tbuckley/cabot-search huggingface dataset:
Treatment of tuberculosis
Authors: D. Maher
Journal: BMJ (2003)

Concordance is a key step 

The importance of people taking medicines extends beyond individuals to communities when medicines are crucial for treatment of communicable diseases and prevention of transmission. In this editorial we discuss the relevance of the concept of concordance (a term introduced to emphasise patients' beliefs about treatment)1 to the treatment of communicable disease, taking tuberculosis as an example. Tuberculosis is one of the leading causes of death due to an infectious agent, and the control of tuberculosis depends on effective treatment of the infectious patients, and therefore on people taking medicines.

The likelihood of successful treatment of tuberculosis depends on the extent to which patients complete the prescribed treatment regimen (usually called compliance with, or adherence to, treatment). Interrupted treatment of tuberculosis results in ongoing transmission of disease. Without support throughout the full course of treatment, many patients with tuberculosis adhere to treatment until symptoms have resolved and then stop, since patients may equate disease and therefore the need to continue treatment with illness (symptoms).2 The consequent risks of failure of …
Is It Ever Safe To Stop Azole Therapy for Coccidioides immitis Meningitis?
Authors: Daniel H. Dewsnup
Journal: Annals of Internal Medicine (1996)

Objective: To determine 1) whether patients with coccidioidal meningitis who had achieved remission with oral azole therapy were cured and 2) when oral azole therapy could be discontinued in these patients. Design: Data were gathered on patients with coccidioidal meningitis who had successfully responded to azole therapy in previous clinical trials. Setting: Referral centers, including university, county, and veterans' hospitals and clinics. Patients: 18 patients in whom azole therapy for meningitis had been discontinued, usually because of a presumption of cure. Main Outcome Measures: Clinical and cerebrospinal fluid relapse. Results: 14 of 18 patients (78% [95% CI, 52% to 94%]) had relapse with disseminated disease after discontinuation of therapy, for a total of 1 nonmeningeal and 15 meningeal relapses to date. Relapse occurred both soon and late (range, 0.5 to 30 months) after therapy was discontinued. The characteristics of patients who did not have relapse, including the particular azole used, the duration of therapy, the reason therapy was discontinued, and the cerebrospinal fluid indices before discontinuation, were similar to the characteristics of patients who had relapse. Relapse had serious consequences in some patients; 3 patients died. Conclusion: Our data suggest 1) that disease is only suppressed in patients with meningitis who achieve remission while receiving azole therapy and 2) that discontinuing azole therapy is unsafe. The alternative is lifelong treatment with azoles; this appears to be acceptable, because toxicity is uncommon with triazole therapy, even long-term triazole therapy.
Gene expression signatures associated with the in vitro resistance to two tyrosine kinase inhibitors, nilotinib and imatinib
Authors: T-M Kim, S-A Ha, H K Kim, J Yoo, S Kim, S-H Yim, S-H Jung, D-W Kim, Y-J Chung, J W Kim
Journal: Blood Cancer Journal (2011)

The use of selective inhibitors targeting Bcr-Abl kinase is now established as a standard protocol in the treatment of chronic myelogenous leukemia; however, the acquisition of drug resistance is a major obstacle limiting the treatment efficacy. To elucidate the molecular mechanism of drug resistance, we established K562 cell line models resistant to nilotinib and imatinib. Microarray-based transcriptome profiling of resistant cells revealed that nilotinib- and imatinib-resistant cells showed the upregulation of kinase-encoding genes (AURKC, FYN, SYK, BTK and YES1). Among them, the upregulation of AURKC and FYN was observed both in nilotinib- and imatinib-resistant cells irrespective of exposure doses, while SYK, BTK and YES1 showed dose-dependent upregulation of expression. Upregulation of EGF and JAG1 oncogenes as well as genes encoding ATP-dependent drug efflux pump proteins such as ABCB1 was also observed in the resistant cells, which may confer alternative survival benefits. Functional gene set analysis revealed that molecular categories of 'ATPase activity', 'cell adhesion' or 'tyrosine kinase activity' were commonly activated in the resistant clones. Taken together, the transcriptome analysis of tyrosine kinase inhibitors (TKI)-resistant clones provides the insights into the mechanism of drug resistance, which can facilitate the development of an effective screening method as well as therapeutic intervention to deal with TKI resistance.
Evolving Concepts of Mitral-Valve Prolapse
Authors: Joseph K. Perloff
Journal: New England Journal of Medicine (1982)

Almost half a century separates the Journal's first article on an auscultatory sign in what is now called mitral-valve prolapse1 from the article in the present issue in which Tei et al. describe still another auscultatory sign.2 The voluminous literature on mitral prolapse continues to increase. A list confined to key references exceeded 90 entries just three years ago.3 Two articles appeared in the Journal during the past year,4 , 5 and another only two weeks ago.6 Before the estimated prevalence of 6 per cent7 can be judged properly, it must be determined whether the term "mitral-valve prolapse" consistently connotes a disease . . .
P829 LIVER MITOCHONDRIAL FATTY ACID OXIDATION IS ALTERED IN MORBID OBESE PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS
Authors: N. Helmy, A. Mansouri, V. Lenoir, M. Ziol, C. Esnous, B. Dousset, F. Bouillaud, C. Vons, C. Prip-Buus
Journal: Journal of Hepatology (2014)
Time-Dependent Impact of Diabetes on Mortality in Patients With Stroke
Authors: Andrea Icks, Heiner Claessen, Stephan Morbach, Gerd Glaeske, Falk Hoffmann
Journal: Diabetes Care (2012)

OBJECTIVE To estimate the impact of diabetes on mortality in patients after first stroke event. RESEARCH DESIGN AND METHODS Using claims data from a nationwide statutory health insurance fund (Gmünder ErsatzKasse), we assessed all deaths in a cohort of 5,757 patients with a first stroke between 2005 and 2007 (69.3% male, mean age 68.1 years, 32.2% with diabetes) up to 2009. By use of Cox regression, we estimated time-dependent hazard ratios (HRs) to compare patients with and without diabetes stratified by sex. RESULTS The cumulative 5-year mortality was 40.0 and 54.2% in diabetic men and women, and 32.3 and 38.1% in their nondiabetic counterparts, respectively. In males, mortality was significantly lower in diabetic compared with nondiabetic patients in the first 30 days (multiple-adjusted HR 0.67 [95% CI 0.53–0.84]). After approximately a quarter of a year, the diabetes risk increased, yielding crossed survival curves. Later on, mortality risk tended to be similar in diabetic and nondiabetic men (1–2 years: 1.42 [1.09–1.85]; 3–5 years: 1.00 [0.67–1.41]; time dependency of diabetes, P = 0.008). In women, the pattern was similar; however, time dependency was not statistically significant (P = 0.89). Increasing age, hemorrhagic stroke, renal failure (only in men), levels of care dependency, and number of prescribed medications were significantly associated with mortality. CONCLUSIONS We found a time-dependent mortality risk of diabetes after first stroke in men. Possible explanations may be type of stroke or earlier and more intensive treatment of risk factors in diabetic patients.
1028-121 Stressful Public Speaking Elevates Plasma β -Endorphins
Authors: Rungroj Krittayaphong, Martha N. Ballenger, Guy E. De Gent, Eileen A. Dittman, William Maixner, William McCartney, Robert Golden, Gary Koch, Kathleen Light, David S. Sheps
Journal: Journal of the American College of Cardiology (1995)
SET-NUP214 is a recurrent γδ lineage-specific fusion transcript associated with corticosteroid/chemotherapy resistance in adult T-ALL
Authors: Raouf Ben Abdelali, Anne Roggy, Thibaut Leguay, Agata Cieslak, Aline Renneville, Aurore Touzart, Anne Banos, Edouard Randriamalala, Denis Caillot, Bruno Lioure, Alain Devidas, Hossein Mossafa, Claude Preudhomme, Norbert Ifrah, Hervé Dombret, Elizabeth Macintyre, Vahid Asnafi
Journal: Blood (2014)
New Aspects of Therapeutic Coloscopy
Authors: P. Frühmorgen, J. Zeus, L Demling
Journal: Endoscopy (1975)

Within 1523 coloscopic examinations, on 299 occasions, the primarily diagnostic procedure was, at the same time, a therapeutic one. We were able to develop reliable methods, suitable also for routine application, for the electro-surgical removal of polypoid lesions of the colon (n = 282) with the aid of closed or open high-frequency loops, for the extraction of foreign bodies (n = 1) and for the removal of non-absorbable suture material (n = 5). Although not yet “ripe” for routine applications, we have already gained initial experience with treatment by injection (n = 5) and successful electro-coagulation of bleeding and non-bleeding haemangiomas (n = 5), and have carried out first experimental investigations into the application of the laser in the colon. In an further case we made an electro-resection of an inoperable carcinoma as a palliative treatment.
The Antiatherogenic Effect of Iridium192 upon the Cholesterolfed Rabbit*
Authors: Meyer Friedman, Leland Felton, Sanford Byers
Journal: Journal of Clinical Investigation (1964)

A 20-cm length of Ir192 wire was placed for 48 hours in the proximal portion of the aortas of a series of rabbits. The rabbits, when subsequently fed a diet containing excess cholesterol, failed to exhibit significant atherosclerosis, as compared to the control animals, in that pontion of the aorta which received the irradiation. The histological and chemical studies performed upon these rabbits suggest that the antiatherogenic effect of the irradiation was due primarily to the suppression of the intimal hyperplastic response to a persistent hypercholesteremia usually observed in the rabbit's aorta.
Deaths associated with respiratory tract infection in childhood.
Authors: P S Gardner, D C Turk, W A Aherne, T Bird, M D Holdaway, S D Court
Journal: BMJ (1967)

the number of children who die from respiratory tract infections has decreased markedly during the period in which antibacterial drugs have become available.The figures given in Table I illustrate this point clearly, but they also show that such deaths have by no means been eliminated and that the extent of the improvement is much less among infants than among older children.TABLE I.-Numbers of Children Who Died in Newcastle upon Tyne from Lower Respiratory Tract Infections No. of Deaths During Approximate Age in Years Ratio of Deaths
Prostaglandin Pathway Gene Therapy for Sustained Reduction of Intraocular Pressure
Authors: Román A Barraza, Jay W McLaren, Eric M Poeschla
Journal: Molecular Therapy (2009)

Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in prostaglandin (PG) biosynthesis. In the eye, loss of COX-2 expression in aqueous humor–secreting cells has been associated with primary open-angle glaucoma (POAG). Reduction of intraocular pressure (IOP) is the main treatment goal in this disease. We used lentiviral vectors to stably express COX-2 and other PG biosynthesis and response transgenes in the ciliary body epithelium and trabecular meshwork (TM), the ocular suborgans that produce aqueous humor and regulate its outflow, respectively. We show that robust ectopic COX-2 expression and PG production require COX-2 complementary DNA (cDNA) sequence optimization. When COX-2 expression was coupled with a similarly optimized synthetic PGF2α receptor transgene to enable downstream signaling, gene therapy produced substantial and sustained reductions in IOP in a large animal model, the domestic cat. This study provides the first gene therapy for correcting the main cause of glaucoma. Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in prostaglandin (PG) biosynthesis. In the eye, loss of COX-2 expression in aqueous humor–secreting cells has been associated with primary open-angle glaucoma (POAG). Reduction of intraocular pressure (IOP) is the main treatment goal in this disease. We used lentiviral vectors to stably express COX-2 and other PG biosynthesis and response transgenes in the ciliary body epithelium and trabecular meshwork (TM), the ocular suborgans that produce aqueous humor and regulate its outflow, respectively. We show that robust ectopic COX-2 expression and PG production require COX-2 complementary DNA (cDNA) sequence optimization. When COX-2 expression was coupled with a similarly optimized synthetic PGF2α receptor transgene to enable downstream signaling, gene therapy produced substantial and sustained reductions in IOP in a large animal model, the domestic cat. This study provides the first gene therapy for correcting the main cause of glaucoma.
Dietary Nitrate Supplementation Improves Revascularization in Chronic Ischemia
Authors: Ulrike B. Hendgen-Cotta, Peter Luedike, Matthias Totzeck, Martina Kropp, Andreas Schicho, Pia Stock, Christos Rammos, Michael Niessen, Christian Heiss, Jon O. Lundberg, Eddie Weitzberg, Malte Kelm, Tienush Rassaf
Journal: Circulation (2012)

Background— Revascularization is an adaptive repair mechanism that restores blood flow to undersupplied ischemic tissue. Nitric oxide plays an important role in this process. Whether dietary nitrate, serially reduced to nitrite by commensal bacteria in the oral cavity and subsequently to nitric oxide and other nitrogen oxides, enhances ischemia-induced remodeling of the vascular network is not known. Methods and Results— Mice were treated with either nitrate (1 g/L sodium nitrate in drinking water) or sodium chloride (control) for 14 days. At day 7, unilateral hind-limb surgery with excision of the left femoral artery was conducted. Blood flow was determined by laser Doppler. Capillary density, myoblast apoptosis, mobilization of CD34 + /Flk-1 + , migration of bone marrow–derived CD31 + /CD45 − , plasma S-nitrosothiols, nitrite, and skeletal tissue cGMP levels were assessed. Enhanced green fluorescence protein transgenic mice were used for bone marrow transplantation. Dietary nitrate increased plasma S-nitrosothiols and nitrite, enhanced revascularization, increased mobilization of CD34 + /Flk-1 + and migration of bone marrow–derived CD31 + /CD45 − cells to the site of ischemia, and attenuated apoptosis of potentially regenerative myoblasts in chronically ischemic tissue. The regenerative effects of nitrate treatment were abolished by eradication of the nitrate-reducing bacteria in the oral cavity through the use of an antiseptic mouthwash. Conclusions— Long-term dietary nitrate supplementation may represent a novel nutrition-based strategy to enhance ischemia-induced revascularization.
Assessment of wall shear stress in arteries, applied to the coronary circulation
Authors: T J BENSON, R M NEREM, T J PEDLEY
Journal: Cardiovascular Research (1980)

Time dependent wall shear rates cannot be directly or accurately measured in arteries using presently available techniques. Here a simple method is presented for calculating them from a single measured velocity waveform (either centreline or cross-sectionally averaged velocity). The method involves only Fourier analysis and the application of given formulae, and it is expected to be approximately valid in any segment of artery which has no branches or sharp curves for a distance of several diameters. It is shown, however, that a frequency response of 30 Hz is required in the velocity measuring device if the resulting wall shear rate waveform is to be accurate throughout the cycle, although 10 Hz is adequate if only the rms value is desired. This restriction on accuracy applies to this or any other method of estimating time-dependent wall shear. The method is applied to a prediction of wall shear in the left coronary arteries of the horse, based on measured velocities where they are available and calculated ones where they are not; the results show that in vivo the amplitude of wall shear fluctuations is much greater than the mean. The method is also applied to a scaled down model of the horse coronaries, thought to be representative of man; here the unsteadiness is still important but no longer dominant. The variation of wall shear with distance along the artery is discussed in the context of atherogenesis.
Demonstration of the presence of slow conduction during sustained ventricular tachycardia in man: use of transient entrainment of the tachycardia.
Authors: K Okumura, B Olshansky, R W Henthorn, A E Epstein, V J Plumb, A L Waldo
Journal: Circulation (1987)

To test the hypothesis that an area of slow conduction is present during reentrant ventricular tachycardia in man, and that the earliest activation site during ventricular tachycardia is within or orthodromically just distal to the area of slow conduction in the reentry loop, we studied 12 episodes of ventricular tachycardia (mean rate 185 +/- 32 beats/min) that were induced in nine patients with ischemic heart disease. Rapid ventricular pacing was performed at selected sites during ventricular tachycardia while recording electrograms from an early activation site relative to the onset of the QRS complex (site A) and from a site close to the pacing site (site B). Rapid pacing from the right ventricular apex during ventricular tachycardia with a right bundle branch block pattern and from selected left ventricular sites during ventricular tachycardia with a left bundle branch block pattern (mean pacing rate 202 +/- 38 beats/min) resulted in constant ventricular fusion beats on the electrocardiogram except for the last captured beat (i.e., the ventricular tachycardia was entrained) in 11 of 12 episodes. During entrainment: sites A and B were activated at the pacing rate, conduction time from the last pacing impulse to the last captured ventricular electrogram at site A (St-A interval) was 359 +/- 69 msec and spanned the diastolic interval, while that at site B (St-B interval) was only 28 +/- 13 msec, site A had the same ventricular electrogram morphology as that during ventricular tachycardia, while site B had a different electrogram morphology, indicating that site A was activated in the same direction during entrainment as during ventricular tachycardia. Eight episodes of ventricular tachycardia were entrained at two or more different pacing rates. The St-A interval increased during pacing at the faster rate(s) in four of eight episodes, while the St-B interval remained unchanged. Rapid ventricular pacing performed from the same site during sinus rhythm (mean pacing rate 201 +/- 37 beats/min) resulted in an St-A interval of 103 +/- 37 msec (p less than .001 vs the value during entrainment) and an St-B interval of 31 +/- 15 msec (p = NS vs the value during entrainment). It is concluded that an area of slow conduction not demonstrable during sinus rhythm exists during ventricular tachycardia, and that the earliest activation site during ventricular tachycardia is at or orthodromically distal to this area of slow conduction.
Marjorie Mary Brearley
Authors: A. B Neil
Journal: BMJ (2003)

Former senior medical officer Pontefract (b Irthington 1920; q Leeds 1943), d 13 November 2002.


After house jobs in obstetrics and gynaecology Marjorie joined the Royal Army Medical Corps and was posted to Rawalpindi and later to Lahore. Following demobilisation she became a registrar in general medicine at Leeds General Infirmary before going into public health medicine with particular interest in the 



assessment of children. From 1974 until her retirement Marjorie was a senior medical officer in Pontefract, where she ran both office and assessment centres. She was always fond of walking, especially in the Lake District. She leaves a husband, Tom, and two children.
Improving the training of SHOs
Authors: E. Paice, P. Leaver
Journal: BMJ (1999)

The General Medical Council has turned its attention to the training of senior house officers. Its new guidance, The Early Years , follows Tomorrow's Doctors on undergraduate education and The New Doctor on the preregistration year, but it lacks the bite of its influential precursors and in its present form is unlikely to provoke similar change.

The document recommends high quality education and training, flexible enough to meet the personal needs and professional aspirations of senior house officers. It emphasises the importance of careers advice, clinical and educational supervision, and provision for welfare. It refers to the particular needs of overseas doctors.

None of this is new. 1 2 Colleges and postgraduate deans have promoted induction programmes, training agreements, structured teaching, consultant appraisal, log books, structured training rotations, flexible training schemes, and (with the BMA) improvements in hours of work. Improvements have occurred in all these aspects, and there is evidence that consultants are taking their role as educators increasingly seriously.3 Nevertheless, although most senior house officers enjoy their work, others are overwhelmed by the responsibility and find the grade both depressing and demotivating. 4 5

Part of the problem derives from lack of clarity about the purpose of the grade. Sandwiched …
Computer Searching of the Medical Literature
Authors: DEXTER D. MAR
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 April 1986Computer Searching of the Medical LiteratureDEXTER D. MAR, Pharm.D.DEXTER D. MAR, Pharm.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-104-4-582_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Haynes and colleagues have contributed a valuable report on an important decision-making tool, computer-based retrieval of the medical literature (1). They have attempted a comparative evaluation of various sources of MEDLINE to assist clinicians in making rational choices.We agree with Dr. Haynes and associates' conclusions that more research is clearly needed to determine systems of choice for computer-novice clinicians and that cost effectiveness is a significant factor. In light of these conclusions, however, their recommendation that clinicians use the National Library of Medicine (NLM) service (or any service) seems premature. Clearly, their method of using...Reference1. HAYNESMCKIBBONWALKER RKC. Computer searching of the medical literature: an evaluation of MEDLINE searching systems. Ann Intern. Med. 1985;103:812-6. LinkGoogle Scholar1. . The Basics of Searching MEDLINE: a Guide for Health Professionals. Bethesda, Maryland: National Library of Medicine; 1985. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1986Volume 104, Issue 4Page: 582-583KeywordsComparative effectiveness researchComputersLibraries Issue Published: 1 April 1986 PDF DownloadLoading ...