Monitoring 6 weeks of progressive endurance training with plasma glutamine.

The distinction between positive and negative training adaptation is an important prerequisite in the identification of any marker for monitoring training in athletes. To investigate the glutamine responses to progressive endurance training, twenty healthy males were randomly assigned to a training group or a non-exercising control group. The training group performed a progressive (3 to 6 x 90 minute sessions per week at 70 % V.O (2max)) six-week endurance training programme on a cycle ergometer, while the control group did not participate in any exercise during this period. Performance assessments (V.O (2max) and time to exhaustion) and resting blood samples (for haemoglobin concentration, haematocrit, cortisol, ferritin, creatine kinase, glutamine, uric acid and urea analysis) were obtained prior to the commencement of training (Pre) and at the end of week 2, week 4 and week 6. The training group showed significant improvements in time to exhaustion (p < 0.01), and V.O (2max) (p < 0.05) at all time points (except week 2 for V.O (2max)), while the control group performance measures did not change. In the training group, haemoglobin concentration and haematocrit were significantly lower (p < 0.01) than pretraining values at week 2 and 4, as percentage changes in plasma volume indicated a significant (p < 0.01) haemodilution (+ 6 - 9 %) was present at week 2, 4 and 6. No changes were seen in the control group. In the training group, plasma glutamine (week 2, 4 and 6), creatine kinase (week 2 and 4), uric acid (week 2 and 4) and urea (week 2 and 4) all increased significantly from pretraining levels. No changes in cortisol or ferritin were found in the training group and no changes in any blood variables were present in the control group. Plasma glutamine was the only blood variable to remain significantly above pretraining (966 +/- 32 micromol . 1 (-1)) levels at week 6 (1176 +/- 24 micromol . 1 (-1); p < 0.05) The elevation seen here in glutamine levels, after 6 weeks of progressive endurance training, is in contrast to previous reports of decreased glutamine concentrations in overtrained athletes. In conclusion, 6 weeks of progressive endurance training steadily increased plasma glutamine levels, which may prove useful in the monitoring of training responses.

Quantification of terbutaline in urine by enzyme-linked immunosorbent assay and capillary electrophoresis after oral and inhaled administrations.

The International Olympic Committee and World AntiDoping Agency restricts the use of beta2-agonists and only the inhaled administration of terbutaline, salbutamol, formoterol and salmeterol is permitted for therapeutic reasons. The aim of this study was to develop a test for the quantitation of terbutaline in urine and evaluate different parameters to distinguish between oral and inhaled administration of the drug. Urine samples were collected from asthmatic and non-asthmatic recreational swimmers who had received repeated doses of oral (3x2.5 mg plus 1x5 mg during 24 h) and inhaled (12x0.5 mg in 24 h with half of it being in the last 4 h) racemic terbutaline, and single oral (5 mg) or single inhaled doses (1 mg). Total terbutaline concentrations (free+conjugated) were determined by enzyme-linked immunosorbent assay. Results showed that after oral administrations urinary terbutaline concentrations were higher than those detected after inhalation. For confirmation purposes, a chiral capillary electrophoretic procedure was established and validated. A solid-phase extraction with Bond-Elut Certify cartridges was undertaken, separation performed using a 50 mM phosphate buffer (pH 2.5) containing 10 mM of (2-hydroxypropyl)-beta-cyclodextrin as running buffer and diode-array UV detection set at 204 nm. The proposed procedure is rapid, selective and sensitive allowing quantitation of free terbutaline enantiomers in urine. No statistical differences were found between total free terbutaline concentrations [S-(+)+R-(-)] in urine collected after oral and inhaled administrations of the drug. After oral doses enantiomeric [S-(+)]/[R-(-)] ratios lower than those obtained after inhalation were observed probably due to an enantioselective metabolism that take place in the intestine, but differences between both routes of administration were not statistically significant. Although different trends were observed after oral and inhaled doses in total terbutaline, total free terbutaline concentrations and in ratios between its enantiomers, differences observed were not sufficiently significant to establish cut-off values to clearly distinguish between both routes of administration.

Long-term effects of exercise on blood pressure and lipids in healthy women aged 40-65 years: The Sedentary Women Exercise Adherence Trial (SWEAT).

OBJECTIVES: To evaluate the long-term effects of regular moderate or vigorous intensity exercise on blood pressure and blood lipids in previously sedentary older women. DESIGN: Subjects were randomly assigned to either a supervised centre-based (CB) or a minimally supervised home-based (HB) exercise program, initially for 6 months. Within each program, subjects were further randomized to exercise either at moderate (40-55% heart rate reserve, HRres) or vigorous intensity (65-80% HRres). After 6 months, all groups continued a HB moderate or vigorous exercise program for another 12 months. METHODS: Healthy, sedentary women (aged 40-65 years) (n = 126) were recruited from the community. Subjects exercised three times per week for 30 min. They were evaluated at baseline, 6, 12 and 18 months. RESULTS: There was a significant fall of 2.81 mmHg in systolic blood pressure (P = 0.049) and 2.70 mmHg in diastolic blood pressure (P = 0.004) after correction for age and baseline values with moderate exercise, but not with vigorous-intensity exercise. When this analysis was repeated with the change in body mass included, the results were unchanged. After correction for potential confounding factors, there was a significant fall in total cholesterol and low density lipoprotein cholesterol with vigorous but not moderate exercise at 6 months (P < 0.05) but not at 18 months. CONCLUSIONS: In this largely normotensive population of older women, a moderate, but not vigorous exercise program, achieved sustained falls in resting systolic and diastolic blood pressure over 18 months. The study demonstrates that, in older women, moderate intensity exercise is well accepted, sustainable long-term and has the health benefit of reduced blood pressure.

Inflammation, peritoneal transport, and response to erythropoietin in peritoneal dialysis patients.

The aim of the present study was to examine the association between 4-hour dialysate-to-plasma ratio of creatinine (D/PCr), erythropoietin (EPO) responsiveness [EPO (U/week)/hemoglobin (g/L)], and C-reactive protein (CRP). Subjects were 54 prevalent peritoneal dialysis (PD) patients [mean age: 58 years; 30 women, 24 men; 28 with diabetes; 15 on continuous ambulatory peritoneal dialysis (CAPD); 39 on continuous cycling peritoneal dialysis (CCPD); mean Kt/V: 2.44]. In 17 patients, CRP was elevated (> 15 mg/L), and in 39 patients, 4-hour D/PCr was high or high-average (> or = 0.65). Mean hemoglobin (Hb) was 115.5 +/- 12.9 g/L; median EPO dose was 2800 U/week, and median EPO/Hb was 24.5. A nonsignificant negative correlation was noted between CRP and hemoglobin (r = -0.25, p = 0.07), but no correlations were seen between CRP and 4-hour D/PCr, or hemoglobin and 4-hour D/PCr. No correlation was seen between EPO/Hb and 4-hour D/PCr or CRP. Multiple linear regression (stepwise, alpha = 0.05) was performed with outcome hemoglobin and independent variables EPO [U/week (forced in)], percent transferrin saturation [TSAT (forced in)], age, sex, diabetes mellitus, serum albumin, CRP, time on PD, 4-hour D/PCr, normalized protein catabolic rate (nPCR), ferritin, intact parathyroid hormone (iPTH), aluminum, and angiotensin converting enzyme inhibitor (ACEI) use. Serum albumin (1.27, p < 0.01) and diabetes mellitus (-6.69, p = 0.04) were the only significant predictors of hemoglobin. With serum albumin removed from the model, age (but not CRP) became significant. These results do not support an association between peritoneal transport and EPO responsiveness, mediated by inflammation. The association between serum albumin and hemoglobin appears to be confounded by age more than by inflammation.

The relationship between dialysate protein loss and membrane transport status in peritoneal dialysis patients.

Peritoneal dialysis (PD) patients lose significant quantities of protein and albumin during the dialysis procedure. The losses are greater in high transporters. The aim of the present study was to investigate the relationship between peritoneal membrane transport characteristics and protein losses. We studied 33 PD patients [14 men, 19 women; mean age: 53.5 years (range: 21-80 years)]. Fourteen patients had diabetes, and 22 were on automated PD. Dialysis adequacy was good, with a mean Kt/V of 2.63 (range: 1.51-4.89). Patients underwent a standard peritoneal equilibration test (PET). In addition, dialysate albumin (Alb) and protein (Pro) were measured at 0, 1, 2, and 4 hours, after lack of interference from unspent dialysate was ensured. Of the 33 patients, 23 were high or high-average transporters [based on 4-hour dialysate-to-plasma ratio of creatinine (D/PCr > or = 0.65)]. Protein losses owing to PD ranged from 3.5 g/day to 13.2 g/day (median: 5.9 g/day), of which 1.9-7.14 g/day (median: 3.21 g/day) was albumin. The 4-hour D/PCr correlated with the 4-hour D/PAlb (r = 0.62, p < 0.01), and 4-hour D/PPro (r = 0.63, p < 0.01). This finding persisted after correction for volume, indicating that it was not simply a concentration effect. The 4-hour D/PAlb and 4-hour D/PPro also correlated with the 24-hour PD albumin and protein losses. These results suggest a strong association between D/PCr and D/P for proteins. This observation is consistent with the increased protein losses through PD in high transporters and may be related to the inferior outcomes in this group.

Laboratory protocol for exercise asthma to evaluate salbutamol given by two devices.

PURPOSE: As new delivery devices and formulations are being introduced for drugs given by inhalation, there is a need to evaluate their equivalence with old preparations. One way to do this is to investigate their equivalence in protecting from exercise-induced asthma (EIA). METHODS: We used a protocol for EIA to compare the protective effect of salbutamol delivered by the pressurised metered dose inhaler (pMDI) and the new Diskus dry powder device. Twenty-seven asthmatic subjects with moderately severe EIA completed an exercise test on four separate days at two study centers. Exercise was performed by cycling for 8 min while inhaling dry air (0% RH, 20-24 degrees C). The target workload in W was predicted as (53.76 x predicted FEV1) - 11.07 and 95% of this target was achieved at 4 min of exercise. This target was chosen in order to achieve ventilation between 50 and 60% of predicted maximum in the last 4 min. RESULTS: There was no significant difference in the workload, ventilation, or heart rate achieved on the study days. The severity of EIA was measured as the % fall in FEV1. EIA severity was similar on the placebo and control day and the coefficient of variation was 19.4%. The mean +/- SD % fall on the control, placebo, salbutamol by Diskus, and pMDI were 42.0% +/- 15, 39.4% +/-17.6, 13.4% +/- 13.2, and 8.5% +/- 13.8, respectively. Salbutamol significantly inhibited the % fall in FEV1 after exercise, and there was no difference between the preparations. CONCLUSION: The protocol described here is suitable for evaluating equivalence of salbutamol preparations in protecting against EIA and could be used to evaluate the protective effect of other medications.

Apolipoprotein(a) phenotype, albumin clearance, and plasma levels of lipoprotein(a) in peritoneal dialysis.

This cross-sectional study was undertaken to examine the relationship between plasma lipoprotein(a) [Lp(a)] level and peritoneal dialysis (PD) albumin clearance while controlling for the influence of the apolipoprotein(a) [apo(a)] phenotype. Plasma Lp(a) level, PD albumin clearance, and apo(a) phenotype (high vs. low molecular weight, HMW vs. LMW) were determined in 54 PD patients. Apo(a) phenotypes were 24 LMW and 30 HMW. The plasma Lp(a) level was high (> 65 nmol/l) in 17 of 24 patients with LMW phenotype versus 2 of 30 with HMW phenotype (chi2, p < 0.01). Spearman correlation coefficients of Lp(a) with PD, urine, and total albumin clearances were -0.05 (p = 0.74), -0.04 (p = 0.80), and -0.09 (p = 0.51), respectively. The apo(a) isoform size was the only significant predictor of Lp(a) in multivariate analysis. In this study, there was no association between PD albumin clearance and Lp(a) level. The association between apo(a) phenotype and Lp(a) level is in keeping with studies in the general population. There is a strong genetic influence on Lp(a) level in PD patients.

Randomised trial of personalised computer based information for patients with schizophrenia.

OBJECTIVES: To compare use, effect, and cost of personalised computer education with community psychiatric nurse education for patients with schizophrenia. DESIGN: Randomised trial of three interventions. Modelling of costs of alternatives. PARTICIPANTS: 112 patients with schizophrenia in contact with community services; 67 completed the intervention. INTERVENTIONS: Three interventions of five educational sessions: (a) computer intervention combining information from patient's medical record with general information about schizophrenia; (b) sessions with a community psychiatric nurse; (c) "combination" (first and last sessions with nurse and remainder with computer). MAIN OUTCOME MEASURES: Patients' attendance, opinions, change in knowledge, and psychological state; costs of interventions and patients' use of NHS community services; modelling of costs for these three, and alternative, interventions. RESULTS: Rates of completion of intervention did not differ significantly (71% for combination intervention, 61% for computer only, 46% for nurse only). Computer sessions were shorter than sessions with nurse (14 minutes v 60 minutes). More patients given nurse based education thought the information relevant. Of 20 patients in combination group, 13 preferred the sessions with the nurse and seven preferred the computer. There were no significant differences between groups in psychological outcomes. Because of the need to transport patients to the computer for their sessions, there was no difference between interventions in costs, but computer sessions combined with other patient contacts would be substantially cheaper. CONCLUSIONS: The computer based patient education offered no advantage over sessions with a community psychiatric nurse. Investigation of computer use combined with other health service contacts would be worth while.

Discrimination of prohibited oral use of salbutamol from authorized inhaled asthma treatment.

BACKGROUND: The administration of salbutamol is permitted only by inhalation by the International Olympic Committee (IOC) for the management of asthma and exercise-induced asthma in athletes. The establishment of criteria to distinguish between the (IOC) authorized use (inhaled) and the (IOC) prohibited use (oral) of salbutamol appeared possible using simultaneous evaluation of variables based on the concentration of nonconjugated enantiomers of salbutamol excreted in urine. METHODS: Urine was collected from asthmatic and nonasthmatic swimmers who had received various preexercise doses of oral (five doses of 4 mg) or inhaled (two doses of 100 microgram) salbutamol. Urine was also obtained from subjects who had received the maximum dosage of inhaled salbutamol advisable for competing athletes to provide protection from exercise-induced asthma and treatment of asthma (1600 microgram in 24 h, 800 microgram being in the last 4 h). All samples were analyzed to determine the total amount of unchanged salbutamol excreted in urine and the ratio between the S: and R: enantiomers. RESULTS: The discriminant function D = -3.776 + 1.46 x 10(-3) ([S:(+)] + [R:(-)]) + 1.012 ([S:(+)]/[R(-)]) can be used to classify data into two groups, inhaled and oral. The confirmatory criterion suggested (cutoff at D = 1.06, 4 SD from the mean D value of the inhaled distribution) has been verified in different sets of samples showing suspicious concentrations by conventional screening procedures in doping control. An 11.8% false-negative (oral classified as inhaled) rate is assumed with the confirmatory criterion proposed, but virtually no false positives (inhaled classified as oral) are obtained (<1 in 33 000). CONCLUSIONS: The overall procedure recommended is to screen all samples and to apply the confirmation criterion proposed to samples showing free racemic salbutamol concentrations >500 microgram/L by gas chromatography-mass spectrometry or free + conjugated racemic salbutamol concentrations >1400 microgram/L by ELISA.

Distinction of inhaled and oral salbutamol by urine analysis using conventional screening procedures for doping control.

Salbutamol administration in athletes is permitted only by inhalation, for the management of asthma. The authors discuss different criteria for suspecting oral use of salbutamol, taking into account the data obtained by application of two conventional screening procedures for doping control: gas chromatography/mass spectrometry (GC/MS) and enzyme-linked immunosorbent assay (ELISA). Urine samples obtained after administration of oral and inhaled salbutamol to asthmatic and nonasthmatic swimmers were analyzed using both analytical approaches. As expected, concentrations obtained by the ELISA test (detection of total salbutamol) were higher than those obtained using the GC/MS procedure (detection of nonsulfated salbutamol). After oral administration, the ELISA test detected significantly higher salbutamol concentrations than those detected after inhalation, reflecting the greater doses administered orally. Urine samples with total salbutamol greater than 1400 ng/mL were obtained after oral doses, but no sample reached this value after inhaled doses. Higher concentrations of nonsulfated salbutamol have also been detected after oral intake, although there is an overlap between the distributions of concentrations after oral and inhaled doses. A cut-off concentration of 500 ng/mL can be used for nonsulfated salbutamol to select suspicious samples, giving 11.8% false negative results and 4.3% false positive results. An additional criterion evaluated was the androsterone-salbutamol peak height ratio, which was lower after oral doses because of the higher concentrations of salbutamol in urine. This ratio was lower than 2 for all the samples collected after oral administration, although 6.8% false positive samples resulted because of low concentrations of androsterone in female urine. Several possibilities for detecting suspicious samples from athletes who have taken prohibited oral salbutamol are available with conventional screening procedures in doping control.

Mouse to elephant: biological scaling and Kt/V.

The construct Kt/V is used by the nephrology community in prescribing dialysis dose. The concerns that have been raised as to what value of V to use in the calculation of Kt/V touch on the more central question of whether filtration rate should be normalized by a parameter other than V. Within the animal kingdom, a number of physiological variables scale to body size according to an equation of the form Y = YoMb, where Yo is a constant, M is body mass, and b is a scaling exponent. Glomerular filtration rate (GFR) in mammals weighing from 30 g to 503 kg scales to body weight with an exponent of 0.77. Hence, GFR per unit body weight (or Kt/V) decreases significantly with increasing body size. Metabolic rate also scales to body size in a wide range of mammals according to the same general equation and with a scaling exponent of 0.75. Because GFR and metabolic rate scale to body mass with virtually the same exponent, a ratio of the two yields a constant independent of body size. We propose that the ratio (filtration rate/metabolic rate) replace Kt/V. Such a ratio would underscore the linkage between filtration rate (and dialysis therapy) and the metabolic demands of the body.

Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in peritoneal dialysis patients.

OBJECTIVE: The aim of the present study was to examine the association between infection with Chlamydia pneumoniae and symptomatic atherosclerosis in peritoneal dialysis (PD) patients. DESIGN: Cross-sectional study. SETTING: Peritoneal Dialysis Unit of Kingston General Hospital. PATIENTS: Fifty-five prevalent PD patients. OUTCOME MEASURES: (1) Infection with C. pneumoniae diagnosed by detection of DNA in peripheral blood mononuclear cells (PBMCs) using polymerase chain reaction. (2) Symptomatic atherosclerosis involving the coronary, cerebral, or peripheral circulation. RESULTS: The DNA of C. pneumoniae was detected in PBMCs in 33 patients (60.0%). Atherosclerosis was present in 16 of 33 (48%) PBMC C. pneumoniae DNA-positive patients, and in 10 of 22 (45%) PBMC C. pneumoniae DNA-negative patients (p = 0.83). Using multiple logistic regression and controlling for a number of known cardiovascular risk factors, PBMC C. pneumoniae DNA status was not predictive of atherosclerosis. The only significant independent predictors of atherosclerosis were diabetes and age. CONCLUSIONS: In prevalent PD patients, a high prevalence of symptomatic atherosclerosis and of Chlamydia pneumoniae DNA in PBMCs were seen; however, the results of the present study do not support the presence of an association between infection with C. pneumoniae and atherosclerosis.

A randomised, controlled study of the effects of aerobic exercise and dietary fish on coagulation and fibrinolytic factors in type 2 diabetics.

Type 2 diabetes is associated with disturbances in coagulation and fibrinolysis. Prospective studies show that increased tissue plasminogen activator (tPA) antigen increases the risk of cardiovascular mortality. The present study examined the hypothesis that combining a regime of moderate aerobic exercise with one daily fish meal as part of a low-fat diet (30% total energy) would improve coagulation and fibrinolytic factors in dyslipidaemic type 2 diabetic patients. In a randomised. controlled, 8-week trial, 55 sedentary type 2 diabetic subjects with serum triglycerides >1.8 mmol/l and/or HDL-C <1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g omega3 fatty acids/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate <100 bpm) exercise program. Plasma levels of fibrinogen, coagulation factor VIIc, tPA and plasminogen activator inhibitor (PAI-1) antigen were measured before and after intervention. In the 49 subjects who completed the study, the fish diet alone, moderate exercise alone and the combination of fish and moderate exercise all led to significant reductions in tPA antigen concentrations (-2.1 ng/ml, p = 0.02. -1.9 ng/ml, p = 0.03, -2.0 ng/ml, p = 0.01, respectively) compared to controls. In multivariate regression, changes in fasting blood glucose (positively) and erythrocyte omega3 fatty acid composition (inversely) were independent predictors of the change in tPA antigen. The fish diet alone contributed to a significant rise in coagulation factor VIIc compared to controls (4.9%, p = 0.02), which was prevented by moderate exercise. No significant effects on PAI-1 antigen and fibrinogen were seen. In view of recent epidemiological findings, the reduction in tPA antigen with both fish and moderate exercise in these dyslipidaemic type 2 diabetic patients could reflect a reduced thrombotic potential and decreased cardiovascular risk. Furthermore, a small, albeit significant, increase in coagulation factor VIIc associated with fish can be prevented by a concomitant programme of moderate exercise.

The pathophysiology and management of renal bone disease in dialysis patients.

As renal function declines, changes in mineral metabolism occur including phosphate retention, calcitriol deficiency, and the development of secondary hyperparathyroidism. Renal bone disease related to disordered mineral metabolism may result in increased patient morbidity and mortality. Uncontrolled parathyroid hormone (PTH) secretion will result in osteitis fibrosa, a high turnover bone disease. The use of calcium and aluminum-based phosphate binders and vitamin D sterols may contribute to the development of low turnover bone diseases such as osteomalacia and aplastic bone disease. Prevention and control of renal bone disease is an important goal for the interdisciplinary health care team. This paper discusses disordered mineral metabolism and its relationship to renal bone disease. Case studies illustrate the development and treatment of renal bone disease related to secondary hyperparathyroidism and aluminum intoxication.

Cardiac troponin I in patients receiving renal replacement therapy.

Current markers of myocardial injury lack specificity in patients with end-stage renal disease (ESRD). In particular, a false positive creatine kinase-MB (CKMB) elevation occurs in 5-10% of patients with ESRD. The aim of this study was to ascertain the relationship between CKMB and cardiac troponin I (cTnI), a new, highly sensitive and specific marker for myocardial injury, in the authors' dialysis population and compare their specificities. Blood samples were obtained from 112 dialysis patients (35 in peritoneal dialysis; 77 in hemodialysis). Patients were asymptomatic for cardiac ischemia and skeletal muscle injury. Mean +/- SD CKMB mass was 3.16 +/- 2.26 microg/L (range, 0.34-13.62), and cTnI was 0.025 +/- 0.061 ng/ml (range, 0.001-0.496). CKMB and cTnI levels did not correlate (r2 = 0.002; p = 0.61). CKMB mass concentration was significantly higher in men and in diabetics. No patient had a cTnI level greater than 1.5 microg/L, and eight asymptomatic patients had a CKMB mass greater than 6.7 microg/L. These data suggest a specificity of 100% for cTnI vs 94.6% for CKMB at these cutoff values. It is suggested that cTnI replace CKMB as a marker of myocardial injury in patients with ESRD.

The influence of exercise-induced plasma volume changes on the interpretation of biochemical parameters used for monitoring exercise, training and sport.

A number of studies have demonstrated considerable plasma volume changes during and after exposure to different environmental and physiological conditions. These changes are thought to result from transient fluid shifts into (haemodilution) and out of (haemoconcentration) the intravascular space. If the levels of plasma constituents are to be routinely measured for research purposes or used as indicators of training adaptation or the health of an athlete, then it is important to consider the dynamic nature of plasma volume. Controversy still exists over the relevance of plasma volume interactions with plasma constituent levels, and while some investigators have taken plasma volume shifts into account, others have chosen to ignore these changes. Bouts of acute exercise have been shown to produce a transient haemoconcentration immediately after long distance running, bicycle ergometry and both maximal and submaximal swimming exercise. While these changes are transient, lasting only a few hours, other studies have reported a longer term haemodilution following acute exercise. In addition, endurance training has been shown to cause long term expansion of the plasma volume. It would, therefore, seem important to consider the influence of plasma volume changes on plasma solutes routinely measured for research, and as markers of training adaptation, prior to arriving at conclusions and recommendations based purely on their measured plasma level. To further confound this issue, plasma volume changes are known to be associated with heat acclimatisation, hydration state, physical training and postural changes, all of which may differ from one experiment or exercise bout to the next, and should thus be taken into account.