Neurobehavioural effects of occupational exposure to cadmium: a cross sectional epidemiological study.

BACKGROUND: A patient with unexplained minor behavioural changes associated with an axonal sensorimotor polyneuropathy had a history of chronic occupational exposure to cadmium (Cd). Although animal studies have shown that Cd is a potent neurotoxicant, little is known about its toxicity for the human central nervous system. The aim of this study was to investigate the toxic potential of chronic occupational exposure to Cd on neurobehavioural functions. METHODS: A cross sectional epidemiological study was conducted ina group of Cd workers and an age matched control group. Eighty nine adult men (42 exposed to Cd and 47 control workers) were given a blinded standardised examination that consisted of computer assisted neurobehavioural tests (neurobehavioural examination system), a validated questionnaire to assess neurotoxic complaints (neurotoxicity symptom checklist--60, NSC-60), and a standardised self administered questionnaire to detect complaints consistent with peripheral neuropathy and dysfunction of the autonomic nervous system. Historical and current data on biomonitoring of exposure to Cd, either the highest value of Cd in urine (CdU in microgram Cd/g creatinine) of each Cd worker during work (CdUmax) or the current value (CdUcurrent) of each control, were available as well as data on microproteinuria. RESULTS: Cd workers (CdUmax: mean (range), 12.6 (0.4-38.4)) performed worse than the controls (CdUcurrent: mean (range), 0.7 (0.1-2.0)) on visuomotor tasks, symbol digit substitution (p = 0.008), and simple reaction time to direction (p = 0.058) or location (p = 0.042) of a stimulus. In multiple linear regression analysis, symbol digit substitution, simple direction reaction time test, and simple location reaction time test were significantly related to CdUmax, (beta = 0.35 (p < 0.001), beta = 0.25 (p = 0.012), and beta = 0.23 (p = 0.021) respectively). More complaints consistent with peripheral neuropathy (p = 0.004), complaints about equilibrium (p = 0.015), and complaints about concentration ability (p = 0.053) were found in the group exposed to Cd than in the control group, and these variables correlated positively with CdUmax (peripheral neuropathy: beta = 0.38, p < 0.001; equilibrium: beta = 0.22, p = 0.057; concentration ability: beta = 0.27, p = 0.020). CONCLUSION: Slowing of visuomotor functioning on neurobehavioural testing and increase in complaints consistent with peripheral neuropathy, complaints about equilibrium, and complaints about concentration ability were dose dependently associated with CdU. Age, exposure to other neurotoxicants, or status of renal function could not explain these findings. The present study also indicates that an excess of complaints may be detected in Cd workers before signs of microproteinuria induced by Cd occur.

Cadmium: a possible etiological factor in peripheral polyneuropathy.

Uncovering the exact cause of polyneuropathies seems to be impossible in up to 24% of the cases. Experimental studies have shown that cadmium (Cd), which is a well-known occupational and environmental hazard, can be a potent neurotoxicant for the peripheral nervous system. Moreover, Cd has a half-life of more than 15 years in humans. We hypothesize that older workers may be more susceptible to an increased Cd body burden, and may develop a peripheral polyneuropathy (PNP) over time. A blinded epidemiological survey was performed in 13 retired, long-term Cd-exposed workers and 19 age-matched controls. Historical Cd biomonitoring data were available over the last two decades. A neurological clinical examination, nerve conduction studies, and needle EMG were performed, and a standardized questionnaire was given to evaluate polyneuropathy complaints. If two of the following four criteria, i.e. complaints of polyneuropathy, neurophysiological changes compatible with polyneuropathy, distal symmetrical areflexia, or distal symmetrical anesthesia for vibration sense, temperature or blunt-sharp discrimination were present, the diagnosis of PNP was made. Two (11%) of the control and seven (54%) of the retired Cd workers met the PNP criteria OR: 9.92 (95%CI 1.60-61.6), Fisher exact test p=0.015. The existence of a polyneuropathy was related to the level of the Cd body burden as reflected by urinary Cd multiple logistic regression p=0.016, OR=1.26, (95%CI, 1.04-1.51), but not to blood lead (p=0.352). Our findings favour the hypothesis of a promoting role of increased cadmium body burden in the development of PNP at older age.

Reversibility of microproteinuria in cadmium workers with incipient tubular dysfunction after reduction of exposure.

The study aimed at assessing the evolution of cadmium (Cd)-induced renal tubular dysfunction in Cd workers according to the severity of the microproteinuria observed at the time the exposure was substantially decreased. Male workers employed in the Cd production industry for whom formerly high exposure had markedly decreased by 1984 and for whom standardized medical data were available during two observation periods (1980-1984 and 1990-1992) were eligible for the study. A total of 32 Cd workers fulfilling this profile were divided into two groups on the basis of historical records of urinary Cd concentration (Cd-U) covering the period until 1984. The workers with Cd-U values of > 10 micrograms Cd/g creatinine were subdivided further on the basis of the urinary concentration of beta 2-microglobulin (beta 2 MG-U) measured during the first observation period (1980-1984). In each group, the tubular microproteinuria as reflected by beta 2 MG-U and the concentration of retinol-binding protein in urine as well as the internal Cd dose as reflected by the concentration of Cd in blood and urine were compared between the first and second (1990-1992) observation periods. Increased microproteinuria was often diagnosed in cases with Cd-U values of > 10 micrograms Cd/g creatinine. The evolution of tubular renal function has been found to depend on the extent of the body burden of Cd (as reflected by Cd-U) and the severity of the initial microproteinuria at the time high Cd exposure was reduced or ceased. When reduction of Cd exposure took place while beta 2 MG-U did not exceed the upper reference limit of 300 micrograms/g creatinine, the risk of developing tubular dysfunction at a later stage was likely to be low, even in cases with historical Cd-U values occasionally > 10 but always < 20 micrograms Cd/g creatinine. When the microproteinuria was mild (beta 2 MG-U > 300 and < or = 1,500 micrograms/g creatinine) at the time exposure was reduced, and the historical Cd-U values had never exceeded 20 micrograms Cd/g creatinine, there was indication of a reversible tubulotoxic effect of Cd. When severe microproteinuria (beta 2 MG-U > 1,500 micrograms/g creatinine) was diagnosed in combination with historical Cd-U values exceeding 20 micrograms Cd/g creatinine, Cd-induced tubular dysfunction was progressive in spite of reduction or cessation of Cd exposure.

Quantification of the extent and severity of perfusion defects in canine myocardium by PET polar mapping.

UNLABELLED: This study validates perfusion defect extent and severity as derived by PET polar maps in vivo against measurements derived from radiolabeled microspheres. METHODS: In seven open-chest dogs, either the left anterior descending (n = 11) or left circumflex coronary artery (n = 13) were ligated sequentially from distal to proximal. After each occlusion, gated PET images were acquired with 13N-ammonia (20 mCi) while radiolabeled microspheres were administered into the left atrium. The transaxial PET images were reoriented into left ventricular short-axis cuts, including the apex, and polar maps were generated from circumferential activity profiles. PET polar maps were then compared with polar maps derived from microspheres after normal databases for 13N-ammonia and for microspheres were established. Nitrogen-13 or microsphere activities of less than 1.5 s.d. below the mean were defined as hypoperfused. RESULTS: The extent (percent of left ventricular mass) and mean severity of the hypoperfused myocardium in the postmortem microsphere measurements ranged from 3% to 69% and 3% to 58%, respectively. The estimated extent by summed PET and by microspheres correlated by y = 4.95 + 0.95x (r = 0.91, s.e.e. = 0.085, p < 0.001) and mean severity by y = 5.52 + 0.87x (r = 0.85, s.e.e. = 0.101, p < 0.001). The extent and severity were similar for summed and gated PET studies. CONCLUSION: The current study validated a polar map approach that provides accurate, quantitative assessment of the extent and severity of myocardial perfusion defects in vivo. Gating did not yield an improved correlation between PET and microsphere measurements. Thus, ungated PET images can be used to assess accurately the extent and severity of perfusion defects.