Language outcomes subsequent to treatment of brainstem tumour in childhood

While the occurrence and management of brainstem tumours in children would not traditionally indicate potential direct structural impact on classical language centres, recent theories have implicated some involvement of the brainstem in a functional language and cognitive neural loop between the cerebellum and the cerebral hemispheres. Thus, the present paper explored the impact of treatment for brainstem tumour on the general and high-level language abilities of six children treated for brainstem tumour, in addition to phonological awareness skills. Group analysis revealed that children treated for brainstem tumour demonstrated intact language and phonological awareness abilities in comparison to an age- and gender-matched control group. Individual analysis revealed only one of six children treated for brainstem tumour revealed evidence of language disturbances, with an additional child demonstrating an isolated mildly reduced score on one phonological awareness task. Language deficits identified in a child treated with a combination of both radiotherapy and chemotherapy were noted in the high-level language area of lexical generation. Findings highlighted that no overt language disturbances were evident in children treated for brainstem tumour. However, further analysis into higher-level language skills in the present study indicated that both general and high-level language abilities require long-term monitoring in this population.

In vivo dynamics of axon pathfinding in the Drosophila CNS: A time-lapse study of an identified motoneuron

We developed a system for time-lapse observation of identified neurons in the central nervous system (CNS) of the Drosophila embryo. Using this system, we characterize the dynamics of filopodia and axon growth of the motorneuron RP2 as it navigates anteriorly through the CNS and then laterally along the intersegmental nerve (ISN) into the periphery. We find that both axonal extension and turning occur primarily through the process of filopodial dilation. In addition, we used the GAL4-UAS system to express the fusion protein Tau-GFP in a subset of neurons, allowing us to correlate RP2's patterns of growth with a subset of axons in its environment. In particular, we show that RP2's sharp lateral turn is coincident with the nascent ISN. (C) 1998 John Wiley & Sons, Inc.

Combination therapy with tacrolimus and anti-thymocyte globulin for the treatment of steroid-resistant acute graft-versus-host disease developing during cyclosporine prophylaxis

We report our experience with the combination of anti-thymocyte globulin (ATGAM) and tacrolimus in the treatment of 20 patients with steroid refractory and dependent acute graft-versus-host disease (GVHD) transplanted between August 1996 and February 2000. All patients received cyclosporine-based GVHD prophylaxis. Thirteen patients developed a maximum of grade TV, five grade III and two grade II acute GVHD, with 15 patients being refractory to steroids and five dependent on steroids. Patients were treated with ATGAM (15 mg/kg for 5 d) and tacrolimus (0.025-0.1 mg/kg/d) in addition to continuation of their high-dose steroids and cessation of their cyclosporine. Within 28 d of treatment, we observed eight complete responses (CR), six partial responses (PR) and six with no response. Overall response (CR + PR) was predicted by GVHD severity. Infectious complications occurred in 80% of patients. The median survival was 86.5 d (range, 21-1081 d) with 35% of patients remaining alive, Survival following combination therapy was significantly more likely in men (P < 0.001), skin-only GVHD (P = 0.027), less severe GVHD (P = 0.048), and in responders to tacrolimus and ATGAM (P< 0.001). In conclusion, concurrent introduction of ATGAM and tacrolimus is a promising therapeutic combination for GVHD refractory to steroids and cyclosporine.

Comparison of tafenoquine (WR238605) and primaquine in the post-exposure (terminal) prophylaxis of vivax malaria) in Australian Defence Force personnel

On return from duty in North Solomons Province (including Bougainville Island), Papua New Guinea, 586 Australian Defence Force personnel received either primaquine (14-d) or tafenoquine (3-d) post-exposure malaria prophylaxis. Within 12 months, 6 of the 214 volunteers receiving primaquine and 7 of 378 receiving tafenoquine had developed vivax malaria. Overall, volunteers preferred the shorter course of tafenoquine.

Plasma concentrations of tafenoquine, a new long-acting antimalarial agent, in Thai soldiers receiving monthly prophylaxis

We measured plasma tafenoquine concentrations in Thai soldiers given a monthly regimen of tafenoquine to determine whether these concentrations adequately suppressed malarial infections on the Thai- Cambodian border. After receiving a treatment course of artesunate and doxycycline, 104 male soldiers were administered a loading dose of tafenoquine ( 400 mg daily for 3 days), followed by tafenoquine monthly ( 400 mg every 4 weeks) for 5 months. Consecutive monthly mean ( +/- standard deviation) trough plasma tafenoquine concentrations were 223 +/- 41, 127 +/- 29, 157 +/- 51. 120 +/- 24, and 88 +/- ng/ mL. Only 1 soldier developed malaria during the study. At the time of malaria diagnosis, his plasma tafenoquine concentration was 40 ng/ mL, which was similar to 3- fold lower than the trough concentrations of the other soldiers. Although low tafenoquine concentrations appear to be uncommon, additional investigations are needed to determine the relationship between plasma tafenoquine concentrations and suppression of malaria.

Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P-falciparum malaria

We assessed monthly doses of tafenoquine for preventing Plasmodium vivax and multidrug-resistant P. falciparum malaria. In a randomized, double-blind, placebo-controlled study, 205 Thai soldiers received either a loading dose of tafenoquine 400 mg ( base) daily for 3 days, followed by single monthly 400-mg doses (n = 104), or placebo (n = 101), for up to 5 consecutive months. In volunteers completing follow-up (96 tafenoquine and 91 placebo recipients), there were 22 P. vivax, 8 P. falciparum, and 1 mixed infection. All infections except 1 P. vivax occurred in placebo recipients, giving tafenoquine a protective efficacy of 97% for all malaria (95% confidence interval [CI], 82%-99%), 96% for P. vivax malaria (95% CI, 76%-99%), and 100% for P. falciparum malaria ( 95% CI, 60%-100%). Monthly tafenoquine was safe, well tolerated, and highly effective in preventing P. vivax and multidrug-resistant P. falciparum malaria in Thai soldiers during 6 months of prophylaxis.

Comparative analysis of CNS populations in knockout mice with altered growth hormone responsiveness

Recently we have shown that growth hormone (GH) inhibits neuronal differentiation and that this process is blocked by suppressor of cytokine signalling-2 (SOCS2). Here we examine several cortical and subcortical neuronal populations in GH hyper-responsive SOCS2 null (-/-) mice and GH non-responsive GH receptor null (GHR-/-) mice. While SOCS2-/- mice showed a 30% decrease in density of NeuN positive neurons in cortex compared to wildtype, GHR-/- mice showed a 25% increase even though brain size was decreased. Interneuron sub-populations were variably affected, with a slight decrease in cortical parvalbumin expressing interneurons in SOCS2-/- mice and an increase in cortical calbindin and calretinin and striatal cholinergic neuron density in GHR-/- mice. Analysis of glial cell numbers in cresyl violet or glial fibrillary acidic protein (GFAP) stained sections of cortex showed that the neuron: glia ratio was increased in GHR-/- mice and decreased in SOCS2-/- mice. The astrocytes in GHR-/- mice appeared smaller, while they were larger in SOCS2-/- mice. Neuronal soma size also varied in the different genotypes, with smaller striatal cholinergic neurons in GHR-/- mice. While the size of layer 5 pyramidal neurons was not significantly different from wildtype, SOCS2-/- neurons were larger than GHR-/- neurons. In addition, primary dendritic length was similar in all genotypes but dendritic branching of pyramidal neurons in the cortex appeared sparser in GHR-/- and SOCS2-/- mice. These results suggest that GH, possibly regulated by SOCS2, has multiple effects on central nervous system (CNS) development and maturation, regulating the number and size of multiple neuronal and glial cell types.

Adult CNS explants as a source of neural progenitors

Adult neural progenitors have been isolated from diverse regions of the CNS using methods which primarily involve the enzymatic digestion of tissue pieces; however, interpretation of these experiments can be complicated by the loss of anatomical resolution during the isolation procedures. We have developed a novel, explant-based technique for the isolation of neural progenitors, Living CNS regions were sectioned using a vibratome and small, well-defined discs of tissue punched out. When Cultured. explants from the cortex, hippocampus, cerebellum, spinal cord, hypothalamus, and caudate nucleus all robustly gave rise to proliferating progenitors. These progenitors were similar in behaviour and morphology to previously characterised multipotent hippocampal progenitor lines. Clones from all regions examined could proliferate from single cells and give rise to secondary neurospheres at a low but consistent frequency. Immunostaining demonstrated that clonal cortical progenitors were able to differentiate into both neurons and glial cells, indicating their multipotent characteristics. These results demonstrate it is possible to isolate anatomically resolved adult neural progenitors from small amounts of tissue throughout the CNS, thus, providing a tool for investigating the frequency and characteristics of progenitor cells from different regions. (c) 2005 Elsevier B.V. All rights reserved.

Mefloquine and doxycycline malaria prophylaxis in Australian soldiers in East Timor

Objectives: To describe the tolerability of mefloquine in Australian soldiers for malaria prophylaxis, including a comparison with doxycycline. Design: Open-label, prospective study and cross-sectional questionnaire and interview. Setting and participants: Two contingents of Australian soldiers, each deployed to East Timor for peacekeeping duties over a 6-month period (April 2001-October 2001 and October 2001-May 2002). Outcome measures: Withdrawals during the study; adverse events relating to mefloquine prophylaxis; willingness to use mefloquine again on deployment. Results: Of 1157 soldiers starting on mefloquine, 75 (6.5%) withdrew because of adverse responses to the drug. There were three serious adverse events of a neuropsychiatric nature, possibly relating to mefloquine. Fifty-seven per cent of soldiers using mefloquine prophylaxis reported at least one adverse event, compared with 56% using doxycycline. The most commonly reported adverse effects of both drugs were sleep disturbance, headache, tiredness and nausea. Of the 968 soldiers still taking mefloquine at the end of their deployments, 94% indicated they would use mefloquine again. Of 388 soldiers taking doxycycline prophylaxis who were deployed with the first mefloquine study contingent, 89% indicated they would use doxycycline again. Conclusions: Mefloquine was generally well tolerated by Australian soldiers and should continue to be used for those intolerant of doxycycline.

Does anticipation of back pain predispose to back trouble?

Limb movement imparts a perturbation to the body. The impact of that perturbation is limited via anticipatory postural adjustments. The strategy by which the CNS controls anticipatory postural adjustments of the trunk muscles during limb movement is altered during acute back pain and in people with recurrent back pain, even when they are pain free. The altered postural strategy probably serves to protect the spine in the short term, but it is associated with a cost and is thought to predispose spinal structures to injury in the long term. It is not known why this protective strategy might occur even when people are pain free, but one possibility is that it is caused by the anticipation of back pain. In eight healthy subjects, recordings of intramuscular EMG were made from the trunk muscles during single and repetitive arm movements. Anticipation of experimental back pain and anticipation of experimental elbow pain were elicited by the threat of painful cutaneous stimulation. There was no effect of anticipated experimental elbow pain on postural adjustments. During anticipated experimental back pain, for single arm movements there was delayed activation of the deep trunk muscles and augmentation of at least one superficial trunk muscle. For repetitive arm movements, there was decreased activity and a shift from biphasic to monophasic activation of the deep trunk muscles and increased activity of superficial trunk muscles during anticipation of back pain. In both instances, the changes were consistent with adoption of an altered strategy for postural control and were similar to those observed in patients with recurrent back pain. We conclude that anticipation of experimental back pain evokes a protective postural strategy that stiffens the spine. This protective strategy is associated with compressive cost and is thought to predispose to spinal injury if maintained long term. © Guarantors of Brain 2004; all rights reserved