Brief report: Evaluation of an interactive intervention designed to reduce pediatric distress during radiation therapy procedures

OBJECTIVE: To evaluate the efficacy of an interactive intervention in reducing distress related to radiation therapy (RT) among pediatric cancer participants as measured by occurrence of sedation, observed behavioral distress (OBD), and heart rate (HR). METHODS: Seventy-nine children receiving RT simulation were assigned randomly to a STARBRIGHT Hospital Pals group (i.e., interactive intervention group; IG) or modified control group (MCG). The interactive intervention included filmed modeling, exposure to an interactive Barney character, and passive auditory distraction. RESULTS: Children in the IG experienced significantly lower HR when compared with MCG participants. No differences were found in terms of sedation or OBD. CONCLUSIONS: The interactive intervention was effective at reducing RT-related distress (as measured by HR) and would be a useful tool in pediatric radiation oncology settings.     

Temporal bone histopathology in alport syndrome

OBJECTIVE: To determine the histopathologic abnormalities within the cochlea in Alport syndrome. BACKGROUND: Alport syndrome, which manifests as hereditary nephritis and sensorineural hearing loss (SNHL), is caused by mutations in genes that code for the proportional, variant3, proportional, variant4, and proportional, variant5 chains of type IV collagen. The proportional, variant3, proportional, variant4, and proportional, variant5 chains of type IV collagen are present in the basement membrane of the organ of Corti. Previous temporal bone studies have failed to identify histopathologic correlates for the SNHL. METHODS: We examined temporal bones from nine individuals with a clinical diagnosis of Alport syndrome. One of our cases also had genetic testing that showed a mutation in the type IV collagen proportional, variant5 chain gene. RESULTS: By light microscopy, eight of nine cases demonstrated two unique pathologic changes: 1) a "zone of separation" between the basilar membrane and overlying cells of the organ of Corti and 2) presence of cells filling the tunnel of Corti and extracellular spaces of Nuel. The cytologic losses of hair cells, stria vascularis, and cochlear neuronal cells were insufficient to account for the observed SNHL in our cases. Electron microscopy was performed in four cases; all four demonstrated the following: 1) the zone of separation that was observed at light microscopy occurred between the basement membrane and the basilar membrane, 2) the cells within the tunnel of Corti and spaces of Nuel were morphologically similar to supporting cells, and 3) the basement membrane of strial capillaries and the spiral vessel (under the basilar membrane) were normal. CONCLUSIONS: The histopathologic correlates of cochlear involvement in Alport syndrome are abnormalities of the basement membrane of cells of the organ of Corti and dysmorphogenesis (cellular infilling of the tunnel and extracellular spaces) of the organ of Corti. We hypothesize that these abnormalities result in SNHL by altering cochlear micromechanics.     

Functional organization of parietal neuronal responses to optic-flow stimuli

We analyzed the dissimilarity matrix of neuronal responses to moving visual stimuli using tree clustering and multidimensional scaling (MDS). Single-cell activity was recorded in area 7a while random dots moving coherently in eight different kinds of motion (right-, left-, up-, and downward, clockwise, counterclockwise, expansion, contraction) were presented to behaving monkeys with eyes fixated. Tree clustering analyses showed that the [rightward, leftward], [upward, downward], and [clockwise, counterclockwise]] motions were clustered in three separate branches (i.e., horizontal, vertical, and rotatory motion, respectively). In contrast, expansion was in a lone branch, whereas contraction was also separate but within a larger cluster. The distances among these clusters were then subjected to an MDS analysis to identify the dimensions underlying the tree clustering observed. This analysis revealed two major factors in operation. The first factor separated expansion from all other stimulus motions, which seems to reflect the prominence of expansion during the common activity of locomotion. In contrast, the second factor separated planar motions from motion in depth, which suggests that the latter may hold a special place in visual motion processing.     

Addicted schoolchildren: prevalence and characteristics of areca nut chewers among primary school children in Karachi,Pakistan

OBJECTIVES: To evaluate the habits of betel quid use and areca nut chewing among school-aged children in Karachi, Pakistan. Areca nut (betel nut) is chewed by itself, in various scented preparations, and in betel quid (containing betel leaf, areca nut, slaked lime, condiments, sweeteners and sometimes tobacco) in various parts of Pakistan and India. It is associated with carcinogenesis, foreign body aspiration in children and oral submucous fibrosis, and may aggravate asthma. METHODS: We selected a stratified random sample of 160 primary school children between 4 and 16 years of age in Baba Island, Karachi. RESULTS: Seventy-four per cent of the children (118/159) used areca nut and 35% (55/159) used betel quid daily. More boys chewed areca nut than girls (72% vs 30%). The proportion of areca nut users increased by grade (from 48% in first grade to 90% in fifth grade). Most areca users first tried it with a family member (42%) or a friend (26%), and most (68%) consumed three or more packets a day. Children with fathers with three or fewer years of education were more likely to use areca nut (OR 3.2; 95% CI 1.2-8.4), and children whose mothers helped with homework less likely (OR 0.5; 95% CI 0.2-0.91; P = 0.027) to use it. Boys (OR 6.6; 95% CI 2.3-18.7) and areca nut users (OR 8.8; 95% CI2.8-27.0) were more likely to use betel quid. CONCLUSION: To reduce the use of areca nut, the Pakistan Government should consider imposing taxes on it, limiting advertising and actively communicating its health risks to the public.     

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales,Australia. III. Release,persistence and rate of spread of an identifiable strain of myxoma virus

An identifiable strain of myxoma virus was introduced into four local populations of wild rabbits Oryctolagus cuniculus on the southern tablelands of New South Wales (NSW) and its spread in the presence of other field strains was monitored for 6 months. The main vector in this region was considered to be the European rabbit flea Spilopsyllis cuniculi. Each population of rabbits was of a high density and living in groups of warrens covering areas from 59 to 87 hectares. Rabbits occupying centrally located warrens were inoculated with the virus in late September or early October (spring) and the subsequent appearance of myxomatosis across the sites monitored by trapping, shooting and visual observations. Samples, taken from rabbits with myxomatosis, were examined by polymerase chain reaction (PCR) that allowed identification of the introduced strain. On all four sites the introduced virus spread from the inoculated rabbits in the centrally located warrens to rabbits in surrounding warrens. On Sites 1 and 3, this spread continued across the entire site persisting for at least 118 and 174 days respectively. On Sites 2 and 4, the virus was detected for 78 and 62 days respectively and the subsequent inability to detect the introduced virus correlated with the appearance of an unrelated field strain. Using three different methods of calculation, rates of spread ranged from 3.7 to 17.8 m d(-1).     

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales,Australia. I. Natural occurrence of myxomatosis

A survey of rabbit populations in the southern tablelands of New South Wales, Australia, was carried out to establish the pattern of occurrence of myxomatosis in preparation for a deliberate release of myxoma virus. Myxomatosis was first detected in December and cases were found on most sites through to May. The serological profiles of rabbit populations suggested that their susceptibility to myxoma virus was generally low in winter and highest in spring and summer reflecting the presence of increasing numbers of susceptible young rabbits. This was consistent with the pattern of rabbit breeding, as determined from the distribution of births and reproductive activity in females and males, which occurred maximally in spring and early summer. The serology and age structure of rabbit populations on sites suggested that some rabbit populations can escape an annual myxomatosis epizootic. Although fleas were present on rabbits throughout the year and therefore not considered to be a limiting factor in the spread of myxomatosis, their numbers peaked at times coincident with peak rabbit breeding. It was concluded that mid to late spring was an optimal time for a deliberate release.     

Beta-platelet-derived growth factor receptor mediates motility and growth of Ewing's sarcoma cells

The Ewing's sarcoma family of tumors (ESFT) contain a translocation, t(11;22), which results in the novel oncogenic fusion protein EWS/FLI1. Platelet-derived growth factors (PDGF) and their receptors (PDGFR) are involved in the induction and proliferation of numerous solid tumors and are the potential candidates for novel targeted antitumor therapy. Since a relation was reported between PDGF-C and EWS/FLI1, we sought to characterize the PDGF signaling pathway in ESFT. Eight out of nine ESFT cell lines were found to express significant levels of beta-PDGFR. Interestingly, none of the tested cell lines expressed alpha-PDGFR, which is the receptor isotype required for PDGF-C binding. By immunohistochemical staining 47 of 52 (90.4%) archival tumor samples from patients with ESFT were positive for beta-PDGFR. ESFT cell lines were treated with PDGF-AA or PDGF-BB ligands to evaluate downstream signaling. Autophosphorylation of beta-PDGFR and tyrosine phosphorylation of PLC-gamma, PI3Kp85 and Shc were detected only in PDGF-BB-stimulated cells that express beta-PDGFR. Receptor function was further evaluated using chemotaxis assays that showed TC-32 cell migration towards PDGF-BB. A specific PDGFR kinase inhibitor AG1295 blocked beta-PDGFR activation, downstream signaling, growth in cell culture and chemotaxis of TC-32 cells. AG1295 also delayed tumor formation and prolonged survival in an ESFT animal model. We conclude that ESFT express beta-PDGFR and that this is a functional and potentially crucial signaling pathway. Therefore, beta-PDGFRs may provide a novel therapeutic target in ESFT that can be utilized to design better treatment modalities.     

Tumor expression of 4-1BB ligand sustains tumor lytic T cells

Inadequate costimulation by solid tumors is generally believed to induce immune tolerance during primary tumor growth. We looked for tumor-specific immunity vs. tolerance in patients with Ewing's sarcoma. Circulating T cells from patients with progressively growing Ewing's tumors displayed MHC restricted tumor-induced proliferation and robust tumor lysis. Tumor-reactive T cells reside within the memory CD3+CD8+ subset and are CD28-/4-1BB+. Autologous Ewing's tumors expressed 4-1BBL, and tumor-induced T cell proliferation and activation required costimulation by 4-1BBL. Stimulation of PBL with anti-CD3/4-1BBL, but not anti-CD3/anti-CD28 induced tumor lytic effectors. Similarly, in a xenograft model, anti-CD3/4-1BBL expanded T cells controlled primary growth and prevented metastasis of autologous tumors while nonactivated and anti-CD3/anti-CD28 activated CD8+ cells did not. These results question prevailing models of tumor induced tolerance accompanying progressive tumor growth; rather, we show coexistence of progressive tumor growth and anti-tumor immunity, with costimulation provided by the tumor itself. They further demonstrate a potential new therapeutic role for 4-1BBL mediated costimulation in expanding tumor reactive CTLs for use in the adoptive immunotherapy of cancer.