Cannabis and driving: A new perspective

Cannabis and driving is an emerging injury‐prevention concern. The incidence of driving while affected by cannabis is rising in parallel with increased cannabis use in the community. Younger drivers are at particular risk. Improvements in research methodology, technology and laboratory testing methods have occurred in the last 10 years. These cast doubt on earlier results and conclusions. Studies now show that cannabis has a significant impairing effect on driving when used alone and that this effect is exaggerated when combined with alcohol. Of particular concern is the presence of cannabis as the sole psychoactive drug in an increasing number of road fatalities and the lack of any structural response to this problem. A review of testing methods, laboratory and real driving studies, and recent epidemiological studies is presented. Suggestions for methods of further data collection and future public policy are made.     

Successful tracheal autotransplantation with a vascularized omental flap.

A major problem in tracheal transplantation is the restoration of an adequate vascular supply to the transplanted trachea. In 12 piglets, a segment (6 rings) of thoracic trachea was removed and the excised segment was then sutured back in place. In 9 animals (group A), a vascularized omental flap was wrapped around the autotransplanted trachea. In the other 3 pigs (group B), the omentum was not used. Eight of 9 group A pigs were killed, 1 or 2 months later, having had no signs of airway obstruction; the 9th pig was killed after 14 days because of airway obstruction. The 3 pigs in group B were killed after 11 to 13 days because of progressive respiratory obstruction. In the 8 asymptomatic pigs in group A, the omental flap was viable and tracheal growth was normal with no differences in diameter between normal and autotransplanted trachea. Histologically intact cartilage was lined with respiratory epithelium. In the one group A pig who was killed early, the omental flap was necrotic. In this pig and in the 3 group B animals, extensive tracheal necrosis and nonviable cartilage were observed. These findings indicate that in the pig, a 6-ring segment of trachea can be transplanted with vascularization provided by an omental flap.     

A noninvasive, in vivo model for studying strain adaptive bone modeling

We present a noninvasive, in vivo model for strain application in the tibiae of rats. The hind limb of each animal was placed into a device that applied four point bending to the tibia. Bending was applied in the medial-lateral direction causing compression on the lateral surface of the tibia and tension on the anteromedial surface. The peak strain magnitudes were estimated to be between 1600 and 3500 mu strain. In this pilot work, data were collected from 12 rats. The rats received either one cycle per day, four cycles per day, 12 cycles per day, 36 cycles per day, or 108 cycles per day of bending. The experimental (right) tibiae from all of the rats showed new bone formation after 12 days. The control (left) tibiae showed no new bone formation over this period. A better organized, dense bony reaction occurred in regions of lesser strains than in regions of higher strains, where there was a large accumulation of bone easily identified as woven. The organization and density of the newly formed bone appeared to be inversely related to the peak strains in the region. After 40 days of daily loading, the new bone area appeared to be more compact and better mineralized. However, bone formation was still occurring after 40 days. The results of this study suggest that woven bone formation occurred due to the bending stimulus and not due to pathology.     

Diagnostic delay after dimenhydrinate use in vomiting children.

OBJECTIVE: To determine whether the use of dimenhydrinate was associated with delay in the diagnosis and management of treatable illnesses or with direct adverse effects in children with vomiting presenting to an emergency department. DESIGN: Questionnaire survey and review of drug reaction and telephone inquiry records. SETTING: The emergency department of a tertiary care children's hospital and a provincial poison information centre. PATIENTS: The parents of 148 children who presented with vomiting completed the questionnaire. The database at the poison information centre included 474 reports of adverse drug reactions over an 8-year period and 105 reports of telephone inquiries over a 4-year period. MAIN RESULTS: Twenty-one (14%) of 148 children had received dimenhydrinate before arrival at the emergency department. The patients who had received dimenhydrinate were more likely than the others to present more than 12 hours after the onset of vomiting (14 [67%] of 21 v. 43 [34%] of 127, p less than 0.01). The discharge diagnoses for those who had received dimenhydrinate included asthma, pelvic inflammatory disease and urinary tract infection. No clinically important direct adverse reactions to dimenhydrinate were documented. CONCLUSIONS: The use of dimenhydrinate in children with vomiting is associated with a risk of delay in the diagnosis of treatable medical conditions.     

Analysis of reticulocyte counts using various methods.

The precision and accuracy of manual reticulocyte counts using the Miller disc reticle, other ruled reticle and no reticle are compared with the reticulocyte results from the automated Hematrak 590 instrument. Two slides of each of 50 patient blood specimens were sent to the hematology laboratories of each of six participating hospitals. In addition to between-method comparison (precision), the manual method results using the three different counting techniques were each compared with the Hematrak results to determine if there were significant differences in reported results (accuracy). Statistical analysis revealed that the Miller disc method was the most precise and accurate manual method as compared with the Hematrak. Methods without a Miller disc reported significantly higher reticulocyte counts. Imprecision was also higher among non-Miller manual methods. By using the Miller disc, the accuracy and precision of manual methods may be increased to that of the automated Hematrak method.     

Noradrenergic activation of immediate early genes in rat cerebral cortex.

Previous studies have shown that stimulation of adrenergic receptors in the brain increases the expression of the immediate early gene (IEG), c-fos, in vivo (Mol. Brain Res., 6(1989) 39-45). The present study was undertaken to determine whether this also holds for other IEGs which have been shown to be activated in brain cell culture by adrenergic agonists. Both yohimbine injection and stressful stimulation, two treatments causing brain norepinephrine (NE) release, were found to cause a parallel, transient activation of at least 5 IEGs (c-fos, nur77, tis-7, zif-268 and tis-21) in the rat cortex. Genes that are not immediate early (beta-actin, NGF and HSP70) were found not to be affected in the interval used (6 h). The responses were mediated predominantly by beta-adrenoceptors with some contribution from alpha 1 receptors. The parallel activation of multiple genes by noradrenergic receptors may enable the coding of different biochemical responses to the activation of different receptors.     

Food deprivation and hypothalamic neuropeptide gene expression: effects of strain background and the diabetes mutation.

We have used a novel method to identify genes expressed in the hypothalamus which may be potentially involved in controlling food intake and energy metabolism. We assumed that food deprivation, a powerful stimulus of food intake, would stimulate the activity of neural pathways involved in feeding behavior which should be reflected in an increase in the synthesis of any relevant neuropeptide and its messenger RNA. A study of 5 neuropeptides in 5 strains of mice has identified neuropeptide Y (NPY) as a gene whose expression in the hypothalamus is controlled by nutritional status, suggesting that hypothalamic NPY neurons are a link in the neural network regulating feeding behavior and energy metabolism. In addition, we have studied the effect of the diabetes mutation on neuropeptide gene expression during fasting and refeeding. Our findings suggest that abnormal NPY and enkephalin gene expression in the hypothalamus may be two important determinants of the expression of the diabetes mutation.     

Cytokeratin expression in a congenital multipotential primitive neuroectodermal tumor

A case of an uncommon congenital primitive neuroectodermal cerebellar tumor (PNET) in a 5-month-old child is reported. After subtotal surgical resection, the residual tumor did not respond to radiation and chemotherapy. Histologically, the tumor was composed of small, round, undifferentiated cells and several other patterns like astrocytomatous, oligodendrogliomatous, and ependymomatous structures. Immunostaining was positive for most of the cells for vimentin and S 100, fewer were positive for glial fibrillary acid protein (GFAP) and neuron-specific enolase, and only a few for synaptophysin. Surprisingly, the tumor showed strong expression of several monoclonal cytokeratins (CK) with different molecular weights, together with epithelial membrane antigen. Furthermore, we found a coexpression of the tumor cells for CK and vimentin, while CK-GFAP and CK-S 100 were negative. Ultrastructurally, intracyto-plasmic intermediate filaments could be observed corresponding to immunohistochemical CK expression. The very strong CK and vimentin expression in this case was interpreted as a sign of the embryonic nature of the tumor.