Local anaesthetic systemic toxicity following oral ingestion in a child: Revisiting dibucaine.
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SUBMITTER: Dias R
PROVIDER: S-EPMC5530745 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:Introduction Although uncommon, local anaesthetic systemic toxicity (LAST) may impose fatal risk to the patients. We investigated the awareness of LAST and knowledge on local anaesthetics among our postgraduate trainees. Materials and Methods A total of 134 postgraduate trainees from the departments of general surgery (Surgical), orthopaedic surgery (Ortho), otorhinolaryngology (ENT), obstetrics and gynaecology (OBGYN), as well as anaesthesiology and intensive care (Anaesth) were recruited. A validated questionnaire was used to assess awareness and knowledge. All participants attended a medical-education session and completed the questionnaire as preassessment and postassessment. Data were analysed, and comparisons between disciplines were conducted. Results The trainees' awareness of LAST was overall poor at preassessment which improved almost 6-folds at postassessment. Surprisingly, only 20 (45.5%) participants from the anaesthesiology group had awareness of LAST at preassessment, and none of the participants were from surgical, orthopaedic, and obstetrics and gynaecology departments. Preassessment scores were significantly higher in the anaesth group as compared to all other groups; with a difference in the average score for Anaesth vs Surgical of 3.46 (95%, CI:2.17, 4.74), Anaesth vs Ortho of 3.64 (95%, CI:2.64, 4.64), Anaesth vs ENT of 3.43 (95%, CI:2.20, 4.67), and Anaesth vs OBGYN of 6.93 (95%, CI:5.64, 8.21). However, there was no significant difference of awareness scores between all participants at postassessment scores. Conclusion The overall level of awareness was poor. However, the implementation of an education session significantly improved the knowledge and awareness across all disciplines.
| S-EPMC9675600 | biostudies-literature
Project description: Not available
| S-EPMC8543182 | biostudies-literature
Project description:IntroductionOver 16 000 mastectomies are performed in England and Wales annually. Acute postoperative pain and nausea are common. The most frequently occurring long-term complications are chronic pain (up to 50%) and reduced shoulder function (reported at 35%). Regional techniques that improve acute postoperative pain relief may reduce the incidence of these complications. This study assesses the effectiveness of a 24-hour continuous local anaesthetic in the subpectoral plane in improving postoperative pain and quality of life in patients undergoing mastectomy.Methods and analysisThis is a randomised, double blind, placebo-controlled, two-centre, parallel group trial in women undergoing mastectomy with or without axillary involvement. One hundred and sixty participants will be randomised in a 1:1 ratio to receive either 0.25% levobupivacaine or 0.9% saline by subpectoral infusion postoperatively for 24 h. All participants will be provided with an intravenous morphine patient-controlled analgesia (PCA) system. Participants will be followed-up for 24 h in hospital and at approximately 14 days and 6 months postoperatively. Joint primary outcome measures are total morphine consumption and total pain score (captured via patient-recorded visual analogue scale (VAS) 4 hourly) during the first 24 h postoperatively. Primary statistical analysis of total pain is based on the area under the curve of pain versus time graph. Secondary outcomes include PCA attempts in first 24 h; VAS pain scores and shoulder function by goniometry at 24 h, 14 days (approximately) and 6 months; Verbal Rating Scale pain scores in first 24 h; Brief Pain Inventory and Oxford Shoulder Score at 6 months; duration of hospital stay; incidence of postoperative nausea and vomiting; cost-effectiveness.Ethics and disseminationThe study is approved by the South West England Research Ethics Committee (12/SW/0149).Resultswill be published in a peer-reviewed journal and presented at local, national and international scientific meetings.Trial registrationISRCTN46621916. EudraCT 2011-005775-16.
| S-EPMC4179566 | biostudies-literature
Project description:INTRODUCTION:Steroidal alkaloids are found in plants of the genus Veratrum. Their toxicity manifests as gastrointestinal symptoms followed by a Bezold-Jarisch reflex: hypopnea, hypotension, and bradycardia. Some Veratrum steroidal alkaloids are also teratogens interfering with the hedgehog-2 signaling pathway, which causes cyclopsia and holoprosencephaly. We present a case of accidental poisoning from Veratrum parviflorum mistaken for the edible Allium tricoccum (ramps, wild leek). CASE HISTORY:A 27-year-old man and his 25-year-old wife presented to the emergency department with nausea, vomiting, hypotension, and bradycardia after foraging and ingesting plants that they believed to be a local native species of wild leek. METHODS:We collected and analyzed the implicated fresh plant material and both patients' serum/plasma. We used liquid chromatography-mass spectroscopy and high-resolution electrospray ionization time of flight tandem mass spectrometry to extract and characterize steroidal alkaloids from the foraged plant and patients' serum. RESULTS:Our V. parviflorum samples contained verazine, veratramine, veratridine, and cyclopamine. DISCUSSION:Steroidal alkaloids have been previously isolated from Veratrum viride and Veratrum album and toxicity has been reported mainly from V. album species. CONCLUSION:V. parviflorum toxicity manifests with gastrointestinal and cardiac symptoms. Treatment is symptomatic and supportive as with previous case reports of toxicity with other Veratrum species.
| S-EPMC6086754 | biostudies-literature
Project description:Regulatory agencies rely upon rodent in vivo acute oral toxicity data to determine hazard categorization, require appropriate precautionary labeling, and perform quantitative risk assessments. As the field of toxicology moves toward animal-free new approach methodologies (NAMs), there is a pressing need to develop a reliable, robust reference data set to characterize the reproducibility and inherent variability in the in vivo acute oral toxicity test method, which would serve to contextualize results and set expectations regarding NAM performance. Such a data set is also needed for training and evaluating computational models. To meet these needs, rat acute oral LD50 data from multiple databases were compiled, curated, and analyzed to characterize variability and reproducibility of results across a set of up to 2441 chemicals with multiple independent study records. Conditional probability analyses reveal that replicate studies only result in the same hazard categorization on average at 60% likelihood. Although we did not have sufficient study metadata to evaluate the impact of specific protocol components (eg, strain, age, or sex of rat, feed used, treatment vehicle, etc.), studies were assumed to follow standard test guidelines. We investigated, but could not attribute, various chemical properties as the sources of variability (ie, chemical structure, physiochemical properties, functional use). Thus, we conclude that inherent biological or protocol variability likely underlies the variance in the results. Based on the observed variability, we were able to quantify a margin of uncertainty of ±0.24 log10 (mg/kg) associated with discrete in vivo rat acute oral LD50 values.
| S-EPMC9237992 | biostudies-literature
Project description:BackgroundAcute toxicity means the ability of a substance to cause adverse effects within a short period following dosing or exposure, which is usually the first step in the toxicological investigations of unknown substances. The median lethal dose, LD50, is frequently used as a general indicator of a substance's acute toxicity, and there is a high demand on developing non-animal-based prediction of LD50. Unfortunately, it is difficult to accurately predict compound LD50 using a single QSAR model, because the acute toxicity may involve complex mechanisms and multiple biochemical processes.ResultsIn this study, we reported the use of local lazy learning (LLL) methods, which could capture subtle local structure-toxicity relationships around each query compound, to develop LD50 prediction models: (a) local lazy regression (LLR): a linear regression model built using k neighbors; (b) SA: the arithmetical mean of the activities of k nearest neighbors; (c) SR: the weighted mean of the activities of k nearest neighbors; (d) GP: the projection point of the compound on the line defined by its two nearest neighbors. We defined the applicability domain (AD) to decide to what an extent and under what circumstances the prediction is reliable. In the end, we developed a consensus model based on the predicted values of individual LLL models, yielding correlation coefficients R(2) of 0.712 on a test set containing 2,896 compounds.ConclusionEncouraged by the promising results, we expect that our consensus LLL model of LD50 would become a useful tool for predicting acute toxicity. All models developed in this study are available via http://www.dddc.ac.cn/admetus.
| S-EPMC4047767 | biostudies-literature
Project description:Itaconate-producing neutrophils regulate local and systemic inflammation following trauma
2023-11-08 | GSE221134 | GEO
Project description:Cylindrospermopsin (CYN) is a toxin associated with numerous species of freshwater cyanobacteria throughout the world. It is postulated to have caused an episode of serious illnesses in Australia through treated drinking water, as well as lethal effects in livestock exposed to water from farm ponds. Toxicity included effects indicative of both hepatic and renal dysfunction. In humans, symptoms progressed from initial hepatomegaly, vomiting, and malaise to acidosis and hypokalemia, bloody diarrhea, and hyperemia in mucous membranes. Laboratory animal studies predominantly involved the intraperitoneal (i.p.) route of administration and confirmed this pattern of toxicity with changes in liver enzyme activities and histopathology consistent with hepatic injury and adverse renal effects. The aim of this study was designed to assess subchronic oral exposure (90 d) of purified CYN from 75 to 300 µg/kg/d in mouse. At the end of the dosing period, examinations of animals noted (1) elevated organ to body weight ratios of liver and kidney at all dose levels, (2) treatment-related increases in serum alanine aminotransferase (ALT) activity, (3) decreased blood urea nitrogen (BUN) and cholesterol concentrations in males, and (4) elevated monocyte counts in both genders. Histopathological alterations included hepatocellular hypertrophy and cord disruption in the liver, as well as renal cellular hypertrophy, tubule dilation, and cortical tubule lesions that were more prominent in males. A series of genes were differentially expressed including Bax (apoptosis), Rpl6 (tissue regeneration), Fabp4 (fatty acid metabolism), and Proc (blood coagulation). Males were more sensitive to many renal end points suggestive of toxicity. At the end of exposure, toxicity was noted at all dose levels, and the 75 µg/kg group exhibited significant effects in liver and kidney/body weight ratios, reduced BUN, increased serum monocytes, and multiple signs of histopathology indicating that a no-observed-adverse-effect level could not be determined for any dose level.
| S-EPMC6764423 | biostudies-literature
Project description:The incidence of pleural disease is increasing, and interventions are crucial in this subspecialist area of respiratory medicine. One of the cornerstones of pleural effusion investigation and management is medical, which is also known as local anaesthetic thoracoscopy. This allows fluid drainage, biopsy for diagnosis and preventative measures for further fluid potential build-up. This article summarises the evidence around this procedure through a narrative review of the available evidence.
| S-EPMC9601808 | biostudies-literature
Project description:RationaleMeal ingestion triggers secretion of a variety of gut and endocrine peptides important in diabetes research which are routinely measured by immunoassays. However, similarities between some peptides (glucagon, oxyntomodulin and glicentin) can cause specificity issues with immunoassays. We used a liquid chromatography/tandem mass spectrometry (LC/MS/MS) methodology to unambiguously monitor multiple gut peptides in human plasma.MethodsA simple acetonitrile-based protein precipitation step, followed by evaporation and solid-phase extraction, removed high-abundance proteins from samples prior to nano-LC/MS/MS analysis on an Orbitrap Q-Exactive Plus mass spectrometer using a data-dependent methodology. Database searching using PEAKS identified multiple gut-derived peptides, including peptides in the mid-pg/mL range. The relative levels of these and previously characterised peptides were assessed in plasma samples from gastrectomised and control subjects during an oral glucose tolerance test.ResultsAnalysis of plasma extracts revealed significantly elevated levels of a number of peptides following glucose ingestion in subjects who had undergone gastrectomy compared with controls. These included GLP-1(7-36), GLP-1(9-36), glicentin, oxyntomodulin, GIP(1-42), GIP(3-42), PYY(1-36), PYY(3-36), neurotensin, insulin and C-peptide. Motilin levels decreased following glucose ingestion. Results showed good correlation with immunoassay-derived concentrations of some peptides in the same samples. The gastrectomy group also had higher, but non-glucose-dependent, circulating levels of peptides from PIGR and DMBT1.ConclusionsOverall, the approach showed that a fast, generic and reproducible LC/MS/MS methodology requiring only a small volume of plasma was capable of the multiplexed detection of a variety of diabetes-related peptides.
| S-EPMC7614168 | biostudies-literature