tbuckley/cabot-search huggingface dataset:
Estimation of inflammation by Doppler ultrasound: quantitative changes after intra-articular treatment in rheumatoid arthritis
Authors: L Terslev
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To evaluate the use of ultrasound, including quantitative Doppler analysis of synovial vascularisation, before and after intra-articular treatment with glucocorticosteroids in patients with rheumatoid arthritis (RA). <b>Methods:</b> 51 patients with RA were followed prospectively after an intra-articular glucocorticosteroid injection. Disease modifying antirheumatic drug treatment was kept unchanged and no further injections given in this observation period. At baseline, disease activity was estimated clinically by target join pain on a 100 mm visual analogue scale, on which the target joint was scored 0–3 for swelling and tenderness, and by ultrasound measurements of grey scale pixels, colour Doppler pixels, and the spectral Doppler resistive index (RI) as indicators of synovial swelling and inflammation. After four weeks, the measurements were repeated on the same joint. An observer unaware of the sequence and patient number evaluated the ultrasound images. <b>Results:</b> At one month follow up after the glucocorticosteroid injection, a marked decrease in the fraction of colour pixels was seen in 41/51 patients (Student's <i>t</i> test p&lt;0.001). Correspondingly, the RI increased indicating a diminished flow to the synovium (Student's <i>t</i> test p&lt;0.01). Both the fraction of colour pixels and the RI values corresponded with the clinical evaluation and with the subjective effect of the treatment. The synovial membrane volume estimated by total amount of pixels showed a significant decrease by 31% after treatment. <b>Conclusion:</b> Ultrasound-Doppler seems to be a promising tool for the estimation of synovial activity in arthritis. After intra-articular glucocorticosteroid, changes in RI and fraction of colour pixels may both be used as quantitative measurements of the blood flow.
Multilocular inoculation tuberculosis of the skin after stay in Africa: detection of mycobacterial DNA using polymerase chain reaction
Authors: Nenoff P, Rytter M, Schubert S, Kuhn H, Mittag M, Glander Hj, Haustein Uf
Journal: British Journal of Dermatology (2000)

Journal Article Multilocular inoculation tuberculosis of the skin after stay in Africa: detection of mycobacterial DNA using polymerase chain reaction Get access P. Nenoff, P. Nenoff Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar M. Rytter, M. Rytter Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar S. Schubert, S. Schubert Department of Internal Medicine and Search for other works by this author on: Oxford Academic Google Scholar H. Kuhn, H. Kuhn Institute of Pathology, University of Leipzig, Liebigstr. 21, D‐04103 Leipzig, GermanyE‐mail: nenp@server3.medizin.uni‐leipzig.de Search for other works by this author on: Oxford Academic Google Scholar M. Mittag, M. Mittag Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar H‐J. Glander, H‐J. Glander Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar U‐F. Haustein U‐F. Haustein Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 1, 1 July 2000, Pages 226–228, https://doi.org/10.1046/j.1365-2133.2000.03640.x Published: 01 July 2000
Abnormal Brain Activation During Inhibition and Error Detection in Medication-Naive Adolescents With ADHD
Authors: Katya Rubia, Anna B. Smith, Michael J. Brammer, Brian Toone, Eric Taylor
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Patients with attention deficit hyperactivity disorder (ADHD) and a medication history have shown abnormal brain activation in prefrontal and striatal brain regions during cognitive challenge. Previous findings have been confounded, however, by potential long-term effects of stimulant medication exposure and group discrepancies in task performance. The aim of this study was to investigate whether medication-naive adolescents with ADHD would still show abnormal brain activation in prefrontal brain regions during motor response inhibition in a task designed to control for intergroup performance discrepancies. METHOD: Rapid, event-related functional magnetic resonance imaging was used to compare brain activation in 16 medication-naive ADHD adolescents and 21 IQ-, age-, and sex-matched healthy comparison volunteers during a challenging, idiosyncratically adjusted task that required withholding of a triggered motor response. The design, which manipulated task parameters to force each subject to fail on 50% of trials, ensured that subjects worked at the edge of their own inhibitory performance, thereby controlling for intersubject and intergroup performance discrepancies and furthermore allowing for investigation of differences in brain activation related to inhibition and inhibition failure. RESULTS: Medication-naive adolescents with ADHD showed significantly reduced brain activation in the right inferior prefrontal cortex during successful motor response inhibition and in the precuneus and posterior cingulate gyrus during inhibition failure, both of which correlated with behavioral scores of ADHD. CONCLUSIONS: The study shows that abnormal brain activation during inhibitory challenge in ADHD is specific to the disorder, since it persists when medication history and performance discrepancies are excluded.
AN EXERCISE PROFESSIONAL LED, COMMUNITY BASED, DIETARY AND EXERCISE PROGRAMME FOR KNEE OSTEOARTHRITIS
Authors: D Evans, D Gibbons, N Hazard, R Williams, A Jones, R Martin
Journal: British Journal of Sports Medicine (2013)

NICE guidance stipulates exercise and weight loss as ‘Core’ treatments for Osteoarthritis (OA). Typically, NHS physiotherapists and dieticians deliver these treatments within the secondary health care setting. Given increasing demands placed upon secondary health care professionals, we conducted a novel, community based, registered exercise professional led, exercise and dietary intervention in obese patients with established knee OA, to evaluate its efficacy and potentially widespread use within the National Exercise Referral Scheme in Wales. 81 patients (BMI&lt;30) with knee OA were invited (mean age 57 y, BMI 39.5 kg/m 2 ) from Orthopaedic, Rheumatology and Primary care settings. 58 patients declined to take part. 1 patient was excluded at assessment due to medical concerns. The pilot was a 16 week dietary and exercise programme delivered in the community setting. Patients performed 2 x1 hour per week of a 10-station exercise carousel incorporating aerobic and resistance exercise aimed at quadriceps and hamstring strengthening. 1 hour per week of dietary education was given, using Public Health Wales’ ‘Foodwise for Life’ programme, and 3 sessions of practical cooking skills over 16 weeks. Primary outcome measures were the Oxford Knee Score (OKS); Quality of Life (QoL) (EQ-5D+EQ-VAS); physical function (6 minute walk test (6MWT) and 30 second sit-stand (30 s s-s)). Secondary measures; body weight; resting Blood Pressure(BP); resting heart rate (RHR). 18 patients completed the 16 week programme. Improvements were seen in OKS (p=0.048), 6MWT (p&lt;0.001), 30 s s-s (p&lt;0.001), EQ-VAS (p=0.01), weight (p=0.001) and systolic BP (p&lt;0.001). No significant improvements were seen in diastolic BP (p=0.96), RHR (p=0.11) and EQ-5D (p=0.11). This pilot suggests a community based, exercise professional led intervention for patients with knee OA as a clinically effective therapeutic resource for health professionals.
A history lesson
Authors: M. P. C. Smith
Journal: BMJ (2010)

Debates on the legitimacy of a diagnosis of attention deficit hyperactivity disorder (ADHD) in children or adults are still raging1 2 because of a lack of understanding of the history of the disorder. Drug companies have indeed marketed the concept of adult ADHD to potential consumers1—as they did childhood ADHD to parent-teacher associations in the …
Parathyroid Hormone Activates TRPV5 via PKA-Dependent Phosphorylation
Authors: Theun de Groot, Kyupil Lee, Michiel Langeslag, Qi Xi, Kees Jalink, René J.M. Bindels, Joost G.J. Hoenderop
Journal: Journal of the American Society of Nephrology (2009)

Low extracellular calcium (Ca<sup>2+</sup>) promotes release of parathyroid hormone (PTH), which acts on multiple organs to maintain overall Ca<sup>2+</sup> balance. In the distal part of the nephron, PTH stimulates active Ca<sup>2+</sup> reabsorption <i>via</i> the adenylyl cyclase–cAMP–protein kinase A (PKA) pathway, but the molecular target of this pathway is unknown. The transient receptor potential vanilloid 5 (TRPV5) channel constitutes the luminal gate for Ca<sup>2+</sup> entry in the distal convoluted tubule and has several putative PKA phosphorylation sites. Here, we investigated the effect of PTH-induced cAMP signaling on TRPV5 activity. Using fluorescence resonance energy transfer, we studied cAMP and Ca<sup>2+</sup> dynamics during PTH stimulation of HEK293 cells that coexpressed the PTH receptor and TRPV5. PTH increased cAMP levels, followed by a rise in TRPV5-mediated Ca<sup>2+</sup> influx. PTH (1 to 31) and forskolin, which activate the cAMP pathway, mimicked the stimulation of TRPV5 activity. Remarkably, TRPV5 activation was limited to conditions of strong intracellular Ca<sup>2+</sup> buffering. Cell surface biotinylation studies demonstrated that forskolin did not affect TRPV5 expression on the cell surface, suggesting that it alters the single-channel activity of a fixed number of TRPV5 channels. Application of the PKA catalytic subunit, which phosphorylated TRPV5, directly increased TRPV5 channel open probability. Alanine substitution of threonine-709 abolished both <i>in vitro</i> phosphorylation and PTH-mediated stimulation of TRPV5. In summary, PTH activates the cAMP-PKA signaling cascade, which rapidly phosphorylates threonine-709 of TRPV5, increasing the channel9s open probability and promoting Ca<sup>2+</sup> reabsorption in the distal nephron.
Oscillatory and Steady Laminar Shear Stress Differentially Affect Human Endothelial Redox State
Authors: Gilles W. De Keulenaer, David C. Chappell, Nobukazu Ishizaka, Robert M. Nerem, R. Wayne Alexander, Kathy K. Griendling
Journal: Circulation Research (1998)

Abstract —Atherosclerotic lesions are found opposite vascular flow dividers at sites of low shear stress and oscillatory flow. Since endothelial proinflammatory genes prominent in lesions are regulated by oxidation-sensitive transcriptional control mechanisms, we examined the redox state of cultured human umbilical vein endothelial cells after either oscillatory or steady laminar fluid shear stress. Endothelial oxidative stress was assessed by measuring activity of the superoxide (O 2 · − )–producing NADH oxidase (a major source of reactive oxygen species in vascular cells), intracellular O 2 · − levels, induction of the redox-sensitive gene heme oxygenase-1 (HO-1), and abundance of Cu/Zn superoxide dismutase (Cu/Zn SOD), an antioxidant defense enzyme whose level of expression adapts to changes in oxidative stress. When cells were exposed to oscillatory shear (±5 dyne/cm 2 , 1 Hz) for 1, 5, and 24 hours, NADH oxidase activity and the amount of HO-1 progressively increased up to 174±16% ( P &lt;0.05) and 505±111% ( P &lt;0.05) versus static conditions, respectively, whereas levels of Cu/Zn SOD remained unchanged. This upregulation of HO-1 was completely blocked by the antioxidant N -acetylcysteine (NAC, 20 mmol/L). In contrast, steady laminar shear (5 dyne/cm 2 ) induced NADH oxidase activity and NAC-sensitive HO-1 mRNA expression only at 1 and 5 hours, a transient response that returned toward baseline at 24 hours. Levels of Cu/Zn SOD mRNA and protein were increased after 24 hours of steady laminar shear. Furthermore, intracellular O 2 · − , as measured by dihydroethidium fluorescence, was higher in cells exposed to oscillatory than to laminar shear. These data are consistent with the hypothesis that continuous oscillatory shear causes a sustained activation of pro-oxidant processes resulting in redox-sensitive gene expression in human endothelial cells. Steady laminar shear stress initially activates these processes but appears to induce compensatory antioxidant defenses. We speculate that differences in endothelial redox state, orchestrated by different regimens of shear stress, may contribute to the focal nature of atherosclerosis.
Organization of Rheumatism Research and Treatment in Sweden
Authors: J. A. Hojer
Journal: Annals of the Rheumatic Diseases (1946)

As I understand the term,," rheumatism research " includes clinicaf investigation for further differ- entiation, and search for the aetiological factor or factors in acute rheumatic fever and chronic arthritis." When this factor is discovered and established ", says an old textbook, " it should be easy to determine its precise relations to the fairly well studied lesions in several organs."Un- fortunately, we know too little to say much about it.In Sweden we thought that in present circumstances we could do nothing better than build an institute for research.This institute, which we hope will open early in 1948, is called " The Institute of Gustav V for Research into the Chief Invaliding Diseases, especially Rheumatism and Poliomyelitis ". * Summary of a lecture given before the Empire Rheumatism Council on October 26, 1946.many threads connecting these two deficiency diseases with the problem of vitamins.Similarly, from rheumatism as a clinical disease there are fine rootlets leading down to the origin of the evil.Laboratory research devises new methods which are necessary if such work is to be pursued to its con- clusions, but these methods must be applied to the clinically diseased patient.By following the small but important and often long overlooked clinical features, the research worker may get inspiration.
Ischaemic preconditioning is protein kinase C dependent but not through stimulation of adrenergic or adenosine receptors in the isolated rat heart
Authors: E. Bugge, K. Ytrehus
Journal: Cardiovascular Research (1995)

The aim was (1) to clarify whether alpha adrenoceptor and adenosine receptor stimulation is involved in the anti-infarct effect of ischaemic preconditioning in the rat heart, and (2) to test the hypothesis that signal transduction through membrane bound protein kinase C is essential for the protection.Isolated, buffer perfused rat hearts were subjected to 30 min of regional ischaemia and 120 min of reperfusion. The risk zone was determined by fluorescent particles, and infarct size was determined by staining with triphenyltetrazolium chloride.Ischaemic preconditioning with three cycles of 5 min ischaemia plus 5 min of reperfusion significantly reduced infarct size as compared to non-preconditioned group [4.5(SEM 0.6)% of the risk zone v 45.5(5.7)%, P < 0.001]. Blockade of alpha adrenoceptors alone and simultaneous blockade of alpha adrenoceptors with phenoxybenzamine (10 microM) and adenosine receptors with sulphophenyltheophylline (100 microM) did not prevent the protective effect of ischaemic preconditioning [infarct size = 2.4(0.4) and 5.6(1.9)% respectively, NS v the non-treated preconditioned group]. Blocking either the membrane binding of protein kinase C with polymyxin B (1 microM) or direct inhibition of protein kinase C activity with chelerythrine (2 microM) completely abolished the infarct size reducing effect of ischaemic preconditioning [32.4(3.3)% and 48.2(4.0)% respectively, P < 0.005 v non-treated preconditioned group: NS v the non-preconditioned group].In the rat heart infarct model the protective effect of ischaemic preconditioning is not mediated through stimulation of alpha adrenoceptors alone or the combined stimulation of alpha adrenergic and adenosine receptors, and it is dependent on activation of membrane bound protein kinase C.
Skin-Resident Murine Dendritic Cell Subsets Promote Distinct and Opposing Antigen-Specific T Helper Cell Responses
Authors: Botond Z. Igyártó, Krystal Haley, Daniela Ortner, Aleh Bobr, Maryam Gerami-Nejad, Brian T. Edelson, Sandra M. Zurawski, Bernard Malissen, Gerard Zurawski, Judith Berman, Daniel H. Kaplan
Journal: Immunity (2011)
Trends in the Supply of Medical Personnel in the Russian Federation
Authors: T. Michael Ryan
Journal: JAMA (1996)

IN THE former Soviet Union the supply of personnel for even skilled professional occupations was characterized by an emphasis on quantity of output rather than quality of training. That defining feature resulted from the untrammeled power of the Soviet leadership to impose its priorities for socioeconomic development in a polity that did not allow independent professional associations. By the time the "administrative-command" system of planning started to be discredited in the late 1980s, the Soviet Union had far outstripped its capitalist rivals with respect to the ratio of physicians to population. Predictably, Soviet authorities published cross-national comparisons that had propaganda value at home and abroad. They were able to show, for example, that Japan had less than half and the United States less than two thirds of the Soviet Union's ratio of physicians to total population (Table 1).<sup>1</sup> The authorities did not attempt to adjust this quantitative indicator to
A morphine-oxycodone combo pill: toward the "holy grail" for opioids or a justifiably rejected drug?
Authors: S. M. Wolfe
Journal: BMJ (2014)

In 1997, the Australian drug company QRx took out a US patent entitled, “Production of analgesic synergy by co-administration of sub-analgesic doses of a mu opioid agonist and a kappa-2 opioid agonist” for MoxDuo, a combination pill containing morphine and oxycodone.1 Early in its development, according to the FDA, QRx stated that its product “would provide a synergistic effect resulting in the need for lower overall opioid doses and an improved safety profile.”2

In a November 2012 memo referring to the results of a recently completed randomized clinical trial on MoxDuo, the company stated: “The 75 year search for a product having opioid efficacy without the typically associated adverse events has been compared with that for the Holy Grail.”1 The company was referring to a review of the history of opioid research in the British Journal of Pharmacology .3

The QRx memo continued, “To the best of our knowledge, MoxDuo IR [instant release] is the first opioid product to demonstrate a lower risk of respiratory depression in a clinical study comparing morphine equivalent (equianalgesic) doses. These important benefits provide the potential for …
478 INFECTIONS DURING PEGINTERFERON (PEGIFN)/RIBAVIRIN (RBV) THERAPY ARE ASSOCIATED WITH THE MAGNITUDE OF DECLINE IN THE LYMPHOCYTE COUNT: RESULTS OF THE IDEAL STUDY
Authors: M. Melia, N. Brau, F. Poordad, E.J. Lawitz, M. Shiffman, J. McHutchison, A. Muir, G. Galler, J. McCone, L. Nyberg, W. Lee, R. Ghalib, E. Schiff, J. Long, S. Noviello, C.A. Brass, L.D. Pedicone, J. Albrecht, M.S. Sulkowski
Journal: Journal of Hepatology (2011)
Influenza infection: the origin and role of IL10
Authors: L Cunningham
Journal: Thorax (2009)

With fears of an influenza pandemic looming, understanding the mechanism by which pathogenic strains of influenza cause lethal lung injury could not be more relevant. Interleukin 10 (IL10) is an anti-inflammatory cytokine recognised to prevent excessive injury in bacterial and parasitic infections. This series of elegant experiments focuses on the role of IL10 in influenza-infected mice, the proportion of IL10 produced …
The Accuracy of Diagnosis of an Online Consultation Service Compared With Physical Consultation With a Dermatologist
Authors: Evelyn Grünig, Sabine Schmidt-Weitmann, Christiane Brockes-Bracht, Günther F. L. Hofbauer
Journal: JAMA Dermatology (2015)

Results | Twenty-three of 200 (11.5%)LST larvae attached to 8 of the 10 participants during the 15-minute period.Tick attachment could easily be verified by observing the splayed palps and inserted hypostome (Figure 1B).On 1 research participant, there was immediate lesion development-two 1-to 2-mm erythematous macules (Figure 2A)-while 5 other participants developed erythematous pruritic papules within 48 hours (Figure 2B).In the participant who developed immediate lesions, these 2 macules became papulovesicular within 48 hours (Figure 2C), as did 3 other lesions on the same person on the other arm (Figure 2D).Discussion | We show here that tissue damage from insertion of LST mouthparts and degranulating mast cells may be evident in as little as 15 minutes and may manifest as macules, papules, or vesicles.A previous study 6 showed that A americanum was the predominant species found attached to humans in Mississippi during a 10-year time span, and 10 of 36 (27.8%)LST larvae found on humans were either partially or completely engorged.That study, as well as these new data, indicate that the LST is an aggressive humanbiting tick species that may readily produce cutaneous lesions in humans.
Structural, Functional, and Molecular MR Imaging of the Microvasculature
Authors: Michal Neeman, Hagit Dafni
Journal: Annual Review of Biomedical Engineering (2003)

▪ Abstract Magnetic resonance imaging (MRI) is widely applied for functional imaging of the microcirculation and for functional and structural studies of the microvasculature. The interest in the capabilities of MRI in noninvasively monitoring changes in vascular structure and function expanded over the past years, with specific efforts directed toward the development of novel imaging methods for quantification of angiogenesis. Molecular imaging approaches hold promise for further expansion of the ability to characterize the microvasculature. Exciting applications for MRI are emerging in the study of the biology of microvessels and in the evaluation of potential pharmaceutical modulators of vascular function and development, and preclinical MRI tools can serve for the design of mechanism-of-action-based noninvasive clinical methods for monitoring response to therapy. The aim of this review is to provide a current snapshot of recent developments in this rapidly evolving field.