Early childhood factors influencing health-related quality of life in adolescents at 13 years

Early childhood factors influencing health-related quality of life in adolescents at 13 years . Wilkins , A.J. , O'Callaghan , M.J. , Najman , J.M. , Williams , G.M. & Shuttlewood , G. ( 2004 ) Journal of Paediatrics and Child Health 40 , 102 – 109 .     

Health-related quality of life of severely obese children and adolescents

Context One in seven US children and adolescents is obese, yet little is known about their health‐related quality of life (QOL). Objective To examine the health‐related QOL of obese children and adolescents compared with children and adolescents who are healthy or those diagnosed as having cancer. Design, setting and participants Cross‐sectional study of 106 children and adolescents (57 males) between the ages of 5 and 18 years [mean (SD) 12.1 (3) years], who had been referred to an academic children's hospital for evaluation of obesity between January and June 2002. Children and adolescents had a mean (SD) body mass index (BMI) of 34.7 (9.3) and BMI z‐score of 2.6 (0.5). Main outcome measures Child self‐report and parent‐proxy report using a paediatric QOL inventory generic core scale (range 0–100). The inventory was administered by an interviewer for children aged 5 through 7 years. Scores were compared with previously published scores for healthy children and adolescents and children and adolescents diagnosed as having cancer. Results Compared with healthy children and adolescents, obese children and adolescents reported significantly (P < 0.001) lower health‐related QOL in all domains [mean (SD) total score, 67 (16.3) for obese children and adolescents; 83 (14.8) for healthy children and adolescents]. Obese children and adolescents were more likely to have impaired health‐related QOL than healthy children and adolescents [odds ratio (OR) 5.5; 95% confidence interval (CI) 3.4–8.7] and were similar to children and adolescents diagnosed as having cancer (OR 1.3; 95% CI 0.8–2.3). Children and adolescents with obstructive sleep apnoea reported a significantly lower health‐related QOL total score [mean (SD), 53.8 (13.3)] than obese children and adolescents without obstructive sleep apnoea [mean (SD), 67.9 (16.2)]. For parent‐proxy report, the child or adolescent's BMI z‐score was significantly inversely correlated with total score (r = ?0.246; P = 0.01), physical functioning (r = ?0.263; P < 0.01), social functioning (r = ?0.347; P < 0.001), and psychosocial functioning (r = ?0.209; P = 0.03). Conclusions Severely obese children and adolescents have lower health‐related QOL than children and adolescents who are healthy and similar QOL as those diagnosed as having cancer. Physicians, parents and teachers need to be informed of the risk for impaired health‐related QOL among obese children and adolescents to target interventions that could enhance health outcomes.     

Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways.     

Psychosocial Factors and Prediction of Headaches in College Adults

The current study evaluated psychosocial variables that may contribute to the experience of headache in college adults. One hundred ninety-nine participants, 103 women and 96 men, completed head pain logs for 4 weeks after completing measures assessing psychosocial variables. Multiple regression analyses indicated that level of emotional functioning, perception of stress, and gender were predictive of future headache frequency, intensity, and duration. Family history and health habits did not predict headache activity. These findings are consistent with research investigating psychosocial variables and headache activity.     

Induction of Donor-Specific Allograft Tolerance by Short-Term Treatment with LF15-0195 After Transplantation. Evidence for a Direct Effect on T-Cell Differentiation

A 20-day treatment with LF15-0195, a deoxyspergualine analog, induced long-term heart allograft survival in the rat without signs of chronic rejection. LF15-0195-treated recipients did not develop an anti-donor alloantibody response. Analysis of graft-infiltrating cells, IL10, TNFalpha, IFNgamma mRNA and iNOS protein expression in allografts, 5 days after transplantation, showed that they were markedly decreased in allografts from LF15-0195-treated recipients compared with allografts from untreated recipients. Surprisingly, spleen T cells from LF15-0195 recipients, 5days after grafting, were able to proliferate strongly in vitro, when stimulated with donor cells, but had reduced mRNA expression for IFNy compared with spleen T cells from untreated graft recipients. Furthermore, when T cells from naive animals were stimulated in vitro, using anti-CD3 and anti-CD28, LF15-0195 also increased T-cell proliferation in a dose-dependent fashion: however, these cells expressed less of the Th1 -related cytokines, IFNgamma and IL2, compared with untreated cells, suggesting that LF15-0195 could act on T-cell differentiation. In conclusion, we show here that a short-term treatment with LF15-0195 induced long-term allograft tolerance, decreasing the in situ anti-donor response, and we illustrate evidence for the development of regulatory mechanisms.     

Human Lyme arthritis and the immunoglobulin G antibody response to the 37-kilodalton arthritis-related protein of Borrelia burgdorferi

In Borrelia burgdorferi-infected C3H-scid mice, antiserum to a differentially expressed, 37-kDa spirochetal outer-surface protein, termed arthritis-related protein (Arp), has been shown to prevent or reduce the severity of arthritis. In this study, we determined the immunoglobulin G (IgG) antibody responses to this spirochetal protein in single serum samples from 124 antibiotic-treated human patients with early or late manifestations of Lyme disease and in serial serum samples from 20 historic, untreated patients who were followed longitudinally from early infection through the period of arthritis. These 20 patients were representative of the spectrum of the severity and duration of Lyme arthritis. Among the 124 antibiotic-treated patients, 53% with culture-proven erythema migrans (EM) had IgG responses to recombinant glutathione S-transferase (GST)-Arp, as did 59% of the patients with facial palsy and 68% of those with Lyme arthritis. In addition, 75 to 80% of the 20 past, untreated patients had reactivity with this protein when EM was present, during initial episodes of joint pain, or during the maximal period of arthritis. There was no association at any of these three time points between GST-Arp antibody levels and the severity of the maximal attack of arthritis or the total duration of arthritis. Thus, after the first several weeks of infection, 60 to 80% of patients had IgG antibody responses to GST-Arp, but this response did not correlate with the severity or duration of Lyme arthritis.