Biomedical subjects

J M Saxton

Publications and source records attributed to J M Saxton.

13 recordsLinked to original sources

PubMed2001

The inflammatory response to upper and lower limb exercise and the effects of exercise training in patients with claudication.

PURPOSE: We have previously shown that a program of upper limb exercise training can induce significant improvements in walking distance in patients with claudication. This study assessed whether upper limb exercise avoids the systemic inflammatory responses associated with lower limb exercise and also whether the inflammatory response to acute lower limb exertion is modified by a program of supervised exercise training. METHODS: Fifty-two patients with stable intermittent claudication were randomized into two groups who underwent 6 weeks of supervised upper (n = 26) or lower (n = 26) limb cardiorespiratory exercise training. A parallel control group (n = 15) was provided with lifestyle advice only. Neutrophil activation markers (CD11b and CD66b) and plasma levels of von Willebrand factor (marker of endothelial damage) in response to an acute bout of sustained upper and lower limb exercise were assessed before and after the period of training. Plasma levels of soluble E-selectin (marker of endothelial activation) were also determined before and after the training period. RESULTS: An acute bout of sustained lower limb exercise significantly increased the intensity of CD11b and CD66b expression by peripheral blood neutrophils in all groups, whereas upper limb exercise had no effect. Resting neutrophil expression of CD11b and CD66b and circulating von Willebrand factor levels were unaffected by the training program, as were the inflammatory responses to an acute bout of sustained upper and lower limb muscular work, despite the fact that both training programs significantly increased walking distances. CONCLUSIONS: These findings indicate that upper limb exercise training programs may offer certain advantages over currently prescribed lower limb programs. Our results show that exercising nonischemic muscles in a way that promotes improved cardiorespiratory function and walking capacity can avoid the potentially deleterious systemic inflammatory responses associated with lower limb exertion in patients with stable intermittent claudication.

Adult↗

PubMed2001

Activated parathyroid hormone/parathyroid hormone-related protein receptor in osteoblastic cells differentially affects cortical and trabecular bone.

Parathyroid hormone (PTH), an important regulator of calcium homeostasis, targets most of its complex actions in bone to cells of the osteoblast lineage. Furthermore, PTH is known to stimulate osteoclastogenesis indirectly through activation of osteoblastic cells. To assess the role of the PTH/PTH-related protein receptor (PPR) in mediating the diverse actions of PTH on bone in vivo, we generated mice that express, in cells of the osteoblastic lineage, one of the constitutively active receptors described in Jansen's metaphyseal chondrodysplasia. In these transgenic mice, osteoblastic function was increased in the trabecular and endosteal compartments, whereas it was decreased in the periosteum. In trabecular bone of the transgenic mice, there was an increase in osteoblast precursors, as well as in mature osteoblasts. Osteoblastic expression of the constitutively active PPR induced a dramatic increase in osteoclast number in both trabecular and compact bone in transgenic animals. The net effect of these actions was a substantial increase in trabecular bone volume and a decrease in cortical bone thickness of the long bones. These findings, for the first time to our knowledge, identify the PPR as a crucial mediator of both bone-forming and bone-resorbing actions of PTH, and they underline the complexity and heterogeneity of the osteoblast population and/or their regulatory microenvironment.

Age Factors↗

PubMed2000

Influence of upper- and lower-limb exercise training on cardiovascular function and walking distances in patients with intermittent claudication.

PURPOSE: The effects of upper-limb (arm cranking) and lower-limb (leg cranking) exercise training on walking distances in patients with intermittent claudication was assessed. METHODS: Sixty-seven patients (33 to 82 years old) with moderate to severe intermittent claudication were recruited, and the maximum power generated during incremental upper- and lower-limb ergometry tests was determined, as were pain-free and maximum walking distances (by using a shuttle walk test). Patients were randomly assigned to an upper-limb training group (n = 26) or a lower-limb training group (n = 26). An additional untrained group (n = 15) was recruited on an ad hoc basis in parallel with the main trial by using identical inclusion criteria. This group was subsequently shown to possess a similar demographic distribution to the two exercise groups. Supervised training sessions were held twice weekly for 6 weeks. RESULTS: Both training programs significantly improved the maximum power generated during the incremental upper- and lower-limb ergometry tests (P <. 001), which may reflect an increase in central cardiovascular function that was independent of the training mode. More importantly, pain-free and maximum walking distances also improved in both training groups (P <.001). The improvements in the training groups were similar; there were no changes in the untrained control group. These findings suggest that the symptomatic improvement after upper-limb exercise training may result, in part, from systemic cardiovascular effects rather than localized metabolic or hemodynamic changes. CONCLUSION: Carefully prescribed upper-limb exercise training can evoke a rapid symptomatic improvement in patients with claudication, while avoiding the physical discomfort experienced when performing lower-limb weight-bearing exercise.

Adult↗

PubMed2000

A review of current literature on physiological tests and soft tissue biomarkers applicable to work-related upper limb disorders.

Work-related upper limb disorders (WRULD) are among the most commonly reported occupational illnesses. Epidemiological evidence of work-relatedness has been reported for a number of conditions, including carpal tunnel syndrome, hand/wrist tendinitis, shoulder tendinitis and hand-arm vibration syndrome. A range of electrodiagnostic techniques and psychophysical tests has been used to assess neurological dysfunction associated with WRULD, whereas only very few studies have examined biochemical markers of soft tissue injury. This report reviews key literature on physiological tests and biochemical markers of musculoskeletal stress/injury, which are applicable to studies of WRULD. The paper concludes by proposing new ways that testing might be implemented during occupational health surveillance to enable early warning of impending problems and to provide more insight into the underlying nature of soft tissue disorders.

Arm Injuries↗

PubMed1998

Effect of ex vivo storage on human peripheral blood neutrophil expression of CD11b and the stabilizing effects of Cyto-Chex.

CD11b is the alpha sub-unit of the CD11b/CD18 heterodimeric complex that has a key role in neutrophil-endothelial cell interactions and early events in inflammatory responses. Accurate assessment of CD11b expression by neutrophils can be problematic since the procedures that isolate cells from whole blood can increase antigen expression. This study used whole blood flow cytometry to monitor neutrophil CD11b expression following 0, 1, 2, 3 and 4 h of ex vivo incubation at room temperature and examined the effects of storage at 4 degrees C and the cell stabilization solution, Cyto-Chex, on antigen expression. Cyto-Chex-treated samples were also re-analyzed after 7 days storage at 4 degrees C. Neutrophil CD11b expression was high (> 90%) in five of the seven samples studied and incubation at room temperature induced a progressive upregulation which was significant after 2, 3, and 4 h (p < 0.05). Storage at 4 degrees C tempered this effect, although an increased expression (from baseline) was still observed after 4 h (p < 0.05). Cyto-Chex had no effect on the light scatter characteristics of treated cells and prevented CD11b upregulation in samples stored at room temperature. Furthermore, expression in Cyto-Chex-treated samples after 7 days was not significantly different from that observed in baseline (time 0) samples. In two samples demonstrating low neutrophil CD11b expression, a temperature-independent increase in the proportion of CD11b+ cells was observed over time. However, this increase was attenuated by treatment with Cyto-Chex. These findings indicate that sample storage significantly affects CD11b expression and caution should be exercised when interpreting data. Given that Cyto-Chex had no effect on the light scatter properties of cells and prevents antigen upregulation, this reagent may be useful for studies involving analysis of neutrophil activation antigen expression.

Blood Preservation↗

PubMed1998

Manipulation of knee extensor force using percutaneous electrical myostimulation during eccentric actions: effects on indices of muscle damage in humans.

Percutaneous electrical myostimulation (PES) was used to manipulate the force produced by the knee extensor muscles during eccentric exercise, thereby providing a model to investigate the role of force in muscle damage. Two eccentric exercise bouts of equal work were performed by nine subjects, using fixed voltage PES at 20 Hz (to produce moderate muscle forces) and 100 Hz (to produce high muscle forces). Muscle contractility, serum creatine kinase activity (CK) and muscle soreness (MS) were evaluated before, and up to 14 days after exercise. Data are presented as means+/-SEM, and were analysed using repeated measures analysis of variance (ANOVA), t-tests and Wilcoxon tests. Peak forces were higher during the 100 Hz bout than the 20 Hz bout for repetitions 1 (472+/-60 vs 237+/-23 Newtons), 10 (381+/-26 vs 233+/-26 Newtons), 20 (310+/-24 vs 218+/-24 Newtons), all p < 0.01, t-test and 30 (297+/-27 vs 204+/-21 Newtons), p < 0.05, t-test. Following the 100 Hz bout, maximum voluntary contractile force (MVC) was lower (p<0.01, ANOVA), and CK was higher (p<0.0001, ANOVA) than after the 20 Hz bout. Subjects also reported greater MS on days 2 to 6 (p<0.05, Wilcoxon test) following the 100 Hz bout. Despite a decline in the stimulated 20:100 Hz tetanic force ratio after each bout (p<0.01, ANOVA) there was no difference between bouts (p>0.05, ANOVA). The higher rise in CK and MS after the 100 Hz bout, together with the greater deficit in MVC, suggest that in humans, muscle force is a contributing factor to muscle injury during eccentric actions.

Adolescent↗

PubMed1998

Comparison of eccentric knee extensor muscle actions at two muscle lengths on indices of damage and angle-specific force production in humans.

In this study, we investigated the effects of knee extensor length during eccentric exercise on indices of muscle damage and adaptation. Subjects (n = 7) performed two bouts of 75 maximal voluntary eccentric muscle actions at a knee joint angular velocity of 1.57 rad s(-1). One bout was performed at a short muscle length (bout S) with a knee joint range of motion of 2.79 to 1.40 radians (160 degrees to 80 degrees), and a second with the contralateral knee extensors at a long muscle length (bout L) with a range of motion of 2.01 to 0.7 radians (120 degrees to 40 degrees). The maximum voluntary contractile force (MVC) was measured before and 5 min after exercise, and again on days 3, 5, 7, 10 and 12, at knee angles of 160 degrees, 120 degrees and 80 degrees. Muscle soreness was measured before exercise and on each day after exercise. Serum creatine kinase activity was measured before exercise and on days 3, 5, 7, 10 and 12 post-exercise. The MVC declined after each bout (P < 0.01), with a greater decline after bout L (P < 0.05). Muscle soreness was higher relative to bout S on days 1, 2, 3, 5 and 6 (P < 0.05). Although serum creatine kinase activity was elevated after both exercise bouts (P < 0.01), there was no difference between bouts. Functional muscle damage markers and muscle soreness suggest greater damage after bout L. Post-exercise angle-specific force decrements suggest a transient increase in muscle length after bout L but not bout S.

Adaptation, Physiological↗

PubMed1996

Changes in human skeletal muscle contractile function following stimulated eccentric exercise.

Indices of human skeletal muscle contractile function were examined in nine subjects for up to 9 days following a single bout of stimulated eccentric exercise. Eccentric muscle actions of the knee extensor muscles were evoked by percutaneous electrical myostimulation (PES). Delayed onset muscle soreness (DOMS), elevated serum creatine kinase activity, chronic force loss, and a decline in the 20:100 Hz force ratio were observed in the days postexercise. The exercised knee extensor muscles demonstrated an impaired ability to respond to PES. This was evident by an increased time delay between the start of 100 Hz PES and the onset of contraction immediately postexercise [22.3 (SD 15.9)%, P < 0.01] and 3 days postexercise [14.9 (SD 18.1)%, P < 0.05]. Muscle relaxation rates appeared unaffected by the eccentric exercise protocol, where the muscles showed no differences in the time between the end of PES and the onset of relaxation (P > 0.05). During the days following the exercise, no significant differences were observed in the time between the start of contraction and attainment of 70% of the mean tetanic force following a single 1-s pulse of PES. Similarly, no significant differences were observed in the time between the start of relaxation and attainment of 70% of the total relaxation during the same time. The increased delay in excitation-contraction coupling observed immediately postexercise and 3 days after the exercise, may reflect a damage-induced delay in action potential propagation. Muscle relaxation rates postexercise remained unchanged, which would seem to indicate normal functioning of the sarcoplasmic reticulum, suggesting this was not the site of failure in excitation-contraction coupling.

Adult↗

PubMed1996

Length-specific impairment of skeletal muscle contractile function after eccentric muscle actions in man.

1. The effects of maximum voluntary eccentric muscle actions on forearm flexor strength were studied at three different elbow joint angles (0.87, 1.57 and 2.79 rad) to examine whether subsequent impairment of contractile function is muscle length-specific. 2. A bout of 70 maximum voluntary eccentric muscle actions performed with the forearm flexors elicited delayed muscle soreness, efflux of creatine kinase into the blood, loss of elbow joint range of motion and a prolonged decline in maximum voluntary isometric contraction torque at the three elbow angles monitored (P < 0.01) in 30 subjects. 3. The relative decline in maximum voluntary isometric contraction torque after eccentric exercise differed between elbow angles (P < 0.01). The greatest decline in strength relative to baseline was observed at the most acute elbow angle of 0.87 rad, followed by 1.57 and 2.79 rad respectively. Superimposed electrical stimulation in a subgroup of eight subjects did not increase the torque elicited by the forearm flexors during maximum voluntary contraction tests at the most acute elbow angle (0.87 rad) at any time-point after eccentric exercise, suggesting the disproportionate loss of strength at short muscle length was not due to the inhibitory effects of muscle soreness. 4. Measures of arm circumference and ability to fully flex the elbow (in the same subgroup of eight subjects) suggested the greater decline in strength at the acute elbow angle was not due to the possible confounding influences of muscle swelling and/or impaired muscle shortening ability on strength measurements at short muscle length. 5. These data suggest a shift in the forearm flexor length-tension relationship could account for the disparate decline in strength between elbow angles after eccentric exercise. The disproportionate loss of strength at short muscle length suggests that eccentric exercise evoked a subtle increase in muscle length, perhaps attributable to the cumulative effects of regions of lengthened sarcomeres and/or series elastic elements.

Adolescent↗

PubMed1995

Light concentric exercise during recovery from exercise-induced muscle damage.

Eight male volunteers performed two eccentric exercise bouts using the forearm flexors of first one arm, then the other. The two bouts, consisting of 70 maximum voluntary muscle actions, were separated by a period of three weeks. In the experimental condition of the study, five sets of 10 sub-maximal concentric muscle actions were performed on the four days after the eccentric bout. In the control condition of the study, no concentric work was performed. Repeated measures analysis of variance indicated an increase in serum creatine kinase activity (p < 0.01) and decreases in relaxed elbow angle (p < 0.05) and maximum voluntary contraction force (p < 0.01) at three elbow angles (0.87, 1.57 and 2.79 rad) after both eccentric bouts. However, the serum creatine kinase response to eccentric exercise was reduced in the experimental condition (p < 0.05) and recovery of maximum voluntary force production at the most acute joint angle (0.87 rad) was accelerated (p < 0.01). Although muscle soreness increased after both eccentric bouts (p < 0.05; Wilcoxon test), further concentric exercise evoked temporary relief of muscle soreness two days after the bout (p < 0.05; Wilcoxon test). However, light concentric work had no effect on the other parameters monitored. In practical terms, these results suggest that the therapeutic effects of light concentric work on correlates of exercise-induced muscle damage are minimal.

Acceleration↗

PubMed1995

Neuromuscular dysfunction following eccentric exercise.

This study examined the effects of exercise-induced muscle damage on tremor and proprioception components of neuromuscular function. Six male and six female volunteers (aged 18-30 yr) performed 50 maximal eccentric muscle actions using the forearm flexors of the nondominant arm. Forearm flexor tremor and perception of voluntary force and joint position were monitored to assess changes in neuromuscular function. Data were analyzed using REANOVA. Serum creatine kinase activity increased from a baseline value of 68 +/- 13 IU.l-1 to 2849 +/- 852 IU.l-1 5 d after exercise (P < 0.05). This was accompanied by prolonged impaired joint range of motion (P < 0.01) and reduced maximum strength (P < 0.01). Muscle soreness peaked 3 d postexercise (P < 0.01; Wilcoxon test). Tremor amplitude was increased (P < 0.01) until 48 h after exercise, whereas the power frequency spectrum was unaffected. Perception of joint position at elbow angles of 1.57 rad (P < 0.01) and 2.09 rad (P < 0.05) and perception of force (P < 0.01) were significantly impaired when the control arm acted as the reference. Joint positions were more accurately reproduced when the experimental arm acted as its own reference. The increase in tremor amplitude and loss of proprioceptive function in the days after damage-inducing eccentric exercise suggest significant impairment of neuromuscular function.

Adolescent↗

PubMed1994

Indices of free-radical-mediated damage following maximum voluntary eccentric and concentric muscular work.

This study monitored plasma and skeletal muscle markers of free-radical-mediated damage following maximum eccentric and concentric exercise, to examine the potential role of free radicals in exercise-induced muscle damage. Fourteen male volunteers performed either (1) a bout of 70 maximum eccentric and a bout of 70 maximum concentric muscle actions of the forearm flexors (the bouts being separated by 4 weeks; n = 8) or (2) a bout of 80 maximum eccentric and a bout of 80 maximum concentric muscle actions of the knee extensors (the bouts being separated by 1 week; n = 6). Plasma markers of lipid peroxidation, thiobarbituric acid-reactive substances (TBARS) and diene-conjugated compounds (DCC) were monitored in the arm protocol and skeletal muscle markers of oxidative lipid and protein damage, malondialdehyde (MDA) and protein carbonyl derivatives (PCD) respectively, were monitored in the leg protocol. In both protocols, the contralateral limb was used for the second bout and the order of the bouts was randomised between limbs. Repeated measures ANOVA indicated significant changes from baseline following eccentric arm work on the measures of serum creatine kinase activity (P < 0.05), maximum voluntary torque production (P < 0.01) and relaxed arm angle (P < 0.01). Subjective muscle soreness peaked 2 days after eccentric arm work (P < 0.05, Wilcoxon test). However, there were no changes in the plasma levels of TBARS or DCC following the eccentric or concentric arm exercise. Immediately after concentric leg exercise, skeletal muscle PCD concentrations was significantly higher than that observed immediately after eccentric work (P < 0.05)(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Ultrasonic thrombus ablation: in vitro assessment of a novel device for intracoronary use.

An ultrasonic thrombolysis device designed for intracoronary use was developed and evaluated in vitro to assess efficacy in achieving clot ablation without deleterious effects, such as heat generation and production of large particles during clot ablation. Studies on 31 samples with a bench-top version demonstrated that clot ablation was rapid (typically 2 mL in under 2 minutes) and no macroscopic particles were released. The fluid produced did not reclot. Studies with a clinical version of the device that can be passed through a 10 Fr PTCA guiding catheter confirmed that clot ablation was rapidly achieved. Little particulate material was produced and the maximum temperature achieved did not exceed 52 degrees C. The device functions well in vitro, releasing little particulate material and causing limited local heating. It seems suitable for intracoronary use and will undergo further in vivo testing.

Catheter Ablation↗