tbuckley/cabot-search huggingface dataset:
Effects of Thyroid Hormone on Cardiac β-Adrenergic Responsiveness in Conscious Baboons
Authors: Brian D. Hoit, Saeb F. Khoury, Yanfu Shao, Marjorie Gabel, Stephen B. Liggett, Richard A. Walsh
Journal: Circulation (1997)

Background Many of the cardiovascular manifestations of thyroid hormone excess resemble those produced by sympathoadrenal stimulation. The objective of this study was to determine the effects of thyroid hormone excess on myocardial β-adrenergic expression and responsiveness to infused agonists in the primate heart. Methods and Results The responses of left ventricular isovolumic contraction (dP/dt max ) and relaxation (τ) during graded dobutamine infusion were studied both before and after 4 weeks of thyroid hormone administration in 8 chronically instrumented baboons. At matched (atrially paced) heart rates, thyroid hormone significantly increased resting dP/dt max (3073±1034 versus 2318±829 mm Hg/s, P &lt;.05) and decreased τ (24.0±5.5 versus 28.2±5.4 ms, P &lt;.05). The change from baseline for dP/dt max and τ in response to β 1 -adrenergic stimulation was significant at each dobutamine dose (2.5 to 10 μg·kg −1 ·min −1 ), but when expressed as a percent change, it was similar before versus after thyroid hormone. Similar changes were found when β 2 -adrenergic stimulation was produced by terbutaline infusion in three additional baboons. β-Adrenergic receptor (βAR) expression was higher in five thyroxine-treated than in five control baboons (37.4±1.2 versus 15.7±3.2 fmol/mg, P &lt;.001), and this was due to a greater increase in the β 2 AR (5.9±1.5 to 20.6±1.2 fmol/mg, P &lt;.001) than the β 1 AR (9.7±1.7 to 16.8±0.1 fmol/mg, P &lt;.01) subtype. Conclusions In the primate heart, thyroid hormone produces positive inotropic and lusitropic effects in the resting state and upregulates both β 1 AR and β 2 AR, with the β 2 AR increase predominating. At equivalent rates, however, thyroid hormone excess does not appear to enhance the sensitivity of left ventricular contractility and relaxation to either β 1 - or β 2 -adrenergic stimulation.
Scintigraphic Evaluation of Polyostotic Fibrous Dysplasia
Authors: WILLIAM D. JOHNS, SHIV M. GUPTA, NAILA KAYANI
Journal: Clinical Nuclear Medicine (1987)

Bone scintigraphy is a sensitive imaging modality for detecting early lesions and polyostotic involvement in fibrous dysplasia. Common findings include multiple areas of focal uptake that are often unilateral and typically involve the ribs, tibia, femur, and craniofacial bones. A knowledge of various skeletal manifestations of fibrous dysplasia is helpful to distinguish it from Paget's disease, osteoblastic metastasis, and fractures. Several recent cases representing varying involvement of fibrous dysplasia are presented and the literature is reviewed.
P99 Comparison Of Multiple Breath Washout Using A Commercial Device And A Mass Spectrometer In School Age Children With Cystic Fibrosis
Authors: J. Duncan, E. Raywood, A. Bush, J. Stocks, P. Aurora
Journal: Thorax (2014)

<h3>Background</h3> Lung clearance index (LCI) measured by multiple breath washout (MBW) is a sensitive indicator of early lung disease in Cystic Fibrosis (CF).<sup>1</sup> MBW using sulphur hexafluoride (SF<sub>6</sub>) and mass spectrometry (MS) is currently the gold standard, but equipment is limited to a few centres. Although commercial devices based on SF<sub>6</sub> have been developed, use of SF<sub>6</sub> is expensive and restricted in some countries. Commercial devices using nitrogen (N<sub>2</sub>), which is cheaper and widely available, have been developed recently to increase accessibility of this test in research and clinical practice but have yet to be validated in children. The aim of this study was to compare values of LCI and Functional Residual Capacity (FRC) in children using the N<sub>2-</sub>MBW EasyOne Pro® LAB system (ndd Medical Technologies) and the MS (AMIS 2000, Innovision ApS). <h3>Methods</h3> School-age children with CF and healthy controls completed MBW in triplicate on both the EasyOne Pro® and MS in random order on the same occasion. Within-subject agreement between devices for LCI and FRC was assessed by Bland-Altman analysis. <h3>Results</h3> Of the 50 children recruited, all completed testing using MS, while 5 failed quality control on the EasyOne Pro® LAB. Paired results from both devices were obtained in 26 children with CF (mean age [range]) (13.3y[7.8y-17.4y]) and 19 controls (14.8y [12.5y-16.7y]). LCI was significantly higher in those with CF when using both devices (mean difference[95% CI], CF-controls): 2.47[1.4;3.5] for the MS-SF<sub>6</sub> and 2.20[1.2–3.2] for N<sub>2</sub>-MBW. There were no significant group differences between devices for either LCI (mean difference[95% CI]) -0.14[-0.45;0.16] or FRC -0.15L[-0.2;-0.08]. Within-subject variability was proportional to mean values (see Figure) and ranged from 0.4–15.7% for LCI and 0.0–19.6% for FRC. <h3>Conclusion</h3> Despite some previous reports that N<sub>2-</sub>washout results in higher LCI values than MS-SF<sub>6 </sub>washout, on average, we found similar values in both healthy school-age children and those with CF. Further work is required to examine causes of within-subject variability and assess validity and sensitivity over a wider age range, including preschool children, before commercial N<sub>2</sub>-MBW devices can be confidently used in multi-centre trials. <h3>Reference</h3> Aurora <i>et al</i>. <i>Am J Respir Crit Care Med. </i>2011;183:752–8
Cancer of the Nail Bed
Authors: Frank R. Dutra
Journal: JAMA (1979)

To the Editor.—  The article on squamous cell carcinoma of the nail bed by Long and Espiniella states that a review of the literature on primary nail-bed malignant neoplasms disclosed a total of only 53 reported cases, the majority of which were squamous cell carcinomas, with the remainder consisting of Bowen's disease and basal cell carcinomas.  I believe that this statement should be corrected, since malignant melanomas unquestionably are the most frequent malignant tumors of this region. Although subungual lesions make up only 2% to 3% of all malignant melanomas, there are reports of many more than 53 cases of primary melanomas of the nail bed. For example, one series reported by Pack and Oropeza 1 described 72 patients with such lesions. Furthermore, contrary to the article in JAMA that states that squamous cell carcinoma is the most serious of the primary nail-bed tumors, there is ample evidence that melanomas
Anticoagulant for Westergren Sedimentation
Authors: Joseph G. Fink
Journal: JAMA (1968)

<h3>To the Editor:—</h3> The answer to the query concerning the appropriate anticoagulant for the Westergren method for determining the erythrocyte sedimentation rate (<b>205</b>:653, 1968) does not emphasize the considerable influence that the anticoagulant may have on the results. Gambino et al (<i>Amer J Clin Path</i><b>43</b>: 173, 1965) and Dawson (<i>Brit Med J</i><b>1</b>:1697, 1960) have shown that blood collected in edetic acid (EDTA) yields unreliable and irreproducible erythrocyte sedimentation rates in the Westergren tube, unless a dilution of the whole blood is made in the test procedure. My own experience confirms the work of these authors. In view of the widespread adoption of the EDTA anticoagulant for hematologic studies, it would seem essential to use a diluted blood aliquot in the Westergren technique if this test is to have any value at all, in terms of accurate reflection of clinical status and of standardization.
Hemiparesis in Cervical Spondylosis
Authors: Eliot M. Wallack
Journal: JAMA (1976)

Two patients with hemiparesis were thought to have intracranial lesions. Cervical spondylosis was discovered, and the condition of both patients improved after laminectomy. Although it has been rarely emphasized in the past, cervical spondylosis should be considered in the differential diagnosis of hemiparesis.
Proviral integration site for Moloney murine leukemia virus 1, but not phosphatidylinositol-3 kinase, is essential in the antiapoptotic signaling cascade initiated by IL-5 in eosinophils
Authors: Nicola Andina, Svetlana Didichenko, Jan Schmidt-Mende, Clemens A. Dahinden, Hans-Uwe Simon
Journal: Journal of Allergy and Clinical Immunology (2009)
High-Density Lipoprotein-Cholesterol in Marathon Runners During a 20-Day Road Race
Authors: Rudolph H. Dressendorfer, Charles E. Wade, Conrad Hornick, Gerald C. Timmis
Journal: JAMA (1982)

Plasma high-density lipoprotein (HDL)-cholesterol and lipid levels were measured in 12 male marathon runners (mean age, 40 years) who ran an average of 28 km/day for ten days, rested 70 hours, then continued to run for eight more days, covering a total distance for both running periods of 500 km. Blood samples were obtained on eight mornings. After one week of running, HDL-cholesterol levels increased 18% and triglyceride levels decreased 22%. However, the three-day rest period reversed these changes. As running resumed, HDL-cholesterol levels again increased and triglyceride levels decreased. There were no significant changes in total cholesterol, body weight, or skinfold thickness despite an average caloric intake of 4,800 kcal/day. Heavy beer drinking had no discernible effect on HDL-cholesterol levels, but may have caused mild hepatic injury as suggested by significantly increased serum alanine transferase and γ-glutamyl transferase values. This study demonstrates that HDL-cholesterol levels increase with higher running mileage and decrease within days of stopping exercise when caloric and alcohol intake remain elevated. (<i>JAMA</i>1982;247:1715-1717)
Frequent somatic mutations in components of the RNA processing machinery in chronic lymphocytic leukemia
Authors: A J Ramsay, D Rodríguez, N Villamor, A Kwarciak, J R Tejedor, J Valcárcel, A López-Guillermo, A Martínez-Trillos, X S Puente, E Campo, C López-Otín, V Quesada
Journal: Leukemia (2012)
Multiple Metastatic Calcifications Detected by Bone Scintigraphy and Demonstrated by CT
Authors: YOSHIMASA IMANISHI, MASAKI KISHIRO, OSAMU MIYAZAKI, TATSUKI TOYOKAWA, KAZUNORI KUROKI, HITOSHI HAJI, TOHRU ISHIKAWA
Journal: Clinical Nuclear Medicine (1992)

Metastatic calcifications according to histopathologic and scintigraphic findings have been well-defined. The authors report a postoperative case of hyperparathyroidism with multiple metastatic calcifications in the lung, kidney, stomach, heart, and vessels that were primarily detected by bone scintigraphy and demonstrated by CT. Tc-99m MDP bone scintigraphy showed a markedly increased accumulation of radioactivity diffusely throughout the lung, left ventricular wall, both kidneys, and the gastric cardia and body. In the lung, plain films showed almost normal lung. CT, however, demonstrated patchy, slightly increased densities in the lung bilaterally. Cardiac CT indicated a considerably increased density of the ventricular myocardium and remarkable calcification in or near the atrioventricular septum or annulus fibrosus. Upper abdominal CT demonstrated increased densities diffusely throughout the gastric mucosa and renal cortex. Only vascular calcifications were depicted by plain films. Using both bone scintigraphy and CT provides accurate information about each lesion and each tissue, allowing precise diagnosis of even a questionable lesion in the early stage of metastatic calcification. Early diagnosis and early therapy offer the best chance for cure or palliative therapy.
Sox4 Is a Master Regulator of Epithelial-Mesenchymal Transition by Controlling Ezh2 Expression and Epigenetic Reprogramming
Authors: Neha Tiwari, Vijay K. Tiwari, Lorenz Waldmeier, Piotr J. Balwierz, Phil Arnold, Mikhail Pachkov, Nathalie Meyer-Schaller, Dirk Schübeler, Erik van Nimwegen, Gerhard Christofori
Journal: Cancer Cell (2013)

Highlights•Sox4 is critical for EMT and for experimental primary tumor growth and metastasis•Sox4 directly regulates EMT-relevant genes, among them Ezh2•Ezh2 function and thus H3K27me3 are required for EMT•The expression of Ezh2-regulated genes is predictive for patient survivalSummaryGene expression profiling has uncovered the transcription factor Sox4 with upregulated activity during TGF-β-induced epithelial-mesenchymal transition (EMT) in normal and cancerous breast epithelial cells. Sox4 is indispensable for EMT and cell survival in vitro and for primary tumor growth and metastasis in vivo. Among several EMT-relevant genes, Sox4 directly regulates the expression of Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 (H3K27me3) for gene repression. Ablation of Ezh2 expression prevents EMT, whereas forced expression of Ezh2 restores EMT in Sox4-deficient cells. Ezh2-mediated H3K27me3 marks associate with key EMT genes, representing an epigenetic EMT signature that predicts patient survival. Our results identify Sox4 as a master regulator of EMT by governing the expression of the epigenetic modifier Ezh2.Graphical abstract
Orthopedic Gene Therapy in 2008
Authors: Christopher H Evans, Steven C Ghivizzani, Paul D Robbins
Journal: Molecular Therapy (2008)

Orthopedic disorders, although rarely fatal, are the leading cause of morbidity and impose a huge socioeconomic burden. Their prevalence will increase dramatically as populations age and gain weight. Many orthopedic conditions are difficult to treat by conventional means; however, they are good candidates for gene therapy. Clinical trials have already been initiated for arthritis and the aseptic loosening of prosthetic joints, and the development of bone-healing applications is at an advanced, preclinical stage. Other potential uses include the treatment of Mendelian diseases and orthopedic tumors, as well as the repair and regeneration of cartilage, ligaments, and tendons. Many of these goals should be achievable with existing technologies. The main barriers to clinical application are funding and regulatory issues, which in turn reflect major safety concerns and the opinion, in some quarters, that gene therapy should not be applied to nonlethal, nongenetic diseases. For some indications, advances in nongenetic treatments have also diminished enthusiasm. Nevertheless, the preclinical and early clinical data are impressive and provide considerable optimism that gene therapy will provide straightforward, effective solutions to the clinical management of several common debilitating disorders that are otherwise difficult and expensive to treat.
Furrowed brow over mad cow
Authors: G W Roberts
Journal: BMJ (1995)

Anxieties over the possibility that material from or contact with cows infected with bovine spongiform encephalopathy might cause Creutzfeldt-Jakob disease revolve around three questions. Could it happen? Bovine spongiform encephalopathy in cows, scrapie in sheep and experimental animals, and Creutzfeldt-Jakob disease are all caused by the same class of pathogen and are more accurately called prion diseases.1 Human prion disease is rare, but the public health importance of prion disease far exceeds its rarity for the following reasons. It has been transmitted experimentally to various animal species1 2 (bovine spongiform encephalopathy has been transmitted experimentally in primates), and accidental person to person transmission has occurred.3 In addition, it has been shown that prion disease can be transmitted orally by the ingestion of infected foodstuffs or infected tissues.4 5 The …
EMA consults public on plan to increase transparency of drug trial data
Authors: D. Cohen
Journal: BMJ (2013)

The European Medicines Agency has stated its commitment to publishing clinical trial information on all drugs submitted as part of the licensing process, whether or not they are approved.

In a new draft policy document that has been distributed for consultation,1 the agency suggests that opening up its data would have many benefits for public health. Not only would it make drug development more efficient and aid the gathering of new knowledge, the European regulator said, but it would also allow better informed use of drugs and “enable third parties to verify the regulatory authority’s positions and challenge them where appropriate.”

Academics who have campaigned for access to trial data have broadly welcomed the move.

Tom Jefferson, one of the Cochrane Collaboration team that has accessed and analysed data …
India faces drug resistant leishmaniasis
Authors: G. Mudur
Journal: BMJ (2002)

Untreated patients and drug resistant strains of the Leishmania donovani parasite are obstructing India's efforts to control leishmaniasis, doctors cautioned at a conference in New Delhi last week.

India's health ministry has announced a control plan that is aimed at reducing the incidence of leishmaniasis to 25% by the year 2005 and declaring India free of the infection by 2012.

“Less than 10% of the infected seek medical treatment, and 60% of cases in Bihar, the worst affected state, are resistant to the first line drug,” said Dr Philippe Desjeux, coordinator of leishmaniasis control at the World Health Organization in …
Resection of Carotid Body (Cervical Glomectomy) for Asthma
Authors: Richard H. Overholt
Journal: JAMA (1962)

Intractable asthma which had not been relieved by desensitization, bronchodilators, changes of climate, steroids, and other standard therapeutic methods was treated in 157 patients by removal of one carotid body and in 3 others by removal of both carotid bodies. The glomectomy was done under local anesthesia. Some patients reported noticeable relief either after the novocain was injected into the carotid body, or at the instant of its removal. Slightly over half of the patients were either dramatically or significantly improved. No alterations of blood pressure or of heart rate were observed, and there were no immediate or late untoward sequelae.
The chilling effect of English libel law
Authors: R. Hurley
Journal: BMJ (2009)

<h3>Abstract</h3> Practical biodiversity conservation relies on delineation of biologically meaningful units, particularly with respect to global conventions and regulatory frameworks. Traditional approaches have typically relied on morphological observation, resulting in artificially broad delineations and non-optimal species units for conservation. More recently, species delimitation methods have been revolutionised with High-Throughput Sequencing approaches, allowing study of diversity within species radiations using genome-wide data. The highly mobile elasmobranchs, manta and devil rays (<i>Mobula</i> spp.), are threatened globally by targeted and bycatch fishing pressures resulting in recent protection under several global conventions. However, a lack of global data, morphological similarities, a succession of recent taxonomic changes and ineffectual traceability measures combine to impede development and implementation of a coherent and enforceable conservation strategy. Here, we generate genome-wide Single Nucleotide Polymorphism (SNP) data from among the most globally and taxonomically representative set of mobulid tissues. The resulting phylogeny and delimitation of species units represents the most comprehensive assessment of mobulid diversity with molecular data to date. We find a mismatch between current species classifications, and optimal species units for effective conservation. Specifically, we find robust evidence for an undescribed species of manta ray in the Gulf of Mexico and show that species recently synonymised are reproductively isolated. Further resolution is achieved at the population level, where cryptic diversity is detected in geographically distinct populations, and indicates potential for future traceability work determining regional location of catch. We estimate the optimal species tree and uncover substantial incomplete lineage sorting, where standing variation in extinct ancestral populations is identified as a driver of phylogenetic uncertainty, with further conservation implications. Our study provides a framework for molecular genetic species delimitation that is relevant to wide-ranging taxa of conservation concern, and highlights the potential for genomic data to support effective management, conservation and law enforcement strategies.
Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucose Metabolism
Authors: Nora D. Volkow
Journal: JAMA (2011)

<h3>Context</h3>The dramatic increase in use of cellular telephones has generated concern about possible negative effects of radiofrequency signals delivered to the brain. However, whether acute cell phone exposure affects the human brain is unclear.<h3>Objective</h3>To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity.<h3>Design, Setting, and Participants</h3>Randomized crossover study conducted between January 1 and December 31, 2009, at a single US laboratory among 47 healthy participants recruited from the community. Cell phones were placed on the left and right ears and positron emission tomography with (<sup>18</sup>F)fluorodeoxyglucose injection was used to measure brain glucose metabolism twice, once with the right cell phone activated (sound muted) for 50 minutes (“on” condition) and once with both cell phones deactivated (“off” condition). Statistical parametric mapping was used to compare metabolism between on and off conditions using paired t tests, and Pearson linear correlations were used to verify the association of metabolism and estimated amplitude of radiofrequency-modulated electromagnetic waves emitted by the cell phone. Clusters with at least 1000 voxels (volume &gt;8 cm<sup>3</sup>) and P &lt; .05 (corrected for multiple comparisons) were considered significant.<h3>Main Outcome Measure</h3>Brain glucose metabolism computed as absolute metabolism (μmol/100 g per minute) and as normalized metabolism (region/whole brain).<h3>Results</h3>Whole-brain metabolism did not differ between on and off conditions. In contrast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher for on than off conditions (35.7 vs 33.3 μmol/100 g per minute; mean difference, 2.4 [95% confidence interval, 0.67-4.2]; P = .004). The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism (R = 0.95, P &lt; .001) and normalized metabolism (R = 0.89; P &lt; .001).<h3>Conclusions</h3>In healthy participants and compared with no exposure, 50-minute cell phone exposure was associated with increased brain glucose metabolism in the region closest to the antenna. This finding is of unknown clinical significance.
Hand dermatosis in upper secondary school pupils: 2-year comparison and follow-up
Authors: M. Yngveson, Å. Svensson, A. Johannisson, Å. Isacsson
Journal: British Journal of Dermatology (2000)

Abstract The purpose of this comparative study was to record the prevalence and to estimate the incidence of self-reported hand dermatosis in a cohort of upper secondary school pupils on two different occasions, in 1995 and 1997. A previously validated questionnaire was used. Of the 1273 pupils invited to participate, 1136 (89·2%) responded to the questionnaire. The 1-year prevalence increased, although not significantly, from 9·6% in 1995 to 10·5% in 1997. For girls, the 1-year prevalence increased significantly, from 12·4% to 15·7%, while for boys the 1-year prevalence decreased, but not significantly, from 6·7% to 5·1%. The cumulative incidence was significantly higher (P &amp;lt; 0·001) among the girls (10·5%) than among the boys (2·8%). Multiple logistic regressions showed that the highest risk factors for 1-year prevalence in 1995 were having self-reported childhood eczema, and a family history of atopic eczema or asthma. In 1997, the highest risk factors were self-reported childhood eczema, female gender and a family history of atopic eczema. This study has identified the point at which the genders diverge with regard to hand dermatosis, with boys tending to recover, while girls show a steady or even increasing prevalence.