Model-Based Therapeutic Correction of Hypothalamic-Pituitary-Adrenal Axis Dysfunction

The hypothalamic-pituitary-adrenal (HPA) axis is a major system maintaining body homeostasis by regulating the neuroendocrine and sympathetic nervous systems as well modulating immune function. Recent work has shown that the complex dynamics of this system accommodate several stable steady states, one of which corresponds to the hypocortisol state observed in patients with chronic fatigue syndrome (CFS). At present these dynamics are not formally considered in the development of treatment strategies. Here we use model-based predictive control (MPC) methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels. Suppression of biologically available cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can therefore be designed that maximally exploit system dynamics to provide a robust response to treatment and ensure a positive outcome over a wide range of conditions. Perhaps most importantly, a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and challenges the conventional strategy of supplementing cortisol levels, an approach based on steady-state reasoning

Translation and validation of the Turkish version of the Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire

WOS: 000325962100002PubMed ID: 23765201The Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire is a disease-specific measure of needs-based quality of life developed in the UK and the Netherlands. This study describes translation, validation, and reliability of the scale into Turkish population. The ASQoL was translated into Turkish using the dual-panel process. Content validity was assessed via cognitive debriefing interviews with ankylosing spondylitis (AS) patients. Patients with AS according to modified New York criteria were recruited into the study from 12 hospitals of all part of Turkey. Psychometric and scaling properties were assessed via a two administration survey involving the ASQoL, the Nottingham Health Profile (NHP), Bath AS Functional Index (BASFI), and Bath AS Disease Activity Index (BASDAI). Classical psychometrics assessed reliability, convergent validity (correlation of ASQoL with NHP, BASFI, and BASDAI) and discriminative validity (correlation of ASQoL with perceived AS-severity and general health). Cognitive debriefing showed the new Turkish ASQoL to be clear, relevant, and comprehensive. Completed survey questionnaires were received from 277 AS patients (80 % Male, mean age 42.2/SD 11.6, mean AS duration 9.4 years/SD 9.4). Test-retest reliability was excellent (0.96), indicating low random measurement error for the scale. Correlations of ASQoL with NHP sections were low to moderate (NHP Sleep 0.34; NHP Emotional Reactions 0.83) suggesting the measures assess related but distinct constructs. The measure was able to discriminate between patients based on their perceived disease severity (p < 0.0001) and self-reported general health (p < 0.0001). The Turkish version of ASQoL has good reliability and validity properties. It is practical and useful scale to assess the quality of life in AS patients in Turkish population

The relation between tooth loss and bone mass in postmenopausal osteoporotic women in Turkey: a multicenter study

WOS: 000180078100008PubMed ID: 12491093The purpose of this study was to investigate the associations of tooth loss with skeletal bone mass, years since menopause, educational level, current smoking status, dietary calcium intake, and number of pregnancies in postmenopausal osteoporotic women in Turkey. The study population consisted of 1171 postmenopausal women aged 40-86 years (mean age, 61.19 +/- 7.28 years). A detailed history was obtained from all women, including relevant lifestyle parameters, risk factors, and measurements of weight and height. Women were separated into three groups according to the number of teeth remaining as group 1 (edentulous, 457 women), group 2 (10 or fewer teeth, 232 women), and group 3 (more than 10 teeth remaining, 482 women). There was no significant difference among the three groups in mean age and menopausal age (P < 0.05). Body mass index of group 1 was significantly higher than that of group 2 (P < 0.01). Educational level was significantly different between three groups: groups 1 and 2 (P < 0.001), groups 1 and 3 (P < 0.0001), and groups 2 and 3 (P < 0.001). Educational level was lowest in group 1 and highest in group 3. Despite a low ratio of cigarette smoking in general, a smoking habit was most prevalent in group 3 and least in group 2. The ratio of women receiving adequate calcium was significantly lower in group 1 than in other groups (P < 0.001); mean calcium intake was similar in all groups. The number of pregnancies was significantly higher in group 1 than in other groups (P < 0.001). Lumbar bone mineral density (BMD) of group 1 was significantly lower than that of groups 2 and 3 (P < 0.001). Although no significant difference was found between groups 1 and 3, femoral neck BMD of group 2 was less than in others, and differences between groups 1 and 2 and between groups 2 and 3 (P < 0.001) were significant. Lumbar bone mineral content (BMC) of group 1 was significantly lower than that of groups 2 and 3 (P < 0.001), and lumbar BMC in group 2 was significantly higher than in group 3 (P < 0.05). Femoral neck BMC in group 1 was significantly higher than in groups 2 and 3 (P < 0.001). In conclusion, lumbar BMD and BMC in the edentulous group were significantly lower, whereas femoral neck BMD and BMC were significantly higher in edentulous group compared with the others. Our findings indicated that improvement in lifestyle factors and nutritional strategies for the treatment and prevention of osteoporosis may have additional benefit in reducing tooth loss