Incidence of tricyclic antidepressant-like complications after cyclobenzaprine overdose

Background: The cyclobenzaprine structure is similar to amitriptyline; however, tricyclic antidepressant (TCA)-like wide complex dysrhythmia has not been reported. Our objective was to determine the incidence of TCA-like effects in cyclobenzaprine overdoses as reported to 6 poison centers for 2 years. We compared the incidence of these effects to amitriptyline overdoses collected during the same period. Methods: We performed a retrospective review of 2 years of cases as reported to the Texas Poison Center Network. We identified sole ingestions of cyclobenzaprine and of amitriptyline. Cases had a recorded clinical outcome and clinical effect. A trained reviewer used a standard data collection sheet within a secured electronic database. One investigator audited a random sample of charts. Results: We identified 3974 cases of cyclobenzaprine calls. Of these, we collected 209 cases of acute overdoses without coingestions. There were no deaths. No cases of cyclobenzaprine ingestions were reported to have died or have a wide QRS or ventricular dysrhythmia. Seizures were reported in 2 cases; however, both were unrelated to cyclobenzaprine. Hypotension was reported in 1.4% (3/209) of cases, and a vasopressor was used in one case (0.5%). Patients with an amitriptyline overdose were more likely to have seizure, coma, tachycardia, a wide QRS or ventricular dysrhythmia, and have received sodium bicarbonate or be intubated. Conclusions: Cyclobenzaprine overdoses were not reported to cause widened QRS, ventricular dysrhythmias, or seizures, and hypotension was rarely reported. Tricyclic antidepressant-related effects occurred more often in our comparison group of amitriptyline overdoses

Power Quality Improvement in 3 – Phase System Using Shunt Active Filter

Voltage, current and frequency are the three physical characteristics that mostly define the power quality and a power quality issue is defined as “any occurrence manifested in current, voltage, or frequency deviations that results in damage, upset or failure of end-use equipments”. The higher switching frequency and the non-linearity in the properties of the power electronics devices are mostly responsible for the power quality issue. So importance is being given to the development of Active Power Filters to solve these problems to improve power quality among which shunt active power filter is used to eliminate voltage and load current harmonics and for reactive power compensation. The shunt active power filters have been developed based on control strategies like instantaneous active and reactive power compensation scheme (p-q control) and instantaneous active and reactive current scheme (Id-Iq control). Considering its superior nature, a study on the Id-Iq control scheme based shunt active filter is brought out in this project. The compensation is carried out by the use of PI based controllers. A theoretical study based on both the compensation schemes is done in this project and then the theory of Id-Iq control scheme is implemented in simulation work and its harmonic compensation results are analyzed

Analysis of Foundations and Retaining walls on Industrial waste

The accumulation of industrial waste has poses a serious problem to the industrial growth and to human habitation. Disposal of industrial waste is covering vast track of valuable land. In this study an attempt has been made to evaluate the properties of industrial wastes like fly ash, red mud, crusher dust, blast furnace slag to use as foundation bed and backfill in retaining structures. As most of the industrials wastes are dumped as heaps, studies have been carried out for the footings embedded in sloping ground. Various research have been done in the seismic bearing capacity of footings for horizontal ground, but the study for sloping ground is very limited. The effect of seismic forces on the above footings is also studied using finite element method. The inclined retaining walls with industrial wastes as backfill was analysed. As the variation in geotechnical properties of industrial wastes are obvious due to various reasons, lastly, reliability analysis of foundations on industrial waste using tradition limit equilibrium method is also studied, considering the variability of the parameters contributing to the performance of the system

Toxicokinetic Profiles of α-ketoglutarate Cyanohydrin, a Cyanide Detoxification Product, Following Exposure to Potassium Cyanide

Poisoning by cyanide can be verified by analysis of the cyanide detoxification product, α-ketoglutarate cyanohydrin (α-KgCN), which is produced from the reaction of cyanide and endogenous α-ketoglutarate. Although α-KgCN can potentially be used to verify cyanide exposure, limited toxicokinetic data in cyanide-poisoned animals are available. We, therefore, studied the toxicokinetics of α-KgCN and compared its behavior to other cyanide metabolites, thiocyanate and 2-amino-2-thiazoline-4-carboxylic acid (ATCA), in the plasma of 31 Yorkshire pigs that received KCN (4 mg/mL) intravenously (IV) (0.17 mg/kg/min). α-KgCN concentrations rose rapidly during KCN administration until the onset of apnea, and then decreased over time in all groups with a half-life of 15 min. The maximum concentrations of α-KgCN and cyanide were 2.35 and 30.18 μM, respectively, suggesting that only a small fraction of the administered cyanide is converted to α-KgCN. Although this is the case, the α-KgCN concentration increased \u3e100-fold over endogenous concentrations compared to only a three-fold increase for cyanide and ATCA. The plasma profile of α-KgCN was similar to that of cyanide, ATCA, and thiocyanate. The results of this study suggest that the use of α-KgCN as a biomarker for cyanide exposure is best suited immediately following exposure for instances of acute, high-dose cyanide poisoning

Simultaneous Determination of Cyanide and Thiocyanate in Plasma by Chemical Ionization Gas Chromatography Mass-spectrometry (CI-GC-MS)

An analytical method utilizing chemical ionization gas chromatography-mass spectrometry was developed for the simultaneous determination of cyanide and thiocyanate in plasma. Sample preparation for this analysis required essentially one-step by combining the reaction of cyanide and thiocyanate with pentafluorobenzyl bromide and simultaneous extraction of the product into ethyl acetate facilitated by a phase-transfer catalyst, tetrabutylammonium sulfate. The limits of detection for cyanide and thiocyanate were 1 μM and 50 nM, respectively. The linear dynamic range was from 10 μM to 20 mM for cyanide and from 500 nM to 200 μM for thiocyanate with correlation coefficients higher than 0.999 for both cyanide and thiocyanate. The precision, as measured by %RSD, was below 9 %, and the accuracy was within 15 % of the nominal concentration for all quality control standards analyzed. The gross recoveries of cyanide and thiocyanate from plasma were over 90 %. Using this method, the toxicokinetic behavior of cyanide and thiocyanate in swine plasma was assessed following cyanide exposure

Cyanide Toxicokinetics: The Behavior of Cyanide, Thiocyanate and 2-Amino-2-Thiazoline-4-Carboxylic Acid in Multiple Animal Models

Cyanide causes toxic effects by inhibiting cytochrome c oxidase, resulting in cellular hypoxia and cytotoxic anoxia, and can eventually lead to death. Cyanide exposure can be verified by direct analysis of cyanide concentrations or analyzing its metabolites, including thiocyanate (SCN−) and 2-amino-2-thiazoline-4-carboxylic acid (ATCA) in blood. To determine the behavior of these markers following cyanide exposure, a toxicokinetics study was performed in three animal models: (i) rats (250–300 g), (ii) rabbits (3.5–4.2 kg) and (iii) swine (47–54 kg). Cyanide reached a maximum in blood and declined rapidly in each animal model as it was absorbed, distributed, metabolized and eliminated. Thiocyanate concentrations rose more slowly as cyanide was enzymatically converted to SCN−. Concentrations of ATCA did not rise significantly above the baseline in the rat model, but rose quickly in rabbits (up to a 40-fold increase) and swine (up to a 3-fold increase) and then fell rapidly, generally following the relative behavior of cyanide. Rats were administered cyanide subcutaneously and the apparent half-life (t1/2) was determined to be 1,510 min. Rabbits were administered cyanide intravenously and the t1/2 was determined to be 177 min. Swine were administered cyanide intravenously and the t1/2 was determined to be 26.9 min. The SCN−t1/2 in rats was 3,010 min, but was not calculated in rabbits and swine because SCN−concentrations did not reach a maximum. The t1/2 of ATCA was 40.7 and 13.9 min in rabbits and swine, respectively, while it could not be determined in rats with confidence. The current study suggests that cyanide exposure may be verified shortly after exposure by determining significantly elevated cyanide and SCN− in each animal model and ATCA may be used when the ATCA detoxification pathway is significant

Survey of the quality of experimental design, statistical analysis and reporting of research using animals

For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria

Expert Consensus Guidelines for Stocking of Antidotes in Hospitals That Provide Emergency Care

We provide recommendations for stocking of antidotes used in emergency departments (EDs). An expert panel representing diverse perspectives (clinical pharmacology, medical toxicology, critical care medicine, hematology/oncology, hospital pharmacy, emergency medicine, emergency medical services, pediatric emergency medicine, pediatric critical care medicine, poison centers, hospital administration, and public health) was formed to create recommendations for antidote stocking. Using a standardized summary of the medical literature, the primary reviewer for each antidote proposed guidelines for antidote stocking to the full panel. The panel used a formal iterative process to reach their recommendation for both the quantity of antidote that should be stocked and the acceptable timeframe for its delivery. The panel recommended consideration of 45 antidotes; 44 were recommended for stocking, of which 23 should be immediately available. In most hospitals, this timeframe requires that the antidote be stocked in a location that allows immediate availability. Another 14 antidotes were recommended for availability within 1 hour of the decision to administer, allowing the antidote to be stocked in the hospital pharmacy if the hospital has a mechanism for prompt delivery of antidotes. The panel recommended that each hospital perform a formal antidote hazard vulnerability assessment to determine its specific need for antidote stocking. Antidote administration is an important part of emergency care. These expert recommendations provide a tool for hospitals that offer emergency care to provide appropriate care of poisoned patients

Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret