Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis, also known as chronic fatigue syndrome or ME/CFS, is a multifactorial and debilitating disease that has an impact on over 4 million people in the United States alone. The pathogenesis of ME/CFS remains largely unknown; however, a genetic predisposition has been suggested. In the present study, we used a DNA single-nucleotide polymorphism (SNP) chip representing over 906,600 known SNPs to analyze DNA from ME/CFS subjects and healthy controls. To the best of our knowledge, this study represents the most comprehensive genome-wide association study (GWAS) of an ME/CFS cohort conducted to date. Here 442 SNPs were identified as candidates for association with ME/CFS (adjusted P-value<0.05). Whereas the majority of these SNPs are represented in non-coding regions of the genome, 12 SNPs were identified in the coding region of their respective gene. Among these, two candidate SNPs resulted in missense substitutions, one in a pattern recognition receptor and the other in an uncharacterized coiled-coil domain-containing protein. We also identified five SNPs that cluster in the non-coding regions of T-cell receptor loci. Further examination of these polymorphisms may help identify contributing factors to the pathophysiology of ME/CFS, as well as categorize potential targets for medical intervention strategies.

Myalgic encephalomyelitis: International Consensus Criteria.

The label 'chronic fatigue syndrome' (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term 'myalgic encephalomyelitis' (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization's International Classification of Diseases (ICD G93.3). Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge. Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria. The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions/drafts/reviews/revisions. The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application. Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.

Norandrosterone and noretiocholanolone concentration before and after submaximal standardized exercise.

19-Norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) are the two main urinary indicators used to detect illegal use of nandrolone. Recent studies showed that 19-NA and 19-NE can be endogenously produced in non-treated humans. The concentrations were close to the threshold of the International Olympic Committee (IOC), i.e. 2 ng/ml for men and seem to increase after prolonged intense effort. Androgens are involved in the biosynthesis of estrogens and estrogen has a protective effect against skeletal muscle damage following eccentric exercise. Furthermore, the testicular tissue can synthesize 19-norandrogens from androgens, we hypothetisize that the 19-norandrogen production might be influenced by muscle damage following eccentric exercise. Therefore the purpose of this study is to examine if three different exercise methods will influence the urinary concentration of 19-NA and 19-NE in healthy young subjects. Fifteen amateur hockey players undertook a 30 min submaximal standardized exercise protocol. They were randomised for three different types of exercise, namely a cycle ergometer test (cyclic muscle activity), a treadmill test (concentric muscle activity), or a bench-steptest (eccentric muscle activity) at a target heart rate corresponding to 65 % (+/- 5 %) of Karvonen heart rate. Urine samples were obtained before the test and 60 min and 120 min after the end of exercise. Subjects completed a Likert scale of muscle soreness before and 12 h after exercise. 19-NA and 19-NE were determined by gas chromatography-tandem mass spectrometry (GC-MS-MS). Baseline urinary 19-NA and 19-NE concentrations were under limit of detection of 0.05 ng/ml, except for one sample (0.13 ng/ml). No 19-NA or 19-NE could be detected post exercise. In our experimental conditions, the exercise mode (eccentric or concentric) had no impact on 19-NA or 19-NE excretion. Our findings confirm that the current International Olympic Committee threshold level for nandrolone metabolites is sufficiently high to avoid false positive cases.

Disability evaluation in chronic fatigue syndrome: associations between exercise capacity and activity limitations/participation restrictions.

OBJECTIVE: In an attempt to examine whether impairments in cardiorespiratory fitness are associated with daily functioning in patients with chronic fatigue syndrome (CFS), this study addresses the correlations between exercise capacity and activity limitations/participation restrictions. DESIGN: Prospective observational study. SETTING: An outpatient tertiary care, chronic fatigue clinic at the Vrije Universiteit Brussel (VUB), Belgium. SUBJECTS: Seventy-seven patients fulfilling the 1994 Centers for Disease Control and Prevention (CDC) case definition for CFS. INTERVENTIONS: All patients filled in the Chronic Fatigue Syndrome Activities and Participation Questionnaire (CFS-APQ) and performed a maximal exercise stress test on a bicycle ergometer. Heart rate was monitored continuously by use of an electrocardiograph. Metabolic and ventilatory parameters were measured through spirometry. RESULTS: A statistically significant correlation between the score obtained with the CFS-APQ and the body weight-adjusted peak oxygen uptake (Spearman rho = -0.32; p = 0.005), functional aerobic impairment (rho = 0.33; p = 0.004), workload/body weight (rho = -0.30; p = 0.009), exercise duration (rho = -0.30; p = 0.008), and the percentage of target heart rate achieved (rho = -0.33; p = 0.004) was observed. The correlations between the remaining exercise capacity parameters and the scores obtained with the CFS-APQ all indicated a trend towards association (0.01

Hormonal responses during prolonged exercise are influenced by a selective DA/NA reuptake inhibitor.

OBJECTIVE: A decrease in dopamine activity is thought to lead to a reduction in motivation and arousal and therefore to the "central" component of fatigue. The purpose of the present study was to investigate the effects of a dopamine (DA) noradrenaline (NA) reuptake inhibitor, bupropion (Zyban), on exercise performance and on the hormonal response to exercise. METHODS: Eight healthy well trained male cyclists (Watt(max) 397+/-15 W) participated in the study. Subjects completed one maximal exercise test (to determine maximal power output Watt(max)), and two endurance performance tests (time trials) in a double blind randomised cross-over design. Subjects took either placebo capsules (lactose) or 2 x 300 mg bupropion (BUP). Blood samples were collected for adrenocorticotropin (ACTH), prolactin, cortisol, growth hormone, beta-endorphins, and catecholamines. RESULTS: Performance was not influenced by BUP (placebo: 89+/-1 min; BUP 2 x 300 mg: 89+/-0.7 min). All hormones increased during exercise in all trials. Cortisol plasma concentrations were significantly higher in the BUP trial at rest, at min 60, and at the end of exercise, while beta-endorphins were higher in the BUP trial at the end of exercise and during recovery, and ACTH at the end of exercise. CONCLUSION: From the present results, we can conclude that bupropion had a more marked central noradrenergic effect (compared to dopaminergic) on the hormonal response to exercise, but no effect on the outcome of performance.

Atypical depression as a secondary symptom in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) has gained prominence since 1988 and a substantial amount of research has been done in this domain. However, it is still regarded as a controversial condition. Moreover, most of the symptoms of CFS itself are non-specific, occurring in many illnesses; some of the symptoms are also common in depression. Indeed, an area of continued controversy and debate involves the diagnostic overlap between CFS and psychiatric disorders. Through anecdotal evidence, atypical depression appears to be common in CFS. Recent developments in psychobiology underscore the role of the acute phase response and its associated sickness behavior in affective disorders. Thus, we hypothesize that atypical depression is sickness behavior rather than an affective disorder as shown by anecdotal evidence in CFS.

Type I interferons induce proteins susceptible to act as thyroid receptor (TR) corepressors and to signal the TR for destruction by the proteasome: possible etiology for unexplained chronic fatigue.

In some patients complaining of chronic fatigue such as those suffering from the chronic fatigue syndrome (CFS), no underlying physical cause can be clearly identified and they typically present a normal thyroid function. Several studies indicate a dysregulation in the type I interferons (IFN-alpha/beta) pathway in CFS resulting in a sustained upregulation of 2('),5(')-oligoadenylate synthetases (2-5OAS). Likewise, patients treated with IFN-alpha/beta usually complain of severe fatigue as a limiting side effect. Beside the 2-5OAS, IFN-alpha/beta induce also the expression of three closely related proteins of unknown function termed the 2-5OAS-like (2-5OASL) proteins. The amino acid sequences of the 2-5OASL proteins display 96% identity with the partial sequence of the thyroid receptor interacting protein (TRIP) 14, further contain two typical thyroid hormone receptor (TR) coregulator domains and feature two ubiquitin C-terminal domains. From these observations, we raise the hypothesis that the 2-5OASL proteins are TRIPs capable of, respectively, repressing TR transactivation and/or signaling the receptor for destruction by the proteasome. Such molecular mechanisms could explain the development of a clinical hypothyroid state in presence of a normal thyroid function.

Brain microdialysis in exercise research.

During the last 5 to 10 years, the microdialysis technique has been used to explore neurotransmitter release during exercise. Microdialysis can collect virtually any substance from the brains of freely moving animals with a limited amount of tissue trauma. It allows the measurement of local neurotransmitter release in combination with ongoing behavioural changes such as exercise. Several groups examined the effect of treadmill running on extracellular neurotransmitter levels. Microdialysis probes were implanted in different brain areas to monitor diverse aspects of locomotion (striatum, hippocampus, nucleus accumbens, frontal cortex, spinal cord), food reward (hypothalamus, hippocampus, cerebral cortex), thermoregulation (hypothalamus). Some studies combined microdialysis with running on a treadmill to evaluate motor deficit and improvement following dopaminergic grafts in 6-hydroxydopamine lesioned rats, or combined proton nuclear magnetic resonance spectroscopy and cortical microdialysis to observe intra- plus extracellular brain glucose variations. This method allows us to understand neurotransmitter systems underlying normal physiological function and behaviour. Because of the growing interest in exercise and brain functioning, it should be possible to investigate increasingly subtle behavioural and physiological changes within the central nervous system. There is now compelling evidence that regular physical activity is associated with significant physiological, psychological and social benefits in the general population. In contrast with our knowledge about the peripheral adaptations to exercise, studies relating exercise to brain neurotransmitter levels are scarce. It is of interest to examine the effect of short and long term exercise on neurotransmitter release, since movement initiation and control of locomotion have been shown to be related to striatal neurotransmitter function, and one of the possible therapeutic modalities in movement, and mental disorders is exercise therapy. Until very recently most experimental studies on brain chemistry were conducted with postmortem tissue. However, in part because of shortcomings with postmortem methods, and in part because of the desire to be able to directly relate neurochemistry to behaviour, there has been considerable interest in the development of 'in vivo' neurochemical methods. Because total tissue levels may easily mask small but important neurochemical changes related to activity, it is important to sample directly in the extracellular compartment of nervous tissue in living animals. Since the chemical interplay between cells occurs in the extracellular fluid, there was a need to access this compartment in the intact brain of living and freely moving animals. Estimation of the transmitter content in this compartment is believed to be directly related to the concentration at the site where these compounds are functionally released: in the synaptic cleft. As measurements in the synapse are not yet possible, in vivo measurements in the extracellular fluid appear to provide the most directly relevant information currently available. This article provides an overview of the in vivo microdialysis technique as a method for measuring in the extracellular space, and its application in exercise science. Although this technique has been used in different tissues such as brain, adipose tissue, spinal cord and muscle, in animals as well as humans, we will focus on the use of this in vivo method in brain tissue. Recently two excellent reviews on the application of microdialysis in human experiments especially in subcutaneous tissue have been published, and we refer the interested reader to these articles.

A definition-based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome.

OBJECTIVE: The Holmes and Fukuda criteria are widely used criteria all over the world, yet a specific European study regarding chronic fatigue syndrome (CFS) patient symptomatology has not been conducted so far. This study was performed to answer the need to assess the homogeneity of a large CFS population in relationship to the Fukuda or Holmes definitions and to assess the importance of a symptom severity scale. DESIGN: Multivariate analyses were performed to assess the symptom presentation within a fatigued population and the differences between the Fukuda and Holmes definitions compared with an excluded chronic fatigued group in a large cohort of fatigued patients. SETTING: An outpatient tertiary care setting fatigue clinic in Brussels. MAIN OUTCOME MEASURES: Prevalence and severity of symptoms and signs in a CFS population and in a chronic fatigued population. SUBJECTS AND METHODS: A total of 2073 consecutive patients with major complaints of prolonged fatigue participated in this study. Multivariate analyses were performed to assess the symptom presentation and severity and the differences between the Fukuda and Holmes definitions. RESULTS: Of the 2073 patients complaining of chronic fatigue (CF), 1578 CFS patients fulfilled the Fukuda criteria (100% of CFS group) and 951 (60.3% of the CFS group) fulfilled the Holmes criteria. Discriminant function analysis revealed that the Fukuda and Holmes definitions can be differentiated by symptom severity and prevalence. The Holmes definition was more strongly associated than the Fukuda definition with the symptoms that differentiated the CFS patients from the patients that did not comply with the CFS definitions. The inclusion of 10 additional symptoms was found to improve the sensitivity/specificity and accuracy for selection of CFS patients. CONCLUSIONS: The CFS patients fulfilling the Holmes criteria have an increased symptom prevalence and severity of many symptoms. Patients fulfilling the Fukuda criteria were less severely affected patients which leads to an increase in clinical heterogeneity. Addition of certain symptoms and removal of others would strengthen the ability to select CFS patients.

Exercise performance is not influenced by a 5-HT reuptake inhibitor.

The purpose of the present study was to examine the effect of a selective serotonin (5-HT) reuptake inhibitor (SSRI) on exercise performance during a 90 min time trial. Eight well trained male cyclists (VO2max 68.1 +/- 9.5 ml/kg/min) performed three 90 min time trials at 65% Wattmax. Blood samples were collected via an indwelling venous catheter for adrenocorticotropin hormone (ACTH), prolactin (PRL), cortisol, catecholamines, growth hormone (GH) and beta-endorphins. The evening before and the morning of the time trials, the subjects ingested a capsule containing either placebo (lactose) or 20 mg Fluoxetine-HCI (Prozac, Ely Lilly Belgium). A double blind, randomized, placebo controlled, cross-over design was performed. Performance was not influenced by the SSRI. As expected, all blood parameters increased significantly during exercise (p < 0.05). During the SSRI trial most parameters were slightly lower but only significantly for endorphins and PRL (p < 0.05). The results demonstrate that performance is not influenced by an SSRI, although some plasma hormones indicate a central effect of the drug. Surprisingly, the increases in PRL and endorphins were lower during the SSRI trial, meaning that the hormonal modulation during exercise might be regulated by the interaction between neurotransmitters rather than by serotonin alone.

Effect of exercise on portal vein blood flow in man.

PURPOSE: Doppler pulsed flow and electronic scanning allow for instantaneous measurement of portal vein flow. This method was used to monitor alterations in splanchnic blood flow during exercise. METHODS: Measurements of portal vein blood flow were performed in eight healthy males at rest and at 10-min intervals during cycle ergometry at 70% of maximal aerobic capacity. Subjects stopped cycling briefly (approximately 30 s) and stopped breathing while measurements were made. Flow was calculated from values obtained for velocity of red blood cell passage and cross-sectional area of the vessel. RESULTS: Cross-sectional area decreased during exercise, resulting in a significant decrease in flow over time (P = 0.0001 by ANOVA). The flow within the portal vein had decreased by 80% after 60 min of exercise (absolute flow, 0.63 +/- 0.13 L x min(-1) at rest and 0.13 +/- 0.04 L x min(-1) at 60 min). CONCLUSION: Electronic Doppler flow measurement of portal vein flow is a viable, noninvasive technique that can be used to measure splanchnic blood flow. Values obtained as a result of intensive exercise are in line with earlier results obtained with other techniques.

Exercise capacity in chronic fatigue syndrome.

BACKGROUND: Patients with chronic fatigue syndrome (CFS) suffer from various symptoms, including debilitating fatigue, muscle pain, and muscle weakness. Patients with CFS can experience marked functional impairment. In this study, we evaluated the exercise capacity in a large cohort of female patients with CFS. METHODS: Patients with CFS and matched sedentary control subjects performed a maximal test with graded increase on a bicycle ergometer. Gas exchange ratio was continuously measured. In a second stage, we examined only those persons who achieved a maximal effort as defined by 2 end points: a respiratory quotient of at least 1.0 and an age-predicted target heart rate of at least 85%. Data were assessed using univariate and multivariate statistical methods. RESULTS: The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects. The maximal workload and maximal oxygen uptake attained by the patients with CFS were almost half those achieved by the control subjects. Analyzing only those persons who performed a maximal exercise test, similar findings were observed. CONCLUSIONS: When compared with healthy sedentary women, female patients with CFS show a significantly decreased exercise capacity. This could affect their physical abilities to a moderate or severe extent. Reaching the age-predicted target heart rate seemed to be a limiting factor of the patients with CFS in achieving maximal effort, which could be due to autonomic disturbances. Arch Intern Med. 2000;160:3270-3277.

Relationship between muscle T2* relaxation properties and metabolic state: a combined localized 31P-spectroscopy and 1H-imaging study.

A multi-volume 31P-magnetic resonance spectroscopy localization procedure was implemented to compare directly muscle metabolism and proton T2* relaxation properties in the human plantar flexor muscles during exercise. Localized 31P-spectra were collected simultaneously from the medial gastrocnemius, lateral gastrocnemius and soleus muscles during exercise using beta1-insensitive Hadamard Spectroscopic Imaging (HSI). 1H T2*-weighted gradient-echo images were acquired at rest and immediately following high-intensity plantar flexion exercise. T2* mapping of the individual calf muscles showed that plantar flexion with the knee extended produces significant increases (P < 0.0001) in the mean (SEM) T2* of the medial [35.6 (1.2) ms vs 28.5 (0.5) ms at rest] and lateral gastrocnemius [35.6 (0.9) ms vs 26.2 (0.9) ms at rest], but not in the soleus [26.7 (0.6) ms vs 27.3 (0.8) ms at rest]. In accordance with the changes in T2*, the ratio of inorganic phosphate to phosphocreatine (Pi:PCr) and the intracellular muscle pH shifted significantly in the gastrocnemii, while the soleus showed no change in muscle pH and only a moderate increase in Pi-to-Ph. Comparison of spectroscopic and relaxation parameters in both gastrocnemius muscles revealed a significant relationship between post-exercise T2* and intracellular pH (r = 0.72-0.76) and Pi-to-Ph ratios (r = 0.81-0.88) during exercise. Using an improved method of localization, this study confirms the existence of a strong relationship between transverse relaxation properties and the metabolic state in skeletal muscles engaged in heavy exercise.

A 37 kDa 2-5A binding protein as a potential biochemical marker for chronic fatigue syndrome.

PURPOSE: Recent studies have revealed abnormalities in the ribonuclease L pathway in peripheral blood mononuclear cells of patients with the chronic fatigue syndrome. We conducted a blinded study to detect possible differences in the distribution of 2-5A binding proteins in the cells of patients with chronic fatigue syndrome and controls. PATIENTS AND METHODS: We studied 57 patients with chronic fatigue syndrome and 53 control subjects (28 healthy subjects and 25 patients with depression or fibromyalgia). A radioactive probe was used to label 2-5A binding proteins in unfractionated peripheral blood mononuclear cell extracts and to compare their distribution in the three groups. RESULTS: A 37 kDa 2-5A binding polypeptide was found in 50 (88%) of the 57 patients with chronic fatigue syndrome compared with 15 (28%) of the 53 controls (P < 0.01). When present, the amount of 37 kDa protein was very low in the control groups. When expressed as the ratio of the 37 kDa protein to the 80 kDa protein, 41 (72%) of the 57 patients with chronic fatigue syndrome had a ratio > 0.05, compared with 3 (11%) of the 28 healthy subjects and none of the patients with fibromyalgia or depression. CONCLUSION: The presence of a 37 kDa 2-5A binding protein in extracts of peripheral blood mononuclear cells may distinguish patients with chronic fatigue syndrome from healthy subjects and those suffering from other diseases.

How significant are primary sleep disorders and sleepiness in the chronic fatigue syndrome?

In order to study both the prevalence of Primary Sleep Disorders (PSD) and sleepiness, and their association to the Chronic Fatigue Syndrome (CFS), 46 unselected outpatients (34 women, mean age 36.5) were examined clinically and underwent two nights of all-night polysomnography and multiple sleep latency tests (MSLT). Forty-six percent presented with a Sleep Apnea/Hypopnea Syndrome Index (AHI>=5), 5% with a Periodic Limb Movements syndrome. No subject received a diagnosis of Narcolepsy or Idiopathic Hypersomnia. Thirty percent showed the presence of objective sleepiness as measured by MSLT<10 minutes. Objective and subjective measures of sleepiness were not associated with CFS, nor with the double diagnosis of CFS and a PSD. The presence of PSD or sleepiness was not associated with any of the clinical scales that were used to measure anxiety, depression, somatisation, physical or mental fatigue, or functional status impairment. Fifty-four percent of CFS patients had no PSD, and 69% no sleepiness. These patients could not be distinguished clinically from patients having a PSD or from those with sleepiness. Therefore, it is unlikely that CFS is simply a somatic expression of any PSD observed in our sample or of sleepiness per se.

Dehydroepiandrosterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome.

Previous studies have demonstrated concentrating neuroendocrinological disturbances in chronic fatigue syndrome (CFS) patients, concentrating in particular on low cortisol levels and a hypothalamic deficiency. In order to investigate the dynamic response of the adrenal glands, we measured dehydroepiandrosterone (DHEA) in serum after adreno-corticotropic hormone (ACTH) stimulation during 60 minutes in 22 CFS-patients and 14 healthy controls. We found normal basal DHEA levels, but a blunted serum DHEA response curve to i.v. ACTH injection. This observation adds to the large amount of evidence of endocrinological abnormalities in CFS. Relative glucocorticoid deficiency might contribute to the overall clinical picture in CFS, and could explain some of the immunological disturbances observed in this syndrome.

Autonomic testing in patients with chronic fatigue syndrome.

The purpose of this study was to determine whether chronic fatigue syndrome (CFS) patients show autonomic dysfunction at the cardiac level and if so, to discover whether these abnormalities explain the fatiguability and/or other symptoms in CFS. The study population consisted of 21 CFS patients (Centers for Disease Control and Prevention [CDC] criteria, 1988) and 13 age- and sex-matched healthy controls. The autonomic testing consisted of: (1) postural challenge: registration of heart rate and blood pressure (BP) and heart rate variability in supine and in upright position (tilted to 70 degrees); (2) Valsalva maneuver; (3) handgrip test; (4) cold pressor test; and (5) heart rate response to deep breathing. Statistical analysis was performed using the Mann Whitney rank sum test; results of the test were considered significant at the 0.05 level. After tilting heart rate was significantly higher in CFS patients compared with healthy controls (mean CFS = 88.9 beats/min vs control = 77.9 beats/min; P <0.01). Low frequency power after tilting was significantly higher in CFS patients compared with controls (mean CFS = 0.603 vs control = 0.428; P = 0.02). There was a trend toward an increased heart rate during the cold pressor test. Other parameters did not differ between the CFS and control populations. The observed changes point toward a sympathetic overactivity in CFS patients when they are exposed to stress. Parasympathetic abnormalities could not be observed. Therefore, our findings provide no real explanation for the fatigue and intolerance to physical exertion in these patients.

Validity and reliability in a Flemish population of the WHO-MONICA Optional Study of Physical Activity Questionnaire.

PURPOSE: This study assessed the validity and reliability of a self-administered physical activity questionnaire used in the WHO-MONICA project. METHODS: Subjects (N = 167) were physical education and physical therapy alumni. The questionnaire (MOSPA-Q) covers a 1-yr period and measures the average weekly time and energy expenditure spent in one's occupation, transport-related activities, household chores, and leisure time activities. Test-retest reliability was reported as the intra-class correlation between calculated time or energy expenditure in different questionnaire items determined from two MOSPA-Q administrations. Validity was assessed using biometrical and physiological parameters as criterion measures. RESULTS: Test-retest reliability ranged from 0.45 to 0.92 with the highest correlation coefficients obtained for the leisure time physical activities. The correlation between calculated daily total energy expenditure (TEE, Kcal.d-1) and lean body mass was 0.53 (P < 0.001). The correlation between energy expenditure in leisure time activities (Kcal.wk-1) and VO2peak was 0.44. CONCLUSIONS: The MOSPA-Q provides a relatively valid and reliable estimate of physical activity.

Blood ammonia--heart rate relationship during graded exercise is not influenced by glycogen depletion.

The blood lactate (La) - heart rate (HR) relationship assessed during a graded maximal exercise test (GXT) is often used to provide training guidelines to athletes. Glycogen depletion is a condition that is known to influence the La response during a GXT and therefore can bias the interpretation of La curves. The purpose of our study was to determine an influence of glycogen depletion through long-term exercise (GDE) on blood La and ammonia (NH3) accumulation during a GXT. Eleven persons (5 males, 6 females; 26.3 +/- 4 yrs) performed a cycle ergometer GXT (3 min protocol) on two separate occasions with a 1-week interval. Using a randomized cross-over design, one of the two GXTs was preceded by a GDE. After GDE, blood NH3 increased more rapidly in the depleted versus control state whereas La increased less rapidly in the depleted state. The NH3 to HR relationship was not altered by glycogen depletion. We conclude, therefore, that determination of NH3 during a GXT may provide helpful additional information for training recommendations which is not available through La determination only.

The influence of cold and compression on lymph flow at the ankle.

OBJECTIVE: To investigate the effects of cold application with different temperatures on lymph flow in healthy persons and to examine the effects of the combination of cold and compression on lymph vessels. PARTICIPANTS: Thirty-nine healthy persons were included in the study, and each served as his or her own control. INTERVENTION: Water bags (1 degree, 15 degrees, and 32 degrees) with or without 25 mm Hg pressure were applied to the experimental legs for 30 minutes. Cold, pressure, or both were administered by an Aircast-Cryo-cuff (Aircast Europe GMBH, Rosenheim, Germany). MAIN OUTCOME MEASURES: Skin temperature was measured with a TESTO 901 (Testoterm GMBH, Leuven, Belgium) precision thermometer. Lymph flow was recorded continuously using lymphoscintigraphy. MANOVA with repeated measures was used for data analysis. RESULTS: As expected, skin temperature dropped relative to the temperature of the water. The migration of the tracer was comparable in both ankles during the first 30 minutes of the experiment (rest). When the water bag was applied, lymph flow increased significantly (p < 0.01). The application of water of 1 degree C without pressure influenced lymph evacuation significantly differently from the other temperatures. The application of pressure of 25 mm Hg influenced lymph evacuation significantly at 1 degree C and 32 degrees C. CONCLUSION: These results indicate that lymph evacuation at the ankle is influenced significantly when cold water is applied with or without pressure. When pressure is added to the application of water of 32 degrees C, lymph flow will also increase significantly, indicating the importance of pressure in lymph evacuation.