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PubMedDate not supplied

Severe lead poisoning in pregnancy.

BACKGROUND: Lead freely crosses the placenta. Consequently, gestational lead poisoning is not only harmful to the woman but also to the developing fetus, invariably producing congenital lead poisoning. The scope and consequences of severe lead poisoning in pregnancy (blood lead level > or =45 microg/dL) have not been well characterized. METHODS: We reviewed our experience in the management of women with severe gestational lead poisoning. Additionally, we reviewed the literature on this disorder in an effort to identify patterns in etiology and outcome. RESULTS: Over a 3-year period treatment was provided to 7 severely lead-poisoned women. A 25-year review of the medical literature identified an additional 8 cases. Among these 15 women, 70% were Hispanic, all of whom developed lead poisoning from the ingestion of soil, clay, or pottery ("tierra"). Other sources of lead poisoning were paint chip ingestion (n = 2), household renovation, and use of a complementary-alternative medication (bone meal). Lead poisoning was discovered in the third trimester in 12 (86%) subjects after the women presented with subtle but characteristic findings of severe lead poisoning, including malaise, anemia, or basophilic stippling on blood smear; one woman was identified when she presented after a generalized seizure, having a blood lead level of 104 microg/dL. Five women received chelation therapy during pregnancy with CaNa(2) EDTA, dimercaprol, or succimer. At delivery mean maternal blood lead level was 55 microg/dL, whereas mean neonatal lead level was 74 microg/dL (P =.009). Thirteen neonates underwent chelation, all within the first 28 days of life. No infant in the current series had an identifiable birth defect. CONCLUSIONS: On the basis of this experience we conclude that severe lead poisoning in pregnant women has the following characteristics: 1) it most often occurs because of intentional pica, 2) its presenting features are subtle, often consisting only of malaise and anemia, and 3) blood lead levels in the neonate are higher than simultaneous maternal lead levels.

Female↗
PubMed2006

Lead toxicity in a 14-year-old female with retained bullet fragments.

In the past 3 decades, lead levels in North American children have been declining. Despite the decline in lead exposure, lead toxicity remains a significant childhood environmental health hazard. The usual route of lead exposure is through ingestion, but lead toxicity secondary to retained bullet fragments has been well documented in the adult literature. The diagnosis of lead toxicity is often difficult and delayed secondary to vague and transient symptoms. Recognizing high-risk characteristics of bullet fragments can improve clinician awareness to the possibility of lead toxicity. The primary management of patients with continued lead exposure is to remove the source of exposure. However, in the case of retained bullet fragments, initiation of chelation therapy before surgical removal may be essential in preventing systemic toxicity. We present the case of a 14-year-old female with lead toxicity who presented with an 18-month course of chronic abdominal pain, vomiting, and anorexia 2 years after sustaining a gunshot wound to the right leg. The patient was treated with oral succimer and operative removal of bullet fragments.

Adolescent↗
PubMed2007

Lead toxicity and chelation therapy.

PURPOSE: Common sources of lead exposure, the primary clinical effects of lead toxicity, and current recommendations for managing lead toxicity, including chelation therapy, are reviewed. SUMMARY: Common sources of lead exposure in children and adults include industrial and mining activities, paint, dust, soil, water, air, the workplace, food, trinkets, ethnic folk remedies, and cosmetics. The absorption and biological fate of lead are affected by a variety of factors, including an individual's nutritional status, health, and age. Children with a blood lead concentration of >10 microg/dL and adults with a blood lead concentration of > or = 45 mug/dL should undergo further evaluation. Symptoms and time to onset of symptoms postexposure may vary, and it can be difficult to identify the early, subtle neurologic effects of lead toxicity. The classic symptoms of lead toxicity generally correlate with blood lead concentrations of 25-50 microg/dL in children and 40-60 microg/dL in adults. Management of lead toxicity requires extensive risk assessment and caregiver education. Chelation is generally not indicated for adults with blood lead concentrations of < 45 microg/dL because of the potential risk of adverse drug events and concerns about remobilized lead, and chelation for children with blood lead concentrations of < 45 microg/dL remains controversial. Dimercaprol, edetate calcium disodium, and succimer are the three agents primarily used for chelation. CONCLUSION: Lead toxicity remains a significant public health concern. Elimination of elevated blood lead levels in children can be accomplished by educating appropriate health care providers and caregivers, recognizing potential lead sources, and adopting aggressive prevention and case management measures.

Adult↗
PubMed2005

Chelators as antidotes of metal toxicity: therapeutic and experimental aspects.

The effects of chelating drugs used clinically as antidotes to metal toxicity are reviewed. Human exposure to a number of metals such as lead, cadmium, mercury, manganese, aluminum, iron, copper, thallium, arsenic, chromium, nickel and platinum may lead to toxic effects, which are different for each metal. Similarly the pharmacokinetic data, clinical use and adverse effects of most of the chelating drugs used in human metal poisoning are also different for each chelating drug. The chelating drugs with worldwide application are dimercaprol (BAL), succimer (meso-DMSA), unithiol (DMPS), D-penicillamine (DPA), N-acetyl-D-penicillamine (NAPA), calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA), calcium trisodium or zinc trisodium diethylenetriaminepentaacetate (CaNa(3)DTPA, ZnNa(3)DTPA), deferoxamine (DFO), deferiprone (L1), triethylenetetraamine (trientine), N-acetylcysteine (NAC), and Prussian blue (PB). Several new synthetic homologues and experimental chelating agents have been designed and tested in vivo for their metal binding effects. These include three groups of synthetic chelators, namely the polyaminopolycarboxylic acids (EDTA and DTPA), the derivatives of BAL (DMPS, DMSA and mono- and dialkylesters of DMSA) and the carbodithioates. Many factors have been shown to affect the efficacy of the chelation treatment in metal poisoning. Within this context it has been shown in experiments using young and adult animals that metal toxicity and chelation effects could be influenced by age. These findings may have a bearing in the design of new therapeutic chelation protocols for metal toxicity.

Age Factors↗
PubMed2002

Severe congenital lead poisoning in a preterm infant due to a herbal remedy.

A preterm infant born to a woman with chronic lead poisoning was found to have the highest blood lead level recorded for a surviving neonate. Parenteral calcium disodium edetate, but not oral succimer, was effective in reducing the infant's lead burden in the neonatal period. An exposure assessment revealed the mother's long-term ingestion of lead-contaminated herbal tablets as the source.

Adult↗
PubMed2000

Lightening the lead load in children.

More than 4 percent of preschool-aged children in the United States have blood lead levels above 10 microg per dL (0.50 pmol per L), and these levels have been associated with a decline in IQ. The Centers for Disease Control and Prevention advocates the use of a screening questionnaire to identify lead exposure or toxicity in all children. Primary prevention through the removal of lead from gasoline and paint has led to a reduction of blood lead levels in children. Secondary prevention through paint hazard remediation is effective in homes that have a high lead burden. Children with lead levels of 45 to 69 microg per dL (2.15 to 3.35 pmol per L) should receive chelation therapy using succimer (DMSA) or edetate calcium disodium (CaNa2EDTA). Use of both CaNa2EDTA and dimercaprol (BAL in oil) is indicated in children with blood lead levels higher than 70 microg per dL (3.40 micromol per L). Current treatment recommendations are based on the reduction of blood lead levels, which may not represent a significant overall reduction of the lead burden. Clinical trials of existing agents are needed to determine patient-oriented outcomes, such as the effect on IQ.

Body Burden↗
PubMed2003

[Metal poisoning].

Metals are amongst the oldest toxic substances known to man. In today's industrialized world the sources of exposure to metals are ubiquitous both in the field of work and from polluted water, foodstuffs and the environment. Their toxicity is characterized by the metallic element in question, but this is modified by the type of compound, whether organic or inorganic, and its characteristics of hydrosolubility and liposolubility, which determines its toxicokinetics and thus the possibilities of it reaching its targets. The biomolecules most affected by metals are the proteins with enzymatic activity, which is why their pathology is multisystemic. The principal systems affected are the gastrointestinal, central and peripheral neurological, haematic and renal. Some metallic compounds are carcinogenic. Metals's treatment is conditioned by their chemical reactivity. They can be deactivated and eliminated by the administering of chelating agents that produce complex molecules, which are non-toxic and can be excreted. The principal chelating agents are: BAL (British Anti-Lewisite or dimercaprol) DMPS (2,3-Dimercapto-1-propanesulfonic Acid) and DMSA (meso-2,3-Dimercaptosuccinic or Succimer), EDTA, Penicilamine (b,b-dimethylcysteine) and Deferoxamine. Toxicokinetic characteristics, mechanism of action, clinical picture and treatment of some of the most relevant metals and metalloids: lead, mercury and arsenic, are considered.

Acute Disease↗
PubMed2003

[Managing childhood lead poisoning].

This paper reviews the clinical management of children with lead poisoning. A first step is to define the measures to be used in their assessment and be aware of the limitations. Measurements of blood lead levels can be made on anticoagulated whole blood samples using either: atomic absorption spectroscopy or anodic stripping voltametry. However a more accurate method is fluorescent RX'ray of the skeleton or systematic biochemical tests of lead levels in urine. Remedies include elimination of lead in the environment, changes in children's behavior and dietary checks for adequate calcium and iron intake. Chelation therapy, using Ca edetate and succimer eliminates lead from the skeleton, which is then quickly excleted using a cathartic to help prevent re-absorption. Chelation may save lives where BLLs are very high. There is usually a short term reduction of BLLs with a subsequent rise. Serious cases may require repeat therapies. Chelation should be considered in children with BLLs > = 45 micrograms/dl. Chelation therapy reduces BLLs and associated symptoms. However cognitive decline may be irreversible, indicating that emphasis should be on prevention rather than cure. The English version of this paper is available at: http://www.insp.mx/salud/index.html.

Child↗
PubMed2006

Deaths associated with hypocalcemia from chelation therapy--Texas, Pennsylvania, and Oregon, 2003-2005.

Chelating agents bind lead in soft tissues and are used in the treatment of lead poisoning to enhance urinary and biliary excretion of lead, thus decreasing total lead levels in the body. During the past 30 years, environmental and dietary exposures to lead have decreased substantially, resulting in a considerable decrease in population blood lead levels (BLLs) and a corresponding decrease in the number of patients requiring chelation therapy. Chelating agents also increase excretion of other heavy metals and minerals, such as zinc and, in certain cases, calcium. This report describes three deaths associated with chelation-therapy--related hypocalcemia that resulted in cardiac arrest. Several drugs are used in the treatment of lead poisoning, including edetate disodium calcium (CaEDTA), dimercaperol (British anti-Lewisite), D-penicillamine, and meso-2,3-dimercaptosuccinic acid (succimer). Health-care providers who are unfamiliar with chelating agents and are considering this treatment for lead poisoning should consult an expert in the chemotherapy of lead poisoning. Hospital pharmacies should evaluate whether continued stocking of Na2EDTA is necessary, given the established risk for hypocalcemia, the availability of less toxic alternatives, and an ongoing safety review by the Food and Drug Administration (FDA). Health-care providers and pharmacists should ensure that Na2EDTA is not administered to children during chelation therapy.

Chelating Agents↗
PubMed1998

The efficacy of reducing agents or antioxidants in blocking the formation of dense cells and irreversibly sickled cells in vitro.

We show that N-acetylcysteine (NAC) has the ability to cause statistically significant diminishment in the in vitro formation of irreversibly sickled cells (ISCs) at concentrations greater than 250 micromol/L. Other antioxidants, approved for human use (cysteamine, succimer, dimercaprol), were not efficacious. NAC had the ability to cause statistically significant conversion of ISCs formed in vivo back to the biconcave shape. NAC was also shown to reduce the formation of dense cells and increase the available thiols in beta-actin. We showed that diminishing reduced glutathione (GSH), by treatment with 1-chloro-2,4-dinitrobenzene, resulted in increased dense cells. We conclude the NAC blocks dense cell formation and ISC formation by targeting channels involved in cellular dehydration and beta-actin, respectively. The efficacy of NAC is probably due to its combined antioxidant activity and ability to increase intracellular GSH.

Acetylcysteine↗
PubMed1998

Adsorption of some technetium-99m radiopharmaceuticals onto disposable plastic syringes.

OBJECTIVE: The purpose of this study was to determine the adsorption behavior of some widely used, commercially available 99mTc radiopharmaceuticals onto different types of plastic syringes. METHODS: Kits were reconstituted with 99mTc-pertechnetate diluted with 0.9% saline to produce maximum radioactive concentrations, as stated by the manufacturers. Aliquots of the solutions were transferred to four different brands of 2-ml syringes. The activity in the syringes was measured before and after injections or simulated injections. The amount adsorbed to the plastic syringe barrel and plunger before and after washout also was measured at different time intervals. Comparisons between products from different manufacturers were made for 99mTc succimer (DMSA) and 99mTc macroaggregated albumin (MAA). RESULTS: Some 99mTC preparations undergo significant adsorption to plastic syringes. Adsorption differs considerably between products from different manufacturers. There was significantly higher residual activity in some types of syringes. In some cases the residual was as high as 40%-50% of the initial activity, and most of the adsorption occurred within 15 min of filling the syringe. CONCLUSION: The data suggest that the extent of adsorption depends on pharmaceutical excipients in the kits and/or the type of syringe used. When inappropriate syringes are used, the reduction in the administered activity may result in poor-quality images. Therefore, the compatibility between radiopharmaceutical and syringe should be investigated under normal conditions of preparation and use every time a new brand of syringe or a new radiopharmaceutical comes into use in diagnostic nuclear medicine.

Adsorption↗
PubMedDate not supplied

Comparative effects of chelating agents on pulmonary toxicity of systemic nickel in mice.

N-Benzyl-D-glucaminedithiocarbamate (BGD), diethyldithiocarbamate (DDTC), dihydroxyethyldithiocarbamate (DHED), trans-1,2-cyclohexanediamine N,N,N',N'-tetraacetic acid (CDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) were studied for their protective effects against the pulmonary toxicity in mice induced by acute exposure to nickel. Nickel injection increased lipid peroxidation, lactate dehydrogenase (LDH) activity and the concentrations of protein, phospholipids (PL) and essential metals such as Ca, Fe and Zn and decreased the reduced glutathione (GSH) concentration and alkaline phosphatase (ALP) activity in the lungs. At 30 min after Ni treatment, DMSA, BGD and DDTC effectively depressed Ni concentration in the lungs. At 24 h after Ni treatment, DMSA and BGD were effective in mobilizing Ni from the lungs. Both DMSA and BGD significantly prevented increases in lipid peroxidation and in the concentrations of PL, Ca, Fe and Zn, and decreases in GSH concentration and ALP activity in the lungs of mice caused by Ni injection. Treatment with DMSA or BGD was more effective than that with other chelating agents in decreasing the pulmonary Ni concentration and preventing other changes caused by acute exposure to Ni, resulting in effective protection against Ni-induced pulmonary damage.

Alkaline Phosphatase↗
PubMedDate not supplied

Racemic-2,3-dimercaptosuccinic acid for inorganic mercury mobilization in rats.

The efficiency of racemic-2,3-dimercaptosuccinic acid (rac-DMSA) compared with meso-2,3-dimercaptosuccinic acid (meso-DMSA) in mobilizing inorganic mercury was evaluated in female rats. Chelators were administered orally at a dose of 0.5, 1.0 or 2.0 mmol kg-1 on four consecutive days, 5 days after a single intraperitoneal 203Hg injection (with 0.5 mg HgCl2 kg-1). Both chelators reduced 203Hg retention in whole body and kidney and at higher doses also in the liver. Racemic-DMSA was more efficient at lower dose levels and equal to meso-DMSA at the highest dose level. Kidney retention decreased after rac-DMSA to 27, 10 and 10% of controls and after meso-DMSA to 68, 39 and 10% of control values at the 0.5, 1.0 and 2.0 mmol kg-1 dose level, respectively. Since meso-DMSA is already approved for human use, its stereoisomeric form, rac-DMSA, deserves further attention for treatment of mercury poisoning.

Administration, Oral↗
PubMedDate not supplied

Effects of zinc supplementation during chelating agent administration in cadmium intoxication in rats.

The concomitant administration of zinc during chelation of cadmium (Cd) with meso-2,3-dimercaptosuccinic acid (DMSA) or calcium trisodium diethylenetriamine penta-acetic acid (DTPA) was investigated in male rats subchronically exposed to Cd. The results suggest that the administration of zinc alone after cadmium exposure does not elicit any protective effects. However, when supplemented during treatment with DTPA it produced a significant turnover in the altered biochemical variables and a depletion of Cd concentration in liver and kidneys. Cadmium-induced elevated hepatic metallothionein (MT) contents remained practically unaltered on Zn-DTPA administration, but there was a significant increase in renal MT levels compared to rats administered Cd-DTPA or Cd alone.

Animals↗
PubMedDate not supplied

Combined chelation therapy in reducing tissue lead concentrations in suckling rats.

The very young are more prone to lead poisoning than adults, and the treatment with chelating agents, either as monotherapy or combined treatment, is still a matter of dispute. The purpose of this work was to evaluate the efficiency of three chelating agents administered either as monotherapies or as combined treatments in sucklings. Lead acetate (5 mg Pb kg(-1) i.p.) was administered to the 7-day-old rat pups in eight litters on experimental day 1 and chelating agents on experimental days 2 and 3. Pups were divided into six groups: (1) untreated control; (2) EDTA (calcium disodium ethylendiaminetetraacetate, 0.3 mmol kg(-1) i.p. at 4 p.m.); (3) meso-DMSA (meso-2,3-dimeracaptosuccinic acid, 0.5 mmol kg(-1) p.o. at 10 a.m.); (4) rac-DMSA (racemic-2,3-dimeracaptosuccinic acid, 0.5 mmol kg(-1) p.o. at 10 a.m.); (5) EDTA+meso-DMSA; and (6) EDTA+rac-DMSA. Rats were killed on experimental day 5. Tissue element concentrations were analyzed by atomic absorption spectrometry. Treatment with EDTA did not affect tissue Pb, but it reduced Zn in the carcass and liver. Meso-DMSA reduced Pb in the kidneys and brain, and it did not affect organ essential elements. Rac-DMSA most efficiently reduced Pb concentrations in the carcass, kidneys and brain, but it also reduced Zn and Cu in the liver and Zn in the kidneys. Combined treatments with EDTA never improved the efficiency of either DMSA isoform in decreasing tissue Pb but they did reduce tissue Zn concentrations. All treatments caused the same decrease in the carcass Ca concentrations. The results do not support combined treatment in this age group, which is especially sensitive to trace element deficiencies, and suggest that meso-DMSA might be the treatment of choice in acute lead poisoning in infants.

Animals↗
PubMed2001

Associations of tibia lead, DMSA-chelatable lead, and blood lead with measures of peripheral nervous system function in former organolead manufacturing workers.

BACKGROUND: The goals of the present study were to compare and contrast associations of blood lead, DMSA-chelatable lead, current tibia lead, and back-extrapolated "peak" tibia lead with four peripheral nervous system (PNS) sensory and motor function measures in older males with past exposure to organic and inorganic lead. METHODS: Data were collected from former organolead manufacturing workers with an average of 16 years since last occupational lead exposure. Current tibia lead levels were measured by (109)Cd x-ray fluorescence. Sensory pressure thresholds (index and pinky fingers) and pinch and grip strength were measured with the Pressure-Specified Sensory Device (PSSD). RESULTS: In adjusted analyses, none of the four lead biomarkers was associated with sensory pressure threshold of the index finger or pinch or grip strength. In contrast, all four biomarkers were associated (P < or = 0.10) with pressure threshold of the pinky finger. The final linear regression models accounted for a small proportion of the variance in the sensory (1-3%) and motor measures (10-21%). CONCLUSIONS: This study found no strong association between lead biomarkers and selected PNS sensory or motor function measures among former organolead manufacturing workers with no recent occupational exposure to lead. Previously reported CNS findings in this cohort suggest that the PNS may be less sensitive to the chronic toxic effects of lead in this dose range among adults. It is also possible that the PNS has a greater capacity for repair than does the CNS, or that the PNS measures were less sensitive for detection of lead-related health outcomes than were the CNS measures.

Adult↗
PubMed1993

Dimercaptosuccinic acid in the treatment of depression following lead exposure.

Long-term exposure to lead is known to cause a variety of neurotoxic manifestations, including symptoms of depression. Dimercaptosuccinic acid (DMSA), a recently approved oral chelating agent, can diminish the body burden of lead, but few cases of documented clinical improvement following treatment have been reported. We report a case of moderate to severe depression in a long-term lead worker that appeared to respond dramatically to DMSA. This response suggests a possible therapeutic role for DMSA in the treatment of depression in lead-exposed patients.

Adult↗