tbuckley/cabot-search huggingface dataset:
JAMATheme Issue in Cardiovascular Disease
Authors: J. Michael Gaziano, Philip Greenland, Eric D. Peterson
Journal: JAMA (2014)

2][3] In this issue, we hope to include articles about cardiovascular disease that are relevant to the broad readership of JAMA.We will consider any manuscript that addresses cardiovascular disease in humans.This runs the gamut from first in human investigations to multicenter randomized clinical trials to population-based clinical, genetic, or biomarker epidemiological investigations.Given that JAMA also is interested in translating science into practice, we also encourage submission of studies that examine health care quality, safety, and efficiency; implementation evaluations; and other relevant health policy issues.With the timing of this theme issue, we are especially interested in late-breaking research, particularly late-breaking randomized clinical trials that will be presented at the American Heart Association meeting.We encourage authors who are involved with such studies to contact us as early as possible so that we can discuss our interest in the trial and coordinate timing for submission of the manuscript with the goal of simultaneous
The Importance of a Name
Authors: Jeffrey P. Callen, June K. Robinson
Journal: JAMA Dermatology (2013)

Hrishikesh Belani, MPH; Lianne Gensler, MD; Urmila Bajpai, MD, PhD; Eric Meinhardt, MD; Jonathan Graf, MD; Laura Pincus, MD; Kieron S. Leslie, DTM&H, FRCP
Totally transforming Auchendreich
Authors: Colin Douglas
Journal: BMJ (2006)

Urine differs greatly in ion and solute composition from plasma and contains harmful and noxious substances that must be stored for hours and then eliminated when it is socially convenient to do so. The urinary tract that handles this output is composed of a series of pressurizable muscular compartments separated by sphincteric structures. With neural input, these structures coordinate the delivery, collection, and, ultimately, expulsion of urine. Despite large osmotic and chemical gradients in this waste fluid, the bladder maintains a highly impermeable surface in the face of a physically demanding biomechanical environment, which mandates recurring cycles of surface area expansion and increased wall tension during filling, followed by rapid wall compression during voiding. Afferent neuronal inflow from mucosa and submucosa communicates sensory information about bladder fullness, and voiding is initiated consciously through coordinated central and spinal efferent outflow to the detrusor, trigonal internal sphincter, and external urethral sphincter after periods of relative quiescence. Provocative new findings suggest that in some cases, lower urinary tract symptoms, such as incontinence, urgency, frequency, overactivity, and pain may be viewed as a consequence of urothelial defects (either urothelial barrier breakdown or inappropriate signaling from urothelial cells to underlying sensory afferents and potentially interstitial cells). This review describes the physiologic and anatomic mechanisms by which urine is moved from the kidney to the bladder, stored, and then released. Relevant clinical examples of urinary tract dysfunction are also discussed.
Drug firms take legal steps to prevent European regulator releasing data
Authors: Z. Kmietowicz
Journal: BMJ (2013)

A leading US pharmaceutical company, AbbVie, has taken legal action against Europe’s medicines regulator to try to prevent it from releasing data it holds on the safety and efficacy of one of its drugs.

If successful, the action could jeopardise the European agency’s plans to begin publishing from January 2014 all clinical trial data once it has decided whether to approve a drug for use across the European Union.1

AbbVie has sought an injunction to stop the European Medicines Agency (EMA) from releasing detailed information that it holds on its drug Humira (adalimumab) for rheumatoid arthritis. The move follows two freedom of information requests from Belgian pharmaceutical company UCB in late 2012 for patient level data on the drug’s side effects …
Right Ventricular Isovolumıc Contractıon Acceleration Before and After Percutaneous Closure of Atrial Septal Defects
Authors: Ali Rıza Akyüz, Levent Korkmaz, Turhan Turan, Abdulkadir Kırış, Hakan Erkan, Mustafa Tarık Ağaç, Muslihittin Emre Erkuş, Şükrü Çelik, Ramazan Akdemir
Journal: Journal of the American College of Cardiology (2013)
Sleep-Disordered Breathing and Gestational Diabetes Mellitus
Authors: Miguel Angel Luque-Fernandez, Paul A. Bain, Bizu Gelaye, Susan Redline, Michelle A. Williams
Journal: Diabetes Care (2013)

OBJECTIVE Recently, sleep-disordered breathing (SDB) has been reported to be associated with the development of gestational diabetes mellitus (GDM). Accordingly, as this is emergent area of research that has significant clinical relevance, the objective of this meta-analysis is to examine the relationship between SDB with GDM. RESEARCH DESIGN AND METHODS We searched several electronic databases for all of the studies published before January 2013 and reviewed references of published articles. Meta-analytic procedures were used to estimate the unadjusted and BMI-adjusted odds ratios (ORs) using a random effects model. Significant values, weighted effect sizes, and 95% CIs were calculated, and tests of homogeneity of variance were performed. RESULTS Results from nine independent studies with a total of 9,795 pregnant women showed that SDB was significantly associated with an increased risk of GDM. Women with SDB had a more than threefold increased risk of GDM, with a pooled BMI-adjusted OR 3.06 (95% CI 1.89–4.96). CONCLUSIONS These findings demonstrate a significant association between SDB and GDM that is evident even after considered confounding by obesity. This meta-analysis indicates a need to evaluate the role of early recognition and treatment of SDB early during pregnancy.
What is an appropriate degree of risk?
Authors: N. J. Keegan
Journal: BMJ (2010)

In the light of her recent comments on rosiglitazone in the BMJ and the popular press, I wonder what Godlee would consider to be an appropriate degree of cardiovascular risk for any drug.1

The most recent data from the Office of National Statistics show that deaths related to the illicit use of cocaine have been steadily increasing in this country and …
Acute Granulomatous Hepatitis in the Course of Acquired Toxoplasmosis
Authors: Alan B. Weitberg, Joseph C. Alper, Israel Diamond, Zuzana Fligiel
Journal: New England Journal of Medicine (1979)

TOXOPLASMIC hepatitis has been described as a clinical entity,1 2 3 4 5 6 7 8 usually as the primary manifestation of acute, acquired toxoplasmosis without adenopathy. Hepatitis can occur also as a late complication of the disease, when lymphadenopathy initially predominates.2 We describe a unique case of acquired toxoplasmosis characterized by lymphadenopathy and granulomatous hepatitis. Several reports have discussed toxoplasmic granulomatous hepatitis,5 , 6 but the disease has never been documented convincingly. We provide clear evidence that granulomatous hepatitis is a complication of acquired toxoplasmosis and that the severity of the hepatitis may be significantly greater than previously described.4 , 7 , 8 Case ReportA 28-year-old native of El Salvador immigrated . . .
Effects of altered glucose homeostasis on glucose transporter expression in skeletal muscle of the rat.
Authors: R E Bourey, L Koranyi, D E James, M Mueckler, M A Permutt
Journal: Journal of Clinical Investigation (1990)

Previous studies have suggested that alteration in the expression of the insulin-regulatable glucose transporter of muscle (GLUT-4 protein) may be an important determinant of insulin action. In the present studies, we have examined GLUT-4 mRNA and protein concentrations in muscle after variations in the metabolic status of the intact animal (i.e., 7 d streptozotocin-induced diabetes, 7 d insulin-induced hypoglycemia, and 3 d fasting). These changes in glucose homeostasis were associated with the following changes in GLUT-4 gene products: a decrease of approximately 30% in both mRNA and protein with diabetes; a 50% increase in mRNA and a 2.4-fold increase in protein with insulin injection; and normal mRNA in spite of a 2.7-fold increase in protein with fasting. Fasted diabetics exhibited an increase of 50% in GLUT-4 mRNA and a 2.4-fold increase in protein relative to fed diabetics. In diabetic and insulin-injected groups, the changes in GLUT-4 protein were similar to changes in mRNA, but in fasting, GLUT-4 protein increased without a concomitant change in mRNA. Overall there was no correlation between muscle concentrations of GLUT-4 protein and mRNA. Muscle GLUT-4 protein concentration tended to correlate with plasma glucose (r = -0.57, P less than 0.001), but not with plasma insulin. These results indicate that (a) chronic changes in glucose homeostasis are associated with changes in expression of GLUT-4 protein in muscle; (b) GLUT-4 protein increased in fasted soleus muscle without change in mRNA, thereby differing from fasted adipocytes in which both GLUT-4 products diminish; and (c) no simple relationship exists between total muscle GLUT-4 protein content and whole-body insulin sensitivity.
Cochrane plans to allay fears over industry influence
Authors: R. Moynihan
Journal: BMJ (2003)

The leadership of the global Cochrane Collaboration is acting to allay fears that drug company funding could damage the organisation's independence and credibility.

Jim Neilson, a joint chairman of the collaboration, told the BMJ that the collaboration's international steering group was taking the issue seriously. “We are very conscious of the need to maintain the credibility and unbiased nature of Cochrane reviews.”

The collaboration produces and disseminates systematic reviews of the evidence about healthcare interventions, and the question of industry funding has dominated …
Immunotherapy for Primary Brain Tumors: No Longer a Matter of Privilege
Authors: Peter E. Fecci, Amy B. Heimberger, John H. Sampson
Journal: Clinical Cancer Research (2014)

Abstract Immunotherapy for cancer continues to gain both momentum and legitimacy as a rational mode of therapy and a vital treatment component in the emerging era of personalized medicine. Gliomas, and their most malignant form, glioblastoma, remain as a particularly devastating solid tumor for which standard treatment options proffer only modest efficacy and target specificity. Immunotherapy would seem a well-suited choice to address such deficiencies given both the modest inherent immunogenicity of gliomas and the strong desire for treatment specificity within the confines of the toxicity-averse normal brain. This review highlights the caveats and challenges to immunotherapy for primary brain tumors, as well as reviewing modalities that are currently used or are undergoing active investigation. Tumor immunosuppressive countermeasures, peculiarities of central nervous system immune access, and opportunities for rational treatment design are discussed. See all articles in this CCR Focus section, “Discoveries, Challenges, and Progress in Primary Brain Tumors.” Clin Cancer Res; 20(22); 5620–9. ©2014 AACR.
REDUCED SURVIVAL IN LAMBDA PREDOMINANT CARDIAC AL AMYLOIDOSIS PATIENTS AWAITING ORTHOTOPIC HEART TRANSPLANT
Authors: Sara Tabtabai, Emily Niehaus, Nitasha Sarswat, James R. Stone, Mathew Maurer, Ronald Witteles, Jerry Estep, David Baran, Mark Zucker, Guiseppe Feltrin, David Seldin, Marc Semigran
Journal: Journal of the American College of Cardiology (2014)
What Influences the Frequency of Angiography … Cardiologists?
Authors: Jack V. Tu
Journal: Annals of Internal Medicine (1997)

Letters1 August 1997What Influences the Frequency of Angiography … Cardiologists?Jack V. Tu, MD, PhD, C. David Naylor, MD, DPhil, and Edward L. Hannan, PhDJack V. Tu, MD, PhDUniversity of Toronto; Toronto Ontario M4N 3M5, CanadaState University of New York Albany, NY 12144Search for more papers by this author, C. David Naylor, MD, DPhilUniversity of Toronto; Toronto Ontario M4N 3M5, CanadaState University of New York Albany, NY 12144Search for more papers by this author, and Edward L. Hannan, PhDUniversity of Toronto; Toronto Ontario M4N 3M5, CanadaState University of New York Albany, NY 12144Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-3-199708010-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We are grateful to Drs. Page and Bell for their interest in our study. We agree with them that coronary anatomy is not the only consideration in the management of patients with ischemic heart disease and that the number of cardiologists is probably an important determinant of rates of coronary angiography. On the basis of data from various unpublished and published sources [1, 2], we estimate that New York State has approximately two to three times as many cardiologists per capita as Ontario does. However, we caution that directly comparable data based on identical definitions of a cardiologist ...References1. Ayanian JZ, Hauptman PJ, Guadagnoli E, Antman EM, Pashos CL, McNeil BJ. Knowledge and practices of generalist and specialist physicians regarding drug therapy for acute myocardial infarction. N Engl J Med. 1994; 331:1136-42. Google Scholar2. Canadian Medical Directory. Don Mills, ON: Southam Information and Technology Group; 1995. Google Scholar Author, Article, and Disclosure InformationAuthors: Jack V. Tu, MD, PhD; C. David Naylor, MD, DPhil; Edward L. Hannan, PhDAffiliations: University of Toronto; Toronto Ontario M4N 3M5, CanadaState University of New York Albany, NY 12144 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1997Volume 127, Issue 3Page: 245KeywordsAngiographyCardiovascular therapyCoronary heart diseaseInformation storage and retrievalSurgery ePublished: 15 August 2000 Issue Published: 1 August 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Venous Obstruction of the Upper Extremity Caused by a Malformed Valve of the Subclavian Vein
Authors: C. E. CUCCI, C. G. BOTTINO, V. CIAMPA
Journal: Circulation (1963)

A 39-year-old laborer with a venous obstruction of the left upper extremity was studied by selective phlebography. Surgery revealed that the obstruction was caused by an anomalous venous valve, diaphragm-like, at the middle third of the subclavian vein. The removal of the anomalous valve resulted in complete relief of the obstruction. This is the only known case of venous obstruction caused bv a malformed valve. The authors suggest that the term "primary venous obstruction" of the upper extremity be used instead of "traumatic thrombosis" or "Paget-Schroetter" syndrome, in cases in which the etiology has not been ascertained.
Unusual late complication of renal transplantation.
Authors: D. G. Oreopoulos, M. A. Soyannwo, M. G. McGeown, J. M. Megaw
Journal: BMJ (1969)

<i>l</i>-Ethomoxane (<i>l</i>-S-ethoxy-2-butylaminomethyl-l ,4-benzodioxane hydrochloride) has a veratramine-like negative chronotropic action on dog heart-hung and isolated guinea-pig atrium preparations. The synthetic drug has only one-thirtieth of the potency of veratramine on the dog heart and between one-tenth in and one-twentieth of time potency of veratramine on the guineapig atrium. <i>l</i>-Ethmoxane resembles other polycyclic amines which exhibit veratrarnine-like properties on the heart in that, in contrast to veratramine itself, it has a negative inotropic action as well as a negative chronotropic action. Large doses of <i>l</i>-ethomoxane give rise to an irregular sinus arrhythmia resembling that sometimes seen with veratramine. Both drugs caused slowing in time neurogenic isolated lobster heart, and, in doses too small to affect the resting rate, antagonized the positive chronotropic action of epinephrine. <i>l</i>-Ethomoxane, in common with veratramine, has a nonspecific smooth muscle depressant action, antagonizing responses of isolated guinea-pig ileum to acetylcimobine, barium and histamine.
Targeted Gene Delivery to the Enteric Nervous System Using AAV: A Comparison Across Serotypes and Capsid Mutants
Authors: Matthew J Benskey, Nathan C Kuhn, James J Galligan, Joanna Garcia, Shannon E Boye, William W Hauswirth, Christian Mueller, Sanford L Boye, Fredric P Manfredsson
Journal: Molecular Therapy (2015)

Recombinant adeno-associated virus (AAV) vectors are one of the most widely used gene transfer systems in research and clinical trials. AAV can transduce a wide range of biological tissues, however to date, there has been no investigation on targeted AAV transduction of the enteric nervous system (ENS). Here, we examined the efficiency, tropism, spread, and immunogenicity of AAV transduction in the ENS. Rats received direct injections of various AAV serotypes expressing green fluorescent protein (GFP) into the descending colon. AAV serotypes tested included; AAV 1, 2, 5, 6, 8, or 9 and the AAV2 and AAV8 capsid mutants, AAV2-Y444F, AAV2-tripleY-F, AAV2-tripleY-F+T-V, AAV8-Y733F, and AAV8-doubeY-F+T-V. Transduction, as determined by GFP-positive cells, occurred in neurons and enteric glia within the myenteric and submucosal plexuses of the ENS. AAV6 and AAV9 showed the highest levels of transduction within the ENS. Transduction efficiency scaled with titer and time, was translated to the murine ENS, and produced no vector-related immune response. A single injection of AAV into the colon covered an area of ~47 mm2. AAV9 primarily transduced neurons, while AAV6 transduced enteric glia and neurons. This is the first report on targeted AAV transduction of neurons and glia in the ENS. Recombinant adeno-associated virus (AAV) vectors are one of the most widely used gene transfer systems in research and clinical trials. AAV can transduce a wide range of biological tissues, however to date, there has been no investigation on targeted AAV transduction of the enteric nervous system (ENS). Here, we examined the efficiency, tropism, spread, and immunogenicity of AAV transduction in the ENS. Rats received direct injections of various AAV serotypes expressing green fluorescent protein (GFP) into the descending colon. AAV serotypes tested included; AAV 1, 2, 5, 6, 8, or 9 and the AAV2 and AAV8 capsid mutants, AAV2-Y444F, AAV2-tripleY-F, AAV2-tripleY-F+T-V, AAV8-Y733F, and AAV8-doubeY-F+T-V. Transduction, as determined by GFP-positive cells, occurred in neurons and enteric glia within the myenteric and submucosal plexuses of the ENS. AAV6 and AAV9 showed the highest levels of transduction within the ENS. Transduction efficiency scaled with titer and time, was translated to the murine ENS, and produced no vector-related immune response. A single injection of AAV into the colon covered an area of ~47 mm2. AAV9 primarily transduced neurons, while AAV6 transduced enteric glia and neurons. This is the first report on targeted AAV transduction of neurons and glia in the ENS.
GADGETS FOR THE DISABLED
Authors: D. Brooks
Journal: BMJ (1954)

<b>Objective: </b> To characterize the biochemical mechanisms of expression of the pyruvate dehydrogenase (PDH) E1α subunit exon 10 R302C missense mutation. <b>Background: </b> Mutations in the X-linked E1α subunit gene are responsible for most cases of PDH deficiency, an important cause of neurodevelopmental defects and neurodegeneration with primary lactic acidemia. Although the disease shows extreme allelic heterogeneity, the R302C mutation has been defined in several unrelated cases. <b>Methods: </b> Cell lines expressing selectively either the mutant or wild-type E1α alleles against identical genetic backgrounds were generated from the fibroblasts of a female heterozygous for the R302C mutation. Enzyme activity, mRNA, polypeptide expression, and turnover were studied in each. <b>Results: </b> The residual PDH activity was below measurable levels in the cell line (B5) expressing only the mutant allele and normal in the wild-type polypeptide expressing (A10) cell line, confirming that the R302C mutation alone is sufficient to cause a severe PDH deficiency. The mutant polypeptide was less stable than the wild-type polypeptide, but the steady-state level of the mutant E1α protein was reduced only two- to threefold. <b>Conclusions: </b> The primary mechanism of expression of the R302C mutation must be limitation of catalytic efficiency. We speculate that catalysis may be inhibited in the mutant polypeptide because conformational changes are induced near serine 300, a residue that is particularly important as a regulatory phosphorylation site in the wild-type polypeptide.
Nitric oxide synthesised from L-arginine mediates endothelium dependent dilatation in human veins in vivo
Authors: P. VALLANCE, J. COLLIER, S. MONCADA
Journal: Cardiovascular Research (1989)

Endothelium derived relaxing factor (EDRF) has been identified as nitric oxide, synthesised from the amino acid L-arginine, a process which is inhibited by the L-arginine analogue NG-monomethyl L-arginine (L-NMMA). We have studied the effect of local infusions of L-NMMA on venous reactivity in healthy volunteers. Studies were performed using the veins on the back of the hand. The diameter of a single dorsal hand vein was measured in healthy subjects who had taken 600 mg of aspirin 30 min before the experiment. Changes in diameter were recorded during local infusions of noradrenaline, bradykinin, acetylcholine, glyceryl trinitrate, L- and D-arginine and its NG-monomethyl derivatives. L-NMMA (100 nmol·min−1) stereospecifically inhibited vasodilatation induced by acetylcholine and bradykinin (p<0.02) but not that induced by the endothelium independent vasodilator glyceryl trinitrate. L-NMMA (100 nmol·min−1) potentiated the venoconstrictor effect of a high dose of acetylcholine (100 nmol·min−1) without affecting the action of noradrenaline and without having a direct venoconstrictor effect in doses up to 10 (μmol·min−1. These results show that the venous effects of certain vasodilators in man are mediated through the release of nitric oxide (EDRF) synthesised from L-arginine. They also highlight differences in basal and stimulated production of nitric oxide between arteries and veins.
Liver fibrosis regression after α-IFN and ribavirin combination therapy for chronic hepatitis C (CHC): a 6 year prospective-observational study
Authors: L. Chemello, L. Cavalletto, E. Bernardinello, A. Favaro, I. Mezzocolli, C. Donada, F. Belussi, P. Casarin, R. Colombari, A. Gatta
Journal: Journal of Hepatology (2001)
Insulin, osteoblasts, and energy metabolism: why bone counts calories
Authors: Ryan C. Riddle, Thomas L. Clemens
Journal: Journal of Clinical Investigation (2014)

Recent studies have demonstrated that insulin stimulates bone cells to produce and activate osteocalcin, an endocrine hormone that increases the efficiency of glucose metabolism through its actions on the pancreas and other peripheral tissues. In this issue of the JCI, Wei and colleagues directly explore the contribution of insulin signaling in osteoblasts to the disturbances in whole-body glucose metabolism associated with a high-fat diet. In mice fed a high-fat diet, increased uptake of saturated fatty acids by the osteoblast accelerates the ubiquitination and degradation of the insulin receptor. In this setting, impairments in osteoblast insulin signaling reduce serum levels of undercarboxylated osteocalcin, which in turn exacerbate insulin resistance in muscle and white adipose tissue. These findings underscore the importance of insulin-responsive skeletal cells as components of a newly appreciated endocrine network critical for regulating global energy homeostasis.