Gary A. Green

Understanding NSAIDs: from aspirin to COX-2.

Nonsteroidal anti-inflammatory drugs (NSAIDs) annually account for 70 million prescriptions and 30 billion over-the-counter (OTC) medications sold in the United States alone. Despite our familiarity with these drugs, NSAIDs are full of paradoxes that pose significant challenges for the medical community. Although NSAIDs are among the oldest of drugs, new formulations continue to come to market. Some formulas are safe enough to be sold OTC for use in infants with fever, while others are available only as a prescription medication and are a leading cause of iatrogenic reactions, hospitalizations, and death. Physicians face the choice of prescribing lower cost, older NSAIDs versus the more expensive but potentially safer ones. The use of NSAIDs is clearly increasing. Factors contributing to this increase are the availability of OTC preparations and the aging of the population with a concomitant increase in osteoarthritis. One indication of the popularity of NSAIDs is that following the introduction of 2 new cyclooxygenase-2 (COX-2) selective inhibitors in 1999, these drugs immediately became the most frequently prescribed new drugs in the United States. This article will familiarize the practitioner with the various types of NSAIDs, including the newer COX-2 formulations, their mechanism of action, and potential adverse reactions and efficacy. Although most practitioners are aware of the indications for NSAIDs, research is continuing to explore nontraditional applications. A new framework is being created that will allow new additions to the NSAID class of medications.

Acute and Chronic Brain Injury in United States National Team Soccer Players

We designed a study to determine whether chronic encephalopathy occurs in elite, active soccer players resulting from repetitive heading of the soccer ball. Studies have suggested that the cumulative effects of heading a ball can cause a chronic brain syndrome similar to dementia pugilistica, which is seen in profes sional boxers. Twenty of 25 members of the U.S. Mens National Soccer Team training camp (average age, 24.9; average years of soccer, 17.7), who com pleted a questionnaire on head injury symptoms and had magnetic resonance imaging of the brain, were compared with 20 age-matched male elite track ath letes. The soccer players were surveyed about playing position, teams, number of headers, acute head inju ries, and years of playing experience. An exposure index to headers was developed to assess a dose- response effect of chronic heading. The soccer and track groups were questioned regarding alcohol use and history of acute head traumas. Questionnaire anal ysis and magnetic resonance imaging demonstrated no statistical differences between the two groups. Among the soccer players, symptoms and magnetic resonance imaging findings did not correlate with age, years of play, exposure index results, or number of headers. However, reported head injury symptoms, especially in soccer players, correlated with histories of prior acute head injuries (r = 0.63). These findings suggest that any evidence of encephalopathy in soccer players relates more to acute head injuries received playing soccer than from repetitive heading.

Analysis of over-the-counter dietary supplements.

ObjectiveTo determine if steroids containing over-the-counter (OTC) dietary supplements conform to the labeling requirements of the 1994 Dietary Supplement Health and Education Act (DSHEA). Design12 brands of OTC supplements containing 8 different steroids were randomly selected for purchase in stores that cater to athletes. There are two androstenediones (4- and 5-androstene-3,17-dione), two androstenediols (4- and 5-androstene-3&bgr;, 17&bgr;-diol), and 4 more are 19-nor cogeners (19-nor-4- and 5-androstene-3,17-dione and 19-nor-4- and 5-androstene-3&bgr;, 17&bgr;-diol). Main Outcome Measures12 brands of OTC anabolic–androgenic supplements were analyzed by high-pressure liquid chromatography. ResultsWe found that 11 of 12 brands tested did not meet the labeling requirements set out in the 1994 Dietary Supplement Health and Education Act. One brand contained 10 mg of testosterone, a controlled steroid, another contained 77% more than the label stated, and 11 of 12 contained less than the amount stated on the label. ConclusionsThese mislabeling problems show that the labels of the dietary steroid supplements studied herein cannot be trusted for content and purity information. In addition, many sport organizations prohibit OTC steroids; thus, athletes who use them are at risk for positive urine test results. In this article we provide the details of the analyses, a summary of the steroids by name and structure, and information on the nature of the positive test results. Athletes and their physicians need this information because of the potential medical consequences and positive urine test results.

Detection of Recombinant Human Erythropoietin in Urine by Isoelectric Focusing

BACKGROUND Doping with erythropoietic proteins such as recombinant human erythropoietin (rHuEPO) and darbepoetin alfa is a serious issue in sport. There is little information on the time course of detection of rHuEPO in urine and on methods to evaluate electrophoresis-based data. METHODS We used a recently described isoelectric focusing method for detecting rHuEPO and endogenous EPO in urine obtained from individuals treated with placebo or epoetin alfa. The latter was administered subcutaneously at 50 IU/kg on days 0, 2, 4, 7, 9, 11, 14, 16, and 18. Blood and urine samples were collected during the morning of study days -3, 0, 2, 4, 7, 9, 11, 14, 16, and 18 and on days 2, 3, 4, and 7 postadministration. We developed visual and numerical (two-band ratio) techniques to evaluate the electropherograms for the presence of rHuEPO. RESULTS Compared with the placebo group, the epoetin alfa-treated group responded with increases in hematocrit, reticulocytes, macrocytes, serum EPO, and serum soluble transferrin receptor. The electropherograms showed that the pattern of bands arising from urinary rHuEPO is different from that of endogenous urinary EPO. Both the two-band ratio and the visual technique detected rHuEPO in all 14 epoetin alfa-treated individuals 3 days after the last dose. On the 7th day after the last dose, both techniques detected rHuEPO in approximately one-half of the participants. rHuEPO was not detected in the placebo-treated individuals. CONCLUSIONS The isoelectric focusing method detects rHuEPO in most urine samples collected 3 days after nine doses of epoetin alfa. The numerical two-band ratio was equivalent to a visual method for detecting rHuEPO in urine.

ARE BRAIN INJURIES A SIGNIFICANT PROBLEM IN SOCCER

This article examines the types of forces that the brain is subjected to in soccer, secondary to both acute brain injury and repetitive heading of the ball. The incidence of acute brain injury is reviewed, as well as studies documenting the effects of heading the ball. Finally, 10 actions are proposed that would make soccer a safer sport with respect to brain injuries and provide avenues for further study in this area.

Nutrition Supplements: Science vs Hype.

Aggressive marketing has led millions of recreational and elite athletes to use nutrition supplements in hopes of improving performance. Unfortunately, these aids can be costly and potentially harmful, and the advertised ergogenic gains are often based on little or no scientific evidence. No benefits have been convincingly demonstrated for amino acids, L-carnitine, L-tryptophan, or chromium picolinate. Creatine, beta-hydroxy-beta-methylbutyrate, and dehydroepiandrosterone (DHEA) may confer ergogenic or anabolic effects. Chromium picolinate and DHEA have adverse side effects, and the safety of the other products remains in question.

Doping Control for the Team Physician A Review of Drug Testing Procedures in Sport

Drug testing is now ubiquitous in sport, and it often falls to the team physician to perform a variety of roles including interpreting test results, designing drug-testing programs, acting as medical review officer, and providing therapeutic use exemptions, education, and counseling. Proper understanding of current testing methods for drugs such as anabolic-androgenic steroids, erythropoietin, and growth hormone is essential if the team physician is going to assume these positions. This article outlines the basics of athletic drug testing from the collection process through the interpretation of results to assist the team physician in this field.

Developing and Implementing Major League Baseball's Health and Injury Tracking System

In 2010, Major League Baseball and the Major League Baseball Players Association reached an agreement regarding the development and implementation of an electronic medical record system and a new league-wide injury surveillance system. The systems were developed to create a more efficient method to track medical histories of players longitudinally as they move across Major and Minor league affiliates, as well as to identify and monitor injury trends in the sport, identify areas of specific concern, and conduct epidemiologic research to better optimize player health and safety. The resulting injury surveillance system, the Health and Injury Tracking System (HITS), is a robust system that includes all players from the both the Major and Minor Leagues. HITS also allows for data linkage with other player- and game-level data to inform the development of injury prevention policies and programs. In the present article, we document the development and implementation of HITS; describe its utility for epidemiologic research; illustrate the potential analytic strength of the surveillance system and its ability to inform policy change; and note the potential for this new surveillance system to advance the field of sports injury epidemiology.

Peroneal Nerve Palsy Induced by Cryotherapy

A group of experts from the University of California, Los Angeles, met to discuss a case from another institution. This case conference is part of a series featuring a variety of sports medicine topics.

The influence of diet on isotope ratio mass spectrometry values.

Objectives:Athletes have increasingly used testosterone (T) and other endogenous anabolic steroids that cannot be detected by conventional gas chromatography-mass spectrometry. This led to gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS), which measures the relative amount of 13C in urinary steroids. Because exogenous testosterone is relatively low in 13C content, this study will determine if consuming a diet low in 13C plants, such as soy, can be confused with a GC/C/IRMS-positive test for exogenous testosterone. Design:Cross-sectional study in which 22 vegetarians known to consume a diet depleted of 13C isotope were compared with a geographic control group of 14 subjects consuming a normal diet. Setting:Two distinct subject populations with respect to diet. Subjects:Subjects were recruited from a soy-based cooperative and control volunteers. Twenty-two of 24 research subjects completed the protocol compared with 14 of 22 control subjects. Interventions:Independent variables were δ13C IRMS values, urinary steroid profile, and isoflavone analysis. Main Outcome Measures:Comparisons were made with respect to dietary analysis, isoflavones, and urinary steroid measurements using GC-C-IRMS. Results:The δ13C values for 2 major metabolites of T (androsterone and etiocholanolone) were lower for the vegetarians than the controls (P = 0.005). The vegetarians excreted a median of 23 μmol/d of total isoflavones compared with 2.7 μmol/d for the control group (P = 0.0002). Conclusions:The carbon isotope ratios of urinary testosterone metabolites of vegetarians consuming a diet that is markedly depleted of 13C content were lower than that of control subjects, but not low enough to result in World Anti-Doping Agency criteria for a positive IRMS analysis.