Pituitary-hormone secretion by thyrotropinomas

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells

No long-term impact of low-energy distal radius fracture on health-related quality of life and global quality of life: a case-control study

<p>Abstract</p> <p>Background</p> <p>Changes in patient-reported outcomes like health related quality of life (HRQOL) and global quality of life (GQOL) in patients with low-energy distal radius fracture might be related to fracture, or be within the normal range of variation in an elderly population. Hence, the present study aims to examine: Whether patients with low-energy distal radius fracture attain their pre-fracture levels in HRQOL and GQOL one year after the fracture and compare these levels with age- and sex-matched controls; and whether objective factors predict changes in HRQOL and GQOL during the same one year period.</p> <p>Methods</p> <p>We examined 160 patients and 169 age- and sex matched controls, respectively (mean ± SD) 67 ± 9 and 66 ± 9 years of age. HRQOL was assessed by the Modified Health Assessment Questionnaire (MHAQ) and the Short–Form 36 (SF-36). The Quality of Life Scale (QOLS) assessed GQOL. Paired sample t-tests and multiple linear regression analyses were applied.</p> <p>Results</p> <p>After one year no differences were found in HRQOL (assessed as arm functions, physical health and mental health) compared to pre-fracture level in the patient group. Both patients with distal radius fracture and controls reported a reduced GQOL after one year (p < 0.001). Low-energy distal radius fracture did not predict worsened HRQOL or GQOL one year after inclusion, and few predictors of changes were identified. Worsened arm function was predicted by low BMI (B = -0.20, p = 0.019) at baseline, worsened physical health was predicted by low education (B = 1.37, p = 0.017) at baseline, and living with someone predicted worsened mental health (B = 2.85, p = 0.009)</p> <p>Conclusion</p> <p>Patients with a distal radius fracture seem to manage well despite the fracture, and distal radius fracture is not an independent predictor of worsened HRQOL and GQOL.</p

Safety and effectiveness of adalimumab in a clinical setting that reflects Canadian standard of care for the treatment of rheumatoid arthritis (RA): Results from the CanACT study

<p>Abstract</p> <p>Background</p> <p>This multicenter, open-label, prospective, single cohort study evaluated the effectiveness and safety of adalimumab in a clinical setting reflecting the Canadian standard of care for the treatment of patients with rheumatoid arthritis (RA).</p> <p>Methods</p> <p>Patients ≥ 18 years of age with a history of active RA ≥ 3 months and fulfilling Canadian requirements for biological therapy received adalimumab 40 mg subcutaneously every other week for 12 weeks. Pre-study DMARD treatment regimens, corticosteroids, or NSAIDs were allowed throughout the study. The primary effectiveness outcome measure was the mean change in 28-joint disease activity score (DAS28) from baseline to Week 12. Secondary measures included the proportion of patients achieving joint remission (DAS28 < 2.6) and low-disease activity (DAS28 < 3.2) at Week 12, and European League Against Rheumatism (EULAR: moderate and good) and American College of Rheumatology (ACR: ACR20, 50, and 70) responses, as well as responses in ACR core components at Weeks 4, 8, and 12. Subgroup analysis included a comparison of patients naïve to biological DMARD (BDMARD) therapy versus BDMARD-experienced patients. Safety was assessed in terms of adverse and serious adverse events.</p> <p>Results</p> <p>A total of 879 patients (mean disease duration > 12 years) were enrolled; 772 (87.9%) completed the 12-week period. Adalimumab treatment was associated with rapid and sustained improvements in the signs and symptoms of RA. Significant improvements in mean DAS28 score were observed as early as Week 4. After 12 weeks of adalimumab treatment, 15.3% and 28.9% of patients achieved clinical remission and low-disease activity, respectively. Similarly, significant improvements in ACR core components were observed as early as Week 4, with continued improvements occurring through 12 weeks. Patients naïve to BDMARD therapy demonstrated numerically greater clinical responses when compared with patients who had experienced prior BDMARD therapy, although both subgroups were associated with significant improvements from baseline. The rates and types of adverse events, as well as the results of laboratory measures, demonstrated that adalimumab was generally safe and well-tolerated.</p> <p>Conclusions</p> <p>This study demonstrated that, under conditions reflective of the normal clinical practice in Canada, adalimumab is an effective and safe treatment for patients with RA.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00649545">NCT00649545</a>.</p

Regularity of center-of-pressure trajectories depends on the amount of attention invested in postural control

The influence of attention on the dynamical structure of postural sway was examined in 30 healthy young adults by manipulating the focus of attention. In line with the proposed direct relation between the amount of attention invested in postural control and regularity of center-of-pressure (COP) time series, we hypothesized that: (1) increasing cognitive involvement in postural control (i.e., creating an internal focus by increasing task difficulty through visual deprivation) increases COP regularity, and (2) withdrawing attention from postural control (i.e., creating an external focus by performing a cognitive dual task) decreases COP regularity. We quantified COP dynamics in terms of sample entropy (regularity), standard deviation (variability), sway-path length of the normalized posturogram (curviness), largest Lyapunov exponent (local stability), correlation dimension (dimensionality) and scaling exponent (scaling behavior). Consistent with hypothesis 1, standing with eyes closed significantly increased COP regularity. Furthermore, variability increased and local stability decreased, implying ineffective postural control. Conversely, and in line with hypothesis 2, performing a cognitive dual task while standing with eyes closed led to greater irregularity and smaller variability, suggesting an increase in the “efficiency, or “automaticity” of postural control”. In conclusion, these findings not only indicate that regularity of COP trajectories is positively related to the amount of attention invested in postural control, but also substantiate that in certain situations an increased internal focus may in fact be detrimental to postural control

A walking programme and a supervised exercise class versus usual physiotherapy for chronic low back pain: a single-blinded randomised controlled trial. (The Supervised Walking In comparison to Fitness Training for Back Pain (SWIFT) Trial)

BACKGROUND: Chronic low back pain (CLBP) is a persistent disabling condition with rising significant healthcare, social and economic costs. Current research supports the use of exercise-based treatment approaches that encourage people with CLBP to assume a physically active role in their recovery. While international clinical guidelines and systematic reviews for CLBP support supervised group exercise as an attractive first-line option for treating large numbers of CLBP patients at low cost, barriers to their delivery include space and time restrictions in healthcare settings and poor patient attendance. The European Clinical Guidelines have identified the need for research in the use of brief/minimal contact self-activation interventions that encourage participation in physical activity for CLBP. Walking may be an ideally suited form of individualized exercise prescription as it is easy to do, requires no special skills or facilities, and is achievable by virtually all ages with little risk of injury, but its effectiveness for LBP is unproven. METHODS AND DESIGN: This study will be an assessor-blinded randomized controlled trial that will investigate the difference in clinical effectiveness and costs of an individualized walking programme and a supervised general exercise programme compared to usual physiotherapy, which will act as the control group, in people with chronic low back pain. A sample of 246 patients will be recruited in Dublin, Ireland through acute general hospital outpatient physiotherapy departments that provide treatment for people with CLBP. Patients will be randomly allocated to one of the three groups in a concealed manner. The main outcomes will be functional disability, pain, quality of life, fear avoidance, back beliefs, physical activity, satisfaction and costs, which will be evaluated at baseline, and 3, 6 and 12 months [follow-up by pre-paid postage]. Qualitative telephone interviews and focus groups will be embedded in the research design to obtain feedback about participants' experiences of the interventions and trial participation, and to inform interpretation of the quantitative data. Planned analysis will be by intention to treat (quantitative data) and thematic analysis (qualitative data) DISCUSSION: The trial will evaluate the effectiveness of a walking programme and a supervised general exercise programme compared to usual physiotherapy in people with CLBP. TRIAL REGISTRATION: Current controlled trial ISRCTN1759209

Harpgophytum procumbens for osteoarthritis and low back pain: A systematic review

BACKGROUND: The objective of this review is to determine the effectiveness of Harpagophytum procumbens preparations in the treatment of various forms of musculoskeletal pain. METHODS: Several databases and other sources were searched to identify randomized controlled trials, quasi-randomized controlled trials, and controlled clinical trials testing Harpagophytum preparations in adults suffering from pain due to osteoarthritis or low back pain. RESULTS: Given the clinical heterogeneity and insufficient data for statistical pooling, trials were described in a narrative way, taking into consideration methodological quality scores. Twelve trials were included with six investigating osteoarthritis (two were identical trials), four low back pain, and three mixed-pain conditions. CONCLUSIONS: There is limited evidence for an ethanolic Harpagophytum extract containing less than <30 mg harpagoside per day in the treatment of knee and hip osteoarthritis. There is moderate evidence of effectiveness for (1) the use of a Harpagophytum powder at 60 mg harpagoside in the treatment of osteoarthritis of the spine, hip and knee; (2) the use of an aqueous Harpagophytum extract at a daily dose of 100 mg harpagoside in the treatment of acute exacerbations of chronic non-specific low back pain; and (3) the use of an aqueous extract of Harpagophytum procumbens at 60 mg harpagoside being non-inferior to 12.5 mg rofecoxib per day for chronic non-specific low-back pain (NSLBP) in the short term. Strong evidence exists for the use of an aqueous Harpagophytum extract at a daily dose equivalent of 50 mg harpagoside in the treatment of acute exacerbations of chronic NSLBP

Movement Behavior of High-Heeled Walking: How Does the Nervous System Control the Ankle Joint during an Unstable Walking Condition?

The human locomotor system is flexible and enables humans to move without falling even under less than optimal conditions. Walking with high-heeled shoes constitutes an unstable condition and here we ask how the nervous system controls the ankle joint in this situation? We investigated the movement behavior of high-heeled and barefooted walking in eleven female subjects. The movement variability was quantified by calculation of approximate entropy (ApEn) in the ankle joint angle and the standard deviation (SD) of the stride time intervals. Electromyography (EMG) of the soleus (SO) and tibialis anterior (TA) muscles and the soleus Hoffmann (H-) reflex were measured at 4.0 km/h on a motor driven treadmill to reveal the underlying motor strategies in each walking condition. The ApEn of the ankle joint angle was significantly higher (p<0.01) during high-heeled (0.38±0.08) than during barefooted walking (0.28±0.07). During high-heeled walking, coactivation between the SO and TA muscles increased towards heel strike and the H-reflex was significantly increased in terminal swing by 40% (p<0.01). These observations show that high-heeled walking is characterized by a more complex and less predictable pattern than barefooted walking. Increased coactivation about the ankle joint together with increased excitability of the SO H-reflex in terminal swing phase indicates that the motor strategy was changed during high-heeled walking. Although, the participants were young, healthy and accustomed to high-heeled walking the results demonstrate that that walking on high-heels needs to be controlled differently from barefooted walking. We suggest that the higher variability reflects an adjusted neural strategy of the nervous system to control the ankle joint during high-heeled walking

High-Sensitivity Cardiac Troponin-I Is Elevated in Patients with Rheumatoid Arthritis, Independent of Cardiovascular Risk Factors and Inflammation

We examined the hypothesis that cardiac-specific troponin-I (cTn-I), a biomarker of myocardial injury, is elevated in patients with rheumatoid arthritis (RA).RA patients have an increased incidence of heart failure (HF). Chronic myocardial injury in RA may be a mechanism for the development of HF.We compared cTn-I concentrations measured by high-sensitivity immunoassay in 164 patients with RA and 90 controls, excluding prior or active heart failure. We examined the relationship between cTn-I concentrations and cardiovascular risk factors, inflammation, and coronary artery calcium score (CACS), a measure of coronary atherosclerosis.cTn-I concentrations were 49% higher in patients with RA (median 1.15 pg/mL [IQR 0.73–1.92] than controls (0.77 pg/mL [0.49–1.28](P<0.001). The difference remained statistically significant after adjustment for demographic characteristics (P = 0.002), further adjustment for cardiovascular (CV) risk factors (P = 0.004), inflammatory markers (P = 0.008), and in a comprehensive model of CV risk factors and inflammatory markers (P = 0.03). In patients with RA, cTn-I concentrations were positively correlated with age (rho = 0.359), Framingham risk score (FRS) (rho = 0.366), and systolic blood pressure (rho = 0.248 (all P values ≤0.001)), but not with measures of inflammation or RA drug therapies. cTn-I was significantly correlated with CACS in RA in univariate analysis, but not after adjustment for age, race, sex and FRS (P = 0.79). Further model adjustments for renal function and coronary artery disease confirmed the significance of the findings.High-sensitivity cTn-I concentrations are elevated in patients with RA without heart failure, independent of cardiovascular risk profile and inflammatory markers. Elevated troponin concentrations in RA may indicate subclinical, indolent myocardial injury

Children with cerebral palsy exhibit greater and more regular postural sway than typically developing children

Following recent advances in the analysis of centre-of-pressure (COP) recordings, we examined the structure of COP trajectories in ten children (nine in the analyses) with cerebral palsy (CP) and nine typically developing (TD) children while standing quietly with eyes open (EO) and eyes closed (EC) and with concurrent visual COP feedback (FB). In particular, we quantified COP trajectories in terms of both the amount and regularity of sway. We hypothesised that: (1) compared to TD children, CP children exhibit a greater amount of sway and more regular sway and (2) concurrent visual feedback (creating an external functional context for postural control, inducing a more external focus of attention) decreases both the amount of sway and sway regularity in TD and CP children alike, while closing the eyes has opposite effects. The data were largely in agreement with both hypotheses. Compared to TD children, the amount of sway tended to be larger in CP children, while sway was more regular. Furthermore, the presence of concurrent visual feedback resulted in less regular sway compared to the EO and EC conditions. This effect was less pronounced in the CP group where posturograms were most regular in the EO condition rather than in the EC condition, as in the control group. Nonetheless, we concluded that CP children might benefit from therapies involving postural tasks with an external functional context for postural control

Antagonism of Tetherin Restriction of HIV-1 Release by Vpu Involves Binding and Sequestration of the Restriction Factor in a Perinuclear Compartment

The Vpu accessory protein promotes HIV-1 release by counteracting Tetherin/BST-2, an interferon-regulated restriction factor, which retains virions at the cell-surface. Recent reports proposed β-TrCP-dependent proteasomal and/or endo-lysosomal degradation of Tetherin as potential mechanisms by which Vpu could down-regulate Tetherin cell-surface expression and antagonize this restriction. In all of these studies, Tetherin degradation did not, however, entirely account for Vpu anti-Tetherin activity. Here, we show that Vpu can promote HIV-1 release without detectably affecting Tetherin steady-state levels or turnover, suggesting that Tetherin degradation may not be necessary and/or sufficient for Vpu anti-Tetherin activity. Even though Vpu did not enhance Tetherin internalization from the plasma membrane (PM), it did significantly slow-down the overall transport of the protein towards the cell-surface. Accordingly, Vpu expression caused a specific removal of cell-surface Tetherin and a re-localization of the residual pool of Tetherin in a perinuclear compartment that co-stained with the TGN marker TGN46 and Vpu itself. This re-localization of Tetherin was also observed with a Vpu mutant unable to recruit β-TrCP, suggesting that this activity is taking place independently from β-TrCP-mediated trafficking and/or degradation processes. We also show that Vpu co-immunoprecipitates with Tetherin and that this interaction involves the transmembrane domains of the two proteins. Importantly, this association was found to be critical for reducing cell-surface Tetherin expression, re-localizing the restriction factor in the TGN and promoting HIV-1 release. Overall, our results suggest that association of Vpu to Tetherin affects the outward trafficking and/or recycling of the restriction factor from the TGN and as a result promotes its sequestration away from the PM where productive HIV-1 assembly takes place. This mechanism of antagonism that results in TGN trapping is likely to be augmented by β-TrCP-dependent degradation, underlining the need for complementary and perhaps synergistic strategies to effectively counteract the powerful restrictive effects of human Tetherin