Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2).

BACKGROUND: The reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes. METHODS: TACT2 enrolled 1,000 participants with diabetes and prior myocardial infarction, age 50 years or older between September 2016 and December 2020. Among 959 participants with at least one infusion, 933 had blood and/or urine metals measured at the Centers for Diseases Control and Prevention using the same methodology as in the National Health and Nutrition Examination Survey (NHANES). We compared metal levels in TACT2 to a contemporaneous subset of NHANES participants with CVD, diabetes and other inclusion criteria similar to TACT2's participants. RESULTS: At baseline, the median (interquartile range, IQR) age was 67 (60, 72) years, 27% were women, 78% reported white race, mean (SD) BMI was 32.7 (6.6) kg/m2, 4% reported type 1 diabetes, 46.8% were treated with insulin, 22.3% with GLP1-receptor agonists or SGLT-2 inhibitors, 90.2% with aspirin, warfarin or P2Y12 inhibitors, and 86.5% with statins. Blood lead was detectable in all participants; median (IQR) was 9.19 (6.30, 13.9) µg/L. Blood and urine cadmium were detectable in 97% and median (IQR) levels were 0.28 (0.18, 0.43) µg/L and 0.30 (0.18, 0.51) µg/g creatinine, respectively. Metal levels were largely similar to those in the contemporaneous NHANES subset. CONCLUSIONS: TACT2 participants were characterized by high use of medication to treat CVD and diabetes and similar baseline metal levels as in the general US population. TACT2 will determine whether chelation therapy reduces the occurrence of subsequent CVD events in this high-risk population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov. Identifier: NCT02733185. https://clinicaltrials.gov/study/NCT02733185.

Associations between urinary heavy metal concentrations and blood pressure in residents of Asian countries.

BACKGROUND: Previous studies have suggested that exposures to heavy metals (arsenic, cadmium, lead, and selenium) may be associated with differences in blood pressure. However, the findings of these studies have been inconsistent. This study was performed to examine the associations between urinary heavy metal concentrations and blood pressure among residents of four Asian countries (Bangladesh, Indonesia, Nepal, and Vietnam). METHODS: This cross-sectional study examined 1899 adults in four Asian countries. Urinary concentrations of heavy metals were measured by inductively coupled plasma mass spectrometry. A questionnaire survey was administered regarding individual characteristics. Anthropometric measurements (height and weight) were performed. Systolic and diastolic blood pressures were measured after a short rest. Multiple linear regression models were applied to investigate associations between urinary heavy metal concentrations and blood pressure after adjustments for age, sex, and body mass index. RESULTS: The geometric means of the urinary concentrations of arsenic, cadmium, lead, and selenium were 84.6, 0.885, 2.09, and 16.5 µg/g creatinine, respectively. The urinary arsenic concentrations were slightly higher than those typically reported in non-polluted populations, while urinary cadmium, lead, and selenium concentrations were equivalent or slightly lower. The urinary lead concentrations were positively associated with both systolic and diastolic blood pressure, but urinary selenium concentrations were negatively associated with them. CONCLUSIONS: Variations in the urinary concentrations of lead and selenium were associated with blood pressure at low levels of exposure/intake.

Associations between urinary heavy metal concentrations and blood pressure in residents of Asian countries

BACKGROUND@#Previous studies have suggested that exposures to heavy metals (arsenic, cadmium, lead, and selenium) may be associated with differences in blood pressure. However, the findings of these studies have been inconsistent. This study was performed to examine the associations between urinary heavy metal concentrations and blood pressure among residents of four Asian countries (Bangladesh, Indonesia, Nepal, and Vietnam).@*METHODS@#This cross-sectional study examined 1899 adults in four Asian countries. Urinary concentrations of heavy metals were measured by inductively coupled plasma mass spectrometry. A questionnaire survey was administered regarding individual characteristics. Anthropometric measurements (height and weight) were performed. Systolic and diastolic blood pressures were measured after a short rest. Multiple linear regression models were applied to investigate associations between urinary heavy metal concentrations and blood pressure after adjustments for age, sex, and body mass index.@*RESULTS@#The geometric means of the urinary concentrations of arsenic, cadmium, lead, and selenium were 84.6, 0.885, 2.09, and 16.5 μg/g creatinine, respectively. The urinary arsenic concentrations were slightly higher than those typically reported in non-polluted populations, while urinary cadmium, lead, and selenium concentrations were equivalent or slightly lower. The urinary lead concentrations were positively associated with both systolic and diastolic blood pressure, but urinary selenium concentrations were negatively associated with them.@*CONCLUSIONS@#Variations in the urinary concentrations of lead and selenium were associated with blood pressure at low levels of exposure/intake.

Reduction of in utero lead exposures in South African populations: Positive impact of unleaded petrol.

BACKGROUND: Prenatal exposure to lead (Pb) has been shown to have negative and irreversible health impacts on foetal and early childhood development, affecting morbidity and mortality in adulthood. This study aimed to assess in utero Pb exposure, examine birth outcomes, and identify confounding factors in the large cohort of South African population, following the legislated removal of Pb from petrol. METHODS: Lead was measured in the maternal blood, urine and cord blood using Inductive Coupled Plasma Mass spectrometry (ICP-MS). The statistical analyses included Spearman's correlation, Wilcoxon rank sum (Mann Whitney), Kruskal-Wallis rank tests and multivariate linear regression. RESULTS: Overall, the geometric mean (GM) of Pb in maternal blood (PbB) was 1.32 µg/dL (n = 640; 95% CI, 1.24-1.40). In the subset cohort, the GM of paired maternal PbB and cord blood (PbC) was 1.73 µg/dL (n = 350; 95% CI, 1.60-1.86) and 1.26 µg/dL (n = 317; 95% CI, 1.18-1.35), respectively with a positive correlation between the log PbB and the log PbC (rho = 0.65, p = <0.001). Birth outcomes showed geographical differences in the gestational age (p<0.001), birth length (p = 0.028) and head circumference (p<0.001), Apgar score at 5 min (p<0.001) and parity (p<0.002). In female neonates, a positive association was found between PbC and head circumference (rho = 0.243; p<0.016). The maternal PbB levels were positively correlated with race, educational status, water sources, cooking fuels and use of pesticides at home. CONCLUSIONS: This study has demonstrated not only the positive impact that the introduction of unleaded petrol and lead-free paint has had on in utero exposure to Pb in South Africa, but has also contributed new data on the topic, in a region where such data and scientific investigations in this field are lacking. Future research should evaluate if similar effects can be detected in young children and the adult population.

Synthesis and characterization of new 1-hydroxy-2-pyridinethione derivatives: Their lead complexes and efficacy in the treatment of acute lead poisoning in rats.

A number of new mono- and dihydroxypyridinethione ligands have been synthesized via reaction of dimethylamine and amino acid esters with the active amide obtained from the reaction of 1-hydroxy-2-pyridinethione-4-carboxylic acid (1) and 1,1'-carbonyldiimidazole in DMF. Moreover, the lead complexes of these new ligands were also prepared. Structures of the newly synthesized compounds have been confirmed by different spectroscopic methods such as IR, 1H NMR, and 13C NMR, and by elemental analysis. The effect of these synthesized ligands on the excretion of lead, iron, and zinc, and their distribution in kidneys, liver, and bones in acutely intoxicated rats was investigated and results, for lead, were compared with those of the known drug meso-2,3-dimercaptosuccinic acid (DMSA). Results obtained revealed that compound 5 exhibits remarkable ability in total fecal and urinary excretion of lead and was superior to DMSA. In addition, results show that the concentration of lead in soft tissues and bones was lower in rats treated with HTPL than those treated with DMSA. Furthermore, the concentration of lead in liver tissues obtained from sub-chronic lead-intoxicated rats treated with HTPL was lower than those treated with DMSA and calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA).

Modeling the effect of succimer (DMSA; dimercaptosuccinic acid) chelation therapy in patients poisoned by lead.

CONTEXT: Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer (dimercaptosuccinic acid; DMSA) chelation therapy on blood lead concentrations. MATERIALS AND METHODS: We integrated a two-compartment kinetic succimer model into an existing PBPK lead model and produced a Chelation Lead Therapy (CLT) model. The accuracy of the model's predictions was assessed by simulating clinical observations in patients poisoned by lead and treated with succimer. The CLT model calculates blood lead concentrations as the sum of the background exposure and the acute or chronic lead poisoning. The latter was due either to ingestion of traditional remedies or occupational exposure to lead-polluted ambient air. The exposure duration was known. The blood lead concentrations predicted by the CLT model were compared to the measured blood lead concentrations. RESULTS: Pre-chelation blood lead concentrations ranged between 99 and 150 µg/dL. The model was able to simulate accurately the blood lead concentrations during and after succimer treatment. The pattern of urine lead excretion was successfully predicted in some patients, while poorly predicted in others. CONCLUSIONS: Our model is able to predict blood lead concentrations after succimer therapy, at least, in situations where the duration of lead exposure is known.

Pediatric lead poisoning from folk prescription for treating epilepsy.

BACKGROUND: A case of lead poisoning resulting from the ingestion of a folk remedy for treating epilepsy is reported. RESULTS: The initial blood lead concentration of this 6-y-old boy was 63.6µg/dl upon admission. He presented with abdominal pain, constipation, and irritability. The patient's liver function tests were significantly increased. Through chelation therapy, the blood lead concentration dropped markedly and clinical symptoms greatly improved. His blood and urine samples were collected for the kinetic analysis of lead elimination. CONCLUSIONS: Folk prescriptions for epilepsy should be considered as potential sources of lead intoxication. Lead poisoning should be taken into consideration for unknown causes of abdominal pain.

Metals in Urine and Diabetes in U.S. Adults.

UNLABELLED: Our objective was to evaluate the relationship of urine metals including barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, tungsten, and uranium with diabetes prevalence. Data were from a cross-sectional study of 9,447 participants of the 1999-2010 National Health and Nutrition Examination Survey, a representative sample of the U.S. civilian noninstitutionalized population. Metals were measured in a spot urine sample, and diabetes status was determined based on a previous diagnosis or an A1C ≥6.5% (48 mmol/mol). After multivariable adjustment, the odds ratios of diabetes associated with the highest quartile of metal, compared with the lowest quartile, were 0.86 (95% CI 0.66-1.12) for barium (Ptrend = 0.13), 0.74 (0.51-1.09) for cadmium (Ptrend = 0.35), 1.21 (0.85-1.72) for cobalt (Ptrend = 0.59), 1.31 (0.90-1.91) for cesium (Ptrend = 0.29), 1.76 (1.24-2.50) for molybdenum (Ptrend = 0.01), 0.79 (0.56-1.13) for lead (Ptrend = 0.10), 1.72 (1.27-2.33) for antimony (Ptrend < 0.01), 0.76 (0.51-1.13) for thallium (Ptrend = 0.13), 2.18 (1.51-3.15) for tungsten (Ptrend < 0.01), and 1.46 (1.09-1.96) for uranium (Ptrend = 0.02). Higher quartiles of barium, molybdenum, and antimony were associated with greater HOMA of insulin resistance after adjustment. Molybdenum, antimony, tungsten, and uranium were positively associated with diabetes, even at the relatively low levels seen in the U.S. POPULATION: Prospective studies should further evaluate metals as risk factors for diabetes.

The effects of prenatal exposure to low-level cadmium, lead and selenium on birth outcomes.

To evaluate the current maternal and fetal exposure to cadmium (Cd), lead (Pb) and selenium (Se), and their potential effect on newborn birth outcomes, a cross-sectional study involving an assessment of the levels of these three metals in maternal blood, urine and umbilical cord blood was conducted in 209 pregnant women living in Eastern China. The maternal blood, urine and cord blood samples were collected and measured with inductively coupled plasma mass spectrometry (ICP-MS). The maternal blood concentrations of Cd, Pb and Se (the geometric means (GMs) were 0.48, 39.50 and 143.53 µg L(-1)) were significantly higher than and correlated with those in the cord blood (GM: 0.09, 31.62 and 124.61 µg L(-1)). In the urine samples, the GMs for Cd, Pb and Se were 0.13, 0.48, and 4.78 µg L(-1), respectively. Passive smoking was found to positively correlate with urine Cd (r=0.16) and negatively correlate with urine Se (r=-0.29). The maternal blood Se level was negatively associated with the cord Cd levels (r=-0.41). The blood Cd concentration in the mother could significantly affect the newborn birth weight (r=-0.22), but it was not correlated with birth height. We identified cord Se as a new factor which significantly correlated with birth weight. In conclusion, maternal Cd, Pb, Se exposure correlated with their umbilical cord concentration, and maternal Cd exposure might affect the newborn birth weight. Increasing the Se intake might reduce the cord blood Cd concentration and promote the fetal growth.

Essential and toxic element concentrations in blood and urine and their associations with diet: results from a Norwegian population study including high-consumers of seafood and game.

The first aim of the study was to evaluate calculated dietary intake and concentrations measured in blood or urine of essential and toxic elements in relation to nutritional and toxicological reference values. The second aim was to identify patterns of the element concentrations in blood and urine and to identify possible dietary determinants of the concentrations of these elements. Adults with a known high consumption of environmental contaminants (n=111), and a random sample of controls (n=76) answered a validated food frequency questionnaire (FFQ). Complete data on biological measures were available for 179 individuals. Blood and urine samples were analyzed for selenium, iodine, arsenic, mercury, cadmium and lead. Principal component analysis was used to identify underlying patterns of correlated blood and urine concentrations. The calculated intakes of selenium, iodine, inorganic arsenic and mercury were within guideline levels. For cadmium 24% of the high consumer group and 8% of the control group had intakes above the tolerable weekly intake. Concentrations of lead in blood exceeded the bench-mark dose lower confidence limits for some participants. However, overall, the examined exposures did not give rise to nutritional or toxicological concerns. Game consumption was associated with lead in blood (B(ln) 0.021; 95%CI:0.010, 0.031) and wine consumption. Seafood consumption was associated with urinary cadmium in non-smokers (B(ln) 0.009; 95%CI:0.003, 0.015). A novel finding was a distinct pattern of positively associated biological markers, comprising iodine, selenium, arsenic and mercury (eigenvalue 3.8), reflecting seafood intake (B 0.007; 95%CI:0.004, 0.010). The study clearly demonstrates the significance of seafood as a source of both essential nutrients and toxic elements simultaneously and shows that exposure to various essential and toxic elements can be intertwined.

Imported occupational lead poisoning: report of four cases.

BACKGROUND: In most industrialized countries, occupational lead poisoning has become increasingly rare, however this metal remains a serious health hazard in the rest of the world. REPORT OF CASES: We observedfour male patients (aged 35 / 54 years) who had suffered recurrent abdominal pain due to recent lead exposure (for 7 to 13 months) in two Chinese battery recycling plants. On their return to Italy, three of them presented normocytic, normochromic anaemia. The diagnosis was confirmed by high lead levels in the blood and urine, decreased erythrocyte delta-aminolevulinic acid dehydratase (ALA-D), raised erythrocyte zinc protoporphyrin (ZP), and elevated urinary excretion of b-aminolevulinic acid (ALA-U) and porphyrins. Chelation with EDTA resulted in increased urinary lead excretion, improvement of the clinical picture, decreased ZP, and progressive normalization of the other lead biomarkers (Pb-B, ALA-D, ALA-U, urinary porphyrins). CONCLUSIONS: Temporary work in developing countries may result in imported lead poisoning. Differential diagnosis of this unusual condition requires careful medical history collection and specific toxicological analysis. Preventive measures for workers going abroad are needed.

Determination of Se(IV), Cd(II) and Pb(II) ions in homeopathic drugs by inversion voltammetry method.

The conditions for identification and quantification of Se(IV), Cd(II) and Pb(II) ions in homeopathic drugs by inversion voltammetry method with the use of EAGRAPH software were established. The studies proved that the method was of high sensitivity in established conditions. The detection limits were 0.66 microg/mL, 0.08 microg/mL and 0.12 microg/mL for Se(IV), Pb(II) and Cd(II) ions, respectively. This method was characterized by repeatability of measurements, a wide range of linearity and satisfactory percent recovery.

[Case of lead nephropathy due to chronic occupational lead exposure].

We report a case of a patient with chronic kidney disease likely due to lead nephropathy. He was a manufacturer of Buddhist altar fittings and had chronic lead exposure. The blood lead level was 41 microg/dL and urinary lead excretion at 24 hours after the administration of ethylenediaminetetraacetic acid (EDTA)was 600 microg (first time)and 687 microg (second time), respectively. Urinary lead excretion at 72 hours was 834 microg (first time) and 1,071 microg (second time), respectively. Renal biopsy showed interstitial fibrosis and focal monocyte infiltration. Lead content in the renal biopsy specimen was 130 ng/g of wet weight. We preformed weekly EDTA chelation therapy twelve times. During the therapy, serum creatinine was 1.1 mg/dL. The chelation therapy was interrupted by an episode of acute renal failure due to hypotension and heart failure. Urinary lead excretion exceeding 600 microg at 72 hours after chelation therapy indicated a lead body burden capable of causing lead nephropathy. In this case, urinary lead excretion exceeded 600 microg at 72 hours. Based on the report that repeated lead chelation therapy can slow the progression of non-diabetic chronic kidney disease with 72-hour-urinary lead excretion of 60-600 microg, we performed chelation therapy. This case suggests that lead nephropathy currently can occur in Japan. It is possible that renal dysfunction from lead nephropathy is reversed by minimizing lead exposure and chelation therapy. Lead nephropathy should be included in the differenitial diagnosis of causes of chronic kidney disease and occupational and environmental lead exposure should be investigated carefully during the medical history.

Blood, urine, and hair kinetic analysis following an acute lead intoxication.

A case of lead exposure resulting from the accidental ingestion of a lead-containing solution is reported. Because of clinical management rapidly performed through chelation therapy by 2,3-dimercaptopropane sulfonate sodium and meso-2,3-dimercaptosuccinic acid, blood lead levels of this 51-year-old patient were moderate (412.9 µg/L) and no clinical symptoms were observed. Numerous blood and urine samples were collected for kinetic analysis of lead elimination. However, we report the first case in which hair samples were analyzed to determine the excretion level of lead after acute intoxication.

Maternal exposure to low-level heavy metals during pregnancy and birth size.

We evaluated the effect of environmental, low-level exposure to heavy metals during pregnancy, as estimated by urine analysis, on birth size of the newborns. Spot urine samples were collected from unexposed 78 pregnant women in Tokyo during 2007 and 2008. The urinary concentrations of beryllium (Be), copper (Cu), arsenic (As), zinc (Zn), selenium (Se), molybdenum (Mo), cadmium (Cd), tin (Sn), antimony (Sb), and lead (Pb) were measured by ICP-MS. The birthweight (BW), length (BL) and head circumference (HC) of the newborns delivered to the subjects were measured and relationship with urinary metal concentration was examined. The geometric mean concentration of urinary Be, Cu, As, Zn, Se, Mo, Cd, Sn, Sb, and Pb were 0.031, 12.8, 393, 76.9, 37.6, 79.0, 0.766, 0.232, < 0.21, 0.483 microg g-creatinine(-1), respectively. The mean birth size of the newborn was close to the national average value in Japan. Stepwise multiple regression analysis using birth size as a dependent variable and urinary metal concentrations and covariates as independent variables extracted urinary Cd with a significant negative standardized partial regression coefficient (beta) for BW along with gestational age and maternal BMI. For HC, Sn was selected with a negative beta. The present study suggested that even a low-level Cd body burden of general population has slight but significant negative effect on BW.

Lead-induced peripheral neuropathy following Ayurvedic medication.

Lead poisoning following intake of Ayurvedic medication is one of the recent areas of concern. We report a case of a 58-year-old type II diabetic man who was stable with diet control and 30 mg pioglitazone per day. He took Ayurvedic medication for generalized weakness and developed peripheral neuropathy following its intake. He was found to have high blood and urinary lead levels and was diagnosed to have subacute lead poisoning. He was treated with d-Penicillamine for 8 weeks, following which his lead levels became normal. The use of d-Penicillamine was proved highly effective in treating a case of lead poisoning.

Use of oral dimercaptosuccinic acid (succimer) in adult patients with inorganic lead poisoning.

BACKGROUND: Chelation therapy has been used as a means of reducing the body burden of lead for five decades. Intravenous sodium calcium edetate has been the preferred agent, but there is increasing evidence that dimercaptosuccinic acid (DMSA) is also a potent chelator of lead. METHODS: Oral DMSA 30 mg/kg/day was administered to adults with blood lead concentrations > or = 50 microg/dl. The impact of DMSA on urine lead excretion, on blood lead concentrations and on symptoms was observed. The incidence and severity of adverse effects was also recorded. RESULTS: Thirty-five courses were given to 17 patients. DMSA significantly (P < 0.0001) increased urine lead excretion and significantly (P < 0.0001) reduced blood lead concentrations. Mean daily urine lead excretion exceeded the pre-treatment value by a median of 12-fold with wide variation in response (IQR 8.9-14.8, 95% CI 10.1-14.6). Pre-treatment blood lead concentrations correlated well with 5-day urine lead excretion. Headache, lethargy and constipation improved or resolved in over half the patients within the first 2 days of chelation. DMSA was generally well tolerated, but one course was discontinued due to a severe mucocutaneous reaction. There was a transient increase in alanine aminotransferase (ALT) activity during 14% of chelations. DMSA caused a significant increase in urine copper (P < 0.0001) and zinc (P < 0.05) excretion. CONCLUSION: Oral DMSA 30 mg/kg/day is an effective antidote for lead poisoning, though there is a wide inter- and intra-individual variation in response.

[Effects of chelation therapy with succimer in young rabbits of moderate lead poisoning].

OBJECTIVE: To explore the effect of chelation therapy with succimer (DMSA) in male rabbits of moderate lead poisoning during juvenile stage. METHODS: Twenty-four 45-day-old male New Zealand rabbits were randomly divided into three groups (therapy group, TG; positive control group, PG and negative control group, NG, n=8). The TG and PG were orally exposed to lead acetate (5 mg x kg(-1) x d(-1)) for 6 weeks. Rabbits in TG were orally supplied DMSA 1050 mg/m2 in the first week and 700 mg/m2 in the next two weeks, while the other two groups wren't blood and urinary samples of all rabbits were collected per week. The tissues and organs of all rabbits were collected after 12 weeks. The blood lead levels (BLLs) were determined by atomic absorption spectrometer. The urine lead levels and the lead contents of tissue and organ were determined by inductively coupled plasma-mass spectrometry. Histopathology of tissue and organ was observed by light microscope. RESULTS: Compared with PG, the lead level in the morning urine of TG with DMSA chelating was increased significantly. The level was peaked at (1246.96 +/- 157.91) microg/L on the first day after chelating. While the base line was (40.97 +/- 1.77) microg/L before chelating. Meanwhile, the BLLs were sharply declined from (429.63 +/- 10.82) microg/L to (238.50 +/- 11.82) microg/L. The urine lead levels of TG decreased through the 3-week chelating and 3-week discontinuation. The urine lead levels of these two groups were significantly different (F=2934.35, P<0.01). Compared to each two groups in these three groups, there were significant difference (P<0.01). The authors found the reversion of BLLs in first week after stop chelating. The BLLs of PG presented the slow course of declining in the same time, were (135.50 +/- 7.09) microg/L, very close to the level of TG for (149.88 +/- 11.39) microg/L. Compared with treatment discontinuation for 3 weeks, the urine lead levels and the body weight gain of the therapy group increased more than that of PG, and the BLLs and the lead concentrations in tissues and organs decreased more than that of PG, and histopathology in the liver tissues and testicle tissues were improved. CONCLUSION: DMSA chelating for the rodent models of moderate lead poisoning might reduce the BLLs and soft tissue lead contents quickly and effectively, decrease toxic effects of lead in a short period of time, thus alleviate the impairment of lead poisoning on tissues and organs by decreasing lead burden, and bring out improvement on the growth retardation caused by lead poisoning.

Determining urinary trace elements (Cu, Zn, Pb, As, and Se) in patients with bladder cancer.

OBJECTIVES: Trace elements are essential components of biological structures, but they can be toxic at concentrations beyond those necessary for their biological functions. METHODS: A study group of 30 patients with bladder cancer and a control group of 30 healthy volunteers were measured for trace elements using a graphite furnace atomic absorption spectrophotometer. RESULTS: Urinary zinc and selenium levels in patients were significantly (P < 0.05) higher than those in controls, but urinary copper, arsenic, and lead were not significantly different. CONCLUSION: This case-control study suggests that zinc and selenium concentrations are associated with the proliferation of bladder cancer cells because zinc and selenium are excreted in the urine of bladder cancer patients.