Reproducibility of the parameters of the on-transient cardiopulmonary responses during moderate exercise in patients with chronic obstructive pulmonary disease

To be clinically useful as indices reflective of altered physiological function consequent to interventions in patients with chronic obstructive pulmonary disease (COPD), the time constant (τ) and steady-state amplitude of the kinetic responses for oxygen uptake ( ) carbon dioxide output ( ) ventilation ( ) and heart rate (HR) have to be appropriately differentiable and reproducible. We therefore assessed the reproducibility of τ and steady state amplitude values in 41 patients with severe COPD [mean (SD)] [forced expiratory volume in 1 s=41 (7)% predicted], aged 64 (5) years. Of the total, 6 of the patients (15%) did not produce breath-by-breath data of sufficient quality to warrant kinetic analysis. The remaining 35 patients completed two moderate-intensity 10 min square-wave exercise tests separated by 2 h, both before and after an endurance training programme. Tests were conducted on an electromagnetically-braked cycle ergometer at an exercise intensity corresponding to 80% of the estimated lactate threshold (θ_La) or 50% of peak oxygen uptake if θ_La was insufficiently differentiable. Breath-by-breath measurements of , , and HR were averaged into 10 s bins and the on-transient response kinetics were estimated using a mono-exponential model. Analysing the pre-training and the post-training test 1 and test 2 comparisons together, the test 1 –test 2 differences were not significantly different from 0 for either τ or A. The standard deviation of the test 1 –test 2 differences allowed us to define the magnitude of change that would reach statistical significance. For τ, this averaged some 8, 10, 11 and 8 s, for , , and HR, respectively, for a one-tailed paired-comparisons test (i.e. appropriate for assessing hypothesised improvements resulting from an intervention); for a two-tailed comparison, the differences were approximately 2 s greater. The corresponding one-tailed values for A were 100 ml·min^–1, 95 ml·min^–1, 2.5 1·min^–1 and 4 beats·min^–1, respectively; the two-tailed values were 10%–15% greater. We therefore conclude that both τ and A for moderate-intensity exercise can be reproducibly estimated in patients with COPD when the data set provides a sufficiently large amplitude of response and sufficiently low sample variability to allow appropriate parameter estimation. Electronic Publication     

Ia Afferent input alters the recruitment thresholds and firing rates of single human motor units

Vibration of the patellar tendon recruits motor units in the knee extensors via excitation of muscle spindles and subsequent Ia afferent input to the α-motoneuron pool. Our first purpose was to determine if the recruitment threshold and firing rate of the same motor unit differed when recruited involuntarily via reflex or voluntarily via descending spinal pathways. Although Ia input is excitatory to the α-motoneuron pool, it has also been shown paradoxically to inhibit itself. Our second purpose was to determine if vibration of the patellar tendon during a voluntary knee extension causes a change in the firing rate of already recruited motor units. In the first protocol, 10 subjects voluntarily reproduced the same isometric force profile of the knee extensors that was elicited by vibration of the patellar tendon. Single motor unit recordings from the vastus lateralis (VL) were obtained with tungsten microelectrodes and unitary behaviour was examined during both reflex and voluntary knee extensions. Recordings from 135 single motor units showed that both recruitment thresholds and firing rates were lower during reflex contractions. In the second protocol, 7 subjects maintained a voluntary knee extension at 30 N for approximately 40–45 s. Three bursts of patellar tendon vibration were superimposed at regular intervals throughout the contraction and changes in the firing rate of already recruited motor units were examined. A total of 35 motor units were recorded and each burst of superimposed vibration caused a momentary reduction in the firing rates and recruitment of additional units. Our data provide evidence that Ia input modulates the recruitment thresholds and firing rates of motor units providing more flexibility within the neuromuscular system to grade force at low levels of force production. Electronic Publication     

Magnesium restores high K-induced inactivation of the fast Na channel in guinea pig ventricular muscle

The effect of extracellular magnesium concentration (Mg_o) on the upstroke of the action potential was studied in guinea pig ventricular muscle under various K⁺ concentrations (2.7–19mM). Increased Mg_o shifted the steady state inactivation curve of the fast Na channel in the depolarizing direction and this effect was concentration-dependent (0–20mM). Such an effect could explain the Mg-induced increase in maximum rate of rise of the action potential which Späh and Fleckenstein (1979) proposed to be due to a Mg channel.     

Effect of alkalosis on performance and lactate formation in supramaximal exercise

Summary An increased base binding power of the blood induced by alkali administration to subjects performing a supramaximal exercise has no appreciable effect neither on the maximal performance time nor on the total amount of lactic acid or its rate of appearance in blood.This work has been supported by a grant from the Italian National Research Council. Thanks are due also to Laboratory Glaxo, S.p.A. for facilities and financial support in the course of the experiments.     

Blood pressure and heart rate during rest-exercise and exercise-rest transitions

Summary The transients of mean arterial blood pressure ( ) and heart rate (f _c) during rest-exercise and exercise-rest transitions have been studied in six healthy sport students. After 5 min of rest in an upright position on a cycle ergometer they exercised for 15 min and remained seated for a further 5 min. The subjects exercised at four different constant intensities (40 W, 80 W, 120 W, 160 W) in random order separated by at least 24 h. The was determined by a noninvasive and continuous method. During the first minute of exercise, three phases of response could be distinguished, with the first two showing no clear relationship to intensity. Phase 1 consisted of simultaneous increases in bothf _c and BP during the first 6 s. In phase 2, decreased whilef _c continued to increase. During phase 3, andf _c approximated constant values or a linear increase. Both parameters showed no comparable intensity-independent reactions during the off-transients. In conclusion, during the first 15 s of rest-exercise transitions there seems to be a fast and uniform cardiovascular drive which overrode other influences onf _c.     

Blood Pressure and Heart Rate Changes Accompanying Classical Eyeblink Conditioning In The Rabbit (Oryctolagus Cuniculus)

In two experiments employing 38 rabbits differential classical conditioning of heart rate, blood pressure, and corneoretinal potential (CRP) response were examined using l-sec and 4-sec interstimulus intervals ISI respectively. The conditioned response consisted of HK decelerations and DP depressor responses early in conditioning. However, many, but not all, animals revealed pressor responses and HR accelerations after the CRP discrimination was acquired. Significant correlations were also obtained between BP pressor responses, HR accelerations, and the frequency of CRP CRs. These results were discussed within the context of the orienting and defense reflexes.     

The Relationship Between Cardiac Activity and Sensory Acuity

The relationship between cardiac activity and sensory acuity suggested by Lacey and Lacey was tested by recording heart rates of Ss attempting to detect a threshold-level visual stimulus. Heart rate decelerations during a warning tone preceding the threshold stimulus were found in be greater on hit trials than on miss trials, supporting the suggested relationship.     

中晚期重型乙型肝炎血浆置换与内科治疗生存率的比较

观察血浆置换、内科治疗对中晚期重型乙型病毒性肝炎生存率的影响,探索中晚期重型肝炎的治疗方法。方法观察在内科治疗基础上给予血浆置换患者的肝功能、并发症及疾病的转归,与同期仅予内科综合治疗的患者相比较,对相应的临床资料进行统计学分析,从而了解两种治疗方法的疗效。结果血浆置换组36例,18例好转、18例死亡,内科治疗组32例,13例好转、19例死亡,两组之间患者生存情况无统计学差异;肝功能指标(ALT、AST、SB、ALB、TC、ChE和凝血酶原时间(PT)也无统计学差异。结论与内科治疗相比较,在其基础上给予血浆置换并不能提高中晚期重型病毒性肝炎生存率;中晚期重型肝炎患者的预后决定于其肝功能衰竭的程度。     

Using linked markers to infer the age of a mutation

Advances in sequencing and genotyping technologies over the last decade have enabled geneticists to easily characterize genetic variation at the nucleotide level. Hundreds of genes harboring mutations associated with genetic disease have now been identified by positional cloning. Using variation at closely linked genetic markers, it is possible to predict the times in the past at which particular mutations arose. Such studies suggest that many of the rare mutations underlying human genetic disorders are relatively young. Studies of variation at genetic markers linked to particular mutations can provide insights into human geographic history, and historical patterns of natural selection and disease, that are not available from other sources. We review two approaches for estimating allele age using variation at linked genetic markers. A phylogenetic approach aims to reconstruct the gene tree underlying a sample of chromosomes carrying a particular mutation, obtaining a “direct” estimate of allele age from the age of the root of this tree. A population genetic approach relies on models of demography, mutation, and/or recombination to estimate allele age without explicitly reconstructing the gene tree. Phylogenetic methods are best suited for studies of ancient mutations, while population genetic methods are better suited for studies of recent mutations. Methods that rely on recombination to infer the ages of alleles can be fine‐tuned by choosing linked markers at optimal map distances to maximize the information available about allele age. A limitation of methods that rely on recombination is the frequent lack of a fine‐scale linkage map. Maximum likelihood and Bayesian methods for estimating allele age that rely on intensive numerical computation are described, as well as “composite” likelihood and moment‐based methods that lead to simple estimators. The former provide more accurate estimates (particularly for large samples of chromosomes) and should be employed if computationally practical. Hum Mutat 18:87–100, 2001. © 2001 Wiley‐Liss, Inc.