Lead ingestion, medical emergency and action plan.

Ingestion of lead material represents a therapeutic challenge involving high toxicity, significant clinical impact, and controversy regarding management. We report the case of a 2-year-old girl, who accidentally ingested a fishing sinker. She remained asymptomatic and first level tests were performed (blood lead levels and x-ray to locate object). Because of sinker location in the jejunum, two rectal enemas and polyethylene glycol (PEG) were administered, serial blood lead level measurements were performed. Because of sinker persistence, a colonoscopy was undertaken. She did not require chelation treatment. However, she required follow-up to monitor long-term toxicity and sequels.

[Kidney damage caused by lead exposure: historical aspects].

The article presents an historical analysis of publications devoted lead intoxication to kidney damage developing during contact with lead. It is shown that one of the manifestations of occupational intoxication with this metal can be toxic nephropathy.

Low dose lead exposure at the onset of puberty disrupts spermatogenesis-related gene expression and causes abnormal spermatogenesis in mouse.

Implications of lead (Pb) exposure in dysregulated spermatogenesis in sexually active individuals during adulthood is well established; however, the effect of Pb exposure on spermatogenesis in the early stages of puberty is not clear yet. Moreover, the mechanism of Pb mediated dysregulation of spermatogenesis in adults is also poorly understood. Exposure to environmental toxicants during puberty may cause serious consequences in adulthood causing developmental retardations, especially in the reproductive system. Here we investigated the effects of lead exposure on spermatogenesis at the onset of puberty and the underlying mechanisms of these effects. Male ICR mice were exposed to low (50 mg/L) and high (200 mg/L) doses of Pb through the drinking water for 90 days. At the end of this period, the blood Pb level of the low-dose and high-dose exposure groups were found 6.14 ± 0.34 µg/dL and 11.92 ± 2.92 µg/dL respectively which were in agreement with the US CDC-recommended (5 µg/dL) and Chinese CDC-recommended (10 µg/dL) reference blood Pb level for the children. Although no visible toxicity was observed in either group, Pb exposure caused considerable histopathological changes in testis and epididymis; increased sperm DNA fragmentation indices as well as disrupted sperm heads and head-neck conjunctions. Moreover, both low and high-dose Pb exposures caused aberrant expressions of several important spermatogenesis-related genes in epididymis and testis. These results suggest that although the blood Pb levels are close to the recommended-reference values, low dose Pb exposure at the onset of puberty can disrupt spermatogenesis-related gene expression and cause abnormal mouse spermatogenesis.

Changes in inflammatory cytokines, antioxidants and liver stiffness after chelation therapy in individuals with chronic lead poisoning.

BACKGROUND: Chronic exposure to lead causes lead to accumulate mainly in the liver. In vivo studies have shown that lead toxicity is related to alterations in the inflammatory response. We aimed to evaluate the association between lead poisoning and liver fibrosis as well as the change in the degree of liver fibrosis, levels of inflammatory mediators and glutathione (GSH) after chelation therapy. METHODS: Workers from a battery factory who were exposed to lead for > 12 months and had a blood lead level (BLL) > 70 µg/dL were enrolled (n = 86) in the study. Participants underwent chelation therapy with intravenous CaNa2EDTA for 2 days followed by treatment with oral D-penicillamine for 90 days. The primary outcome was the change in the degree of liver fibrosis, which was presented as liver stiffness (LS) measured by FibroScan®. Secondary outcomes were the changes in the levels of serum GSH and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) after chelation therapy. RESULTS: Among the 86 participants, there was a positive correlation between the duration of lead exposure and LS (r = 0.249, p = 0.021). To avoid the confounding effect of obesity-related steatosis, only 70 individuals who had controlled attenuation parameters < 296 dB/m, BMI < 25 kg/m2 and normal waist circumference were included in the interventional analysis. After chelation, the mean LS significantly decreased from 5.4 ± 0.9 to 4.8 ± 1.4 kPa (p = 0.001). Similarly, all of the inflammatory cytokines studied significantly decreased after chelation (p < 0.001); TNF-α decreased from 371.6 ± 211.3 to 215.8 ± 142.7; the levels of IL-1ß decreased from 29.8 ± 1.7 to 25.9 ± 4.3; and the levels of IL-6 decreased from 46.8 ± 10.2 to 35.0 ± 11.9. On the other hand, the mean GSH level increased significantly from 3.3 ± 3.3 to 13.1 ± 3.7 (p < 0.001) after chelation therapy. CONCLUSION: The duration of lead exposure was significantly correlated with the degree of liver fibrosis. Chelation treatment was associated with increased levels of GSH and decreased levels of proinflammatory cytokines and could potentially reduce the degree of LS. TRIAL REGISTRATION: This study was retrospectively registered and approved by the Thai Clinical Trial Registry (TCTR) on 2019-11-07. The TCTR identification number is TCTR20191108001 .

Lead poisoning; a neglected potential diagnosis in abdominal pain.

BACKGROUND: Abdominal pain may be a presenting symptom of lead poisoning and is often difficult to diagnose. This study aimed to determine the prevalence of abdominal pain in patients seen in the Laghman Hakim Hospital ED and GI clinic who were lead-intoxicated, with or without opiate use disorder. METHODS: Between July 2017 and January 2018, patients seen in the ED and GI clinic of Loghman Hakim Hospital with unexplained abdominal pain or abdominal pain resistant to treatment were enrolled. Informed consent was obtained from potential enrollees. For standardization, a pre-designed data collection tool was developed for uniform data acquisition. Opiate use was determined historically. For this study, lead poisoning was defined as a blood lead level (BLL) greater than or equal to 30 µg/dL (1.45 µmol/L) with concomitant GI symptoms. RESULTS: Of 125 patients admitted, 28 (22.4%) had BLLs higher than 30 µg/dL. None of the patients had signs and symptoms of opioid withdrawal syndrome during evaluation. Elevated BLLs were significantly correlated with oral opium use/abuse, history of addiction for over the preceding 12 years. The daily opium use was more than 2.75 g. There was a statistical correlation between lead toxicity and abdominal pain consistency and intensity, constipation, and paresthesias. Anemia, leukocytosis, and abnormal liver enzyme tests were laboratory findings associated with lead toxicity. Four patients died, one of whom was diagnosed with lead toxicity. CONCLUSION: Lead toxicity should be considered in the potential differential diagnosis of severe and resistant abdominal pain in patients referring to general EDs or GI clinics if a positive history of opium abuse exists.

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.

Chronic occupational exposure to lead leads to significant mucocutaneous changes in lead factory workers.

BACKGROUND: Chronic lead toxicity is a worldwide public health problem. Lead possesses deleterious effects on many organ systems. However, little is known regarding its clinical and biophysical effects on the skin. OBJECTIVE: To investigate mucocutaneous signs and biophysical property changes in skin after chronic lead toxicity. METHODS: One hundred and eighty-seven patients who were car battery workers participated in the study. Complete history and physical examination were performed. Blood was collected for laboratory analyses. Thorough skin examination by dermatologists was carried out in 134 subjects. Additionally, 96 patients with blood lead levels (BLL) >70 µg/dL were further evaluated for skin elasticity, sebum content, transepidermal water loss (TEWL), hydration, pH and pigmentation. An equal number of age-, sex- and skin-type-matched subjects were recruited as controls. RESULTS: The mean BLL of all subjects was 74.15 ± 11.58 µg/dL. The most frequently observed signs were gingival brown pigmentation in 112 (83.6%), gingivitis in 111 (82.8%) and lead line in 66 (49.3%) patients. The lead line was found in subjects with significantly higher BLLs (adjusted mean difference 6.45, 95% CI 2.30-10.60 µg/dL, P = 0.003) and in association with gingivitis (adjusted OR 7.32, 95% CI 2.08-25.74, P = 0.002). Mean BLL of the patients who underwent biophysical assessment was 82.77 ± 9.80 µg/dL. Patients exhibited a statistically significant lower skin hydration observed by corneometer as well as elasticity. The adjusted ORs of having dry skin and lower elasticity were 15.32 (95% CI 4.41-53.24), P < 0.001) and 1.96 (95% CI 1.06-3.60), P = 0.031), respectively. These differences were not significant for sebum content, TEWL, pH and pigmentation. CONCLUSION: Importantly, even in normal-appearing skin, level of hydration and elasticity decreased in lead-intoxicated patients. These results suggest that lead might possess harmful effects on the skin at measurable levels.

Lead exposure induces oxidative stress, apoptosis, and attenuates protection of cardiac myocytes against ischemia-reperfusion injury.

Disrupting role of lead toxicity in heart functions and prognosis of cardiovascular diseases is not well known. This study investigated the interference of lead in heart functions and pacing postconditioning-mediated protection to the heart from ischemia-reperfusion injury. Lead exposure decreased the body weight and increased the heart weight in male rats (p < 0.001). Long-term lead exposure (45 days exposure to lead) increased total oxidant levels (p < 0.001) in the heart. Furthermore, lead exposure abrogated the pacing postconditioning-mediated protection from ischemia-reperfusion injury. The latter effect showed an association with reduced total antioxidants levels (p < 0.001). In the short-term study (5 days exposure to lead), pacing postconditioning protected the heart from ischemia-reperfusion injury despite the reduced total antioxidant levels (p < 0.001). Lead toxicity caused a drastic increase in the heart weight in male rats and apoptosis. The induced oxidative stress showed association with the lack of pacing postconditioning-mediated protection of the heart. However, long-term lead exposure eliminated pacing postconditioning-mediated protection of the heart from ischemia-reperfusion injury.

Folk prescription for treating rhinitis as a rare cause of childhood lead poisoning: a case series.

BACKGROUND: Folk prescriptions continue to be important sources of childhood lead poisoning. Nasal spray folk prescriptions for treating rhinitis has only been reported once previously as a cause of lead poisoning. CASE PRESENTATION: We identified three pediatric cases of severe lead poisoning caused by nasal spray folk medicines prescribed for treating rhinitis. The three patients had similar clinical manifestations including: severe abdominal pain, headache, pale appearance and fatigue. Liver function tests were abnormal. Blood lead levels (BLLs) of the three patients were 91 µg/dL, 91 µg/dL, and 105 µg/dL, respectively. After chelation BLLs decreased. The lead content of the three folk remedies as measured by inductively coupled plasma mass spectrometry (ICP-MS) were 14.8, 22.3, and 33.4%. All the symptoms resolved during a course of chelation therapy. There were no severe side effects of treatment. CONCLUSIONS: Nasal spray folk prescriptions for treating rhinitis may contain extremely high bio-accessible lead content and are potential sources of lead poisoning. Clinicians should be alert to this possibility especially in those children presenting with multisystem symptoms.

Lead exposure may affect gingival health in children.

BACKGROUND: Several studies have reported the harmful effects of lead poisoning. However, the relationship between lead exposure and oral health of children has not been well defined. The aim of this study was to investigate the relationship between blood lead level (BLL) and oral health status of children. METHODS: A total of 351 children (aged 7-15 years) were recruited from the pilot data of the Korean Environmental Health Survey in Children and Adolescents, which was designed to examine environmental exposure and children's health status in South Korea. Blood samples were taken to determine BLLs and oral examinations were performed to assess oral health parameters, including community periodontal index (CPI), gingival index (GI), and plaque index (PI). Information regarding socioeconomic status, oral hygiene behavior, and dietary habits was collected from parents and guardians. RESULTS: The participants were divided equally into four quartiles, with quartile I comprised of children with the lowest BLLs. There were significant differences for PI (p < 0.05) among the quartile groups. Using logistic regression models, we found a significant relationship between BLL and oral health parameters. The crude odds ratios for CPI, GI, and PI in the third quartile were 5.24 (95% CI: 1.48-18.56), 4.35 (95% CI: 1.36-13.9), and 4.17 (95% CI: 1.50-11.54), respectively, while the age and gender-adjusted odds ratios were 7.66 (95% CI: 1.84-31.91), 6.80 (95% CI: 1.80-25.68), and 3.41 (95% CI: 1.12-10.40), respectively. After adjustments for age, gender, parent education level, and frequency of tooth brushing, the adjusted odds ratios were 7.21 (95% CI: 1.72-30.19), 6.13 (95% CI: 1.62-23.19), and 3.37 (95% CI: 1.10-10.34), respectively. CONCLUSIONS: A high BLL might be associated with oral health problems in children, including plaque deposition and gingival diseases.

From Lead Exposure in Early Childhood to Adolescent Health: A Chicago Birth Cohort.

OBJECTIVES: To assess the relationships between childhood lead exposure and 3 domains of later adolescent health: mental, physical, and behavioral. METHODS: We followed a random sample of birth cohort members from the Project on Human Development in Chicago Neighborhoods, recruited in 1995 to 1997, to age 17 years and matched to childhood blood test results from the Department of Public Health. We used ordinary least squares regression, coarsened exact matching, and instrumental variables to assess the relationship between average blood lead levels in childhood and impulsivity, anxiety or depression, and body mass index in adolescence. All models adjusted for relevant individual, household, and neighborhood characteristics. RESULTS: After adjustment, a 1 microgram per deciliter increase in average childhood blood lead level significantly predicts 0.06 (95% confidence interval [CI] = 0.01, 0.12) and 0.09 (95% CI = 0.03, 0.16) SD increases and a 0.37 (95% CI = 0.11, 0.64) point increase in adolescent impulsivity, anxiety or depression, and body mass index, respectively, following ordinary least squares regression. Results following matching and instrumental variable strategies are very similar. CONCLUSIONS: Childhood lead exposure undermines adolescent well-being, with implications for the persistence of racial and class inequalities, considering structural patterns of initial exposure.

Estimators for longitudinal latent exposure models: examining measurement model assumptions.

Latent variable (LV) models are increasingly being used in environmental epidemiology as a way to summarize multiple environmental exposures and thus minimize statistical concerns that arise in multiple regression. LV models may be especially useful when multivariate exposures are collected repeatedly over time. LV models can accommodate a variety of assumptions but, at the same time, present the user with many choices for model specification particularly in the case of exposure data collected repeatedly over time. For instance, the user could assume conditional independence of observed exposure biomarkers given the latent exposure and, in the case of longitudinal latent exposure variables, time invariance of the measurement model. Choosing which assumptions to relax is not always straightforward. We were motivated by a study of prenatal lead exposure and mental development, where assumptions of the measurement model for the time-changing longitudinal exposure have appreciable impact on (maximum-likelihood) inferences about the health effects of lead exposure. Although we were not particularly interested in characterizing the change of the LV itself, imposing a longitudinal LV structure on the repeated multivariate exposure measures could result in high efficiency gains for the exposure-disease association. We examine the biases of maximum likelihood estimators when assumptions about the measurement model for the longitudinal latent exposure variable are violated. We adapt existing instrumental variable estimators to the case of longitudinal exposures and propose them as an alternative to estimate the health effects of a time-changing latent predictor. We show that instrumental variable estimators remain unbiased for a wide range of data generating models and have advantages in terms of mean squared error. Copyright © 2017 John Wiley & Sons, Ltd.

Impaired hypothalamic-pituitary-testicular axis activity, spermatogenesis, and sperm function promote infertility in males with lead poisoning.

Lead poisoning is a stealthy threat to human physiological systems as chronic exposure can remain asymptomatic for long periods of time before symptoms manifest. We presently review the biophysical mechanisms of lead poisoning that contribute to male infertility. Environmental and occupational exposure of lead may adversely affect the hypothalamic-pituitary-testicular axis, impairing the induction of spermatogenesis. Dysfunction at the reproductive axis, namely testosterone suppression, is most susceptible and irreversible during pubertal development. Lead poisoning also appears to directly impair the process of spermatogenesis itself as well as sperm function. Spermatogenesis issues may manifest as low sperm count and stem from reproductive axis dysfunction or testicular degeneration. Generation of excessive reactive oxygen species due to lead-associated oxidative stress can potentially affect sperm viability, motility, DNA fragmentation, membrane lipid peroxidation, capacitation, hyperactivation, acrosome reaction, and chemotaxis for sperm-oocyte fusion, all of which can contribute to deter fertilization. Reproductive toxicity has been tested through cross-sectional analysis studies in humans as well as in vivo and in vitro studies in animals.

The changes of lead exposed workers' ECG and blood pressure by testing the effect of CaNa2EDTA on blood lead.

The role of lead pollution in the induction of hypertension and electrocardiogram (ECG) changes has not been sufficiently recognized. The present study is aimed to calculate the association between lead exposure and blood pressure (BP) and ECG findings. A group of 147 lead-exposed workers from a battery plant and 104 controls were examined for blood lead levels (PbB), BP, and ECG. The exposed workers were followed annually from 2008 to 2010. Furthermore, lead in air dust and fumes were also detected in the breathing zone of the workplace. The PbB of lead-exposed workers were correlated with air lead in worksites from 2008 to 2010. A linear regression of repeated measurement analysis showed that diastolic blood pressure (DBP) in exposed workers decreased consecutively from 2008 to 2010 (p<0.01) with reduced lead exposure; however, this value was not correlated with the incidence of hypertension (p=0.138). Abnormal ECG rates were 35.37%, 38.78%, and 44.90% in 2008, 2009, and 2010, respectively, demonstrating an annual increase (p=0.024). Our study showed that lead exposure was crucial factor in causing ECG abnormalities. No correlation was identified between lead exposure and hypertension, and further study is needed. EDTA for the treatment of blood lead object on lead poisoning (PbB) level, abnormal electrocardiogram and blood pressure increases curative effect, and the better effect of the longer range.