Place of therapeutic cannabis in France and safety data: A literature review.

OBJECTIVES: To date, very few cannabis-based specialities are authorised on the French market despite a growing demand from patients and health professionals. The objective of this study is to review the tolerance profile and the French legislative status of the two main cannabinoids used for therapeutic purposes: tetrahydrocannabiol (THC) associated with psychoactive effects and non-psychoactive cannabidiol (CBD). METHODS: This review is based on relevant articles retrieved by a search in Google Scholar and PubMed databases and on an assessment of the legal texts and summaries of product characteristics available in France. RESULTS: Evidence for the tolerability of CBD during chronic use is reassuring, but a significant risk of drug interactions exists. THC use appears to be associated with a higher proportion of serious adverse effects, including neuropsychological and cardiovascular effects. Inhaled cannabis appears to be associated with greater toxicity than the oral route. These data are presented together with the pharmacokinetic and pharmacodynamic data of THC and CBD. CONCLUSION: The literature reports several frequent but rarely serious adverse effects of CBD during chronic use as well as a significant risk of drug interactions. THC use seems to be associated with a higher proportion of serious adverse effects compared to CBD, particularly at the neuropsychological and cardiovascular levels. Health professionals should be up to date on the particularities of therapeutic cannabis in terms of efficacy, safety and drug interactions.

HLA class I and II alleles are associated with microvascular complications of type 1 diabetes.

Although HLA alleles are associated with type 1 diabetes, association with microvascular complications remains controversial. We tested HLA association with complications in multiplex type 1 diabetes families. Probands from 425 type 1 diabetes families from the Human Biological Data Interchange (HBDI) collection were analyzed. The frequencies of specific HLA alleles in patients with complications were compared with the frequencies in complications-free patients. The complications we examined were: retinopathy, neuropathy, and nephropathy. We used logistic regression models with covariates to estimate odds ratios. We found that the DRB1*03:01 allele is a protective factor for complications (OR=0.58; p=0.03), as is the DQA1*05:01-DQB1*02:01 haplotype found in linkage disequilibrium with DRB1*03:01 (OR=0.59; p=0.031). The DRB1*04:01 allele showed no evidence of association (OR=1.13; p=0.624), although DRB1*04:01 showed suggestive evidence when the carriers of the protective DRB1*03:01 were removed from the analysis. The class II DQA1*03:01-DQB1*03:02 haplotype was not associated with complications, but the class I allele B*39:06 (OR=3.27; p=0.008) suggested a strong positive association with complications. Our results show that in type 1 diabetes patients, specific HLA alleles may be involved in susceptibility to, or protection from, microvascular complications.

A comparison of predictions made by three simulation models of foot-and-mouth disease.

AIMS: To describe results of a relative validation exercise using the three simulation models of foot-and-mouth disease (FMD) in use by the quadrilateral countries (QUADS; Australia, Canada, New Zealand, and United States of America; USA). METHODS: A hypothetical population of farms was constructed and, following the introduction of an FMD-like disease into a single farm, spread of disease was simulated using each of the three FMD simulation models used by the QUADS countries. A series of 11 scenarios was developed to systematically evaluate the key processes of disease transmission and control used by each of the three models. The predicted number of infected units and the size of predicted outbreak areas for each scenario and each model were compared using the Kruskal-Wallis test. Agreement among the three models in terms of geographical areas predicted to become infected were quantified using Fleiss' Kappa statistic. RESULTS: Although there were statistically significant differences in model outputs in terms of the numbers of units predicted to become infected, the temporal onset of infection throughout the simulation period, and the spatial distribution of infected units, these differences were generally small and would have resulted in the same (or similar) management decisions being adopted in each case. CONCLUSIONS: Agreement among the three models in terms of the numbers of premises predicted to become infected, the temporal onset of infection throughout the simulation period, and the spatial distribution of infected premises provides evidence that each of the model developers are consistent in their approach to simulating the spread of disease throughout a population of susceptible individuals. This consistency implies that the assumptions taken by each development team are appropriate, which in turn serves to increase end-user confidence in model predictions. CLINICAL RELEVANCE: Relative validation is one of a number of steps that can be undertaken to increase end-user confidence in predictions made by infectious disease models.

Mortalidade em granjas de crescimento/terminaçäo de suínos nos Estados Unidos / Mortality on grower/finisher-only swine operations in the United States

A mortalidade de suínos, durante um período de 6 meses, variou de 0 a 12 por cento em 53 granjas de crescimento/terminaçäo, que participam do "United States National Animal Health Monitoring System 1995 National Swine Study". Vinte e seis (49,1 por cento) granjas tiveram <2 por cento de mortalidade e 27 (50,9 por cento) tiveram índices >2 por cento. Nove (17,0 por cento) granjas apresentaram mortalidade >4 por cento. A análise pelo teste de Fisher revelou que as granjas que adotavam o sistema "all-in, all-out" eram significativamente mais propensas a apresentar índices <2 por cento que as granjas com manejo contínuo, e que as granjas nas quais todos os suínos terminados eram oriundos de unidades pertencentes às próprias granjas eram significativamente mais propensas a ter mortalidade <2 por cento que as granjas onde os animais (>1) provinham de outras origens. Granjas maiores (com mais de 900 animais entrando na fase de crescimento/terminaçäo) adotavam com maior freqüência o manejo "all-in, all-out" e tiveram menor percentual de mortalidade do que pequenas granjas. O diagnóstico de Salmonella em suínos terminados, realizado 12 meses antes da intervençäo, foi associado ao aumento do percentual de mortalidade geral e diário

Injuries and illnesses in working dogs used during the disaster response after the bombing in Oklahoma City.

OBJECTIVES: To determine characteristics of working dogs used during the disaster response after the bombing in Oklahoma City and risk factors for injuries and illnesses of those dogs, and to document recommendations for future disaster responses. DESIGN: Survey. STUDY POPULATION: Information for 74 working dogs used at the bombing site. PROCEDURES: Dog handlers were identified and asked to complete a questionnaire. Questions were asked about the training and use of each dog, use of paw protection, injuries and illnesses incurred, possible effects after completion of duty at Oklahoma City, and handler's experience. RESULTS: Data were obtained for all 74 dogs used at the site. Handlers of 69 of 74 (93%) dogs responded. The dogs had been extensively trained and were used 491 dog-days at the site, with 46 dogs used in search, 14 in patrol, 12 in explosive-detection duty, and 2 in search/patrol. Fifteen (22%) dogs became ill. Nineteen (28%) dogs incurred 20 injuries. Footpad injuries constituted 18 of the injuries. Only 16 of 69 (23%) dogs were provided with paw protection. Dogs were more likely to be injured when they were used in a search capacity, were used during the first 2 days after the bombing, were German Shepherd Dogs, or were older. CLINICAL IMPLICATIONS: Although working in a high-risk environment, injuries to dogs were few, and most were minor. Specific recommendations could facilitate use of dogs in disaster situations and improve safety for those dogs.

An analysis of mortality in the grower/finisher phase of swine production in the United States.

Over a 6-month period, the mean mortality risk (based on 393 operations participating in the United States National Animal Health Monitoring System 1995 National Swine Study, and representing operations with > or = 300 market hogs in 16 states), was 2.3 +/- 0.2% in the grower/finisher production phase (where figures after the +/- represent the standard error of the estimate). Mortality > or = 4% was experienced by 13.5 +/- 2.9% of grower/finisher operations, while 63.6 +/- 5.3% had < or = 2% mortality. To identify factors associated with > or = 4% mortality, stepwise logistic regression [Statistical Analysis Systems, 1989. SAS/STAT User's Guide, Version 6, 4th edn, Vol. 2. SAS Institute, Cary, NC, 794 pp.] was performed twice: once using operations with all mortality rates, and again excluding operations with between 2% and 4% mortality. Final models were run with SUDAAN [Shah, B.V., Barnwell, B.G., Bieler, G.S., 1996. SUDAAN User's Manual, Version 6.40, 2nd edn. Research Triangle Institute, Research Triangle Park, NC, 492 pp.] to take the sample design into account. In addition, SAS and SUDAAN logistic regression models were developed to analyze factors associated with > 2.3% mortality among grower/finisher pigs. Mean weaning age < or = 28 days entered all models as being associated with increased mortality in the grower/finisher unit. Not obtaining all grower/finisher pigs from farrowing units belonging to the operation was associated with > or = 4% mortality among grower/finisher swine. Not typically giving grower/finisher pigs antibiotics or other agents as disease-preventives or growth-promotants in the feed or water, and ranking producer organizations as very or extremely important sources of antibiotic information were associated with < or = 2.3% mortality in the grower/finisher phase.

Mortality attributed to respiratory problems among finisher pigs in the United States.

In the 1995 National Swine Study of the United States National Animal Health Monitoring System, producers identified respiratory problems as the leading cause of death in pigs during the grower/finisher phase of production. Over a six-month period, 61.7 +/- 4.1% (mean +/- SEM) of operations reported at least one death attributed to respiratory problems among finisher pigs (based on 388 operations representing operations with > or = 300 finisher pigs in 16 states). Mean mortality attributed to respiratory problems was 0.9 +/- 0.1% of finisher pigs per operation. Stepwise logistic regression (using SAS) was used to identify factors associated with operations attributing at least one death to respiratory problems, and to identify factors associated with reporting > or = 2% mortality attributed to respiratory problems. Final models were run with SUDAAN to account for the sampling strategy. Attributing at least one death to respiratory problems was associated with having > or = 3000 pigs enter the grower/finisher unit over a six-month period; diagnosis of Haemophilus (or Actinobacillus) in the past 12 months; and keeping pigs in the grower/finisher unit > 120 days (as compared to < 100 days). Not having a farrowing facility, mean weaning age < 28 days, and < 50% of finisher pigs on solid concrete only were associated with reporting > or = 2% mortality attributed to respiratory problems.

[Iatrogenic rupture of the left mainstem bronchus in tracheobronchial intubation]. / Rottura iatrogena del bronco principale sinistro da intubazione tracheobronchiale.

A 74-year-old woman underwent right thoracotomy to remove a lung neoplasm. After general anesthesia had been induced, a no. 37 Bronchocath (Mallinkrodt) left endobronchial tube (TDL) was inserted. The TDL was initially positioned in the right mainstem bronchus and then had to be removed and repositioned in the left mainstem bronchus. It was not deemed necessary to use a fibrobronchoscope at this stage. During surgery the reduced minute expiratory volume and signs of pneumomediastinum made it necessary to perform tracheobronchoscopy. This led to the diagnosis of a rectilinear rupture of the left mainstem bronchus starting immediately below the carina, at the level of the pars membranacea and extending as far as the origin of the superior lobar bronchus. The left TDL was replaced by a similar right TDL and emergency left thoracotomy was performed following surgical repair of the damage. No problems of note occurred during the postoperative period. The patient did not present any of the predisposing risk factors for rupture of the tracheo-bronchial tree, except for slight fragility of tracheal respiratory mucosa. The anesthetist did not use fibrobronchoscopy or any devices to control the pressure level of TDL sleevs during the intubation and selection of the bronchus. These aids might have prevented the occurrence of a potentially fatal complication.

Likelihood of introducing selected exotic diseases to domestic swine in the continental United States of America through uncooked swill.

To help policy makers determine the need for current regulations (which require cooking of swill prior to feeding to swine), an assessment of the likelihood of exposing domestic swine in the continental United States of America (USA) to selected foreign animal disease agents by feeding uncooked swill was carried out. The hazard was assumed to originate from contraband food items entering the USA and subsequently being discarded in household waste. Such food waste may be collected by licensed waste feeders and fed to swine. This study showed that, of the four diseases studied, the probability of exposure was highest for the classical swine fever (hog cholera) virus. The median annual likelihood of one or more contaminated loads of swill being fed to swine in the continental USA was estimated as follows: classical swine fever virus: 0.063, foot and mouth disease virus: 0.043, swine vesicular disease virus: 0.005, African swine fever virus: 0.005.

Venobronchial fistula: an unusual early complication after central venous catheterization.

Venobronchial fistula is a rare complication of long-term central venous catheterization. We present the uncommon occurrence of a venobronchial fistula as an acute complication of central venous catheterization during open heart surgery. The factors responsible for this unusual complication and the methods to prevent it are discussed.

Prevention of atrial tachyarrhythmias after non-cardiac thoracic surgery by infusion of magnesium sulfate.

The possible role of magnesium sulfate (MgSO4) infusion in the prevention of atrial tachyarrhythmias after non-cardiac thoracic surgery was evaluated through a prospective study of two hundred patients who underwent non-cardiac thoracic surgery. The patients (who fulfilled the following requirements among others: no myocardial infarction in the previous six months, normal renal function, no use of digitalis or antiarrhythmic drugs, not undergone emergency operations or video-assisted thoracic surgery), were randomly assigned to receive MgSO4 infusion in all circumstances (Mg group), or either no treatment or, if aged over 70 or in cases of pneumonectomy or an intrapericardial procedure, application of digoxin starting on the day of operation (control group). 95 patients were enrolled in the Mg group and 105 in the control group. 93 patients in the Mg group and 101 in the control group were evaluated. Post-operative atrial tachyarrhythmias, mainly atrial fibrillation, occurred in 10 patients (10.7%) in the Mg group and in 27 (26.7%) patients in the control group (chi 2 = 7.009, df = 1. p = 0.008). It is concluded that infusion of MgSO4 is an effective means of reducing the incidence of atrial tachyarrhythmias after non-cardiac thoracic surgery.

Hairy leukoplakia: Epstein-Barr virus receptors on oral keratinocyte plasma membranes.

Hairy leukoplakia (HL) is an oral white lesion associated with, and probably caused by, the Epstein-Barr virus (EBV) among persons who are seropositive for infection with human immunodeficiency virus. A unique feature of HL is its localization to the lateral portion of the tongue. To determine site differences for EBV receptors according to epithelial phenotype, these receptors were mapped in oral mucosa with the use of monoclonal antibodies HB5 and B2(specific for the Complement Fraction 3d/EBV receptor on B lymphocytes). Immunoperoxidase and immunofluorescence techniques were employed with the use of both cytologic suspensions and frozen tissue sections of oral epithelium. Pericellular plasma membrane immunoreactants were localized to upper spinous layer cells of the parakeratin phenotype; basal and parabasilar layers as well as all strata of orthokeratinized epithelia were negative. Those cells harboring EBV DNA as detected by in situ hybridization corresponded to cells with C3d/EBV receptors.