Recent skin injuries in children with motor disabilities.

OBJECTIVE: To determine the frequency of recent skin injuries in children with neuromotor disabilities and its association with disability. DESIGN: Cross-sectional study of 168 children with neuromotor disabilities aged 2-16 years. SETTING: Two outpatient child rehabilitation centres. MAIN OUTCOME MEASURES: Children were classified as unrestricted walkers, restricted walkers or wheelchair dependent. Each participant's body surface was systematically examined for recent skin injuries with the exception of the anal-genital area. RESULTS: The mean age of our sample was 7.8 (SD 3.7) years with a 3:2 male/female ratio. Overall, 64% had cerebral palsy, 17% a neuromuscular disease and 19% other motor disabilities. Participants had on average 5.3 (SD 4.5) recent skin injuries (max 19), of which 2.5 were bruises (SD 3.3, max 16), 2.4 were abrasions, scratches or cuts (SD 3.0, max 16) and 0.4 were pressure lesions (SD 0.8, max 4). There was a significant decrease in the frequency of recent skin injuries and of bruises with increasing severity of motor disability. Most of this variation was accounted for by injuries to the lower limbs. There were no significant effects of gender, learning disabilities or other comorbidities. CONCLUSIONS: Children with neuromotor disabilities present a progressive reduction in the number of skin injuries with decreasing mobility. Therefore, recent skin injuries in this population which are unusual by their number, appearance or distribution, should raise at least the same level of suspicion for physical abuse as in children without disabilities.

Tissue homing and persistence of defined antigen-specific CD8+ tumor-reactive T-cell clones in long-term melanoma survivors.

Tumor antigen-specific cytotoxic T cells (CTLs) play a major role in the adaptive immune response to cancers. This CTL response is often insufficient because of functional impairment, tumor escape mechanisms, or inhibitory tumor microenvironment. However, little is known about the fate of given tumor-specific CTL clones in cancer patients. Studies in patients with favorable outcomes may be very informative. In this longitudinal study, we tracked, quantified, and characterized functionally defined antigen-specific T-cell clones ex vivo, in peripheral blood and at tumor sites, in two long-term melanoma survivors. MAGE-A10-specific CD8+ T-cell clones with high avidity to antigenic peptide and tumor lytic capabilities persisted in peripheral blood over more than 10 years, with quantitative variations correlating with the clinical course. These clones were also found in emerging metastases, and, in one patient, circulating clonal T cells displayed a fully differentiated effector phenotype at the time of relapse. Longevity, tumor homing, differentiation phenotype, and quantitative adaptation to the disease phases suggest the contribution of the tracked tumor-reactive clones in the tumor control of these long-term metastatic survivor patients. Focusing research on patients with favorable outcomes may help to identify parameters that are crucial for an efficient antitumor response and to optimize cancer immunotherapy.

Processing of metacaspase into a cytoplasmic catalytic domain mediating cell death in Leishmania major.

Metacaspases are cysteine peptidases that could play a role similar to caspases in the cell death programme of plants, fungi and protozoa. The human protozoan parasite Leishmania major expresses a single metacaspase (LmjMCA) harbouring a central domain with the catalytic dyad histidine and cysteine as found in caspases. In this study, we investigated the processing sites important for the maturation of LmjMCA catalytic domain, the cellular localization of LmjMCA polypeptides, and the functional role of the catalytic domain in the cell death pathway of Leishmania parasites. Although LmjMCA polypeptide precursor form harbours a functional mitochondrial localization signal (MLS), we determined that LmjMCA polypeptides are mainly localized in the cytoplasm. In stress conditions, LmjMCA precursor forms were extensively processed into soluble forms containing the catalytic domain. This domain was sufficient to enhance sensitivity of parasites to hydrogen peroxide by impairing the mitochondrion. These data provide experimental evidences of the importance of LmjMCA processing into an active catalytic domain and of its role in disrupting mitochondria, which could be relevant in the design of new drugs to fight leishmaniasis and likely other protozoan parasitic diseases.

Residuelle Lungenfunktionsveränderungen nach "Adult Respiratory Distress Syndrome" (ARDS) bei Kindern [Residual lung function changes following adult respiratory distress syndrome (ARDS) in children]

Residual lung function abnormalities have been investigated in 9 children (4 boys and 5 girls) a mean 2.7 years after surviving severe adult respiratory distress syndrome (ARDS). All patients had been artificially ventilated for an average of 9.4 days with a FiO2 greater than 0.5 for 34 hours and maximal PEEP levels in the range of 8-20 cm H2O. Since the ARDS, 3 children had presented recurrent respiratory symptoms (moderate exertional dyspnea and cough) and 2 had had evidence of fibrosis on chest radiographs. In all patients abnormal lung functions were found, i.e. ventilation inequalities (8), hypoxemia (7), and obstructive (2) and restrictive (1) lung disease. A significant correlation between respirator therapy and residual lung function was found (duration of FiO2 greater than 0.5 in hours and inspiratory plateau pressure during respirator therapy vs. ventilation inequalities and hypoxemia).