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Biomedical subjects

G A Green

Publications and source records attributed to G A Green.

At least 19 recordsLinked to original sources

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.

Anti-Inflammatory Agents, Non-Steroidal↗

NCAA study of substance use and abuse habits of college student-athletes.

OBJECTIVE: To determine the substance-use patterns of National Collegiate Athletic Association (NCAA) student-athletes for alcohol, amphetamines, anabolic steroids, cocaine/crack, ephedrine, marijuana/hashish, psychedelics/hallucinogens, and smokeless tobacco. DESIGN: Self-reported, anonymous, retrospective survey. PARTICIPANTS: Male and female student-athletes from 30 sports competing at 991 NCAA Division I, II, and III institutions. MAIN OUTCOME MEASURES: Respondents were queried about their use of eight categories of substances in the previous 12-month period. In addition, data were collected regarding substance use according to team, ethnicity, NCAA Division, reasons for use, and the sources for drugs. RESULTS: The overall response rate was 64.3% with 637 of 991 schools reporting with usable data on 13,914 student-athletes. For the eight categories of substance use, alcohol was the most widely used drug in the past year at 80.5%, followed by marijuana at 28.4%, and smokeless tobacco at 22.5%. Although anabolic steroid use was reported at 1.1% overall, some sports demonstrated higher use, and 32.1% obtained their anabolic steroids from a physician other than the institution's team physician. There were wide variations in the pattern of substance abuse according to sport. The results were also analyzed according to division, and it was found that the likelihood of alcohol, amphetamines, marijuana, and psychedelics use is highest in Division III. In addition, the probability of ephedrine use is highest in both Division II and III, while Division II had the highest likelihood of cocaine use. Finally, the results were analyzed according to ethnicity and we found that the likelihood of use of smokeless tobacco, alcohol, ephedrine, amphetamines, marijuana, and psychedelics is highest for Caucasian student-athletes. CONCLUSION: The study demonstrates a wide variation of use across NCAA divisions and sports, as well as among ethnic groups. The majority of student-athletes engage in substance use, especially alcohol. According to the survey, substance use is highest among Division III student-athletes and also among Caucasians. By examining reasons for use, the study will assist professionals in designing specific interventions for various substances. This study provides a methodology for surveying a large number of NCAA student-athletes, which will be repeated every 4 years to identify trends in substance abuse.

Adolescent↗

Analysis of over-the-counter dietary supplements.

OBJECTIVE: To 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). DESIGN: 12 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-3beta, 17beta-diol), and 4 more are 19-nor cogeners (19-nor-4- and 5-androstene-3,17-dione and 19-nor-4- and 5-androstene-3beta, 17beta-diol). MAIN OUTCOME MEASURES: 12 brands of OTC anabolic-androgenic supplements were analyzed by high-pressure liquid chromatography. RESULTS: We 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. CONCLUSIONS: These 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.

Dietary Supplements↗

Sports haematology.

While the crucial role of haemoglobin in aerobic exercise has been well accepted, there is still a great deal of controversy about the optimal haematological parameters in the athletic population. The initial part of this review will examine the question of anaemia in athletes. The most common finding in athletes is a dilutional pseudoanaemia that is caused by a plasma volume expansion, rather than an actual blood loss. It is not a pathological state and normalises with training cessation in 3 to 5 days. This entity should be distinguished from conditions associated with lowered blood counts, such as intravascular haemolysis or iron deficiency anaemia. The evaluation of true anaemia states in the athlete must take into account not only blood losses secondary to exercise, such as foot strike haemolysis or iron losses through sweat, but non-athletic causes as well. Depending on the age and sex of the athlete, consideration must be given to evaluation of the gastrointestinal or genitourinary systems for blood loss. Finally, a comprehensive nutritional history must be taken, as athletes, especially women, are frequently not consuming adequate dietary iron. The second section of the paper will deal with the very contentious issue of sickle cell trait. While there have been studies demonstrating an increased risk of sudden death in people with sickle cell trait, it is still quite rare and should not be used as a restriction to activity. Further, studies have demonstrated that patients with sickle cell trait have an exercise capacity that is probably normal or near normal. However, in the cases of sudden death, it has been secondary to rhabdomyolysis occurring among sickle cell trait athletes performing at intense exertion under hot conditions, soon after arriving at altitude. The recommendations are that athletes with sickle cell trait adhere to compliance with the general guidelines for fluid replacement and acclimatisation to hot conditions and altitude. The final section of the paper examines the issue of haematological manipulation for the purposes of ergogenic improvement. Although experiments with blood doping revealed improvements in running time to exhaustion and maximal oxygen uptake, the introduction of recombinant erythropoietin has rendered blood doping little more than a historical footnote. However, the improvements in performance are not without risk, and the use of exogenous erythropoietin has the potential for increased viscosity of the blood and thrombosis with potentially fatal results. Until a definitive test is developed for detection of exogenous erythropoietin, it will continue to be a part of elite athletics.

Adaptation, Physiological↗

Radial microbrain form of micrencephaly: possible association with carbamazepine.

A premature infant exposed to carbamazepine in utero had a markedly undersized brain on cranial ultrasonogram. Postmortem examination of the brain revealed no evidence of hypoxic-ischemic injury, hemorrhage, infarction, congenital infection, or calcification. The normal cortical gyral pattern, normal residual germinal matrix, and normal cortical lamination suggested the diagnosis of a radial microbrain form of micrencephaly.

Anticonvulsants↗

A Gleason score of 7 predicts a worse outcome for prostate carcinoma patients treated with radiotherapy.

BACKGROUND: In most reported surgical series, prostate carcinoma patients with a Gleason score of 7 have had worse outcomes than those with other moderately differentiated cancers. Because of variations in reporting grade and grouping Gleason scores, radiation series have conflicting results. METHODS: Five hundred sixty-three men with clinical Stage T1-T3, N0 or Nx, M0 adenocarcinoma of the prostate and known pretreatment prostate specific (PSA) levels received external beam radiation only. The median pretreatment PSA was 10.3 ng/mL (range, 0.2-191 ng/mL). The median duration of follow-up was 42 months (range, 2-114 months). Survival without biochemical failure (bNED) was defined as PSA < or = 1.5 ng/mL and not rising when measured on two consecutive occasions. RESULTS: The 5-year rate of bNED control for all 563 patients was 62%. Increasing Gleason score predicted for decreased bNED control (78% for 2-4, 63% for 5-6, 37% for 7, and 33% for 8-10 at 5 years; P = 0.0001 for overall comparison). The bNED control rate for patients with a Gleason score of 7 was significantly less than the rate for those with Gleason 5-6 in both univariate (P = 0.0008) and multivariate (P = 0.0068) analysis. T classification by palpation, pretreatment PSA, and dose were also shown to be independent predictors of bNED control in multivariate analysis. CONCLUSIONS: Even after adjustment for other known prognostic factors, a Gleason score of 7 was associated with worse bNED control than Gleason scores of 2-4 and 5-6 among patients treated with external beam radiotherapy only for clinically localized prostate carcinoma. Patients with a Gleason score of 7 should not be lumped together with those who have a Gleason score of 5-6; they may instead benefit from more aggressive treatment strategies.

Adenocarcinoma↗

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.

Athletic Injuries↗

Health-related fitness and quality of life in organ transplant recipients.

BACKGROUND: The purpose of this study was to describe the levels of health-related fitness and quality of life in a group of organ transplant recipients who participated in the 1996 U.S. Transplant Games. METHODS: A total of 128 transplant recipients were selected on a first reply basis for testing. Subjects with the following organ types were tested: kidney (n=76), liver (n=16), heart (n=19), lung (n=6), pancreas/kidney (n=7), and bone marrow (n=4). Cardiorespiratory fitness (peak oxygen uptake) was measured using symptom-limited treadmill exercise tests with expired gas analysis. The percentage of body fat was measured using skinfold measurements, and the Medical Outcomes Short Form questionnaire (SF-36) was used to evaluate health-related quality of life. RESULTS: Participants achieved near age-predicted cardiorespiratory fitness (94.7+/-32.5% of age-predicted levels). Scores on the SF-36 were near normal. The active subjects (76% of total sample) had significantly higher levels of peak VO2 and quality of life and a lower percentage of body fat compared with inactive subjects (P<0.01). CONCLUSIONS: Although this is a highly select group which is not representative of the general transplant population, the data suggest that near-normal levels of physical functioning and quality of life are possible after transplantation and that those who participate in regular physical activity may achieve even higher levels.

Adult↗

Lifestyles and health risks of collegiate athletes: a multi-center study.

OBJECTIVE: To determine whether college athletes are at greater risk for maladaptive lifestyle and health-risk behaviors than their nonathletic peers and to identify high risk taking groups by gender, sport, and other identifiers. DESIGN: Multicenter, cross-sectional study. SETTING: Seven major geographically represented collegiate institutions in the United States. PARTICIPANTS: A total of 2,298 college athletes and 683 randomized nonathlete controls completed a confidential survey questionnaire between the summer of 1993 and winter of 1994, assessing lifestyle and health-risk behaviors over the previous 12 months. MAIN OUTCOME MEASURES: Self-reports of lifestyle behaviors and health risks in the following areas: motor-vehicle safety, substance abuse, sexually transmitted diseases and contraception, mental health, cancer prevention, nutrition, exercise and general preventive health issues. RESULTS: Athletes demonstrated significantly higher risk-taking behaviors (p < 0.05) than their nonathlete peers in the following areas: less likely always to use seatbelts; less likely always to use helmets with motorcycles, mopeds, and bicycles; more often drive as a passenger with a driver under the influence of alcohol or drugs; greater quantity and frequency of alcoholic beverages; greater frequency of smokeless tobacco and anabolic steroid use; less-safe sex; greater number of sexual partners; less contraceptive use; and more involvement in physical fights. Female athletes reported a higher prevalence of irregular menses, amenorrhea, and stress fractures compared with female nonathletes. Male athletes had more risk-taking behaviors than did female athletes (p < 0.05), and athletes in contact sports demonstrated more risk-taking behaviors than did athletes in noncontact sports (p < 0.05). Athletes with one risk-taking behavior were likely to have multiple risk-taking behaviors (p < 0.05). CONCLUSIONS: College athletes appear to be at higher risk than their nonathletic peers for certain maladaptive lifestyle behaviors. Athlete subgroups at highest risk include male athletes and athletes participating in contact sports. Athletes at risk for one high-risk behavior demonstrated an increased risk for multiple risk-taking behaviors. Preventive health interventions deserve further study to determine strategies for risk reduction in high-risk groups.

Adolescent↗

Quality control for qualitative assays: quantitative QC procedure designed to assure analytical quality required for an ELISA of hepatitis B surface antigen.

An assay for hepatitis B surface antigen (HBsAg) should reliably detect 0.2 microgram/L, the lowest reported concentration in an asymptomatic blood donor. The difference between this concentration and the assay cutoff defines the analytical quality requirement in a total error format. The design of a statistical QC procedure is critically dependent on the precision of the assay. The precision of a developmental ELISA of HBsAg under study ranged from 17.5% to 9.6% for controls containing 0.07 to 1.50 micrograms/L, respectively. Use of one positive control with the 1(3s), QC rule provided an 85% chance of detecting a critical loss of assay sensitivity; use of two positive controls increased the chance of detecting critical loss of assay sensitivity to nearly 100%. These rules are based on the precision of this developmental assay, and must be developed individually for other assays. The development of the proposed QC procedures illustrates how quantitative QC can be provided for qualitative assays.

Blood Donors↗

Inactivation of Ras by Clostridium sordellii lethal toxin-catalyzed glucosylation.

The lethal toxin (LT) from Clostridium sordellii belongs to the family of large clostridial cytotoxins causing morphological alterations in cultured cell lines accompanied by destruction of the actin cytoskeleton. C. sordellii LT exhibits 90% homology to Clostridium difficile toxin B, which has been recently identified as a monoglucosyltransferase (Just, I., Selzer, J., Wilm, M., von Eichel-Streiber, C., Mann, M., and Aktories, K. (1995) Nature 375, 500-503). We report here that LT too is a glucosyltransferase, which uses UDP-glucose as cosubstrate to modify low molecular mass GTPases. LT selectively modifies Rac and Ras, whereas the substrate specificity of toxin B is confined to the Rho subfamily proteins Rho, Rac, and Cdc42, which participate in the regulation of the actin cytoskeleton. In Rac, both toxin B and LT share the same acceptor amino acid, threonine 35. Glucosylation of Ras by LT results in inhibition of the epidermal growth factor-stimulated p42/p44 MAP-kinase signal pathway. LT is the first bacterial toxin to inactivate Ras in intact cells.

3T3 Cells↗

Characterisation of an enterotoxin-negative, cytotoxin-positive strain of Clostridium sordellii.

In ileal loop assay, ELISA and anion-exchange column chromatography, Clostridium sordellii strain 6018 was shown to produce a cytotoxin, but no detectable enterotoxin. DNA sequence and polymerase chain reaction analyses indicated that the lack of enterotoxin activity is not due to a lack of gene transcription, but to lack of a major portion of the enterotoxin gene. This is the first characterisation of such a strain.

Amino Acid Sequence↗

Use of CD23 (BU38) on paraffin sections in the diagnosis of small lymphocytic lymphoma and mantle cell lymphoma.

The CD23 antigen is a low-affinity immunoglubulin E receptor that is expressed during B-cell activation. Recently, it has been shown to be of diagnostic utility in distinguishing between small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL), two entities that can have similar morphologic and immunophenotypic features. Such studies, however, generally required viable cells in cell suspension or cryostat sections for detection of CD23. We evaluated staining for the CD23 antigen in paraffin sections, using BU38, an antibody that detects a fixation-resistant epitope of the antigen. We analyzed 44 SLLs, 3 lymphoplasmacytoid lymphomas, and 39 MCLs. Staining was performed on formalin- or B5-fixed paraffin-embedded tissue sections using L26 (CD20), CD3, Leu22 (CD43), and BU38 (CD23) antibodies. All of the cases were of B-cell phenotype (CD20+), and 42/44 SLLs, 3/3 lymphoplasmacytoid lymphomas, and 33/39 MCLs coexpressed the CD43 antigen. CD23 was positive in 41 (93%) of 44 SLLs. The majority of neoplastic cells (75% or more) stained positively, with a membranous pattern of staining. The staining was moderate in intensity and easily interpreted. Only 1/39 MCLs and 1/3 lymphoplasmacytoid lymphomas were CD23 positive. CD23-positive follicular dendritic cells were, however, present in all of the MCLs, either in residual follicles or in large, disordered meshworks. These results demonstrate that the BU38 antibody can detect CD23 on the cells of SLLs in paraffin sections and that this antibody can have diagnostic utility in routine diagnosis.

Biomarkers, Tumor↗

Cloning and characterization of the cytotoxin L-encoding gene of Clostridium sordellii: homology with Clostridium difficile cytotoxin B.

Hybridization of an oligodeoxyribonucleotide (oligo) probe, designed from a repeated sequence ('oligo rep') at the C terminus of the Clostridium difficile (Cd) cytotoxin (Cyt), revealed that homologies exist between the Cd cyt gene and the genomes of several other clostridia, including Clostridium sordellii (Cs), suggesting a common ancestral cyt amongst the Clostridium genus. This Cd 'oligo rep' probe was used to clone the Cs (strain 6018) cyt. The sequenced (7095 bp) region encodes 2364 amino acids (aa) and corresponds to a protein of 270,614 Da. Cs Cyt has 76% identity with the Cd Cyt and 47% identity with the Cd enterotoxin (Ent). The latter third of the protein consists of repeated units, similar to those found for Cd Cyt. A highly conserved hydrophobic domain can be delineated. Few structural differences are evident between Cd and Cs Cyt to explain their different cellular and sub-cellular effects. A small open reading frame (ORF) encoding a protein of 16,484 Da is located 210 bp downstream from cyt. No homology was evident with any known sequence. The first 30 aa of this ORF may correspond to a signal peptide.

Amino Acid Sequence↗

Acute knee injuries: Part I. History and physical examination.

A thorough history and physical examination are helpful in the diagnosis of meniscal damage, cruciate and collateral ligament sprains and patellar instability, the four major acute knee injuries. When performing a physical examination in a patient with a knee injury, the uninjured knee should always be assessed first and used for comparison. Examination includes passive and active range-of-motion testing, palpation of the joint line spaces, and a variety of maneuvers to evaluate knee stability. Valgus and varus testing provides assessment of the collateral ligaments. The Lachman and pivot shift tests are useful in the evaluation of the anterior cruciate ligament. The posterior drawer and tibial sag tests are used to evaluate the posterior cruciate ligament. The bounce test, McMurray's test and Apley's grind test can aid in the diagnosis of meniscal injury.

Humans↗

Acute knee injuries: Part II. Diagnosis and management.

The most common acute knee injuries are collateral ligament sprains, meniscal damage, cruciate ligament sprains and patellar dislocation or subluxation events. Initial treatment for these soft tissue injuries includes rest, ice application, compression and elevation for the first 24 to 72 hours, as well as anti-inflammatory medication. Accurate assessment, utilizing a thorough history and physical examination and judicious use of radiographic studies, facilitates proper management and return to activity. Athletic patients should be offered the option of surgical reconstruction.

Acute Disease↗

Hyperphosphorylation of calnexin, a chaperone protein, induced by Clostridium difficile cytotoxin.

Exposure of McCoy cultured cells to Clostridium difficile cytotoxin B or okadaic acid (OA), a potent phosphatase inhibitor, results in similar morphological changes. Using two-dimensional gel electrophoresis, we have detected a protein of approximately 77 kDa, with a pI of 4.5 (termed pp77) which is hyperphosphorylated in both cases. The level of phosphorylation of pp77 is increased by 293% and 35% after treatment with C. difficile cytotoxin B or OA, respectively. This protein was identified by microsequencing as calnexin, a protein which exhibits the characteristics of an endoplasmic reticulum (ER) chaperone.

Amino Acid Sequence↗