Biomedical subjects
Publications and source records attributed to E Mak.
A scoring error is identified in the Mini-Mental and the Modified Mini-Mental State test. The major effect of this error is to produce a gap in the total score distribution of the test, resulting in a potential spurious underestimation of the score. Two possible remedies are suggested to resolve this problem.
We undertook an analysis of the hazard functions derived from results published by the Parkinson Study Group following their investigation of deprenyl. Our findings indicate that the action of deprenyl is transient rather than sustained. We also infer that this effect may be mediated through alleviation of symptoms rather than by neuroprotection.
In a double-blind placebo-controlled study, we evaluated the effects of clozapine (75 to 250 mg/day, mean 170.8) on dopaminomimetic psychosis and parkinsonian disability. Clozapine prevented deterioration of psychosis during the increase of dopaminomimetics in the 3 patients who completed the study. Worsening of parkinsonism occurred in 3 of the 6 patients. In the dosage used, clozapine's usefulness was limited by its propensity to produce sedation, confusion, and increased parkinsonism.
We assessed parkinsonian rigidity objectively at the wrist to determine the optimal angular velocity and displacement for detecting abnormality. The wrist was moved passively with a torque motor and the average work done for one complete cycle was computed. This objective rigidity score (ORS) was compared with a clinical rigidity score (CRS). ORS was more pronounced at faster movement velocities in parkinsonian patients, whereas in normal subjects there was only a modest increase in the score. Angular velocities of 140 to 190 degrees/second and displacements of +/- 25 to +/- 30 degrees were most sensitive for detecting parkinsonian rigidity and had good correlation with the CRS.
Non-human primates exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have been employed to study the clinical features of parkinsonism. Monkeys lesioned by unilateral intracarotid administration of MPTP display spontaneous and drug responsive turning behavior. However this seems to correlate poorly with their clinical deficits. We describe an objective measurement of arm movement velocity, applied in 4 cynomolgus monkeys before and after unilateral administration of MPTP. Reduced movement velocities correlated with clinical signs of unilateral flexed arm posture, rigidity, tremor and bradykinesia and could be reversed with L-DOPA therapy. This measurement technique has advantages for the quantitative assessment of parkinsonian deficits and will permit the evaluation of dopaminergic therapy and transplantation in non-human primates.
Colloidal carriers injected intravenously are normally removed rapidly and efficiently by the liver and this represents a major barrier to drug targeting. By coating model microspheres and emulsions with a block co-polymer (poloxamine) it has been possible to keep the carrier circulating in the vascular compartment with little or no uptake by the reticuloendothelial system.
The effect of surface characteristics on the interaction of sterically stabilized polystyrene particles with mouse peritoneal macrophages was studied using a range of poloxamers and poloxamine as coating agents. The coated particles were characterized in terms of thickness of coating layer, surface charge and critical flocculation temperature. The relative phagocytic uptake was found to decrease with increasing adsorbed layer thickness i.e. longer hydrophilic polymer chains of the coating agent and consequently a greater steric stabilization effect.
PHNO is a naphthoxazine compound with selective D2 agonist properties and a molecular structure unrelated to the morphine and ergot derivatives that have been used to treat Parkinson's disease. A double-blind, dose-ranging study on 8 patients showed that it is effective in the treatment of parkinsonism; its duration of effect of up to 6 h could make it useful for patients who experience wearing-off reactions with levodopa.
Dystonic torticollis has been treated with local injections of botulinum toxin in a single blind study of 12 patients. A significant decrease of abnormal movements was recorded, and pain improved. Further studies are desirable to define the optimum dosage and site for injections, and the long term effects of repeated injections.
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The effects of cytochalasin B on bile canalicular structure and function were examined. Three experimental models were used, cultured hepatocytes, isolated perfused liver, and in vivo infused liver. The techniques used were light and electron microscopy and, in selected instances, scanning electron microscopy, electron "stains" for microfilaments, and measurements of bile flow. Microfilament disruption and dilation of bile canaliculi were consistently found and closely paralleled a reduction in bile flow in both in vitro and in vivo infused animals. It is proposed that under normal circumstances, the microfilaments maintain the canaliculi in a contracted or partly contracted state. Hence, the microfilamentous network would provide tone to the canalicular system which would tend to reduce stagnation and facilitate the flow of bile. Removal of normal microfilament contractile function would be expected to produce canalicular ectasia and reduction of bile flow, as was observed. Microfilament dysfunction may therefore be a possible cause of intrahepatic cholestasis. Crucial to this hypothesis are the presence of actin-containing microfilaments in the pericanalicular web, and an action of cytochalasin B on their contractility. Evidence pertaining to these requirements is presented and discused.
Amniocentesis and prenatal diagnosis were done for late maternal age and an abnormality consistent with Tetrasomy 21 (47,XX, + t(21;21] was found in every cell examined of the initial amniotic fluid. Clinical examination revealed a fetus with many of the signs of Down Syndrome and pathological examination revealed gross abnormalities of the internal structures. Follow-up tissues showed mosaic Tetrasomy 21.