Exercise capacity and circulating endothelial progenitor cells in hemodialysis patients.

Mobilization of circulating endothelial progenitor cells (EPCs) is increased after acute exercise and training. This study aims to evaluate whether, in a low performance population, EPC levels may be related to exercise capacity in steady state conditions. Study population consisted of sixteen hemodialysis patients. The distance walked in the 6-minute walking test (6 MWD) and the maximal speed attained in an incremental treadmill test were used to assess the exercise capacity. Physical functioning was measured by the scale on the SF36 questionnaire. Quantification of peripheral blood CD34(+) cells and enumeration of EPCs, assessed as CD34(+) cells coexpressing AC 133 and vascular endothelial growth factor receptor-2, were performed. Hemoglobin concentration, white blood cells, high-sensitivity C-reactive protein, total cholesterol, and triglycerides were measured. Statistical analysis examined the relationship between blood progenitors cells versus performance parameters, laboratory parameters, age, body mass index, hemodialysis duration, and erythropoietin therapy. Univariate analysis revealed a significant association between percentage values of EPC and performance parameters only: 6 MWD (r=0.720; p=0.0017), maximal treadmill speed (r=0.721; p=0.0016), and physical functioning score (r=0.506; p=0.0453). A similar statistical association between EPC absolute values and performance parameters was found. No correlation between CD34 (+) and any parameter under study was observed. Multivariate analysis indicated 6 MWD as the most significant independent factor associated with EPC level. EPC percentage value was significantly lower (p=0.0087) in the worse (6 MWD < 300 m, n=8) than in the better performing group (6 MWD > 300 m, n=8). In a group of renal patients, mobilization of EPCs was related to the degree of exercise capacity, suggesting a possible connection with the cardiovascular risk in low performance populations limited by chronic diseases.

Speed rather than distance: a novel graded treadmill test to assess claudication.

OBJECTIVE: To evaluate a new treadmill test, determining pain threshold speed (PTS) for use in assessment and measuring rehabilitation of patients with intermittent claudication. METHODS AND DESIGN: Twenty-nine patients with claudication were evaluated, and the ankle-brachial index (ABI) was assessed. PTS was determined with a treadmill protocol based on level walking, low starting speed, and progressive increments at a predetermined distance up to the onset of pain. Repeatability and equivalence with a time-based protocol were verified. PTS was compared to pain-free walking distance, 6-minute walking distance, and ABI. RESULTS: PTS was measured in all patients (3.6+/-1.1 km/h). Repeatability and equivalence between established tests were demonstrated. PTS showed a significant correlation with pain-free walking distance (r=0.833; P=0.0001), with 6-minute walking distance (r=0.724; P=0.005), and with ABI in the more ischemic limb (r=0.641; P=0.0001). CONCLUSIONS: PTS is a reliable parameter that correlates well with other established measures. It is useful for determining the degree of functional handicap and for designing and guiding rehabilitation protocols.

Training guided by pain threshold speed. Effects of a home-based program on claudication.

AIM: To verify the effectiveness of a 120 day home-based program guided by the pain threshold speed (PTS). METHODS: Twenty-nine patients with stable claudication were measured for ankle pressure (AP), ankle-brachial index (ABI), PTS, maximal speed (Smax) on treadmill. Daily walking sessions at a speed 20-30% below PTS were prescribed. Determination of the training speed was supervised and facilitated at home. The program included a daily record of exercise data and symptoms, an intermediate PTS re-evaluation to adjust the training speed, and the reassessment of all the parameters after 120 days. RESULTS: Overall patients showed a reduction of systemic blood pressure (151.3+/-14.3 to 147.6+/-18.3 mmHg; 77.1 +/-9.1 to 72.4+/-8, p=0.008) while AP did not. ABI increased from 0.65+/-0.13 to 0.71+/- 0.18 (p=0.01). PTS and Smax rose from 3.2+/-1.1 to 4.2+/-1.5 km/h (p=0.0001) and from 3.9+/-1.3 to 4.6+/-1.3 km/h (p=0.0001), respectively. According to their compliance, patients were divided into 3 groups: 1) trained (T, n=14): exercise at the prescribed speed, 2) free-walkers (FW, n=7): walking speed markedly below PTS and 3) untrained (U, n=8): incomplete program compliance. T group showed symptom reduction up to pain disappearance. The ABI change (0.72+/-0.09 to 0.82+/- 0.16, p<0.02) was correlated to AP increase (r= 0.879). PTS and Smax rose from 3.6+/-1.1 to 5.4+/-0.8 km/h (p<0.02) and from 4.7+/-1.2 to 5.7+/-0.7 (p<0.02), respectively. FW showed improvement of all parameters, and U a better walking efficiency. CONCLUSIONS: In patients with claudication, a low-cost home-based program driven by PTS allows dramatic improvements of functional parameters.

Standard melatonin intake and circadian rhythms of elite athletes after a transmeridian flight.

Many transmeridian travellers, including top athletes, regularly take melatonin to reduce negative jet lag symptoms. Standard (rather than individually tailored) doses are often used. We examined the effects of a standard dose of melatonin on the body temperature rhythms of 12 elite biathletes (eight men and four women) after an eastward transmeridian flight to an international competition. The different effects on body temperature rhythms in men versus women underscore the need for personalized dosing schedules to avoid potential undesirable consequences.

The power output/heart rate relationship in cycling: test standardization and repeatability.

PURPOSE: The purpose of this study was to update and standardize the test for determining the power output/heart rate (PO/HR) relationship in cycling. METHODS: The current protocol was developed in the laboratory using a wind-load cycling simulator. Five hundred incremental tests were carried out by 290 male cyclists during a 2-yr period (1995-1997). The subjects' own bicycles, equipped with a standard crankset with a built-in power measuring system, were used for testing. The test protocol consisted of time-based increments in cadence that were uniform up to submaximal speeds and progressively greater in the final phase. RESULTS: The PO/HR relationship obtained was linear at low to submaximal PO and curvilinear from submaximal to maximal PO. A method was developed for the mathematical identification of the point of transition from the linear to the curvilinear phase (deflection point or heart rate break point). In 484 of the 500 tests performed, the deflection was independent of the final acceleration (PO at deflection 318.4 +/- 42.4 W, PO at final acceleration 351.6 +/- 43.2 W, P < 0.001), whereas in 16 tests the deflection and the start of the final acceleration coincided. To evaluate test repeatability and precision, 15 subjects repeated the test twice within a few days. No significant differences were found for the heart rate at deflection, power output at deflection, or slope of the linear part of the PO/HR relationship obtained in the two tests. CONCLUSION: It is concluded that the deflection point obtained by determining the PO/HR relationship on a wind-load simulator is not an artifact dependent on the incremental test protocol but rather a repeatable physiological phenomenon.

Circadian rhythms, athletic performance, and jet lag.

Rapid air travel across several time zones exposes the traveller to a shift in his/her internal biological clock. The result is a transient desynchronisation of the circadian rhythm, called jet lag, lasting until the rhythm is rephased to the new environmental conditions. The most commonly experienced symptoms are sleep disorders, difficulties with concentrating, irritability, depression, fatigue, disorientation, loss of appetite, and gastrointestinal disturbance. Apart from the decrements in mental and physical performance directly consequent on such symptoms, competitive athletes are also exposed to the additional negative consequences of a shift from the optimal circadian window of performance. A brief summary of the possible negative effects of jet lag on athletic performance and potentially alleviating strategies is given.

The Conconi test: methodology after 12 years of application.

The protocol for the determination of the speed/heart rate relationship during incremental exercise previously described (so-called Conconi test) has been refined and in part modified during 12 years of application. The new protocol calls for time-based increments in exercise intensity that are uniform up to submaximal speeds and progressively greater in the final phase. As in the original article (18), the speed/heart rate relationship is linear at low to moderate speed and curvilinear from submaximal to maximal speeds. A method is presented for the mathematical definition of this relationship, with the calculation of the straight-line equation of the linear phase and the identification of the point of transition from the linear to the curvilinear phase (deflection point or heart rate break-point). Analysis of 300 tests selected at random from those in our data base (more than 5,000 tests) has enabled us to show that the speed at which the deflection point occurs is significantly lower (p < 0.001) than that at which the acceleration of the final phase begins. This fact demonstrates that the break-point is not brought on by the final acceleration called for in the test protocol. Analysis of the speed/heart rate relationship allows for the determination of the following additional functional indices: 1) maximal heart rate (in 21 athletes the maximal heart rate attained in the test and that attained while racing were equal); 2) range of heart beats defining the linear part of the speed/heart rate relationship; 3) range of heart beats from the deflection point to maximal heart rate; and 4) maximal aerobic exercise intensity, obtained through extrapolation of the straight-line equation to maximal heart rate. Data are provided on the conditions of the test subject that modify his speed/heart rate relationship, such as incomplete recovery from previous efforts, inadequate warm-up, or inadequate test procedure with too rapid increments in exercise intensity. Finally, criteria for test acceptability are presented.

Reproducibility of the Conconi test: test repeatability and observer variations.

The repeatability of the the speed/heart rate (S/HR) relationship obtained with the incremental test developed by Conconi et al. (5) was examined by having 75 subjects perform the same running test twice in the course of a few days. From the data obtained, comparisons were made of four variables: 1) speed of deflection, 2) heart rate of deflection, 3) slope, and 4) intercept on the y-axis of the linear portion of the S/HR relationship. Straight-line equations, correlation coefficients (r), and technical errors of measurement (TEM) were obtained by comparing data from the two successive tests. Data analysis suggests that in two successive tests there are some variations in the linear portion of the S/HR relationship. However, the straight lines obtained from the two tests converge at the same deflection point. The problem of assigning a single value to the point of deflection, when determined by means of visual analysis of the S/HR graph, was also examined. For this part of the study, speed and heart rate data previously obtained for 65 subjects were used. The selected tests had been carried out during the course of various studies. The 65 sets of test data were plotted on graph paper and given to six observers for independent evaluation of speed and heart rate of deflection. These observers had different levels of experience in interpreting Conconi test results. The speed and heart rate of deflection values assigned by each observer were compared to the values obtained through mathematical analysis of the tests by computer. Straight-line equations, correlation coefficients (r), and technical errors of measurement (TEM) obtained by comparing visually determined data to those determined through mathematical analysis were calculated for each observer. Only for observers with little experience were some differences found between the observer-assigned and computer-determined results; these differences occurred for both speed and heart rate of deflection. We conclude that visual analysis provides information that is very similar to that obtained through computer analysis. The accuracy of the visually obtained information varies according to the observer's experience.

[Consensus conference. Saving blood: which are still the doubts and the problems?]. / Consensus conference. Risparmiare sangue: quali ancora i dubbi e i problemi?

The consensus conference on blood saving has allowed us to formulate some interesting guidelines. The autologous and homologous transfusion require the patient's consent. For volemic replacement crystalloid solutions are used for phlebotomies below 10-15%, and colloid solutions for those greater than 10-15% of the blood mass. Severe isovolemic hemodilution (Ht < 20%) necessitates the reduction of the dosage of some drugs. A limit of Hb around 9 g/dl after phlebotomy may be acceptable in the absence of cerebral and coronary vascular disease. Phlebotomies are therefore possible also when the Hb values are 10 g/dl (Ht 30%). Hb values around 7 g/dl in the late postoperative period (from day 3 to 6) may be accepted only if well tolerated. The blood salvaged during surgery and at the beginning of the postoperative phase must always be centrifugated, washed and microfiltered. Subsequently, in the first 8 hours it is possible to reinfuse red cells after sedimentation and microfiltration. The techniques of predeposit, hemodilution and recovery are valid especially if associated with careful control of postoperative bleeding by means of aspiration under controlled pressure (at minimum negative values and sometimes positive ones), monitoring of blood loss from drainage and application of elastic compression bandages.

Characterization of polymorphic markers in the von Willebrand factor gene and pseudogene.

Three TaqI restriction fragment length polymorphisms (RFLP) detected by the central portion of von Willebrand factor cDNA, which recognizes the true gene and in addition pseudogenic sequences, were characterized and mapped. Small cDNA fragments which hybridized with DNA from families with von Willebrand disease were used. Two of the RFLP, recognized by 1.7 and 0.45 kb cDNA fragments, are not in linkage either with von Willebrand disease or with RFLP located in the von Willebrand factor (vWF) gene, which indicates their pseudogenic location. These markers located in 22q11, near to the bcr gene, provide new tools for the study of several somatic and constitutional alterations affecting this chromosomal region. The third RFLP is recognized by a cDNA fragment corresponding to the N-terminal portion of mature vWF and is localized in the true gene. Since significant linkage disequilibrium with other informative RFLP is not present, this marker contributes to the definition of family haplotypes associated with von Willebrand disease.

A de novo and heterozygous gene deletion causing a variant of von Willebrand disease.

An abnormal von Willebrand factor (vWF) gene restriction pattern has been found in a patient with von Willebrand disease. Because this gene alteration is not present in his parents or in 50 normal and 25 affected subjects, and the restriction fragment length polymorphism haplotypes are inherited normally in the patient's family, we suggest that a de novo mutation is present. Bands with reduced intensity and additional fragments, observed in several restriction digests, hybridize with noncontiguous copy DNA (cDNA) portions, thus indicating the presence of a heterozygous gene deletion. The deletion removes a genomic region containing at least codons 1147 through 1854 and corresponding to the D3-A3 homologous protein domains. The extent of the vWF pseudogene on chromosome 22 is roughly similar to that of the deleted area. However, the pseudogenic nature of the deletion is excluded by the mapping of bands with reduced intensity in the patient to the true vWF gene. The vWF antigen levels are one fourth of normal and ristocetin cofactor activity is severely impaired. The reduction of high molecular weight multimers in plasma and platelets and the altered triplet morphology are compatible with the presence of a dominant variant of type II von Willebrand disease.

Adaptation of the "Conconi test" to children and adolescents.

A field test for the determination of anaerobic threshold (AT) based on the relationship between work intensity and heart rate was previously developed in adult runners (4) and then applied in various sports activities (3, 5, 9). In the current study the same relationship between running speed (S) and heart rate (HR) was determined in 274 healthy children and adolescents (169 males and 105 females). All tests were performed either outdoors on a 400-m track (n = 159, 110 males and 49 females) or indoors in a gymnasium (n = 115, 59 males and 56 females). The subjects increased their work intensity progressively from low to submaximal speeds. HR was determined by a heart rate monitor (Sport Tester TM PE 3000, Polar Electro, Kempele, Finland). In every subject examined, the linearity of the S-HR relationship was lost at a speed, called deflection speed (Sd), above which the increase in S exceeded the increase in HR. HR at Sd was defined as HRd. The respective test-retest correlation coefficients for Sd, HRd, and slope of the linear part of the graph were 0.990, 0.824, and 0.953 when determined outdoors and 0.996, 0.840, and 0.932 when determined indoors. The outdoor-indoor correlation coefficients were 0.934, 0.855, and 0.282, respectively, for Sd, HRd, and slope. The results suggest that application of this test to children and adolescents in running may prove useful in cross-sectional and longitudinal studies of the development of aerobic power during growth.

A field test for determining the speed obtained through anaerobic glycolysis in runners.

A field test for the evaluation of the speed generated by the anaerobic lactacid mechanism has been developed in runners. The test consists of 1200 m of continuous running: in the first 1000 m the speed corresponding to the anaerobic threshold is progressively reached; in the last 200 m an all-out sprint is performed. The speed at the anaerobic threshold is subtracted from the speed reached in the final 200-m all-out sprint. In 39 runners examined (marathon runners, n = 13; 5000-10000-m runners, n = 10; 400-800-m runners, n = 7; sprinters, n = 9), the additional speed generated above the anaerobic threshold was correlated with the venous blood lactate concentration reached 5 min after the all-out effort (r = 0.93). The anaerobic speeds measured by the test were in keeping with the characteristics of the runners under study, i.e., anaerobic speeds were highest for the sprinters, intermediate for the middle-distance runners, and lowest for the marathon runners. Since the speed generated above the anaerobic threshold by the aerobic fuel breakdown can be subtracted, the contribution of creatine phosphate is minimal, and the speed exceeding the anaerobic threshold is highly correlated with lactate accumulation, the present test should measure the speed generated by anaerobic glycolysis.

Reduction of Hb levels during the racing season in nonsideropenic professional cyclists.

Hematological variables of 40 professional cyclists, all receiving intravenous iron supplementation, were followed during a 15-month period. Mean values for red blood cells (RBC), hemoglobin (Hb), and hematocrit (Ht) were significantly lower during the racing season (RS) than during the nonracing periods (NRP) (RBC: RS = 4.53 +/- 0.34 millions/mm3, NRP = 5.09 +/- 0.36 millions/mm3; line 7 of abstract: Hb: RS = 14.2 +/- 0.9 g/dl, MRS = 15.2 +/- 0.9 g/dl; Ht: RS = 40.7 +/- 2.7% NRP = 44.4 +/- 2.9%; P less than 0.001 for all). However, mean values for ferritin and mean corpuscular hemoglobin (MCH) were significantly higher during the racing season (ferritin: RS = 422 +/- 398 ng/ml, NRP = 311 +/- 321 ng/ml, P less than 0.05; MCH: RS = 31.5 +/- 1.3 pg, NRP = 30.0 +/- 1.4 pg; P less than 0.001). These results suggest that the reductions in RBC, Hb, and Ht found in professional cyclists during the racing season are not the consequence of a diminution of iron stores but rather of reduced erythropoiesis and increased RBC destruction.

An approach to noninvasive fiber type determination by NMR.

In vivo 31P NMR spectroscopy was used to determine the ratios of creatine phosphate (PCr) to adenosine triphosphate (ATP) and inorganic phosphate (Pi) in leg and arm muscles of four sprinters, one marathon runner, and two sedentary subjects. Both ratios were definitely higher in the sprinters indicating that, since muscle ATP and Pi concentrations are constant, the PCr muscle content of these athletes is higher than usual. Sprinters are known to have higher percentages of fast-twitch fibers, which are richer in PCr than slow-twitch fibers. It is concluded that measurements of muscle ATP, PCr, and Pi through in vivo NMR spectroscopy could be used to determine muscle fiber composition.

A frequent factor XII gene mutation in Hageman trait.

An additional TaqI restriction site was mapped in intron 2 of the factor XII gene. The site was found only in subjects with total or partial factor XII deficiency and thus represents the true gene lesion or a very tightly linked restriction fragment length polymorphism. The altered gene identified by this marker is present in four (three heterozygotes and one homozygote) of five unrelated Hageman trait subjects from different Italian regions. In the homozygous state the altered gene gives rise to a very marked reduction of factor XII activity. No deletion was found in the deficient factor XII genes.

Serum erythropoietin in cross-country skiers.

Serum erythropoietin (Epo) activity, hemoglobin (Hb), and hematocrit (Ht) were determined in 21 cross-country skiers during the training season. The Epo levels were not significantly reduced in the skiers relative to the normal population (P less than 0.01 and P less than 0.001, respectively). In 11 athletes Epo, Ht, urinary gamma-glutamyltransferase, N-acetyl-beta-glucosaminidase, and microalbuminuria were determined before and after a 50-km ski race at 1600 m above sea level. A significant increase of these variables (except for Ht) was found after the competition (P less than 0.001). It is concluded that while the reductions in Hb and Ht, which are typical of several endurance exercises, are not accompanied by a renal hypoxia sufficient to stimulate Epo overproduction, the renal hypoxia reached during the strenuous exercise of the race at altitude may be effective in determining blood increases in Epo.