Publications

Chronic distress contributes to the development of obesity and comorbid states. Stress is the disturbance of the complex dynamic equilibrium that all organisms must maintain, and is associated with activation of the Stress system comprising of the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system functions in a baseline circadian fashion and interacts with other systems of the organism to regulate a variety of behavioral, endocrine, metabolic, immune and cardiovascular functions. The experience of perceived or real uncontrollable intense and/or chronic stress (distress) may lead to several psychopathologic conditions, including anxiety, depressive and psychosomatic disorders, substance abuse, obesity and the metabolic syndrome, and osteoporosis, as well as impaired reproductive and immune functions. Developing children and adolescents are particularly vulnerable to the effects of chronic stress. Both behavioral and biological pathways are involved in the connection between chronic stress and obesity in adults and children. Emotional "comfort" eating, lack of sleep, impulsive behaviours and selection of specific foods often characterize stressed individuals. In addition to specific behaviours, dysregulation of the stress system through increased secretion of cortisol and catecholamines, especially in the evening hours, and in concert with concurrently elevated insulin concentrations, leads to development of central obesity, insulin resistance and the metabolic syndrome. In children, chronic alterations in cortisol secretion may have additional effects on cognitive and emotional development, timing of puberty and final stature. Obese children and adolescents are frequently entangled in a vicious cycle between distress, impairing self-image and distorted self-image, maintaining and worsening distress.

Abstract: Obesity has epidemic proportions in Western societies and, because of its significant association with morbidity and mortality, is a major public health issue. Excessive daytime sleepiness (EDS) and fatigue (tiredness without increased sleep propensity)–‐which have been associated with obesity‐–have a significant impact on individual well‐being and public safety. In this article, we review data that challenge the belief that sleep apnea and sleep disruption per se are the primary determinants of obesity‐related daytime sleepiness and fatigue. Specifically, it appears that obesity per se is associated with objective and subjective daytime sleepiness compared to normal‐weight controls regardless of sleep apnea and sleep loss. Indeed, obese patients without sleep apnea are sleepier compared to nonobese controls whereas within the morbidly obese, those who have high sleep efficiency at night are sleepier than those who have low sleep efficiency. In addition, in recent studies based on large random samples of the general population, the primary determinants of subjective EDS were depression and metabolic disturbances, that is, obesity/diabetes, and not sleep apnea or objective sleep disruption. Furthermore, sleepiness and fatigue are very prevalent in conditions associated with insulin resistance, for instance, the polycystic ovary syndrome (PCOS), independently of sleep apnea or obesity, or in conditions of insufficient physical activity. On the basis of these data, we propose that obesity‐related objective daytime sleepiness and fatigue are associated primarily with metabolic and psychological factors and less with sleep apnea and sleep disruption per se . Furthermore, we suggest that objective sleepiness is primarily related to metabolic factors, whereas fatigue appears to be related to psychological distress. Finally, based on data from studies in normal controls and patients with sleep disorders, we propose that the interaction of the hypothalamic‐pituitary‐adrenal (HPA) axis and proinflammatory cytokines determines the level of sleep/arousal within the 24‐h cycle, that is, “hypercortisolemia” plus hypercytokinemia is associated with low sleep efficiency and fatigue, whereas “eucortisolemia” or “hypocortisolemia” plus hypercytokinemia is associated with high sleep efficiency and objective sleepiness.

Due to their lightness and simple connectivity, steel racking systems are typically considered as “low-dissipative” structures, which is reflected in the modern seismic codes by the absence of capacity design and the adoption of low behaviour factors. This limited capability of stress redistribution significantly increases the vulnerability of racks under beyond-design seismic hazards and raises the demand for more resilient designs. Along these lines, the proposed Plastic Ovalization Strategy (POS) attempts to increase the ductility of the individual upright frames comprising the cross-aisle direction of racks, and at the same time to preserve their low-cost and easy-to-assemble nature. This is achieved by tasking the bearing failure mechanism of the diagonal bolt hole to absorb seismic deformations, while capacity design is employed to keep the rest of the structure in the elastic zone. Following a detailed discussion on the motives and basic principles of the strategy, two high-rise racking systems are designed twice by professional engineers, once using standard approaches and then by additionally employing the proposed POS rules. Finally, the two design solutions are compared by conducting a comprehensive seismic assessment, which employs a phenomenological macro-model comprising elastic elements and nonlinear springs to simulate the bearing failure mechanism.

A patient with Churg-Strauss syndrome had pulmonary lesions, vasculitis, gastrointestinal tract involvement, and leukocytosis with hypereosinophilia. A wedge section from the lung showed necrotizing granulomata filled with necrotic eosinophils and fibrinoid, and rimmed by giant cells and eosinophils. Arteries and veins of all sizes were affected with perivascular eosinophilic-rich, palisaded, giant cell granulomata with evidence of partial or complete occlusion. The patient was treated with prednisone, with excellent resolution of his symptoms. Recurrent episodes of pneumonia and wheezing responded to increased levels of prednisone plus bronchodilators and antibiotics. Cardiomyopathy developed after two years while taking prednisone. His condition has been managed with digoxin, diuretics, and increased amount of prednisone. Although our patient has shown clinical improvement in his cardiac status, objective studies show minimal resolution.

Corticotropin-releasing factor, a 41 -amino acid peptide, stimulates pituitary adrenocorticotropic hormone (ACTH) and β-endorphin secretion. Because of its selective stimulation of the corticotrope cells of the pituitary gland, and because of its relative safety, the factor offers a possible means of studying the conditions of aberrant ACTH secretion. The purpose of the present study was to characterize the hormonal responses to the releasing factor in a series of patients with Cushing's disease or the ectopic ACTH secretion syndrome (Cushing's syndrome of adrenal origin) and to explore its possible usefulness in the differential diagnosis of Cushing's disease. The authors studied 22 patients with Cushing's syndrome and 10 control subjects. Thirteen patients (ages, 19 to 62 years) had ACTH-secreting pituitary adenomas (Cushing's disease), and six patients (ages, 25 to 69 years) had nonpituitary ACTH-secreting tumors. A 5-year-old child had micronodular adrenal disease. Two patient's had Cushing's syndrome due to metastatic adrenal carcinoma. Patients in the group with untreated Cushing's disease and those in the group with untreated Cushing's syndrome due to ectopic secretion of ACTH had high evening basal plasma ACTH and cortisol concentrations. Corticotropin-releasing factor was given at a dose of 1 μg/kg of body weight at 8 PM as an intravenous bolus injection. All patients in the first group responded with elevations in plasma ACTH and cortisol. None of the patients with the ectopic ACTH syndrome responded to corticotropin-releasing factor. Three patients who were treated successfully by transsphenoidal adenomectomy had normal or nearly normal plasma ACTH and cortisol responses to corticotropin-releasing factor as early as 1 week after surgery. In these patients, glucocorticoid replacement had been discontinued at least 24 hours before testing. One of them, who had had more pituitary tissue removed than the others, had a slightly subnormal ACTH and cortisol response to the releasing factor. Unsuccessfully treated patients and those treated medically (with cyproheptadine or mitotane) or by bilateral adrenalectomy had plasma ACTH and cortisol patterns, after administration of the releasing factor, that were typical of untreated Cushing's disease. One patient, who had the ectopic ACTH syndrome and showed no response to corticotropin-releasing factor, was given metyrapone for 3 days and showed a response to the releasing factor when retested. No changes in plasma growth hormone, prolactin, lutein-izing hormone, plasma renin activity, insulin, or glucose were noted in either group of patients after administration of corticotropin-releasing factor. No endogenous corticotropin-releasing factor was detected by radioimmunoassay in plasma from any of the patients studied. The disappearance curves of exogenous corticotropin-releasing factor from plasma were similar in both groups of untreated patients (those with Cushing's disease and those with ectopic ACTH syndrome) and were within the normal range. Similarly, patients with Cushing's disease who were receiving medical therapy.

Leptin, a hormone mainly secreted from adipose tissue, communicates a metabolic signal to the adrenal gland. Ob-Receptor (Ob-R) expression was reported in rat, mice and human adrenal glands. This study intended to investigate possible differences in the Ob-R expression and distribution of Ob-R protein in human adrenal tumors as compared to normal adrenal tissue. Proliferative effects of leptin were analyzed in the human adrenocortical carcinoma cell line (NCI-H295). The full length Ob-R mRNA and the isoforms B219.1 and B219.3 could be demonstrated by RT-PCR in all adrenal tumors (n = 8), the tumor cell line (NCI-H295) and normal tissue. In contrast the Ob-R isoform B219.2 was absent in the carcinoma cell line and in most of the adrenal tumors (n = 5), whereas it was present in normal adrenals. The Ob-R protein could be demonstrated in benign and malignant adrenocortical tumors. Pheochromocytomas showed only a weak immunostaining with the human Ob-R antibody. Human leptin did not affect the proliferation or variability of adrenal tumor cells as demonstrated by [3H]-thymidine assay and WST-1 test. In conclusion, although functional leptin receptors are expressed in human adrenal tumors, leptin does not regulate tumor cell proliferation.