Results of voluntary cardiovascular examination of elite athletes in Denmark: Proposal for Nordic collaboration.

We investigated the cardiovascular status of elite athletes in Denmark, the extent of abnormal cardiac findings--both training related and pathologic--and how participating in cardiac examination was perceived by the athletes. A standardized protocol of questionnaires, physical examination, resting electrocardiogram, and 2D echocardiography was used. In total 1347 elite athletes were invited; 516 athletes (38%) from 30 different sports participated. Results were stored in a web-based database for future research and long-term follow-up. Cardiac pathology was infrequent; eight athletes (1.6%) received a cardiac diagnosis; one athlete (0.2%) diagnosed with long QT syndrome was advised against competition level sports. In total, 60 athletes (11.6%) were referred for additional testing. The athletes presented a very low level of psychological stress before and a slight decrease immediately after the examination as measured by the REST-Q 76 Sport questionnaire. Athletes needing further examinations did not present a higher level of stress after the initial examination compared with athletes with normal test results. Overall, very few athletes were diagnosed with a cardiac condition that increased risk of sudden cardiac death. Less than half of the invited athletes volunteered, but participation was not perceived stressful by the enrolled athletes, not even when additional testing was needed.

T-wave morphology analysis of competitive athletes.

BACKGROUND: T-wave morphology has been shown to be more sensitive than QT and QTc interval to describe repolarization abnormalities. The electrocardiogram (ECG) performed in athletes may manifest abnormalities, including repolarization alterations. The aim of this study was to investigate the characteristics of T-wave morphology features in athletes. METHODS: Eighty male elite athletes, consisting of 40 Tour de France cyclists (age 27±5years), 40 soccer players (age 26±6years) and 40 healthy men (age 27±5years) were included. RESULTS: Sinus bradycardia, left ventricular (LV) hypertrophy, incomplete right bundle branch block and early repolarization were documented in 25 %, 20%, 13% and 14% of athletes, respectively. ECG criteria for LV hypertrophy in 12-lead ECG were more common in cyclists (35%) than in soccer players (5%), P<0.0001. Cyclists and soccer players had significantly longer RR interval, and repolarization features than the control group. CONCLUSIONS: T-wave morphology of athletes is different from non-athletes, depending of the sport. Decreased potassium current in cardiomyocytes associated with LVH may contribute to these changes.

Cardiovascular function is better in veteran football players than age-matched untrained elderly healthy men.

The aim of the study was to determine whether lifelong football training may improve cardiovascular function, physical fitness, and body composition. Our subjects were 17 male veteran football players (VPG; 68.1 ± 2.1 years) and 26 healthy age-matched untrained men who served as a control group (CG; 68.2 ± 3.2 years). Examinations included measurements of cardiac function, microvascular endothelial function [reactive hyperemic index (RHI)], maximum oxygen uptake (VO2max), and body composition. In VPG, left ventricular (LV) end-diastolic volume was 20% larger (P < 0.01) and LV ejection fraction was higher (P < 0.001). Tissue Doppler imaging revealed an augmented LV longitudinal displacement, i.e., LV shortening of 21% (P < 0.001) and longitudinal 2D strain was 12% higher (P < 0.05), in VPG. In VPG, resting heart rate was lower (6 bpm, P < 0.05), and VO2max was higher (18%, P < 0.05). In addition, RHI was 21% higher (P < 0.05) in VPG. VPG also had lower body mass index (P < 0.05), body fat percentage, total body fat mass, android fat percentage, and gynoid fat percentage (all P < 0.01). Lifelong participation in football training is associated with better LV systolic function, physical fitness, microvascular function, and a healthier body composition. Overall, VPG have better cardiovascular function compared with CG, which may reduce their cardiovascular morbidity and mortality.

Cardiovascular adaptations to 4 and 12 months of football or strength training in 65- to 75-year-old untrained men.

The study examined the effects of 1 year of football or strength training on cardiovascular function in 65- to 75-year-old men. Twenty-six untrained men (age: 68.2 ± 3.2 years) were randomized to football training (FTG; n = 9), strength training (STG; n = 9), or control (CG; n = 8). In FTG, left ventricular (LV) internal diastolic diameter, end-diastolic volume, and mass index were 8%, 21%, and 18% higher (P < 0.01), respectively, after 12 months, with no changes in STG and CG. After 12 months, LV ejection fraction was increased (P < 0.05) by 8% and 5% in FTG and STG, respectively, and systolic longitudinal two-dimensional strain by 8% and 6%, whereas right ventricular systolic function improved (P < 0.05) by 22% in FTG, but not in STG and CG. In FTG, LV diastolic mitral inflow (E/A) ratio and peak early diastolic velocity (E') improved (P < 0.05) by 25% and 12%, respectively, after 12 months, with no changes in STG and CG. In FTG, maximum oxygen uptake was 16% and 18% higher (P < 0.001) after 4 and 12 months, respectively, and resting heart rate was 6 and 8 beats per minute lower (P < 0.001), respectively, with no changes in STG and CG. In conclusion, football training elicited superior cardiovascular effects compared with strength training in elderly untrained men.

Structural and functional cardiac adaptations to 6 months of football training in untrained hypertensive men.

We investigated the effects of 3 and 6 months of regular football training on cardiac structure and function in hypertensive men. Thirty-one untrained males with mild-to-moderate hypertension were randomized 2:1 to a football training group (n = 20) and a control group receiving traditional recommendations on healthy lifestyle (n = 11). Cardiac measures were evaluated by echocardiography. The football group exhibited significant (P < 0.05) changes in cardiac dimensions and function after just 3 months: Left ventricular (LV) end-diastolic volume increased from 104 ± 25 to 117 ± 29 mL. LV diastolic function improved measured as E/A ratio (1.15 ± 0.32 to 1.54 ± 0.38), early diastolic velocity, E' (11.0 ± 2.5 to 11.9 ± 2.6 cm/s), and isovolumetric relaxation time (74 ± 13 to 62 ± 13 ms). LV systolic function improved measured as longitudinal displacement (10.7 ± 2.1 to 12.1 ± 2.3 mm). Right ventricular function improved with respect to tricuspid annular plane systolic excursion (21.8 ± 3.2 to 24.5 ± 3.7 mm). Arterial blood pressure decreased in both groups, but significantly more in the football training group. No significant changes were observed in the control group. In conclusion, short-term football training improves LV diastolic function in untrained men with mild-to-moderate arterial hypertension. Furthermore, it may improve longitudinal systolic function of both ventricles. The results suggest that football training has favorable effects on cardiac function in hypertensive men.

Long-term musculoskeletal and cardiac health effects of recreational football and running for premenopausal women.

We examined long-term musculoskeletal and cardiac adaptations elicited by recreational football (FG, n=9) and running (RG, n=10) in untrained premenopausal women in comparison with a control group (CG, n=9). Training was performed for 16 months ( approximately 2 weekly 1-h sessions). For FG, right and left ventricular end-diastolic diameters were increased by 24% and 5% (P<0.05), respectively, after 16 months. Right ventricular systolic function measured by tricuspid annular plane systolic excursion (TAPSE) increased (P<0.05) in FG after 4 months and further (P<0.05) after 16 months (15% and 32%, respectively). In RG and CG, cardiac structure, E/A and TAPSE remained unchanged. For FG, whole-body bone mineral density (BMD) was 2.3% and 1.3% higher (P<0.05) after 16 months, than after 4 and 0 months, respectively, with no changes for RG and CG. FG demonstrated substantial improvements (P<0.05) in fast (27% and 16%) and slow (16% and 17%) eccentric muscle strength and rapid force capacity (Imp30ms: 66% and 65%) after 16 months compared with 4 and 0 months, with RG improving Imp30ms by 64% and 46%. In conclusion, long-term recreational football improved muscle function, postural balance and BMD in adult women with a potential favorable influence on the risk of falls and fractures. Moreover, football training induced consistent cardiac adaptations, which may have implications for long-term cardiovascular health.

Beneficial effects of recreational football on the cardiovascular risk profile in untrained premenopausal women.

The present study examined the cardiovascular health effects of 16 weeks of recreational football training in untrained premenopausal women in comparison with continuous running training. Fifty healthy women were matched and randomized to a football (FG, n=25) or a running (RG, n=25) group and compared with a control group with no physical training (CO, n=15). Training was performed for 1 h twice a week. After 16 weeks, systolic and diastolic blood pressure was reduced (P<0.05) in FG (7+/-2 and 4+/-1 mmHg) and systolic blood pressure was lowered (P<0.05) in RG (6+/-2 mmHg). After 16 weeks, resting heart rate was lowered (P<0.05) by 5+/-1 bpm both in FG and RG, and maximal oxygen uptake was elevated (P<0.05) by 15% in FG and by 10% in RG (5.0+/-0.7 and 3.6+/-0.6 mL/min/kg, respectively). Total fat mass decreased (P<0.05) by 1.4+/-0.3 kg in FG and by 1.1+/-0.3 kg in RG. After 16 weeks, pulse pressure wave augmentation index (-0.9+/-2.5 vs 4.2+/-2.4%), skeletal muscle capillarization (2.44+/-0.15 vs 2.07+/-0.05 cap/fib) and low-density lipoprotein/high-density lipoprotein cholesterol ratio were improved (P<0.05) in FG, but not altered in RG. No changes were observed in CO. In conclusion, regular recreational football training has significant favorable effects on the cardiovascular risk profile in untrained premenopausal women and is at the least as efficient as continuous running.

Football as a treatment for hypertension in untrained 30-55-year-old men: a prospective randomized study.

The present study investigated whether football has favorable effects in the treatment of mild-to-moderate arterial hypertension in untrained middle-aged men. Twenty-five untrained males aged 31-54 year with mild-to-moderate hypertension were randomized to a football training group (FTG, two 1-h sessions per week) and a control group receiving physician-guided traditional recommendations on cardiovascular risk factor modification (doctoral advice group, DAG). After 3 months, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lowered (P<0.05) by 12 +/- 3 and 7 +/- 1 mmHg in FTG, respectively, whereas no significant changes were observed for DAG, with the 3 months values being lower (P<0.05) in FTG than DAG (SBP: 138 +/- 2 vs 148 +/- 2 mmHg; DBP: 84 +/- 2 vs 92 +/- 2 mmHg). The resting heart rate was lowered (P<0.05) by 12 +/- 2 b.p.m. in FTG after 3 months (67 +/- 3 vs 79 +/- 3 b.p.m.), whereas no change was observed for DAG. After 3 months, FTG had higher (P<0.05) VO(2max) (8 +/- 2%; 35.0 +/- 1.6 vs 32.5 +/- 1.3 mL/min/kg) and lower (P<0.05) fat mass (1.7 +/- 0.6 kg), whereas no change was observed for DAG. In conclusion, football training is an attractive non-pharmacological supplement to the treatment of mild-to-moderate arterial hypertension in untrained middle-aged men.

Improvement of systolic and diastolic heart function after physical training in sedentary women.

The present study examined the cardiac effects of football training and running for inactive pre-menopausal women by standard echocardiography and tissue Doppler imaging. Thirty-seven subjects were randomized to two training groups (football: FG; n=19; running; RG; n=18) training 1 h with equal average heart rates twice a week for 16 weeks and compared with a matched inactive control group (CG; n=10). During the training period, left ventricular end-diastolic volume increased by 13% in FG and 11% in RG (P<0.05). Left ventricular posterior wall thickness increased in FG from 8.5+/-1.4 to 9.0+/-1.3 mm (P<0.05). Right ventricle diameter increased by 12% in FG and 10% in RG (P<0.05). Tissue Doppler imaging demonstrated increased left ventricular systolic and diastolic performances in both training groups. Peak systolic velocity increased by 26% in FG and 17% in RG (P<0.05) and left ventricular longitudinal displacement increased in both groups by 13% (P<0.05). Isovolumetric relaxation time decreased significantly more in FG than in RG (26% vs 14%, respectively P<0.05). In conclusion, 16 weeks of football and running exercise training induced significant changes of cardiac dimensions and had favorable effects on both left ventricular systolic and diastolic function. These training-induced cardiac adaptations appeared to be more consistent after football training compared with running.

Predictive factors of response to cisplatin-based chemotherapy and the relation of response to survival in patients with metastatic urothelial cancer.

PURPOSE: To identify pretreatment variables predicting overall and complete response to cisplatin-based chemotherapy for metastatic urothelial cancer, and to study the relation between response and the duration of survival. PATIENTS AND METHODS: A total of 119 evaluable patients with recurrent locally advanced or metastatic urothelial cancer received cisplatin-based combination chemotherapy in four consecutive phase II studies from 1987 to 1997. The relationship of pretreatment variables and response was evaluated with logistic regression, and prognostic factors for survival were analyzed with Cox's multivariate model. RESULTS: Response was achieved in 49% of the patients with a complete response rate of 15%. Good performance status and absence of bone metastases were independently predictive of overall response. Good performance status and normal hemoglobin were independently predictive of complete response. Median survival was 8.9 months. Performance status, alkaline phosphatase, s-creatinine, liver and bone metastases were independent prognostic factors for survival. Median survival was 12.4 months in responding patients and 6.3 in nonresponding patients. Response to chemotherapy was included in the multivariate model and was the strongest prognostic factor for survival. CONCLUSION: The presence of bone metastases, low hemoglobin or poor performance status predicts decreased chance of response to chemotherapy. Response to chemotherapy is an independent prognostic factor for prolonged survival in patients with metastatic urothelial cancer.

Gastrointestinal osmoreceptors and renal sodium excretion in humans.

The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered by a nasogastric tube as isotonic or hypertonic saline (850 mM). In additional experiments, salt loading was replaced by oral water loading (3.5% of total body water). Plasma sodium concentration increased after hypertonic saline (+3.1 +/- 0.7 mM), decreased after water loading (-3.8 +/- 0.8 mM), and remained unchanged after isotonic saline. Oncotic pressure decreased by 9.4 +/- 1.2, 3.7 +/- 1.2, and 10.7 +/- 1.3%, respectively. Isotonic saline induced an increase in renal sodium excretion (104 +/- 15 to 406 +/- 39 micromol/min) that was larger than seen with hypertonic saline (85 +/- 15 to 325 +/- 39 micromol/min) and water loading (88 +/- 11 to 304 +/- 28 micromol/min). Plasma ANG II decreased to 22 +/- 6, 35 +/- 6, and 47 +/- 5% of baseline after isotonic saline, hypertonic saline, and water loading, respectively. Plasma atrial natriuretic peptide (ANP) concentrations and urinary excretion rates of endothelin-1 were unchanged. In conclusion, stimulation of osmoreceptors by intragastric infusion of hypertonic saline is not an important natriuretic stimulus in sodium-replete subjects. The natriuresis after intragastric salt loading was independent of ANP but can be explained by inhibition of the renin-angiotensin system.

Volume expansion natriuresis during servo control of systemic blood pressure in conscious dogs.

The importance of arterial blood pressure (BP) and ANG II for the renal natriuretic response (NaEx) to volume expansion (3.5% body wt) was investigated during converting enzyme blockade (enalaprilate, 2 mg/kg). In separate experiments, BP was clamped either 30 mm Hg above or a few millimeters mercury below baseline by servo-controlled infusion of ANG II or sodium nitroprusside, respectively, so that volume expansion did not change BP. Enalapril decreased BP by 8 mm Hg. Without clamping, volume expansion returned BP to that of preenalapril control and increased NaEx 10-fold (40+/-10 to 377+/-69 micromol/min). During high pressure clamping (133+/-2 mm Hg), peak NaEx after volume expansion was 6% of control experiments. During low pressure clamping, NaEx was 68% of control experiments (45+/-15 to 256+/-64 micromol/min). The results show that 1) in absence of ANG II, volume expansion elicited pronounced natriuresis without increases in BP beyond baseline, 2) in the presence of hypertensive amounts of ANG II, the volume expansion-induced natriuresis was almost eliminated, and 3) nitroprusside prevented the increase in BP but not sodium excretion during volume expansion. ANG II appears to dominate the control of NaEx; however, when absent, volume expansion may still induce marked natriuresis even at constant BP, possibly via nitric oxide-mediated mechanisms.

Blood pressure and plasma catecholamines in acute and prolonged hypoxia: effects of local hypothermia.

This study measured the pressor and plasma catecholamine response to local hypothermia during adaptation to hypobaric hypoxia. Eight healthy men were studied at rest and after 10 and 45 min of local cooling of one hand and forearm as well as after 30 min of rewarming at sea level and again 24 h and 5 days after rapid, passive transport to high altitude (4,559 m). Acute mountain sickness scores ranged from 5 to 16 (maximal attainable score: 20) on the first day but were reduced to 0-8 by the fifth day. Systolic blood pressure, heart rate, and plasma epinephrine increased on day 1 at altitude compared with sea level but declined again on day 5, whereas diastolic and mean blood pressures continued to rise in parallel with plasma norepinephrine. With local cooling, an increased vasoactive response was seen on the fifth day at altitude. Very high pressures were obtained, and the pressure elevation was prolonged. Heart rate increased twice as much on day 5 compared with the other two occasions. Thoracic fluid index increased with cooling on day 5, suggesting an increase in pulmonary vascular resistance. In conclusion, prolonged hypoxia seems to elicit an augmented pressor response to local cooling in the systemic and most likely also the pulmonary circulation.

Granisetron compared with prednisolone plus metopimazine as anti-emetic prophylaxis during multiple cycles of moderately emetogenic chemotherapy.

This randomized, double-blind, double-dummy parallel study compared the anti-emetic efficacy and tolerability of the serotonin antagonist granisetron with prednisolone plus the dopamine D2 antagonist metopimazine during nine cycles of moderately emetogenic chemotherapy. Chemotherapy naive women with stage I or II breast cancer scheduled to intravenous cyclophosphamide, fluorouracil and methotrexate or cyclophosphamide, epirubicin and fluorouracil every 3 weeks were included. Patients received a single intravenous dose of granisetron 3 mg or a 3-day oral treatment with prednisolone 25 mg once a day plus metopimazine 30 mg four times a day. A total of 223 women were enrolled and 218 patients (97.8%) were evaluable for efficacy. Granisetron (n = 109) was superior to prednisolone plus metopimazine (n = 109) in the prophylaxis of acute nausea and vomiting during the first cycle of chemotherapy (P < 0.001) and prednisolone plus metopimazine was superior on days 2-5 (P = 0.002). Overall, granisetron was superior on days 1-5 (P = 0.009). The median number of cycles completed with granisetron was five (95% confidence interval 4-6) compared with two (95% confidence interval 2-2) for prednisolone plus metopimazine (P = 0.0019). Constipation and rash were reported more frequently with granisetron (P < 0.001 and P = 0.043 respectively) and palpitations more frequently with prednisolone plus metopimazine (P = 0.015). In conclusion, the number of cycles completed with granisetron was significantly higher than the number completed with prednisolone plus metopimazine, but the anti-emetic efficacy of both treatments declined during multiple cycles of moderately emetogenic chemotherapy.

Isotonic and hypertonic sodium loading in supine humans.

The hypothesis that hypertonic saline infusion induces a greater natriuresis than infusion of the same amount of sodium as isotonic saline was tested in 8 supine subjects on fixed sodium intake of 150 mmol NaCl day(-1). Sodium loads equivalent to the amount of sodium contained in 10% of measured extracellular volume were administered intravenously over 90 min either as isotonic saline or as hypertonic saline (850 mmol L(-1)). A third series without saline infusion served as time control. Experiments lasted 8 h. Water balance and sodium loads were maintained by replacing the excreted amounts every hour. Plasma sodium concentrations only increased following hypertonic saline infusion (by 2.7 +/- 0.3 mmol L(-1)). Oncotic pressure decreased significantly more with isotonic saline (4.1 +/- 0.3 mmHg) than with hypertonic saline (3.2 +/- 0.2 mmHg), indicating that isotonic saline induced a stronger volumetric stimulus. Renal sodium excretion increased more than a factor of four with isotonic and hypertonic saline but also increased during time control (factor of three). Cumulated sodium excretions following isotonic (131 +/- 13 mmol) and hypertonic saline (123 +/- 10 mmol) were statistically identical exceeding that of time control (81 +/- 9 mmol). Plasma angiotensin II decreased in all series but plasma ANP concentrations and urinary excretion rates of endothelin-1 remained unchanged. In conclusion, hypertonic saline did not produce excess natriuresis. However, as the two loading procedures induced similar natriureses during different volumetric stimuli, part of the natriuresis elicited by hypertonic saline could be mediated by stimulation of osmoreceptors involved in renal sodium excretion. The supine position does not provide stable time control conditions with regard to renal excretory function.

Long-term continuous 5-fluorouracil infusion in patients with advanced head and neck cancer.

Forty-two patients with advanced head and neck cancer entered this phase II trial of long-term continuous 5-fluorouracil (5-FU) infusion at a dose of 300 mg/m2/day for a maximum of 16 weeks. Objective response rate was 15% in 41 evaluable patients. Median time to progression was 2.9 months, and median survival 4 months. Toxicity was generally mild. Reversible stomatic and hand-foot syndrome WHO grade III-IV was observed in 5 and 3 patients, respectively. Haematologic toxicity and emesis were less pronounced with no grade III-IV toxicity. One patient had to discontinue treatment because of ataxia. No catheter-related toxicity and no treatment-related mortality were observed. In the present study long-term continuous infusion of 5-FU has only modest activity in terms of response rate, but the activity is comparable with other single-agent regimens. The treatment is well tolerated, with minimal toxicity making it usable in a palliative situation.

Osmoregulatory control of renal sodium excretion after sodium loading in humans.

The hypothesis that renal sodium handling is controlled by changes in plasma sodium concentration was tested in seated volunteers. A standard salt load (3.08 mmol/kg body wt over 120 min) was administered as 0.9% saline (Isot) or as 5% saline (Hypr) after 4 days of constant sodium intake of 75 (LoNa+) or 300 mmol/day (HiNa+). Hypr increased plasma sodium by approximately 4 mmol/l but increased plasma volume and central venous pressure significantly less than Isot irrespective of diet. After LoNa+, Hypr induced a smaller increase in sodium excretion than Isot (48 +/- 8 vs. 110 +/- 17 micromol/min). However, after HiNa+ the corresponding natriureses were identical (135 +/- 33 vs. 139 +/- 39 micromol/min), despite significant difference between the increases in central venous pressure. Decreases in plasma ANG II concentrations of 23-52% were inversely related to sodium excretion. Mean arterial pressure, plasma oxytocin and atrial natriuretic peptide concentrations, and urinary excretion rates of endothelin-1 and urodilatin remained unchanged. The results indicate that an increase in plasma sodium may contribute to the natriuresis of salt loading when salt intake is high, supporting the hypothesis that osmostimulated natriuresis is dependent on sodium balance in normal seated humans.

Salivary gland carcinomas: prognostic significance of simple mucin-type carbohydrate antigens.

The prognosis of salivary gland carcinomas is difficult to assess. Simple mucin-type carbohydrates (T and sialosyl-T antigens, Tn and sialosyl-Tn antigens) have been shown to be of value in predicting prognosis for carcinomas in other locations. We studied the prognostic significance of the expression of these structures in a retrospective study of 133 patients with salivary gland carcinomas, using immunohistochemistry and a panel of well-defined monoclonal antibodies (MAbs) on formalin-fixed paraffin-embedded tissues. Sialosyl-Tn, T and sialosyl-T antigens were not correlated with prognosis. Univariate analyses showed no overall difference in survival or locoregional control between patients with Tn-positive and patients with Tn-negative tumours, but indicated that expression of the Tn antigen was associated with early locoregional recurrences and deaths. Tn was, however, not an independent prognostic factor by multivariate regression analysis.