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1.
J Postgrad Med ; 70(2): 105-108, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38629272

ABSTRACT

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.


Subject(s)
Arsenic Poisoning , Peripheral Nervous System Diseases , Humans , Arsenic/urine , Arsenic Poisoning/complications , Chelating Agents/therapeutic use , Chelation Therapy , Chronic Disease , Dimercaprol/therapeutic use , Peripheral Nervous System Diseases/chemically induced , Treatment Outcome
2.
Proc Natl Acad Sci U S A ; 120(45): e2309156120, 2023 Nov 07.
Article in English | MEDLINE | ID: mdl-37903261

ABSTRACT

Cobalt-containing alloys are useful for orthopedic applications due to their low volumetric wear rates, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. Unfortunately, these prosthetics release significant levels of cobalt ions, which was only discovered after their widespread implantation into patients requiring hip replacements. These cobalt ions can result in local toxic effects-including peri-implant toxicity, aseptic loosening, and pseudotumor-as well as systemic toxic effects-including neurological, cardiovascular, and endocrine disorders. Failing metal-on-metal (MoM) implants usually necessitate painful, risky, and costly revision surgeries. To treat metallosis arising from failing MoM implants, a synovial fluid-mimicking chelator was designed to remove these metal ions. Hyaluronic acid (HA), the major chemical component of synovial fluid, was functionalized with British anti-Lewisite (BAL) to create a chelator (BAL-HA). BAL-HA effectively binds cobalt and rescues in vitro cell vitality (up to 370% of cells exposed to IC50 levels of cobalt) and enhances the rate of clearance of cobalt in vivo (t1/2 from 48 h to 6 h). A metallosis model was also created to investigate our therapy. Results demonstrate that BAL-HA chelator system is biocompatible and capable of capturing significant amounts of cobalt ions from the hip joint within 30 min, with no risk of kidney failure. This chelation therapy has the potential to mitigate cobalt toxicity from failing MoM implants through noninvasive injections into the joint.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Humans , Hip Prosthesis/adverse effects , Hyaluronic Acid , Dimercaprol , Chelation Therapy , Prosthesis Failure , Arthroplasty, Replacement, Hip/adverse effects , Metals , Cobalt , Chelating Agents/therapeutic use , Ions
3.
Nat Commun ; 11(1): 6094, 2020 12 15.
Article in English | MEDLINE | ID: mdl-33323937

ABSTRACT

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.


Subject(s)
Antivenins/administration & dosage , Antivenins/therapeutic use , Snake Bites/drug therapy , Animals , Asia , Benzamidines , Central America , Dimercaprol/pharmacology , Dimercaprol/therapeutic use , Disease Models, Animal , Drug Combinations , Drug Evaluation, Preclinical , Guanidines , Kaplan-Meier Estimate , Male , Mice , Neutralization Tests , Serine Proteases/drug effects , Toxins, Biological , Viper Venoms
4.
BMC Nephrol ; 20(1): 374, 2019 10 17.
Article in English | MEDLINE | ID: mdl-31623560

ABSTRACT

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.


Subject(s)
Anuria/complications , Arsenic Poisoning/therapy , Chelating Agents/therapeutic use , Continuous Renal Replacement Therapy , Kidney Failure, Chronic/complications , Lead Poisoning/therapy , Adult , Animals , Arsenic Poisoning/complications , Dimercaprol/therapeutic use , Edetic Acid/therapeutic use , Humans , Kidney Failure, Chronic/therapy , Lead Poisoning/complications , Male , Renal Dialysis , Succimer/therapeutic use , Unithiol/therapeutic use
7.
Mil Med ; 182(3): e1843-e1848, 2017 03.
Article in English | MEDLINE | ID: mdl-28290970

ABSTRACT

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.


Subject(s)
Foreign Bodies/complications , Lead Poisoning/etiology , Lead/toxicity , Wounds, Gunshot/complications , Abdominal Pain/etiology , Adult , Chelating Agents/pharmacology , Chelating Agents/therapeutic use , Chelation Therapy/methods , Constipation/etiology , Dimercaprol/pharmacology , Dimercaprol/therapeutic use , Hepatitis/etiology , Humans , Jaundice/etiology , Lead Poisoning/diagnosis , Male , Wounds, Gunshot/surgery
8.
J Med Toxicol ; 10(1): 40-4, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23760886

ABSTRACT

INTRODUCTION: Mercuric chloride poisoning is rare yet potentially life-threatening. We report a case of poisoning with a potentially significant amount of mercuric chloride which responded to aggressive management. CASE REPORT: A 19-year-old female presented to the Emergency Department with nausea, abdominal discomfort, vomiting of blood-stained fluid, and diarrhea following suicidal ingestion of 2-4 g of mercuric chloride powder. An abdominal radiograph showed radio-opaque material within the gastric antrum and the patient's initial blood mercury concentration was 17.9 µmol/L (or 3.58 mg/L) at 3 h post-ingestion. Given the potential toxicity of inorganic mercury, the patient was admitted to the intensive care unit and chelation with dimercaprol was undertaken. Further clinical effects included mild hemodynamic instability, acidosis, hypokalemia, leukocytosis, and fever. The patient's symptoms began to improve 48 h after admission and resolved fully within a week. DISCUSSION: Mercuric chloride has an estimated human fatal dose of between 1 and 4 g. Despite a reported ingestion of a potentially lethal dose and a high blood concentration, this patient experienced mild to moderate poisoning only and she responded to early and appropriate intervention. Mercuric chloride can produce a range of toxic effects including corrosive injury, severe gastrointestinal disturbances, acute renal failure, circulatory collapse, and eventual death. Treatment includes close observation and aggressive supportive care along with chelation, preferably with 2,3-dimercapto-1-propane sulfonate or 2,3-meso-dimercaptosuccinic acid.


Subject(s)
Indicators and Reagents/toxicity , Mercuric Chloride/toxicity , Mercury Poisoning/drug therapy , Suicide, Attempted , Adult , Chelating Agents/administration & dosage , Chelating Agents/therapeutic use , Chelation Therapy , Dimercaprol/administration & dosage , Dimercaprol/therapeutic use , Female , Humans , Indicators and Reagents/chemistry , Indicators and Reagents/pharmacokinetics , Injections, Intramuscular , Mercuric Chloride/antagonists & inhibitors , Mercuric Chloride/pharmacokinetics , Mercury/blood , Mercury/chemistry , Mercury Poisoning/blood , Mercury Poisoning/therapy , Treatment Outcome , Young Adult
9.
Pak J Pharm Sci ; 26(6): 1267-70, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24191337

ABSTRACT

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))].


Subject(s)
Gold , Mercury/adverse effects , Mining , Occupational Exposure , Adult , Dimercaprol/therapeutic use , Humans , Iran , Male , Mercury/blood , Mercury/urine , Middle Aged , Penicillamine/therapeutic use
10.
Hum Exp Toxicol ; 31(2): 193-6, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21803782

ABSTRACT

Elemental mercury (Hg) is the only metal which evaporates in room temperature and its inhalation may cause toxicity. Hg poisoning may occur by mishandling the metal, particularly in children who play with it. Wide-spectrum of the clinical presentations of chronic Hg poisoning may cause misdiagnosis, particularly when history of exposure is unknown. We report two cases of accidental Hg poisoning, which initially had been diagnosed and treated for brucellosis. The patients were two brothers (7 and 14 years old) who presented with pain in their lower extremities, sweating, salivation, weight loss, anorexia and mood changes on admission. Meticulous history taking revealed that they had played with a ball of Hg since 3 months before admission. The level of urinary Hg was 125.9 and 54.2 9 g/L in the younger and older brother, respectively (normal ≤25 g/L). The patients were successfully treated by dimercaprol and discharged in good condition 24 days after admission. These cases are being reported to emphasize the importance of acrodynia as a differential diagnosis for brucellosis in endemic areas.


Subject(s)
Acrodynia/diagnosis , Acrodynia/drug therapy , Acrodynia/urine , Adolescent , Brucellosis/drug therapy , Chelating Agents/therapeutic use , Chelation Therapy , Child , Diagnosis, Differential , Dimercaprol/therapeutic use , Humans , Iran , Male , Mercury
12.
Hum Exp Toxicol ; 28(1): 63-5, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19411562

ABSTRACT

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.


Subject(s)
Arsenic Poisoning/pathology , Oxides/poisoning , Suicide, Attempted , Acute Disease , Aged , Arsenic Poisoning/therapy , Arsenic Trioxide , Arsenicals , Charcoal/therapeutic use , Chelating Agents/therapeutic use , Chelation Therapy , Dimercaprol/therapeutic use , Gastric Lavage/methods , Humans , Intubation, Gastrointestinal/methods , Male , Treatment Outcome
13.
Middle East J Anaesthesiol ; 19(6): 1411-6, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18942257

ABSTRACT

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.


Subject(s)
Drug Contamination , Lead Poisoning/diagnosis , Narcotics/adverse effects , Opium/adverse effects , Quadriplegia/chemically induced , Adult , Chelating Agents/therapeutic use , Diagnosis, Differential , Dimercaprol/therapeutic use , Edetic Acid/therapeutic use , Humans , Lead/blood , Lead Poisoning/blood , Lead Poisoning/drug therapy , Male , Opioid-Related Disorders/complications , Quadriplegia/diagnosis
16.
Can J Cardiol ; 24(5): 397-9, 2008 May.
Article in English | MEDLINE | ID: mdl-18464946

ABSTRACT

A case of left bundle branch block and a dilated, nonhypertrophic cardiomyopathy associated with ingestion of colloidal gold and silver as an 'energy tonic' is described. The cardiac disease was reversed within two months by a course of dimercaprol (Akorn Inc, USA) (British antiLewisite) and vitamin E. This is the first case of gold and silver cardiomyopathy in humans, and highlights the risks of these colloidal metal 'health supplements'.


Subject(s)
Bundle-Branch Block/chemically induced , Cardiomyopathy, Dilated/chemically induced , Chelating Agents/therapeutic use , Dimercaprol/therapeutic use , Gold Colloid/adverse effects , Silver/adverse effects , Tocopherols/therapeutic use , Adult , Bundle-Branch Block/diagnosis , Bundle-Branch Block/drug therapy , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/drug therapy , Dietary Supplements/adverse effects , Echocardiography , Electrocardiography , Female , Humans
17.
J Environ Biol ; 28(2 Suppl): 333-47, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17929749

ABSTRACT

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.


Subject(s)
Antioxidants/therapeutic use , Arsenic Poisoning/drug therapy , Chelating Agents/therapeutic use , Environmental Pollutants/poisoning , Acetylcysteine/therapeutic use , Animals , Ascorbic Acid/therapeutic use , Chelation Therapy , Dimercaprol/therapeutic use , Drug Therapy, Combination , Humans , Melatonin/therapeutic use , Oxidative Stress/drug effects , Plant Extracts/therapeutic use , Selenium/therapeutic use , Succimer/analogs & derivatives , Succimer/therapeutic use , Taurine/therapeutic use , Thioctic Acid/therapeutic use , Vitamin E/therapeutic use , Zinc/therapeutic use
18.
J Emerg Med ; 32(3): 289-94, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17394994

ABSTRACT

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.


Subject(s)
Arsenic Poisoning/therapy , Chelation Therapy , Mercuric Chloride/poisoning , Mercury Poisoning/therapy , Oxides/poisoning , Adult , Arsenic Trioxide , Arsenicals , Decontamination , Dimercaprol/therapeutic use , Drug Therapy, Combination , Humans , Male , Polyethylene Glycols/therapeutic use , Solvents/therapeutic use , Succimer/therapeutic use , Suicide, Attempted , Therapeutic Irrigation
19.
Rev Neurol (Paris) ; 162(3): 374-7, 2006 Mar.
Article in French | MEDLINE | ID: mdl-16585894

ABSTRACT

INTRODUCTION: Chronic arsenic toxicity is a global health problem affecting millions of people. Acute arsenic poisoning is less frequent and it is most often lethal. Therefore, its consequences are not well known, more precisely its neurological consequences. OBSERVATION: We report a case of Guillain-Barré-like syndrome and encephalopathy after acute arsenical poisoning in a 50 year-old man. After 4 month follow-up, the improvement was slow and limited with persistent motor and proprioceptive deficits. DISCUSSION: The most frequent neurological complication induced by acute arsenical poisoning is a distal, symmetrical, sensory, axonal polyneuropathy. Yet the clinical course and the electrophysiological findings may also suggest a Guillain-Barré like syndrome. Moreover, the chelating is not very effective on the neurological complications. CONCLUSION: Any discrepancies in the clinical course of a Guillain-Barré syndrome shall lead to reconsider the diagnosis. The association of gastro-intestinal disorders, skin lesions, and encephalopathy and mood disorders leads to discuss intoxication with heavy metal and more precisely with arsenic. Moreover, the chelating is not very effective on the neurological complications.


Subject(s)
Arsenic Poisoning/diagnosis , Guillain-Barre Syndrome/diagnosis , Acute Kidney Injury/chemically induced , Arsenic Poisoning/drug therapy , Arsenic Poisoning/physiopathology , Chelating Agents/therapeutic use , Chelation Therapy , Diagnosis, Differential , Dimercaprol/therapeutic use , Gastrointestinal Diseases/chemically induced , Humans , Male , Mental Disorders/chemically induced , Middle Aged , Mood Disorders/chemically induced , Neural Conduction , Paranoid Disorders/chemically induced , Skin Diseases/chemically induced , Suicide, Attempted
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