tbuckley/cabot-search huggingface dataset:
Online music model could work for journals
Authors: Nicholas D Moore
Journal: BMJ (2005)

Right to die" Legal view of right to life and death could threaten philosophy of palliative careEditor-Grayling claims that the "right to life" means quite a rich life; withholding treatment with death as the result and giving treatment that causes death are indistinguishable; and death is the ultimate analgesic. 1 Grayling also implies that the double effect is widely abused.The EC Convention for the Protection of Human Rights and Fundamental Freedoms protects against intentional deprivation of life. 2 Quality of life is not mentioned, and terminating a life at a person's request is clearly not permitted."Right to life" is perhaps a "right not to be killed," in medicine, generally relating to survival and not assisted death.However, some interpret it as giving patients a right to cardiopulmonary resuscitation regardless of the clinical circumstances 3 ; extrapolation to all potential interventions at the life-death interface could have disastrous consequences for the medical profession.Patients obviously can wish for their life to be terminated without needing to explain why, and they arguably have a right to attempt suicide.However, a right to assisted dying equates to a right that somebody else will kill or help to kill them on request-very different from withholding treatment or the double effect.Withholding treatment relates to interventions unable to produce the desired benefit. 4 In palliative care withholding treatment does not directly cause death that arises from an irreversible and unsustainable pathological burden.And death without adequate analgesia is possibly the ultimate pain for everyone.Judicious use of analgesia is an essential part of good terminal care, and, in 15 years as a doctor, I have yet to see a death attributable to deliberate analgesic overdose by a doctor.Palliative care affirms life until the moment of death, regarding death from advanced incurable disease as a natural process. 5 It aims to relieve pain and other distressing symptoms, enhance remaining quality of life, and neither hasten nor postpone death.These human "death rights" should perhaps be protected by legislation.Ill-conceived legislative changes that take the right to life or the right to death beyond sensible limits or give certain doctors the right to kill on request could jeopardise palliative care.
Age-Dependent Association of Apolipoprotein E Genotype With Coronary and Aortic Atherosclerosis in Middle-Aged Men
Authors: Erkki Ilveskoski, Markus Perola, Terho Lehtimäki, Pekka Laippala, Vesa Savolainen, Jarkko Pajarinen, Antti Penttilä, Kaisa H. Lalu, Antti Männikkö, Kimmo K. Liesto, Timo Koivula, Pekka J. Karhunen
Journal: Circulation (1999)

Background —Apolipoprotein E (apoE) polymorphism is one of the genetic determinants of serum cholesterol values. The apoE ε4 allele has been associated with advanced coronary heart disease (CHD) diagnosed by angiography, but the role of the apoE genotype in atherosclerosis has not been confirmed at vessel-wall level, nor is any age-dependent effect of the apoE genotype on the development of CHD known. Methods and Results —The right and left anterior descending coronary arteries (RCA and LAD) and the aorta from 700 male autopsy cases (Helsinki Sudden Death Study) in 1981-1982 and 1991-1992 (average age 53 years, range 33 to 70 years) were stained for fat, and all areas covered with fatty streaks, fibrotic plaques, and complicated lesions were measured. In the RCA and LAD, the apoE genotype was significantly associated with the area of total atherosclerotic lesions in men &lt;53 years old but not with that in older men ( P =0.0085 and P =0.041, respectively, for age-by-genotype interaction). Men &lt;53 years old with the ε4/3 genotype showed 61% larger total atherosclerotic lesion area in the RCA ( P =0.0027) and 26% larger area in the LAD ( P =0.12) than did men with the ε3/3. The apoE ε4/3 was also associated with atherosclerotic lesions in the abdominal ( P =0.014) and thoracic ( P =0.12) aorta, but this effect, unlike that of the coronary arteries, was not age-related. Conclusions —In men, the apoE ε4 allele is a significant genetic risk factor for coronary atherosclerosis in early middle age. This suggests that at older age, other known risk factors of CHD play a more important role in the atherosclerotic process than apoE polymorphisms.
Spontaneous Bacterial Peritonitis and Pneumoperitoneum
Authors: Eugene B. Loftin
Journal: JAMA (1983)

<h3>To the Editor.—</h3> A recent article by Woelfel and Hansbrough described a 63-year-old man with spontaneous bacterial peritonitis and pneumoperitoneum (1983;249:921). My surgical colleague (Arthur R. Marks, MD, of Fairfield, Ill) and I have recently seen a similar case. <h3>Report of a Case.—</h3> A 55-year-old man was admitted to Fairfield Memorial Hospital on June 22, 1982, with complaints of abdominal pain of two days' duration associated with "chills" but no fever. He had undergone resection of adenocarcinoma of the colon in August 1981. Sigmoidoscopy and air-contrast study of the colon were done in March 1982 and showed no evidence of recurrence and no intraperitoneal air. The abdominal examination on admission showed active bowel sounds and diffuse tenderness to palpation but no rebound tenderness. Roentgenograms of the abdomen taken when the patient was upright showed subdiaphragmatic intraperitoneal gas above the dome of the liver. On complete blood cell count, he had
Studies on the Antithrombin and Heparin Co-factor Activities of a Fraction Adsorbed from Plasma by Aluminum Hydroxide
Authors: FRANK C. MONKHOUSE, EVELYN S. FRANCE, WALTER H. SEEGERS
Journal: Circulation Research (1955)

A chemical method has been devised for the quantitative determination of plasma antithrombin. A concentrate of antithrombin has been prepared from plasma. It also contains heparin cofactor activity. The two distinct activities could not be separated and may quite possibly be the properties of a single substance. When the concentrate is combined with heparin the capacity of the concentrate to destroy thrombin is not increased but there is interference with the thrombin fibrinogen interaction. In a mixture of the concentrate and thrombin there is simultaneous destruction of antithrombin, and thrombin activities. Small amounts of the concentrate significantly prolong the clotting time of blood.
Serum levels of novel noggin and sclerostin-immune complexes are elevated in ankylosing spondylitis
Authors: Florence W L Tsui, Hing Wo Tsui, Facundo Las Heras, Kenneth P H Pritzker, Robert D Inman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Unravelling the basis of joint inflammation and ankylosis represents a major challenge in ankylosing spondylitis (AS) research. As noggin (NOG) and sclerostin (SOST) have recently been associated with the disease process in mouse and human studies, respectively, we explored the immune responses to these two molecules in AS. <h3>Methods</h3> Immune complexes (IC) composed of IgG autoantibodies to NOG and SOST were detected by immunoprecipitation and Western blot analyses. Epitope-specific IgG were measured using peptide-binding ELISA. Serum samples were obtained from healthy controls and patients with AS, mechanical back pain (MBP) and inflammatory bowel disease (IBD) with or without concomitant AS. <h3>Results</h3> NOG and SOST-IgG IC were present in NOG-treated and untreated <i>ank/ank</i> (progressive ankylosis), but not in wild-type mice. Higher than normal levels of NOG and SOST-IgG IC are present in AS sera (p&lt;0.001). We showed a SOST peptide (SOST-S146, with homology to a bacterial glycotransferase peptide) binds to a NOG peptide (NOG-N54), which contains a N-glycosylation site. AS patients have higher levels of IgG recognising the NOG-N54 and SOST-S146 peptides compared to the levels in normal controls, IBD and MBP patients (one way analysis of variance p&lt;0.0001). <h3>Conclusions</h3> This is the first report showing IgG autoantibodies to NOG and SOST in normal individuals, and higher levels of NOG and/or SOST-IgG IC probably contribute to neo-ossification in AS patients. These novel findings hold the promise of earlier diagnosis, better management of AS with comorbidities and new therapeutic approaches to modulate ankylosis in AS.
The Effect of Smoking Cessation and Subsequent Resumption on Absorption of Inhaled Insulin
Authors: Reinhard H.A. Becker, Sue Sha, Annke D. Frick, Robert J. Fountaine
Journal: Diabetes Care (2006)

OBJECTIVE—To assess the absorption profile of inhaled insulin in healthy, actively smoking subjects at baseline, after smoking cessation, and after smoking resumption and compare it with nonsmoking subjects. RESEARCH DESIGN AND METHODS—Insulin pharmacokinetics and glucodynamics were measured in 20 male smoking subjects (10–20 cigarettes/day) and 10 matched nonsmoking subjects after receiving inhaled insulin (1 mg) or the approximate subcutaneous insulin equivalent (3 units) in a randomized cross-over fashion. All smokers then received inhaled insulin 12 h, 3 days, and 7 days into a smoking cessation period. They then resumed smoking for 2–3 days before again receiving inhaled insulin 1 h after the last cigarette. RESULTS—Before smoking cessation, maximum insulin concentration (Cmax) and area under the curve (AUC) for insulin concentration time (AUC-Insulin0–360) with inhaled insulin were higher, and time to Cmax (tmax) shorter, in smokers than nonsmokers (Cmax 26.8 vs. 9.7 μU/ml; AUC-Insulin0–360 2,583 vs. 1,645 μU · ml−1 · min−1; tmax 20 vs. 53 min, respectively; all P &amp;lt; 0.05), whereas with subcutaneous insulin, systemic exposure was unchanged (AUC-Insulin0–360 2,324 vs. 2,269 μU · ml−1 · min−1; P = NS). After smoking cessation, AUC-Insulin0–360 decreased with inhaled insulin by up to 50% within 1 week and approached nonsmoker levels. Cmax decreased and tmax increased relative to baseline but were still not comparable with nonsmoker values. Smoking resumption completely reversed the effect of smoking cessation. Glucodynamics corroborated the observed findings in insulin pharmacokinetics. CONCLUSIONS—Cessation and resumption of smoking greatly altered the pharmacokinetics of inhaled insulin. As rapid changes in systemic insulin exposure increase hypoglycemia risk, inhaled insulin should not be used in people with diabetes who choose to continue smoking. This is consistent with recommendations that people with diabetes refrain from smoking altogether.
Immune-Induced Epithelial to Mesenchymal Transition <i>In vivo</i> Generates Breast Cancer Stem Cells
Authors: Marta Santisteban, Jennifer M. Reiman, Michael K. Asiedu, Marshall D. Behrens, Aziza Nassar, Kimberly R. Kalli, Paul Haluska, James N. Ingle, Lynn C. Hartmann, Masoud H. Manjili, Derek C. Radisky, Soldano Ferrone, Keith L. Knutson
Journal: Cancer Research (2009)

The breast cancer stem cell (BCSC) hypotheses suggest that breast cancer is derived from a single tumor-initiating cell with stem-like properties, but the source of these cells is unclear. We previously observed that induction of an immune response against an epithelial breast cancer led in vivo to the T-cell-dependent outgrowth of a tumor, the cells of which had undergone epithelial to mesenchymal transition (EMT). The resulting mesenchymal tumor cells had a CD24(-/lo)CD44(+) phenotype, consistent with BCSCs. In the present study, we found that EMT was induced by CD8 T cells and the resulting tumors had characteristics of BCSCs, including potent tumorigenicity, ability to reestablish an epithelial tumor, and enhanced resistance to drugs and radiation. In contrast to the hierarchal cancer stem cell hypothesis, which suggests that breast cancer arises from the transformation of a resident tissue stem cell, our results show that EMT can produce the BCSC phenotype. These findings have several important implications related to disease progression and relapse.
Analysis of human skin surface lipid during treatment with anti-androgens
Authors: SHUSHMA PATEL, W.C. NOBLE
Journal: British Journal of Dermatology (1987)

Journal Article Analysis of human skin surface lipid during treatment with anti‐androgens Get access SHUSHMA PATEL, SHUSHMA PATEL Department of Microbial Diseases, Institute of Dermatology, United Medical anil Denial Schools of Guy's and St Thomas's Hospitals, London U.K. Search for other works by this author on: Oxford Academic Google Scholar W.C. NOBLE W.C. NOBLE Department of Microbial Diseases, Institute of Dermatology, United Medical anil Denial Schools of Guy's and St Thomas's Hospitals, London U.K. Professor W.C.Noble, Department of Microbial Diseases, Institute of Dermatology (UMDS), Lambeth Hospital, London SEII 4TH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 6, 1 December 1987, Pages 735–740, https://doi.org/10.1111/j.1365-2133.1987.tb07353.x Published: 01 December 1987
Changes in nystagmus on raising body temperature in clinically suspected and proved multiple sclerosis.
Authors: J V Jestico, P D Ellis
Journal: BMJ (1976)

Electronystagmography was used to record the appearance or alteration of nystagmus after raising the body temperature by a heat cradle. Nystagmus was increased or provoked in 13 out of 15 patients with clinically proved multiple sclerosis, in eight out of 12 suspected cases, but in no normal controls. No positive results were obtained in 12 patients with other neurological diseases, even when nystagmus was part of the clinical picutre. The technique is simple to use and may have a role in the diagnosis of multiple sclerosis.
A foray into unfamiliar territory
Authors: Charles P Swainson
Journal: BMJ (2006)

I went to a GP surgery one day recently. Not as a patient, you understand, but as a visitor. I have seen my own GP only once in the past five years, for trivial complaints, and haven't visited a general practice to see how they work for 10 years. As the medical director of a large teaching board in Scotland, with responsibility for primary care as well as hospital services, it was time for me to learn.

I chose a practice in one of the most deprived areas of my patch. Car parking was easy to find on one of the streets around the corner from the practice. The reception area was nicely furnished and freshly painted, with signs clearly showing where to go and which doctors were consulting that morning. The receptionists were busy but polite and welcoming. I noticed that their desks had no telephones, so they were not interrupted and could deal with everyone almost as soon as they arrived.

> The GPs were wearing chinos, open …
More on Control of Nosocomial Infection in Hospitals
Authors: Paul F. Wehrle
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The response to the inquiry presented only one side of a most complex question. The table on page 579 was published apparently without peer review and certainly without evidence that numbers of bacterial colonies above the "acceptable number of colonies" have been associated with illness among hospitalized patients. This table may be accepted as fact by the unwary and lead to extensive although misguided monitoring of the environment, with waste of laboratory resources and possibly resultant destructive litigation, leading to serious charges. Three of the four examples of environmental contamination resulting in disease represent the result of poor maintenance of air conditioners. Bacteriologic monitoring isn't needed to detect bird feathers in air conditioners! The fourth example, a contaminated nebulizer, is an easily correctable hazard, and one of the many that have been identified promptly by appropriate surveillance techniques. The AHA Committee on Infections Within Hospitals has considered
A 51-Year-Old Woman With Bipolar Disorder Who Wants to Quit Smoking
Authors: S. A. Schroeder
Journal: JAMA (2009)

Smoking among patients with mental illness is a major and underappreciated public health problem. The case of Ms G, a 51-year-old woman with bipolar disorder who wishes to quit smoking, illustrates the importance and feasibility of smoking cessation in patients with psychiatric disorders. Persons with chronic mental illness and/or substance abuse constitute 22% of the US population yet are estimated to consume 44% of cigarettes. As many as 200 000 of the 435 000 annual deaths related to smoking in the United States are estimated to occur in this population. On average, patients with mental illness die 25 years earlier than the general population, and smoking is a major contributor to these premature deaths. In the past, mental health clinicians have tended not to address smoking cessation with their patients, but increasing evidence suggests that such reticence is unwarranted, as smoking cessation in this population is feasible. The approach to cessation should include standard interventions of counseling and pharmacotherapy, for which substantial evidence of efficacy exists in patients with and without mental illness. If patients with mental illness are to achieve wellness, smoking cessation must be an integral component of their treatment regimen.
Disentangling Mild Traumatic Brain Injury and Stress Reactions
Authors: Richard A. Bryant
Journal: New England Journal of Medicine (2008)

The study by Hoge and colleagues in this issue of the Journal provides an important profile of the sequelae of mild traumatic brain injury in military personnel after combat.1 The findings demonstrate that mild traumatic brain injury results in increased rates of psychological, health, and functional problems. Although the study provides strong evidence for impairments in military personnel serving in Iraq and Afghanistan, it also raises a number of critical questions concerning the impairments that may be attributed to mild traumatic brain injury.One striking finding from this study is that although mild traumatic brain injury predicted a range of . . .
Abstract 4467: Targeting both PI3K/mTOR and EGFR pathways leads to synergistic anti-tumor activity in erlotinib resistant non-small-cell lung cancers.
Authors: Pramod P. Mehta, Sangita M. Baxi, Marlena Walls, Stella Chen, Hengmiao Cheng, Gang Li, Tod Smeal, Min-Jean Yin
Journal: Cancer Research (2013)

Abstract NSCLCs with EGFR mutations, such as a deletion in exon 19 (del E746-A750) or point mutation in exon 21 (L858R), are sensitive to TKI (gefitinib and erlotinib) treatments. However, acquired resistance to TKI therapy occurs in patients after 12-14 months. Approximately 50% of these resistant patients have developed secondary (gatekeeper) T790M mutation in EGFR; many other resistance mechanisms also have been described including a PIK3CA mutation and PTEN deletion. In this study, we characterize a dual PI3K/mTOR inhibitor, PF-4979064, in combination with a pan-ErbB inhibitor, PF-299804 (dacomitinib) in erlotinib resistant NSCLC lines NCI-H1975 (harboring EGFR and PIK3CA mutation) and NCI-H1650 (harboring EGFR and PTEN deletion). As a clinically relevant concentration of PF-299804 only induces moderate anti-tumor activity in both H1975 and H1650 cells, PF-4979064 was added in a variety of cellular and animal studies to determine whether the combination was able to achieve a synergistic induction of anti-tumor activity. Results demonstrate that the combination of PF-4979064 and PF-299804 lead to a synergistic inhibition in cell proliferation and xenograft tumor growth in both the NCI-H1975 and NCI-H1650 models. Our results further suggest that there is a rationale to examine a potential clinical development plan combining the dual PI3K/mTOR inhibitor (PF-4979064) and dacomitinib (PF-299804) in NSCLC patients who have developed resistance to erlotinib and have a concomitant PIK3CA mutation or PTEN deletion. Citation Format: Pramod P. Mehta, Sangita M. Baxi, Marlena Walls, Stella Chen, Hengmiao Cheng, Gang Li, Tod Smeal, Min-Jean Yin. Targeting both PI3K/mTOR and EGFR pathways leads to synergistic anti-tumor activity in erlotinib resistant non-small-cell lung cancers. [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 4467. doi:10.1158/1538-7445.AM2013-4467
Acute Alcohol Action and Desensitization of Ligand-Gated Ion Channels
Authors: Alex M. Dopico, David M. Lovinger
Journal: Pharmacological Reviews (2009)

Ethanol exerts its biological actions through multiple receptors, including ion channels. Ion channels that are sensitive to pharmacologically relevant ethanol concentrations constitute a heterogeneous set, including structurally unrelated proteins solely sharing the property that their gating is regulated by a ligand(s). Receptor desensitization is almost universal among these channels, and its modulation by ethanol may be a crucial aspect of alcohol pharmacology and effects in the body. We review the evidence documenting interactions between ethanol and ionotropic receptor desensitization, and the contribution of this interaction to overall ethanol action on channel function. In some cases, such as type 3 serotonin, nicotinic acetylcholine, GABA-A, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors, ethanol actions on apparent desensitization play a significant role in acute drug action on receptor function. In a few cases, mutagenesis helped to identify different areas within a receptor protein that differentially sense <i>n</i>-alcohols, resulting in differential modulation of receptor desensitization. However, desensitization of a receptor is linked to a variety of biochemical processes that may alter protein conformation, such as the lipid microenvironment, post-translational channel modification, and channel subunit composition, the relative contribution of these processes to ethanol interactions with channel desensitization remains unclear. Understanding interactions between ethanol and ionotropic receptor desensitization may help to explain different ethanol actions 1) when ethanol is evaluated in vitro on cloned channel proteins, 2) under physiological or pathological conditions or in distinct cell domains with modified ligand concentration and/or receptor conformation. Finally, receptor desensitization is likely to participate in molecular and, possibly, behavioral tolerance to ethanol, which is thought to contribute to the risk of alcoholism.
Hashimoto??s Thyroiditis Presenting as Hot and Cold Nodules
Authors: RIAD A. SULIMANI, MAHMOUD EL-DESOUKI
Journal: Clinical Nuclear Medicine (1990)

A case of Hashimoto's thyroiditis is presented. I-123 thyroid scintigraphy demonstrated a hot nodule in the left lobe and a cold nodule in the right, which was well visualized by TI-201 imaging. This unusual scintigraphic appearance is demonstrated, and its possible explanation discussed.
BK channels in innate immune functions of neutrophils and macrophages
Authors: Kirill Essin, Maik Gollasch, Susanne Rolle, Patrick Weissgerber, Matthias Sausbier, Erwin Bohn, Ingo B. Autenrieth, Peter Ruth, Friedrich C. Luft, William M. Nauseef, Ralph Kettritz
Journal: Blood (2008)