Fat intake and adiposity in 8 to 11-year-old obese children.

OBJECTIVE: To investigate the relationships between diet composition, body composition, and macronutrient oxidation at rest in obese and non-obese children. DESIGN: Cross-sectional study on fat intake, adiposity and postabsorptive macronutrients oxidation rates. SUBJECTS: 82 prepubertal (age: 9.1 +/- 1.1 y) children, 30 obese (FM = 32.6 +/- 6.1%) and 52 non-obese (FM = 15.6 +/- 5.1%). MEASUREMENTS: Subcutaneous skinfold thickness for body composition, diet history for energy and nutrient intake, indirect calorimetry for resting metabolic rate (RMR) and RQ measurement. RESULTS: Energy intake (EI) was comparable in obese and non-obese children. Adjusted for RMR by ANCOVA, using RMR as the covariate, EI was significantly lower in obese than in non-obese children indicating either a blunted physical activity or a systematic underestimation of EI. Protein and carbohydrate intakes expressed as a percentage of total energy intake (%EI) were not significantly different in the two groups. Lipid intake (%EI) was slightly but significantly higher in the obese than in the non-obese group either unadjusted or adjusted for RMR by ANCOVA. The postabsorptive RQ was significantly lower in obese than in non-obese children. In the total group, %FM was weakly but significantly correlated to lipid intake (%EI). CONCLUSION: Obese prepubertal children have a higher relative fat intake than non-obese children and their FM is associated with this factor. The lower postabsorptive RQ of obese children may indicate a compensatory mechanism to achieve fat equilibrium by enhanced fat oxidation.

Missed appointments in an adolescent outpatient clinic: descriptive analyses of consultations over 8 years.

Missed appointments represent an important medical and economical issue. Few studies on the subject are reported in the literature, particularly regarding adolescents. Our aim was to characterize missed and cancelled appointments in a multidisciplinary outpatient clinic for adolescents, to assess the effectiveness of a policy aimed at reducing missed appointments by introducing payment for those missed appointments not cancelled in advance, and to compare the rates between staff and resident physicians. A total of 32,816 consultations (representing 35 patients aged 12-20 years, 82.4% females) between 1999 and 200 were analysed. The missed appointment rate was 11.8% whilst another 10.9% were cancellations. Females cancelled more than males (11.3% vs. 8.4%, AOR 1.31, 99% CI 1.08-1.59), but there was no difference for missed appointments (11.6% vs. 12.3%, AOR 0.88, 99% CI 0.61-1.08). April and June to October (vacation months) were associated with more missed appointments. Globally mornings had higher rates of missed appointments than afternoons (13.6% vs. 11.2%, AOR 1.25, 99% CI 1.11-1.40). There was a slight difference in missed appointment rates between staff physicians and residents (10.4%; 11.8%, AOR 1.20, 99% CI 1.08-1.33). Missed appointment rates before and after the new policy on missed appointments were similar (1999-2003: 11.9%; 2004-2006: 11.6%, AOR 0.96, 99% CI 0.83-1.10). Conversely, cancellation rates increased from 8.4% (1999-2003) to 14.5% (2004-2006) (AOR 1.83, 99% CI 1.63-2.05). Attendance rates among adolescents show variations depending on vacation and school hours. Being attentive to these factors could help prevent missed appointments. Although having to pay for missed appointments does not increase attendance, it increases cancellations with the advantage that the appointment can be rescheduled.

Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial.

BACKGROUND: In uveal melanoma (UM) with metastatic disease limited to the liver, the effect of an intrahepatic treatment on survival is unknown. We investigated prospectively the efficacy and toxicity of hepatic intra-arterial (HIA) versus systemic (IV) fotemustine in patients with liver metastases from UM. PATIENTS AND METHODS: Patients were randomly assigned to receive either IV or HIA fotemustine at 100 mg/m(2) on days 1, 8, 15 (and 22 in HIA arm only) as induction, and after a 5-week rest period every 3 weeks as maintenance. Primary end point was overall survival (OS). Response rate (RR), progression-free survival (PFS) and safety were secondary end points. RESULTS: Accrual was stopped after randomization of 171 patients based on the results of a futility OS analysis. A total of 155 patients died and 16 were still alive [median follow-up 1.6 years (range 0.25-6 years)]. HIA did not improve OS (median 14.6 months) when compared with the IV arm (median 13.8 months), hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.79-1.50, log-rank P = 0.59. However, there was a significant benefit on PFS for HIA compared with IV with a median of 4.5 versus 3.5 months, respectively (HR 0.62; 95% CI 0.45-0.84, log-rank P = 0.002). The 1-year PFS rate was 24% in the HIA arm versus 8% in the IV arm. An improved RR was seen in the HIA (10.5%) compared with IV treatment (2.4%). In the IV arm, the most frequent grade ≥3 toxicity was thrombocytopenia (42.1%) and neutropenia (62.6%), compared with 21.2% and 28.7% in the HIA arm. The main grade ≥3 toxicity related to HIA was catheter complications (12%) and liver toxicity (4.5%) apart from two toxic deaths. CONCLUSION: HIA treatment with fotemustine did not translate into an improved OS compared with IV treatment, despite better RR and PFS. Intrahepatic treatment should still be considered as experimental. EUDRACT NUMBER AND CLINICALTRIALSGOV IDENTIFIER: 2004-002245-12 and NCT00110123.

Interleukin-8 secretion by fibroblasts induced by low density lipoproteins is p38 MAPK-dependent and leads to cell spreading and wound closure.

We have previously reported (Dobreva, I., Waeber, G., Mooser, V., James, R. W., and Widmann, C. (2003) J. Lipid Res. 44, 2382-2390) that low density lipoproteins (LDLs) induce activation of the p38 MAPK pathway, resulting in fibroblast spreading and lamellipodia formation. Here, we show that LDL-stimulated fibroblast spreading and wound sealing are due to secretion of a soluble factor. Using an antibody-based human protein array, interleukin-8 (IL-8) was identified as the main cytokine whose concentration was increased in supernatants from LDL-stimulated cells. Incubation of supernatants from LDL-treated cells with an anti-IL-8 blocking antibody completely abolished their ability to induce cell spreading and mediate wound closure. In addition, fibroblasts treated with recombinant IL-8 spread to the same extent as cells incubated with LDL or supernatants from LDL-treated cells. The ability of LDL and IL-8 to induce fibroblast spreading was mediated by the IL-8 receptor type II (CXCR-2). Furthermore, LDL-induced IL-8 production and subsequent wound closure required the activation of the p38 MAPK pathway, because both processes were abrogated by a specific p38 inhibitor. Therefore, the capacity of LDLs to induce fibroblast spreading and accelerate wound closure relies on their ability to stimulate IL-8 secretion in a p38 MAPK-dependent manner. Regulation of fibroblast shape and migration by lipoproteins may be relevant to atherosclerosis that is characterized by increased LDL cholesterol levels, IL-8 production, and extensive remodeling of the vessel wall.

Corneal Opacities in Trisomy 8 Mosaic Syndrome : Clinical, Histologic and Genetic Features

Purpose: To describe the clinical, histologic and genetic findings of corneal opacities in the trisomy 8 mosaic syndrome. Methods: 3 children aged 8 years (Patients A), 6 years (Patients B) and 1 month (Patients C) respectively, were referred with corneal opacities for ophthalmologic evaluation. The 2 older patients had been previously diagnosed with trisomy 8 mosaicism, while the third was diagnosed after the ocular examination. Automated lamellar keratoplasty (ALTK) was performed on the most amblyopic eye. Histopathologic analysis with immunohistochemical markers and cytogenetic studies by FISH using haploid probes for chromosome 8 and chromosome 16 (control) were performed on the excised corneal lesion. Results: All patients presented vascularized corneal opacities involving the superficial stroma, and amblyopia with a bilateral involvement in two of them (Patients A and B). Post-operative follow-up (range 6-20 months) was satisfactory, with the graft remaining clear and improved visual acuity, allowing iso-acuity and stereoscopy in the one month old child (Patients C). The clinically observed corneal opacities corresponded histopathologically to the replacement of the normal anterior corneal stroma by a choristomatous loose richly vascularized connective tissue containing mucopolysacharides. Bowman's membrane was absent. There were no adnexal structures. The overlaying epithelium expressed keratin 3 in all three cases. Keratin 19 was found in the suprabasal epithelial cells in one case but was absent in the other cases. There were no expression of keratin 7 and 1 as well as MUC5AC in the epithelial cells. FISH analysis from 100 interphase cells of the affected tissue and normal conjontival probe revealed normal diploid cells. Conclusions: In this series, the corneal opacities associated with trisomy 8 mosaic syndrome share a common clinical, histopathological and genetic features. ALTK should be considered at diagnosis to prevent amblyopia in these children.

Total energy expenditure and patterns of activity in 8-10-year-old obese and nonobese children.

Total energy expenditure (TEE) and patterns of activity were measured by means of a heart rate (HR)-monitoring method in a group of 8-10-year-old children including 13 obese children (weight, 46 +/- 10 kg; fat mass: 32 +/- 9%) and 16 nonobese children (weight, 31 +/- 5 kg; fat mass, 18 +/- 5%). Time for sleeping was not statistically different in the two groups of children (596 +/- 33 vs. 582 +/- 43 min; p = NS). Obese children spent more time doing sedentary activities (400 +/- 129 vs. 295 +/- 127 min; p < 0.05) and less time in nonsedentary activities (449 +/- 126 vs. 563 +/- 135 min; p < 0.05) than nonobese children. Time spent in moderate or vigorous activity-i.e., time spent at a HR between 50% of the maximal O2 uptake (peak VO2) and 70% peak VO2 (moderate) and at a HR > or = 70% peak VO2 (vigorous)-was not statistically different in obese and nonobese children (88 +/- 69 vs. 52 +/- 35 min and 20 +/- 21 vs. 16 +/- 13 min, respectively; p = NS). TEE was significantly higher in the obese group than in the nonobese group (9.46 +/- 1.40 vs. 7.51 +/- 1.67 MJ/day; p < 0.01). The energy expenditure for physical activity (plus thermogenesis) was significantly higher in the obese children (3.98 +/- 1.30 vs. 2.94 +/- 1.39 MJ/day; p < 0.05). The proportion of TEE daily devoted to physical activity (plus thermogenesis) was not significantly different in the two groups, as shown by the ratio between TEE and the postabsorptive metabolic rate (PMR): 1.72 +/- 0.25 obese vs 1.61 +/- 0.28 non-obese. In conclusion, in free-living conditions obese children have a higher TEE than do nonobese children, despite the greater time devoted to sedentary activities. The higher energy cost to perform weight-bearing activities as well as the higher absolute PMR of obese children help explain this apparent paradox.

IL-4 rapidly produced by V beta 4 V alpha 8 CD4+ T cells instructs Th2 development and susceptibility to Leishmania major in BALB/c mice.

BALB/c mice develop aberrant T helper 2 (Th2) responses and suffer progressive disease after infection with Leishmania major. These outcomes depend on the production of interleukin-4 (IL-4) early after infection. Here we demonstrate that the burst of IL-4 mRNA, peaking in draining lymph nodes of BALB/c mice 16 hr after infection, occurs within CD4+ T cells that express V beta 4 V alpha 8 T cell receptors. In contrast to control and V beta 6-deficient BALB/c mice, V beta 4-deficient BALB/c mice were resistant to infection, demonstrating the role of these cells in Th2 development. The early IL-4 response was absent in these mice, and T helper 1 responses occurred following infection. Recombinant LACK antigen from L. major induced comparable IL-4 production in V beta 4 V alpha 8 CD4+ cells. Thus, the IL-4 required for Th2 development and susceptibility to L. major is produced by a restricted population of V beta 4 V alpha 8 CD4+ T cells after cognate interaction with a single antigen from this complex organism.