The Dutch version of the self-report Child Activity and Limitations Interview in adolescents with chronic pain

Purpose: To assess the factor structure, related constructs and internal consistency of the Child Activity Limitation Interview 21-Child version for use in Dutch-language countries.

Methods: Cross-sectional validation study: After forward and back translation of the Dutch version of the Child Activity Limitation Interview 21-Child adolescents (11–21 years old) with chronic musculoskeletal pain completed an assessment. The assessment contained the Dutch Child Activity Limitation Interview, and questionnaires about demographics, pain intensity, functional disability, anxiety and depression. Internal consistency and construct validity were evaluated through exploratory factor analysis (principal axis factoring with oblique rotation) and hypotheses testing using pain intensity, activity limitations, anxiety and depression as comparative constructs.

Results: Seventy-four adolescents completed the assessment. Exploratory factor analysis resulted in a two-factor structure, explaining 50% of the variance. Internal consistency was good (Cronbach’s α?=?0.91 total scale, α?=?0.90 Factor 1, α?=?0.80 Factor 2). All nine hypotheses were confirmed.

Conclusion: The Dutch version can be used to assess pain-related disability in Dutch-speaking adolescents comparable to the study sample. Scores on both subscales provide insight into the severity of the pain-related disability in both daily routine and more physically vigorous activities.

• Implications for Rehabilitation

• Chronic pain is a disabling disorder which not only impacts physically but restricts quality of life.

• This study provides clinicians a questionnaire to measure pain-related disability and quantify the impact of pain on the daily living of adolescents.

• The advantage of the Dutch version of the Child Activity and Limitations Interview over other measurements is that it can distinguish limitations in daily activities from more physically vigorous activities.

     

Occult celiac disease prevents penetrance of hemochromatosis

AIM:To report a patient with C282Y homozygocity,depleted body iron and intestinal atrophy caused by celiac disease (CD) who experienced resolution of the enteropathy with subsequent normalization of iron metabolism upon gluten free diet. METHODS:To obtain information on the tissue distribution and quantitative expression of proteins involved in duodenal iron trafficking,we determined the expression of divalent-metal transporter 1 (DMT1),ferroportin 1 (FP1) and transferrin receptor (TfR1) by means of immunohist-ochemistry and real-time PCR in duodenal biopsies of this patient. RESULTS:Whereas in hereditary hemochromatosis patients without CD, DMT1 expression was up-regulated leading to excessive uptake of iron, we identified a significant reduction in protein ana mRNA expression of DMT1 as a compensatory mechanism in this patient with HH and CD. CONCLUSION:Occult CD may compensate for increased DMT1 expression in a specific subset of individuals with homozygous C282Y mutations in the hemochromatosis (HFE) gene,thus contributing to the low penetrance of HH.     

Validation of a new pediatric joint scoring system from the International Hemophilia Prophylaxis Study Group: Validity of the hemophilia joint health score

Objective

Repeated hemarthrosis in hemophilia causes arthropathy with pain and dysfunction. The Hemophilia Joint Health Score (HJHS) was developed to be more sensitive for detecting arthropathy than the World Federation of Hemophilia (WFH) physical examination scale, especially for children and those using factor prophylaxis. The HJHS has been shown to be highly reliable. We compared its validity and sensitivity to the WFH scale.

Methods

We studied 226 boys with mild, moderate, and severe hemophilia at 5 centers. The HJHS was scored by trained physiotherapists. Study physicians at each site blindly determined individual and total joint scores using a series of visual analog scales.

Results

The mean age was 10.8 years. Sixty‐eight percent were severe (93% of whom were treated with prophylaxis), 15% were moderate (24% treated with prophylaxis), and 17% were mild (3% treated with prophylaxis). The HJHS correlated moderately with the physician total joint score (r_s = 0.42, P < 0.0001) and with overall arthropathy impact (r_s = 0.42, P < 0.0001). The HJHS was 97% more efficient than the WFH at differentiating severe from mild and moderate hemophilia. The HJHS was 74% more efficient than the WFH at differentiating subjects treated with prophylaxis from those treated on demand. We identified items on the HJHS that may be redundant or rarely endorsed and could be removed from future versions.

Conclusion

Both the HJHS and WFH showed evidence of strong construct validity. The HJHS is somewhat more sensitive for mild arthropathy; its use should be considered for studies of children receiving prophylaxis.     

Inhibition of hepatic scavenger receptor-class B type I by RNA interference decreases atherosclerosis in rabbits

ObjectiveScavenger receptor-class B type I (SR-BI), the receptor for HDL-cholesterol, plays a key role in HDL metabolism, whole body cholesterol homeostasis, and reverse cholesterol transport. We investigated the in vivo impact of hepatic SR-BI inhibition on lipoprotein metabolism and the development of atherosclerosis employing RNA interference.MethodsSmall hairpin RNA plasmid specific for rabbit SR-BI was complexed with galactosylated poly-l-lysine, allowing an organ-selective, receptor-mediated gene transfer. Rabbits were fed a cholesterol-rich diet, and were injected with plasmid-complexes once a week.ResultsAfter 2 weeks of treatment hepatic SR-BI mRNA levels were reduced by 80% accompanied by reduced SR-BI protein levels and a modulation of the lipoprotein profile. Rabbits treated with SR-BI-specific plasmid-complexes displayed higher cholesteryl ester transfer from HDL to apoB-containing lipoproteins, lower HDL-cholesterol, and higher VLDL-cholesterol levels, when compared to controls. In a long-term study, this gene therapeutic intervention led to a similar modulation of the lipoprotein profile, to lower total cholesterol levels, and most importantly to a 50% reduction of the relative atherosclerotic lesion area.ConclusionOur results are another indication that the role of SR-BI in lipoprotein metabolism and atherogenesis in rabbits – a CETP-expressing animal model displaying a manlike lipoprotein profile may be different from the one found in rodents.     

MGMT and MSH6 immunoexpression for functioning pituitary macroadenomas

Purpose

Knowledge of biological behavior is crucial for clinical management of functioning pituitary macroadenomas. For recurrent cases unresponsive to standard treatment, temozolomide (TMZ) has been used as a therapeutic alternative. MGMT (O6-methyl-guanine-DNA methyltransferase) and MSH6 (mutS homolog 6) immunoexpression have been linked to the response to TMZ treatment and MGMT immunoexpression has been additionally linked to early recurrence of non-functioning pituitary adenomas. The aim of this study was to assess the prognostic value of MGMT and MSH6 immunoexpression for aggressive functioning pituitary adenomas.

Methods

The study cohort comprised a single center series of 76 patients who underwent an operation for functioning pituitary macroadenoma. We retrospectively compared 38 patients with postoperative persistent or recurrent disease with another set of 38 patients who were in endocrine remission.

Results

Low-to-moderate MGMT immunoexpression (<50%) was significantly more frequent in the group with persistent/recurrent disease than in cases of endocrine remission (66 vs. 21%, p?<?0.001). Furthermore, adenomas with low-to-moderate MGMT immunoexpression were significantly more often recurrent (76 vs. 30%, p?<?0.001) and invasive (64 vs. 28%, p?=?0.002).

Conclusion

In our series, low-to-moderate MGMT immunoexpression was the only marker that significantly correlated with surgical invasiveness and recurrence in functioning pituitary macroadenomas. Therefore, in the future, MGMT status may be considered an additional marker for understanding the biological behavior of pituitary adenomas.

     

C5a anaphylatoxin is a major regulator of activating versus inhibitory FcgammaRs in immune complex-induced lung disease

IgG Fc receptors (FcgammaRs, especially FcgammaRIII) and complement (in particular, C5a anaphylatoxin) are critical effectors of the acute inflammatory response to immune complexes (ICs). However, it is unknown whether and how these two key components can interact with each other in vivo. We use here a mouse model of the acute pulmonary IC hypersensitivity reaction to analyze their potential interaction. FcgammaRIII and C5aR are coexpressed on alveolar macrophages (AMs), and both FcgammaRIII and C5aR mutant mice display impaired immune responses. We find that recombinant human C5a (rhC5a) can control inverse expression of various FcgammaRs, and costimulation of ICs with rhC5a results in strong enhancement of FcgammaRIII-triggered cellular activation in vitro and in vivo. Moreover, we show here that early IC-induced bioactive C5a, and its interaction with C5aR, causes induction of activating FcgammaRIII and suppression of inhibitory FcgammaRII on AMs that appears crucial for efficient cytokine production and neutrophil recruitment in lung pathology. Therefore, C5a, which is a potent chemoattractant, has a broader critical function in regulating the inhibitory/activating FcgammaRII/III receptor pair to connect complement and FcgammaR effector pathways in immune inflammation.     

Responsiveness of exercise parameters in children with inflammatory myositis

OBJECTIVE: Juvenile dermatomyositis (DM) is an inflammatory myopathy in which the immune system targets the microvasculature of the skeletal muscle and skin, leading to significant muscle weakness and exercise intolerance, although the precise etiology is unknown. The goal of this study was to investigate the changes in exercise capacity in children with myositis during active and inactive disease periods and to study the responsiveness of exercise parameters. METHODS: Thirteen children with juvenile DM (mean+/-SD age 11.2+/-2.6 years) participated in this study. Patients performed a maximal exercise test using an electronically braked cycle ergometer and respiratory gas analysis system. Exercise parameters were analyzed, including peak oxygen uptake (VO2peak), peak work rate (Wpeak), and ventilatory anaerobic threshold (VAT). All children were tested during an active period of the disease and during a remission period. From these data, 4 different response statistics were calculated. RESULTS: The children performed significantly better during a remission period compared with a period of active disease. Most exercise parameters showed a very large response. The 5 most responsive parameters were Wpeak, Wpeak (percent predicted), oxygen pulse, VO2peak, and power at the VAT. CONCLUSION: We found in our longitudinal study that children with active juvenile DM had significantly reduced exercise parameters compared with a remission period. Moreover, we found that several parameters had very good responsiveness. With previously established validity and reliability, exercise testing has been demonstrated to be an excellent noninvasive instrument for the longitudinal followup of children with myositis.