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991.
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993.
Klumpers LE Beumer TL van Hasselt JG Lipplaa A Karger LB Kleinloog HD Freijer JI de Kam ML van Gerven JM 《British journal of clinical pharmacology》2012,74(1):42-53
AIMS
Among the main disadvantages of currently available Δ9-tetrahydrocannabinol (THC) formulations are dosing difficulties due to poor pharmacokinetic characteristics. Namisol® is a novel THC formulation, designed to improve THC absorption. The study objectives were to investigate the optimal administration route, pharmacokinetics (PK), pharmacodynamics (PD) and tolerability of Namisol®.METHODS
This first in human study consisted of two parts. Panel I included healthy males and females (n = 6/6) in a double-blind, double-dummy, randomized, crossover study with sublingual (crushed tablet) and oral administration of Namisol® (5 mg THC). Based on these results, male and female (n = 4/5) participants from panel I received oral THC 6.5 and 8.0 mg or matching placebo in a randomized, crossover, rising dose study during panel II. PD measurements were body sway; visual analogue scales (VAS) mood, psychedelic and heart rate. THC and 11-OH-THC population PK analysis was performed.RESULTS
Sublingual administration showed a flat concentration profile compared with oral administration. Oral THC apparent t1/2 was 72–80 min, tmax was 39–56 min and Cmax 2.92–4.69 ng ml−1. THC affected body sway (60.8%, 95% CI 29.5, 99.8), external perception (0.078 log mm, 95% CI 0.019, 0.137), alertness (−2.7 mm, 95% CI −4.5, −0.9) feeling high (0.256 log mm, 95% CI 0.093, 0.418) and heart rate (5.6 beats min–1, 95% CI 2.7, 6.5). Namisol® was well tolerated.CONCLUSIONS
Oral Namisol® showed promising PK and PD characteristics. Variability and tmax of THC plasma concentrations were smaller for Namisol® than reported for studies using oral dronabinol and nabilone. This study was performed in a limited number of healthy volunteers. Therefore, future research on Namisol® should study clinical effects in patient populations. 相似文献994.
Oliver A. Silverson Nicole G. Lemaster Carolyn M. Hettrich Nicholas R. Heebner Tim L. Uhl 《Journal of Athletic Training》2021,56(6):586
ContextA single clinical assessment device that can be used to objectively measure scapular motion in each anatomical plane is not currently available. The development of a novel electric goniometer would allow scapular motion in all 3 anatomical planes to be quantified.ObjectiveTo investigate the reliability and validity of an electric goniometer for measuring scapular motion in each anatomical plane during upper extremity elevation.DesignCross-sectional study.SettingLaboratory.Patients or Other ParticipantsSixty participants (29 women, 31 men; age = 30 ± 14 years, height = 1.73 ± 0.10 m, mass = 75.32 ± 16.90 kg) recruited from the general population.Intervention(s)An electric goniometer was used to record clinical measurements of scapular position at rest and total arc of motion (excursion) during active upper extremity elevation in 2 testing sessions separated by several days. Measurements were recorded independently by 2 examiners. In 1 session, scapular motion was recorded simultaneously using a 14-camera, 3-dimensional optical motion-capture system.Main Outcome Measure(s)Reliability analysis included examination of clinical measurements for scapular position at rest and excursion during each condition. Both the intrarater reliability between testing sessions and the interrater reliability recorded in the same session were assessed using intraclass correlation coefficients (ICCs [2,3]). The criterion validity was examined by comparing the mean excursion values of each condition recorded using the electric goniometer and the 3-dimensional optical motion-capture system. Validity was assessed by evaluating the average difference and root mean square error.ResultsThe between-sessions intrarater reliability was moderate to good (ICC [2,3] range = 0.628–0.874). The within-session interrater reliability was moderate to excellent (ICC [2,3] range = 0.545–0.912). The average difference between total excursion values recorded using the electric goniometer and the 3-dimensional optical motion-capture system ranged from −7° to 4°, and the root mean square error ranged from 7° to 10°.ConclusionsThe reliability of scapular measurements was best when a standard operating procedure was used. The electric goniometer provided an accurate measurement of scapular excursions in all 3 anatomical planes during upper extremity elevation. 相似文献
995.
Paula F. Polastri José A. Barela Tim Kiemel John J. Jeka 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2012,223(1):99-108
Flexible and stable postural control requires adaptation to changing environmental conditions, a process which requires re-weighting of multisensory stimuli. Recent studies, as well as predictions from a computational model, have indicated a reciprocal re-weighting relationship between modalities when a sensory stimulus changes amplitude. As one modality is down-weighted, another is up-weighted to compensate (and vice versa). The purpose of this study was to investigate the dynamics of intra- and inter-modality re-weighting process by examining postural responses to manipulation of proprioception and visual modalities simultaneously. Twenty-two young adults were placed in a visual cave and stood on a variable-pitch platform for thirteen trials of 250 s apiece. The platform was rotated at constant frequency of 0.4 Hz and amplitudes of 0.3 (low) or 1.5 (high) degrees. Platform amplitude was manipulated in two conditions: low-to-high or high-to-low. The visual stimulus was displayed at constant frequency of 0.35 Hz and amplitude of 0.08 degrees. The results showed both fast and slow changes in center of mass (CoM) response to the switch in platform amplitude. On both timescales, CoM response changed in a reciprocal manner relative to platform amplitude. When the platform amplitude increased (low-to-high condition), CoM response decreased relative to the platform and increased relative to the visual stimulus, indicating both intra-modality and inter-modality sensory re-weighting. In the high-to-low condition, however, there was no change in CoM response relative to visual stimulus, indicating that re-weighting may also be dependent on the absolute level of gain. Sway variability at frequencies other than the stimulus frequency also showed a reciprocal relationship with CoM gain relative to platform. Overall, these results indicate that dynamics of multisensory re-weighting is clearly more complicated than the schemes proposed by current adaptive models of human postural control. 相似文献
996.
BACKGROUND: We assessed the impact of postoperative sensory abnormalities and bruising after long saphenous vein (LSV) stripping on short-term quality of life (QOL). METHODS: Seventy patients with LSV incompetence were recruited before surgery. Surgery involved saphenofemoral disconnection, stripping of the LSV in the thigh, and multiple stab avulsions in all patients. Sensory abnormalities (subjective and objective) and bruising were recorded at two follow-up visits (mean, 8 and 47 days). The bruised area was traced manually, and the surface area was estimated by placing the tracing on a square chart. A QOL assessment was performed before surgery and repeated during the second visit by using the Aberdeen Varicose Veins Questionnaire. Minitab version 13.32 was used for statistical analysis. RESULTS: Eight patients either did not complete follow-up or were excluded from the final analysis. Final analysis was performed on 63 limbs in 62 patients (27 men and 35 women; age, 19-75 years). The overall incidence of postoperative sensory abnormality was 40% (25/63 limbs). This included numbness or decreased sensation in 36.5% (23/63), paresthesia in 8% (5/63), and dysesthesia in 1.6% (1/63). Irrespective of the presence of sensory abnormalities, QOL scores improved after surgery (mean change in QOL score, -7.58 and -7.52; SE, 1.1 and 1.3 in those with and without sensory abnormalities, respectively). There was no significant difference either in the degree of improvement in the QOL score (P = .972; t test) or in the proportion of patients with an improved score (P = .69; Fisher exact test) between the groups with and without sensory abnormalities. Postoperative bruising at first follow-up ranged from 28 to 1419 cm(2) (mean, 500.7 cm(2); median, 438 cm(2)). Both groups--those who bruised less than the median value (438 cm(2)) and those who bruised more than the median value--showed improved postoperative QOL scores (mean change in QOL score, -7.64 and -7.46; SE, 1.3 and 1.3, respectively). There was no significant difference either in the degree of improvement in the QOL score (P = .924; t test) or in the proportion of patients with an improved score (P = .422; Fisher exact test). All patients with persistent bruising at the second follow-up (26%) also showed an improvement in the QOL score (mean change in QOL score, -10.29). CONCLUSIONS: Conventional surgery for varicose veins with stripping of the LSV is associated with significant morbidity of sensory abnormalities and bruising. However, this does not adversely affect postoperative improvement in short-term QOL. 相似文献
997.
This study examined the impact of a three-year intervention project conducted in the Hoima district of Uganda, which sought to engage men in sexual and reproductive health as clients, equal partners and advocates of change. Structured surveys with 164 self-reported heterosexual men aged 18–54 years were used to assess knowledge and attitudes towards sexual and reproductive health. Data from these were analysed using Stata and SPSS. Additionally, five focus groups were conducted with the female partners and male beneficiaries of the project and with project peer educators. Four interviews were conducted with project staff and male beneficiaries. Data from these and the focus groups were analysed using a thematic approach. Following the intervention, a significantly greater number of men accessed, and supported their partners in accessing sexual health services services, had gained sexual and reproductive health awareness, reported sharing domestic duties and contraceptive decision-making, and displayed a decreased tolerance for domestic violence. It was more difficult to assess men's involvement and behaviours as advocates of change, which sheds light on the complexities of a gender transformative project and the importance of evaluating such projects from both men's and their partners' perspectives and at different levels of the male involvement model in sexual and reproductive health. 相似文献
998.
Matakidou A el Galta R Webb EL Rudd MF Bridle H;GELCAPS Consortium Eisen T Houlston RS 《Human molecular genetics》2007,16(19):2333-2340
To assess whether DNA repair gene variants influence the clinical behaviour of lung cancer we examined the impact of a comprehensive panel of 109 non-synonymous single-nucleotide polymorphisms (nsSNPs) in 50 DNA repair genes on overall survival (OS) in 700 lung cancer patients. Fifteen nsSNPs were associated with OS, significantly greater than that expected (P = 0.04). SNPs associated with prognosis mapped primarily to two repair pathways--nucleotide excision repair (NER): ERCC5 D1104H (P = 0.004); ERCC6 G399D (P = 0.023), ERCC6 Q1413R (P = 0.025), POLE (P = 0.014) and base excision repair: APEX1 D148E (P = 0.028); EXO1 E670G (P = 0.007); POLB P242R (P = 0.018). An increasing number of variant alleles in EXO1 was associated with a poorer prognosis [hazard ratio (HR) = 1.24; P = 0.0009]. A role for variation in NER and BRCA2/FA pathway genes as determinants of OS was provided by an analysis restricted to the 456 patients treated with platinum-based agents. Our data indicate that the pathway-based approach has the potential to generate prognostic markers of clinical outcome. 相似文献
999.
Green A Gerein N Mirzoev T Bird P Pearson S Anh le V Martineau T Mukhopadhyay M Qian X Ramani KV Soors W 《Health policy (Amsterdam, Netherlands)》2011,100(2-3):167-173
This article reports on a comparative analysis to assess and explain the strengths and weaknesses of policy processes based on 9 case-studies of maternal health in Vietnam, India and China. Policy processes are often slow, inadequately coordinated and opaque to outsiders. Use of evidence is variable and, in particular, could be more actively used to assess different policy options. Whilst an increasing range of actors are involved, there is scope for further opening up of the policy processes. This is likely, if appropriately managed with due regard to issues such as accountability of advocacy organisations, to lead to stronger policy development and greater subsequent ownership; it may however be a more messy process to co-ordinate. Coordination is critical where policy issues span conventional sectoral boundaries, but is also essential to ensure development of policy considers critical health system and resource issues. This, and other features related to the nature of a specific policy issue, suggests the need both to adapt processes for each particular policy issue and to monitor the progress of the policy processes themselves. The article concludes with specific questions to be considered by actors keen to enhance policy processes. 相似文献
1000.
Tim H. Scott‐Taylor Jonathan O'B Hourihane Stephan Strobel 《Pediatric allergy and immunology》2010,21(6):935-944
Scott‐Taylor TH, Hourihane J, Strobel S. Correlation of allergen‐specific IgG subclass antibodies and T lymphocyte cytokine responses in children with multiple food allergies.Pediatr Allergy Immunol 2010: 21: 935–944.© 2010 John Wiley & Sons A/S Cytokines can affect the quantity and class of allergen‐specific immunoglobulins through the T cell polarization that accompanies atopy. Antigen‐specific IgG subclasses and IgE antibodies were compared with intracellular T cell cytokine changes to sensitizing antigens in 23 children with multiple food allergies and 20 healthy controls. Allergic children showed higher levels of total and food‐specific IgE, IgG1 and IgG4 to peanut, milk and egg than non‐atopic children or adults, coinciding with a TH2 cytokine response to sensitizing antigens. IgG1 and IgG4 antibodies specific to milk and egg and peanut protein were elevated relative to age‐matched healthy children (p ≤ 0.05) and, in milk‐ and egg‐sensitized children, correlated with cytokine responses (p < 0.05). Peanut‐sensitized children additionally had elevated levels of IgG2 and IgG3 also which correlated inversely (p < 0.003 and p < 0.04, respectively) with IFNγ production. Elevated allergen‐specific IgG subclass antibodies in sensitized children correlated with total IgE levels (p ≤ 0.05) in all three food allergen groups. The ratio of specific IgG1 to IgG4 was highest in those with high IgE, inverted with resolution of allergy, and correlated with total IgE levels (p ≤ 0.01) in milk‐ and egg‐sensitized children. The correlation of TH2 responses with allergen‐specific antibodies would implicate polarized T cells in food allergic children in IgE hypersensitivity and overproduction of particular IgG subclasses alike. IgG1:IgG4 ratio declines with allergy sensitization and may denote emerging tolerance. 相似文献