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Biomedical subjects

R R Lauwerys

Publications and source records attributed to R R Lauwerys.

At least 37 records · Page 2Linked to original sources
PubMed1994

Hypertension caused by low-level lead exposure: myth or fact?

BACKGROUND: Several reports on the possible association between low-level lead exposure and blood pressure reflect diverging views. This meta-analysis aimed to find a common denominator in the published literature and to estimate whether a relationship exists between blood pressure and levels of lead in the blood. METHODS: Of the studies reviewed, 23 provided sufficient details to be considered. The meta-analysis included 33 groups with a total of 33 141 subjects, who had been recruited from the general population in 13 surveys and from occupational groups in 10 studies. In all but four studies the results were adjusted for age, and most studies took into account additional confounding factors. RESULTS: The association between blood pressure and blood lead was similar in both men and women. In the combined studies, a twofold increase in blood lead concentration was associated with a 1.0 mmHg rise in systolic pressure (confidence interval 0.4-1.6 mmHg; P = 0.002) and with a 0.6 mmHg increase in diastolic pressure (confidence interval 0.2-1.0 mmHg; P = 0.02). The association with systolic pressure strongly relied on the inclusion of a large study (n = 3851) in which women's blood pressure was measured at the end of pregnancy. The association with diastolic pressure was largely due to a population survey in the USA (n = 6289). There was no relationship across studies between the strength of the blood pressure-blood lead relationship and the mean blood lead concentration. CONCLUSION: The published evidence suggests that there can only be a weak positive association between blood pressure and lead exposure. Any such relationship may not be causal and is unlikely to entail any public-health implication in terms of hypertension-related complications. Nevertheless, these assumptions need to be confirmed in prospective population studies.

Blood Pressure↗
PubMed1994

Cadmium: exposure markers as predictors of nephrotoxic effects.

Cadmium (Cd) is a cumulative element with a biological half-life of > 10 years in humans. The total amount of Cd accumulated in the liver and in the kidney can be measured in vivo by neutron activation (or x-ray fluorescence), but this technique does not necessarily measure the fraction that is biologically active. At low exposure (i.e., general environmental exposure or moderate occupational exposure), blood Cd is mainly influenced by the last 2 to 3 months of exposure. Under such conditions, the Cd concentration in urine mainly reflects the amount of Cd stored in the body, particularly in the kidney. In Europe and the US, the Cd reference values are usually < 2 nmol/mmol creatinine. Because most of the Cd in urine is probably bound to metallothionein, the changes in the urinary metallothionein concentration parallel those of Cd. The determination of Cd concentration in hair is of limited value because in humans it is difficult to distinguish between externally deposited and endogenous Cd. Fecal Cd is a good indicator of the oral daily intake. The results of several cross-sectional epidemiologic studies of the relation between the prevalence of renal dysfunction and Cd concentration in urine led us to propose a biological limit value for Cd of 5 and 2 nmol/mmol creatine for adult male workers and the general population, respectively.

Adult↗
PubMed1993

Short report: low-level lead exposure does not increase the blood pressure in the general population. Cadmibel Study Group.

OBJECTIVE: Long-term exposure to high concentrations of lead may adversely affect several organ systems, but the possible influence of low-level lead exposure on blood pressure remains debatable. The present study examined this relationship in a cross-sectional population survey. METHODS: Blood pressure and lead exposure were measured in 1648 subjects (827 males, 821 females; mean age 45 years), drawn at random from the general population, but not being treated for hypertension. RESULTS: Systolic/diastolic blood pressure averaged 131/77 mmHg in the males and 124/74 mmHg in the females. Blood lead was higher in males than in females (0.5 versus 0.3 mumol/l), but the opposite was observed for zinc protoporphyrin (1.0 versus 1.1 micrograms/g haemoglobin). After adjustment for significant covariates (age, body mass index, pulse rate, serum creatinine and serum calcium, and for contraceptive pill intake and menopause in females), systolic pressure was negatively correlated with blood lead in males; the partial correlations with blood lead were not significant for systolic pressure in females nor for diastolic pressure in either sex. Neither males nor females showed a significant relationship between blood pressure and lead exposure assessed from the zinc protoporphyrin level in blood. CONCLUSIONS: This study does not support the hypothesis that exposure to lead is associated with increased blood pressure in the population at large.

Adult↗
PubMed1993

Markers of early renal changes induced by industrial pollutants. I. Application to workers exposed to mercury vapour.

Several markers of renal changes have been measured in a cohort of 50 workers exposed to elemental mercury (Hg) and in 50 control workers. After application of selection criteria 44 exposed and 49 control workers were retained for the final statistical analysis. Exposed workers excreted on average 22 micrograms Hg/g creatinine and their mean duration of exposure was 11 years. Three types of renal markers were studied--namely, functional markers (creatinine and beta 2-microglobulin in serum, urinary proteins of low or high molecular weight); cytotoxicity markers (tubular antigens and enzymes in urine), and biochemical markers (eicosanoids, thromboxane, fibronectin, kallikrein, sialic acid, glycosaminoglycans in urine, red blood cell membrane negative charges). Several bloodborne indicators of polyclonal activation were also measured to test the hypothesis that an immune mechanism might be involved in the renal toxicity of elemental Hg. The main renal changes associated with exposure to Hg were indicative of tubular cytotoxicity (increased leakage of tubular antigens and enzymes in urine) and biochemical alterations (decreased urinary excretion of some eicosanoids and glycosaminoglycans and lowering of urinary pH). The concentrations of anti-DNA antibodies and total immunoglobulin E in serum were also positively associated with the concentration of Hg in urine and in blood respectively. The renal effects were mainly found in workers excreting more than 50 micrograms Hg/g creatinine, which corroborates our previous estimate of the biological threshold of Hg in urine. As these effects, however, were unrelated to the duration of exposure and not accompanied by functional changes (for example, microproteinuria), they may not necessarily represent clinically significant alterations of renal function.

Adult↗
PubMed1993

Markers of early renal changes induced by industrial pollutants. II. Application to workers exposed to lead.

The present study has been carried out in the framework of a collaborative research project on the development of new markers of nephrotoxicity. A battery of more than 20 potential indicators of renal changes has been applied to 50 workers exposed to lead (Pb) and 50 control subjects. After application of selection criteria 41 exposed and 41 control workers were eventually retained for the final statistical analysis. The average blood Pb concentration of exposed workers was 480 micrograms/l and their mean duration of exposure was 14 years. The battery of tests included parameters capable of detecting functional deficits (for example, urinary proteins of low or high molecular weight), biochemical alterations (for example, urinary eicosanoids, glycosaminoglycans, sialic acid) or cell damage (for example, urinary tubular antigens or enzymes) at different sites of the nephron or the kidney. The most outstanding effect found in workers exposed to Pb was an interference with the renal synthesis of eicosanoids, resulting in lower urinary excretion of 6-keto-PGF1 alpha and an enhanced excretion of thromboxane (TXB2). The health significance of these biochemical alterations, detectable at low exposure to Pb is unknown. As they were not associated with any sign of renal dysfunction, they may represent reversible biochemical effects or only contribute to the degradation of the renal function from the onset of clinical Pb nephropathy. The urinary excretion of some tubular antigens was also positively associated with duration of exposure to Pb. Another effect of Pb that might deserve further study is a significant increase in urinary sialic acid concentration.

Adult↗
PubMed1993

Markers of early renal changes induced by industrial pollutants. III. Application to workers exposed to cadmium.

Cadmium (Cd) was the third heavy metal investigated in the European collaborative research project on the development and validation of new markers of nephrotoxicity. Fifty workers exposed to Cd and 50 control workers were examined. After application of selection criteria 37 workers (mean age 43) exposed to Cd for an average of 11.3 years; and 43 age matched referents were retained for final analysis. The average concentrations of Cd in blood (Cd-B) and urine (Cd-U) of exposed workers were 5.5 micrograms Cd/l and 5.4 micrograms Cd/g creatinine respectively. By contrast with lead and mercury, Cd had a broad spectrum of effects on the kidney, producing significant alterations in amounts of almost all potential indicators of nephrotoxicity that were measured in urine--namely, low and high molecular weight proteins, kidney derived antigens or enzymes, prostanoids, and various other biochemical indices such as glycosaminoglycans and sialic acid. An increase in beta 2-microglobulin and a decrease of sialic acid concentration were found in serum. Dose-effect/response relations could be established between most of these markers and Cd-U or Cd-B. The thresholds of Cd-U associated with a significantly higher probability of change in these indicators were estimated by logistic regression analysis. Three main groups of thresholds could be identified: one around 2 micrograms Cd/g creatinine mainly associated with biochemical alterations, a second around 4 micrograms Cd/g creatinine for high molecular weight proteins and some tubular antigens or enzymes, and a third one around 10 micrograms Cd/g creatinine for low molecular weight proteins and other indicators. The recent recommendation by the American Conference of Governmental Industrial Hygienists (ACGIH) of 5 micrograms Cd/g creatinine in urine as the biological exposure limit for occupational exposure to Cd appears thus justified, although for most of the effects occurring around this threshold the link with the subsequent development of overt Cd nephropathy is not established. In that respect, the very early interference with production of some prostanoids (threshold 2 micrograms Cd/g creatinine) deserves further investigation; although this effect might contribute to protect the filtration capacity of the kidneys, it might also play a part in the toxicity of Cd on bone.

Adult↗
PubMed1993

Adducts to macromolecules in the biological monitoring of workers exposed to polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants. Human exposure occurs through diet, smoking, and polluted air. In some groups of workers exposed to PAHs, epidemiological studies have revealed an increased mortality risk for neoplasms. This paper reviews the principal methods that have been developed recently for the detection of PAH adducts to white blood cell DNA and blood proteins (hemoglobin, albumin) and summarizes observations made on occupationally exposed subjects.

Blood Proteins↗
PubMed1992

Nephropathies and exposure to perchloroethylene in dry-cleaners.

Even in specific risk groups, the relation between exposure to organic solvents and chronic renal diseases remains controversial. Thus, in a collaborative European study, we assessed the renal effects of occupational exposure to perchloroethylene (PCE) in dry-cleaners compared with matched controls who were simultaneously examined. Single high and low molecular weight proteins, kidney-derived antigens and enzymes, and prostanoids were measured in urine. beta 2-microglobulin, creatinine, laminin fragments, and anti-glomerular basement membrane antibodies were also measured in serum. A canonical function based on 23 such variables correctly classified 93% of individuals as either PCE-exposed or controls; with 13 markers, group membership was identified in 87% of subjects. Increased high molecular weight protein in urine was frequently (17/50 vs 1/50, p less than 0.0001) associated with tubular alterations. Changes were consistent with diffuse abnormalities along the nephron in workers exposed to low levels of PCE (median 15 parts per million). Generalised membrane disturbances might account for the increased release of laminin fragments, fibronectin, and glycosaminoglycans, for high molecular weight proteinuria, and for the increased shedding of epithelial membrane components from tubular cells with different location along the nephron (brush-border antigens and Tamm-Horsfall glycoprotein). These findings of early renal changes indicate that solvent-exposed subjects, especially dry-cleaners, need to be monitored for the possible development of chronic renal diseases.

Adolescent↗
PubMed1992

Impairment of renal function with increasing blood lead concentrations in the general population. The Cadmibel Study Group.

BACKGROUND: Nephropathy is known to occur in persons with heavy exposure to lead. Whether exposure to lead in the general population leads to impaired renal function is not known. METHODS: We studied renal function and indexes of lead exposure in a random population sample of 965 men and 1016 women (age range, 20 to 88 years). In all the subjects we measured creatinine clearance and blood concentrations of lead and zinc protoporphyrin (an indirect measure of blood lead level). RESULTS: The mean (+/- SD) creatinine clearance rate was 99 +/- 30 ml per minute in the men and 80 +/- 25 ml per minute in the women. In the men the geometric mean blood lead concentration was 114 micrograms per liter (0.55 mumol per liter) (range, 23 to 725 micrograms per liter [0.11 to 3.5 mumol per liter]), and in the women 75 micrograms per liter (0.36 mumol per liter) (range, 17 to 603 micrograms per liter [0.08 to 2.9 mumol per liter]); the zinc protoporphyrin values in blood averaged 1.0 and 1.1 micrograms per gram of hemoglobin, respectively. The creatinine clearance rate was inversely correlated with blood lead and zinc protoporphyrin values in the men and the women both before and after adjustments for age, bodymass index, and diuretic treatment. A 10-fold increase in blood lead concentration was associated with a reduction of 10 to 13 ml per minute in creatinine clearance. We also found a positive correlation between serum beta 2-microglobulin (which is inversely related to the glomerular filtration rate) and blood lead in men, between serum beta 2-microglobulin and zinc protoporphyrin in both sexes, and between serum creatinine and zinc protoporphyrin in men. CONCLUSIONS: Exposure to lead may impair renal function in the general population. The alternative hypothesis that renal impairment may lead to an increase in the blood lead concentration cannot be excluded, however.

Adult↗
PubMed1992

Transfer of cadmium from a sandy acidic soil to man: a population study.

This population study included 230 subjects (age range 20-83 years) who consumed vegetables grown in kitchen gardens on a sandy acidic soil (mean pH approximately 6.3). The study investigated the association between the Cd (cadmium) levels in blood and urine and the Cd concentration in the soil (range 0.2-44 ppm). Seventy-six subjects were current smokers and 122 participants lived in a district with known Cd pollution. Urinary Cd in the 230 subjects averaged 8.7 nmole/24 hr, (range 1.3 to 47 nmole/24 hr) after age adjustment positively correlated with the Cd level in the soil; a twofold increase of the Cd concentration in the soil was accompanied by a 7% rise in urinary Cd in men (R2 = 0.05; P = 0.04) and by a 4% rise in women (R2 = 0.02; P = 0.05). Blood Cd averaged 11.5 nmole/liter (range 1.8-41 nmole/liter) and was negatively associated with the Cd level in the soil. After adjustment for significant covariates (smoking and serum gamma-glutamyl transpeptidase in both sexes, and age and serum ferritin in women), a twofold increase in the Cd concentration in the soil was accompanied by a 6% decrease in blood Cd in men (R2 = 0.03; P = 0.09) and by a 10% decrease in women (R2 = 0.06; P less than 0.01). In conclusion, in a rural population, consuming vegetables grown on a sandy acidic soil, 2 to 4% of the variance of urinary Cd was directly related to the Cd level in the soil. The negative correlation with blood Cd, a measure of more recent exposure, was biased by the implementation of preventive measures in the polluted district.

Adult↗
PubMed1992

Intestinal-type alkaline phosphatase in urine as an indicator of mercury induced effects on the S3 segment of the proximal tubule.

Intestinal-type alkaline phosphatase (IAP) is a specific and sensitive marker for alterations of the S3 segment of the human proximal tubule, the preferred part for several nephrotoxins. We studied IAP and other renal parameters in mercury-exposed workers and their controls. IAP excretion is clearly increased in the exposed workers, compared to other parameters, indicating that the determination of this enzyme can be a useful screening test of renal effects in occupational mercury exposure.

Acetylglucosaminidase↗
PubMed1992

Assessment of the permissible exposure level to manganese in workers exposed to manganese dioxide dust.

The prevalence of neuropsychological and respiratory symptoms, lung ventilatory parameters, neurofunctional performances (visual reaction time, eye-hand coordination, hand steadiness, audioverbal short term memory), and several biological parameters (calcium, iron, luteinising hormone (LH), follicle stimulating hormone (FSH), and prolactin concentrations in serum, blood counts, manganese (Mn) concentration in blood and in urine) were examined in a group of workers (n = 92) exposed to MnO2 dust in a dry alkaline battery factory and a matched control group (n = 101). In the battery plant, the current exposure of the workers to airborne Mn was measured with personal samplers and amounted on average (geometric mean) to 215 and 948 micrograms Mn/m3 for respirable and total dust respectively. For each worker, the lifetime integrated exposure to respirable and total airborne Mn dust was also assessed. The geometric means of the Mn concentrations in blood (MnB) and in urine (MnU) were significantly higher in the Mn exposed group than in the control group (MnB 0.81 v 0.68 microgram/100 ml; MnU 0.84 v 0.09 microgram/g creatinine). On an individual basis, MnU and MnB were not related to various external exposure parameters (duration of exposure, current exposure, or lifetime integrated exposure to airborne Mn). On a group basis, a statistically significant association was found between MnU and current Mn concentrations in air. No appreciable difference between the exposed and the control workers was found with regard to the other biological measurements (calcium, LH, FSH, and prolactin in serum). Although the erythropoietic parameters and serum iron concentration were in the normal range for both groups, there was a statistically significant trend towards lower values in the Mn exposed workers. The prevalences of reported neuropsychological and respiratory symptoms, the lung function parameters, and the audioverbal short term memory scores did not differ between the control and exposed groups. The Mn workers, however, performed the other neurofunctional tests (visual reaction time, eye-hand coordination, hand steadiness) less satisfactorily than the control workers. For these tests, the prevalences of abnormal results were related to the lifetime integrated exposure to total and respirable Mn dust. On the basis of logistic regression analysis it may be inferred that an increased risk of peripheral tremor exists when the lifetime integrated exposure to Mn dust exceeds 3575 or 730 micrograms Mn/m3 x year for total and respirable dust respectively. The results clearly support a previous proposal by the authors to decrease the current time weighted average exposure to Mn dust.

Adolescent↗
PubMed1991

Urinary excretion of proteins and enzymes in workers exposed to hydrocarbons in a shoe factory.

A cross-sectional study was conducted to determine whether exposure to hydrocarbons in a shoe factory may produce renal effects that can be detected by determination of the urinary excretion of proteins and enzymes. The study population included 59 women who had been exposed to petroleum naphtha and toluene and 24 age-matched control women. The time-weighted average exposure to petroleum naphtha, toluene and ethylacetate was 1,619,81 and 160 mg/m3, respectively. The integrity of the renal structures or functions was assessed by measuring the urinary excretion of total protein, beta 2-microglobulin, retinol-binding protein, albumin, transferrin, lysozyme, lactate dehydrogenase and beta-N-acetylglucosaminidase (NAG). The only parameter that was significantly influenced by hydrocarbon exposure was the urinary activity of beta-N-acetylglucosaminidase. Although the health significance of this renal change, which was not accompanied by changes in the urinary excretion of low- or high-molecular-weight proteins, is unclear, the results of the present study are in agreement with our previous observations suggesting that long-term moderate exposure to solvents does not entail a significant risk for the development of nephrotoxicity.

Acetates↗
PubMed1991

Disturbance of sialic acid metabolism by chronic cadmium exposure and its relation to proteinuria.

In workers exposed to Cd (8 years on the average), we have found a significant decrease of sialic acid in erythrocyte membranes (22.61 +/- 1.84 vs 25.80 +/- 3.01 micrograms/mg of protein in controls, p less than 0.05) and an increase of sialic acid concentration in both urine (276.7 +/- 132.3 vs 174.5 +/- 70.9 micrograms/g of creatinine, p less than 0.05) and plasma (761.8 +/- 83.5 vs 640.4 +/- 70.7 micrograms/ml, p less than 0.01). In rats exposed to Cd (100 ppm in drinking water for 5.5 months), we have observed a reduction of the sialic acid level in erythrocyte membranes (31.4 +/- 1.2 vs 33.4 +/- 1.1 micrograms/mg of protein, p less than 0.01) and glomeruli (12.5 +/- 1.3 vs 13.9 +/- 1.6 micrograms/mg of protein, p less than 0.05). These effects in Cd treated rats were accompanied by a loss of the glomerular barrier selectively as reflected by an increased urinary output of albumin and transferrin. After 10 months of Cd exposure, the albuminuria and transferrinuria were negatively correlated with the sialic acid content of glomerular membranes (r = -0.47 and -0.51, p less than 0.05), which suggests that the depletion of sialic acid is involved in the loss of glomerular barrier function induced by long term Cd exposure. In Cd-treated rats, sialidase activity was enhanced in kidney cortex and in serum but not in glomeruli.

Adult↗
PubMed1991

Effects of exposure to cadmium on calcium metabolism: a population study.

The objective was to investigate the hypothesis that environmental exposure to cadmium may affect calcium metabolism in the population at large. The 1987 participants (965 men and 1022 women), from 20 to 80 years old, constituted a random sample of the population of four Belgian districts. The urinary excretion of cadmium, a measure of lifetime exposure, averaged 9.3 nmol/24 h in men (range 0.4-324 nmol/24 h) and 7.1 nmol/24 h (range 0.1-71 nmol/24 h) in women. Serum alkaline phosphatase activity and the urinary excretion of calcium correlated significantly and positively with urinary cadmium excretion in both men and women, and serum total calcium concentration negatively with urinary cadmium excretion in men only. The regression coefficients obtained after adjustment for significant covariates indicated that when urinary cadmium excretion increased twofold, serum alkaline phosphatase activity and urinary calcium excretion rose by 3-4% and 0.25 mmol/24 h respectively, whereas in men serum total calcium concentration fell by 6 mumol/l. After adjustment for significant covariates the relation between serum total calcium concentration and urinary cadmium excretion was not significant in women. The findings suggest that even at environmental exposure levels calcium metabolism is gradually affected, as cadmium accumulates in the body. The morbidity associated with this phenomenon in industrialised countries remains presently unknown and requires further investigation.

Adult↗