tbuckley/cabot-search huggingface dataset:
Blockade of cardiac sodium channels. Competition between the permeant ion and antiarrhythmic drugs.
Authors: M J Barber, D J Wendt, C F Starmer, A O Grant
Journal: Journal of Clinical Investigation (1992)

A number of basic and clinical studies suggest that elevation of external sodium concentrations, [Na]o, may reverse the cardiotoxic effect of local anesthetic-class drugs. The mechanisms of reversal are uncertain. The blocking action of lidocaine and disopyramide were studied over a range of [Na]o. Both whole-cell voltage clamp and single-channel recordings were performed on isolated rabbit myocytes at 17 and 22 degrees C, respectively. In the presence of lidocaine, an inactivated channel blocker, the level of steady-state block in response to pulse train stimulation was not affected by variations in [Na]o from 20 to 150 mM. Estimates of the rate of dissociation of drug from the channel also were unaffected. In contrast, steady-state block by disopyramide, a drug that blocks open channels, was decreased as [Na]o was increased. Single-channel measurements suggest that the influence of [Na]o on channel current amplitude was small, 12% for a 25 mM increase in [Na]o. This increase in single-channel current amplitude would affect drug-free channels only, in that our studies suggest that drug-associated channels do not conduct. The association rate constant of disopyramide with open single sodium channels was decreased from 10 x 10(6) to 5 x 10(6)/M per s by an increase in [Na]o from 120 to 180 mM. Elevation of [Na]o may reverse the blocking action of local anesthetic-class drugs by an increase in single-channel current amplitude or by a decrease in drug association rate with the sodium channel. The occurrence of the latter action depends on the mode of block of the specific agent.
Unblocking coronary arteries
Authors: M. Purkiss
Journal: BMJ (1982)

of staff were able to complete their deliveries and did not subsequently take time off work.No compound fractures were sustained by these persons, although, as suggested by Dr Snook, radiological investigation should be considered following deep limb bites.For those injured, the lower limb was bitten in 70%0 of attacks, the upper limb in 27%, and the trunk in 3%h of attacks.To reduce the number of bitten postal staff, it should be noted that 16 of the 53 upper limb injuries occurred when mail was placed through front- door letter boxes into the expectant jaws beyond.Apparently the tempting sight of intruding digits cannot be resisted.The attacks were otherwise unprovoked.Avoidance may be a learned response: 76% of the staff attacked during these three years were bitten only once.The expression "once bitten, twice shy," therefore has numerical support.
Some Recollections of Sir William Osler at Oxford
Authors: A. D. Gardner
Journal: JAMA (1969)

Two separate periods of my life brought me into frequent contact with Sir William Osler, with ample opportunity to feel and see the influence of his powerful mind and personality on myself, my friends, and colleagues in the Oxford medical school. The first period was when I was a preclinical student in 1905 to 1908. Osler was in his late fifties, and full of vigor, having come to Oxford as Regius Professor of Medicine in 1904. We were a very small band of medical students, not more than 20, I think, in the whole University—itself less than 3,000 students. I myself had taken my degree in jurisprudence (law), and had moved over enthusiastically to medicine. At that time the University offered only a preclinical course, of which, however, the physiology course was reputed the best in the country. In this setting, Osler's clinical preeminence made little impact on us, though
Assessing Quality of Life During Chemotherapy for Pleural Mesothelioma: Feasibility, Validity, and Results of Using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire and Lung Cancer Module
Authors: Anna K. Nowak, Martin R. Stockler, Michael J. Byrne
Journal: Journal of Clinical Oncology (2004)

Purpose To assess the feasibility and validity of using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and Lung Cancer Module (QLQ-LC13) to describe health-related quality of life (HRQL) in patients with pleural mesothelioma undergoing combination chemotherapy, to identify the most impaired aspects of HRQL, and to assess the impact of chemotherapy on HRQL. Patients and Methods Fifty-three patients received cisplatin on day 1 and gemcitabine on days 1, 8, and 15 of a 28-day cycle for a maximum of six cycles. HRQL was assessed using the EORTC QLQ-C30 and QLQ-LC13. Results Compliance was 100% at baseline but subsequently decreased. At baseline, role function and social function were the most impaired domains, and the worst-rated symptoms were fatigue, dyspnea, pain, insomnia, appetite loss, and cough. Dyspnea, pain, insomnia, and cough improved with chemotherapy, although functional domains and chemotherapy-related symptoms deteriorated. Fatigue remained unchanged. Few patients reported hemoptysis. Functional domains and symptoms scales from the QLQ-C30 demonstrated predictive validity for survival. The predictive value of QLQ-LC13 pain scores was improved by combining three pain items into a single score. Dyspnea scores were correlated strongly with lung function as measured by forced vital capacity. Conclusion This study supports the validity of the EORTC QLQ-C30 and LC13 as outcome measures for trials of chemotherapy in mesothelioma. Although the most prominent symptoms reported were concordant with clinical experience, impairments in role and social function and insomnia were worse than expected. Future research should focus on how best to apply, analyze, and interpret existing, validated HRQL instruments in mesothelioma research and practice, not on the development of new ones.
Intractable mycobacterial infections associated with genetic defects in the receptor for interferon gamma: what does this tell us about immunity to mycobacteria?
Authors: G. A. Rook
Journal: Thorax (1997)

The attenuated strain of Mycobacterium bovis bacille Calmette-Gue ´rin (BCG) is the most widely used vaccine in the world.In most children, inoculation of live BCG vaccine is harmless although it occasionally leads to a benign regional adenitis.In rare cases, however, vaccination causes disseminated BCG infection, which may be lethal.Impaired immunity of the host is generally thought to be the pathogenic mechanism.Disseminated BCG infection has been reported in children with inherited immune disorders.Most of these children had severe combined immunodeficiency, which is characterized by an absence of T cells, and some had chronic granulomatous disease, which is marked by an impairment of the phagocyte respiratory burst.Rare cases of BCG infection have also been reported in association with the acquired immunodeficiency syndrome.We examined the five genes coding for interferon-, interferon-R1, IRF1, TNF-, and TNF-R1 in a child with fatal idiopathic disseminated BCG infection.We found a mutation of the gene for interferon-R1.There was no detectable interferon-R1 on the cells from the affected child.These findings provide further evidence of the importance of interferonin the response to mycobacterial infection.
Adrenal Cortical Tumours
Authors: G. Lumb
Journal: BMJ (1950)

PNEUMONIA MEDIBJOURNALTwenty-five active and 4 inactive cases of pulmonary tuber- culosis were disclosed.Twenty-seven further cases of disease were revealed.They included tuberculous effusion (6), bronchiectasis (11), new growth (4), lung abscess (1), spontaneous pneumothorax (1), cardiac (3), and cough fracture (1).It has been argued that radiography should be widely applied to the symptom-complex of "pneumonia."
Children with asthma: will nebulised salbutamol reduce hospital admissions?
Authors: J L Pearce, H M Wesley
Journal: BMJ (1985)

To find out how many children with acute asthma responded to one or two doses of nebulised salbutamol and whether this response could be predicted 100 children were studied prospectively from two district hospitals. Twenty three children needed only one nebulised dose and 19 responded to two. Significant factors differentiating these responders from the remainder were age (24 (63%) of those aged 6 or more responded compared with only six (19%) of those aged 3 or less); regular treatment with a beta 2 sympathomimetic; and use of a rotahaler or aerosol. Those requiring more intensive treatment had faster pulse and respiratory rates on admission and one hour after the first nebulised dose. Another useful clinical sign was persistent supraclavicular indraw. Pulsus paradoxus and peak expiratory flow rate were of limited value in the younger children who had worse asthma. Of 29 children receiving intravenous treatment, 18 (62%) were aged 3 or less, whereas only two (7%) were aged 6 or over. The older children who responded initially to nebulised salbutamol could have been safely reassessed at home, which would have considerably reduced hospital admissions.
Role of protein kinase C in pitavastatin-induced human paraoxonase I expression in Huh7 cells
Authors: Kaoru Arii, Tadashi Suehiro, Yukio Ikeda, Yoshitaka Kumon, Mari Inoue, Syojiro Inada, Hiroshi Takata, Ayako Ishibashi, Kozo Hashimoto, Yoshio Terada
Journal: Metabolism (2010)
Measuring performance in the NHS
Authors: M. McKee, T. Sheldon
Journal: BMJ (1998)

Last Wednesday the government launched its consultation paper on assessing performance,1 the latest element of its strategy to reform the NHS.2 It proposes moving from a narrow focus on activity and financial targets to a wider view of what the NHS is seeking to achieve and suggests a framework for achieving it. The intention to concentrate on issues that concern patients and health professionals, rather than meaningless measures such as the efficiency index,3 is welcome. But the paper is strangely silent on how to make these new measures work.

The paper proposes six areas where performance should be assessed: improving the health of the general population; fair access to services; effective delivery of appropriate care; efficiency; patient-carer experience; and the outcome of NHS care. Comparative information will be published, and targets for improvement in each of these areas will be an integral part of performance management in the NHS. Although the consultation document does not mention it, …
Admissions from emergency departments rise as four hour target approaches
Authors: H. Mooney
Journal: BMJ (2009)

The number of patients leaving emergency departments each minute rises with the approach of the government’s four hour maximum waiting time target, research has shown. The rise is especially marked in the 10 minutes before the deadline expires, with 6% of all patients attending emergency departments in England being seen and treated in this time. 

The research, published by the NHS Information Centre on 18 November, also shows that the percentage of patients leaving emergency departments who are admitted to hospital rises markedly …
NICE guidance has failed to end “postcode prescribing”
Authors: Caroline White
Journal: BMJ (2004)

<h3>Introduction</h3> Bipolar disorder (BD) is a severe mental health disorder that affects 2% of the adult population. Individuals with this disorder are at a higher risk for morbidity and functional difficulties. They may also experience significant challenges in their activities of daily living (ADLs). This systematic review will identify all available studies that examine subsets of ADLs that impact individuals with BD. <h3>Methods and analysis</h3> MEDLINE, Embase, CINAHL and APA PsycINFO will be searched to identify observational studies that examined functioning, independence or performance across a variety of ADLs. Title and abstract, full-text screening and a risk of bias assessment will be conducted in duplicate. An overarching table that summarises the level of functioning across different ADLs or an ‘ADL profile’ will be developed, and if there are sufficient data, these will be separated based on the phases of BD, such as manic/hypomanic, depressed and euthymic. <h3>Ethics and dissemination</h3> As this systematic review uses information from previous literature, this review does not require ethics approval. This review will help identify the trends in daily activities that individuals struggle with and can help healthcare practitioners identify specific areas of need for support. We plan to disseminate the results in a peer-reviewed journal and conferences targeting occupational therapists and mental health clinicians. <h3>PROSPERO registration number</h3> CRD42021255089.
Diabetes Mellitus in the Internal Medicine Literature
Authors: Charles R Shuman
Journal: Diabetes Care (1978)

The format of Mini-Reviews is the presentation of abstracts of selected articles, with commentary on the topics raised by these articles. Previous Mini-Reviews in DIABETES CARE examined the literature on Psychosocial Issues in Diabetes, and Diabetes in the Pediatric Literature. All summaries in this Mini-Review of Diabetes Mellitus in the Internal Medicine Literature are verbatim.
Researchers, Readers, and Reporting Guidelines
Authors: Robert M. Golub, Phil B. Fontanarosa
Journal: JAMA (2015)

Lesley A. Stewart, PhD; Mike Clarke, DPhil; Maroeska Rovers, PhD; Richard D. Riley, PhD; Mark Simmonds, PhD; Gavin Stewart, PhD; Jayne F. Tierney, PhD; for the PRISMA-IPD Development Group
COMBINED QUANTITATION OF PULMONARY THALLIUM WASHOUT AND MYOCARDIAL THALLIUM ACTIVITY ANALYSIS ENHANCES THE DETECTION OF CORONARY ARTERY DISEASE
Authors: Ronald D. Levy, Alan Rozanski, Ernest Garcia, Jack M. Gutman, Jamshid Maddahi, Nancy L. Pantaleo, Ken Van Train, Alan D. Waxman, H. J.C. Swan, Daniel S. Berman
Journal: Clinical Nuclear Medicine (1981)

Levy, Ronald D.; Rozanski, Alan; Garcia, Ernest; Gutman, Jack M.; Maddahi, Jamshid; Pantaleo, Nancy L.; Train, Ken Van; Waxman, Alan D.; Swan, H. J.C.; Berman, Daniel S. Author Information
Experts question latest MMR research
Authors: O. Dyer
Journal: BMJ (2002)

A new US study proposing a link between the measles, mumps, and rubella (MMR) vaccine and autism in children could further inflame the controversy surrounding MMR vaccination in Britain.

The research, led by Vijendra Singh, professor of immunology research at Utah State University,was prominently covered in the Daily Mail and other British media on 9 August but received a frosty response from most British experts.

The researchers examined blood samples from 125 autistic children and 92 …
THE EXTINCTION OF TUBERCULOSIS.The President's Address before the Medical and Chirurgical Faculty of Maryland, delivered April 24, 1894.
Authors: GEORGE H. ROHÉ
Journal: JAMA (1894)

This Ninety-Sixth Annual Convention of this Faculty should be to us an occasion of congratulation. During the past year our losses in membership have been few, and our gains not inconsiderable. The semi-annual meeting held in Annapolis last November was very successful, in point of attendance as well as in the character of the work accomplished. In an address at the opening of that meeting, I said: "A legitimate object of organization is to use it as a power to secure legislation. Not legislation for our benefit as physicians, but legislation for the public good. The medical profession wants nothing for itself from the Legislature. The legislation in which the profession is interested is such as will be for the benefit of the whole people. Public health laws, medical registration laws, lunacy laws, were all intended for the good of the public, although always originated, and their enactment promoted by
Endothelial Healing in Vein Grafts
Authors: Afshin Ehsan, Michael J. Mann, Giorgio Dell’Acqua, Koichi Tamura, Ruediger Braun-Dullaeus, Victor J. Dzau
Journal: Circulation (2002)

Although inhibition of neointimal hyperplasia by cell cycle gene blockade therapy results in improved endothelial cell function in experimental vein grafts, little is known either about endothelial healing immediately after vein grafting or about the effect of this therapy on the healing process.Scanning electron microscopy demonstrated an immediate decrease in vein graft endothelial cell density associated with vein graft wall stretch, followed by a return to baseline by postoperative day 3. En face detection of bromodeoxyuridine incorporation confirmed a rapid endothelial proliferation by 48 hours. Despite inhibition of underlying vascular smooth muscle cell proliferation, E2F decoy oligonucleotide did not inhibit either endothelial bromodeoxyuridine incorporation or the return to baseline cell density. This differential response to E2F decoy was also observed in human umbilical vein endothelial cell culture, which resisted the E2F decoy inhibition of cell growth that was observed in human umbilical artery smooth muscle cells, despite evidence for nuclear localized delivery of the oligonucleotide into both cell types. Furthermore, the reduction of E2F binding activity seen in a nuclear gel shift assay of cultured smooth muscle cells was not observed in endothelial cells.These results suggest a burst of graft endothelial cell proliferation that allows a rapid restoration of cell density in the monolayer. Additionally, there is a selective effect of E2F decoy gene therapy on target smooth muscle cells with sparing of this endothelial healing.
Stepwise radiofrequency ablation of Barrett’s esophagus preserves esophageal inner diameter, compliance, and motility
Authors: H. Beaumont, J. Gondrie, B. McMahon, R. Pouw, H. Gregersen, J. Bergman, G. Boeckxstaens
Journal: Endoscopy (2009)

See also: Commentaire de travail de H. Beaumont et al., pp. 2Endoscopy 2009; 41(01): 94-94DOI: 10.1055/s-0032-1306720
Vitamin D3 differentially regulates parathyroid hormone/parathyroid hormone-related peptide receptor expression in bone and cartilage
Authors: Norio Amizuka, Mei Yee Kwan, David Goltzman, Hidehiro Ozawa, John H. White
Journal: Journal of Clinical Investigation (1999)

Transcription of the mouse parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTHR) gene is controlled by promoters P1 and P2. We performed transcript-specific in situ hybridization and found that P2 is the predominant promoter controlling PTHR gene expression in bone and cartilage. Treatment with 1α,25-dihydroxyvitamin D3 (D3) in vivo specifically downregulated P2-specific transcripts in osteoblasts, but not in chondrocytes, under conditions where it enhanced bone resorption. Treatment of the osteoblastic cell line MC3T3-E1 with D3 in vitro reduced expression of both P2-specific transcripts and PTHR protein. This effect was not blocked by cycloheximide, indicating that D3 inhibits PTHR expression by downregulating transcription of the P2 promoter. A similar inhibitory effect of D3 was not observed in the chondrocytic cell line CFK2. Gene-transfer experiments showed that P2, but not P1, is active in both MC3T3-E1 and CFK2 cells, and that D3 specifically inhibited P2 promoter activity in MC3T3-E1, but not in CFK2 cells. Inhibition of P2 activity by D3 required promoter sequences lying more that 1.6 kb upstream of the P2 transcription start site. Thus, the P2 promoter controls PTHR gene expression in both osteoblasts and chondrocytes. D3 downregulates PTHR gene transcription in a cell-specific manner by inhibiting P2 promoter activity in osteoblasts, but not in chondrocytes.
T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-α subunit controlled by the Rac activator Dock2
Authors: Yoshihiko Tanaka, Shinjiro Hamano, Kazuhito Gotoh, Yuzo Murata, Yuya Kunisaki, Akihiko Nishikimi, Ryosuke Takii, Makiko Kawaguchi, Ayumi Inayoshi, Sadahiko Masuko, Kunisuke Himeno, Takehiko Sasazuki, Yoshinori Fukui
Journal: Nature Immunology (2007)
Breach of self tolerance in rheumatoid arthritis: a role for Th17 effector T cells?
Authors: A. Patakas, R. Benson, P. Conigliaro, J. Brewer, I. McInnes, P. Garside
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> While many studies on rheumatoid arthritis have focused on the active phase of the disease, the events that lead to the initial breach of self-tolerance remain ill defined. The authors have developed a model of breach of self-tolerance where a Th1 response to irrelevant antigen (OVA) results in arthropathy associated with spontaneous induction of autoreactive T and B cell responses. Here the authors investigate the role of Th17 cells, a subset of interleukin (IL)-17 producing CD4<sup>+</sup> T important in autoimmunity, in the initial events leading to breach of self-tolerance in experimental arthritis. <h3>Methods</h3> The authors employed TcR adoptive transfer systems together with novel arthritis model to analyse the role of Th17 cells in the events that lead to breach of self-tolerance in experimental arthritis <h3>Results</h3> Transfer of OVA specific Th17 cells induced similar levels of inflammation as Th1 cells, and could induce a breach of self-tolerance as demonstrated by CII specific T and B cell responses. Whereas the transferred OVA specific Th1 population retained its phenotype, the transferred Th17 population displayed significantly reduced IL-17 production. Furthermore, the CII specific T cells in both the Th1 and Th17 recipients were characterised by IFN-γ and not IL-17, production. <h3>Conclusion</h3> The fact that the OVA-specific T cell responses in both Th1 and Th17 transfer models are characterised by IFN-γ production and not IL-17 suggests that the ensuing breach of self-tolerance is driven by IFN-γ producing cells. In support of this, the evolving CII response is also characteristic of a Th1 rather than Th17 response. These studies highlight the plasticity of transferred cell populations in vivo, and support the use of blocking and fate-mapping studies to definitively address how auto-reactive responses develop.
THE REMOVAL OF FOREIGN BODIES FROM THE EYE.
Authors: O. HAAB
Journal: JAMA (1902)

The treatment of injuries to the eye brought about by foreign bodies will always be an important and interesting domain of an oculist's work. For in such cases of injury we have to deal not only with the foreign body but very often with an infection of the eye induced thereby, that is to say, with a factor calling for the greatest circumspection and skill in the operator. He has a hard battle to fight, not being yet sure of victory, a battle for which he has still to seek and prove new weapons. In well-known important operations on the eye, such as operations for cataract and glaucoma, we have decided rules to follow; they are stated in every textbook and manual. But this is hardly the case in the operations relative to and the treatment of injuries to the eye brought about by foreign bodies. It is even still
A Perfect Storm
Authors: William J. Janssen, Harold R. Collard, Sanjay Saint, Steven E. Weinberger
Journal: New England Journal of Medicine (2005)

A 21-year-old male college student presented to the student health center with two days of extreme fatigue. Over the course of the previous two months, frequent headaches, difficulty concentrating, and decreased exercise tolerance had developed. He recently had had several days of nasal congestion and sore throat, but these symptoms had improved. A cursory physical examination was normal, but pulse oximetry revealed an oxygen saturation of only 55 percent.