213 research outputs found
Effects of Renal Denervation on Insulin Sensitivity and Inflammatory Markers in Nondiabetic Patients with Treatment-Resistant Hypertension
Increased sympathetic activity is important in the pathogenesis of hypertension and insulin resistance. Afferent signaling from the kidneys elevates the central sympathetic drive. We investigated the effect of catheter-based renal sympathetic denervation (RDN) on glucose metabolism, inflammatory markers, and blood pressure in nondiabetic patients with treatment-resistant hypertension. Eight subjects were included in an open-labelled study. Each patient was studied before and 6 months after RDN. Endogenous glucose production was assessed by a 3-3H glucose tracer, insulin sensitivity was examined by hyperinsulinemic euglycemic clamp, hormones and inflammatory markers were analyzed, and blood pressure was measured by office blood pressure readings and 24-hour ambulatory blood pressure monitoring. Insulin sensitivity (M-value) increased nonsignificantly from 2.68 ± 0.28 to 3.07 ± 0.41 (p=0.12). A significant inverse correlation between the increase in M-value and BMI 6 months after RDN (p=0.03) was found, suggesting beneficial effects on leaner subjects. Blood pressure decreased significantly, but there were no changes in hormones, inflammatory markers, or endogenous glucose production. Our results indicate that RDN may improve insulin sensitivity in some patients with treatment-resistant hypertension, albeit confirmation of these indications of beneficial effects on leaner subjects awaits the outcome of larger randomized controlled studies
Rotigaptide protects the myocardium and arterial vasculature from ischaemia reperfusion injury
Aim:
Ischaemia-reperfusion injury (IRI) causes impaired endothelial function and is a major component of the adverse effects of reperfusion following myocardial infarction. Rotigaptide increases gap junction conductance via connexin-43. We tested the hypothesis that rotigaptide reduces experimental myocardial infarction size and ameliorates endothelial IRI in humans.
Methods:
Myocardial infarction study: porcine myocardial infarction was achieved by catheter-induced occlusion of the left anterior descending artery. In a randomized double-blind study, rotigaptide (n = 9) or placebo (n = 10) was administered intravenously as a 10 min bolus prior to reperfusion and continuously during 2 h of reperfusion. Myocardial infarction size (IS) was assessed as proportion of the area at risk (AAR). Human translational study: forearm IRI was induced in the presence or absence of intra-arterial rotigaptide. In a randomized double-blind study, forearm arterial blood flow was measured at rest and during intra-arterial infusion of acetylcholine (5–20 μg min–1; n = 11) or sodium nitroprusside (2–8 mg min–1; n = 10) before and after intra-arterial infusion of placebo or rotigaptide, and again following IRI.
Results:
Myocardial infarction study: Rotigaptide treatment was associated with a reduction of infarct size (IS/AAR[%]: 18.7 ± 4.1 [rotigaptide] vs. 43.6 ± 4.2 [placebo], P = 0.006). Human translational study: Endothelium-dependent vasodilatation to acetylcholine was attenuated after ischaemia-reperfusion in the presence of placebo (P = 0.007), but not in the presence of rotigaptide (P = NS). Endothelium-independent vasodilatation evoked by sodium nitroprusside was unaffected by IRI or rotigaptide (P = NS).
Conclusions:
Rotigaptide reduces myocardial infarction size in a porcine model and protects from IRI-related endothelial dysfunction in man. Rotigaptide may have therapeutic potential in the treatment of myocardial infarction
Avoiding nocebo and other undesirable effects in chiropractic, osteopathy and physiotherapy: An invitation to reflect
Introduction
While the placebo effect is increasingly recognised as a contributor to treatment effects in clinical practice, the nocebo and other undesirable effects are less well explored and likely underestimated. In the chiropractic, osteopathy and physiotherapy professions, some aspects of historical models of care may arguably increase the risk of nocebo effects.
Purpose
In this masterclass article, clinicians, researchers, and educators are invited to reflect on such possibilities, in an attempt to stimulate research and raise awareness for the mitigation of such undesirable effects.
Implications
This masterclass briefly introduces the nocebo effect and its underlying mechanisms. It then traces the historical development of chiropractic, osteopathy, and physiotherapy, arguing that there was and continues to be an excessive focus on the patient's body. Next, aspects of clinical practice, including communication, the therapeutic relationship, clinical rituals, and the wider social and economic context of practice are examined for their potential to generate nocebo and other undesirable effects. To aid reflection, a model to reflect on clinical practice and individual professions through the ‘prism’ of nocebo and other undesirable effects is introduced and illustrated. Finally, steps are proposed for how researchers, educators, and practitioners can maximise positive and minimise negative clinical context
Symmetry of the remanent state flux distribution in superconducting thin strips: Probing the critical state
The critical-state in a thin strip of YBaCuO is studied by magneto-optical
imaging. The distribution of magnetic flux density is shown to have a specific
symmetry in the remanent state after a large applied field. The symmetry was
predicted [PRL 82, 2947 (1999)] for any Jc(B), and is therefore suggested as a
simple tool to verify the applicability of the critical-state model. At large
temperatures we find deviations from this symmetry, which demonstrates
departure from the critical-state behavior. The observed deviations can be
attributed to an explicit coordinate dependence of since both a surface
barrier, and flux creep would break the symmetry in a different way.Comment: 5 pages including 5 eps figures, submitted to PR
Central peak position in magnetization loops of high- superconductors
Exact analytical results are obtained for the magnetization of a
superconducting thin strip with a general behavior J_c(B) of the critical
current density. We show that within the critical-state model the magnetization
as function of applied field, B_a, has an extremum located exactly at B_a=0.
This result is in excellent agreement with presented experimental data for a
YBCO thin film. After introducing granularity by patterning the film, the
central peak becomes shifted to positive fields on the descending field branch
of the loop. Our results show that a positive peak position is a definite
signature of granularity in superconductors.Comment: $ pages, 6 figure
European Headache Federation recommendations for placebo and nocebo terminology
Background and aim
Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials.
Methods
The working group identified relevant questions and agreed upon recommendations. Because no data were required to ans
Enhancement of the high-field critical current density of superconducting MgB2 by proton irradiation
A relatively high critical temperature, Tc, approaching 40 K, places the
recently-discovered superconductor magnesium diboride (MgB2) intermediate
between the families of low- and copper-oxide-based high-temperature
superconductors (HTS). Supercurrent flow in MgB2 is unhindered by grain
boundaries, unlike the HTS materials. Thus, long polycrystalline MgB2
conductors may be easier to fabricate, and so could fill a potentially
important niche of applications in the 20 to 30 K temperature range. However,
one disadvantage of MgB2 is that in bulk material the critical current density,
Jc, appears to drop more rapidly with increasing magnetic field than it does in
the HTS phases. The magnitude and field dependence of Jc are related to the
presence of structural defects that can "pin" the quantised magnetic vortices
that permeate the material, and prevent them from moving under the action of
the Lorentz force. Vortex studies suggest that it is the paucity of suitable
defects in MgB2 that causes the rapid decay of Jc with field. Here we show that
modest levels of atomic disorder, induced by proton irradiation, enhance the
pinning, and so increase Jc significantly at high fields. We anticipate that
chemical doping or mechanical processing should be capable of generating
similar levels of disorder, and so achieve technologically-attractive
performance in MgB2 by economically-viable routes.Comment: 5 pages, 4 figures, to be published in Nature (in press
The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – A secondary analysis
BACKGROUND AND PURPOSE: Placebo response rates in clinical trials vary considerably and are observed frequently. For new drugs it can be difficult to prove effectiveness superior to placebo. It is unclear what contributes to improvement in the placebo groups. We wanted to clarify, what elements of clinical trials determine placebo variability. METHODS: We analysed a representative sample of 141 published long-term trials (randomized, double-blind, placebo-controlled; duration > 12 weeks) to find out what study characteristics predict placebo response rates in various diseases. Correlational and regression analyses with study characteristics and placebo response rates were carried out. RESULTS: We found a high and significant correlation between placebo and treatment response rate across diseases (r = .78; p < .001). A multiple regression model explained 79% of the variance in placebo variability (F = 59.7; p < 0.0001). Significant predictors are, among others, the duration of the study (beta = .31), the quality of the study (beta = .18), the fact whether a study is a prevention trial (beta = .44), whether dropouts have been documented (beta = -.20), or whether additional treatments have been documented (beta = -.17). Healing rates with placebo are lower in the following diagnoses; neoplasms (beta = -.21), nervous diseases (beta = -.10), substance abuse (beta = -.14). Without prevention trials the amount of variance explained is 42%. CONCLUSION: Medication response rates and placebo response rates in clinical trials are highly correlated. Trial characteristics can explain some portion of the variance in placebo healing rates in RCTs. Placebo response in trials is only partially due to methodological artefacts and only partially dependent on the diagnoses treated
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