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Prekallikrein-Kallikrein conversion rate as a predictor of contrast material catastrophies

An in vitro is described that attempts to detect patients with a potential for adverse systemic reactions to contrast material. This test involves measuring the rate of conversion of prekallikrein to kallikrein under certain standard conditions. In a preliminary retrospective study, the test could be used to identify such patients with a sensitivity of 88%, a specificity of 82%, and a predictive value of 79%.     

Betamethasone effects on chorioamnionitis induced by intra-amniotic endotoxin in sheep

OBJECTIVE: Intra-amniotic administration of endotoxin in sheep is a model of subclinical chorioamnionitis. Intrauterine inflammation alters lung development to improve postnatal lung function and may predispose the infant to lung and brain injury. We describe the effects of intra-amniotic endotoxin on cytokines and white cell responses in the membranes and amniotic fluid and investigate the hypothesis that betamethasone treatment suppresses these responses. STUDY DESIGN: Pregnant ewes were allocated at random to receive either intra-amniotic saline solution (control animals), maternal intramuscular betamethasone, intra-amniotic endotoxin by ultrasound guidance (10 mg Escherichia coli 055:B5), or a combination of the betamethasone and endotoxin treatments. Lambs were delivered abdominally at 110 to 125 days of gestation at time points that ranged from 2 hours to 15 days after treatment. RESULTS: When compared with saline solution-injected control animals, the intra-amniotic injection of endotoxin increased white cell counts in amniotic fluid. Levels of interleukin-8, but not interleukin-6, were significantly increased in amniotic fluid from 5 hours to 15 days after intra-amniotic endotoxin injection, and interleukin-8 levels were not decreased by concurrent treatment with betamethasone. After endotoxin treatment, interleukin-1beta and interleukin-8 messenger RNA were expressed in chorion, and interleukin-6 messenger RNA expression was localized to chorionic blood vessel epithelium. The half-life of endotoxin in the amniotic fluid was 1.7 days, and levels remained measurable 15 days after injection. CONCLUSION: These findings confirm that the fetus can survive within amniotic fluid that contains endotoxin, white cells, and cytokines for periods of weeks or more. Betamethasone treatment can suppress the initial inflammation in the amnion-chorion, but interleukin-8 levels and inflammatory cells in amniotic fluid were not suppressed 5 and 15 days after betamethasone treatment, presumably because of the slow clearance of bioactive endotoxin from the amniotic fluid.     

Lung injury and surfactant metabolism after hyperventilation of premature lambs

We asked whether lung injury and surfactant metabolism differed in preterm lambs after a 1-h period of hyperventilation to P(CO2) values of 25-30 mm Hg. The lambs then were surfactant treated and conventionally ventilated (CV) or high-frequency oscillatory ventilated (HFOV) for an additional 1 or 8 h. The results were compared with lambs that were not hyperventilated or surfactant treated but were ventilated with CV or HFOV. The 1-h hyperventilation resulted in increased alveolar protein, increased recovery of intravascular [131I]albumin in the lungs, and an increase in tumor necrosis factor-alpha mRNA. There were no differences between CV or HFOV in alveolar or total lung recoveries of saturated phosphatidylcholine (Sat PC), tracer doses of [14C]Sat PC and [125I]surfactant protein-B, or in percent Sat PC in large aggregate surfactant in surfactant-treated lambs. The lambs not hyperventilated or treated with surfactant had lower large aggregate pools and lower recoveries of [14C]Sat PC and [125I]surfactant protein-B in total lungs than for the surfactant-treated lungs, but there were no differences between the CV and HFOV groups. Hyperventilation followed by surfactant treatment resulted in a mild injury, but the subsequent use of CV or HFOV did not result in differences in surfactant metabolism.     

Spinal administration of the monoacylglycerol lipase inhibitor JZL184 produces robust inhibitory effects on nociceptive processing and the development of central sensitization in the rat

Background and Purpose

The cannabinoid receptor-mediated analgesic effects of 2-arachidonoylglycerol (2-AG) are limited by monoacylglycerol lipase (MAGL). 4-nitrophenyl 4-[bis (1,3-benzodioxol-5-yl) (hydroxy) methyl] piperidine-1-carboxylate (JZL184) is a potent inhibitor of MAGL in the mouse, though potency is reportedly reduced in the rat. Here we have assessed the effects of spinal inhibition of MAGL with JZL184 on nociceptive processing in rats.

Experimental Approach

In vivo spinal electrophysiological assays in anaesthetized rats were used to determine the effects of spinal administration of JZL184 on spinal nociceptive processing in the presence and absence of hindpaw inflammation. Contributions of CB₁ receptors to these effects was assessed with AM251. Inhibition of 2-oleoylglycerol hydrolytic activity and alterations of 2-AG in the spinal cord after JZL 184 were also assessed.

Key Results

Spinal JZL184 dose-dependently inhibited mechanically evoked responses of wide dynamic range (WDR) neurones in naïve anaesthetized rats, in part via the CB₁ receptor. A single spinal administration of JZL184 abolished inflammation-induced expansion of the receptive fields of spinal WDR neurones. However, neither spinal nor systemic JZL184 altered levels of 2-AG, or 2-oleoylglycerol hydrolytic activity in the spinal cord, although JZL184 displayed robust inhibition of MAGL when incubated with spinal cord tissue in vitro.

Conclusions and Implications

JZL184 exerted robust anti-nociceptive effects at the level of the spinal cord in vivo and inhibited rat spinal cord MAGL activity in vitro. The discordance between in vivo and in vitro assays suggests that localized sites of action of JZL184 produce these profound functional inhibitory effects.

Linked Articles

This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue-8     

Injection drug use among street-involved youth in a Canadian setting

Background  

Street-involved youth contend with an array of health and social challenges, including elevated rates of blood-borne infections and mortality. In addition, there has been growing concern regarding high-risk drug use among street-involved youth, in particular injection drug use. We undertook this study to examine the prevalence of injection drug use and associated risks among street-involved youth in Vancouver, Canada.     

Risk factors for development of dehydration in children aged under five who have acute watery diarrhoea: a case-control study

Objective: To identify risk factors for development of dehydration in under five year olds with acute watery diarrhoea.Design: Hospital based unmatched case-control study.Setting: Diarrhoea Treatment Unit, Government Medical College Hospital, Nagpur, India.Participants: The study included 387 cases of diarrhoea having severe or moderate dehydration and 387 controls suffering from diarrhoea with mild or no dehydration.Risk factors: The study included infancy, female sex, religion, residing in urban slums or rural area, under nutrition, cessation of breast feeding during diarrhoeal episode, fluid intake decreased/stopped during diarrhoea, ORS not received, home available fluids (HAF) not received, both ORS and HAF not received, non-washing of hands by mother before preparation of food, after defaecation, after disposal of faeces, history of measles in the previous six months, frequency of stools >8/d, frequency of vomiting more than twice per day and temperature more than 99°F, as risk factors for development of dehydration.Statistical analysis: Univariate analysis included OR, 95% CI for OR and Chi-square test. Multivariate analysis was carried out by unconditional multiple logistic regression (MLR).Results: This study identified the significance of infancy, religion, severe undernutrition, non-washing of hands by mother before preparation of food, frequency of stool >8/d, frequency of vomiting >2/d, history of measles in previous six months, withdrawal of breast feeding during diarrhoea, withdrawal of fluids during diarrhoea and not giving ORS, HAF or both during diarrhoea, in the outcome of development of moderate or severe dehydration.Conclusions: Timely intervention in the preventable risk factors included in this study may prevent the development of moderate or severe dehydration in the children suffering form acute watery diarrhoea.     

Individual,Social, and Environmental Factors Associated with Initiating Methamphetamine Injection: Implications for Drug Use and HIV Prevention Strategies

The purpose of this study was to determine the incidence and predictors of initiating methamphetamine injection among a cohort of injection drug users (IDU). We conducted a longitudinal analysis of IDU participating in a prospective study between June 2001 and May 2008 in Vancouver, Canada. IDU who had never reported injecting methamphetamine at the study’s commencement were eligible. We used Cox proportional hazards models to identify the predictors of initiating methamphetamine injection. The outcome was time to first report of methamphetamine injection. Time-updated independent variables of interest included sociodemographic characteristics, drug use patterns, and social, economic and environmental factors. Of 1317 eligible individuals, the median age was 39.9 and 522 (39.6%) were female. At the study’s conclusion, 200 (15.2%) participants had initiated injecting methamphetamine (incidence density: 4.3 per 100 person-years). In multivariate analysis, age (adjusted hazard ratio [aHR]: 0.96 per year older, 95%CI: 0.95–0.98), female sex (aHR: 0.58, 95%CI: 0.41–0.82), sexual abuse (aHR: 1.63, 95%CI: 1.18–2.23), using drugs in Vancouver’s drug scene epicentre (aHR: 2.15 95%CI: 1.49–3.10), homelessness (aHR: 1.43, 95%CI: 1.01–2.04), non-injection crack cocaine use (aHR: 2.06, 95%CI: 1.36–3.14), and non-injection methamphetamine use (aHR: 3.69, 95%CI: 2.03–6.70) were associated with initiating methamphetamine injection. We observed a high incidence of methamphetamine initiation, particularly among young IDU, stimulant users, homeless individuals, and those involved in the city’s open drug scene. These data should be useful for the development of a broad set of interventions aimed at reducing initiation into methamphetamine injection among IDU.     

Radiologically guided balloon dilation of gastrointestinal strictures. Part I. Technique and factors influencing procedural success

Radiologically guided balloon catheters were used to dilate 94 gastrointestinal strictures in 92 patients over a 6-year period. Fifty strictures were esophageal and 44 nonesophageal (22 gastroenterostomies, 11 antral-pyloric strictures, four colorectal strictures, four enteroenterostomies, and three miscellaneous strictures). Factors influencing the success of stricture intubation included patient age, stricture location (esophageal vs. nonesophageal and proximal vs. distal esophageal), and association with a surgical anastomosis. Malignancy was associated with greater postdilation irregularity and a smaller increase in stricture diameter, as measured radiographically. Procedural failures occurred in 8% of cases (2% of esophageal and 30% of nonesophageal lesions). Two small, asymptomatic mucosal tears were seen after dilation (one esophageal and one colonic); no other procedural complications occurred. Following successful dilation, 16 patients (17%; six with esophageal and ten with non-esophageal strictures) had recurrence of symptoms during short-term (30-day) follow-up.