20 research outputs found
Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.
BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH
Movement Behavior of High-Heeled Walking: How Does the Nervous System Control the Ankle Joint during an Unstable Walking Condition?
The human locomotor system is flexible and enables humans to move without falling even under less than optimal conditions. Walking with high-heeled shoes constitutes an unstable condition and here we ask how the nervous system controls the ankle joint in this situation? We investigated the movement behavior of high-heeled and barefooted walking in eleven female subjects. The movement variability was quantified by calculation of approximate entropy (ApEn) in the ankle joint angle and the standard deviation (SD) of the stride time intervals. Electromyography (EMG) of the soleus (SO) and tibialis anterior (TA) muscles and the soleus Hoffmann (H-) reflex were measured at 4.0 km/h on a motor driven treadmill to reveal the underlying motor strategies in each walking condition. The ApEn of the ankle joint angle was significantly higher (p<0.01) during high-heeled (0.38±0.08) than during barefooted walking (0.28±0.07). During high-heeled walking, coactivation between the SO and TA muscles increased towards heel strike and the H-reflex was significantly increased in terminal swing by 40% (p<0.01). These observations show that high-heeled walking is characterized by a more complex and less predictable pattern than barefooted walking. Increased coactivation about the ankle joint together with increased excitability of the SO H-reflex in terminal swing phase indicates that the motor strategy was changed during high-heeled walking. Although, the participants were young, healthy and accustomed to high-heeled walking the results demonstrate that that walking on high-heels needs to be controlled differently from barefooted walking. We suggest that the higher variability reflects an adjusted neural strategy of the nervous system to control the ankle joint during high-heeled walking
International Paediatric Mitochondrial Disease Scale
OBJECTIVE : There is an urgent need for reliable and universally
applicable outcome measures for children with mitochondrial
diseases. In this study, we aimed to adapt the currently available
Newcastle Paediatric Mitochondrial Disease Scale
(NPMDS) to the International Paediatric Mitochondrial
Disease Scale (IPMDS) during a Delphi-based process with
input from international collaborators, patients and caretakers,
as well as a pilot reliability study in eight patients.
Subsequently, we aimed to test the feasibility, construct validity
and reliability of the IPMDS in a multicentre study.
METHODS : A clinically, biochemically and genetically heterogeneous
group of 17 patients (age 1.6–16 years) from five different expert centres from four different continents were
evaluated in this study.
RESULTS : The feasibility of the IPMDS was good, as indicated
by a low number of missing items (4 %) and the positive
evaluation of patients, parents and users. Principal component
analysis of our small sample identified three factors, which
explained 57.9 % of the variance. Good construct validity
was found using hypothesis testing. The overall interrater reliability
was good [median intraclass correlation coefficient
for agreement between raters (ICCagreement) 0.85; range
0.23–0.99).
CONCLUSION : In conclusion, we suggest using the IPMDS for
assessing natural history in children with mitochondrial diseases. These data should be used to further explore construct
validity of the IPMDS and to set age limits. In parallel,
responsiveness and the minimal clinically important difference
should be studied to facilitate sample size calculations
in future clinical trials.The work of SK and JS was sponsored by ZonMW
(The Netherlands Organization for Health Research and Development).http://link.springer.com/journal/10545am2017Paediatrics and Child Healt