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Siegel, Arthur

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Siegel

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Arthur

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Siegel, Arthur
Author's Publications: search.filters.isAuthorOfPublication.a80fa391-7899-45f9-9ac6-d2cd81f7781e

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    Can pre-race aspirin prevent sudden cardiac death during marathons?
    (British Journal of Sports Medicine, 2017) Siegel, Arthur; Noakes, Timothy D
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    Reprising Ramadan-Related Angina Pectoris: A Potential Strategy for Risk Reduction
    (International Scientific Literature, Inc., 2016) Siegel, Arthur; Bhatti, Nasir A.; Wasfy, Jason
    Patient: Male, 69 Final Diagnosis: Coronary artery disease Symptoms: Angina pectoris Medication: Aspirin Clinical Procedure: Coronary artery bypass surgery Specialty: Cardiology Objective: Unusual clinical course Background: A preponderance of evidence supports short-term aspirin usage to reduce transiently increased cardiovascular risk in clinical conditions that promote acute myocardial ischemia. Case Report: We report on the case of a 69-year-old male of Muslim Indian heritage with multiple cardiovascular risk factors who experienced the onset of angina pectoris while fasting for Ramadan for more than 16 hours daily for 30 days in July 2015. While symptom free for 2 months on medical management after ending his fast, he underwent quadruple coronary artery bypass surgery for severe 4-vessel disease following an acute anterior myocardial infarction. A percutaneous coronary intervention with stent placement was subsequently required for persistent myocardial ischemia on stress-MIBI testing due to occlusion of the graft to left anterior descending artery. Presently asymptomatic, he decided to forgo fasting for Ramadan in June 2016. Conclusions: Based on this case, measures for primary cardiovascular prevention among the 1.2 billion susceptible males at similar high short-term cardiac risk while fasting for Ramadan are proposed. The value of aspirin for attenuating high short-term cardiovascular risk in clinical conditions conferring transient inflammatory stress is considered. Low-dose aspirin usage at evening meals while fasting for Ramadan is prudent for primary cardiovascular protection of males who may have non-obstructive coronary atherosclerosis to mitigate the risk for rupture of potentially vulnerable plaques. Based in part on conclusive evidence for protection of middle-aged males from first myocardial infarction in a randomized prospective primary prevention trial, this measure is concordant with recommendations from sub-specialty societies for primary cardiovascular prevention for persons at above-average risk demonstrated by validated biomarkers and from the United States Preventive Services Task Force.
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    Prerace aspirin to protect susceptible runners from cardiac arrest during marathons: is opportunity knocking?
    (BMJ Publishing Group, 2015) Siegel, Arthur
    While endurance exercise such as marathon training is cardioprotective, an increasing frequency of race-related cardiac arrests and sudden death has been observed in middle-aged men since the year 2000. An evidence-based strategy for prevention is considered based on identifying atherothrombosis as the underlying cause in this susceptible subgroup. Review of all articles on PubMed related to acute cardiac events during marathons. Male gender and the marathon compared with the half-marathon were identified as significant risk factors for race-related cardiac arrests, which events increased 2.3-fold in the latter half of a 10-year prospective registry beginning in the year 2000. There were 50 cardiac arrests in runners who were 86% male with a mean age of 42 years. The main cause of sudden death was atherosclerotic heart disease in those over the age of 40 including myocardial infarction in 12 of 13 (93%) cases over the age of 45 as assessed retrospectively. Inflammatory biomarkers predicting acute cardiac events and hypercoagulability with in vivo platelet activation were demonstrated in same-aged asymptomatic middle-aged men during marathons. Excess cardiac morbidity and mortality in middle-aged men during marathons is mediated by atherothrombosis which may render non-obstructive coronary atherosclerotic plaques vulnerable to rupture. Prerace low-dose aspirin usage is prudent to protect susceptible runners from a high, if transient, risk for cardiac arrest during races as evidence-based to prevent first myocardial infarctions in same-aged healthy men.
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    Drug-Related Hyponatremic Encephalopathy: Rapid Clinical Response Averts Life-Threatening Acute Cerebral Edema
    (International Scientific Literature, Inc., 2016) Siegel, Arthur; Forte, Sophie S.; Bhatti, Nasir A.; Gelda, Steven
    Patient: Female, 63 Final Diagnosis: Drug-induced hyponatremic encephalopathy Symptoms: Seizures • coma Medication: Hypertonic 3% saline infusion Clinical Procedure: — Specialty: Internal Medicine Objective: Unusual clinical course Background: Drug-induced hyponatremia characteristically presents with subtle psychomotor symptoms due to its slow onset, which permits compensatory volume adjustment to hypo-osmolality in the central nervous system. Due mainly to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), this condition readily resolves following discontinuation of the responsible pharmacological agent. Here, we present an unusual case of life-threatening encephalopathy due to adverse drug-related effects, in which a rapid clinical response facilitated emergent treatment to avert life-threatening acute cerebral edema. Case Report: A 63-year-old woman with refractory depression was admitted for inpatient psychiatric care with a normal physical examination and laboratory values, including a serum sodium [Na+] of 144 mEq/L. She had a grand mal seizure and became unresponsive on the fourth day of treatment with the dual serotonin and norepinephrine reuptake inhibitor [SNRI] duloxetine while being continued on a thiazide-containing diuretic for a hypertensive disorder. Emergent infusion of intravenous hypertonic (3%) saline was initiated after determination of a serum sodium [Na+] of 103 mEq/L with a urine osmolality of 314 mOsm/kg H20 and urine [Na+] of 12 mEq/L. Correction of hyposmolality in accordance with current guidelines resulted in progressive improvement over several days, and she returned to her baseline mental status. Conclusions: Seizures with life-threatening hyponatremic encephalopathy in this case likely resulted from co-occurring SIADH and sodium depletion due to duloxetine and hydrochlorothiazide, respectively. A rapid clinical response expedited diagnosis and emergent treatment to reverse life-threatening acute cerebral edema and facilitate a full recovery without neurological complications.
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    Divergent Levels of Marker Chromosomes in an hiPSC-Based Model of Psychosis
    (Elsevier, 2017) TCW, Julia; Carvalho, Claudia M.B.; Yuan, Bo; Gu, Shen; Altheimer, Alyssa N.; McCarthy, Shane; Malhotra, Dheeraj; Sebat, Jonathan; Siegel, Arthur; Rudolph, Uwe; Lupski, James R.; Levy, Deborah; Brennand, Kristen J.
    Summary In the process of generating presumably clonal human induced pluripotent stem cells (hiPSCs) from two carriers of a complex structural rearrangement, each having a psychotic disorder, we also serendipitously generated isogenic non-carrier control hiPSCs, finding that the rearrangement occurs as an extrachromosomal marker (mar) element. All confirmed carrier hiPSCs and differentiated neural progenitor cell lines were found to be mosaic. We caution that mar elements may be difficult to functionally evaluate in hiPSC cultures using currently available methods, as it is difficult to distinguish cells with and without mar elements in live mosaic cultures.
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    Late-onset Alzheimer’s disease is associated with inherent changes in bioenergetics profiles
    (Nature Publishing Group UK, 2017) Sonntag, Kai-C.; Ryu, Woo-In; Amirault, Kristopher M.; Healy, Ryan A.; Siegel, Arthur; McPhie, Donna; Forester, Brent; Cohen, Bruce
    Body-wide changes in bioenergetics, i.e., energy metabolism, occur in normal aging and disturbed bioenergetics may be an important contributing mechanism underlying late-onset Alzheimer’s disease (LOAD). We investigated the bioenergetic profiles of fibroblasts from LOAD patients and healthy controls, as a function of age and disease. LOAD cells exhibited an impaired mitochondrial metabolic potential and an abnormal redox potential, associated with reduced nicotinamide adenine dinucleotide metabolism and altered citric acid cycle activity, but not with disease-specific changes in mitochondrial mass, production of reactive oxygen species, transmembrane instability, or DNA deletions. LOAD fibroblasts demonstrated a shift in energy production to glycolysis, despite an inability to increase glucose uptake in response to IGF-1. The increase of glycolysis and the abnormal mitochondrial metabolic potential in LOAD appeared to be inherent, as they were disease- and not age-specific. Our findings support the hypothesis that impairment in multiple interacting components of bioenergetic metabolism may be a key mechanism contributing to the risk and pathophysiology of LOAD.