Assessment of the acute acrylonitrile-induced neurotoxicity in rats.

Acrylonitrile (VCN) is an aliphatic nitrile which is used extensively in manufacturing of synthetic fibers, plastics, and rubber. Although the neurotoxicity of VCN is recognized, no thorough characterization of this effect has been reported. Current studies were designed to quantitatively characterize the acute phase of VCN-induced cholinomimetic neurotoxicity, and to determine the effects of dose, route of administration, and atropine on such toxicity. Administration of a single gavage or subcutaneous doses of 20, 40, or 80 mg VCN/kg to male Sprague-Dawley rats causes two distinctive phases of acute neurotoxic effects. Signs observed in the early phase had a rapid onset, and were cholinomimetic in nature. They included salivation, lacrimation, chromodacryorrhea, polyuria, miosis, vasodilatation in face, ears and extremities, increased gastric secretion, and diarrhea. A late phase developed hours after VCN dosing, and the toxic signs included depression, convulsions, and respiratory failure followed by death at high doses. These results revealed that the cholinomimetic toxicity induced by VCN was dose related regardless of the route of administration. In another study, rats were pretreated with atropine (1 mg/kg, IP) prior to VCN (40 mg/kg) in order to investigate the role of the cholinergic system. Atropine protected rats against VCN-induced cholinomimetic neurotoxicity, suggesting possible involvement of the cholinergic system. Finally, this work provides essential basic information for studying the biochemical, pharmacological, and neurological basis of VCN-induced neurotoxicity in the rat.     

Ventricular shape biomarkers for Alzheimer's disease in clinical MR images

The aim of this work was to identify ventricular shape-based biomarkers in MR images to discriminate between patients with Alzheimer's disease (AD) and healthy elderly. Clinical MR images were collected for 58 patients and 28 age-matched healthy controls. After normalizing all the images the ventricular cerebrospinal fluid was semiautomatically extracted for each subject and an innovative technique for fully automatic shape modeling was applied to generate comparable meshes of all ventricles. The search for potential biomarkers was carried out with repeated permutation tests: results highlighted well-defined areas of the ventricular surface being discriminating features for AD: the left inferior medial temporal horn, the right medial temporal horn (superior and inferior), and the areas close to the left anterior part of the corpus callosum and the head of the right caudate nucleus. The biomarkers were then used as features to build an intelligent machine for AD detection: a Support Vector Machine was trained on AD and healthy subjects and subsequently tested with leave-1-out experiments and validation tests on previously unseen cases. The results showed a sensitivity of 76% for AD, with an overall accuracy of 84%, proving that suitable biomarkers for AD can be detected in clinical MR images.     

Background sodium current underlying respiratory rhythm regularity

Rhythm-generating neural circuits underlying diverse behaviors such as locomotion, sleep states, digestion and respiration play critical roles in our lives. Irregularities in these rhythmic behaviors characterize disease states – thus, it is essential that we identify the ionic and/or cellular mechanisms that are necessary for triggering these rhythmic behaviors on a regular basis. Here, we examine which ionic conductances underlie regular or ‘stable’ respiratory activities, which are proposed to underlie eupnea, or normal quiet breathing. We used a mouse in vitro medullary slice preparation containing the rhythmogenic respiratory neural circuit, called the preBötzinger complex (preBötC), that underlies inspiratory respiratory activity. We varied either [K⁺]_o or [Na⁺]_o, or blocked voltage-gated calcium channels, while recording from synaptically isolated respiratory pacemakers, and examined which of these manipulations resulted in their endogenous bursting becoming more irregular. Of these, lowering [Na⁺]_o increased the irregularity of endogenous bursting by synaptically isolated pacemakers. Lowering [Na⁺]_o also decreased the regularity of fictive eupneic activity generated by the ventral respiratory group (VRG) population and hypoglossal motor output. Voltage clamp data indicate that lowering [Na⁺]_o, in a range that results in irregular population rhythm generation, decreased persistent sodium currents, but not transient sodium currents underlying action potentials. Our data suggest that background sodium currents play a major role in determining the regularity of the fictive eupneic respiratory rhythm.     

Binary weight-of-evidence evaluations of chemical interactions—15 years of experience

The paper reflects on the last 15 years of experience in the field of mixtures risk assessment. It summarizes results found in various documents developed by the Agency for Toxic Substances and Disease Registry (ATSDR) of the weight-of-evidence (WOE) approach applied to 380 binary combinations of chemicals. Of these evaluations, 156 assessments indicated possible additivity of effects [=], 76 indicated synergism (greater-than-additive effects [>]), and 57 indicated antagonism (less-than-additive effects [<]). However, 91 combinations lacked the minimum information needed for making any assessments and, hence, were undetermined.The paper provides examples of the rationale behind some of the WOE decisions and discusses the importance of expert judgments in risk assessment evaluations. Examples are given regarding the importance of human variability in mixtures’ ability to affect human health and regarding the dose versus effect relationships.     

Turkish general practitioners and complementary/alternative medicine

BACKGROUND: Complementary and alternative medicine (CAM) is in the spotlight of society. However, what is the position of physicians at this point? OBJECTIVES: To determine general practitioners' (GP) knowledge, attitudes, and approaches to CAM. METHODS: All GPs (n=521) practicing in Bursa Province, Turkey were surveyed by a questionnaire. RESULTS: Responses from 49% of GPs were analyzed. Altogether, most of our physicians (96.5%) had not received any education about CAM, wanted to learn more (74.4%), and their knowledge levels were low (60.8%). About half of them (51%) believed in the efficiency of CAM, whereas 38.0% did not. GPs desire more information about herbal medicine and acupuncture. Only 29% of GPs were using some type of CAM for themselves. CONCLUSIONS: GPs are aware of the subject's importance and want to learn more about CAM and improve their knowledge. It would be reasonable to provide training possibilities for GPs, primarily for the CAM types highly used by the population and most requested by the physicians.     

Pill-induced esophageal injury: endoscopic features and clinical outcomes

BACKGROUND AND STUDY AIMS: Pill-induced esophageal injury is a common but under-reported problem. The purpose of this study was to explore the clinical and endoscopic features, and the outcome of pill-related esophageal injury. PATIENTS AND METHODS: Endoscopy records for the period from January 1997 to June 2003 were searched for reports of esophageal pathology. The records of patients with pill-induced esophageal injury were evaluated. RESULTS: A total of 92 patients with pill-induced esophageal injury were identified (33 men, 59 women; mean age 59, range 25-87). Common symptoms were odynophagia (n = 69, 75 %), chest pain (n = 55, 60 %), vomiting (n = 53, 58 %), dysphagia (n = 31, 33 %), and hematemesis (n = 14, 15 %). The endoscopic findings in the esophagus were: erythema in 76 patients (83 %), erosions in 53 patients (58 %), ulcers in 24 patients (26 %), seven of which were "kissing" ulcers, esophageal ulcer with bleeding in 17 patients (18 %), and esophageal strictures in seven patients (8 %). The causative pills were nonsteroidal anti-inflammatory drugs in 38 patients (41 %), tetracyclines in 20 patients (22 %), potassium chloride tablets in nine patients (10 %), alendronate in eight patients (9 %), and other drugs in 17 patients (18 %). Underlying diseases included diabetes in 60 patients (65 %), ischemic heart disease in 39 patients (42 %), and hypothyroidism in four patients (4 %). The mean hospital stay was 1.94 days; 14 patients (15 %) required injection of epinephrine 1 : 10,000 to control bleeding; and two patients died. CONCLUSIONS: Pill-induced injury may present as erosions, kissing ulcers, and multiple small areas of ulceration with bleeding, mainly in the middle third of the esophagus. Advanced age, female gender, diabetes, and ischemic heart disease were common associations. The majority of patients made an uneventful recovery.     

Determinants of third dose of diphtheria–tetanus–pertussis (DTP) completion among children who received DTP1 at rural immunization centres in Pakistan: a cohort study

Objective  In Pakistan, a high proportion of children fail to complete third dose of diphtheria-tetanus-pertussis (DTP3) after having received the first dose (DTP1). A cohort study was conducted to identify the factors predicting three doses of diphtheria–tetanus–pertussis (DTP3) completion among children who have received DTP1 at six centres of Expanded Programme on Immunization (EPI) in rural Pakistan.
Method  We analyzed a cohort of mother–child pairs enrolled at DTP1 between November 2005 and May 2006 in the standard care group of a larger randomized controlled trial. Data were collected from mothers on a structured questionnaire at enrolment, and each child was followed up at clinic visits for 90 days to record dates of DTP2 and DTP3. Multivariable log-binomial regression analysis was performed to identify the independent predictors of DTP3 completion.
Results  Only 39% (149/378) of enrolled children completed DTP3 during the follow-up period. After adjusting for the centre of enrolment in multivariable analysis, DTP3 completion was higher among children who were ≤60 days old at enrolment [adjusted risk ratio (Adj. RR) 1.39, 95% confidence interval (CI): 1.06–1.82], who were living in a household with monthly household income >Rs. 3000 (US$ 50) (Adj. RR 1.76, 95% CI: 1.16–2.65), and who were living ≤10 min away from EPI centre (Adj. RR 1.31, 95% CI: 1.04–1.66).
Conclusions  Interventions targeting childhood immunization dropouts should focus on bringing more children to EPI centres on-time for initial immunization. Relocation of existing EPI centres and creation of new EPI centres at appropriate locations may decrease the travel time to the EPI centres and result in fewer immunization dropouts.