While increasing levels of recreational sports participation are incrementally cardioprotective, ... more While increasing levels of recreational sports participation are incrementally cardioprotective, strenuous physical exertion transiently increases the risk for acute cardiac events including sudden death. The frequency of marathon-related cardiac arrests has been increasing since the year 2000 mainly in middle-aged men due to atherosclerotic coronary artery disease. Coronary artery calcium scores and post-race cardiac biomarkers are recommended to identify runners who might benefit the most from pre-race aspirin for enhanced primary prevention.
The COVID-19 pandemic has decreased life-expectancy in the United States in 2021, causing over on... more The COVID-19 pandemic has decreased life-expectancy in the United States in 2021, causing over one million deaths especially in elderly persons with medical co-morbidities. While now waning, this epidemic continues to cause more than 500 fatalities per week mostly in individuals over70 years of age who are unvaccinated. Since viral epidemics have been shown to increase mortality due to atherosclerotic coronary heart disease and low-dose aspirin has been shown to reduce first myocardial infarctions by 44%, we recommend consideration of expanding the use of aspirin for primary cardiovascular prevention to reduce the cardiac morbidity and excess mortality associated with COVID-19 infections. Such aspirin use may be seen as especially appropriate for vulnerable elderly persons who qualify for treatment with Paxlovid (ritonavir-boosted nirmatrelvir) but are currently excluded for such in primary prevention guidelines of subspecialty societies. The rationale for this approach is further s...
Elevated serum creatine kinase MB isoenzyme (CK-MB) activity in marathon runners after competitio... more Elevated serum creatine kinase MB isoenzyme (CK-MB) activity in marathon runners after competition may arise from injury to skeletal muscle, myocardium, or a combined tissue source. Normal radionuclide myocardial scintigraphy and the selective increase in skeletal muscle CK-MB reported in such runners strongly suggest a peripheral source. To understand this biochemical finding, the authors examined gastrocnemius muscles by electron microscopy from 40 male marathon runners at intervals after competition and from 12 male nonrunners. Muscle from runners showed post-race ultrastructural changes of focal fiber injury and repair: intra- and extracellular edema with endothelial injury; myofibrillar lysis, dilation and disruption of the T-tubule system, and focal mitochondrial degeneration without inflammatory infiltrate (1-3 days). The mitochondrial and myofibrillar damage showed progressive repair by 3-4 weeks. Late biopsies showed central nuclei and satellite cells characteristic of the ...
Cocaine stimulates the release of adrenocorticotropin hormone (ACTH) and cortisol in both clinica... more Cocaine stimulates the release of adrenocorticotropin hormone (ACTH) and cortisol in both clinical and preclinical studies, but the temporal sequence of cocaine-induced changes in other hormones and affective states is unclear. The purpose of this study was to analyze the pattern and temporal concordance of cocaine-induced changes in ACTH, cortisol, dihydroepiandrosterone (DHEA), epinephrine, heart rate and subjective reports of euphoria. Six healthy men who met Diagnostic and Statistical Manual-IV (DSM-IV) criteria for cocaine abuse provided informed consent for participation. Cocaine (0.4 mg/kg) or saline placebo was infused intravenously over 1 min under double-blind conditions. Euphoria, ACTH, epinephrine and heart rate increased significantly within 8 to 12 min after i.v. cocaine administration in all subjects (P<0.01-0.001). Moreover, the increases in euphoria, ACTH, epinephrine and heart rate each were significantly correlated with increases in plasma cocaine levels (P<0.001). Euphoria increased significantly within 2 min after i.v. cocaine injection, as plasma cocaine levels were increasing, and peak euphoria was reported at 10 min (P<0.001). Peak ACTH values were measured at 8.7 (+/-0.8) min after cocaine injection (P<0.01). Peak levels of epinephrine were measured at 10 (+/-1) min after cocaine injection (P<0.05). Peak increases in heart rate occurred at 11.7 (+/-1.1) min after cocaine injection (P<0.05). Peak levels of cortisol and DHEA were measured at 36 (+/-4.0) and 28.7 (+/-4.3) min after cocaine injection (P<0.01 and P<0.01). The temporal concordance between cocaine-induced stimulation of ACTH, epinephrine and subjective euphoria suggests that these hormonal changes are significant concomitants of the abuse-related effects of cocaine. The similarities between these hormonal profiles, the subjective effects of cocaine and the effects of "stress" are discussed.
Recent epidemiologic studies confirm that heavy physical exertion can trigger myocardial infarcti... more Recent epidemiologic studies confirm that heavy physical exertion can trigger myocardial infarction. Diagnosis of acute myocardial injury in marathon runners is complicated by elevations of serum creatine kinase MB isoenzyme activity in asymptomatic finishers with normal post-race infarct-avid myocardial scintigraphy. Such isoenzyme elevations can arise from exertional rhabdomyolysis of skeletal muscle biochemically altered by training, from silent injury to the myocardium or from a combined tissue source. To assess silent myocardial cell necrosis in marathon runners, we performed quantitative anti-myosin myocardial scintigraphy after competition with serum immunoassays for creatine kinase MB isoenzyme and troponin T. Therefore, 8 male marathon runners with a mean age of 52 years underwent quantitative antimyosin myocardial scintigraphy immediately following the 1988 and 1993 Boston Marathons. Serum immunoassays for creatine kinase MB isoenzyme by a chemiluminescent method (CLIA) and troponin T by an enzyme-linked immunosorbent assay were performed in 4 runners after the 1993 race. Quantitative antimyosin myocardial scintigraphy was normal in all runners including 3 who participated after both races 5 years apart. Post-race serum creatine kinase MB isoenzyme and/or troponin T levels were in a range otherwise diagnostic of acute myocardial infarction in 3 of 4 subjects. Normal quantitative antimyosin myocardial imaging in asymptomatic marathon runners excludes silent myocardial cell necrosis as the source of elevated serum protein markers. Such imaging may be the optimal diagnostic modality for detection of myocardial cell necrosis in symptomatic athletes when results of conventional testing are inconclusive.
Prolonged strenuous exercise may trigger acute myocardial infarction (AMI), as exemplified by the... more Prolonged strenuous exercise may trigger acute myocardial infarction (AMI), as exemplified by the occurrence of sudden cardiac death during marathon running. Serum creatine kinase MB (CK-MB) may be elevated in asymptomatic marathon runners after competition from exertional rhabdomyolysis of skeletal muscle altered by training, limiting its utility for evaluating acute cardiac injury in such athletes. Myoglobin and CK-MB2 isoform levels are emerging as earlier markers of AMI and troponin subunits as more specific than serum CK-MB mass. We tested runners before and sequentially after the 1995 Boston Marathon for conventional and newer markers including myoglobin, CK-MB mass and isoforms, cardiac troponin T, and cardiac troponin I using standard laboratory methods and rapid format assays if available. The mean serum values for myoglobin, CK-MB mass, CK-MB/myoglobin rapid panel tests, and CK-MB2 isoforms were normal or negative pre-race and elevated or positive 4 and 24 h after competition. These markers lack specificity for acute cardiac injury in trained runners. While the mean serum values for cardiac troponins T and I remained normal, 9 of 45 runners (20%) showed an increase in subunits by first-generation assays. All runners remained asymptomatic for cardiac disease and completed subsequent marathons 1 year later, making reversible myocardial injury or stunning unlikely. Elevated values of serum markers for AMI, including first-generation assays for both troponin subunits should be interpreted with caution in trained runners.
Diabetic ketoacidosis may be the first manifestation of diabetes, particularly in the young patie... more Diabetic ketoacidosis may be the first manifestation of diabetes, particularly in the young patient. In most instances, a careful history will disclose the presence of diabetic symptoms for several days or months. Whereas a relative resistance to insulin is a well-recognized feature of diabetic acidosis, such resistance is usually of moderate intensity and only transient. We report an unusual case of diabetic ketoacidosis because it occurred in a previously unknown diabetic with documented absence of glycosuria on the preceding day that required 9,200 units of insulin to achieve metabolic control. Most important, it was associated with a fatal brain-stem infarction. Patient Summary A 26-year-old, gravida 2, para 0, married woman was admitted for threatened abortion. Review of systems did not suggest any evidence of diabetes. Repeated urine testing for sugar was negative. There was no family history of diabetes mellitus. Physical examination was unremarkable except for scant bleeding through a
Cocaine is a potent vasoconstrictor that has been shown to alter hemoglobin, hematocrit, and red ... more Cocaine is a potent vasoconstrictor that has been shown to alter hemoglobin, hematocrit, and red blood cell counts in both animals and humans. The present study evaluated whether cocaine administration induces splenic constriction in men and whether spleen-volume changes temporally correlate with altered hematologic parameters. Spleen volume was assessed at baseline and after cocaine administration (0.4 mg/kg) by using magnetic resonance imaging. A group of five healthy men, aged 31 ± 2 (SE) yr and reporting occasional cocaine use (13 ± 5 lifetime exposures), participated. Cocaine reduced spleen volume by 20 ± 4% ( P < 0.03) 10 min after drug administration. Spleen volume returned to normal (101 ± 3% baseline) within 35 min after cocaine administration, indicating that the reduction is a transient phenomenon. In subjects administered cocaine from whom blood samples were obtained ( n = 3), cocaine increased hemoglobin levels, hematocrit, and red blood cell count to 104.5 ± 0.9, 10...
While increasing levels of recreational sports participation are incrementally cardioprotective, ... more While increasing levels of recreational sports participation are incrementally cardioprotective, strenuous physical exertion transiently increases the risk for acute cardiac events including sudden death. The frequency of marathon-related cardiac arrests has been increasing since the year 2000 mainly in middle-aged men due to atherosclerotic coronary artery disease. Coronary artery calcium scores and post-race cardiac biomarkers are recommended to identify runners who might benefit the most from pre-race aspirin for enhanced primary prevention.
The COVID-19 pandemic has decreased life-expectancy in the United States in 2021, causing over on... more The COVID-19 pandemic has decreased life-expectancy in the United States in 2021, causing over one million deaths especially in elderly persons with medical co-morbidities. While now waning, this epidemic continues to cause more than 500 fatalities per week mostly in individuals over70 years of age who are unvaccinated. Since viral epidemics have been shown to increase mortality due to atherosclerotic coronary heart disease and low-dose aspirin has been shown to reduce first myocardial infarctions by 44%, we recommend consideration of expanding the use of aspirin for primary cardiovascular prevention to reduce the cardiac morbidity and excess mortality associated with COVID-19 infections. Such aspirin use may be seen as especially appropriate for vulnerable elderly persons who qualify for treatment with Paxlovid (ritonavir-boosted nirmatrelvir) but are currently excluded for such in primary prevention guidelines of subspecialty societies. The rationale for this approach is further s...
Elevated serum creatine kinase MB isoenzyme (CK-MB) activity in marathon runners after competitio... more Elevated serum creatine kinase MB isoenzyme (CK-MB) activity in marathon runners after competition may arise from injury to skeletal muscle, myocardium, or a combined tissue source. Normal radionuclide myocardial scintigraphy and the selective increase in skeletal muscle CK-MB reported in such runners strongly suggest a peripheral source. To understand this biochemical finding, the authors examined gastrocnemius muscles by electron microscopy from 40 male marathon runners at intervals after competition and from 12 male nonrunners. Muscle from runners showed post-race ultrastructural changes of focal fiber injury and repair: intra- and extracellular edema with endothelial injury; myofibrillar lysis, dilation and disruption of the T-tubule system, and focal mitochondrial degeneration without inflammatory infiltrate (1-3 days). The mitochondrial and myofibrillar damage showed progressive repair by 3-4 weeks. Late biopsies showed central nuclei and satellite cells characteristic of the ...
Cocaine stimulates the release of adrenocorticotropin hormone (ACTH) and cortisol in both clinica... more Cocaine stimulates the release of adrenocorticotropin hormone (ACTH) and cortisol in both clinical and preclinical studies, but the temporal sequence of cocaine-induced changes in other hormones and affective states is unclear. The purpose of this study was to analyze the pattern and temporal concordance of cocaine-induced changes in ACTH, cortisol, dihydroepiandrosterone (DHEA), epinephrine, heart rate and subjective reports of euphoria. Six healthy men who met Diagnostic and Statistical Manual-IV (DSM-IV) criteria for cocaine abuse provided informed consent for participation. Cocaine (0.4 mg/kg) or saline placebo was infused intravenously over 1 min under double-blind conditions. Euphoria, ACTH, epinephrine and heart rate increased significantly within 8 to 12 min after i.v. cocaine administration in all subjects (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01-0.001). Moreover, the increases in euphoria, ACTH, epinephrine and heart rate each were significantly correlated with increases in plasma cocaine levels (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Euphoria increased significantly within 2 min after i.v. cocaine injection, as plasma cocaine levels were increasing, and peak euphoria was reported at 10 min (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Peak ACTH values were measured at 8.7 (+/-0.8) min after cocaine injection (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). Peak levels of epinephrine were measured at 10 (+/-1) min after cocaine injection (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Peak increases in heart rate occurred at 11.7 (+/-1.1) min after cocaine injection (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Peak levels of cortisol and DHEA were measured at 36 (+/-4.0) and 28.7 (+/-4.3) min after cocaine injection (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01 and P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). The temporal concordance between cocaine-induced stimulation of ACTH, epinephrine and subjective euphoria suggests that these hormonal changes are significant concomitants of the abuse-related effects of cocaine. The similarities between these hormonal profiles, the subjective effects of cocaine and the effects of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;stress&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; are discussed.
Recent epidemiologic studies confirm that heavy physical exertion can trigger myocardial infarcti... more Recent epidemiologic studies confirm that heavy physical exertion can trigger myocardial infarction. Diagnosis of acute myocardial injury in marathon runners is complicated by elevations of serum creatine kinase MB isoenzyme activity in asymptomatic finishers with normal post-race infarct-avid myocardial scintigraphy. Such isoenzyme elevations can arise from exertional rhabdomyolysis of skeletal muscle biochemically altered by training, from silent injury to the myocardium or from a combined tissue source. To assess silent myocardial cell necrosis in marathon runners, we performed quantitative anti-myosin myocardial scintigraphy after competition with serum immunoassays for creatine kinase MB isoenzyme and troponin T. Therefore, 8 male marathon runners with a mean age of 52 years underwent quantitative antimyosin myocardial scintigraphy immediately following the 1988 and 1993 Boston Marathons. Serum immunoassays for creatine kinase MB isoenzyme by a chemiluminescent method (CLIA) and troponin T by an enzyme-linked immunosorbent assay were performed in 4 runners after the 1993 race. Quantitative antimyosin myocardial scintigraphy was normal in all runners including 3 who participated after both races 5 years apart. Post-race serum creatine kinase MB isoenzyme and/or troponin T levels were in a range otherwise diagnostic of acute myocardial infarction in 3 of 4 subjects. Normal quantitative antimyosin myocardial imaging in asymptomatic marathon runners excludes silent myocardial cell necrosis as the source of elevated serum protein markers. Such imaging may be the optimal diagnostic modality for detection of myocardial cell necrosis in symptomatic athletes when results of conventional testing are inconclusive.
Prolonged strenuous exercise may trigger acute myocardial infarction (AMI), as exemplified by the... more Prolonged strenuous exercise may trigger acute myocardial infarction (AMI), as exemplified by the occurrence of sudden cardiac death during marathon running. Serum creatine kinase MB (CK-MB) may be elevated in asymptomatic marathon runners after competition from exertional rhabdomyolysis of skeletal muscle altered by training, limiting its utility for evaluating acute cardiac injury in such athletes. Myoglobin and CK-MB2 isoform levels are emerging as earlier markers of AMI and troponin subunits as more specific than serum CK-MB mass. We tested runners before and sequentially after the 1995 Boston Marathon for conventional and newer markers including myoglobin, CK-MB mass and isoforms, cardiac troponin T, and cardiac troponin I using standard laboratory methods and rapid format assays if available. The mean serum values for myoglobin, CK-MB mass, CK-MB/myoglobin rapid panel tests, and CK-MB2 isoforms were normal or negative pre-race and elevated or positive 4 and 24 h after competition. These markers lack specificity for acute cardiac injury in trained runners. While the mean serum values for cardiac troponins T and I remained normal, 9 of 45 runners (20%) showed an increase in subunits by first-generation assays. All runners remained asymptomatic for cardiac disease and completed subsequent marathons 1 year later, making reversible myocardial injury or stunning unlikely. Elevated values of serum markers for AMI, including first-generation assays for both troponin subunits should be interpreted with caution in trained runners.
Diabetic ketoacidosis may be the first manifestation of diabetes, particularly in the young patie... more Diabetic ketoacidosis may be the first manifestation of diabetes, particularly in the young patient. In most instances, a careful history will disclose the presence of diabetic symptoms for several days or months. Whereas a relative resistance to insulin is a well-recognized feature of diabetic acidosis, such resistance is usually of moderate intensity and only transient. We report an unusual case of diabetic ketoacidosis because it occurred in a previously unknown diabetic with documented absence of glycosuria on the preceding day that required 9,200 units of insulin to achieve metabolic control. Most important, it was associated with a fatal brain-stem infarction. Patient Summary A 26-year-old, gravida 2, para 0, married woman was admitted for threatened abortion. Review of systems did not suggest any evidence of diabetes. Repeated urine testing for sugar was negative. There was no family history of diabetes mellitus. Physical examination was unremarkable except for scant bleeding through a
Cocaine is a potent vasoconstrictor that has been shown to alter hemoglobin, hematocrit, and red ... more Cocaine is a potent vasoconstrictor that has been shown to alter hemoglobin, hematocrit, and red blood cell counts in both animals and humans. The present study evaluated whether cocaine administration induces splenic constriction in men and whether spleen-volume changes temporally correlate with altered hematologic parameters. Spleen volume was assessed at baseline and after cocaine administration (0.4 mg/kg) by using magnetic resonance imaging. A group of five healthy men, aged 31 ± 2 (SE) yr and reporting occasional cocaine use (13 ± 5 lifetime exposures), participated. Cocaine reduced spleen volume by 20 ± 4% ( P < 0.03) 10 min after drug administration. Spleen volume returned to normal (101 ± 3% baseline) within 35 min after cocaine administration, indicating that the reduction is a transient phenomenon. In subjects administered cocaine from whom blood samples were obtained ( n = 3), cocaine increased hemoglobin levels, hematocrit, and red blood cell count to 104.5 ± 0.9, 10...
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