Economic evaluation of exercise-based cardiac rehabilitation in patients with a recent acute coronary syndrome.

Health care decision-making requires evidence of the cost-effectiveness of medical therapies. We evaluated the cost-effectiveness of exercise-based cardiac rehabilitation (ECR) implemented according to guidelines. All the patients (n = 204) had experienced a recent acute coronary syndrome and were randomized to a 1-year ECR (n = 109) or usual care (UC) group (n = 95). The patients' health-related quality of life was followed using the 15D instrument and health care costs were collected from electronic health registries. The cost-effectiveness of ECR was estimated based on intervention and health care costs and quality-adjusted life years (QALYs) gained. The total average cost per patient was lower in ECR than in UC. The incremental cost was divided by the baseline-adjusted incremental QALYs (0.045), yielding an incremental cost-effectiveness ratio of -€24511/QALYs. A combined endpoint of mortality, recurrent coronary event, or hospitalization for a heart failure occurred for five patients in ECR and 16 patients in UC (HR 3.9, 95% CI 1.4-10.6, P = 0.004, relative risk reduction 73%, number needed to treat eight). ECR is a dominant treatment option and decreases the occurrence of adverse cardiac events. These results are useful for decision-making when planning optimal utilization of resources in Finnish health care.

Autonomic Function Predicts Fitness Response to Short-Term High-Intensity Interval Training.

We tested the hypothesis that baseline cardiac autonomic function and its acute response to all-out interval exercise explains individual fitness responses to high-intensity interval training (HIT). Healthy middle-aged sedentary men performed HIT (n=12, 4-6×30 s of all-out cycling efforts with 4-min recovery) or aerobic training (AET, n=9, 40-60 min at 60% of peak workload in exercise test [Loadpeak]), comprising 6 sessions within 2 weeks. Low (LF) and high frequency (HF) power of R-R interval oscillation were analyzed from data recorded at supine and standing position (5+5 min) every morning during the intervention. A significant training effect (p< 0.001), without a training*group interaction, was observed in Loadpeak and peak oxygen consumption (VO2peak). Pre-training supine LF/HF ratio, an estimate of sympathovagal balance, correlated with training outcome in Loadpeak (Spearman's rho [rs]=-0.74, p=0.006) and VO2peak (rs=- 0.59, p=0.042) in the HIT but not the AET group. Also, the mean change in the standing LF/HF ratio in the morning after an acute HIT exercise during the 1(st) week of intervention correlated with training response in Loadpeak (rs=- 0.68, p=0.014) and VO2peak (rs=-0.60, p=0.039) with HIT but not with AET. In conclusion, pre-training cardiac sympathovagal balance and its initial alterations in response to acute HIT exercise were related to fitness responses to short-term HIT.

Temporal dynamics of the circadian heart rate following low and high volume exercise training in sedentary male subjects.

PURPOSE: Increased risk of arrhythmic events occurs at certain times during the circadian cycle with the highest risk being in the second and fourth quarter of the day. Exercise improves treatment outcome in individuals with cardiovascular disease. How different exercise protocols affect the circadian rhythm and the associated decrease in adverse cardiovascular risk over the circadian cycle has not been shown. METHODS: Fifty sedentary male participants were randomized into an 8-week high volume and moderate volume training and a control group. Heart rate was recorded using Polar Electronics and investigated with Cosinor analysis and by Poincaré plot derived features of SD1, SD2 and the complex correlation measure (CCM) at 1-h intervals over the 24-h period. RESULTS: Moderate exercise significantly increased vagal modulation and the temporal dynamics of the heart rate in the second quarter of the circadian cycle (p = 0.004 and p = 0.007 respectively). High volume exercise had a similar effect on vagal output (p = 0.003) and temporal dynamics (p = 0.003). Cosinor analysis confirms that the circadian heart rate displays a shift in the acrophage following moderate and high volume exercise from before waking (1st quarter) to after waking (2nd quarter of day). CONCLUSIONS: Our results suggest that exercise shifts vagal influence and increases temporal dynamics of the heart rate to the 2nd quarter of the day and suggest that this may be the underlying physiological change leading to a decrease in adverse arrhythmic events during this otherwise high-risk period.

Altered relationship between R-R interval and R-R interval variability in endurance athletes with overtraining syndrome.

Autonomic dysfunction decreases within-subject correlation between R-R interval length (RRi) and vagally mediated RRi variability in cardiac disease. We tested the hypothesis that overtraining syndrome (OTS) may also weaken this relationship. Nine OTS and 10 control endurance athletes underwent 24-h electrocardiogram monitoring, which was repeated in eight OTS and nine control athletes after 6 months, when two OTS athletes still had symptoms of OTS. The power of high-frequency (HF) oscillations of RRi was analyzed in 5-min epochs over the whole recording. Quadratic regression was performed between 5-min values of RRi and log-transformed (ln) HF to obtain R(2) for each recording. The relationship between RRi and HFln was higher in the OTS athletes than controls [R(2): 0.87 (90% confidence interval, CI: 0.84-0.89) vs 0.78 (90% CI: 0.72-0.84); P = 0.034; effect size = 1.22]. Large decrease in R(2) was observed in six recovered OTS athletes after 6 months follow-up [ΔR(2): -0.12 (90% CI: -0.25-0.01); P = 0.11; effect size = 1.44] with no changes in the controls. Mean values of RRi and its variability did not differ between the groups. The within-subject correlation between RRi and vagally mediated RRi variability was stronger in endurance athletes with OTS compared with controls. The present findings may improve the detection of OTS and recovery from OTS in endurance athletes.

Degradation of coeliac disease-inducing rye secalin by germinating cereal enzymes: diminishing toxic effects in intestinal epithelial cells.

Currently the only treatment for coeliac disease is a lifelong gluten-free diet excluding food products containing wheat, rye and barley. There is, however, only scarce evidence as to harmful effects of rye in coeliac disease. To confirm the assumption that rye should be excluded from the coeliac patient's diet, we now sought to establish whether rye secalin activates toxic reactions in vitro in intestinal epithelial cell models as extensively as wheat gliadin. Further, we investigated the efficacy of germinating cereal enzymes from oat, wheat and barley to hydrolyse secalin into short fragments and whether secalin-induced harmful effects can be reduced by such pretreatment. In the current study, secalin elicited toxic reactions in intestinal Caco-2 epithelial cells similarly to gliadin: it induced epithelial cell layer permeability, tight junctional protein occludin and ZO-1 distortion and actin reorganization. In high-performance liquid chromatography and mass spectroscopy (HPLC-MS), germinating barley enzymes provided the most efficient degradation of secalin and gliadin peptides and was thus selected for further in vitro analysis. After germinating barley enzyme pretreatment, all toxic reactions induced by secalin were ameliorated. We conclude that germinating enzymes from barley are particularly efficient in the degradation of rye secalin. In future, these enzymes might be utilized as a novel medical treatment for coeliac disease or in food processing in order to develop high-quality coeliac-safe food products.

Neuromuscular function during therapeutic knee exercise under water and on dry land.

OBJECTIVES: To compare muscle activity and resistive drag force during knee extension-flexion exercises while barefoot and while wearing a Hydro Boot (increased frontal area) both under water and on dry land. DESIGN: Participants performed the exercises while seated on an elevator chair under water. SETTING: A hydrotherapy pool. PARTICIPANTS: Eighteen healthy persons (10 women, 8 men). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Isokinetic and isometric forces were measured with a dynamometer. The electromyographic activity of the quadriceps (vastus medialis, vastus lateralis) and hamstring muscles (biceps femoris) was recorded. The underwater drag for the range of motion was calculated by using the general fluid equation. RESULTS: The underwater electromyographic patterns showed an early decrease in the concentric activity of the agonists with coincidental activation of the antagonists. In addition, the electromyographic amplitudes were similar between the 2 underwater conditions, but the Hydro Boot produced a higher level (p < .001) of drag than did the barefoot condition. As expected, in most cases the forces on dry land were higher (p < .001) than underwater drag. In flexion, however, the peak drag with Hydro Boot and isokinetic force did not differ. CONCLUSIONS: Increasing the frontal area of the lower leg with a Hydro Boot significantly increased the level of water resistance, thus, providing flexion forces that approach those measured on dry land. This type of water training offers stimulation to enhance the functional capacity and performance of the neuromuscular system. In addition, hydrodynamic principles and forces that influence the exercising limb must be considered to ensure appropriate progression.

Electromyographic and kinematic analysis of therapeutic knee exercises under water.

OBJECTIVE: This study aimed to evaluate muscle function and kinematics during commonly used knee rehabilitation exercises performed in water. DESIGN: Maximal effort single extension and flexion trials in still water and repeated extension-flexion trials in flowing water in barefoot condition were analysed from 18 healthy participants (8 men, 10 women). BACKGROUND: Despite the fact that water exercises are widely used, there are only few studies involving biomechanical and hydrodynamical analysis of aquatic exercises in rehabilitation. METHODS: Electromyography of the quadriceps (vastus medialis, vastus lateralis) and hamstring muscles (biceps femoris, semitendinosus) and angular velocities of the movements were recorded under water. RESULTS: In the repeated extension-flexion exercises the early reduction of agonist activity occurred concurrently with a high level of activity of the antagonists. In the single trial exercises the level of antagonistic activity was low throughout the range of motion, whereas the level of agonist activity was higher during the final phase of the range of motion as compared with the repeated exercises. Angular velocity patterns and values were similar between the two types of exercises. CONCLUSIONS: The present data demonstrated that the flowing properties of water modified the neuromuscular function of the quadriceps and hamstring muscles acting as agonists and antagonists in the knee flexion-extension exercises.

Changes in cardiac autonomic regulation after prolonged maximal exercise.

Harmful cardiac events occurs frequently after exercise. However, the cardiac autonomic regulation after vigorous exercise is not well known. This study was designed to assess heart rate (HR) variability before and after a 75 km cross-country skiing race. HR variability was assessed by using standard statistical measures along with spectral and quantitative Poincarè plot analysis of HR variability in 10 healthy male subjects (age 36 +/- 11 years). The average HR was at the same level 1 day after the race as before the race, but on the second day, HR was significantly lower (P<0.001) compared with the prerace and 1 day after values. The normalized high-frequency (HF) spectral component of HR variability (nuHF) was lower (P<0.01) on the first day after the maximal exercise compared with the pre-exercise values but returned to or even exceeded the prerace level on the second day (P<0.01). The changes in short-term R-R interval variability analysed from the Poincaré plot were similar to those observed in the HF spectral component. The normalized low-frequency (LF) spectral component of HR variability (nuLF) was higher (P<0.01) on the first day after the exercise compared with the prerace levels and it also returned to the pre-exercise level or even dropped below it on the second day after the race. The mean time it took the HF spectral component to return to the pre-exercise level was 4.2 +/- 4.2 h (ranging from 0 to 12 h). This recovery time correlated inversely with the maximal oxygen consumption (VO2max) measured during the bicycle exercise test before the skiing race (r=-0.712, P<0.016). The cardiac vagal outflow is blunted for several hours after prolonged vigorous exercise. The recovery time of reduced vagal outflow depends on individual cardiorespiratory fitness and there is an accentuated rebound of altered autonomic regulation on the second day after prolonged exercise.

Determination of hydrodynamic drag forces and drag coefficients on human leg/foot model during knee exercise.

OBJECTIVE: The purpose of this laboratory experiment was to measure hydrodynamic drag forces in barefoot/hydro-boot conditions and accordingly, to determine the coefficients of drag on human leg/foot model during simulated knee extension-flexion exercise. DESIGN: The prosthesis of the human lower leg was set in a water tank and connected into an isokinetic force dynamometer to measure resistive forces during knee motion. BACKGROUND: Quantifying resistance for aquatic exercises has been a challenge in hydrotherapy. The use of models of foot/leg provides a practical method to calculate coefficients of drag and to estimate resistance for rehabilitation purposes in musculoskeletal and amputee patients. METHODS: The dynamometer produced constant angular velocities of 250 degrees /s, 270 degrees /s and 300 degrees /s to the prosthesis. The baseline for measurements was performed in barefoot condition. A hydro-boot was used to study effects of increased frontal area (30%) of the leg on drag forces and coefficients. RESULTS: The maximal drag force values were 61 N (300 degrees /s) in barefoot and 270 N (270 degrees /s) in hydro-boot condition. Related drag coefficient values during the range of motion were from 0.3 to 0.1 and from 1 to 0.8, respectively. CONCLUSIONS: Drag force and related drag coefficient were highest during the early part of extension (150-140 degrees flexion) as the model was opposing the lift forces with the influence of water resistance. The effect of velocity was remarkable on drag forces but minimal on drag coefficient values. RelevanceThe drag forces and coefficients of this experiment can be clinically utilised to calculate hydrodynamic forces to develop progressive knee exercise programs as well as to design of prosthesis for amputee patients.

An efficient approach for screening minimal PKS genes from Streptomyces.

Degenerated oligonucleotide primers were designed to amplify fragments of ketosynthase genes from polyketide antibiotics producing Streptomyces spp. and bacterial strains enriched from soil samples. Cell lysates were used as templates in amplification, so time-consuming DNA purification was avoided. A phylogenetic tree constructed from the amino acid sequences of the amplified fragments shows a distribution of spore pigments and antibiotics in separate classes. In addition, several different subgroups form within the antibiotics group. Anthracyclines were divided into separate branches according to the starter unit used in biosynthesis.

Incorrectly folded aromatic polyketides from polyketide reductase deficient mutants.

Compounds produced by the polyketide ketoreductase deficient Streptomyces mutants HO61 and P67 are described. The structures of the compounds indicate that ketoreductase activity is required for correct condensation of the polyketide chain in the biosynthesis of aromatic polyketides.

Human isometric force production and electromyogram activity of knee extensor muscles in water and on dry land.

This study was designed to determine trial-to-trial and day-to-day reproducibility of isometric force and electromyogram activity (EMG) of the knee extensor muscles in water and on dry land as well as to make comparisons between the two training conditions in muscle activity and force production. A group of 20 healthy subjects (12 women and 8 men) were tested three times over 2 weeks. A measurement session consisted of recordings of maximal and submaximal isometric knee extension force with simultaneous recording of surface EMG from the vastus medialis, vastus lateralis and biceps femoris muscles. To ensure identical measurement conditions the same patient elevator chair was used in both the dry and the wet environment. Intraclass correlation coefficients (ICC) and coefficients of variation (CV) showed high trial-to-trial (ICC = 0.95-0.99, CV = 3.5%-11%) and day-to-day reproducibility (ICC=0.85-0.98, CV=11%-19%) for underwater and dry land measurements of force and EMG in each muscle during maximal contractions. The day-to-day reproducibility for submaximal contractions was similar. The interesting finding was that underwater EMG amplitude decreased significantly in each muscle during maximal (P < 0.01-P < 0.001) and submaximal contractions (P < 0.05-P < 0.001). However, the isometric force measurements showed similar values in both wet and dry conditions. The water had no disturbing effect on the electrodes as shown by slightly lowered interelectrode resistance values, the absence of artefacts and low noise levels of the EMG signals. It was concluded that underwater force and EMG measurements are highly reproducible. The significant decrease of underwater EMG could have electromechanical and/or neurophysiological explanations.

Folding of the polyketide chain is not dictated by minimal polyketide synthase in the biosynthesis of mithramycin and anthracycline.

BACKGROUND: Mithramycin, nogalamycin and aclacinomycins are aromatic polyketide antibiotics that exhibit antitumour activity. The precursors of these antibiotics are formed via a polyketide biosynthetic pathway in which acetate (for mithramycinone and nogalamycinone) or propionate (for aklavinone) is used as a starter unit and nine acetates are used as extender units. The assembly of building blocks is catalyzed by the minimal polyketide synthase (PKS). Further steps include regiospecific reductions (if any) and cyclization. In the biosynthesis of mithramycin, however, ketoreduction is omitted and the regiospecificity of the first cyclization differs from that of anthracycline antibiotics (e.g. nogalamycin and aclacinomycins). These significant differences provide a convenient means to analyze the determinants for the regiospecificity of the first cyclization step. RESULTS: In order to analyze a possible role of the minimal PKS in the regiospecificity of the first cyclization in polyketide biosynthesis, we expressed the mtm locus, which includes mithramycin minimal PKS genes, in Streptomyces galilaeus, which normally makes aclacinomycins, and the sno locus, which includes nogalamycin minimal PKS genes, in Streptomyces argillaceus, which normally makes mithramycin. The host strains are defective in the minimal PKS, but they express other antibiotic biosynthesis genes. Expression of the sno minimal PKS in the S. argillaceus polyketide-deficient strain generated mithramycin production. Auramycins, instead of aclacinomycins, accumulated in the recombinant S. galilaeus strains, suggesting that the mithramycin minimal PKS is responsible for the choice of starter unit. We also describe structural analysis of the compounds accumulated by a ketoreductase-deficient S. galilaeus mutant; spectroscopic studies on the major polyketide compound that accumulated revealed a first ring closure which is not typical of anthracyclines, suggesting an important role for the ketoreductase in the regiospecificity of the first cyclization. CONCLUSIONS: These experiments clearly support the involvement of ketoreductase and a cyclase in the regiospecific cyclization of the biosynthetic pathway for aromatic polyketides.

Isolation and characterization of 8-demethoxy steffimycins and generation of 2,8-demethoxy steffimycins in Streptomyces steffisburgensis by the nogalamycin biosynthesis genes.

Streptomyces steffisburgensis (NRRL 3193, ATCC 27466) is described as a steffimycin producer. Steffimycin belongs to the anthracycline group of aromatic polyketide antibiotics. The structural analysis of the products accumulated by the wild type ATCC 27466 strain revealed three different forms of 8-demethoxy steffimycin suggesting the loss of C-8 hydroxylation/methylation activity. In our approach to generate new anthracycline molecules, we used this strain as a host in gene cloning. The genes encoding the polyketide ketoreductase and aromatase enzymes of nogalamycin biosynthesis caused the production of 2-demethoxy steffimycins in S. steffisburgensis.

Temperature changes in deep muscles of humans during ice and ultrasound therapies: an in vivo study.

Therapeutic ultrasound can be a very effective treatment modality when used correctly in the treatment of musculoskeletal conditions and wound healing. However, many protocols for the administration of ultrasound have not been scientifically tested. The purpose of this study was to measure muscle temperature changes during a frequently used protocol, ie., preicing prior to ultrasound application. A 23-gauge hypodermic needle microprobe was inserted 5 cm deep into the medial aspect of the anesthetized triceps surae muscle of 16 subjects. Two groups consisting of eight subjects each were tested for temperature changes during: a) ultrasound treatment on precooled tissue or b) ultrasound with no preceding treatment. Each treatment consisted of 10 minutes of continuous ultrasound delivered topically at 1.5 watts/cm2. A significant difference between the two treatment methods was measured (F = 19.06, p < 0.01). Ultrasound alone increased tissue temperature an average of 4.0 +/- .83 degrees C, whereas ultrasound preceded by 5 minutes of ice increased tissue temperature only 1.8 +/- 1.0 degrees C above original baseline level. At a depth of 5 cm, ultrasound preceded by ice treatment yielded little or no thermal benefits.