Arthur J Siegel

McLean Hospital · Alcohol and Drug Abuse Research Center

Background: The increased mutational burden for rare structural genomic variants in schizophrenia and other neurodevelopmental disorders has so far not yielded therapies targeting the biological effects of specific mutations. We identified two carriers (mother and son) of a triplication of the gene encoding glycine decarboxylase, GLDC, presumably...

While proficient cardiac resuscitation has improved survival following cardiac arrest during road races in Japan, this accomplishment does not address coronary artery disease as the underlying cause of an increasing frequency of cardiac arrest in middle-aged men during marathons and ironman triathlons in the United States since the year 2000. Based...

Variants in CNTNAP2, a member of the neurexin family of genes that function as cell adhesion molecules, have been associated with multiple neuropsychiatric conditions such as schizophrenia, autism spectrum disorder and intellectual disability; animal studies indicate a role for CNTNAP2 in axon guidance, dendritic arborization and synaptogenesis. We...

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 exh...

Background: Schizophrenia (SZ) is a severe mental disorder with heritability estimated at ~80%. Genetic variants in contactin-associated protein-like 2 (CNTNAP2) have been reported in SZ. This gene is critically involved in normal neuronal synchronization and myelin production. Deletions in this gene would therefore be expected to impact white matt...

Document S1. Supplemental Experimental Procedures, Figures S1?S4, and Tables S1?S4

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 confirme...

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 w...

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 discon...

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....

Neurodevelopmental disorders, such as autism spectrum disorders and schizophrenia, are complex disorders with a high degree of heritability. Genetic studies have identified several candidate genes associated with these disorders, including contactin-associated protein-like 2 (CNTNAP2). Traditionally, in animal models or in vitro, CNTNAP2 has been s...

To determine the acute effects of cigarette smoking on hypothalamic-pituitary-adrenal (HPA) axis hormones and subjective states as a function of the menstrual cycle in nicotine-dependent women. Seventeen healthy nicotine-dependent women were studied during the follicular and/or luteal phase of the menstrual cycle. Because of observation of a possib...

Objectives: Prevention of sudden cardiac death is the number one clinical priority in sports cardiology. While the overall cardiovascular risk of long distance running is acknowledged as low, the frequency of cardiac arrests and sudden death has increased in middle-aged males during marathons since the year 2000. An evidence-based strategy for prot...

Objectives: While endurance exercise such as training for marathons is cardioprotective, cardiac arrests and sudden death occur in previously healthy runners during races predominantly in middle-aged males due to atherosclerotic heart disease. Recent evidence related to this problem is reviewed herein including epidemiologic studies and findings re...

Despite evidence that exercise is beneficial for serious mental illness, it continues to be an under utilized adjunct treatment strategy. Thus, the aims of this study were to examine if self-selected or volunteer exercise programs are feasible in a structured outpatient program and who might choose to participate in such a program. Individuals with...

Contemporary data for three Central American countries (Costa Rica Guatemala and Nicaragua) surveyed by the Latin American Migration Project were analyzed to determine if migration length and remittance transfers had an influence on fertility. The analysis was structured to separate societal influences on fertility attributable to migration from th...

Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant augmentation strategy for depressed men. We sought to assess the antidepressant effects of testosterone augmentation of a serotonergic antidepressant in depressed, hypogonadal men. For this study, we recruited 100 medically healthy adult men with majo...

Dysnatremia may cause life-threatening encephalopathy in marathon runners. Hypernatremia and exercise-associated hyponatremia (EAH) may manifest with mental status changes and, if untreated, progress to coma and death. We reviewed the on-site blood sodium testing and treatment in collapsed runners at the finish-line medical tent at the Boston marat...

Nalbuphine, a mixed mu-/kappa-opioid analgesic, may have potential as a new medication for the treatment of cocaine abuse. Kappa-opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and both kappa-selective and mixed mu-/kappa-opioids reduce cocaine self-administration by rhesus monkeys. Because cocaine's int...

Cited By (since 1996):7, Export Date: 23 March 2014, Source: Scopus

Exercise-associated hyponatremia (EAH) is a potentially fatal fluid imbalance largely resulting from sustained fluid intake beyond the capacity for fluid excretion during endurance exercise. Common symptoms include vomiting, confusion, altered mental status, and seizures; however, these symptoms can also be seen with hypernatremic encephalopathy, m...

We measured analytes in collapsed Boston Marathon runners to compare with changes in asymptomatic runners. Of collapsed runners at the 2007 marathon, 18.2% had a measurable cardiac troponin T (cTnT) value with a mean postrace level of 0.017 ng/mL (0.017 microg/L; SD, 0.02 ng/mL [0.02 microg/L]). Three subjects had cTnT values above the cutoff (0.10...

Although the primary cause of exercise-associated hyponatremia (EAH) is relative overconsumption of fluids beyond the kidneys' ability to excrete excess fluid, the mechanisms limiting maximum renal excretory ability during exercise remain to be elucidated. The objective of the study was to: 1) perform a comprehensive evaluation of the endocrine sec...

Smoking one cigarette produces rapid nicotine dose-related increases in hypothalamic-pituitary-adrenal (HPA) axis hormones, mood, and heart rate, but relatively little is known about the effects of smoking several cigarettes successively. Twenty-four healthy adult men who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DS...

Hyponatremia (serum sodium concentration < 136 mEq/L) is a prevalent and potentially dangerous medical comorbidity in psychiatric patients. MEDLINE was used to identify peer-reviewed publications that described the role of arginine vasopressin (AVP) in the pathogenesis of hyponatremia, the presentation and treatment of hyponatremia in psychiatric p...

Exercise-associated hyponatremia (EAH), as defined by a blood sodium concentration [Na+] less than 135 mmol/L, may lead to hypotonic encephalopathy with fatal cerebral edema. Understanding the pathogenetic role of antidiuresis may lead to improved strategies for prevention and treatment. Normonatremic marathon runners were tested pre- and post-race...

Nalbuphine (Nubain) is a mixed action mu-kappa agonist used clinically for the management of pain. Nalbuphine and other mu-kappa agonists decreased cocaine self-administration in preclinical models. Cocaine stimulates the hypothalamic-pituitary-adrenal (HPA) axis, but the effects of nalbuphine on the HPA axis are unknown. Analgesic doses (5 and 10...

Exercise-associated hyponatraemia (EAH) is an acute-onset imbalance in the tonicity of extracellular fluids during or after endurance exercise which results in a blood sodium concentration <135 mmol/L. Both excessive fluid intake and a concurrent decrease in urine formation contribute to this rapid-onset, predominantly dilutional, decrease in serum...

Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participant...

We report changes in cardiac troponin-T (TnT) and a new plasma stroke biomarker panel (D-dimer, B-natriuretic peptide [BNP], matrix metalloproteinase-9 [MMP-9], S-100 b, Biosite Diagnostics, San Diego, CA) in 30 nonprofessional marathon runners before and immediately after the 2005 Boston Marathon. Following competition, there was a statistically s...

Exercise-associated hyponatremia (EAH) has emerged in recent years as a life-threatening complication of endurance sports that may lead to fatal cerebral and pulmonary edema. Defined as a serum sodium concentration <135 mEq/L (1 mEq/L = 1 mmol/L), symptomatic EAH is a dilutional hyponatremia with abnormal fluid retention mediated by decreased urine...

We used the ADVIA 2120 Hematology System (Bayer HealthCare, Diagnostics Division, Tarrytown, NY) to study the effects of vigorous exercise on CBC count, WBC differential, RBC fragmentation, and platelet activation parameters in 32 healthy participants in a 26.2-mile (42.2-km) marathon. The runners demonstrated increases in hematocrit and platelet c...

The acute effects of smoking a low- or high-nicotine cigarette on hypothalamic-pituitary-adrenal (HPA) hormones, subjective responses, and cardiovascular measures were studied in 20 healthy men who met American Psychiatric Association Diagnostic and Statistical Manual IV criteria for nicotine dependence. Within four puffs (or 2 min) after cigarette...

Kappa opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and reduce cocaine self-administration by rhesus monkeys. We compared the cardiovascular and subjective effects of acute doses of the mu/kappa opioid nalbuphine alone (5 mg/70 kg, intravenous (i.v.)), with cocaine alone (0.2 mg/kg, i.v.), and with nal...

Recommendations for prevention and treatment of medical emergencies in participants in marathon races center on maintenance of adequate hydration status and administration of fluids. Recently, new recommendations for fluid replacement for marathon runners were promulgated by medical and athletic societies. These new guidelines encourage runners to...

Context.—Recommendations for prevention and treatment of medical emergencies in participants in marathon races center on maintenance of adequate hydration status and administration of fluids. Recently, new recommendations for fluid replacement for marathon runners were promulgated by medical and athletic societies. These new guidelines encourage ru...

Cocaine and nicotine have a number of similar behavioral and neurobiological effects. This study compared the acute effects of cocaine and cigarette smoking on luteinizing hormone (LH), testosterone (T), and prolactin. Twenty-four men who met American Psychiatric Association Diagnostic and Statistical Manual criteria for cocaine abuse or nicotine d...

Prostate-specific antigen (PSA) is an important tumor marker for the most frequently diagnosed cancer in the United States. A major limitation of this marker is falsely elevated results in patients who are found not to have prostate cancer. The effects of vigorous physical exertion on PSA concentrations are controversial. To determine the effects o...

Cocaine abuse is associated with increased rates of infections, including human immunodeficiency virus, and cocaine has immunomodulatory effects in experimental animal and cellular models. When challenged by antigens, tissues release cytokine polypeptides that signal a complex balance of cellular and humoral immune responses. Placement of indwellin...

Context.—Prostate-specific antigen (PSA) is an important tumor marker for the most frequently diagnosed cancer in the United States. A major limitation of this marker is falsely elevated results in patients who are found not to have prostate cancer. The effects of vigorous physical exertion on PSA concentrations are controversial. Objective.—To det...

Testosterone supplementation may produce antidepressant effects in men, but until recently it has required cumbersome parenteral administration. In an 8-week randomized, placebo-controlled trial, the authors administered a testosterone transdermal gel to men aged 30-65 who had refractory depression and low or borderline testosterone levels. Of 56 m...

Participants in marathon races may require medical attention and the performance of laboratory assays. We report the changes in basic biochemical parameters, cardiac markers, CBC counts, and WBC differentials observed in participants in a marathon before, within 4 hours, and 24 hours after a race. The concentrations of glucose, total protein, album...

Participants in marathon races may require medical attention and the performance of laboratory assays. We report the changes in basic biochemical parameters, cardiac markers, CBC counts, and WBC differentials observed in participants in a marathon before, within 4 hours, and 24 hours after a race. The concentrations of glucose, total protein, album...

Exertional collapse in endurance athletes during competition is potentially lifethreatening. Beyond dysregulation of body temperature, which can be readily diagnosed and treated based on physical examination, changes in intravascular volume and tonicity of extracellular fluids may result in hyponatremic encephalopathy with acute cerebral edema. As...

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...

Although increasing levels of regular physical activity are incrementally cardioprotective,(1,2) prolonged strenuous exercise such as marathon running may trigger acute myocardial infarction(3) and sudden cardiac death.(4,5) The mechanism of such events is not well understood but may be due to hemodynamic, vasoconstrictive, and prothrombotic effect...

In contrast to nonspecific elevations of myoglobin and creatine kinase-MB (CK-MB) in athletes due to exertional rhabdomyolysis of trained skeletal muscle.(1,2) reported increases in cardiospecific troponins after competition may indicate silent injury to the myocardium.(3-8) We therefore undertook serial testing of multiple cardiac markers used to...

Cocaine stimulates luteinizing hormone (LH) release in rhesus monkeys and in men, but its effects on LH in women are unknown. Cocaine (0.2 and 0.4 mg/kg i.v.) was administered to groups of follicular and luteal phase women (N = 22) and to men (N = 12) to examine the influence of gender and menstrual cycle phase on cocaine and LH interactions. All s...

Cocaine stimulates luteinizing hormone (LH) release in rhesus monkeys and in men, but its effects on LH in women are unknown. Cocaine (0.2 and 0.4 mg/kg i.v.) was administered to groups of follicular and luteal phase women (N = 22) and to men (N = 12) to examine the influence of gender and menstrual cycle phase on cocaine and LH interactions. All s...

Mechanisms that mediate cocaine-induced cardiovascular events following vasoconstriction are incompletely understood. To examine the effects of cocaine in moderate doses on hematologic and hemostatic parameters that influence blood viscosity and thrombotic potential. Changes in hemoglobin concentration, hematocrit, and red blood cell counts were me...

Preclinical and clinical studies suggest that females may be less vulnerable to cocaine's toxic effects than males. The pharmacokinetics of intravenous cocaine (0.2 and 0.4 mg/kg) were measured in 12 men and 22 women with a history of cocaine abuse, matched with respect to age and body mass index (BMI). Women were studied during the follicular and...

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 as...

Psychotropic drugs, as well as some psychiatric disorders, can produce neurotoxic and life-threatening abnormalities of water and electrolyte balance that require prompt and appropriate medical intervention. Compulsive fluid intake by psychotic patients (primary polydipsia) can produce delirium due to water intoxication with hyponatremia. Several p...

The purpose of this study was to determine the covariance between plasma cocaine and ACTH pharmacokinetics. Twelve healthy male occasional cocaine users participated in a double blind study. Intravenous cocaine (0.2 mg/kg) or placebo was infused over 1 min, and samples for cocaine, ACTH and cortisol analysis were collected at 2, 4, 8, 12, 16, 20, 3...

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...

The possibly limited adverse effects of risperidone encourage interest in its use in geriatric patients. Medical records of 122 hospitalized psychogeriatric patients (> or = 65 years old) newly treated with risperidone were reviewed and scored for indications, doses, and effects of this novel neuroleptic. Subjects (83 women, 39 men), mean +/- SD ag...

C a 6-fold increase in the absolute incidence of exercise-related sudden cardiac death in middle-aged men compared with younger men, Thompson's1 conclusion that vigorous physical activity transiently increases the risk of acute cardiac events agrees with relative risk analysis for a triggering effect of myocardial infarction during exercise.2 3 Exp...

The authors review their experience with transfers of hospitalized psychiatric inpatients to general hospitals because of adverse drug reactions (ADRs). A total of 29 medical transfers related to ADRs were found in a review of 10,994 psychiatric inpatient admissions that occurred in a 30-month period between 1990 and 1993 (0.264%). Most cases invol...

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...

Elevated cardiac enzyme values in asymptomatic marathon runners after competition can arise from skeletal muscle through exertional rhabdomyolysis, silent injury to the myocardium, or a combined tissue source. Peak post-race levels of the MB isoenzyme of creatine kinase are similar to values in patients with acute myocardial infarction. Previously...

Elevations of the MB isoenzyme of creatine kinase (CK-MB) in serum of endurance trained athletes may quantitatively resemble findings in patients with acute myocardial infarction. This creates a diagnostic dilemma when endurance trained athletes, such as runners, are evaluated for cardiorespiratory symptoms or heat injury during or after races. Ser...

Elevations of the MB isoenzyme of creatine kinase (CK-MB) in serum of endurance trained athletes may quantitatively resemble findings in patients with acute myocardial infarction. This creates a diagnostic dilemma when endurance trained athletes, such as runners, are evaluated for cardiorespiratory symptoms or heat injury during or after races. Ser...

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 unders...