Chronic arsenic poisoning: A sinister cause of peripheral neuropathy in a young couple.

ABSTRACT: Arsenic compounds are colorless and odorless and toxicity can occur either acutely following ingestion of arsenicals with gastrointestinal disturbances or due to chronic exposure usually presenting with dermatologic lesions and peripheral neuropathy. We report a young couple who presented with signs and symptoms of painful sensorimotor peripheral neuropathy in a typical "stocking and glove" pattern. They had raised urinary arsenic levels with normal blood levels and thus, a diagnosis of chronic arsenic poisoning due to contaminated water intake was made after detecting elevated arsenic levels in their home water supply. Both patients underwent chelation therapy with dimercaprol for 14 days and reported subjective and objective improvement in symptoms with the reduction in urinary arsenic levels at the end of therapy.

Treatment of lead and arsenic poisoning in anuric patients - a case report and narrative review of the literature.

BACKGROUND: Heavy metal poisoning can cause debilitating illness if left untreated, and its management in anuric patients poses challenges. Literature with which to guide clinical practice in this area is rather scattered. CASE PRESENTATION: We present a case of symptomatic lead and arsenic poisoning from use of Ayurvedic medicine in a 28-year-old man with end-stage kidney disease on chronic hemodialysis. We describe his treatment course with chelating agents and extracorporeal blood purification, and review the relevant literature to provide general guidance. CONCLUSION: Cumulative clinical experience assists in identifying preferred chelators and modalities of extracorporeal blood purification when managing such patients. However, a larger body of real-world or clinical trial evidence is necessary to inform evidence-based guidelines for the management of heavy metal poisoning in anuric patients.

Interventions for paracetamol (acetaminophen) overdose.

BACKGROUND: Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various interventions to treat paracetamol poisoning, depending on the clinical status of the person. These interventions include inhibiting the absorption of paracetamol from the gastrointestinal tract (decontamination), removal of paracetamol from the vascular system, and antidotes to prevent the formation of, or to detoxify, metabolites. OBJECTIVES: To assess the benefits and harms of interventions for paracetamol overdosage irrespective of the cause of the overdose. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2017), CENTRAL (2016, Issue 11), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), and Science Citation Index Expanded (1900 to January 2017). We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov database (US National Institute of Health) for any ongoing or completed trials (January 2017). We examined the reference lists of relevant papers identified by the search and other published reviews. SELECTION CRITERIA: Randomised clinical trials assessing benefits and harms of interventions in people who have ingested a paracetamol overdose. The interventions could have been gastric lavage, ipecacuanha, or activated charcoal, or various extracorporeal treatments, or antidotes. The interventions could have been compared with placebo, no intervention, or to each other in differing regimens. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials. We used fixed-effect and random-effects Peto odds ratios (OR) with 95% confidence intervals (CI) for analysis of the review outcomes. We used the Cochrane 'Risk of bias' tool to assess the risks of bias (i.e. systematic errors leading to overestimation of benefits and underestimation of harms). We used Trial Sequential Analysis to control risks of random errors (i.e. play of chance) and GRADE to assess the quality of the evidence and constructed 'Summary of findings' tables using GRADE software. MAIN RESULTS: We identified 11 randomised clinical trials (of which one acetylcysteine trial was abandoned due to low numbers recruited), assessing several different interventions in 700 participants. The variety of interventions studied included decontamination, extracorporeal measures, and antidotes to detoxify paracetamol's toxic metabolite; which included methionine, cysteamine, dimercaprol, or acetylcysteine. There were no randomised clinical trials of agents that inhibit cytochrome P-450 to decrease the activation of the toxic metabolite N-acetyl-p-benzoquinone imine.Of the 11 trials, only two had two common outcomes, and hence, we could only meta-analyse two comparisons. Each of the remaining comparisons included outcome data from one trial only and hence their results are presented as described in the trials. All trial analyses lack power to access efficacy. Furthermore, all the trials were at high risk of bias. Accordingly, the quality of evidence was low or very low for all comparisons. Interventions that prevent absorption, such as gastric lavage, ipecacuanha, or activated charcoal were compared with placebo or no intervention and with each other in one four-armed randomised clinical trial involving 60 participants with an uncertain randomisation procedure and hence very low quality. The trial presented results on lowering plasma paracetamol levels. Activated charcoal seemed to reduce the absorption of paracetamol, but the clinical benefits were unclear. Activated charcoal seemed to have the best risk:benefit ratio among gastric lavage, ipecacuanha, or supportive treatment if given within four hours of ingestion. There seemed to be no difference between gastric lavage and ipecacuanha, but gastric lavage and ipecacuanha seemed more effective than no treatment (very low quality of evidence). Extracorporeal interventions included charcoal haemoperfusion compared with conventional treatment (supportive care including gastric lavage, intravenous fluids, and fresh frozen plasma) in one trial with 16 participants. The mean cumulative amount of paracetamol removed was 1.4 g. One participant from the haemoperfusion group who had ingested 135 g of paracetamol, died. There were no deaths in the conventional treatment group. Accordingly, we found no benefit of charcoal haemoperfusion (very low quality of evidence). Acetylcysteine appeared superior to placebo and had fewer adverse effects when compared with dimercaprol or cysteamine. Acetylcysteine superiority to methionine was unproven. One small trial (low quality evidence) found that acetylcysteine may reduce mortality in people with fulminant hepatic failure (Peto OR 0.29, 95% CI 0.09 to 0.94). The most recent randomised clinical trials studied different acetylcysteine regimens, with the primary outcome being adverse events. It was unclear which acetylcysteine treatment protocol offered the best efficacy, as most trials were underpowered to look at this outcome. One trial showed that a modified 12-hour acetylcysteine regimen with a two-hour acetylcysteine 100 mg/kg bodyweight loading dose was associated with significantly fewer adverse reactions compared with the traditional three-bag 20.25-hour regimen (low quality of evidence). All Trial Sequential Analyses showed lack of sufficient power. Children were not included in the majority of trials. Hence, the evidence pertains only to adults. AUTHORS' CONCLUSIONS: These results highlight the paucity of randomised clinical trials comparing different interventions for paracetamol overdose and their routes of administration and the low or very low level quality of the evidence that is available. Evidence from a single trial found activated charcoal seemed the best choice to reduce absorption of paracetamol. Acetylcysteine should be given to people at risk of toxicity including people presenting with liver failure. Further randomised clinical trials with low risk of bias and adequate number of participants are required to determine which regimen results in the fewest adverse effects with the best efficacy. Current management of paracetamol poisoning worldwide involves the administration of intravenous or oral acetylcysteine which is based mainly on observational studies. Results from these observational studies indicate that treatment with acetylcysteine seems to result in a decrease in morbidity and mortality, However, further evidence from randomised clinical trials comparing different treatments are needed.

Dimercaprol is an acrolein scavenger that mitigates acrolein-mediated PC-12 cells toxicity and reduces acrolein in rat following spinal cord injury.

Acrolein is one of the most toxic byproducts of lipid peroxidation, and it has been shown to be associated with multiple pathological processes in trauma and diseases, including spinal cord injury, multiple sclerosis, and Alzheimer's disease. Therefore, suppressing acrolein using acrolein scavengers has been suggested as a novel strategy of neuroprotection. In an effort to identify effective acrolein scavengers, we have confirmed that dimercaprol, which possesses thiol functional groups, could bind and trap acrolein. We demonstrated the reaction between acrolein and dimercaprol in an abiotic condition by nuclear magnetic resonance spectroscopy. Specifically, dimercaprol is able to bind to both the carbon double bond and aldehyde group of acrolein. Its acrolein scavenging capability was further demonstrated by in vitro results that showed that dimercaprol could significantly protect PC-12 cells from acrolein-mediated cell death in a dose-dependent manner. Furthermore, dimercaprol, when applied systemically through intraperitoneal injection, could significantly reduce acrolein contents in spinal cord tissue following a spinal cord contusion injury in rats, a condition known to have elevated acrolein concentration. Taken together, dimercaprol may be an effective acrolein scavenger and a viable candidate for acrolein detoxification.

Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice.

Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated in this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned.

The treatment of Wilson's disease, a rare genetic disorder of copper metabolism.

Wilson's disease is a rare autosomal recessive disease characterised by the deposition of copper in the brain, liver; cornea, and other organs. The overload of copper inevitably leads to progressive liver and neurological dysfunction. Copper overload in patients with Wilson's disease is caused by impairment to the biliary route for excretion of dietary copper A combination of neurological, psychiatric and hepatic symptoms can make the diagnosis of Wilson's disease challenging. Most symptoms appear in the second and third decades of life. The disease affects between one in 30,000 and one in 100,000 individuals, and is fatal if left untreated. Five drugs are currently available to treat Wilson's disease: British Anti-Lewisite; D-penicillamine; trientine; zinc sulfate or acetate; and ammonium tetrathiomolybdate. Each drug can reduce copper levels and/or transform copper into a metabolically inert and unavailable form in the patient. The discovery and introduction of these five drugs owes more to the inspiration of a few dedicated physicians and agricultural scientists than to the resources of the pharmaceutical industry.

Mercury exposure of gold mining workers in the northwest of Iran.

Mercury exposure is a health concern in the occupational settings like gold mining and chloralkali industries and blood and urine levels of mercury are used as exposure indicators. In this study, blood and urine concentrations of mercury were determined using hydride generation atomic absorption spectrophotometery (HGAAS) in sixteen gold miners with neuropsychiatric symptoms. The patients treated with two chelating agents, dimercaprol and D-penicillamine. The mean serum mercury levels before and after chelation therapy were 208.14 µg/L(-1) and 10.50 µg/L(-1), respectively. The mean urinary mercury levels before and after chelation therapy were 134.70 µg/L(-1) and 17.23 µg/L(-1), respectively. The results of this study showed that there are significant differences between concentration of blood and urine mercury before and after intervention (p<0.005). There were no significant differences between in the biochemistry parameters of patients before and after treatment. This study indicated that the gold miners in the northwest of Iran had been exposed to high levels of mercury vapors [Hg((0))].

Copper sulphate toxicity in a young male complicated by methemoglobinemia, rhabdomyolysis and renal failure.

Copper sulphate is a compound prepared by the action of sulphuric acid on copper II. Copper sulphate is widely used asfungicide, herbicide and for photography. In a human being, it can lead to anemia. Medical literature is lacking regarding accidental or suicidal poisoning cases of copper sulphate in Pakistan. We present a case of accidental ingestion of copper sulphate resulting in severe acute toxicity, which was successfully managed by intensive supportive measures and Dimercaprol (BAL).

Severe lead poisoning requiring hospitalization: A case report.

Cases of severe childhood lead poisoning (a blood lead level (BLL) ≥45 mcg/dL) in the United States have decreased with time. Clinicians will encounter such cases only rarely. When such cases arise, however, recognizing their complexities and identifying resources that can help in management are important. We present here a case of severe childhood lead poisoning, highlighting the variable presentation, the rebound phenomenon of BLL after chelation, the usefulness of the zinc protoporphyrin as an adjunctive monitoring parameter, and the importance of early involvement of an inter-professional team.

A therapeutic combination of two small molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite.

Snakebite is a medical emergency causing high mortality and morbidity in rural tropical communities that typically experience delayed access to unaffordable therapeutics. Viperid snakes are responsible for the majority of envenomings, but extensive interspecific variation in venom composition dictates that different antivenom treatments are used in different parts of the world, resulting in clinical and financial snakebite management challenges. Here, we show that a number of repurposed Phase 2-approved small molecules are capable of broadly neutralizing distinct viper venom bioactivities in vitro by inhibiting different enzymatic toxin families. Furthermore, using murine in vivo models of envenoming, we demonstrate that a single dose of a rationally-selected dual inhibitor combination consisting of marimastat and varespladib prevents murine lethality caused by venom from the most medically-important vipers of Africa, South Asia and Central America. Our findings support the translation of combinations of repurposed small molecule-based toxin inhibitors as broad-spectrum therapeutics for snakebite.

Arsenic Toxicity: Molecular Targets and Therapeutic Agents.

: High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As2+ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As2+-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.

Mercury poisoning: prevention by spironolactone.

The renal tubular necrosis and calcification as well as the mortality induced by mercuric chloride in the rat are readily prevented by prior treatment with well-tolerated amounts of spironolactone.

Acute arsenic self-poisoning for suicidal purpose in a dentist: a case report.

Arsenic is a classical poison that has been historically used since ancient times for homicidal purposes. More recently, episodes of deliberate or unintentional arsenic self-poisoning have been increasingly reported. We describe here a case of a 77-year old male patient with a history of major depression, who attempted suicide by ingestion of 4 g of arsenic trioxide. The man, a dentist by profession, used arsenic preparations for pulp devitalization. The patient was admitted to our hospital 5 h after arsenic ingestion with nausea and vomiting. Plain radiograph of the abdomen showed radio-opaque material in the stomach and small intestine. Nasogastric lavage, activated charcoal, and chelators were used to remove arsenic. On day 3, endoscopy disclosed the presence of gastritis and superficial ulcers. The patient developed significant anemia (Hb: 8.7 g/dL on day 7) without significant signs of hemolysis. He gradually recovered from anemia within 5 months. The patient did not suffer any adverse outcome in spite of having ingesting 4 g of arsenic, approximately 20 times the lethal dose.

Quadriplegia due to lead-contaminated opium--case report.

PURPOSE: Utilization of lead-contaminated opium may lead to severe motor neuron impairment and quadriplegia. CASE REPORT: Forty years oriented old male, opium addict, was admitted to the ICU, with headache, nausea and abdominal pain, and weakness in his lower and upper extremities without definitive diagnosis. The past medical and occupational history was negative. Laboratory investigation showed; anemia (Hb 7.7 g/dl), slightly elevated liver function tests, elevated total bilirubin, and ESR. Abdominal sonography and brain CT scan were normal. EMG and NCV results and neurologic examination were suggestive for Guillain-Barre. He underwent five sessions of plasmapheresis. Blood lead level was > 200 microg/dl. He received dimercaprol (BAL) and calcium disodium edetate (CaEDTA) for two five days session. Upon discharge from ICU all laboratory tests were normal and blood lead level was reduced, but he was quadriplegic. CONCLUSION: The delayed treatment of lead poisoning may lead to irreversible motor neuron defect.

Successful treatment of potentially fatal heavy metal poisonings.

Pure inorganic heavy metal ingestions for suicidal intent are a rare occurrence. Most case reports on this subject focus on the serious neurological, hepatic, or renal side effects. We describe two cases of significant heavy metal poisonings (arsenic trioxide and mercuric chloride) that were successfully managed with aggressive decontamination and combined chelation therapy. Both chemicals were obtained in pure powder form through the Internet.

Arsenic induced oxidative stress and the role of antioxidant supplementation during chelation: a review.

Arsenic is a naturally occurring metalloid, ubiquitously present in the environment in both organic and inorganic forms. Arsenic contamination of groundwater in the West Bengal basin in India is unfolding as one of the worst natural geoenvironmental disaster to date. Chronic exposure of humans to high concentration of arsenic in drinking water is associated with skin lesions, peripheral vascular disease, hypertension, Blackfoot disease and high risk of cancer The underlying mechanism of toxicity includes the interaction with the sulphydryl groups and the generation of reactive oxygen species leading to oxidative stress. Chelation therapy with chelating agents like British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3 dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against arsenic poisoning. The treatment with these chelating agents however is compromised with certain serious drawbacks/side effects. The studies show that supplementation of antioxidants along with a chelating agent prove to be a better treatment regimen. This review attempts to provide the readers with a comprehensive account of recent developments in the research on arsenic poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects.

[Two different clinical cases of acute arsenic trioxide intoxication]. / Dwa przypadki ostrego zatrucia arszenikiem o róznym przebiegu klinicznym.

This paper describes two different cases of acute suicidal arsenic trioxide intoxication. Case no 1. A 38-year-old man, alcohol abuser, who ingested 4-5 g dental paste, which corresponds to 2.2-2.7 g of pure arsenic trioxide, developed gastritis with vomiting and abdominal pain, but without diarrhea. No cardiovascular collapse or renal failure were observed. The patient developed also symptoms of central nervous system injury (minor left paresis) and transient hepatic impairment. A head CT revealed no pathological changes in the brain. Hepatic disturbance recovered in a few days and the patient could be discharged on the 12 day. Case no 2. A 57-year-old man, who ingested few grams of pure arsenic developed vomiting, abdominal pain and severe diarrhea. Cardiovascular collapse as a result of intravascular volume depletion, vasodilatation and myocardial dysfunction was observed. The patient died on the first day of hospitalization. In both cases treatment included gastric lavage, BAL therapy, haemodialysis and supportive measures.

Severe Systemic Lead Toxicity Resulting From Extra-Articular Retained Shrapnel Presenting as Jaundice and Hepatitis: A Case Report and Review of the Literature.

INTRODUCTION: Despite greater than 60,000 nonfatal firearm injuries per year in the United States, retained shrapnel is a relatively rare cause of systemic lead toxicity with less than 100 cases reported in the medical literature since 1867. While intra-articular retained shrapnel as a cause of lead toxicity is well-described, extra-articular fragments are less well known to cause symptomatic disease. CASE REPORT: A 31-year-old man initially presented with abdominal pain, constipation, jaundice, and elevated liver transaminases approximately 3 weeks after suffering a left lower extremity injury during athletic activity. The patient was found to have steatohepatitis after extensive inpatient and outpatient gastroenterological workup to include upper and lower endoscopy, liver ultrasound, and biopsy of the liver to confirm the diagnosis. Imaging was incidentally notable for retained gunshot in the left flank and large shell fragment containing seroma in the left thigh. The patient was initially discharged with improved pain, but later presented to a primary care clinic with weight loss and continued pain. This was followed by a subsequent progression to diffuse weakness, ultimately resulting in an inability to ambulate. The patient was readmitted to a tertiary care medical center, 3 months after the initial presentation. Physical exam was then notable for 70-lb weight loss from initial admission and diffuse peripheral weakness with global muscle atrophy. Following a broad differential workup, he was found to have a blood lead level of 129 µg/dL, and hemoglobin of 7.7 g/dL with basophilic stippling on peripheral smear. The patient was transferred to the intensive care unit for chelation therapy with dimercaprol and calcium ethylenediaminetetraacetic acid. Lead levels initially decreased, but rose when patient was transitioned to oral therapy with succimer. Surgery was consulted for removal of multiple retained fragments, which were analyzed by the Joint Pathology Center and found to contain lead. The patient's motor function gradually improved on oral chelation and he was discharged to a subacute rehabilitation facility. CONCLUSION: This complex case describes a rare cause for a relatively common clinical presentation, jaundice and hepatitis, and reinforces the importance of longitudinal follow up and reassessment of a patient with an unknown illness and worsening clinical condition. Diagnosis of systemic lead toxicity is challenging because of its protean clinical manifestations, and relative rarity with the advent of strict environmental lead controls and decrease in lead-based paint and industrial products. Furthermore, extra-articular lead remains a rare cause of systemic toxicity, and the surgical standard of care has been to not remove these fragments in gunshot victims. This case adds to a small amount of evidence that lead screening may be of value in selected patients with extra-articular retained shrapnel, especially those with seroma and osteophyte formation in the wound.