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Parkinson’s disease is a common movement disorder affecting approximately 127,000 people in the UK, with an estimated two thirds having speech-related problems. Currently there is no preferred approach to speech and language therapy within the NHS and there is little evidence for the effectiveness of standard NHS therapy or Lee Silverman voice treatment. This trial aims to investigate the feasibility and acceptability of randomizing people with Parkinson’s disease-related speech or voice problems to Lee Silverman voice treatment or standard speech and language therapy compared to a no-intervention control. The PD COMM pilot is a three arm, assessor-blinded, randomized controlled trial. Randomization will be computer-generated with participants randomized at a ratio of 1:1:1. Participants randomized to intervention arms will be immediately referred to the appropriate speech and language therapist. The target population are patients with a confirmed diagnosis of idiopathic Parkinson’s disease who have problems with their speech or voice. The Lee Silverman voice treatment intervention group will receive the standard regime of 16 sessions between 50 and 60 minutes in length over four weeks, with extra home practice. The standard speech and language therapy intervention group will receive a dose determined by patients’ individual needs, but not exceeding eight weeks of treatment. The control group will receive standard care with no speech and language therapy input for at least six months post-randomization. Outcomes will be assessed at baseline (pre-randomization) and post- randomization at three, six, and 12 months. The outcome measures include patient-reported voice measures, quality of life, resource use, and assessor-rated speech recordings. The recruitment aim is at least 60 participants over 21 months from 11 sites, equating to at least 20 participants in each arm of the trial. This trial is ongoing and recruitment commenced in May 2012. This study will provide information on the feasibility and acceptability of randomizing participants to different speech and language therapies or control/deferred treatment. The findings relating to recruitment, treatment compliance, outcome measures, and effect size will inform a future phase III randomized controlled trial. International Standard Randomised Controlled Trial Number Register: ISRCTN75223808 registered 22 March 2012.

4-Biphenylmethanol (4HMB) and 4-chloromethylbiphenyl (4CMB) selectively inhibited mitochondrial protein synthesis and induced the mitochondrial mutation petite in yeast cells. 4HMB was more potent than 4CMB in antimitochondrial activity. Benzyl chloride (BC) affected mitochondria only marginally but was more generally toxic than the biphenyls. Results indicated that 4HMB and 4CMB had carcinogenic potential but this was unlikely in the case of BC.

We have shown previously that three antibodies--anti-galactocerebroside (GC), anti-glial fibrillary acidic protein (GFAP), and the A2B5 monoclonal antibody--can be used to help distinguish three classes of glial cells in the rat optic nerve: oligodendrocytes are GC+, GFAP-, almost all type-1 astrocytes are A2B5-, GFAP+, and almost all type-2 astrocytes are A2B5+, GFAP+. In the present study we have used these antibodies to examine the timing and sequence of the development of the three types of glial cells in vivo. We show that type-1 astrocytes first appear at embryonic Day 16 (E16), oligodendrocytes at birth (E21), and type-2 astrocytes between postnatal Days 7 and 10 (P7-10). Moreover, we demonstrate quantitatively that astrocytes in the optic nerve develop in two waves, with more than 95% of type-1 astrocytes developing before P15 and more than 95% of type-2 astrocytes developing after P15. Finally, we provide indirect evidence that type-2 astrocytes do not develop from type-1 astrocytes in vivo, supporting previous direct evidence that the two types of astrocytes develop from two serologically distinct precursor cells in vitro.