Long-term effects of cannabis on brain structure.

The dose-dependent toxicity of the main psychoactive component of cannabis in brain regions rich in cannabinoid CB1 receptors is well known in animal studies. However, research in humans does not show common findings across studies regarding the brain regions that are affected after long-term exposure to cannabis. In the present study, we investigate (using Voxel-based Morphometry) gray matter changes in a group of regular cannabis smokers in comparison with a group of occasional smokers matched by the years of cannabis use. We provide evidence that regular cannabis use is associated with gray matter volume reduction in the medial temporal cortex, temporal pole, parahippocampal gyrus, insula, and orbitofrontal cortex; these regions are rich in cannabinoid CB1 receptors and functionally associated with motivational, emotional, and affective processing. Furthermore, these changes correlate with the frequency of cannabis use in the 3 months before inclusion in the study. The age of onset of drug use also influences the magnitude of these changes. Significant gray matter volume reduction could result either from heavy consumption unrelated to the age of onset or instead from recreational cannabis use initiated at an adolescent age. In contrast, the larger gray matter volume detected in the cerebellum of regular smokers without any correlation with the monthly consumption of cannabis may be related to developmental (ontogenic) processes that occur in adolescence.

Driving under the influence of cocaine or therapeutic administration of cocaine?

Introduction: In forensic toxicology, cocaine is better known for its powerful stimulating effects of nervous system and its high potential for recreational abuse, than for his therapeutic use. However, cocaine is still use as a topical anesthetic and peripheral vasoconstrictor in surgeries of eye, ear, nose and throat. Last decade, an increase of the presence of cocaine and metabolites in blood samples of drivers suspected to drive under the influence of drugs (DUID) was observed in Switzerland (Augsburger et al., Forensic Sci Int 153 (2005) 11-15; Senna et al., Forensic Sci Int 198 (2010) 11-16). Observed blood concentration ranges of cocaine and benzoylecgonine were 10-925 μg/L and 20-5200 μg/L, respectively. Since 2005, zero-tolerance approach was introduced in the Swiss legislation for different substances, especially cocaine (analytical cutoff: 15 μg/L). Thus, the interpretation often amounts to determine if the concentration is situated above or under the limit. However, it is important for the interpretation to take into account the context and to be critical with the obtained results, at the risk of ending in erroneous conclusions. Methods: Systematical toxicological analyses were performed on blood and urine, if available, for 5 DUID cases, as already published (Augsburger et al., Forensic Sci Int 153 (2005)). Positive results were confirmed and drugs were quantified in biological samples by GCMS, GC-MS/MS or LC-MS/MS. Results: Administration of cocaine after traffic accident was identified in five cases. All people were admitted to the emergency room because of severe trauma. Maxillofacial surgery was done shortly after admission to the emergency room, involving use of nasal application of cocaine (swab). For all cases, use of cocaine swab was not mentioned in the document filled by the police and by medical staff requested for blood and urine sampling. The information was obtained retrospectively after consultation of the medical records, without precise indication of the application time or dose. Case 1. A 83-year old man (pedestrian) was hit by a car. Blood (+11h after the accident): cocaine (16 μg/L), benzoylecgonine (370 μg/L). Urine: cocaine (1700 μg/L), benzoylecgonine (560 μg/L). Case 2. A 84-year old woman (pedestrian) was hit by a car. Blood (+1.5h after the accident): cocaine (230 μg/L), benzoylecgonine (370 μg/L). Urine was not available. Hair (+4 months after the accident): segment 1 (0-2 cm), cocaine not detected; segment 2 (2-4 cm), cocaine: <0.5 ng/mg. Case 3. A 66-year old man was involved in a car/car accident. He died 2 hours and 5 minutes after the crash. Blood (+1.5h after the accident): cocaine and metabolites not detected. Blood (+2h after the accident): cocaine (1750 μg/L), benzoylecgonine (460 μg/L). Blood (post-mortem): cocaine (370 μg/L), benzoylecgonine (200 μg/L). Urine (+1.5h after the accident): cocaine not detected. Case 4. A 57-year old woman on a motor scooter was hit by a car. She died 2 hours and 10 minutes after the crash. Blood (+0.5h after the accident): cocaine and metabolites not detected. Urine (post-mortem): cocaine (<20 μg/L), benzoylecgonine (120 μg/L). Case 5. A 30-year old man was involved in a car accident. Blood (+4h after the accident): cocaine (29 μg/L), benzoylecgonine (< 20 μg/L). Urine (+4h after the accident): cocaine and metabolites not detected. Ethanol (1,32 g/kg) and cannabinoids (THC (2,0 μg/L), THCCOOH (38 μg/L)) were also detected in blood. Conclusion: To our knowledge, this is the first description of DUID cases involving therapeutic use of cocaine after an accident. These results indicate that even if a per se law is effective for prosecution case of DUID, a critical interpretation of the results is always needed, especially if a medical intervention occurs after an accident.

Instruments for investigating fitness to drive - needs and expectations in primary care: a qualitative study

Background: Primary care physicians are often requested to assess their patients' fitness to drive. Little is however known on their needs to help them in this task. Aims: The aim of this study is to develop theories on needs, expectations, and barriers for clinical instruments helping physicians assess fitness to drive in primary care. Methods: This qualitative study used semi-structured interviews to investigate needs and expectations for instruments used to assess fitness to drive. From August 2011 to April 2013, we recorded opinions from five experts in traffic medicine, five primary care physicians, and five senior drivers. All interviews were integrally transcribed. Two independent researchers extracted, coded, and stratified categories relying on multi-grounded theory. All participants validated the final scheme. Results: Our theory suggests that for an instruments assessing fitness to drive to be implemented in primary care, it need to contribute to the decisional process. This requires at least five conditions: 1) it needs to reduce the range of uncertainty, 2) it needs to be adapted to local resources and possibilities, 3) it needs to be accepted by patients, 4) choices of tasks need to adaptable to clinical conditions, 5) and interpretation of results need to remain dependant of each patient's context. Discussion and conclusions: Most existing instruments assessing fitness to drive are not designed for primary care settings. Future instruments should also aim to support patient-centred dialogue, help anticipate driving cessation, and offer patients the opportunity to freely take their own decision on driving cessation as often as possible.

Tackling Societal Challenges Related to Ageing and Transport Transition: An Introduction to Philosophical Principles of Causation Adapted to the Biopsychosocial Model

In geriatrics, driving cessation is addressed within the biopsychosocial model. This has broadened the scope of practitioners, not only in terms of assessing fitness to drive, but also by helping to maintain social engagements and provide support for transport transition. Causes can be addressed at different levels by adapting medication, improving physical health, modifying behaviour, adapting lifestyle, or bringing changes to the environment. This transdisciplinary approach requires an understanding of how different disciplines are linked to each other. This article reviews the philosophical principles of causality between fields and provides a framework for understanding causality within the biopsychosocial model. Understanding interlevel constraints should help practitioners overcome their differences, and favor transversal approaches to driving cessation.

Discretionary medical reporting of potentially unfit drivers: a questionnaire-based survey in Southeast Switzerland

In Switzerland, every physician has the right to report a patient that is potentially unfit to drive to the licensing authority without violating medical confidentiality. Verified information regarding physicians' attitudes concerning this discretionary reporting and the frequency of such reports are not available. In order to answer these questions, 635 resident physicians were sent a questionnaire. The response rate was 52%. On average, the responding physicians--for all specialties--reported 0.31 patients (SD 0.64, 95% CI 0.24-0.38) in the year before the survey and 1.00 patient (SD 1.74, 95% CI 0.81-1.20) in the past 5 years. Seventy-nine percent of the responding physicians indicated knowing the current legal requirements for driving in Switzerland. In applied logistic regression analysis, only two factors correlate significantly with reporting: male sex (odds ratio 5.4) and the specialty "general medicine" (odds ratio 3.4). Ninety-seven percent of the physicians were against abolishing medical discretionary reporting and 29% were in favor of introducing mandatory reporting. The great majority of the questioned physicians supported the discretionary reporting of drivers that are potentially unfit to drive as currently practiced in Switzerland. The importance and the necessity of a regular traffic medicine-related continuing education for medical professionals are shown by the low number of reports per physician.

Physicians' knowledge and continuing medical education regarding fitness to drive: a questionnaire-based survey in Southeast Switzerland

Valid information for physicians in Switzerland concerning knowledge and continuing education in traffic medicine is not available. Also, their attitude to the legally prescribed periodic driving fitness examinations is unclear. In order to gain more information about these topics, 635 resident physicians in Southeast Switzerland were sent a questionnaire (response rate 52%). In a self-estimation, 79% of the queried physicians claimed to know the minimal medical requirements for drivers which are important in their specialty. Statistically significant differences existed between the specialties, whereby general practitioners most frequently claimed to know the minimal medical requirements (90%). It appears that the minimal medical requirements for drivers are well known to the queried physicians. Fifty-two percent of the physicians favored an expansion of continuing education in traffic medicine. Such an expansion was desired to a lesser extent by physicians without knowledge of the minimal requirements (p < 0.001). A clear majority of the medical professionals adjudged the legally prescribed periodic driving fitness examinations as being an expedient means to identify unfit drivers. A national standardized form for reporting potentially unfit drivers to the licensing authorities was supported by 68% of the responding physicians. Such a form could simplify and standardize the reports to the licensing authorities.

The association between air pollution and blood pressure in traffic controllers in Santo Andre, Sao Paulo, Brazil

Background: Urban air pollutants are associated with cardiovascular events. Traffic controllers are at high risk for pollution exposure during outdoor work shifts. Objective: The purpose of this study was to evaluate the relationship between air pollution and systemic blood pressure in traffic controllers during their work shifts. Methods: This cross-sectional study enrolled 19 male traffic controllers from Santo Andre city (Sao Paulo, Brazil) who were 30-60 years old and exposed to ambient air during outdoor work shifts. Systolic and diastolic blood pressure readings were measured every 15 min by an Ambulatory Arterial Blood Pressure Monitoring device. Hourly measurements (lags of 0-5 h) and the moving averages (2-5 h) of particulate matter (PM(10)), ozone (O(3)) ambient concentrations and the acquired daily minimum temperature and humidity means from the Sao Paulo State Environmental Agency were correlated with both systolic and diastolic blood pressures. Statistical methods included descriptive analysis and linear mixed effect models adjusted for temperature, humidity, work periods and time of day. Results: Interquartile increases of PM(10) (33 mu g/m(3)) and O(3) (49 mu g/m(3)) levels were associated with increases in all arterial pressure parameters, ranging from 1.06 to 2.53 mmHg. PM(10) concentration was associated with early effects (lag 0), mainly on systolic blood pressure. However, O(3) was weakly associated most consistently with diastolic blood pressure and with late cumulative effects. Conclusions: Santo Andre traffic controllers presented higher blood pressure readings while working their outdoor shifts during periods of exposure to ambient pollutant fluctuations. However, PM(10) and O(3) induced cardiovascular effects demonstrated different time courses and end-point behaviors and probably acted through different mechanisms. (C) 2011 Elsevier Inc. All rights reserved.

The effects of chronic exposure to traffic derived air pollution on the ocular surface

Objectives: The purpose of this study was to explore the clinical relevance of chronic exposure to ambient levels of traffic derived air pollution on the ocular surface. Methods: A panel study involving 55 volunteers was carried out in Sao Paulo, Brazil. We measured the mean individual levels of nitrogen dioxide (NO(2)) exposure for 7 days. All subjects answered the Ocular Symptom Disease Index (OSDI) and a symptoms inventory. Subsequently, subjects underwent Schirmer I test, biomicroscopy, vital staining and tear breakup time (TOUT) assessment. Subject`s mean daily exposure to NO(2) was categorized in quartiles. Statistical analysis was performed using one-way ANOVA, Tukey HSD and Chi-Square tests. Results: A dose-response pattern was detected between OSDI scores and NO(2) quartiles (p < 0.05). There was a significant association between NO(2) quartiles and reported ocular irritation (X(2) = 9.2, p < 0.05) and a significant negative association between TBUT and NO(2) exposure (p < 0.05, R = -0.316. Spearman`s correlation). There was a significant increase in the frequency of meibomitis in subjects exposed to higher levels of NO(2) (p < 0.05). Conclusions: Subjects exposed to higher levels of traffic derived air pollution reported more ocular discomfort symptoms and presented greater tear film instability, suggesting that the ocular discomfort symptoms and tear breakup time could be used as convenient bioindicators of the adverse health effects of traffic derived air pollution exposure. (C) 2010 Elsevier Inc. All rights reserved.

Effects of ambient levels of air pollution generated by traffic on birth and placental weights in mice

Objective: To examine whether there is an association between fetal and/or placental weight and exposure to ambient levels of air pollution in mice. Design: Chronic experiments on mice that were exposed to polluted vs. clean air. Setting: Environmental exposure to atmospheric pollution. Animal(S): Female Swiss mice (n = 70) were maintained at different stages of gestation in an exposure chamber located at an intersection with heavy traffic in a major city in Brazil. Control mice were maintained in a similar chamber, located adjacent to the exposure chamber but equipped with filters for particles and reactive gases. Intervention(s): Animals were divided into six groups as follows: no exposure, exposure to a polluted chamber throughout gestation, exposure to a polluted chamber during the 1st week of pregnancy, exposure to a polluted chamber during the 2nd and 3rd weeks, exposure to a polluted chamber during the 1st and 2nd week, and exposure to a polluted chamber during the 3rd week. Main Outcome Measure(S): At the end of the gestational period, the determination of fetal and placental weight was performed after cesarean section. Result(s): Exposure to air pollution during the 1st week of pregnancy promoted a significant reduction in fetal weight. Mice exposed to polluted air, in any phase of gestation, presented with lower placental weight in comparison to mice maintained in clean chambers. Conclusion(s): Exposure to ambient levels of traffic pollution at early phases of gestation is a determinant for decreased final fetal weight. Placental weight is reduced with exposure to air pollution at any phase of gestation. (Fertil Steril (R) 2008;90:1921-4. (C)2008 by American Society for Reproductive Medicine.)

Quality assurance in road traffic analyses in Switzerland.

Swiss laboratories performing toxicological road traffic analyses have been authorized for many years by the Swiss Federal Roads Office (FEDRO). In 2003 FEDRO signed a contract with the Swiss Society of Legal Medicine (SSLM) to organize the complete quality management concerning road traffic analyses. For this purpose a multidisciplinary working group was established under the name of "road traffic commission (RTC)". RTC has to organize external quality control, to interpret the results of these controls, to perform audits in the laboratories and to report all results to FEDRO. Furthermore the working group can be mandated for special tasks by FEDRO. As an independent organization the Swiss Center for Quality Control (CSCQ) in Geneva manages the external quality controls in the laboratory over the past years. All tested drugs and psychoactive substances are listed in a federal instruction. The so-called 'zero tolerance substances' (THC, morphine, cocaine, amphetamine, methamphetamine, MDMA and MDEA) and their metabolites have to be tested once a year, all other substances (benzodiazepines, zolpidem, phenobarbital, etc.) periodically. Results over the last years show that all laboratories are generally within the confidence interval of +/-30% of the mean value. In cases of non-conformities measures have to be taken immediately and reported to the working group. External audits are performed triennially but accredited laboratories can combine this audit with the approval of the Swiss Accreditation Service (SAS). During the audits a special checklist filled in by the laboratory director is assessed. Non-conformities have to be corrected. During the process of establishing a new legislation, RTC had an opportunity of advising FEDRO. In collaboration with FEDRO, RTC and hence SSLM can work actively on improving of quality assurance in road traffic toxicological analyses, and has an opportunity to bring its professional requests to the federal authorities.

Application of 3D documentation and geometric reconstruction methods in traffic accident analysis: with high resolution surface scanning, radiological MSCT/MRI scanning and real data based animation

The examination of traffic accidents is daily routine in forensic medicine. An important question in the analysis of the victims of traffic accidents, for example in collisions between motor vehicles and pedestrians or cyclists, is the situation of the impact. Apart from forensic medical examinations (external examination and autopsy), three-dimensional technologies and methods are gaining importance in forensic investigations. Besides the post-mortem multi-slice computed tomography (MSCT) and magnetic resonance imaging (MRI) for the documentation and analysis of internal findings, highly precise 3D surface scanning is employed for the documentation of the external body findings and of injury-inflicting instruments. The correlation of injuries of the body to the injury-inflicting object and the accident mechanism are of great importance. The applied methods include documentation of the external and internal body and the involved vehicles and inflicting tools as well as the analysis of the acquired data. The body surface and the accident vehicles with their damages were digitized by 3D surface scanning. For the internal findings of the body, post-mortem MSCT and MRI were used. The analysis included the processing of the obtained data to 3D models, determination of the driving direction of the vehicle, correlation of injuries to the vehicle damages, geometric determination of the impact situation and evaluation of further findings of the accident. In the following article, the benefits of the 3D documentation and computer-assisted, drawn-to-scale 3D comparisons of the relevant injuries with the damages to the vehicle in the analysis of the course of accidents, especially with regard to the impact situation, are shown on two examined cases.

Virtopsy -- noninvasive detection of occult bone lesions in postmortem MRI: additional information for traffic accident reconstruction

In traffic accidents with pedestrians, cyclists or motorcyclists, patterned impact injuries as well as marks on clothes can be matched to the injury-causing vehicle structure in order to reconstruct the accident and identify the vehicle which has hit the person. Therefore, the differentiation of the primary impact injuries from other injuries is of great importance. Impact injuries can be identified on the external injuries of the skin, the injured subcutaneous and fat tissue, as well as the fractured bones. Another sign of impact is a bone bruise. The bone bruise, or occult bone lesion, means a bleeding in the subcortical bone marrow, which is presumed to be the result of micro-fractures of the medullar trabeculae. The aim of this study was to prove that bleeding in the subcortical bone marrow of the deceased can be detected using the postmortem noninvasive magnetic resonance imaging. This is demonstrated in five accident cases, four involving pedestrians and one a cyclist, where bone bruises were detected in different bones as a sign of impact occurring in the same location as the external and soft tissue impact injuries.