Changes in motor cortex neural discharge associated with the development of cerebellar limb ataxia

1. The relation between changes in motor cortex neural (MCN) discharge and the development of limb ataxia during cerebellar dysfunction was studied in 4 Cebus monkeys. Elbow movements with decreased accelerations or with tremor were produced by reversible cerebellar nuclear cooling. Discharge from 160 neurons was analyzed in detail. 2. During cerebellar cooling 37 of 80 neurons that discharged before movement onset decreased their phasic, but not their tonic, activity. This could not be explained by decreased peak velocities during cerebellar cooling. It is suggested that this decreased phasic discharge is related to the less abrupt onset and smaller magnitude of agonist EMG activity, and to the decreased initial accelerations, without decreased peak velocities, observed in limb movements during cerebellar dysfunction. This view implies that the cerebellum is involved in some way in the generation of commands to agonist alpha-motoneurons. 3. No evidence was found that 3- to 4-Hz cerebellar intention tremor is driven by a purely central oscillator. All 28 neurons that discharged strongly in relation to cerebellar tremor in movements responded strongly and reciprocally to limb perturbations. 4. A number of changes were observed during cerebellar nuclear cooling in kinematically related neural discharge associated with disordered elbow movements: an increase in discharge of some velocity- and acceleration-like neurons, a decrease in (reciprocal) inhibition, and a shift from an acceleration-like to a velocity-like discharge in some neurons. 5. Fourteen of 29 neurons with muscle-like discharge patterns discharged in a servoassistance-like manner during cerebellar dysfunction that was consistent with them contributing to tremor. 6. The results indicate that a variety of disorders, i.e., in the generation of central commands that initiate movements and in the regulation of the gain and phase of proprioceptive feedback, contribute to the development of limb ataxia during cerebellar dysfunction.     

Overarm throwing speed in cerebellar subjects: effect of timing of ball release

Cerebellar subjects cannot throw fast and show variability in ball speed from throw to throw. One possible reason is that they release the ball at times when arm speed is not at its maximal value. Therefore, we investigated the hypothesis that the slow and variable speeds of throws made by cerebellar subjects are caused by their known large variability in the timing of ball release. Eight cerebellar subjects and matched controls were instructed to make overarm throws fast and accurately. Angular positions of arm segments were recorded with search coils at 1,000 Hz. Timing of ball release was measured with respect to the time of occurrence of seven arm kinematic reference points. All cerebellar subjects showed strong relations between ball speed and the timing of ball release, with faster ball speeds associated with late ball release. In agreement, faster ball speeds were also associated with longer hand paths to ball release, and with balls which went low on the target. However, when timing of ball release was optimal for achieving maximal ball speed in the cerebellar subjects, their fastest ball speeds were on average only 67% those of controls. Similarly, peak forearm angular velocity (one measure of arm speed) in the cerebellar group was 58% that of the control group. It is concluded that the large variability in timing ball release in cerebellar subjects contributes to their variability in ball speed, but is only a minor factor in their inability to throw fast. The major reason why cerebellar subjects do not throw fast is that they do not generate fast arm speeds.     

The effects of weak magnetic fields on radical recombination reactions in micelles

PURPOSE: To demonstrate the effects of weak magnetic fields (> approximately 1 mT) on chemical reactions involving free radicals, in the context of possible effects of environmental electromagnetic radiation on biological systems. MATERIALS AND METHODS: Transient absorption, flash photolysis experiments have been performed to study the kinetics and yields of radical reactions. The triplet state of benzophenone has been used as a convenient source of radical pairs, whose identity is largely immaterial to the investigation of the so-called Low Field Effect. Hydrogen abstraction from surfactant molecules in micelles yields a pair of neutral radicals, one large and one small, in a region of restricted translational and rotational motion. RESULTS: In alkyl sulphate and sulphonate micelles a weak field increases the concentration of free radicals that escape from the micelle to an extent that depends on the structure, dynamics and volume of the space in which the radical pairs are confined. The effect (up to 10%) is typically largest at 1-2 mrT. Smaller effects are found for Brij and TX100 micelles. CONCLUSIONS: Low Field Effects depend strongly on the local environment of the radical pair. Larger effects than observed here might be expected for radicals formed from singlet (rather than triplet) precursors, as would be the case in biological reactions.     

Transfer of telemedical support to Cornwall from a national telemedicine network during a solar eclipse

During late 1998 and early 1999, planning officers in Cornwall predicted a huge increase in summer visitors to the county to observe the August solar eclipse. There was the possibility that a mass gathering in Cornwall could overload existing arrangements for handling accident and emergency patients. We therefore set up a telemedicine system to support the county's minor injury units (MIUs) from hospitals throughout the UK. Six main hospital accident and emergency departments outside Cornwall with existing links to their own MIUs were twinned with 10 of the 11 MIUs in Cornwall before the expected date of the gathering. The network was live for nine days, starting four days before the eclipse, and 2045 patients were seen in the 10 MIUs. There were 93 telemedicine calls from the 10 MIUs, involving 91 patients. Overall, 4.6% of the patients required a telemedicine consultation. Fifty-seven calls were made during working hours. Thirty-four patients were referred for further management, of whom 18 were referred on the same day. The transfer of telemedical support to a national network was successful.     

Carfentanil structural analogs found in street drugs by paper spray mass spectrometry and their characterization by high-resolution mass spectrometry

Carfentanil is one of the most potent synthetic opioids ever developed, with an estimated analgesic potency approximately 20–100 times that of fentanyl and 10,000 times that of morphine. Carfentanil has been appearing in the illicit drug supply in many regions and has been linked to fatal overdose events. A subset of 59 street drug samples obtained in Victoria, B.C., that were confirmed to contain carfentanil were analyzed by mass spectrometry for this study. Carfentanil quantitation by paper spray mass spectrometry ranged from 0.05 to 2.95 w/w% (median = 0.32%) in the original drug sample. Paper spray mass spectrometry analysis also detected two unknown peaks at m/z 380.2 and 381.2 in 31 of these 59 samples (53%). Initial tandem mass spectrometry experiments revealed structural similarities between these unknown compounds and carfentanil, suggesting they were potential structural analogs, possibly arising from incomplete purification during synthesis. High-resolution mass spectrometry determined the chemical formulas of these compounds as C₂₃H₂₉N₃O₂ (m/z 380.2333) and C₂₃H₂₉N₂O₃ (m/z 381.2137). Literature and tandem mass spectrometry results were used to determine the identity of these potential new psychoactive substances, C₂₃H₂₉N₃O₂ as desmethylcarfentanil amide and C₂₃H₂₉N₂O₃ as desmethylcarfentanil acid. μ-Opioid receptor binding modeling determined that the binding poses of these analogs were nearly identical to that of carfentanil with relative binding energy calculations of 0.544 kJ/mol (desmethylcarfentanil amide) and −0.171 kJ/mol (desmethylcarfentanil acid); these data suggest they may share the toxic effects of carfentanil and have similar potencies.     

Detecting arsenic-related skin lesions: experiences from a large community-based survey in Bangladesh

A cross-sectional survey was conducted in Matlab, Bangladesh, to determine the prevalence of skin lesions (a three-step procedure) associated with arsenic exposure and discuss validity and feasibility in relation to recommended screening algorithms. Cases with skin lesions were identified by screening above 4 years of age (n = 166,934). Trained field teams conducted a careful house-to-house screening and identified 1682 individuals with skin lesions, who were referred to physicians for confirmation. Physicians diagnosed 579 cases as probable and documented all these with digital photographs. Two experts inspected all photographs for consensus agreement that was reached for 504 cases. Using the experts' opinions as reference, the positive predictive value of the physicians' diagnosis was 87% (male = 82% vs. female = 94%; p < 0.01). The physicians had difficulties in separating arsenic-induced keratosis from differential diagnoses, while probability for correct diagnosis was high for arsenic-related pigmentation changes. Including information on current arsenic concentration in drinking water (which was masked at time of skin examination) or urine in the diagnostic algorithm should have increased the number of false negative cases. In the present transition of drinking water sources these markers of current exposure levels provide no information on past exposure. A 2-3 step procedure with house-to-house screening and clinic-based confirmation of arsenic-induced skin lesions is a feasible approach. Information on arsenic concentration in current water sources or in urine should not have improved the precision in the diagnosis. These results may have policy implications for community screening of arsenic-related skin lesions in Bangladesh and elsewhere.