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Focuses on topics on hydration and its disorders to be presented by several speakers at the 35th American Medical Athletic Association Medical Symposium at the Boston Marathon in Massachusetts in 2006. Scott Montain on strategies for optimal fluid replacement during marathon running; P.Z. Pearce on his experience in diagnosis and treatment of the disorders in collapsed Ironman-triathlon triathletes; Review of studies on the pathogenesis of dehydration and hyponatremia.

A letter to the editor is presented in response to the article "Experience Tells Us" by John C. Hagan III.

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 determine the effects of marathon running on PSA levels. Design.--Measurement of total and free PSA levels in the sera of participants in a marathon before and within 4 and 24 hours after the race. Results.--None of the participants had elevated total PSA levels before the race. Although we found no statistically significant changes in average total or free PSA concentrations at either time point, after the marathon, 2 (11%) of 18 runners had total PSA concentrations outside the standard reference range. Changes in total PSA levels did not correlate with age or prerace PSA concentrations. Free PSA levels were not statistically significantly changed after the race and did not allow a reliable determination of exercise-induced PSA elevations. Conclusions.--Although it may not be necessary for men to abstain from exercise involving running before blood draws for PSA analysis, elevated PSA concentrations may be observed in some individuals after participation in a major sporting event. In these cases, repeat measurements should be considered at a time significantly removed from such exercise. [ABSTRACT FROM AUTHOR]

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 resulting in reduced availability of the N -methyl-D-aspartate receptor coagonists glycine and D-serine and N -methyl-D-aspartate receptor hypofunction. Both carriers had a diagnosis of a psychotic disorder. We carried out two double-blind, placebo-controlled clinical trials of N -methyl-D-aspartate receptor augmentation of psychotropic drug treatment in these two individuals. Glycine was used in the first clinical trial, and D-cycloserine was used in the second one. Glycine or D-cycloserine augmentation of psychotropic drug treatment each improved psychotic and mood symptoms in placebo-controlled trials. These results provide two independent proof-of-principle demonstrations of symptom relief by targeting a specific genotype and explicitly link an individual mutation to the pathophysiology of psychosis and treatment response. [ABSTRACT FROM AUTHOR]

Abstract: 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 interactions with the hypothalamic-pituitary-adrenal and (HPA) hypothalamic-pituitary-gonadal (HPG) axes may contribute to its reinforcing properties, we examined the effects of cocaine alone and in combination with nalbuphine. Neuroendocrine effects of a single dose of cocaine alone (0.2 mg/kg, IV), with nalbuphine (5 mg/70 kg, IV)+cocaine (0.2 mg/kg, IV) in combination were compared in seven adult men (ages 18–35) who met DSM-IV criteria for current cocaine abuse. Cocaine alone, and in combination with nalbuphine was administered on separate test days under placebo-controlled, double blind conditions. Cocaine stimulated ACTH, cortisol, and LH, whereas cocaine+nalbuphine in combination produced a smaller increase in ACTH, and decreased cortisol and LH. Thus it appears that nalbuphine attenuated cocaine''s effects on ACTH, cortisol, and LH. These data are consistent with our earlier report that nalbuphine modestly attenuated cocaine''s positive subjective effects, and that the subjective and cardiovascular effects of cocaine+nalbuphine in combination were not additive. [Copyright &y& Elsevier]

Abstract: 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 mg/70 kg) of IV nalbuphine were administered to healthy male cocaine abusers, and plasma levels of PRL, ACTH and cortisol were measured before and at 10, 17, 19, 23, 27, 31, 35, 40, 45, 60, 75, 105, and 135 min after nalbuphine administration. Subjective effects were measured on a Visual Analog Scale (VAS). Prolactin (PRL) increased significantly within 17 min (P =.04) and reached peak levels of 22.1±7.1 ng/ml and 54.1±11.3 at 60 min after low and high dose nalbuphine administration, respectively. VAS reports of “Sick,” “Bad” and “Dizzy” were significantly higher after 10 mg/70 kg than after 5 mg/70 kg nalbuphine (P =.05–.0001), and were significantly correlated with increases in PRL (P =.05–.0003). However, sedation and emesis were observed only after a 10 mg/70 kg dose of nalbuphine. Interestingly, ACTH and cortisol levels did not change significantly after administration of either dose of nalbuphine. Taken together, these data suggest that nalbuphine had both mu- and kappa-like effects on PRL (PRL increase) but did not increase ACTH and cortisol. [Copyright &y& Elsevier]

The acute effects of smoking a Iow- 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 smoking began, plasma nicotine levels and heart rate increased significantly (P<0.01), and peak ratings of 'high' and 'rush' on a Visual Analogue Scale were reported. Reports of 'high,' 'rush,' and 'liking' and reduction of 'craving' were significantly greater after smoking a high-nicotine cigarette than a Iow-nicotine cigarette (P<0.05). Peak plasma nicotine levels after high-nicotine cigarette smoking (23.9 ± 2.6 ng/ml) were significantly greater than after Iownicotine cigarette smoking (3.63 ± 0.59 ng/ml) (P<0.001). After smoking a Iow-nicotine cigarette, adrenocorticotropin hormone (ACTH), cortisol, dehydroepiandrosterone (DHEA), and epinephrine did not change significantly from baseline. After high-nicotine cigarette smoking began, plasma ACTH levels increased significantly above baseline within 12 min and reached peak levels of 21.88 ± 5.34 pml/l within 20 min. ACTH increases were significantly correlated with increases in plasma nicotine (r = 0.85; P < 0.0001), DHEA (r=0.66; P = 0.002), and epinephrine (r = 0.86; P < 0.0001). Cortisol and DHEA increased significantly within 20 min (P < 0.05) and reached peak levels of 424 ± 48 and 21.13 ± 2.55 ng/ml within 60 and 30 min, respectively. Thus cigarette smoking produced nicotine dose-related effects on HPA hormones and subjective and cardiovascular measures. These data suggest that activation of the HPA axis may contribute to the abuse-related effects of cigarette smoking. [ABSTRACT FROM AUTHOR]

Objective: 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. Method: Of 56 men screened, 24 (42.9%) displayed morning serum total testosterone levels of 350 ng/dl or less (normal range=270-1070). Of these men, 23 entered the study. One responded to an initial 1-week single-blind placebo period, and 22 were subsequently randomly assigned: 12 to 1% testosterone gel, 10 g/ day, and 10 to identical-appearing placebo. Each subject continued his existing antidepressant regimen. Ten subjects receiving testosterone and nine receiving placebo completed the 8-week trial. Results: The groups were closely matched on baseline demographic and psychiatric measures. Subjects receiving testosterone gel had significantly greater improvement in scores on the Hamilton Depression Rating Scale than subjects receiving placebo. These changes were noted on both the vegetative and affective subscales of the Hamilton Depression Rating Scale. A significant difference was also found on the Clinical Global Impression severity scale but not the Beck Depression Inventory. One subject assigned to testosterone reported increased difficulty with urination, suggesting an exacerbation of benign prostatic hyperplasia; no other subject reported adverse events apparently attributable to testosterone. Conclusions: These preliminary findings suggest that testosterone gel may produce antidepressant effects in the large and probably underrecognized population of depressed men with low testosterone levels. [ABSTRACT FROM AUTHOR]

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 on the high prevalence of subclinical coronary artery disease by cardiac computed tomography in endurance athletes with low conventional cardiac risk-factor profiles, we recommend coronary artery calcium scores as a more reliable and independent predictor of incident cardiac events, including death, as validated among adults aged 30-46 years. Scores of over 100 Agatston units indicate a 10-year cardiac risk of 7.5%, at which additional measures for primary prevention are recommended, including aspirin, as shown conclusively to reduce first myocardial infarctions in same-aged men in a prospective double-blind controlled trial. Targeted screening for subclinical coronary atherosclerosis with coronary artery calcium scores is prudent to guide appropriately dosed aspirin use to mitigate the increasing frequency of sports-related sudden cardiac death due to plaque rupture., (Copyright © 2018 Elsevier Inc. All rights reserved.)