A systematic review of interventions to reduce psychological distress in pediatric patients receiving radiation therapy

Objective

Radiation therapy (RT) is a cornerstone for management of pediatric cancer. For younger patients, unintended radiation to critical organs is a concern and children need to remain immobile. Distress in children is common so many centres sedate pediatric patients. Children often are unable to remain still, due to anxiety. Interventions to reduce distress could also reduce sedation rates. The objectives of this systematic review were to: review the interventions used to address pediatric RT patients' distress and anxiety and assess their effectiveness.

Pediatric urography: comparison of metrizamide and methylglucamine diatrizoate

A non-ionic contrast medium (metrizamide) was compared to an ionic agent (methylglucamine diatrizoate) for pediatric urography. Fifty children were divided into two age groups: under 5, and 5 to 10. In younger children, metrizamide gave more excellent images (19% vs. 0%) and fewer inadequate images (0% vs. 18%) than methylglucamine diatrizoate (p = 0.06). In older children, metrizamide likewise gave more excellent images (44% vs. 14%) and fewer inadequate images (0% vs. 7%). The same pattern was seen when the two groups were combined (excellent, 28% vs. 8%; inadequate, 0% vs. 12%) (p = 0.05). Differences with respect to changes in hematocrit, serum osmolality, serum sodium, and SGOT were statistically significant, but not adverse reactions. In terms of both efficacy and safety, the authors conclude that metrizamide is preferred for pediatric urography.     

Effect of a short-term in vitro exposure to the marine toxin domoic acid on viability, tumor necrosis factor-alpha, matrix metalloproteinase-9 and superoxide anion release by rat neonatal microglia

Background

The excitatory amino acid domoic acid, a glutamate and kainic acid analog, is the causative agent of amnesic shellfish poisoning in humans. No studies to our knowledge have investigated the potential contribution to short-term neurotoxicity of the brain microglia, a cell type that constitutes circa 10% of the total glial population in the brain. We tested the hypothesis that a short-term in vitro exposure to domoic acid, might lead to the activation of rat neonatal microglia and the concomitant release of the putative neurotoxic mediators tumor necrosis factor-α (TNF-α), matrix metalloproteinases-2 and-9 (MMP-2 and -9) and superoxide anion (O₂-).

Results

In vitro, domoic acid [10 μM-1 mM] was significantly neurotoxic to primary cerebellar granule neurons. Although neonatal rat microglia expressed ionotropic glutamate GluR4 receptors, exposure during 6 hours to domoic acid [10 μM-1 mM] had no significant effect on viability. By four hours, LPS (10 ng/mL) stimulated an increase in TNF-α mRNA and a 2,233 % increase in TNF-α protein In contrast, domoic acid (1 mM) induced a slight rise in TNF-α expression and a 53 % increase (p < 0.01) of immunoreactive TNF-α protein. Furthermore, though less potent than LPS, a 4-hour treatment with domoic acid (1 mM) yielded a 757% (p < 0.01) increase in MMP-9 release, but had no effect on MMP-2. Finally, while PMA (phorbol 12-myristate 13-acetate) stimulated O₂- generation was elevated in 6 hour LPS-primed microglia, a similar pretreatment with domoic acid (1 mM) did not prime O₂- release.

Conclusions

To our knowledge this is the first experimental evidence that domoic acid, at in vitro concentrations that are toxic to neuronal cells, can trigger a release of statistically significant amounts of TNF-α and MMP-9 by brain microglia. These observations are of considerable pathophysiological significance because domoic acid activates rat microglia several days after in vivo administration.     

Mutation screening of the BTK gene in 56 families with X-linked agammaglobulinemia (XLA): 47 unique mutations without correlation to clinical course

OBJECTIVES: To determine the utility of single-stranded conformation polymorphism (SSCP) analysis for mutation screening in the BTK (Bruton's tyrosine kinase) gene, we investigated 56 X-linked agammaglobulinemia (XLA) families. To obtain genotype/ phenotype correlations, predicted protein aberrations were correlated with the clinical course of the disease. PATIENTS: This study included 56 patients with XLA, with or without a positive family history, who were diagnosed on the basis of their clinical features, low peripheral B-cell count, and low immunoglobulin levels. Ten patients with isolated hypogammaglobulinemia and 50 healthy males served as controls. METHODS: SSCP analysis was performed for the entire BTK gene, including the exon-intron boundaries and the promoter region. Structural implications of the missense mutations were investigated by molecular modeling, and the functional consequences of some mutations also were evaluated by in vitro kinase assays and Western blot analysis. RESULTS: We report the largest series of patients with XLA to date. All but 5 of the 56 index patients with XLA screened with SSCP analysis showed BTK gene abnormalities, and in 2 of the 5 SSCP-negative patients, no BTK protein was found by Western blot analysis. There were 51 mutations, including 37 novel ones, distributed across the entire gene. This report contains the first promoter mutation as well as 14 novel missense mutations with the first ones described for the Tec homology domain and the glycine-rich motif in the SH1 domain. Each index patient had a different mutation, except for four mutations, each in two unrelated individuals. This result supports the strong tendency for private mutations in this disease. No mutations were found in the controls. CONCLUSIONS: Our results demonstrate that molecular genetic testing by SSCP analysis provides an accurate tool for the definitive diagnosis of XLA and the discrimination of borderline cases, such as certain hypogammaglobulinemia or common variable immunodeficiency patients with overlapping clinical features. Genotype/ phenotype correlations are not currently possible, making prediction of the clinical course based on molecular genetic data infeasible.     

Engraftment with peripheral blood stem cells collected by large-volume leukapheresis for patients with lymphoma

Seven patients with refractory lymphomas underwent marrow reconstitution with peripheral blood stem cells (PBSCs) harvested by large-volume leukapheresis (LVL). PBSCs were collected from all patients more than 1 month after the last cycle of chemotherapy, and no patient received growth factors. The median number of LVL procedures performed per patient was 4.5, with a mean volume of 24.5 L of blood processed per procedure to obtain 7 x 10(8) mononuclear cells per kg. Autologous PBSCs and platelets were frozen at a controlled rate in plasma and 10-percent dimethyl sulfoxide and stored in the vapor phase of liquid nitrogen. This group of patients was compared to a control group (n = 18) who received medullary marrow (MM) transplants for the same diagnoses under the same protocols during the same period. Posttransplant days to white cell engraftment (PBSC = 17, MM = 15.5) were no different. Days to platelet independence were significantly longer in the LVL PBSC group (PBSC = 33, MM = 16; p < 0.05). This pattern of engraftment is typical of patients treated in this manner. Although Day 0 platelet counts (PBSC = 75.5 x 10(9)/L, MM = 85 x 10(9)/L) and total single-donor unit platelet use (PBSC = 8, MM = 9) were no different, Day 1 platelet counts (PBSC = 128 x 10(9)/L, MM = 61.5 x 10(9)/L; p < 0.05) and Day 14 platelet use (PBSC = 5, MM = 8; p < 0.05) were significantly different, because of the transfusion of cryopreserved autologous platelets with PBSCs on Day 0.     

Influence of weight and frequency on thigh and lower-trunk motion during repetitive lifting employing stoop and squat techniques

Changes in kinematics as a function of lifting weight and frequency was investigated in sagittal symmetric repetitive lifting. For every lift cycle (lowering and lifting) the motion range between the upright position (0 degrees ) and the maximum angular displacement of the thigh and lower-trunk body segments was recorded. Ten subjects performed five repetitive lifting bouts with different weight/frequency combinations, using both stoop and squat lifting techniques. In total, 6384 lifts were analysed. The lifting weight or frequency did not influence the motion ranges in stoop lifting. In squat lifting the weight lifted did not appear to have any influence on the motion ranges, while the thigh motion range was significantly smaller at lifting frequency of 20 lifts min(-1) than at a frequency of 10. A significant gradual decrease in the thigh motion range and corresponding increase in the lower-trunk motion range were seen for a majority of the subjects during squat lifting at frequency 20. These changes suggest that quadriceps muscle strength is the limiting factor in repetitive squat lifting. Also the variation in motion ranges was greater in squat lifting than in stoop lifting. RELEVANCE: Forestry work involves frequent lifting. However, compliance in using squat lifting technique, which is recommended for safe lifting, is sometimes poor. Fatigue may be one of the determinants for changes in kinematics and choice of technique in lifting tasks.