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Self-inactivating (SIN)-lentiviral vectors have safety and efficacy features that are well suited for transduction of hematopoietic stem cells (HSCs), but generation of vector at clinical scale has been challenging. Approximately 280 liters of an X-Linked Severe Combined Immunodeficiency Disorder (SCID-X1) SIN-lentiviral vector in two productions from a stable cell line were concentrated to final titers of 4.5 and 7.2×10(8) tu/ml. These two clinical preparations and three additional development-scale preparations were evaluated in human CD34(+) hematopoietic cells in vitro using colony forming cell (CFU-C) assay and in vivo using the NOD/Lt-scid/IL2Rγ(null) (NSG) mouse xenotransplant model. A 40-hour transduction protocol using a single vector exposure conferred a mean NSG repopulating cell transduction of 0.23 vector genomes/human genome with a mean myeloid vector copy number of 3.2 vector genomes/human genome. No adverse effects on engraftment were observed from vector treatment. Direct comparison between our SIN-lentiviral vector using a 40-hour protocol and an MFGγ(c) γ-retroviral vector using a five-day protocol demonstrated equivalent NSG repopulating cell transduction efficiency. Clonality survey by linear amplification-mediated polymerase chain reaction (LAM-PCR) with Illumina sequencing revealed common clones in sorted myeloid and lymphoid populations from engrafted mice demonstrating multipotent cell transduction. These vector preparations will be used in two clinical trials for SCID-X1.

Unlabelled: To assess the effect of the duration of epilepsy on the outcome of epilepsy surgery in non-lesional medically refractory temporal lobe epilepsy we reviewed the outcome of 76 patients., Methods: All patients had anterior temporal resections for "non-lesional" temporal epilepsy (excluding any patient with tumours or vascular malformations but including patients with hippocampal sclerosis). Outcome at one year was assessed using Engel's scale., Results: 67% had a good outcome (Engel I or II). The mean duration of epilepsy was 23.0 years (range 2.9-46.9 years). Overall, there was no significant difference between patients with good outcome (mean duration 22.4 years) and poor outcome (mean duration 24.2 years) (p=0.49). The proportion of patients with good outcome was slightly higher in the shorter duration groups. (Duration less than 10 years 75%, 10-19 years 71%, 20-29 years 65%, 30-39 years 62%, and 40-49 years 60% good outcome, p=0.95)., Conclusion: We found no significant associations between outcome and duration of epilepsy., (Copyright 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: Iatrogenic intracranial aneurysms are rare in children., Case Report: A 15-year-old girl presented in coma with a fixed dilated left pupil six weeks following removal of a long-standing left-sided ventriculoperitoneal shunt. Computed tomography (CT) and cerebral angiography revealed a left temporoparietal intracerebral haemorrhage with a fusiform distal middle cerebral artery aneurysm. The patient underwent image-guided localisation of the aneurysm to enable evacuation of the haemorrhage and resection of the fusiform aneurysm., Conclusion: A high index of suspicion is required for diagnosis and early treatment to prevent unnecessary morbidity and mortality.

Two pairs of C(2)-symmetric tetrahydroxyazepanes [(-), (+)-1 and (-), (+)-2] have been synthesized from the enantiomeric chiro-inositols and evaluated as glycosidase inhibitors. Alternative syntheses of ido-tetrahydroxyazepanes (-)- and (+)-2 from myo-inositol were also developed. The key synthetic transformations were glycol fission and cyclization of the derived dialdehydes by double reductive amination. The D-manno-tetrahydroxyazepane [(-)-1] showed selective inhibition of alpha-L-fucosidase and beta-D-galactosidase, while the enantiomer [(+)-1] was a selective inhibitor of an alpha-D-galactosidase. In contrast, the L-ido-tetrahydroxyazepane (+)-2 was a broad spectrum hexosidase inhibitor, but showed none of the reported hexosaminidase inhibition. Its enantiomer (-)-2 is a poor hexosidase inhibitor.