Prolonged cycling lowers subsequent running mechanical efficiency in collegiate triathletes.

BACKGROUND: A significant challenge that non-elite collegiate triathletes encounter during competition is the decline in running performance immediately after cycling. Therefore, the purpose of this study was to determine if performing a 40-km bout of cycling immediately before running would negatively influence running economy and mechanical efficiency of running during simulated race conditions in collegiate triathletes. METHODS: Eight competitive club-level collegiate triathletes randomly performed two trials: cycling for 40 km (Cycle-Run) or running for 5 km (Run-Run), immediately followed by a four-minute running economy and mechanical efficiency of running test at race pace on an instrumented treadmill. Blood lactate, respiratory exchange ratio, mechanical work, energy expenditure, and muscle glycogen were also measured during the four-minute running test. RESULTS: Mechanical efficiency of running, but not running economy, was significantly lower in Cycle-Run, compared to Run-Run (42.1 ± 2.5% vs. 48.1 ± 2.5%, respectively; p = 0.027). Anaerobic energy expenditure was significantly higher in the Cycle-Run trial, compared to the Run-Run trial (16.3 ± 2.4 vs. 7.6 ± 1.1 kJ; p = 0.004); while net (151.0 ± 12.3 vs. 136.6 ± 9.6 kJ; p = 0.204) and aerobic energy expenditure (134.7 ± 12.3 vs. 129.1 ± 10.5 kJ; p = 0.549) were not statistically different between trials. Analysis of blood lactate, respiratory exchange ratio, mechanical work, and changes in muscle glycogen revealed no statistically significant differences between trials. CONCLUSIONS: These results suggest that mechanical efficiency of running, but not running economy, is decreased and anaerobic energy expenditure is increased when a 40-km bout of cycling is performed immediately before running in collegiate triathletes.

Do we really need cadavers anymore to learn anatomy in undergraduate medicine?

With the availability of numerous adjuncts or alternatives to learning anatomy other than cadavers (medical imaging, models, body painting, interactive media, virtual reality) and the costs of maintaining cadaver laboratories, it was considered timely to have a mature debate about the need for cadavers in the teaching of undergraduate medicine. This may be particularly pertinent given the exponential growth in medical knowledge in other disciplines, which gives them valid justification for time in already busy medical curricula. In this symposium, the pros and cons of cadaver use in modern medical curricula were debated and audience participation encouraged.

Review article: nonclinical and clinical pharmacology, pharmacokinetics and pharmacodynamics of etrolizumab, an anti-ß7 integrin therapy for inflammatory bowel disease.

BACKGROUND: Novel treatments with superior benefit-risk profiles are needed to improve the long-term prognosis of patients with inflammatory bowel disease (IBD). Etrolizumab-a monoclonal antibody that specifically targets ß7 integrins-is currently under phase III clinical evaluation in IBD. AIM: This review summarises the available pharmacological and pharmacokinetic/pharmacodynamic data for etrolizumab to provide a comprehensive understanding of its mechanism of action (MOA) and pharmacological effects. METHODS: Published and internal unpublished data from nonclinical and clinical studies with etrolizumab are reviewed. RESULTS: Etrolizumab exerts its effect via a unique dual MOA that inhibits both leucocyte trafficking to the intestinal mucosa and retention within the intestinal epithelial layer. The gut-selectivity of etrolizumab results from its specific targeting of the ß7 subunit of α4ß7 and αEß7 integrins. Etrolizumab does not bind to α4ß1 integrin, which mediates lymphocyte trafficking to tissues including the central nervous system, a characteristic underlying its favourable safety with regard to progressive multifocal leucoencephalopathy. Phase I/II studies in patients with ulcerative colitis (UC) showed linear pharmacokinetics when etrolizumab was administered subcutaneously at 100 mg or higher once every 4 weeks. This dose was sufficient to enable full ß7 receptor occupancy in both blood and intestinal tissues of patients with moderate to severe UC. The phase II study results also suggested that patients with elevated intestinal expression of αE integrin may have an increased likelihood of clinical remission in response to etrolizumab treatment. CONCLUSION: Etrolizumab is a gut-selective, anti-ß7 integrin monoclonal antibody that may have therapeutic potential for the treatment of IBD.

4-Aminopyridine derivatives enhance impulse conduction in guinea-pig spinal cord following traumatic injury.

4-Aminopyridine (4-AP), a potassium channel blocker, is capable of restoring conduction in the injured spinal cord. However, the maximal tolerated level of 4-AP in humans is 100 times lower than the optimal dose in in vitro animal studies due to its substantially negative side effects. As an initial step toward the goal of identifying alternative potassium channel blockers with a similar ability of enhancing conduction and with fewer side effects, we have synthesized structurally distinct pyridine-based blockers. Using isolated guinea-pig spinal cord white matter and a double sucrose gap recording device, we have found three pyridine derivatives, N-(4-pyridyl)-methyl carbamate (100 microM), N-(4-pyridyl)-ethyl carbamate (100 microM), and N-(4-pyridyl)-tertbutyl (10 microM) can significantly enhance conduction in spinal cord white matter following stretch. Similar to 4-AP, the derivatives did not preferentially enhance conduction based on axonal caliber. Unlike 4-AP, the derivatives did not change the overall electrical responsiveness of axons to multiple stimuli, indicating the axons recruited by the derivatives conducted in a manner similar to healthy axons. These results demonstrate the ability of novel constructs to serve as an alternative to 4-AP for the purpose of reversing conduction deficits.

Effect of stretching on agonist-antagonist muscle activity and muscle force output during single and multiple joint isometric contractions.

Eight moderately active male subjects where tested for peak force in an isometric knee extension test and peak force and rate of force development in an isometric squat test. Both tests where performed at a 100 degrees knee angle and average integrated electromyography (IEMG) was measured from the vastus medialis (VM), vastus lateralis (VL) and biceps femoris (BF) muscles. Subjects performed the two conditions, stretching (S) or control (C) in a randomized order. Subjects where tested for baseline strength measures in both the isometric knee extension and isometric squat and then either stretched or sat quietly for 10 min. Following S or C subjects where then tested at six time points. Following S peak force in the isometric knee extension was significantly (P < or = 0.05) less than C at 1, 2, 8 and 16 min post. No significant difference in peak force was found between S and C in the isometric squat. However, following S the rate of force development in the isometric squat was significantly less than C at immediately post. No significant differences where observed in IEMG of the VM or VL between S and C in either the isometric knee extension or isometric squat. However, IEMG significantly decreased in the BF at 1 min post after S in comparison with C in both the isometric knee extension and isometric squat. Stretching appears to decrease muscle force output in a single joint isometric contraction and rate of force development in a multiple joint isometric contraction. Possible changes in agonist-antagonist muscle activity patterns need to be further examined.

Effects of effort and EMG levels on short-latency stretch reflex modulation after varying background muscle contractions.

It is known that the short-latency stretch reflex (SLSR) is modulated by the background muscle activity when it is elicited at matched torque levels. This study was designed to examine the effects of muscle contraction types before a stretch perturbation on SLSR in the human soleus muscle (SOL) when SLSR was elicited at the same levels of effort and at matched electromyographic (EMG) activity levels. A mechanical stretch perturbation was applied to the calf muscles when the ankle joint reached a ninety degree tibio-tarsal joint angle after the muscles performed an isometric (pre-ISO), shortening (pre-SHO) and lengthening contraction (pre-LEN). Subjects were seated on an ankle ergometer chair and developed 0%, 10%, 20%, 30%, 40%, 50%, 60% and 70% ankle joint torque (AJT) of maximum voluntary isometric plantar flexion contraction at 80 degrees in pre-SHO, at 90 degrees in pre-ISO and at 100 degrees in pre-LEN. After that, isometric or dynamic contractions started, and the subjects were asked to maintain effort levels as, needed, to maintain the target torque levels until the end of the stretch. They relaxed their muscles fully after the stretch. This chain of processes was consecutively repeated 10 times. EMG signals obtained from SOL were averaged after they were high-pass filtered and full-wave rectified. Some major findings resulted: (1) there were no differences in SLSR area in the active muscle between pre-ISO and pre-SHO, whereas its waveform was steeper in pre-ISO than in pre-SHO. (2) SLSR p-to-p amplitude and waveform were larger and steeper in the active muscle than in the relaxed one in all conditions, whereas they were independent of the effort levels once the muscle was activated. This led to steady SLSR modulation in response to the background muscle contraction in the active muscle regardless of whether the SLSR was elicited at matched AJT or EMG activity levels. These findings suggest that SLSR is closely related to the muscle spindle sensitivity influenced by the following factors: (1) the background muscle contraction type, and (2) gamma motoneuron activity set by CNS based on the effort level.

Effects of power training on muscle structure and neuromuscular performance.

The present study examines changes in muscle structure and neuromuscular performance induced by 15 weeks of power training with explosive muscle actions. Twenty-three subjects, including 10 controls, volunteered for the study. Muscle biopsies were obtained from the gastrocnemius muscle before and after the training period, while maximal voluntary isometric contractions (MVC) and drop jump tests were performed once every fifth week. No statistically significant improvements in MVC of the knee extensor (KE) and plantarflexor muscles were observed during the training period. However, the maximal rate of force development (RFD) of KE increased from 18,836+/-4282 to 25,443+/-8897 N (P<0.05) during the first 10 weeks of training. In addition, vertical jump height (vertical rise of the center of body mass) in the drop jump test increased significantly (P<0.01). Simultaneously, explosive force production of KE muscles measured as knee moment and power increased significantly; however, there was no significant change (P>0.05) in muscle activity (electromyography) of KE. The mean percentage for myosin heavy chain and titin isoforms, muscle fiber-type distributions and areas were unchanged. The enhanced performance in jumping as a result of power training can be explained, in part, by some modification in the joint control strategy and/or increased RFD capabilities of the KE.

Effects of power training on mechanical efficiency in jumping.

The present study investigates the effects of power training on mechanical efficiency (ME) in jumping. Twenty-three subjects, including ten controls, volunteered for the study. The experimental group trained twice a week for 15 weeks performing various jumping exercises such as drop jumps, hurdle jumps, hopping and bouncing. In the maximal jumping test, the take-off velocity increased from 2.56 (0.24) m.s(-1) to 2.77 (0.18) m.s(-1) ( P<0.05). In the submaximal jumping of 50% of the maximum, energy expenditure decreased from 660 (110) to 502 (68) J.kg(-1).min(-1) ( P<0.001) while, simultaneously, ME increased from 37.2 (8.4)% to 47.4 (8.2)% ( P<0.001). Some muscle enzyme activities of the gastrocnemius muscle increased during the training period: citrate synthase from 35 (8) to 39 (7) micromol.g(-1) dry mass.min(-1) ( P<0.05) and beta-hydroxyacyl CoA dehydrogenase from 21 (4) to 23 (5) micromol.g(-1) dry mass.min(-1) ( P<0.05), whereas no significant changes were observed in phosphofructokinase and lactate dehydrogenase. In the control group, no changes in ME or in enzyme activities were observed. In conclusion, the enhanced performance capability of 8% in maximal jumping as a result of power training was characterized by decreased energy expenditure of 24%. Thus, the increased neuromuscular performance, joint control strategy, and intermuscular coordination (primary factors), together with improved aerobic capacity (secondary factor), may result in reduced oxygen demands and increased ME.

Short-latency stretch reflex modulation in response to varying soleus muscle activities.

The current investigation examined the effect of various types of background muscle contractions on the short-latency stretch reflex (SLR) elicited from the soleus muscle while subjects were in a sitting position. A stretch was applied to the calf muscles while they performed an isometric (pre-ISO), shortening (pre-SHO) and lengthening contraction (pre-LEN) with several pre-contraction levels. The ankle was at a 90 degrees tibio-tarsal joint angle when the perturbation was applied. Subjects developed and maintained a given pre-load level, which was maintained at various percentages of the maximum voluntary isometric plantar flexion torque. This was performed at 80 degrees in pre-SHO, 90 degrees in pre-ISO and 100 degrees in pre-LEN for about 2s before the contractions. The SLRs in trials with 0, 35 and 50% of the maximum voluntary contraction torque level were compared among the three conditions. The main results were as follows. (1) Pre-ISO and pre-SHO showed an equal SLR area and a different SLR waveform in the active muscle. (2) Pre-LEN showed the smallest SLR area of three conditions in the active muscle. (3) Pre-LEN showed shorter SLR latencies than the other conditions. (4) Pre-SHO showed a longer SLR latency in the relaxed muscle than in the active muscle. (5) The SLR area was larger in the active muscle than in the relaxed muscle. These findings demonstrate that the muscle contraction type and the pre-contraction level before a stretch perturbation have a considerable influence on the latency, the area and the waveform of the SLR. In particular, the equal area and the different waveforms of the SLR between pre-ISO and pre-SHO were a unique finding in the present study. They might result from differences in muscle spindle sensitivity and afferent input from various receptors induced by the present motor task.

Stretch-reflex mechanical response to varying types of previous muscle activities.

This study was designed to examine the effects of varying types of background muscle activity on the stretch-reflex mechanical response. A rapid stretch was applied to the calf muscles after an isometric (pre-ISO), shortening (pre-SHO) and lengthening contraction (pre-LEN) with several pre-contraction levels, respectively. The stretch perturbation was applied with the tibio-tarsal joint angle at 90 degrees. The ankle joint torque elicited by the stretch showed a first peak (non-reflex torque: NRT), a transient drop and a second peak (reflex torque: RT). The muscle activities before the stretch clearly influenced the stretch-reflex mechanical response. The NRT reached the largest peak with the longest duration in pre-ISO. The peak NRT increased with the pre-contraction level in pre-ISO and pre-LEN, whereas it remained unchanged in pre-SHO. The RT responded to the stretch-reflex EMG response most quickly and reached the largest peak in pre-ISO. Pre-ISO generated the mechanical response most efficiently against the size of the stretch-reflex EMG response. Pre-SHO showed lower peak RT than pre-ISO in spite of the similar size of stretch-reflex EMG response. The peak RT was closely related to the peak NRT in all conditions. Consequently, the peak RT also increased with the pre-contraction level in pre-ISO and pre-LEN, whereas it remained unchanged in pre-SHO. In conclusion, a stretch after an isometric contraction evoked a larger stretch-reflex mechanical response more efficiently than that after phasic contractions when a given effort was being maintained.

A complicated relationship: fulfilling the interactive needs of the T lymphocyte and the dendritic cell.

T cells recognize antigenic peptides displayed on the surface of MHC-bearing antigen-presenting cells (APCs), and with sufficient costimulation become activated. However, the ability of an APC (even bearing the correct peptide) to initiate and fulfill the requirements for T cell activation is not easily achieved. Naive T cells use multiple copies of a single receptor to survey the vast array of peptides presented on an APC, and require multiple receptor engagements to initiate T cell activation. Dendritic cells (DCs) are specialized cells with optimal capabilities for priming naive CD4+ T cells. Activation occurs, after initial antigen recognition by T cells, followed by a rapid dialogue between the T cells and the DCs. The resulting changes in both the cytoskeleton and the expression or regulation of cell-surface molecules on both cell types act to further strengthen engagement. In this report, we review the fundamentals of CD4+ T helper cell : DC interactions and discuss recent data concerning the molecular characteristics of this engagement.

Changes in myosin heavy chain composition with heavy resistance training in 60- to 75-year-old men and women.

The purpose of this investigation was to assess the myosin heavy chain (MHC) expression in the vastus lateralis muscle from elderly men and women, and to determine whether heavy resistance training influences its expression. Twenty healthy, mildly physically active subjects gave their informed consent to participate in the study. The experimental group consisted of seven men and seven women [mean (SD) age 65.5 (4.1) years] and the control group consisted of three men and three women [mean (SD) age 62.3 (3.6) years]. The 6-month resistance training program was divided into two phases with weeks 1-12 consisting of high-intensity resistance training, and weeks 13-24 involving power training. Muscle biopsy samples were taken from the vastus lateralis muscle at week 0 and week 24 using the needle biopsy technique. The male and female experimental groups both exhibited a significant decrease (P < or = 0.05) in the percentage of MHC IIb, while the experimental female group also demonstrated a significant increase (P < or = 0.05) in the expression of MHC IIa, after 24 weeks of heavy resistance training. There was no change in MHC expression within the control group. The male [130.4 (25.3) kg vs 171.1 (30.5) kg] and female [58.2 (8.3) kg vs 77.9 (11.1) kg] experimental groups exhibited a significant increase (P < or = 0.05) in the maximal strength values for the 1 repetition maximum (1RM) squat exercise. The control group showed no change in strength for the 1RM squat exercise for either the male [115.8 (35.10 kg vs 123.8 (47.2) kg] or female [57.5 (99.0) kg vs 58.3 (2.9) kg] groups. The results clearly show that elderly subjects undergoing heavy resistance training have the ability to produce a similar shift in the expression of MHC isoforms from MHC IIb to MHC IIa, as has been shown to occur in younger subjects. This highlights the plasticity of human skeletal muscle in response to heavy resistance training, even at older ages.

Influence of exercise training on physiological and performance changes with weight loss in men.

PURPOSE: The purpose of this study was to examine the physiological effects of a weight-loss dietary regimen with or without exercise. METHODS: Thirty-five overweight men were matched and randomly placed into either a control group (C; N = 6) or one of three dietary groups; a diet-only group (D; N = 8), a diet group that performed aerobic exercise three times per week (DE; N = 11); and a diet group that performed both aerobic and strength training three times per week (DES; N = 10). RESULTS: After 12 wk, D, DE, and DES demonstrated a similar and significant (P < or = 0.05) reduction in body mass (-9.64, -8.99, and -9.90 kg, respectively) with fat mass comprising 69, 78, and 97% of the total loss in body mass, respectively. The diet-only group also demonstrated a significant reduction in fat-free mass. Maximum strength, as determined by 1-RM testing in the bench press and squat exercise was significantly increased for DES in both the bench press (+19.6%) and squat exercise (+32.6%). Absolute peak O2 consumption was significantly elevated in DE (+24.8%) and DES (+15.4%). There were no differences in performance during a 30-s Wingate test for the DE and DES, whereas D demonstrated a significant decline in peak and mean power output. Resting metabolic rate (RMR) (kcal x d(-1)) was not significantly different for any of the groups except for the DE group. There were no significant changes in basal concentrations of serum glucose, BUN, cortisol, testosterone, and high density lipoprotein (HDL) cholesterol for any of the groups. Serum total cholesterol and low density lipoprotein (LDL) cholesterol were significantly decreased for all dietary groups. Serum triglycerides were significantly reduced for D and DES at week 6 and remained lower at week 12 for D, while triglycerides returned to baseline values for DES. CONCLUSIONS: These data indicate that a weight-loss dietary regimen in conjunction with aerobic and resistance exercise prevents the normal decline in fat-free mass and muscular power and augments body composition, maximal strength, and maximum oxygen consumption compared with weight-loss induced by diet alone.

Plasma proenkephalin peptide F and human B cell responses to exercise stress in fit and unfit women.

In vitro studies have connected immune cell function to Peptide F. The primary purpose of this investigation was to examine the responses of plasma Peptide F and epinephrine along with the changes in B cell antibody production in vivo in physically fit and unfit women in response to physical exercise on a cycle ergometer at 60% and 80% of peak oxygen consumption. Seven aerobically fit and eight untrained (i.e., unfit) women between the ages of 18 and 30 volunteered to participate in this investigation. Blood samples (analyzed for plasma Peptide F and epinephrine along with the number of antibody-producing B cells) were obtained 24 hours prior to the exercise session, pre-exercise, during each exercise intensity, and five minutes post-exercise. The fit group had a significantly higher plasma Peptide F concentration after the 80% exercise intensity along with significantly higher numbers of antibody producing B cells compared to the unfit group. The results of this investigation show that physically fit women have an enhanced secondary response of B cells to a specific antigen under conditions where Peptide F is increased. Such data demonstrate that physical fitness as promoted by the Public Health Service (e.g., Healthy People 2000) influences the underlying hormonal and immune cell responses when challenged by physical exercise stress.

Effect of resistance exercise on free radical production.

The purposes of this investigation were to see whether free radical production changed with high intensity resistance exercise and, secondly, to see whether vitamin E supplementation would have any effect on free radical formation or variables associated with muscle membrane disruption. Twelve recreationally weight-trained males were divided into two groups. The supplement group (S) received 1200 IUs of vitamin E once a day (3 x 400 IU x d[-1]) for a period of 2 wk. The placebo group (P) received cellulose-based placebo pills once a day for the same period of time. Creatine kinase activity was significantly elevated between preexercise and immediately postexercise, 6 h postexercise, and 24 h postexercise for both groups. The placebo group also had a significant increase in creatine kinase activity at 48 h postexercise. There was a significant difference in creatine kinase activity between the groups at 24 h after exercise. Plasma malondialdehyde significantly increased from preexercise levels for the P group at 6 and 24 h postexercise. Plasma malondialdehyde concentrations significantly increased in the S group between preexercise and immediately postexercise levels. This study indicates that high intensity resistance exercise increases free radical production and that vitamin E supplementation may decrease muscle membrane disruption.

Physiological adaptations to a weight-loss dietary regimen and exercise programs in women.

Thirty-one women (mean age 35.4 +/- 8.5 yr) who were overweight were matched and randomly placed into either a control group (Con; n = 6), a diet-only group (D; n = 8), a diet+aerobic endurance exercise training group (DE; n = 9), or a diet+aerobic endurance exercise training+strength training group (DES; n = 8). After 12 wk, the three dietary groups demonstrated a significant (P

Responses of IGF-I to endogenous increases in growth hormone after heavy-resistance exercise.

The purpose of this study was to examine the effects of a heavy-resistance exercise protocol known to dramatically elevate immunoreactive growth hormone (GH) on circulating insulin-like growth factor I (IGF-I) after the exercise stimulus. Seven men (23.1 +/- 2.4 yr) volunteered to participate in this study. Each subject was asked to perform an eight-station heavy-resistance exercise protocol consisting of 3 sets of 10 repetition maximum resistances with 1-min rest between sets and exercises followed by a recovery day. In addition, a control day followed a nonexercise day to provide baseline data. Pre- and postexercise (0, 15, and 30 min) blood samples were obtained and analyzed for lactate, creatinine kinase, GH, and IGF-I. Postexercise values for lactate and GH were significantly (P < 0.05) elevated above preexercise and resting baseline values. The highest mean GH concentration after the heavy-resistance exercise protocol was 23.8 +/- 11.8 micrograms/l, observed at the immediate postexercise time point. Significant increases in creatine kinase were observed after the exercise protocol and during the recovery day. No significant relationships were observed between creatine kinase and IGF-I concentrations. No significant changes in serum IGF-I concentrations were observed with acute exercise or between the recovery and control days. Thus, these data demonstrate that a high-intensity bout of heavy-resistance exercise that increases circulating GH did not appear to affect IGF-I concentrations over a 24-h recovery period in recreationally strength-trained and healthy young men.

Automated order-entry mechanisms to influence prescribing.

On-line prescribing is available in many hospitals in the United States and has distinct advantages. On-line drug prescribing can be influenced by the use of automated prompts that guide and direct the prescriber to the preferred agent, dosage, or regimen. The authors have adapted screen prompts to facilitate appropriate prescribing as defined by pharmacy and therapeutic (P&T) committee decisions, restricted drug or target drug initiatives, drug-usage evaluation (DUE) actions, departmental guidelines and order-sets, and other institutional directives. Objective evidence for the effectiveness of on-line prompts is provided for H2-antagonists and antibiotics. As computer technology advances even further and is increasingly utilized in the health care setting, on-line interventions to facilitate appropriate prescribing may become increasingly useful.

Physician usage of the computer to access a hospital information system.

This retrospective descriptive study was undertaken to determine the characteristics of physicians who use the computer to access a Hospital Information System (HIS). A convenience sample of 630 staff physicians at a 640-bed metropolitan tertiary care teaching medical center was analyzed utilizing the variables of age, specialty, years in practice, gender, and frequency of use. A significant difference (p < or = .01) in age was found with the user physician being younger than the nonuser; no significance was found (p < or = .01) in specialty, years in practice, or gender.