Oxidative storm in a patient with acute rotenone-containing plant poisoning.

A 64-year-old woman presented with coma, seizure, and lactic acidosis after ingesting 80 yam bean seeds. This rotenone-containing seeds cause cellular asphyxia via blockage of the mitochondrial electron transport. Subsequent oxidative stress results in the formation of lipid peroxidation (LPO). Rotenone analysis via liquid chromatography mass spectrometry revealed the following: 31,590 ng/mL in cooked yam bean seed and 100 ng/mL in the blood. We attempted to use N-acetylcysteine to alleviate oxidative stress and documented the continuous decline in the plasma concentration of LPO.

Allyl isothiocyanate (AITC) inhibits pregnane X receptor (PXR) and constitutive androstane receptor (CAR) activation and protects against acetaminophen- and amiodarone-induced cytotoxicity.

Antagonizing the action of the pregnane X receptor (PXR) may have important clinical implications for preventing inducer-drug interactions and improving therapeutic efficacy. We identified a widely distributed isothiocyanate, allyl isothiocyanate (AITC), which acts as an effective antagonist of the nuclear receptor pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3). HepG2 cells were used to assay reporter function, mRNA levels, and protein expression. Catalytic activities of the PXR and CAR target genes, CYP3A4 and CYP2B6, respectively, were also assessed in differentiated HepaRG cells. Protective effects of AITC on rifampin-induced cytotoxicity were observed, and transient transfection assays showed that AITC was able to effectively attenuate the agonist effects of rifampin and CITCO on human PXR and CAR activity, respectively. AITC-mediated reduction in the transcriptional activity of PXR and CAR correlated well with the suppression of CYP3A4 and CYP2B6 expression in HepG2 cells, which reflected the reduced catalytic activities of both of these genes following AITC treatment in differentiated HepaRG cells. Furthermore, AITC disrupts the co-regulations of PXR with several important co-regulators. Furthermore, the antagonist effect of AITC against PXR was found in HepaRG cells upon addition of acetaminophen (APAP) and amiodarone, indicating that AITC protects cells from drug-induced cytotoxicity. Taken together, our results show that AITC inhibits the transactivation effects of PXR and CAR and reduces the expression and function of CYP3A4 and CYP2B6. Additionally, AITC reversed the cytotoxic effects of APAP and amiodarone induced by PXR ligand. Results from this study suggest that AITC could be a powerful agent for reducing potentially dangerous interactions between transcriptional inducers of CYP enzymes and therapeutic drugs.

Inhibition of cytochrome P450 2C9 expression and activity in vitro by allyl isothiocyanate.

The growing interest in the use of natural herbal products and dietary supplements to treat and prevent diseases raises the question of medicinal drug safety. Allyl isothiocyanate, a hydrolysis product of a glucosinolate, sinigrin, has multiple beneficial properties, and based on this fact, allyl isothiocyanate-containing dietary supplements have been developed. To date, no studies of the effects of this compound on the cytochrome P450 2C9 have been reported. In this study, we found that allyl isothiocyanate reduced catalytic activity, messenger ribonucleic acid, and protein expression of cytochrome P450 2C9 in HepaRG cells. An investigation of the transcriptional activity of the pregnane X receptor and the constitutive androstane receptor revealed that allyl isothiocyanate disrupted the transcriptional coregulation effects of the pregnane X receptor/constitutive androstane receptor with several important coregulators and interfered with the assembly of transcriptional complexes of the cytochrome P450 2C9 pregnane X receptor/constitutive androstane receptor-response element. The decrease of cytochrome P450 2C9 expression and activity mediated by allyl isothiocyanate suggested that this agent could alter the metabolism of drugs metabolized by cytochrome P450 2C9. This may cause food/dietary supplement-drug interactions or alter the therapeutic effects, and even the toxicity of drugs coadministered with allyl isothiocyanate. Since the consumption of allyl isothiocyanate-containing food/dietary supplements continues to increase, it is important to predict and ultimately avoid interactions with concomitant drugs. It is required that these possible pharmacokinetic interactions be characterized and the recommendations available to patients and healthcare professionals be improved.

Reassessing clinical presentations of emamectin benzoate poisoning: A comprehensive study.

BACKGROUND: The mechanism of emamectin benzoate (EMB-a macrocyclic lactone insecticide like abamectin) action involves the disruption of glutamate-gated chloride channels and GABA receptors in insects, leading to paralysis and death. EMB overdose can breach the blood-brain barrier, resulting in severe poisoning and altered consciousness. AIM: Review EMB poisoning presentations in patients and reevaluate clinical manifestations. MATERIALS AND METHODS: This retrospective study reviewed (August 31, 2008-August 31, 2023) medical university hospital records. We analyzed symptoms, patient characteristics, vital signs, Glasgow Coma Scale scores, laboratory findings, and outcomes. RESULTS: Ten patients (males: 6, females: 4, median age = 64.5 years) experienced EMB poisoning. Common symptoms included sore throat, gastrointestinal distress, dyspnea, and altered consciousness; two patients showed laryngeal corrosive injuries. Management involved activated charcoal administration, gastric lavage, and intensive care unit admission. DISCUSSION: Sore throat and corrosive injuries were distinctive presentations of EMB poisoning, warranting vigilance. Potential mechanisms of corrosive injury include skin and eye irritation effects of EMB, the solvents of which might exert corrosive action. CONCLUSION: EMB poisoning manifests as diverse symptoms, including sore throat, gastrointestinal symptoms, central nervous system depression, and potential aspiration pneumonia. Recognizing and promptly managing EMB poisoning are crucial for enhancing patient outcomes and minimizing complications.

The impact of polymorphisms in STAT6 on treatment outcome in HCV infected Taiwanese Chinese.

Genetic polymorphisms observed in various disease states associated with sensitivity or resistance to specific treatments have been a robust area of investigation for decades, with the potential to allow clinicians to make evidence-based decisions on the appropriate course of treatment. This study aimed to evaluate whether genetic polymorphisms of the signal transducer and activator of transcription 6 gene (STAT6) could be associated with a sustained virological response (SVR) among patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2) who were treated with peginterferon plus ribavirin (PEG-IFNα-RBV). We analyzed the associations between SVR to PEG-IFNα-RBV therapy and 4 single nucleotide polymorphisms (SNPs) in STAT6. This study included Taiwanese Chinese patients infected with either HCV-1 (n = 265) or HCV-2 (n = 195) in the presence or absence of an SVR. Among the STAT6 SNPs examined, the dosage effect of the A allele and allele frequency in rs1059513 were inversely correlated with SVR in patients infected with HCV-1 (P = 0.0179 and P = 0.0235, respectively). This effect was not observed in patients infected with HCV-2. The GG, GGG, and GGGC STAT6 haplotypes comprising 2, 3, and 4 SNPs (rs1059513, rs703817, rs324015, and rs3024974) were found to be associated with SVR, and their presence may increase the probability of a successful treatment outcome in patients infected with HCV-1 (P = 0.0273, 0.0352, and 0.0368, respectively). Moreover, a multivariate logistic regression model for predicting an SVR revealed that the presence of the GGGC haplotype carriers mutually affected the outcome of PEG-IFNα-RBV treatment. The presence of STAT6 SNPs and the association with SVR demonstrated that STAT6 polymorphisms might influence the therapeutic outcomes of patients infected with HCV-1 under standard-of-care (SOC) treatment.

Genetic variation in NOS2A is associated with a sustained virological response to peginterferon plus ribavirin therapy for chronic hepatitis C in Taiwanese Chinese.

This study aimed to evaluate whether genetic polymorphisms of the inducible nitric oxide synthase (iNOS) gene NOS2A could be associated with a sustained virological response (SVR) among patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2) who were treated with peginterferon plus ribavirin (PEG-IFNα-RBV). We analyzed the associations between SVR to PEG-IFNα-RBV therapy and two single nucleotide polymorphisms (SNPs) in NOS2A. This study included Taiwanese Chinese patients infected with either HCV-1 (n = 265) or HCV-2 (n = 195) with or without a SVR. Among the NOS2A SNPs examined, the combination of genotypes A/A and A/G of rs2248814 was inversely correlated with SVR in patients infected with HCV-1 (P = 0.0048), particularly in males (P = 0.0281). This effect was not observed in patients infected with HCV-2. The AC NOS2A haplotype comprising two SNPs (rs2248814 and rs2072324) was found to be associated with SVR, and its presence may decrease the chances for a successful outcome of treatment of patients infected with HCV-1 (P = 0.0053). HCV-1 infected patients who carried the A-C diplotype will have a lower success rate of achieving a SVR (P = 0.0117). In addition, a multivariate logistic regression model for predicting a SVR revealed that the presence of the A-C diplotype interactively affected the outcome of PEG-IFNα-RBV treatment. The presence of NOS2A SNPs and the association with SVR showed that NOS2A polymorphisms may influence the therapeutic outcomes of patients infected with HCV-1 under standard of care treatment.

Late diagnosis of an outbreak of leanness-enhancing agent-related food poisoning.

INTRODUCTION: Ractopamine is a leanness-enhancing agent approved in the United States and 26 other countries to reduce body fat content, increase muscle mass, and improve growth rate of certain food-producing animals. Other ß-agonists with stronger pharmacologic effects, especially clenbuterol, had been illegally used as leanness-enhancing agents in the United States, China, and the European Union, and foodborne poisonings related to clenbuterol residue in meat or liver were rarely reported in the European Union and China. We describe an unusual outbreak of leanness-enhancing agent-related food poisoning in Taiwan and its associated diagnostic challenge. REPORT OF THE OUTBREAK: Twelve patients presented to the emergency department of a regional hospital after having dinner together. Their clinical manifestations included nausea, vomiting, palpitation, facial flush, trunk or limb numbness, tremor, headache, weakness, chill, and dyspnea. Laboratory workup revealed the presence of hypokalemia, leukocytosis, and hyperglycemia. Poisoning attributable to ß-agonists was suspected; however, the diagnosis of leanness-enhancing agent poisoning was delayed because there was no leftover meat for analysis and because the veterinary medicine was illegal in Taiwan. Clenbuterol and salbutamol were eventually detected in 10 patients' urine sample by using liquid chromatography-tandem mass spectrometry, and the concentrations ranged from 54 to 806 µg/L and from 0 to 4052 µg/L, respectively. CONCLUSION: ß-Agonist leanness-enhancing agent-related food poisonings are rarely encountered, especially in those countries where relevant veterinary medicines are banned, and may thus pose diagnostic challenge to both emergency physicians and clinical toxicologists.

Rat Bait, Not Healthy Rice!

Bromadiolone, a potent, long-acting anticoagulant rodenticide is frequently tinted to a red or pink color and mixed with cereals as rat bait. Six peoples working in a small factory suffered from a severe bleeding tendency several weeks after consuming a rice meal that was tainted with bromadiolone mistaken to be healthy food. High serum levels of bromadiolone and excessive bleeding were found in these individuals, and they needed vitamin K1 therapy for weeks. These cases indicated that long-acting anticoagulant rodenticide might induce cumulative toxicity in repeated, low-dose exposure, and the blood levels of bromadiolone might be an indicator for antidote therapy if available.

Association of genetic variations in GNB1 with response to peginterferon plus ribavirin therapy for chronic hepatitis C in a Chinese population in Taiwan.

BACKGROUND: The aim of this study was to evaluate whether polymorphisms in the guanine nucleotide binding (G protein), beta polypeptide 1 (GNB1) gene are associated with a rapid virological response (RVR) among HCV genotype 1 (HCV-1) and 2 (HCV-2) infected patients receiving peginterferon plus ribavirin treatment (PEG-IFNα-RBV). METHODS: We analyzed the association between RVR to PEG-IFNα-RBV therapy and 4 tagging single nucleotide polymorphisms (SNPs) of the GNB1 gene. This study included 265 HCV-1 and 195 HCV-2 infected patients in a Chinese population in Taiwan. RESULTS: Among the GNB1 SNPs examined, the combination of genotypes G/G and G/T populations of rs12126768 was significant inversely correlated with RVR in HCV-1 infected patients (P = 0.0330), whereas HCV-2 infected patients, combination of A/A and A/C genotypes populations at rs4648727 responded better to the PEG-IFNα-RBV treatment (P = 0.0089). However, there were no significant differences in the allele frequencies of those SNPs between RVR responders and non-responders. Several RVR susceptibility GNB1 haplotypes were identified, and the ACAT haplotype of the 4 SNPs may increase the successful outcomes of HCV-1 and HCV-2 infected patients (P = 0.0261 and P = 0.0253, respectively). CONCLUSION: The data for GNB1 SNPs and the association of RVR showed that GNB1 polymorphisms might be associated with the therapeutic outcomes of HCV-1 and HCV-2 infected patients under standard of care (SOC) treatment.

Paraquat induces lung alveolar epithelial cell apoptosis via Nrf-2-regulated mitochondrial dysfunction and ER stress.

Paraquat (1,1'-dimethyl-4,4'-bipyridinium chloride; PQ) is widely and commonly used as a herbicides in the world. PQ has been reported to be a major hazard because it causes lung injury. However, the molecular mechanisms underlying PQ-induced lung toxicity still need to be elucidated. Here, we found that PQ significantly decreases cell viability, increases sub-G1 hypodiploids DNA contents and caspase 3/7 activity in lung alveolar epithelial cell-derived L2 cells, which also caused mitochondrial dysfunction, and decreased the mRNA expression of Bcl-2 and increased that of Bax, Bak, and p53. Moreover, the protein expressions of Bax and Bak were increased in PQ-treated cells. In addition, when PQ was exposed to L2 cells, the expressions of ER stress-related signaling genes (including Grp78, CHOP, and caspase-12 mRNA) and proteins (including phospho-eIF-2α, CHOP, Grp78, calpain I and -II, and caspase-12) were significantly increased. PQ also decreased the protein expressions of pro-caspase-9/7/3. Next, we investigated the role of Nrf-2 in PQ-induced alveolar epithelial cell toxicity. In L2 cells, PQ induced Nrf-2 translocation from the cytosol to the nucleus. Cells transfected with Nrf-2 siRNA significantly reversed the PQ-induced toxicity, including depolarization of MMP, increased the Bax, Bak, p53 mRNAs expression, decreased the Bcl-2 mRNA expression, increased the caspase 3/7 activity, Grp78, CHOP, and caspase-12 mRNAs and protein expression, and decreased that of pro-caspase-3. Taken together, these results suggest that Nrf-2-regulated mitochondria and ER stress-related pathways are involved in the PQ-induced alveolar epithelial cell injury.

Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation.

Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is predominantly regulated by a nuclear receptor, pregnane X receptor (PXR). Sesamin, a major lignan constituent in sesame seeds and oil, exhibits a variety of biological functions; however, the effect of sesamin on the modulation of CYP3A4 is not well understood. In this study, the effects of sesamin on the PXR-CYP3A4 pathway were characterized, as well as the underlying mechanisms of those effects. Sesamin potently attenuated CYP3A4 induction in a dose-dependent manner by blocking the activation of PXR. The PXR inducer-mediated inhibition of CYP3A4 was further evidenced by the ability of sesamin to attenuate the effects of several PXR ligands in the CYP3A4 reporter assay. Further mechanistic studies showed that sesamin inhibited PXR by interrupting the interacting with coregulators. These results may lead to the development of new therapeutic and dietary approaches to reduce the frequency of inducer-drug interaction. Sesamin was established as a novel inhibitor of PXR and may be useful for modulating DMEs expression and drug efficacies. Modification of CYP3A4 expression and activity by consumption of sesamin may have important implications for drug safety.

Oral administration of injectable vitamin K1 in brodifacoum intoxication.

Brodifacoum is a highly potent and long-acting anticoagulant rodenticide (LAAR). LAAR poisoning possibly leads to long term bleeding problems and needs vitamin K1 treatment for several months. Due to economic concern, tablet preparation of vitamin K1 was not available in most of the countries, including Taiwan. In literature, few reports had pointed out that injectable form of vitamin K could be used orally in patients on anticoagulant therapy with supratherapeutic state. Here, we reported a family with 3 members suffering from brodifacoum poisoning with severe coagulopathy needed to prolong hospitalization for intravenous vitamin K1 therapy, and successfully managed with injectable formula orally for about 5 months. Oral administration of injectable vitamin K1 might be a suitable substitute for intravenous route in long-term treatment for LAAR poisonings.

Local Cytotoxic Effects in Cobra Envenoming: A Pilot Study.

The cobra (genus Naja (N.)) is one of the most common venomous snakes. Due to its frequency and deadly complications of muscle paralysis, local necrosis, and chronic musculoskeletal disability, it should not be ignored. The pathology of devastating tissue destruction, even though specific antivenoms exist, is not fully clear. Here, we attempted to dig in envenomed tissues to study the clinical toxicology of cobra venom. Four cases of N. atra snake envenomation, in which the subjects developed advanced tissue injury, were involved in this study. We used enzyme-ligand sandwich immunoassay (ELISA) to assay the whole venom, cytotoxin A3 and short-chain neurotoxin (sNTX) in blood, bullae, wound discharge, and debrided tissue. We found that persistently high concentrations of venom and toxins, especially cytotoxin A3, were detected in bullae, wound discharge fluid and necrotic tissue of these patients even after large doses of specific antivenom treatment, and wide excision and advanced debridement could largely remove these toxins, lessen the size of necrosis, and promote wound healing. We also found that the point-of-care apparatus, ICT-Cobra kit, might be used to promptly monitor the wound condition and as one of the indicators of surgical intervention in cases of cobra envenomation in Taiwan.

Subclinical abnormalities in workers with continuous low-level toluene exposure.

Short-term exposure to a high concentration (TWA > 100 ppm) of toluene can cause hepatotocixity and neurotoxicity in humans. Data on the effects of exposure to low levels of toluene, however, are controversial. In addition, few studies on the effects of toluene exposure on the autonomic nervous system have been conducted. Urine samples from 34 male factory workers in Taiwan who were exposed to low levels of toluene either intermittently (n = 13) or continuously (n = 21) were taken on a Monday morning after a 2-day hiatus and at the end of the workweek on Friday evening. Urinary hippuric acid levels were measured using high-performance liquid chromatography (HPLC). A complete blood work-up was also performed for each subject. The prevalence and severity of neurotoxic symptoms were investigated by a self-reported questionnaire, a neuropsychiatric battery, and sympathetic and peripheral nerve function tests. The mean value of urinary hippuric acid corrected for creatinine (Cr) was 0.34 ± 0.18 g/g Cr on Monday morning and 0.43 ± 0.26 g/g Cr on Friday evening. The difference in the mean value of urinary hippuric acid between the two periods (p < 0.01) and the odds ratio of impairment of sympathetic (OR = 4.13, p = 0.11) and peripheral nerves (OR = 6.94, p = 0.074) were higher in workers continuously exposed to toluene. In addition, workers who were continuously exposed to toluene had a lower mean platelet count (216 ± 41 × 10(6) /µL) than workers who were intermittently exposed (252 ± 40 × 10(6)/µL), (p = 0.018). Furthermore, there was a positive relationship between neurological abnormalities and a self-reported neuropsychiatric measurement (r = 0.35-0.66, p < 0.05) in all workers. These data suggest that continuous exposure to low levels of toluene may be associated with sympathetic and peripheral nerve dysfunction and sub-clinical hematological damage. Further research needs to be carried out regarding how chronic exposure to low-levels of toluene affects workers.

Lead poisoning due to incense burning: an outbreak in a family.

BACKGROUND: In Asia and some other regions of the world, incense burning is an important folk and cultural activity. However, this ritual can cause health impacts, such as chronic respiratory diseases and neoplasms. Herein, we describe a family with lead poisoning possibly related to the frequent use of incense sticks at home. CASE REPORT: A 65-year-old homemaker with severe anemia, pitting edema of the lower legs, bone pain, abdominal pain, and exertional dyspnea for several months presented to our clinic. Her blood workup indicated severe anemia with basophilic stippling in red blood cells and blood lead level (BLL) of 59.75 µg/dL. Her husband, three children, and four grandchildren who lived with her also had high BLLs. As a Daoist clergy person, she had been exposed to a large amount of smoke from every day use of incense for >30 years. In the field investigation, the chronic dust deposited in hidden corners of their home had considerably higher lead content and other toxic metals. DISCUSSION: Our observations indicated chronic, frequent exposure to smoke from incense burning may be a cause of lead poisoning. Strict avoidance of incense smoke is a significant step toward preventing lead poisoning in children in societies with the custom of incense burning.

Early onset pneumonia in patients with cholinesterase inhibitor poisoning.

BACKGROUND AND OBJECTIVE: Organophosphates and carbamates are potent cholinesterase inhibitors that are widely used as insecticides in agriculture. Pneumonia is a frequent complication of cholinesterase inhibitor poisoning (CIP) and a risk factor for death. The aim of this retrospective study was to assess the risk factors for pneumonia in patients with CIP. METHODS: The medical records of 155 patients, who were treated for CIP in a 1300-bed medical centre in central Taiwan, from January 2002 to December 2004, were retrospectively analysed. Pneumonia was diagnosed by a new or persistent infiltrate on CXR, as well as clinical symptoms. Demographic data, comorbidities, acute respiratory failure and in-hospital mortality were also recorded. RESULTS: Of the 155 patients, 31 (20%) died and 92 (59.4%) developed acute respiratory failure. Thirty-four patients (21.9%) were diagnosed with early onset pneumonia during hospitalization. Acute respiratory failure (OR 12.10, 95% CI: 2.55-57.45), underlying cardiovascular disease (OR 3.02, 95% CI: 1.02-8.91), undergoing gastric lavage at peripheral hospitals (OR 6.23, 95% CI: 1.52-25.98) and development of respiratory failure at the study centre after gastric lavage (OR 3.43, 95% CI: 1.17-10.0) were predictive factors for early onset pneumonia. Cardiopulmonary resuscitation (OR 23.58, 95% CI: 6.03-92.29), early onset pneumonia (OR 7.45, 95% CI: 2.02-27.5) and lower Glasgow coma score (OR 1.26, 95% CI: 1.08-1.48) were predictive factors for mortality. CONCLUSIONS: Pneumonia was a significant risk factor for death in patients with CIP. In addition to aggressive management of patients with CIP who develop respiratory failure, careful respiratory evaluation before and after gastric lavage would help to decrease the incidence of early onset pneumonia in patients with CIP.

A Rapid and International Applicable Diagnostic Device for Cobra (Genus Naja) Snakebites.

Cobra snakes (genus Naja) are some of the most dangerous snake species in Asia and Africa, as their bites cause severe life-threatening respiratory failure and local tissue destruction, especially in the case of late diagnosis. The differential diagnosis of snakebite envenomation still mainly relies upon symptomatology, the patient's description, and the experience of physicians. We have designed a rapid test, immunochromatographic test of cobra (ICT-Cobra), which obtained fair results in improving the diagnosis and treatment of Naja (N.) atra snakebites in Taiwan. In this study, we further investigated the feasibility of applying the kit for the detection of other cobra venoms based on the potential interspecies similarity. We firstly demonstrated the cross-reactivity between eight venoms of medically important cobra species and the rabbit anti-N. atra IgG that was used in ICT-Cobra by Western blotting and sandwich enzyme-linked immunosorbent assay. Then, ICT-Cobra was used to detect various concentrations of the eight venoms to elucidate its performance. Noticeable correlations between the cross-reactivity of venoms from genus Naja snakes and existing geographical characteristics were found. ICT-Cobra could detect venoms from other Asian cobras with variable detection limits comparable to those observed for N. atra, but the kit was less successful in the detection of venom from African cobras. The similar but slightly different venom components and the interaction between venom and rabbit anti-N. atra IgG led to variations in the detection limits. The transcontinental usage of ICT-Cobra might be possible due to the cross-reactivity of antibodies and similarities among the larger-sized proteins. This study showed that the close immunological relationships in the genus Naja could be used to develop a venom detection kit for the diagnosis of cobra envenomation in both Asian and African regions. Additional clinical studies and technical adjustments are still needed to improve the efficacy and broadening the application of ICT-Cobra in the future.

The prevalence of esophageal cancer after caustic and pesticide ingestion: A nationwide cohort study.

Habits such as smoking and alcohol drinking and existing esophageal malfunction are considered the main risk factors for esophageal carcinogenesis. Caustic ingestion of acidic or alkaline agents or strong irritants can induce severe esophageal corrosive injury and increase esophageal cancer risk. We studied the relationship between esophageal carcinoma and acute detergent or pesticide poisoning by using nationwide health insurance data. Methodology/Principle findings: We compared a pesticide/detergent intoxication cohort (N = 21,840) and an age- and gender-matched control cohort (N = 21,840) identified from the National Health Insurance Research Database between 2000 and 2011. We used the multivariable Cox proportional model to determine esophageal carcinoma risk. The overall incidence density of esophageal cancer was 1.66 per 10,000 person-years in the comparison cohort and 4.36 per 10,000 person-years in the pesticide/detergent intoxication cohort. The corresponding adjusted hazard ratio (HR) for esophageal cancer was 2.33 (95% confidence interval [CI] = 1.41-3.86) in the pesticide/detergent intoxication cohort compared with the control cohort. Patients with corrosive and detergent intoxication did not have a higher risk of esophageal cancer (adjusted HR = 0.98, 95% CI = 0.29-3.33) than those without pesticide/detergent intoxication. However, patients with pesticide intoxication had a significantly higher risk of esophageal cancer (adjusted HR = 2.52, 95% CI = 1.52-4.18) than those without pesticide/detergent intoxication. Conclusion: In the present study, after adjusting for conventional risk factors, we observed that pesticide intoxication could exert substantial effects through increased esophageal cancer risk. However, patients with detergent intoxication may not have an increased risk of esophageal cancer.

Presentations of tetramethylammonium hydroxide dermal exposure and the valuable potential of diphoterine solution in decontamination: a retrospective observational study.

BACKGROUND: Tetramethylammonium hydroxide (TMAH) is a quaternary ammonium compound that is both a base corrosive and a cholinergic agonist, and it is widely used in the photoelectric and semiconductor industries. It causes corrosive skin injuries and systemic cholinergic toxicity with death primarily resulting from respiratory failure without efficacious early decontamination. METHODS: A retrospective observational study was performed of all cases of TMAH exposure reported to the Taiwan Poison Control Center between July 2010 and October 2017. Retrieved medical records were independently reviewed by two trained clinical toxicologists. RESULTS: Despite immediate (< 5 min) skin decontamination with copious amounts of tap water, one patient exposed to 25% TMAH involving ≥5% of total body surface area (TBSA) developed significant systemic toxicity. Patients exposed to 25% TMAH involving ≤1% TBSA developed first-degree chemical skin injuries but no systemic toxicity. Among patients exposed to lower concentrations (≤2.38%) of TMAH, the majority only experienced first-degree chemical skin injuries without systemic signs. Patients exposed to 0.5% TMAH involving nearly their entire TBSA developed no chemical skin injuries or systemic toxicity. All patients who had only first-degree chemical skin injuries did not develop systemic toxicity after exposure to either 2.38% or 25% TMAH. CONCLUSIONS: TMAH acts as an alkaline corrosive and cholinergic agonist. Systemic signs attributable to TMA+ can rapidly lead to respiratory failure and death after dermal exposure. We have demonstrated that an amphoteric solution may be efficacious for skin decontamination on-site immediately to prevent or ameliorate such toxicity. This practice especially carries a valuable potential in managing victims (patients) who have been exposed to those chemicals with immediate life-threatening toxicity (e.g. TMAH), suggesting that its early utilization deserves further study.