Medicine and science in the fight against doping in sport.

The fight against doping in sports commenced as a result of the death of a Danish cyclist during the Rome Olympic Games in 1960. The International Olympic Committee (IOC) established a Medical Commission (IOC-MC) which had the task of designing a strategy to combat the misuse of drugs in Olympic Sport. Some International Sport Federations (IF) and National Sports Federations followed suit, but progress was modest until the world's best male sprinter was found doped with anabolic steroids at the Olympic Games in Seoul in 1988. Further progress was made following the cessation of the cold war in 1989 and in 1999 public authorities around the world joined the Olympic Movement in a unique partnership by creating WADA--the 'World Anti-Doping Agency'. The troubled history of the anti-doping fight from the 1960s until today is reviewed. In particular, the development of detection methods for an ever increasing number of drugs that can be used to dope is described, as are the measures that have been taken to protect the health of the athletes, including those who may need banned substances for medical reasons.

Exercise-induced asthma and competitive athletics.

Although swimming is their optimum sport and exercise, asthmatics should be encouraged to embrace a full and varied program of sport and physical education. Sports exclusion should be infrequent as possible. Pre-exercise cromolyn sodium with significantly reduce exercise-induced asthma (EIA) and salbutamol may be administered pre-exercise should EIA supervene. "Warm-up" is recommended. The current ruling which classes selective beta2-adrenocepter agonists as doping agents in sports should be rescinded.

Comparative aspects of available exercise systems.

Comparative studies have demonstrated that running is the greatest stimulus to exercise-induced asthma (EIA) and is the preferred laboratory test model to examine EIA and its modifications. Swimming provokes least EIA and is the exercise of choice for asthmatics. The frequency and magnitude of EIA produced by running is not altered by regular swimming training.

The use of anti-asthmatic drugs. Do they affect sports performance?

Recent major advances in pharmacological management have provided asthmatics with a satisfactory range of drugs to control asthma. These include sodium cromoglycate (cromolyn sodium), H1-antagonists, belladonna alkaloids, methyl xanthines, glucocorticoids and beta 2-adrenoceptor stimulants. Despite the tendency for most asthmatics to develop bronchoconstriction after exercise, sport and physical activity are now accepted as valuable in the overall management of patients with asthma. Thus, control of exercise-induced asthma (EIA) is essential, if asthmatics are to participate safely in physical activity and without respiratory disadvantage in competitive sport. Fortunately, inhibition or minimization of exercise-induced asthma may be achieved in most asthmatics by pre-exercise aerosol beta 2-agonists supplemented if necessary by sodium cromoglycate and/or theophylline. Regular medication as required to attain and maintain normal ventilatory function throughout each day is the objective in all patients with asthma and appears to be a prerequisiste to control exercise-induced asthma. The introduction of anti-doping controls into high performance sport has presented added difficulties for the asthmatic athlete. Although not always so, currently all of the classes of drugs previously noted are acceptable for the treatment of asthma and exercise-induced asthma. Anomalies may exist in the banning of 2 beta 2-adrenoceptor agonists, fenoterol and orciprenaline (metaproterenol). All sympathomimetic amines with alpha- or predominantly beta-stimulation are banned. The perpetuation of the need to report the use of beta 2-agonists prior to competition appears unnecessary. Although relatively little specific research has been undertaken, there is minimal evidence to suggest that asthmatics can derive any additional ergogenic advantage from medication to control asthma and exercise-induced asthma. beta 2-agonists, sodium cromoglycate and glucocorticoids administered by the aerosol route are not considered to be ergogenic. Some doubts have been raised concerning theophylline and its enhancement of both cardiac and respiratory muscle function. Investigations as to the validity of the suggestion that theophylline could augment physical performance appear warranted. It is reported that some athletes may be unnecessarily taking oral and perhaps parenteral glucocorticoids to obtain certain side effects. Any decision to ban these agents except for aerosol or local use could be supported.

Asthmatic drugs and competitive sport. An update.

Almost all asthmatics are prone to asthma triggered by moderate to severe exercise. Fortunately there are a number of pharmaceutical agents now available which can prevent and/or reverse exercise-induced asthma (EIA) and allow many asthmatics to participate in vigorous physical activities with minimum respiratory disadvantage. Regular exercise is an accepted part of the management of asthma and EIA can now be controlled so successfully that a number of elite sportspersons, in almost all types of sporting events, are asthmatic. This control of EIA, which is essential if asthmatics are to participate safely, requires that the patient and his/her doctor initiate a strategy to manage the disease during sport and other physical activities. In recent years the mortality and morbidity from asthma have been increasing and this has indicated the need to improve patient care. One of the most important innovations aiming to improve the control and treatment of asthma has been the recent development of the 6 point asthma management plan which is a strategy to simplify and optimise the long term management of asthma. It aims to improve the quality of life of most asthmatics and more importantly, prevent deaths due to asthma. Because antidoping controls operate in many high performance sports it is essential that the EIA management plan rely on those medications which are permitted. The list of allowable drugs is in continual flux as new ones are added and others are challenged on the grounds of possible ergogenicity. All aerosol beta 2-agonists except fenoterol, the khellin derivatives, theophylline, ipratropium bromide and the aerosol corticosteroids are currently permitted. Some nonasthmatic athletes who are aware of the improved performance of asthmatic athletes when using pre-exercise medication have been known to take antiasthma medication in the hope that it might improve their performance. Current evidence indicates, however, that the permitted medications are not ergogenic and do not give the asthmatic any advantage over the nonasthmatic athlete but merely removes the respiratory disadvantage under which he/she competes.

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.

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.

Operation for non-union of stress fracture of the tarsal navicular.

Stress fractures of the tarsal navicular do not heal predictably with conservative treatment, so we recommend operation if the fracture remains symptomatic, and radiographs show wide separation of a complete fracture, extension of an incomplete fracture, delayed healing, or a medullary cyst. An autologous bone graft is inserted after en-bloc resection of the fracture surfaces. It is important that the fracture is fully exposed to its distal limits before the graft is inserted. We have grafted 19 fractures in 18 patients. Six fractures were complete, 12 incomplete and one had a residual medullary cyst. Of the 15 patients with adequate follow-up, 12 had been able to return to a pre-injury level of activity by five to 12 months.

Sports medicine in the seventies.

One question which is frequently asked of me is "What is Sports Medicine?" A somewhat facetious friend has replied "It's a lurk designed to get a good parking spot at the football finals and a seat in the stand for the test match. There's even the bait of a free trip to the Olympic Games," he adds jealously. But whilst admitting that these statements can be true, there are many mundane tasks to be accomplished, usually in your own time, or that which, by rights, belongs to your family; many lectures to prepare and deliver, and much criticism to endure, when you fail to cure overnight, the football star's ruptured cruciate ligament or neurotic, spoilt temperament or both.

Stress fractures of the lower limbs in runners.

Stress fractures are a common sports injury and running can cause fractures in most bones from the metatarsals to the pubic rami. Pain after an increase in or modification to a running programme is the initial symptom; there will be point tenderness over bone. Rest from running for six to 10 weeks is necessary but alternative exercise must be prescribed for those 'addicted' to running.

Physical Activity and the Asthmatic.

In brief: Recent studies suggest that avoiding exercise is unwarranted and detrimental for asthmatics. Although exercise provokes bronchospasm in most asthmatics, the severity of exercise-induced asthma can be reduced by several factors: control of exercise duration; less intense, intermittent exercise; warm-ups; warmer, humid inspired air; aerobic fitness; and drugs. Regular vigorous activity increases fitness, enhances tolerance to attacks, and provides more social and psychological independence. The recent development of protective medications has made such activity possible for many asthmatics. Preexercise cromolyn sodium and beta adrenergic agonists are recommended for blocking or reversing attacks.

Drug Tests for Athletes-Pro and Con.

Concerns about the costs and effectiveness of drug testing in reducing drug use and abuse among athletes has sparked a debate about whether testing should be continued, expanded in scope, or discontinued. THE PHYSICIAN AND SPORTSMEDICINE has asked physicians Daniel F. Hartley, Herman Adlercreutz. K. D. Fitch, and E. C. Percy for their views on the subject. Their comments are preceded by an introduction by Allan J. Ryan. MD.

Management of allergic Olympic athletes.

Twenty percent of the recent Australian Olympic athletes have had an allergic disorder. Because of the ban on all sympathomimetic drugs except some beta 2-agonists. Olympic team physicians have a major responsibility to ensure that no competitor is disqualified for infringing on the antidoping rules of the Medical Commission of the International Olympic Committee. Inadvertent contravention of these regulations may occur because numerous banned sympathomimetics are available to athletes and their coaches without medical prescription and are frequently contained in combination preparations. The unbroken 24 yr in which asthmatics have won Olympic medals have been both before and after the introduction of drug tests. Currently a comprehensive range of preventive and therapeutic medications are available for asthmatics to compete with minimal respiratory disadvantage. It was, however, during a period of unnecessary restriction that an American swimmer forfeited his gold medal because of prerace ingestion of a banned sympathomimetic agent. Should adverse air quality be encountered during the Los Angeles Olympics, allergic competitors will be among the most inconvenienced . Athletes with allergic rhinitis and sinusitis will be the most disadvantaged because sympathomimetic vasoconstrictors remain banned. It is strongly recommended that the Medical Commission of the International Olympic Committee meet with an appropriate body of experts (i.e., the American Academy of Allergy and Immunology) to review this ban on vasoconstrictor agents.

Specificity of exercise in exercise-induced asthma.

Ventilatory function after three types of exercise-running, cycling, and swimming-was studied in 10 control subjects and 40 asthmatic patients. All performed eight minutes of submaximal aerobic exercise during each of the programmes, which were conducted in a randomly selected order. Biotelemetric monitoring of heart rates was used to equate the intensity of the exertion undertaken during the three systems of exercise. No control subject showed any significant variation in ventilatory capacity after exercise, and the responses after the three forms of exercise did not differ.In asthmatics exercise-induced asthma was observed after 72.5% of running tests, 65% of cycling tests, and 35% of swimming tests. In addition, those patients who developed exercise-induced asthma after swimming were noted to have significantly smaller falls in FEV(1) levels than were recorded after running and cycling. These results were statistically significant (P <0.01).The unexplained aetiology of increased airways resistance after exercise in asthmatics is discussed. This study indicates that swimming should be recommended in preference to running or cycling as an exercise programme for adults and children with asthma.

Asthma and athletic performance.

Exercise-induced asthma (EIA) is a manifestation of bronchial hyper-reactivity that poses a special problem for the asthmatic engaging in competitive and recreational sports. Recent Olympic successes by swimmers with asthma are not surprising in view of the lessened asthmogenicity of swimming. Neither the cause of EIA nor the reason why some forms of exercise have a greater propensity to provoke EIA is known. Preexercise prophylactic medication with selective beta 2-sympathomimetic agents or cromolyn sodium will reduce or abolish EIA in the majority of asthmatics if administered just before the event. Other agents are less effective or as yet not fully evaluated. With suitable control of exercise-induced asthma, asthmatics should not be unnecessarily restricted, and competitive sports or physical recreation can then occupy an identical role in their lives as it does for their non-asthmatic contemporaries.

Rimiterol and the prevention of exercise-induced asthma.

The potential for rimiterol to protect athletes from exercise-induced asthma (EIA) has not been fully established. Ten athletes with asthma (15 to 30 years of age) undertook 8 minutes of submaximal exercise (80% of anaerobic threshold) on the treadmill ergometer, once after inhaling rimiterol and once after inhaling a placebo. Treatment with all bronchodilator drugs was stopped for the 12 hours preceding each exercise test. Two puffs (400 micrograms) of rimiterol or placebo were administered in a double-blind crossover manner 2 minutes before each exercise test. Lung function measurements were made before exercise and immediately, 5, 10, 15, 20, 25, and 30 minutes after completion of exercise. The results of a two-way analysis of variance revealed significant (p less than 0.01) difference in the FEV1 scores obtained after rimiterol inhalation and placebo inhalation, 5, 10, 15, 20, 25, and 30 minutes after cessation of exercise. After inhalation of rimiterol, there were no significant changes in FEV1. After inhaling the placebo, significant reductions (p less than 0.01) in FEV1 occurred after cessation of exercise (5, 10, 15, and 20 minutes). All subjects exhibited EIA after placebo, and none after rimiterol. The mean maximum drop after exercise in FEV1 after inhalation of rimiterol (2.807 +/- 5.55) and placebo (24.54 +/- 8.4) was significantly different (t = 6.849). It was concluded that inhalation of rimiterol 2 minutes before exercise afforded significant protection from EIA in all subjects tested.

The effect of "warm-up" on exercise-induced asthma.

To determine the effect of "warm-up" on exercise-induced asthma (EIA) 18 subjects ( mean age 19.7 years) performed five minutes of submaximal treadmill running to achieve a heart rate (HR) of 85% of predicted maximum for age. One such exercise test was preceded by "warm-up" and one was not. "Warm-up" consisted of three minutes of treadmill walking or jogging to attain 60% of predicted maximun HR for age. An identical incidence (77.8%) and severity (38.1% mean decrease in FEV1) of EIA was recorded after treadmill running whether preceded by "warm-up" or not. While this study does not support the concept that "warm-up" could reduce the likelihood of EIA, it is recommended that a longer, more intense "warm-up" involving interval exercise should be evaluated before rejecting the view that "warm-up" ameliorates EIA.

Continuous and intermittent running in the provocation of asthma.

With total work constant, continuous running has been found to provoke more severe asthma than any of four different intermittent running regimes. This constitutes the first definite support for the clinical impression that exercise is better tolerated by asthmatics when broken into brief periods separated by intervals of recovery.