aortic pressure were recorded before each inflation and at 1-minute intervals after inflation. Inflation duration during autoperfusion angioplasty (513 +/- 303 seconds) was longer than for the pre- (107 +/- 55 seconds, p = 0.0004) and post- (139 +/- 71 seconds, p = 0.0006) standard dilatations. The maximum ST-segment elevation and depression in any lead during autoperfusion angioplasty (0.3 +/- 0.5 and 0.6 +/- 0.8 mm) was significantly less than for the pre- (2.4 +/- 1.7 mm, p = 0.002 and 2.2 +/- 1.3 mm, p = 0.0004) or post- (1.9 +/- 1.3 mm, p = 0.002 and 1.6 +/- 1.3 mm, p = 0.018) standard dilatations at the same point in time. Maximal chest pain score during autoperfusion (3.2 +/- 3.5) was lower than for the pre- (6.1 +/- 2.1, p = 0.003) but not the post- (5.2 +/- 3.1, p = 0.07) standard angioplasty. All 11 patients underwent successful, uncomplicated procedures. We conclude that this autoperfusion catheter significantly reduces ischemic symptoms and signs during coronary angioplasty, allowing prolonged periods of balloon inflation.
P773Uric acid regulates multiple interacting major cellular pathways in human aortic endothelial cells: a global proteome approach
Authors: A Oberbach, V Adams, N Schlichting, N Jehmich, U Voelker, FW Mohr, J Neuhaus
Journal: Cardiovascular Research (2014)

Background: Uric acid (UA) is the end product of the purine metabolism and hyperuricemia has been identified as one major risk factor for cardiovascular diseases. Lowering of serum UA levels seems to improve endothelial dysfunction. Though UA is a potent anti-oxidant it can also induce oxidative stress after entering the endothelial cells via urate transporters. There is growing evidence for multiple UA action on various other cellular pathways contributing to the adverse effects of high UA serum concentrations. Materials and Methods: In this study we sought to elucidate concentration-dependent effects of UA (100 μM, 300 μM, 500 μM) on human aortic endothelial cells. We used NanoLC-MS/MS to analyse protein lysates of HAEC after UA stimulation and ingenuity pathway analysis (IPA) to reveal putative cellular pathways regulated by UA. For validation purposes we measured the abundance or activity of key proteins prototypic for the identified pathway using ELISA, Western blotting, immunohistochemistry and quantified NO production by DAF confocal lasermicroscopy. Results: Our global proteome shot-gun approach and IPA identified ubiquitin-proteasome system (UPS) and eIF4 signalling as the major pathways regulated by UA. Further k-means clustering analysis revealed 11 additional pathways, of which we further validated: NOS signalling, superoxide signalling and hypoxia as the most interesting pathways in respect to endothelial function. We found a complex regulatory network between those pathways demonstrating that 500 μM UA, which is well above the concentration regarded as pathological in clinical settings, leads to diminishing of NO bioavailability. Abatement of NO was accompanied by an increase of eNOS activity but up-regulation of oxidative stress and increase of nitrotyrosinylated proteins (NTP). These finding speak in favour for a drainage of the NO pool to NTP. In addition we found down-regulation of eIF4 and up-regulation of UPS demonstrating the impact of high UA concentrations on HAEC. Conclusions: In summary our data indicate that the control of UA levels is of utmost importance for the cellular homeostasis of endothelial cells. Therefore, consequent hyperuricemia therapy is necessary to counteract cardiovascular strain by elevated sUA levels.
Partners in practice
Authors: C. M Bond
Journal: BMJ (1992)

cardinal symptoms of a pharyngeal pouch also include spontaneous regurgitation, weight loss, and dysphagia.2Barium swallow is the principal means of diagnosing both oesophageal achalasia3 and pharyngeal pouch.Moreover, there is a very real risk of a traumatic oesophageal perforation as a result of entering an unknown pouch, even with a flexible endoscope.Barium swallow is a simple, non-traumatic, cheap, and safe outpatient in- vestigation suitable for most patients with suspected oesophageal pathology, and traumatic oesophageal perforation due to endoscopy in the absence of a barium swallow would be difficult to defend.
KNG1 Ile581Thr and susceptibility to venous thrombosis
Authors: Pierre-Emmanuel Morange, Tiphaine Oudot-Mellakh, William Cohen, Marine Germain, Noémie Saut, Guillemette Antoni, Marie-Christine Alessi, Marion Bertrand, Anne-Marie Dupuy, Luc Letenneur, Mark Lathrop, Lorna M. Lopez, Jean-Charles Lambert, Joseph Emmerich, Philippe Amouyel, David-Alexandre Trégouët
Journal: Blood (2011)
OPTIMIZATION OF VV DELAY OF CRT IS MORE REPRODUCIBLE USING PEAK VELOCITIES THAN USING VELOCITY TIME INTEGRAL, AS WELL AS BEING QUICKER
Authors: Punam A. Pabari, Andreas Kyriacou, Michela Moraldo, Alun D. Hughes, Jamil Mayet, Darrel P. Francis
Journal: Journal of the American College of Cardiology (2011)
Miosis during L-Dopa Therapy
Authors: A. S. D. Spiers, D. B. Calne, P. M. Fayers
Journal: BMJ (1970)

The pupillary diameter of 11 patients with Parkinson's disease was significantly decreased four hours after ingestion of L-dopa. It is suggested that this miosis may be caused by diminished noradrenaline output at sympathetic nerve endings, or alternatively by an action on the central nervous system.
Estrogen Replacement Therapy and Endometrial Hyperplasia-Reply
Authors: Howard Judd
Journal: JAMA (1996)

<h3>In Reply.</h3> —We thank Drs Subbiah and Tsang for their thoughtful letters about our article. Subbiah indicates a need for evaluating the biologic effects of the various estrogen components in CEEs and we would welcome and encourage such studies. Regarding the impact that CEE had on the endometrium, other estrogenic compounds also have been shown to promote the development of endometrial hyperplasia. These include piperazine estrone sulfate, estradiol valerate, estriol hemisuccinate, and transdermal estradiol.<sup>1-3</sup>Even the so-called antiestrogen, tamoxifen, appears to promote the development of endometrial hyperplasia.<sup>4</sup>Thus, the promotion of endometrial overgrowth is likely a generic response to the class of steroids called estrogens and not to any one single estrogen. Tsang questions if it is possible to predict which women with endometrial hyperplasia will revert to normal with progestin therapy and suggests the measurement of ER/PRs may predict the response of hyperplasia to progestin therapy. We
A SIMPLE METHOD OF MECHANICAL FIXATION FOR FRACTURE OF LONG BONES
Authors: J. E. Adams
Journal: BMJ (1918)

THiE methods commlonly emnployed in the operative treat- inient of fractures arc all more or less laborious, andl-altlhouLglh the results amply justify the necessary ex- penditure of time and trouble, it appears to me that the methods of carpentry as' exemplified by the use of plates, bolts, and screws, require modification in their application to a surgical problem.The use of a bone graft may be more strictly surgical, buit it is certainly laborious even with electrical saws and siinila' apparatus at the surgeon's disposal.Simplicity in all operative procedures is greatly to be desired, for, when the technique of an operation is easy, the risks of failure are correspondingly diminislhed.In the case of broken bones it is also most desirable to have a method of fixation applicable to compound as well as simple fractures, and it
Early intervention with allogeneic hematopoietic cell transplantation during chemotherapy-induced aplasia in patients with high-risk acute myeloid leukemia
Authors: F Stölzel, U Platzbecker, B Mohr, C Röllig, J M Middeke, C Thiede, M Füssel, M Hänel, M Schaich, G Ehninger, J Schetelig, M Bornhäuser
Journal: Leukemia (2013)
Primary Cutaneous B-Cell Lymphoma Treated With Radiotherapy: A Comparison of the European Organization for Research and Treatment of Cancer and the WHO Classification Systems
Authors: Benjamin D. Smith, Earl J. Glusac, Jennifer M. McNiff, Grace L. Smith, Peter W. Heald, Dennis L. Cooper, Lynn D. Wilson
Journal: Journal of Clinical Oncology (2004)

To determine the relationship between the WHO and European Organization for Research and Treatment of Cancer (EORTC) pathologic classifications for primary cutaneous B-cell lymphoma (CBCL) and the implication of this relationship on initial treatment.Patients with primary CBCL treated with radiotherapy were identified retrospectively. Initial biopsy specimens were reviewed by two dermatopathologists and classified according to the EORTC and WHO systems. Primary outcomes were recurrence-free and overall survival.Thirty-four patients were identified; initial biopsy specimens were adequate for classification in 32 patients. Four different composite histopathologic subtypes of lymphoma were identified: 53% (17 of 32) follicle center cell by EORTC and diffuse large B-cell by WHO (FCC/DLB), 25% (eight of 32) follicle center cell by EORTC and follicular by WHO (FCC/Fol), 13% (four of 32) marginal zone by EORTC and WHO (MZ/MZ), and 9% (three of 32) large B-cell of the leg by EORTC and diffuse large B-cell by WHO (Leg/DLB). Five-year relapse-free survival ranged from 62% to 73% for FCC/DLB, FCC/Fol, and MZ/MZ but was 33% for Leg/DLB (P =.6). Five-year overall survival was 100% for FCC/DLB, FCC/Fol, and MZ/MZ but was 67% for Leg/DLB (P =.07). At 5 years, 21% of all patients had developed extracutaneous disease.Two-thirds of primary cutaneous FCC lymphomas by EORTC criteria satisfy WHO criteria for DLB lymphoma. Unlike DLB lymphoma presenting in nodal or noncutaneous sites, these lesions are associated with an indolent course and may be treated with local radiotherapy alone.
Vascular effects of environmental oestrogens: implications for reproductive and vascular health
Authors: R. K. Dubey
Journal: Human Reproduction Update (2000)

Environmental oestrogens are defined as xenobiotics structurally resembling oestrogen, and are divided into two broad categories, xeno-oestrogens and phyto-oestrogens. Environmental oestrogens may contribute importantly to the increased incidence of reproductive disorders in the modern environment. Although the mechanisms by which environmental oestrogens induce their deleterious effects on the reproductive system remain poorly defined, it is likely that the vascular effects of these compounds play a critical role. In this regard, oestradiol strongly regulates both angiogenesis and vascular remodelling by influencing the growth and function of vascular endothelial cells (EC) and smooth muscle cells (SMC). Since blood vessels, by undergoing angiogenesis, vascular regression and vascular remodelling, actively participate in the normal functioning of reproductive organs, environmental oestrogens---by mimicking or antagonizing the vascular effects of oestradiol---may induce abnormalities in vascular function and structure leading to reproductive disorders such as pre-eclampsia, endometriosis, impaired follicular development, inefficient implantation, impotence and infertility. The purpose of the present review is to summarize the evidence regarding the vascular effects of xeno-oestrogens and phyto-oestrogens and to discuss the implications for these effects on the reproductive system.