Application of continuous passive motion in patients with distal radius fractures: A randomized clinical trial.

The aim of this study was to know if applying continuous passive motion (CPM) in addition to routine exercises is more effective than routine exercises alone in pain reduction, range of motion (ROM) and function improvement after distal radius fractures (DRFs). In this randomized controlled trial, 21 patients with non-stabilized DRF after pin removal were randomly assigned to experimental and control groups. The experimental group received stretching exercises with CPM machine for 2×15min per session. Both groups received routine exercises for 1h, three times a week for 4 weeks. The primary outcome measure was pain evaluated on a visual analog scale (VAS), and the secondary outcome measures were disability evaluated by the patient-rated wrist/hand evaluation and ROM (goniometry) at 4, 6, and 12 weeks. Univariate analysis of covariance (ANCOVA) and a one-way repeated measure mixed model analysis of variance (ANOVA) were used for data analysis. Twenty-one participants completed the 12-week follow-up. Pain relief, ROM and functional improvement revealed that the treatment was successful in both groups. We detected no significant differences (p>0.05) between the two groups at the end of the follow-up period regarding pain, ROM, and function. Using a CPM machine had no additional effect on pain reduction, ROM and function improvement compared with routine exercises in patients with DRF.

Distribution of the vesicular transporter for acetylcholine in the rat central nervous system.

In order to develop another selective marker for cholinergic cell bodies and fibres, we have raised a highly specific polyclonal antibody against a peptide derived from the C-terminus of a recently cloned putative vesicular acetylcholine transporter. This antibody recognizes the vesicular acetylcholine transporter protein on western blots of membranes from transfected monkey fibroblast COS cells as well as from various rat brain regions but not from untransfected COS cells or rat liver. In separate mapping studies, the antibody was found to stain cell bodies and fibres in all of the regions of the nervous system known to be cholinergic, including (i) the various nuclei of the basal nuclear complex and their projections to the hippocampus, amygdala, and cerebral cortex, (ii) the caudate-putamen nucleus, accumbens nucleus, olfactory tubercle, and islands of Calleja complex, (iii) the medial habenula, (iv) the mesopontine cholinergic complex and its projections to the thalamus, extrapyramidal motor nuclei, basal forebrain, cingulate cortex, raphe and reticular nuclei, and some cranial nerve nuclei, and (v) the somatic motor and autonomic nuclei of the cranial and spinal nerves. In many of these cholinergic neurons, it is possible to detect immunoreactivity for the vesicular acetylcholine transporter in proximal portions of processes and their branches, as well as in numerous puncta in close association with them. Some of these puncta are large and surround cell bodies and processes of neurons in several regions, including the somatic motor neurons of cranial nerve nuclei in the brainstem and in the ventral horn of the spinal cord. Double immunofluorescence studies indicated that neurons positive for the vesicular acetylcholine transporter also stained for the biosynthetic enzyme of acetylcholine, choline acetyltransferase. We conclude that antibody against the C-terminus of the putative vesicular acetylcholine transporter provides another marker for cholinergic neurons that, unlike in situ hybridization procedures, labels terminals as well as cell bodies. Therefore this antibody has the potential to reveal changes in number and morphology of cholinergic cell bodies and their terminal varicosities that occur in both physiologic and pathologic conditions.

Differential distribution of the putative vesicular transporter for acetylcholine in the rat central nervous system.

The organization and distribution of the mRNA for the putative vesicular transporter for acetylcholine (VAChT) was studied in the rat brain by use of digoxigenin-labeled riboprobes and in situ hybridization technology. Signal was observed in all neural regions deduced to contain cholinergic somata on the basis of previous histochemical investigations employing choline acetyltransferase riboprobes and prior immunocytochemical studies with antibodies against choline acetyltransferase. It was absent in areas believed to contain no cholinergic neurons. Anti-sense riboprobes hybridized to the mRNA for the putative VAChT: (a) the projection neurons of the various nuclei of the basal nuclear complex, (b) the local circuit cells of the dorsal and ventral striata, (c) the projection neurons of the mesopontine complex, (d) perikarya in the ventral 2/3 of the medial habenula, (e) the somatic motor and autonomic cells of cranial nerves 3-7 and 9-12, as well as perikarya in the dorsal and ventral cochlear nuclei presumably giving rise to efferent fibers of cranial nerve 8, and (f) the alpha-motor and gamma-efferent motor neurons of the spinal cord. In addition, the mRNA for the VAChT was found in a few somata, probably ectopically located cells of the basal nuclear complex, in the internal capsule, central nucleus of the amygdala, entopeduncular nucleus, and zona incerta. It was also detected in some cell bodies in the reticular part of the substantia nigra, probably the rostral extension of the mesopontine complex, in the parabigeminal nucleus, and around the central canal in the spinal cord but not in cortical, hippocampal, and cerebellar perikarya. It is concluded that, like choline acetyltransferase, the mRNA for the putative acetylcholine vesicular transporter is another specific marker for neurons utilizing acetylcholine as a neurotransmitter. Further investigations of that transporter could have important implications for various diseases involving cholinergic systems, such as Alzheimer's disease.

Molecular cloning of a putative vesicular transporter for acetylcholine.

Classical neurotransmitters such as acetylcholine (ACh) require transport into synaptic vesicles for regulated exocytotic release. The Caenorhabditis elegans gene unc-17 encodes a protein with homology to mammalian transporters that concentrate monoamine neurotransmitters into synaptic vesicles. Mutations in unc-17 protect against organophosphorus toxicity, indicating a role in cholinergic neurotransmission. Using the relationship of unc-17 to the vesicular amine transporters, we first isolated a related sequence from the electric ray Torpedo californica [Torpedo vesicular ACh transporter (TorVAChT)] that is expressed by the electric lobe but not by peripheral tissues. Using the relationship of the Torpedo sequence to unc-17, we then isolated the cDNA for a rat homologue (rVAChT). Northern blot analysis shows expression of these sequences in the basal forebrain, basal ganglia, and spinal cord but not cerebellum or peripheral tissues. In situ hybridization shows expression of rVAChT mRNA in all cholinergic cell groups, including those in the basal forebrain, brainstem, and spinal cord that previously have been shown to express choline acetyltransferase mRNA. The human VAChT gene also localizes to chromosome 10 near the gene for choline acetyltransferase. Taken together, these observations support a role for rVAChT in vesicular ACh transport and indicate its potential as a novel marker for cholinergic neurons.