Understanding the basics of cannabidiol from cannabis to apply to therapeutics in epilepsy.

The compounds present in cannabis have been in use for both recreational and medicinal purposes for many centuries. Changes in the legislation in South Africa have led to an increase in the number of people interested in using these compounds for self-medication. Many of them may approach their general practitioner as the first source of information about possible therapeutic effects. It is important that medical professionals are able to give patients the correct information. Cannabidiol (CBD) is one of the main compounds in cannabis plants, and there is evidence that it can successfully treat certain patients with epilepsy. This review looks at the most recent evidence on the use of CBD in the treatment of epilepsy and explores the mechanisms behind these beneficial effects.

Laser-induced direct space-selective precipitation of CdS nanoparticles embedded in a transparent silica xerogel.

A simple method, suitable for direct space-selective precipitation of semiconducting nanoparticles inside a transparent silica xerogel, is presented. The porous silica monoliths, prepared by the sol-gel method, are first loaded with specific CdS precursors. Then, the samples can be irradiated using either a femtosecond laser to generate the nanoparticles inside the deep volume of the silica matrix or a continuous visible laser to yield a nanocrystal growth under the surface. The resulting CdS nanoparticles are characterized using absorption and Raman spectroscopies, x-ray diffraction analysis and transmission electron microscopy.

Cardiotoxic effects of pavetamine extracted from Pavetta harborii in the rat.

Previous studies have shown that crude extracts from Pavetta harborii as well as dried plant material have cardiotoxic effects on rats and sheep that can lead to heart failure. The active component has since been isolated and identified. This substance has been named pavetamine. The aim of this study was to determine whether pavetamine has cardiotoxic effects similar to those seen in previous reports, when administered to rats intraperitoneally. Sprague Dawley rats received two doses, initially 4 mg/kg and then 3 mg/kg pavetamine respectively and were monitored for 35 days before cardiodynamic parameters were measured by inserting a fluid-filled catheter into the left ventricle via the right carotid artery. These values were compared to those of control rats that had received only saline. Pavetamine significantly reduced systolic function and body mass in the treated rats, which indicates that it has the potential to induce heart failure in this animal model.

First direct observation of two protons in the decay of 45Fe with a time-projection chamber.

The decay of the ground-state two-proton emitter 45Fe was studied with a time-projection chamber and the emission of two protons was unambiguously identified. The total decay energy and the half-life measured in this work agree with the results from previous experiments. The present result constitutes the first direct observation of the individual protons in the two-proton decay of a long-lived ground-state emitter. In parallel, we identified for the first time directly two-proton emission from 43Cr, a known beta-delayed two-proton emitter. The technique developed in the present work opens the way to a detailed study of the mechanism of ground state as well as beta-delayed two-proton radioactivity.

Systematic review of multidisciplinary interventions in heart failure.

OBJECTIVE: To determine the impact of multidisciplinary interventions on hospital admission and mortality in heart failure. DESIGN: Systematic review. Thirteen databases were searched and reference lists from included trials and related reviews were checked. Trial authors were contacted if further information was required. SETTING: Randomised controlled trials conducted in both hospital and community settings. PATIENTS: Trials were included if all, or a defined subgroup of patients, had a diagnosis of heart failure. INTERVENTIONS: Multidisciplinary interventions were defined as those in which heart failure management was the responsibility of a multidisciplinary team including medical input plus one or more of the following: specialist nurse, pharmacist, dietician, or social worker. Interventions were separated into four mutually exclusive groups: provision of home visits; home physiological monitoring or televideo link; telephone follow up but no home visits; and hospital or clinic interventions alone. Pharmaceutical and exercise based interventions were excluded. MAIN OUTCOME MEASURES: All cause hospital admission, all cause mortality, and heart failure hospital admission. RESULTS: 74 trials were identified, of which 30 contained relevant data for inclusion in meta-analyses. Multidisciplinary interventions reduced all cause admission (relative risk (RR) 0.87, 95% confidence interval (CI) 0.79 to 0.95, p = 0.002), although significant heterogeneity was found (p = 0.002). All cause mortality was also reduced (RR 0.79, 95% CI 0.69 to 0.92, p = 0.002) as was heart failure admission (RR 0.70, 95% CI 0.61 to 0.81, p < 0.001). These results varied little with sensitivity analyses. CONCLUSION: Multidisciplinary interventions for heart failure reduce both hospital admission and all cause mortality. The most effective interventions were delivered at least partly in the home.

Unrecognized hypo- and hyperglycemia in well-controlled patients with type 2 diabetes mellitus: the results of continuous glucose monitoring.

The aim of this study was to determine the prevalence and extent of glycemic excursions (hypo- and hyperglycemic) in elderly patients with well-controlled type 2 diabetes using a Continuous Glucose Monitor System (CGMS) (Medtronic MiniMed). Elderly patients (>65 years old) with type 2 diabetes were recruited if their glycosylated hemoglobin (HbA1c) was <7.5% and if their oral hypoglycemic therapy included a sulfonylurea. Patients were asked to undergo two consecutive 72-h periods of continuous glucose monitoring at baseline and then again at 1 month (total 288 h). Patients were asked to record four self-monitored capillary blood glucose levels each day for calibration of the monitor and also to record meal times, exercise, and symptoms of hypoglycemia. The number of hyperglycemic (>144 mg/dL), hypoglycemic (<50 mg/dL), and borderline-hypoglycemic (50-65 mg/dL) events were determined (an event was defined as a glucose value that persisted for at least 15 min with or without symptoms). Twenty-five patients (21 men, four women) 73.9 +/- 4.4 years old with an HbA1c of 6.2 +/- 0.8% were each monitored for an average of 187.57 h. The mean glucose values were: fasting, 139 +/- 40 mg/dL; 2 h post-breakfast, 167 +/- 58 mg/dL; 2 h post-lunch, 157 +/- 53 mg/dL; and 2 h post-dinner, 149 +/- 49 mg/dL. Twenty patients (80%) experienced a total of 103 hypoglycemic events, and 14 of these patients experienced 54 events where the glucose levels were 144 mg/dL 2 h postprandial) were recorded after 57% of all meals (breakfast 60%, lunch 57.5%, dinner 55.2%). The CGMS was generally well tolerated, but 52% of patients could not be studied for the full 12 days of monitoring. Thus hypoglycemia and excessive postprandial glycemic excursions are common in well-controlled patients with type 2 diabetes treated with a sulfonylurea with or without metformin. The CGMS is a useful research and clinical tool to assess glycemia in patients with type 2 diabetes but is not tolerated by all subjects.

Development of postural adaptation to arm raising.

We studied the development of the coordination between posture and movement by analyzing the shifts of the center of pressure (CoP) associated with arm raising. Three groups of children aged 3-5 years, 6-8 years, and 9-10 years and an adult group were tested. The subjects were required to raise their arms to the horizontal position while standing still, with their hands free or loaded (5% of the body weight). The arm movements were recorded by a TV-image processor, and the changes in position of the CoP were measured by a force platform and analyzed before, during, and after the arm movement. The data show that the CoP moved forward during arm raising, that additional load induced a greater shift in all age groups, and that the relative amplitude of the shift decreased with age. The greatest changes occurred between ages 3-5 years and 6-8 years. The pre- and postmovement CoP shift suggests qualitative changes in the postural adaptation to movement between these two age groups: the anticipatory postural adjustments moved from a supporting function to a compensatory function, yielding an increasing functional convergence between the feedforward and the feedback modes of postural control, and an increasing rapidness in recovering postural stability after arm movement. The postural behavior shown by the 9- to 10-year-old children and by the adults in the arms-free condition suggests an increased tolerance to unbalance when postural oscillations do not jeopardize static equilibrium.

The role of cromakalim and a nitric oxide synthase blocker in cardiac arrhythmia in the intact baboon model.

The arrhythmogenic effect of adenosine triphosphate (ATP)-sensitive potassium channel openers is controversial and may be dependent on the type of animal model used. Information on the effect of these drugs in the normal primate model is limited. The purpose of this study was first to determine the arrhythmogenic properties of cromakalim in the baboon and second to determine whether N-omega-nitro-L-arginine methyl ester (L-NAME) has any effect on the induced arrhythmia. Adult (2-4 years old) baboons (Papio ursinus) were anesthetized with a continuous i.v. infusion of ketamine (100 mg/ ml), diazepam (5 mg/ml), and saline (ratio 2:2:50) at a rate of 40-60 ml/h. Sympathetic responses were inhibited by administration of propranolol (1 mg/kg) before the start of the experiments. Cromakalim (30 microg/kg) was administered before and after L-NAME (7.5 mg/kg), and the parameters were monitored for 15 min after each intervention. A Millar double-tipped microcatheter was used to record left ventricular and aortic pressures. Lead II of the ECG was monitored. During a 15-min period after administration of cromakalim, 22.3 +/- 6.0 abnormal ventricular complexes were recorded. L-NAME administration significantly reduced these abnormal complexes to 4.5 +/- 2 (paired t test, p < or = 0.05). We therefore conclude that cromakalim has arrhythmogenic properties in the baboon and that these can be attenuated by L-NAME.

Feedforward versus feedback control in children and adults subjected to a postural disturbance.

Any action performed by standing subjects is generally accompanied by compensatory postural activities, which reduce or abolish the postural disturbance generated by the movements and keep the subjects' center of gravity within the supporting base. These postural activities are triggered by either anticipatory and/or feedback-based control processes, depending on the information available and on the behavioral context. To investigate the respective involvement of these two components in postural control during development, we studied the extent to which the postural equilibrium of children (3-to 10-year-olds) and adults was disturbed by the same physical event, an unloading, depending on whether it was initiated by the subject or externally imposed. The subjects were standing on a force platform with their eyes closed, holding a load (5% of their own body weight) in their hands, with arms vertical and forearms horizontal. Two conditions were applied: (1) the subjects voluntarily released the load and (2) the load was unpredictably removed. The unloading resulted in a backward movement of the center of pressure, which was smaller with self-initiated than imposed disturbances in all age groups. This difference varied depending mainly on the age-related changes in the relative amplitude of the self-initiated disturbance, which decreased between 3- to 5-, and 6- to 8-year-olds (who showed no marked postural instability after self-initiated unloading), and increased again in the two older groups (9- to 10-year-olds and adults), in which it also became more consistent It was concluded that feedforward control. becomes more efficient as children grow up, but that its relative contribution to postural control does not show a monotonic pattern of development.

Audit of chest X-rays in general practice--a case for local guidelines?

OBJECTIVE: To investigate the use of the chest X-ray (CXR) in a typical urban practice with reference to the Royal College of Radiology (RCR) guidelines. DESIGN: A retrospective review of all requests over a two-year period. SETTING: Urban general practice with 9,463 registered patients. RESULTS: A total of 569 CXRs were performed in 482 patients. Thirty per cent of the CXRs were assessed as being "not indicated" and a significant percentage of requests did not come within the RCR guidelines. The guidelines advise a six weeks' delay following onset of chest wall pain prior to chest X-ray. We assessed the application of the rule in this patient group. A large percentage of those X-rayed were referred at less than the recommended six weeks' interval from time of presentation and the vast majority of CXRs were entirely normal. The "six weeks rule" was developed further in patients with cough, differentiating between simple and productive cough. Those with productive cough who were otherwise well had no significant findings in contrast to the unwell group where several abnormalities were noticed. Radiology-recommended follow-up films were further studied. Where the CXR was carried out after a time interval of less than three weeks, several showed incomplete resolution and a further film was required. CONCLUSION: The RCR guidelines might be adapted to apply to those with simple cough or to those with productive cough who are otherwise well. This simple recommendation, in addition to the RCR guidelines, we feel would reduce the number of unnecessary CXRs performed in general practice.

Stability of cardiodynamic and some blood parameters in the baboon following intravenous anaesthesia with ketamine and diazepam.

The stability of cardiodynamic and some blood parameters during a slow, continuous infusion of a combination of ketamine and diazepam is reported. Contractility (dP/dt), myocardial relaxation (Tln), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), arterial blood pressure and certain blood parameters were assessed in 3 male and 3 female juvenile baboons (Papio ursinus). Anaesthesia was induced with 15 mg/kg ketamine i.m. and maintained with a continuous i.v. infusion (40-60 ml/h) of ketamine and diazepam. The mixture consisted of 2 ml ketamine (100 mg/ml), 2 ml diazepam (5 mg/ml) and 50 ml saline. A period of 75 +/- 10 min was allowed for preparation of the animals, after which lead II of the ECG, femoral artery blood pressure and left ventricular pressure were recorded at 15-min intervals for a period of 2 h: the total duration of anaesthesia was 195 min. Arterial blood samples were analysed at 30-min intervals for blood gases, electrolytes, glucose and insulin. Left ventricular parameters were derived from the left ventricular pressure curve. Tln, LVSP and LVEDP showed small fluctuations. Contractility decreased (p < 0.037) at the 195-min interval. No arrhythmias or ECG changes were seen, while blood pressure decreased gradually. Serum calcium concentration decreased and blood glucose levels increased gradually over time. Anaesthesia and analgesia were sufficient and no other drugs were necessary. The animals appeared sedated and dazed 60-80 min after the procedure. A continuous infusion of a combination of ketamine and diazepam for a duration of 150 min can provide stable anaesthesia for cardiodynamic measurements.

Patient, nurse and physician views of dyspnea.

Dyspnea, the subjective sensation of laboured or difficult breathing, is a frequent complaint of patients with terminal disease. Among terminally ill cancer patients, for example, the incidence has been reported to be as high as 74 per cent. Dyspnea is multidimensional, having both physiological and psychological aspects, and, for most people, it worsens as the disease progresses. It is an extremely distressing symptom for both the patient and the family; virtually all dyspneic patients report anxiety or fear of suffocation, a fear that, in turn, exacerbates the dyspnea.

Some adverse cardiodynamic effects of prostaglandin E2 in congestive heart failure.

The cardiodynamic effects of prostaglandin E(2) (PGE(2)) were studied in both healthy sheep and in animals with congestive heart failure (CHF). Merino ewes were equipped surgically with high fidelity micromanometers and left ventricular pressures measured. Heart rate, left ventricular systolic and end-diastolic pressures, +dP/dt and T(ln) were calculated on a computer from the recorded pressure curves. The paired t-test was used to determine the statistical significance of the differences. PGE(2) (25 mu g/kg) significantly improved the cardiac contractility and relaxation rate of healthy sheep and significantly reduced the heart rate, while the loading conditions under which the heart operates were not significantly affected. In contrast to healthy sheep, PGE(2) significantly reduced the contractility and relaxation rate of sheep with congestive heart failure and significantly increased the preload while heart rate and afterload were significantly reduced. The study suggests that despite the promising vasodilatory, positive inotropic and relaxation rate actions of PGE(2) in normal hearts, PGE(2) might not be a suitable therapeutic agent for CHF, because of the worsening effect it has on the cardiodynamics and loading conditions of the failing heart.

Availability of visual and proprioceptive afferent messages and postural control in elderly adults.

The ability of young and elderly adults to keep a stable upright posture while facing changes in the availability of visual and/or propriomuscular information was investigated. The two sensory sources of information were alternatively available and withdrawn, jointly and separately, during 10-s alternating sequences. Vision was modified by means of liquid-crystal goggles, and proprioception was altered by means of tendon vibration of both antagonistic ankle muscles. Elderly adults were less stable than young adults when vision was withdrawn. Both groups were greatly affected when propriomuscular inputs were altered by vibration. Under constant visual conditions and following a propriomuscular perturbation (i.e., vibration), elderly adults were unable to take advantage of the reinsertion of propriomuscular inputs. They showed a transient, decreased stability and were unable to fully recover during a 10-s period, whereas young adults were able to rapidly integrate the information to stabilize their posture. When both propriomuscular and visual inputs were withdrawn and concurrently reinserted, the elderly adults did not show a transitory increase in the velocity of the center of foot pressure. The present results extend findings on the inability of elderly adults to reconfigure rapidly the postural set following reinsertion of sensory inputs. The results also suggest that elderly adults have difficulties in taking advantage of sensory redundancy in postural control.

Prophylactic use of human endotoxin-core hyperimmune gammaglobulin to prevent endotoxaemia in colostrum-deprived, gnotobiotic lambs challenged orally with Escherichia coli.

The efficacy of human IgG polyclonal antibody to endotoxin-core in preventing endotoxaemia and subsequent disease was studied in colostrum-deprived gnotobiotic lambs challenged orally at about 5 h old with 10(9) cfu Escherichia coli. Human endotoxin-core hyperimmune gammaglobulin was given intravenously to 5 lambs at 1.9 g IgG/kg bodyweight prior to challenge. Human albumin was given intravenously to 3 control lambs. Bacteraemia was observed in all lambs, but the incidence was lower (P < 0.01) and the onset later (P < 0.05) in gammaglobulin pre-treated lambs. These lambs showed no signs of disease, whereas clinical endotoxaemia, manifesting as watery mouth disease, was diagnosed in 2 of the 3 control lambs which were killed between 18 and 22 h after challenge. Thus, prophylactic treatment of colostrum-deprived lambs with human IgG enriched in endotoxin-core antibodies was effective in reducing the degree of bacteraemia and preventing endotoxaemia, leukopenia and clinical disease following oral challenge with E. coli.

Age effects on reflex and postural responses to propriomuscular inputs generated by tendon vibration.

The effects of aging on two sensorimotor levels of propriomuscular function were investigated in a young (20- to 44-year-old) and an elderly (60- to 86-year-old) population by eliciting segmental reflex and postural responses via the same muscle spindle inflow generated by applying the same pattern of tendon vibration. The latency and amplitude of the reflex responses to vibration (tonic vibration reflex) of the biceps and triceps brachii did not depend on the subjects' age. No major age-related changes were observed in the deep reflexes of the lower limbs. The postural responses to the same vibratory stimulation applied to both the soleus or the tibialis anterior muscles (vibration-induced falling) did not show any changes in latency depending on either age or the visual conditions, whereas the intensity of these responses decreased both with age and when the use of vision was possible. Our results suggest that the two levels at which the same propriomuscular messages were processed are differentially affected by aging. The lower reflex level does not undergo any noticeable impairment, whereas the higher postural control level deteriorates in the elderly, which might be partly responsible for the balance problems which tend to occur more frequently with advancing age.

Resolving power of the perceptual- and sensorimotor systems in 6- to 10-year-old children.

Children aged 6 to 10 were tested on their ability to move accurately and to perceptually evaluate their motor response. Subjects performed a directional and an amplitude visuo-manual aiming task without vision of their moving limb. They were asked to correct their error, after completion of their movements, only if they felt they were not accurate. Terminal aiming errors and correction responses (adjustments) were analyzed, and threshold detection was determined relative to terminal aiming error. Action accuracy and evaluation of action accuracy are two abilities that do not develop synchronously. Moreover, the relationship between these abilities depends on whether accuracy and direction or amplitude are required. Amplitude undergoes more corrections than direction, suggesting that the spatial system of reference involved depends more upon the coding of the final position than on direction. Two spatial comparators, operating on the basis of two types of evaluation, seem to have a variably distinct contribution to movement and perception accuracy, according to age.

The dose-related hyper-and-hypokalaemic effects of salbutamol and its arrhythmogenic potential.

1. The hypokalaemic effect of salbutamol after more than 30 min of administration has been well described. A hyper-and-hypokalaemic effect for adrenaline has been reported, but no such hyperkalaemic effect for salbutamol. 2. The possible hyper-and-hypokalaemic effects of salbutamol with the concomitant potential for pro-arrhythmia were assessed in the baboon (Papio ursinus). 3. Male and female baboons were anaesthetized with ketamine (15 mg kg-1) and maintained with 6% pentobarbitone as spontaneously breathing animals. Six baboons in each group received either 10, 100 or 500 micrograms kg-1 salbutamol i.v. Lead II of the ECG and femoral i.a. blood pressure were recorded continuously for 10 min. Arterial blood samples were collected at 0 min and then after 3 and 10 min of salbutamol administration. 4. All the animals developed sinus tachycardia (above 200 beats min-1) within 30 s of each dose of salbutamol administration and the high heart rate persisted throughout the experiment. All the animals were hyperkalaemic after 3 min and hypokalaemic after 10 min for each dose of salbutamol. Left ventricular conduction defects were seen in 3 animals during the hyperkalaemic phase. No arrhythmia was seen during the hypokalaemic phase. 5. Salbutamol has a transient hyperkalaemic and a more prolonged hypokalaemic effect in the baboon. The hypokalaemia could not be associated with arrhythmia although conduction defects were associated with the hyperkalaemia. 6. Since salbutamol is used as a bronchodilator in asthmatic patients and to treat acute hyperkalaemia, it is suggested that caution should be exercised when using salbutamol in high doses to treat acute asthma especially during the first few minutes of administration. The finding of hyperkalaemia with salbutamol questions its use in the treatment of hyperkalaemia.