Localized and controlled delivery of chemotherapeutics directly in brain-tumor for prolonged periods may radically improve the prognosis of recurrent glioblastoma. Here, we report a unique method of nanofiber by fiber controlled delivery of anti-cancer drug, Temozolomide, in orthotopic brain-tumor for one month using flexible polymeric nano-implant. A library of drug loaded (20 wt%) electrospun nanofiber of PLGA-PLA-PCL blends with distinct in vivo brain-release kinetics (hours to months) were numerically selected and a single nano-implant was formed by co-electrospinning of nano-fiber such that different set of fibres releases the drug for a specific periods from days to months by fiber-by-fiber switching. Orthotopic rat glioma implanted wafers showed constant drug release (116.6 μg/day) with negligible leakage into the peripheral blood (<100 ng) rendering ~1000 fold differential drug dosage in tumor versus peripheral blood. Most importantly, implant with one month release profile resulted in long-term (>4 month) survival of 85.7% animals whereas 07 day releasing implant showed tumor recurrence in 54.6% animals, rendering a median survival of only 74 days. In effect, we show that highly controlled drug delivery is possible for prolonged periods in orthotopic brain-tumor using combinatorial nanofibre libraries of bulk-eroding polymers, thereby controlling glioma recurrence.
Survival after decompressive hemicraniectomy was better than previously reported using medical management alone. A vegetative state was avoided and functional independence was possible, especially in younger patients. Increasing age was a statistically significant predictor of disability and long-term functional dependence.
Reports of long-term effects of subthalamic (STN) stimulation for Parkinson's disease (PD) are few, mostly open-label evaluations and from Western centers. We used single-blind and open-label motor, cognitive and quality of life (QOL) evaluations to study the effects of bilateral STN stimulation in 45 patients over 5 years. Our patients showed a stable and substantial reduction in the cardinal signs of PD, motor fluctuations, and dyskinesias but less so for axial signs. The reduction in medications and the intensity of electrical stimulation needed also remained stable during follow up. Although the total QOL and its parkinsonism and social components showed sustained benefits till 5 years, the gains in emotional and systemic subsets were short lasting. Global scores for mood and cognition did not show significant worsening. Benefits of STN stimulation on the cardinal signs, motor complications, and QOL of advanced PD were substantial and sustained till 5 years. The initial benefits in axial motor signs and emotional and psychological aspects of QOL did not show similar stability. In general, the procedure had insignificant impact on cognition and mood. This is the first report of STN stimulation in Asian patients with PD.
Cases of N. farcinica infections are being reported increasingly because of recent changes in taxonomy and diagnostic methodology. This change in epidemiology has implications for therapy because of the organism's pathogenicity and natural resistance to multiple antimicrobial agents, including third-generation cephalosporins. Any delay in starting appropriate antibiotic therapy can have adverse consequences.
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