Effects of human immunodeficiency virus type 1 resistance to protease inhibitors on reverse transcriptase processing, activity, and drug sensitivity.

Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease inhibitors often display a reduced replicative capacity as a result of an impairment of protease function. Such fitness-impaired viruses display Gag precursor maturation defects. Here, we report that some protease inhibitor-resistant viruses also display abnormalities in the processing of reverse transcriptase (RT) by the protease. In three recombinant viruses carrying resistant protease sequences from patient plasma, we observed a marked decrease in the amount of mature RT subunits and of particle-associated RT activity compared to their parental pretherapy counterparts. We investigated the possibility that a decrease in the amount of particle-associated mature RT could affect the sensitivity of the corresponding virus to RT inhibitors. We observed a twofold increase of sensitivity to zidovudine (AZT) when a virus which carried AZT mutations was processed by a resistant protease. Interestingly, the presence of AZT-resistance mutations partially rescued the replication defect associated with the mutated protease. The interplay between resistance to protease inhibitors and to RT inhibitors described here may be relevant to the therapeutic control of HIV-1 infection.

Effect of manipulating visual feedback parameters on eye and finger movements.

Thirteen healthy subjects were asked to maintain a constant index finger position in Experiment 1 or a constant eye position in Experiment 2 using visual feedback. The finger or eye position along with a stationary baseline target was displayed on an oscilloscope placed in front of the subject. Experiments 1 and 2 were carried out under sixteen combinations of delay and amplification of displacement on the screen (i.e., gain). In Experiment 1, increasing the gain in the visual feedback decreased the Root Mean Square (RMS) errors while increasing the delay increased these errors. An interaction between gains and delays was also observed in Experiment 1. In Experiment 2, the RMS errors were systematically higher than those recorded in Experiment 1 for the finger. No systematic pattern was recognized across all conditions of gains and delays for eye movements in Experiment 2. This study clearly illustrates differences in dynamics of motor control systems regulating eye and finger positions, respectively.

Diadochokinesimetry: a study of patients with Parkinson's disease and manganese exposed workers.

Diadochokinesia, the ability to perform rapid alternating movements is often impaired in patients with extrapyramidal disease. It is a common sign among patients with Parkinsonism or manganism. In the present study we compare patients with Parkinson's disease (n = 11), workers formerly exposed to manganese (n = 10) and control subjects (n = 11) performing rapid alternating hand movements for 5 s under four conditions repeated twice (natural cadence and maximal speed with one or two hands). Data recorded using a diadochokinesimeter built in our laboratory and connected to a 486/33 microcomputer were digitized in real time while subjects rotated back and forth hand held foam spheres connected to flexible rods articulated with optical encoders. Significant differences were found between control subjects and patients with Parkinson's disease, but not with manganese exposed workers, in most variables examined. However, trajectory length (a combination of movement amplitude and velocity) indicated that manganese exposed workers and patients with Parkinson's disease were significantly different from the controls in functional asymmetries between right and left hand. In addition, workers and patients tend to have marked differences between the performance of right and left hands. Improved quantitative measurement of rapid alternating movements may prove to be an important tool in early and differential diagnosis of Parkinson's disease and manganese exposure.

Muscle performance and gross motor function of children with spastic cerebral palsy.

The purpose of this study was to determine whether, and to what extent, performance on a measure of motor function (Gross Motor Function Measure, GMFM) was related to the physiological fitness of children with cerebral palsy (CP). Two elements of physiological function were measured: aerobic power and anaerobic power of the arms and legs. 15 boys and eight girls aged between seven and 13.9 years with spastic CP participated in the study. There was a good relationship between the standing and walking, running and jumping sub-sections and the total score of the GMFM on one hand, and anaerobic capacity of the legs on the other. However, the relationships for the arms were limited, indicating that the GMFM is not a suitable tool for providing information about aerobic fitness in children with CP, or about anaerobic power of the arms.

Anaerobic endurance and peak muscle power in children with spastic cerebral palsy.

The aim of this study was to provide information on anaerobic muscle endurance (mean power) and peak muscle power in children with spastic cerebral palsy. We measured peak power and mean power of the upper and lower limbs in 29 boys and 20 girls, aged from 6 to 14 years, by means of the Wingate Anaerobic Test. In addition, the physical components (physical capacity, upper limb, and lower limb) of a system used for evaluating function in the physically disabled were assessed. Of the 49 subjects, 46 and 37 successfully completed the arm and leg Wingate Anaerobic Test, respectively. Compared with norms for age and gender (healthy, nonathletic children), peak and mean power in the patients, even when corrected for body weight, were distinctly subnormal. The performance of subjects with quadriplegia was 3 to 4 SDs below the mean for controls. Twenty-five of diplegic and hemiplegic subjects had values below 2 SDs. When the data were analyzed according to the severity of the cerebral palsy, with the use of the physical capacity, upper limb, and lower limb score, those children with moderate to severe cerebral palsy had values for mean and peak power of the arm and leg 3 to 4 SDs below the normal mean. Values for children with only mild cerebral palsy also fell below the mean, but the data were more scattered, especially for the leg. The lower muscle performance may reflect both quantitative and qualitative differences in the upper- and lower-limb muscles, due to altered innervation and, in the more severely affected children, disuse.

The organization of stepping in patients with Parkinson's disease: bradykinesia or discoordination?

The purpose of this experiment was to quantify and analyse multijoint coordination of patients with Parkinson's disease (N = 5) and control subjects (N = 5) during forward and backward stepping motions executed at different cadences. Coordinates of reflective markers placed on the shoulder, hip, knee, ankle and metatarsal joints were recorded in the sagittal plane using a video motion analysis system. Kinematic and kinetic analyses provided angular displacements and velocities as well as joint moments of force and powers. Results suggest the presence of two types of discoordination: one type is velocity-dependent, hence related to bradykinesia, whereas the other type appears to reflect qualitatively different coordination patterns.

Sensitivity and specificity of the extended scale for dementia.

The Extended Scale for Dementia was introduced as a test for grading the intellectual function of patients with dementia. Its use in discriminating demented patients from nondemented control subjects has been explored. The test had a sensitivity of 93% and a specificity of 96% in patients over the age of 65 years, but the sensitivity fell to 75% in those younger than 65 years. The scale may be useful, particularly for patients over the age of 65 years, in helping to distinguish dementia from normality.

Problems in genetics: getting help.

The authors discuss the role of the family physician in identifying families who would benefit from genetic counselling. They outline reasons for referral, as well as the referral process itself, and review the genetic counselling process, with particular emphasis on the initial assessment. The importance of understanding the family's expectations, obtaining a family history, and confirming diagnosis is stressed. A list of genetic centres across Canada is appended.

Relationships between electromyography and kinematics in human stepping strategies.

Kinematic and electromyographic (EMG) parameters were analyzed on phase plane diagrams of human stepping motions performed over an obstacle of varying height. A videomotion analysis system was used to record the displacement of 5 reflective markers placed on the subject's lower limb joints. Surface bipolar electrodes were placed on the rectus and biceps femoris muscles. Results revealed systematic differences in the EMG patterns of the rectus femoris between initial and subsequent trials in the 3 conditions of obstacle height. In the initial trials there was an episode of EMG activity right before or during the transition from knee flexion to extension. In the subsequent trials this episode was shifted toward maximum knee extension velocity, leaving a period of silence between the initial burst and this episode. On the other hand, the biceps femoris was rarely silent and particularly active during the flexion phase, reflecting its possible role in active knee flexion and postural control during the dynamic phase of stepping. The increase in phase plane size with obstacle height appears related to the amplitude of the initial EMG burst of the rectus femoris. Phase plane diagrams combined with EMG appear to be an appropriate approach to explore the dynamics of human movement strategies. The results suggest that control mechanisms for the flexion and extension phases are different and may be involved in fine tuning the stepping strategy for subsequent trials.

Influence of different types of physical fatigue on a visual detection task.

The present study was designed to investigate the effects of different types of physical fatigue-past demand for exertion-on the performance of a visual detection task performed with and without masking. 31 male subjects were first administered a VO2 max test and familiarized with the detection task. They were divided into two groups to control potential effects of masking. They were subjected to three experimental treatment involving the utilization of different sources of energy: (a) a short anaerobic alactic acid effort recruiting phosphocreatine, (b) a supramaximal effort (anaerobic lactic acid) recruiting glycogen without oxygen, and (c) a progressive (partially anaerobic) effort recruiting glycogen and oxygen. All three were performed on a treadmill. Blood samples were collected for the anaerobic lactacid and the partially anaerobic exercises. Once fatigued, all subjects undertook the detection task. A 2 X 3 X 2 X 8 analysis of variance, with repeated measures on the last three factors, was applied to the data (mask/no mask X type of exercise X pre-post performance measures X location of the letter to be detected). No significant difference was found for either the main effects or interactions, except for the location of the letter and the mask/no mask condition. It appears therefore that a physically fit population (mean VO2 max = 62.39 ml X kg(-1) X min(-1)) shows no detectable decrement in a perceptual task performed after fatiguing exercises recruiting various types of energy sources.

The effects of physical or perceptual work loads on a coincidence/anticipation task.

This study was designed to analyze the effects of physical or perceptual work loads on a coincidence/anticipation task. Three experimental treatments were applied: (1) a physical work load, (2) a perceptual work load, and (3) a combination of the physical and the perceptual work loads. The dependent variable was performance on a coincidence/anticipation task, a throw at a moving target. Time errors and accuracy scores were recorded. The type of work load does not affect any of the dependent variables. However, all types of work load generated definite improvement pre- and posttest for the temporal constant error; better performance, as measured by constant error, was recorded for all subjects when the speed of the apparent movement being intercepted was 4.7 km/hr. Temporal variability was reduced in the subject performance at 8.1 km/hr.