A view from New Zealand: comments on the prolonged QT theory of SIDS causation.
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Biomedical subjects
Publications and source records attributed to P M Clarkson.
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OBJECTIVES: This study examines the late outcome in patients with simple transposition of the great arteries (TGA) after a Mustard operation. BACKGROUND: Continuing medical follow-up for patients after the Mustard procedure, now extending to three decades, is required. The quality of life of adult survivors has not been well documented. METHODS: Survival and quality of life among 113 hospital survivors of the Mustard operation performed for simple TGA between 1964 and 1982 were assessed by medical review and a lifestyle questionnaire. The incidence of right ventricular failure and echocardiographic right ventricular dysfunction (RVD) were determined. A measure of lifestyle, the ability index, was determined. RESULTS: Actuarial survival was 90%, 80%, and 80% at 10, 20, and 28 years, respectively, with 76% of survivors being New York Heart Association class 1. Sudden death, with an incidence of 7% without identifiable risk factors, was the most common cause of late demise. RVD was identified in 18% of patients who had echocardiography, but there was right ventricular failure in only two patients. Seventy-five percent of current survivors lead a normal life, 20% have some symptoms or lifestyle modification, and 5% are unable to work. CONCLUSIONS: The survival of patients to 28 years with the Mustard repair has been good. Late sudden death is the most worrisome feature. There is a 97% freedom from right ventricular failure to date. The quality of life of late survivors is good, most achieving a normal level of education and employment.
PURPOSE: This study investigated the release and clearance of plasma CK-MM (muscle) isoforms following two bouts of eccentric exercise to determine whether enhanced enzyme clearance could in part explain the blunted creatine kinase (CK) response to a second bout of exercise. METHODS: Nonweight trained college-aged male subjects performed both bouts of 50 forced lengthening contractions of the forearm flexor muscles separated by 6 d either with the same arm (CON; N = 4) or with one arm followed by the contralateral arm (EXP; N = 4). Range of motion, arm circumference, maximal isometric strength, perceived muscle soreness, total CK (TCK), and MM variants were assessed. Each MM isoform was measured as a percentage of TCK activity and in absolute activity (IU.L-1) following isoelectric separation and densitometry. The MM1:MM3 ratio, calculated from absolute concentrations, was used to indicate periods of release and clearance. RESULTS: Non-CK criterion measures indicated that similar damage occurred in both arms for EXP (P > 0.05), whereas CON exhibited a blunted response on bout 2 (P < 0.01). Postbout 1, TCK peaked at 96 h for CON (3530 +/- 927 IU.L-1) and EXP (6683 +/- 433 IU.L-1) (P < 0.01). Postbout 2, CON TCK showed no additional increase; however, a second rise in EXP TCK reached its highest point by day 5 (3602 +/- 1190 IU.L-1). Expectedly, %MM1 and the MM1: MM3 ratio were increased after bout 1 in both groups (P < 0.01). New CK release was observed postbout 2 in both groups as indicated by an increase in %MM1 (P < 0.01), despite no increase in TCK after bout 2 for CON and a smaller CK response for EXP. CONCLUSION: Accelerated clearance of CK seems to be one factor contributing to the blunted response of this enzyme following a repeated bout of exercise.
Several authors have suggested that estrogen may serve to protect skeletal muscle from exercise-induced damage. The present study examined the effects of regularly ingesting estrogen, in the form of oral contraceptives, on postexercise muscle damage following a bench-stepping regimen. Women currently ingesting oral contraceptives (OC) were compared with eumennorheic controls (CG). All subjects performed a 50-min stepping exercise during the midluteal phase of their menstrual cycle. Muscle damage was evaluated on 2, 3, and 5 days postexercise using several established indirect indicators: perceived soreness, strength and range of motion changes, girth measurements, and creatine kinase (CK) activity. Subjects on OC reported significantly lower quadriceps soreness (p < 0.05) relative to the CG (peak soreness = 4.0 and 7.8, respectively, on a scale of 1-10 where 1 is normal and 10 is very, very sore). These results indicate that oral contraceptive use attenuates soreness following an exhaustive stepping activity but cannot support a relationship between estrogen ingestion and other indices of exercise-induced muscle damage.
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This study investigated whether a fatiguing concentric exercise performed immediately before eccentric exercise would exacerbate eccentric exercise-induced muscle damage. One arm of nine female subjects (mean +/- s: 23.3 +/- 6.7 years) performed 12 maximal eccentric actions of the elbow flexors (ECC), and the other arm performed 100 repetitions of isokinetic concentric actions of the elbow flexors followed by the same eccentric exercise (CON-ECC). The two exercise regimens (ECC and CON-ECC) were separated by 2 weeks and presented in a counterbalanced order. Changes in muscle soreness level, maximal isometric force generation, relaxed and flexed elbow joint angle, upper arm circumference and plasma creatine kinase activity were compared between the ECC and CON-ECC conditions. All measures changed significantly after both ECC and CON-ECC; however, there were significant differences in the changes between the conditions. A lower level of soreness, a faster recovery of maximal isometric force generation, a smaller decrease in relaxed elbow joint angle and a smaller increase in upper arm circumference and creatine kinase activity were evident after the CON-ECC condition compared to the ECC condition. Thus, it would seem that muscle damage was attenuated by performance of previous concentric exercise. An additional experiment using a different group of subjects (n = 5) showed that warm-up exercise before the eccentric exercise also attenuated eccentric exercise-induced muscle damage.
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High-force eccentric exercise induces neuromuscular dysfunction and may augment the cardiovascular response to exercise. This investigation sought to determine whether changes in strength and sense of force following high-force eccentric exercise alter heart rate and blood pressure responses during isometric contractions. Subjects (4F,6M) performed 50 maximum resistance eccentric actions with one arm (ECC arm). Contractions at 10% of the ECC arm maximum were held for 7 min on two pre-exercise days. The force output perceived to be the same as 10% of the pre-exercise maximum was determined using a force matching task. This force, 35.6, 27.2, and 21.1% lower on days 1, 3, and 5 post-exercise, was held during isometric contractions on these days, respectively. Despite a lowering of absolute contraction force, heart rate (P < 0.05) and blood pressure (P < 0.001) responses during contractions using the ECC arm were consistently elevated relative to the control arm. However, subjects perceived that they were exerting forces similar to those achieved before eccentric exercise-induced neuromuscular dysfunction. These findings suggest that perceived effort following strength loss induced by mechanically stressful exercise dictates the cardiovascular responses during isometric contractions.
It is estimated that most individuals are not ingesting sufficient amounts of chromium in their diets. Although there is little information on chromium intake in athletes, many athletes ingest more calories than do non-athletes so their chromium intake should be adequate. However, athletes who restrict calories to maintain low bodyweights could compromise their chromium status. Some evidence also shows that exercise may increase chromium loss into the urine. At present, it is not known whether this loss necessitates additional chromium in the diet or whether the body will increase retention in response to the loss. Chromium deficiency is thought to contribute to glucose intolerance and unhealthy blood lipid profiles. The primary function of chromium is to potentiate the effects of insulin, and thereby alter glucose, amino acid and fat metabolism. Chromium supplements have been purported to increase muscle mass and decrease body fat. However, the preponderance of evidence has not supported this claim. There is little information available on the long term use of chromium supplements, but at present, supplements within the Estimated Safe and Adequate Daily Dietary Allowance (ESADDI) level do not appear harmful. The prudent course of action for athletes would be to ingest foods rich in chromium and perhaps take a multivitamin/mineral supplement containing no more than the ESADDI of chromium.
Many types of drugs are used by athletes to improve performance. This paper reviews the literature on 3 categories of drugs: those that enhance performance as stimulants (amphetamines, ephedrine, and cocaine), those that are used to reduce tremor and heart rate (beta-blockers) and those involved in bodyweight gain or loss (anabolic-androgenic steroids, growth hormone, beta 2-agonists, and diuretics). Limitations of research on these drugs as they relate to performance enhancement are also discussed. The numerous studies that have assessed the effects of amphetamines on performance report equivocal results. This may be due to the large interindividual variability in the response to the drug and the small sample sizes used. Most studies, however, show that some individuals do improve exercise performance when taking amphetamines, which may be attributed to their role in masking fatigue. As a stimulant, ephedrine has not been found to improve performance in the few studies available. More recently, ephedrine has been purported to be effective as a fat burner and used by athletes to maintain or improve muscle mass. Although research on individuals with obesity supports the use of ephedrine for fat loss, no studies have been done on athletes. The few studies of cocaine and exercise suggest that little to no performance gains are incurred from cocaine use. Moreover, the sense of euphoria may provide the illusion of better performance when, in actuality, performance was not improved or was impaired. beta-Blockers have been found to reduce heart rate and tremor and to improve performance in sports that are not physiologically challenging but require accuracy (e.g. pistol shooting). However, there is evidence that some individuals may be high responders to beta-blockers to the extent that their heart rate response is so blunted as to impair performance. Although equivocal, several studies have reported that anabolic-androgenic steroids increase muscle size and strength. However, most studies are not well controlled and use insufficient drug doses. One recent well controlled study did find an increase in muscle mass and strength with supraphysiological doses, and the improvements were greater in participants who were also resistance training. There is little information available on the effects of growth hormone on muscle mass or performance in athletes, although data suggest that growth hormone administration does not increase muscle protein synthesis. beta 2-Agonists, such as clenbuterol and salbutamol, when administered orally appear to improve muscular strength due to their potential role in increasing muscle mass. However, studies have not been done using athletes. Diuretics results in a loss of body water and hence bodyweight that can be advantageous for sports with strict bodyweight classifications. There is insufficient evidence on possible performance decrements in the field that could result from dehydration induced by the diuretics. Overall, the most significant concern in studies of drug use is the large inter-individual variability in responses to a drug. Further studies are needed to understand why some individuals are more responsive than others and to assess whether the responses are consistent for a given individual. Most studies of drug effectiveness have not used athletes. The effectiveness of many drugs may be reduced in highly trained athletes because there is a lower margin for improvement.
There is a large inter-subject variability in serum creatine kinase (CK) response after eccentric exercise. This study examined and compared the variability of CK activity, other serum protein increases (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, aldolase, myoglobin),changes in muscle damage indicators (maximal isometric force: MIF, relaxed and flexed elbow joint angle: RANG and FANG, circumference: CIR, and muscle soreness level: SOR), and changes in magnetic resonance (MR) images. Ten male subjects (21.7 +/- 1.6 yrs) performed 24 maximal eccentric actions of the elbow flexors, and measurements except MR images were taken immediately before and after, and for 10 days after exercise. MR images were taken 7 days after exercise. A large variability in peak CK response (236 - 25,244 IU.I(-1) was found among subjects. Spearman rank-order correlation coefficients (r) revealed significant correlations of peak CK with peak serum protein levels (r = 0.79-0.95), peak changes in MIF (r = 0.73-0.79), RANG (r = 0.69), and CIR (r = 0.91). The higher the peak CK levels, the more profound the abnormality in the MR images and the larger the changes in MR signal intensity (r = 0.90-0.94). It is concluded that the large variability in CK response after exercise seems to be related to the variability in exercise-induced muscle damage.
This study examined muscle swelling and changes in inflammatory markers in the blood following eccentric exercise-induced muscle damage. Subjects (N = 14) who had not been involved in a resistance training program performed 24 maximal eccentric actions of the elbow flexors. Muscle swelling was assessed by measures of the upper arm circumference (CIR), ultrasonography (USG), and magnetic resonance imaging (MRI). Plasma concentrations of interleukin-1 alpha, interleukin-1 beta, interleukin-2, interleukin-6, tumor necrosis factor-alpha, and plasma levels of C-reactive protein, cortisol, and zinc were analyzed. Established indicators of muscle damage (maximal isometric force, range of motion, muscle soreness, and plasma creatine kinase, aspartate aminotransferase, and lactate dehydrogenase activities) were also measured. All measures, including CIR and USG, except for MRI, were assessed immediately before and after and for 5 d post-exercise. MRI was taken at pre- and 1, 3, 6, 10, 23, 31, and 58 d post-exercise. All muscle damage indicators changed significantly after exercise. A large increase in CIR (> 20 mm) was found 4-5 d after exercise, and this coincided with USG, showing an increase in muscle thickness. The echointensity of USG increased with the enlargement of the elbow flexors. MRI displayed enlargement of the biceps brachii and brachialis cross-sectional area that started at 1 d, and lasted until 23 d, post-exercise. The most profound increase in the enlargement and signal intensity of the MRI was found 3 or 6 d after exercise. However, none of the plasma levels of inflammatory makers showed significant muscle swelling, which is indicative of muscle edema, but the inflammatory responses after exercise appear to be different from those accompanying infection or tissue injury.
In [1] qnd [2] Thakor et al. describe a sequential probability ratio test (SPRT) based on threshold crossing intervals (TCI) for the discrimination of ventricular fibrillation (VF) from ventricular tachycardia (VT). However, in applying their algorithm to data from the MIT-BIH malignant arrhythmia database, we observed some overlap in the distributions of TCI for VF and VT resulting in 16% overall error rate for the discrimination. In this communication, we describe a modified SPRT algorithm, using a new feature dubbed blanking variability (BV) as the basis for discrimination. Using the MIT-BIH database, the preliminary results showed that the proposed method decreases the overall error rate to 5%.
Several nutritional modifications have been used by athletes to improve performance. Recent attention has focused on high fat diets, branched-chain amino acids, creatine, carnitine, bicarbonate and phosphate loading, and caffeine. Of these, only caffeine, which is present in food but has no known nutritional value, appears on the list of substances banned by the International Olympic Committee (IOC). While there is a theoretical basis for each of these diet manipulations to enhance performance, there are insufficient data to state unequivocally that high fat diets, branched-chain amino acids, carnitine or phosphate loading are effective. Caffeine has been found to enhance endurance performance, while creatine and bicarbonate loading were generally found to benefit short term strenuous exercise. Acute ingestion of these diet manipulations appears safe, although some, like caffeine and bicarbonate, can cause gastrointestinal disturbances or other problems in certain individuals. Long term use of high fat diets may have negative consequences on health. The safety of long term use of these diet manipulations has not been established.
Eccentric exercise results in muscle soreness, structural damage, prolonged losses in strength and range of motion, and neuromuscular dysfunction. Greater and longer lasting fatigue occurs after eccentric compared with concentric and isometric exercise. Higher forces are achieved during eccentric contractions with less ATP usage and greater increases in temperature. Although mechanisms involved in the damage and repair process are not well understood, active strain during eccentric contractions is suggested to cause the initial damage which increases over 2-3 days, followed by regeneration.
Exercise has been shown to increase indirect measures of lipid peroxidation. However, exercise and training appear to augment the body's anti-oxidant defence system. Whether this augmented defence system can keep up with the increase in lipid peroxidation with exercise is not known. Iron depletion is experienced by many athletes, especially female endurance athletes and adolescents, but iron deficiency anaemia is rare. Iron depletion could affect the ability to train and recover from strenuous exercise, but this has not been examined. There is a concern that female athletes, especially adolescents, are not ingesting sufficient calcium, and this may affect the development of peak bone mass and increase the risk of bone fractures. Further research is needed on mineral and trace mineral intake and loss in athletes. It appears that most athletes have adequate status of chromium, zinc, phosphate and magnesium. Athletes who are restricting energy intake to achieve a low body mass (for example, endurance runners), may not have adequate vitamin or mineral status. More data are needed on vitamin/mineral status of athletes from underdeveloped countries. The general recommendation for athletes is that foods rich in anti-oxidants and minerals should be ingested rather than supplements.
Performance of strenuous physical activity can increase oxygen consumption by 10- to 15-fold over rest to meet energy demands. The resulting elevated oxygen consumption produces an "oxidative stress" that leads to the generation of free radicals and lipid peroxidation. A defense system of free radical scavengers minimizes these dangerous radicals. Indirect measurements of free radicals generated during exercise include assessing products of lipid peroxidation that appear in the blood (e.g., malondialdehyde and conjugated dienes) or expired in the breath (pentane). Changes in antioxidant scavengers and associated enzymes (e.g., glutathione, tocopherol, glutathione peroxidase) also provide clues about demands on the defense system. Physical training has been shown to result in an augmented antioxidant system and a reduction in lipid peroxidation. Supplementation with antioxidants appears to reduce lipid peroxidation but has not been shown to enhance exercise performance. The "weekend athlete" may not have the augmented antioxidant defense system produced through continued training. This may make them more susceptible to oxidative stress. Whether athletes or recreational exercisers should take antioxidant supplements remains controversial. However, it is important that those who exercise regularly or occasionally ingest foods rich in antioxidants.