Walking performance, oxygen uptake kinetics and resting muscle pyruvate dehydrogenase complex activity in peripheral arterial disease

In the present study, we tested the hypothesis that walking intolerance in intermittent claudication (IC) is related to both slowed whole body oxygen uptake (Vo(2)) kinetics and altered activity of the active fraction of the pyruvate dehydrogenase complex (PDCa) in skeletal muscle. Ten patients with IC and peripheral arterial disease [ankle/brachial index (ABI) = 0.73 +/- 0.13] and eight healthy controls (ABI = 1. 17 +/- 0.13) completed three maximal walking tests. From these tests, averaged estimates of walking time, peak Vo(2) and the time constant of Vo(2) (tau) during submaximal walking were obtained. A muscle sample was taken from the gastrocnemius medialis muscle at rest and analysed for PDCa and several other biochemical variables. Walking time and peak Vo(2) were approx. 50 % lower in patients with IC than controls, and tau was 2-fold higher (P < 0.05). r was significantly correlated with walking time (r = -0.72) and peak Vo(2) (r = -0.66) in patients with IC, but not in controls. PDCa was not significantly lower in patients with IC than controls; however, PDCa tended to be correlated with tau (r = -0.56, P = 0.09) in patients with IC, but not in controls (r = -0.14). A similar correlation was observed between resting ABI and tau (r = -0.63, P = 0.05) in patients with IC. These data suggest that the impaired Vo(2) kinetics contributes to walking intolerance in IC and that, within a group of patients with IC, differences in Vo(2) kinetics might be partly linked to differences in muscle carbohydrate oxidation.

Temporal aspects of the VO2 response at the power output associated with VO2peak in well trained cyclists: Implications for interval training prescription

The power output achieved at peak oxygen consumption (VO2 peak) and the time this power can be maintained (i.e., Tmax) have been used in prescribing high-intensity interval training. In this context, the present study examined temporal aspects of the VO2 response to exercise at the cycling power that output well trained cyclists achieve their VO2 peak (i.e., Pmax). Following a progressive exercise test to determine VO2 peak, 43 well trained male cyclists (M age = 25 years, SD = 6; M mass = 75 kg SD = 7; M VO2 peak = 64.8 ml(.)kg(1.)min(-1), SD = 5.2) performed two Tmax tests 1 week apart.1. Values expressed for each participant are means and standard deviations of these two tests. Participants achieved a mean VO2 peak during the Tmax test after 176 s (SD = 40; = 74% of Tmax, SD = 12) and maintained it for 66 s (SD = 39; M = 26% of Tmax, SD = 12). Additionally they obtained mean 95 % of VO2 peak after 147 s (SD = 31; M = 62 % of Tmax, SD = 8) and maintained it for 95 s (SD = 38; M = 38 % of Tmax, SD = 8). These results suggest that 60-70% of Tmax is an appropriate exercise duration for a population of well trained cyclists to attain VO2 peak during exercise at Pmax. However due to intraparticipant variability in the temporal aspects of the VO2 response to exercise at Pmax, future research is needed to examine whether individual high-intensity interval training programs for well trained endurance athletes might best be prescribed according to an athlete's individual VO2 response to exercise at Pmax.

A note on bifurcation from an interval

We study the global bifurcation of nonlinear Sturm-Liouville problems of the form -(pu')' + qu = lambda a(x)f(u), b(0)u(0) - c(0)u' (0) = 0, b(1)u(1) + c(1)u'(1) = 0 which are not linearizable in any neighborhood of the origin. (c) 2005 Published by Elsevier Ltd.

Pharmacokinetic-pharmacodynamic modelling of QT interval prolongation following citalopram overdoses

Aims To develop a pharmacokinetic-pharmacodynamic model describing the time-course of QT interval prolongation after citalopram overdose and to evaluate the effect of charcoal on the relative risk of developing abnormal QT and heart-rate combinations. Methods Plasma concentrations and electrocardiograph (ECG) data from 52 patients after 62 citalopram overdose events were analysed in WinBUGS using a Bayesian approach. The reported doses ranged from 20 to 1700 mg and on 17 of the events a single dose of activated charcoal was administered. The developed pharmacokinetic-pharmacodynamic model was used for predicting the probability of having abnormal combinations of QT-RR, which was assumed to be related to an increased risk for torsade de pointes (TdP). Results The absolute QT interval was related to the observed heart rate with an estimated individual heart-rate correction factor [alpha = 0.36, between-subject coefficient of variation (CV) = 29%]. The heart-rate corrected QT interval was linearly dependent on the predicted citalopram concentration (slope = 40 ms l mg(-1), between-subject CV = 70%) in a hypothetical effect-compartment (half-life of effect-delay = 1.4 h). The heart-rate corrected QT was predicted to be higher in women than in men and to increase with age. Administration of activated charcoal resulted in a pronounced reduction of the QT prolongation and was shown to reduce the risk of having abnormal combinations of QT-RR by approximately 60% for citalopram doses above 600 mg. Conclusion Citalopram caused a delayed lengthening of the QT interval. Administration of activated charcoal was shown to reduce the risk that the QT interval exceeds a previously defined threshold and therefore is expected to reduce the risk of TdP.

Resting energy expenditure is lower than predicted in people taking atypical antipsychotic medication

Resting energy expenditure (REE) is lower than predicted in persons taking atypical antipsychotic medication, and weight management is a significant clinical challenge for some of them. However, to date there have been no published guidelines to assist clinicians in choosing appropriate prediction equations to estimate energy expenditure in persons taking atypical antipsychotic medications. The objectives of this study were to measure REE in a group of men taking the atypical antipsychotic clozapine and to determine whether REE can be accurately predicted for this population using previously published regression equations. REE was measured using indirect calorimetry via a ventilated hood on eight men who had completed at least 6 months of treatment with clozapine. Comparisons between measured REE and predicted REE using five different equations were undertaken. The commonly-used Harris-Benedict and Schofield equations systematically overestimated REE. Predictions of REE from other equations were too variable for clinical use. When estimating energy requirements as part of a weight-management program in men who have been taking clozapine for 6 months, predictions of REE from the equations of Harris-Benedict and Schofield should be reduced by 280 kcal/day.

Sigmoidal cosine series on the interval

We construct a set of functions, say, psi([r])(n) composed of a cosine function and a sigmoidal transformation gamma(r) of order r > 0. The present functions are orthonormal with respect to a proper weight function on the interval [-1, 1]. It is proven that if a function f is continuous and piecewise smooth on [-1, 1] then its series expansion based on psi([r])(n) converges uniformly to f so long as the order of the sigmoidal transformation employed is 0 < r

Heritability and Stability of Resting Blood Pressure in Australian Twins

In Australian twins participating in three different studies (1979-1996), the contribution of genetic and environmental influences to variation in resting systolic (SBP) and diastolic blood pressure (DBP) was studied. The sample consisted of 368 monozygotic and 335 dizygotic twin pairs with measurements for both individuals. Blood pressure measurements in two studies were available for 115 complete twin pairs, and 49 twin pairs had measurements in three studies. This allowed assessment of blood pressure tracking over an average period of 12 years in the age range of 23 to 45 years. Multivariate analyses showed significant heritability (h(2)) of blood pressure in all studies (SBP h(2) = 19%-56%, DBP h(2) = 37%-52%). In addition, the analyses showed that the blood pressure tracking was explained by the same set of genetic factors. These results replicate an earlier finding in Dutch twins that also showed stability of the contribution of genetic factors to blood pressure tracking.

Recurrence interval statistics of cellular automaton seismicity models

The recurrence interval statistics for regional seismicity follows a universal distribution function, independent of the tectonic setting or average rate of activity (Corral, 2004). The universal function is a modified gamma distribution with power-law scaling of recurrence intervals shorter than the average rate of activity and exponential decay for larger intervals. We employ the method of Corral (2004) to examine the recurrence statistics of a range of cellular automaton earthquake models. The majority of models has an exponential distribution of recurrence intervals, the same as that of a Poisson process. One model, the Olami-Feder-Christensen automaton, has recurrence statistics consistent with regional seismicity for a certain range of the conservation parameter of that model. For conservation parameters in this range, the event size statistics are also consistent with regional seismicity. Models whose dynamics are dominated by characteristic earthquakes do not appear to display universality of recurrence statistics.