Prospectively measured 10-year changes in health-related quality of life and comparison with cross-sectional estimates in a population-based cohort of adult women and men

Purpose

To prospectively assess changes in health-related quality of life (HRQOL) over 10 years, by age and sex, and to compare measured within-person change to estimates of change based on cross-sectional data.

Methods

Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for domain and summary components were calculated for men and women separately, stratified by 10-year age groups. Projected changes based on published age- and sex-stratified cross-sectional data were also calculated. Mean differences between the two methods were then estimated, along with the 95 % credible intervals of the differences.

Results

Data were available for 5,569/9,423 (59.1 %) of the original cohort. Prospectively collected 10-year changes suggested that the four physically oriented domains declined in all but the youngest group of men and women, with declines in the elderly men exceeding 25 points. The four mentally oriented domains tended to improve over time, only showing substantial declines in vitality and role emotional in older women, and all four domains in older men. Cross-sectional estimates identified a similar pattern of change but with a smaller magnitude, particularly in men. Correspondence between the two methods was generally high.

Conclusions

Changes in HRQOL may be minimal over much of the life span, but physically oriented HRQOL can decline substantially after middle age. Although clinically relevant declines were more evident in prospectively collected data, differences in 10-year age increments of cross-sectional data may be a reasonable proxy for longitudinal changes, at least in those under 65 years of age. Results provide additional insight into the natural progression of HRQOL in the general population.     

Autism in context 2: Assessment,intervention and services in Australia

Continuing from part 1, part 2 of the autism spectrum disorders review explores clinical practice and service delivery aspects of autism spectrum disorders including current assessment approaches in Australia, family‐centred models of care, and key service structure and delivery issues. Treatments including behavioural interventions, established and emergent medication, and complementary and alternative therapies are discussed. The key role of paediatricians as both individual child and family care providers and advocates, as well as agents of service reform in Australia, is evident. Much still needs to be done.     

Preclinical Evaluation and Dosimetry of [111In]CHX-DTPA-scFv78-Fc Targeting Endosialin/Tumor Endothelial Marker 1 (TEM1)

Purpose

Endosialin/tumor endothelial marker-1 (TEM1) is an attractive theranostic target expressed by the microenvironment of a wide range of tumors, as well as by sarcoma and neuroblastoma cells. We report on the radiolabeling and preclinical evaluation of the scFv78-Fc, a fully human TEM1-targeting antibody fragment cross-reactive with mouse TEM1.

Procedures

The scFv78-Fc was conjugated with the chelator p-SCN-Bn-CHX-A”-DTPA, followed by labeling with indium-111. The number of chelators per molecule was estimated by mass spectrometry. A conventional saturation assay, extrapolated to infinite antigen concentration, was used to determine the immunoreactive fraction of the radioimmunoconjugate. The radiopharmaceutical biodistribution was assessed in immunodeficient mice grafted with Ewing’s sarcoma RD-ES and neuroblastoma SK-N-AS human TEM1-positive tumors. The full biodistribution studies were preceded by a dose-escalation experiment based on the simultaneous administration of the radiopharmaceutical with increasing amounts of unlabeled scFv78-Fc. Radiation dosimetry extrapolations to human adults were obtained from mouse biodistribution data according to established methodologies and additional assumptions concerning the impact of the tumor antigenic sink in the cross-species translation.

Results

[¹¹¹In]CHX-DTPA-scFv78-Fc was obtained with a radiochemical purity >?98 % after 1 h incubation at 42 °C and ultrafiltration. It showed good stability in human serum and >?70 % immunoreactive fraction. Biodistribution data acquired in tumor-bearing mice confirmed fast blood clearance and specific tumor targeting in both xenograft models. The radiopharmaceutical off-target uptake was predominantly abdominal. After a theoretical injection of [¹¹¹In]CHX-DTPA-scFv78-Fc to the reference person, the organs receiving the highest absorbed dose would be the spleen (0.876 mGy/MBq), the liver (0.570 mGy/MBq) and the kidneys (0.298 mGy/MBq). The total body dose and the effective dose would be 0.058 mGy/MBq and 0.116 mSv/MBq, respectively.

Conclusions

[¹¹¹In]CHX-DTPA-scFv78-Fc binds specifically to endosialin/TEM1 in vitro and in vivo. Dosimetry estimates are in the range of other monoclonal antibodies radiolabeled with indium-111. [¹¹¹In]CHX-DTPA-scFv78-Fc could be potentially translated into clinic.

     

Social Phobia Among Depressed Individuals Entering Residential Rehabilitation Programmes: Prevalence and Correlates

Social phobia commonly co-occurs with substance use disorders and depression; however, the prevalence and correlates of social phobia among individuals with both of these disorders remain unknown. Interviews were conducted with 120 individuals entering residential rehabilitation for substance use treatment, who endorsed criteria for major depression and were recruited to a randomised controlled trial. Nearly three quarters (72.5%) of the sample met diagnostic criteria for social phobia. These individuals were more likely to report problematic drinking, more severe anxiety and depressive rumination, and lower distress tolerance, compared to individuals without social phobia. When examining the impact of applying diagnostic exclusion rules for social phobia among this cohort, results indicate that one third (32.2%) of those with social phobia specified their fear was related to a co-occurring mental health and/or substance use disorder. This group—who would not have met diagnostic criteria for social phobia if exclusion rules were strictly followed—experienced more severe depression, anxiety, depressive rumination, and repetitive negative thinking than those who did not make such attributions. The high prevalence and burden associated with social phobia among depressed substance users highlight the importance of screening for, assessing, and treating the disorder upon entry to treatment, irrespective of whether symptoms are related to other conditions.

     

24-h catecholamine excretion: relationships with age and weight

24-hour urines were obtained from groups of volunteer subjects recruited from populations in the UK, USA, Nigeria and the South Pacific. Urines were collected during the course of normal daily activities. HPLC/electrochemical detection was used to measure concentrations of adrenaline and noradrenaline in each urine. Calculated 24-h output of catecholamines was tested for significant linear regression relationships with age, weight and 24-h urine volume in each population. Noradrenaline excretion tended to be positively related to age and to body wt. Adrenaline excretion tended to show little or no relationship with either age or body wt. Relationships based on catecholamine excretion/U creatinine were notably different to those based on absolute catecholamine excretion. Differences were observed in the nature and strength of the relationships in the different populations, indicating the likely importance of interactions with other factors.     

Processing of timbre and rhythm in musicians and non-musicians

Expert musicians and non-musicians of similar educational and social class background were compared in two experiments involving perception of timbre and rhythm. In Experiment 1 where dichotic monitoring for the sound of the violin was required, there was a practice effect but no ear or group differences. The rhythm monitoring experiment produced a group by ear interaction with musicians faster on the right ear than the left and faster than non-musicians on the right ear only. Analysis of strategies reported by subjects showed that verbal labelling did not apparently influence laterality. Lack of evidence for individual laterality effects reinforces the claim that with stringent experimental and subject controls there is minimal evidence for musicians non-musician laterality effects.     

小儿淋巴管瘤的MRI诊断

目的分析小儿淋巴管瘤的磁共振表现及其病理基础。方法对６例经手术病理证实的、年龄７天至７岁的小儿淋巴管瘤患者的磁共振表现进行回顾性分析。结果淋巴管瘤磁共振表现为Ｔ１ＷＩ上呈与肌肉相似或稍高的信号，Ｔ２ＷＩ上高于脂肪信号。５例瘤内可见低信号分隔，１例瘤内见血管流空影，３例见明显包膜，３例边界不清。２例病理诊断为海绵状淋巴管瘤，４例诊断为囊状淋巴管瘤。结论磁共振成像可较好地显示肿瘤的大小、形态及范围，从而指导手术治疗。     

Further investigations into the mechanism of the antihypertensive activity of the angiotensin AT1 receptor antagonist, GR138950.

1. The angiotensin AT1 receptor antagonist, GR138950, produces a long-lasting antihypertensive effect in conscious renal artery ligated hypertensive (RALH) rats but this effect does not correlate temporally with its antagonist profile against angiotensin II (AII). In the present experiments we have compared the inhibitory profiles of GR138950 and enalapril, against angiotensin I (AI), with their respective antihypertensive activities. 2. GR138950 (1 mg kg-1, i.a.) and enalapril (3 mg kg-1, i.a.) reduced blood pressure in RALH rats to a similar degree. Maximum reductions in blood pressure occurred approximately 5-24 h and 3-5 h after administration, respectively. The antihypertensive effect of GR138950 lasted for 24-48 h. However, the effect of enalapril lasted for only 5-24 h. 3. In conscious normotensive rats, inhibition of AI-induced pressor responses was maximal 1 h after systemic administration of GR138950 and enalapril. Dose-response curves to AI were displaced to the right, in a parallel manner, 1406 and 102 fold by GR138950 (1 mg kg-1, i.a.) and enalapril (3 mg kg-1 i.a.), respectively. The inhibitory effect of enalapril lasted for < 24 h whereas that of GR138950 lasted for up to 48 h. 4. Contractile responses to AI were extensively inhibited in aortae removed from either RALH rats or normotensive rats, 1 and 5 h after administration of GR138950 (1 mg kg-1, i.a.). Responses were still significantly reduced 24 h after administration but had returned to control levels after 48 h. Enalapril pretreatment (3 mg kg-1, i.a.) did not inhibit contractile responses to AI in aortae isolated from normotensive rats at any time point. 5. These experiments confirm that GR138950 is an effective and long-lasting antihypertensive agent. GR138950 was a more potent and longer lasting antagonist against AI than has previously been found against AII, and the duration of its antihypertensive activity coincides better with its blockade of responses to AI. Blockade of the effects of AII generated locally within the vascular wall might play an important role in the antihypertensive profile of GR138950.