Diagnostic chelation challenge with DMSA: a biomarker of long-term mercury exposure?

Chelation challenge testing has been used to assess the body burden of various metals. The best-known example is EDTA challenge in lead-exposed individuals. This study assessed diagnostic chelation challenge with dimercaptosuccinic acid (DMSA) as a measure of mercury body burden among mercury-exposed workers. Former employees at a chloralkali plant, for whom detailed exposure histories were available (n = 119), and unexposed controls (n = 101) completed 24-hr urine collections before and after the administration of two doses of DMSA, 10 mg/kg. The urinary response to DMSA was measured as both the absolute change and the relative change in mercury excretion. The average 24-hr mercury excretion was 4.3 microg/24 hr before chelation, and 7.8 microg/24 hr after chelation. There was no association between past occupational mercury exposure and the urinary excretion of mercury either before or after DMSA administration. There was also no association between urinary mercury excretion and the number of dental amalgam surfaces, in contrast to recent published results. We believe the most likely reason that DMSA chelation challenge failed to reflect past mercury exposure was the elapsed time (several years) since the exposure had ended. These results provide normative values for urinary mercury excretion both before and after DMSA challenge, and suggest that DMSA chelation challenge is not useful as a biomarker of past mercury exposure.

Health effects of long-term mercury exposure among chloralkali plant workers.

BACKGROUND: Inorganic mercury is toxic to the nervous system, kidneys, and reproductive system. We studied the health effects of mercury exposure among former employees of a chloralkali plant that operated from 1955 to 1994 in Georgia. METHODS: Former plant workers and unexposed workers from nearby employers were studied. Exposure was assessed with a job-exposure matrix based on historical measurements and personnel records. Health outcomes were assessed with interviews, physical examinations, neurological and neurobehavioral testing, renal function testing, and urinary porphyrin measurements. Exposure-disease associations were assessed with multivariate modeling. RESULTS: Exposed workers reported more symptoms, and tended toward more physical examination abnormalities, than unexposed workers. Exposed workers performed worse than unexposed subjects on some quantitative tests of vibration sense, motor speed and coordination, and tremor, and on one test of cognitive function. Few findings remained significant when exposure was modeled as a continuous variable. Neither renal function nor porphyrin excretion was associated with mercury exposure. CONCLUSIONS: Mercury-exposed chloralkali plant workers reported more symptoms than unexposed controls, but no strong associations were demonstrated with neurological or renal function or with porphyrin excretion.

Outbreak of tuberculosis associated with a floating card game in the rural south: lessons for tuberculosis contact investigations.

We investigated an outbreak of tuberculosis disease and infection in a rural southern county in which an average of less than one case per year had occurred in the previous 10 years. Nine cases of tuberculosis developed. Reinterview 19 months after the patient with the initial case presented revealed that he had participated in an illegal floating card game with two of the other patients; numerous other unacknowledged social connections among the patients existed. Restriction fragment length polymorphism typing revealed that mycobacteria isolated from five of six available specimens matched; the patient from whom the nonmatched mycobacterium was isolated had a coincident relapsed case. The infection rate among contacts decreased as the investigation expanded to include more than one-third of the county residents: from 51% of those named initially to 2% of those at a school screening and from 68% of those named by more than one patient to 20% of those named by only one patient. Maintaining effective tuberculosis control programs in areas in which the incidence is low will be a challenge as rates of tuberculosis continue to decline nationwide.

Effective peer responses to impaired nursing practice.

Chemical dependency within the nursing profession continues to be a significant problem affecting health care delivery. This article presents up-to-date information on responding to a peer who is demonstrating impaired nursing practice. Specific information on the scope and impact of the problem, indicators of impairment, return to practice, and fitness to practice issues are addressed. In addition, the authors share their insight regarding progress, trends, and challenges in responding to impaired practice.

Urinary excretion and DNA binding of coal tar components in B6C3F1 mice following ingestion.

Urinary excretion of polycyclic aromatic hydrocarbon (PAH) metabolites and DNA binding of coal tar components in male mice were investigated following the ingestion of a coal tar adulterated diet. Male B6C3F1 mice were able to tolerate an F0927 basal gel diet which contained from 0.1 to 1% coal tar (tar weight/dry food weight) for 15 days. Mice maintained on a 0.1 and 0.2% coal tar diet had body weight gains similar to those of control animals. However, mice maintained on the 0.5 and 1.0% diet had body weight gains considerably lower than control values. Chemical-DNA adduct formation was detected and quantified in lung and forestomach tissue of animals on 0.1, 0.2, 0.5, and 1% coal tar containing diets. A dose-related effect was observed in lung DNA adduct formation while no dose effect was observed in forestomach tissue. In addition, overall adduct levels in lung tissue were considerably higher than forestomach levels for animals on the 0.5 or 1% diet. In contrast, DNA adduct levels were highest in the forestomach of animals on diets lower in coal tar content (0.1 or 0.2%). Chemical-DNA adducts of coal tar components were also evaluated for four other coal tar samples which varied in chemical composition. Mice were maintained on diets containing 0.25% of each coal tar for 15 days. Chemical-DNA adducts were detected in lung, liver, and spleen for all animals receiving these coal tar diets. DNA adduct patterns were similar while quantitative differences were observed between coal tar samples and tissue sites. Highest adduct levels were detected in lung DNA. Benzo[a]pyrene content in coal tar samples could not account for the DNA adduct levels observed with coal tar ingestion. The urinary excretion of select PAH metabolites following coal tar ingestion was evaluated by using urine collected on days 1 and 14 of diet administration. The levels of 1-hydroxypyrene in urine, the major PAH metabolite detected, correlated with the pyrene content of these coal tars. These data demonstrate that coal tar components are readily bioavailable following ingestion.

Lactate oxidation by three segments of the rabbit proximal tubule.

Oxidation of [U14C]lactate to 14CO2 was measured in vitro, in nonperfused anatomically defined segments of rabbit proximal tubule (S1, proximal convoluted, and S2 and S3, proximal straight tubules). The rate of lactate oxidation was similar in S2 and S3 segments, and within the range of lactate oxidation rates measured in vivo. In contrast, the oxidation rate of S1 segments was significantly lower than that of S2 or S3. In proximal straight tubules, lactate oxidation was inhibited by incubation at 0 degrees C, or by application of 1 mM ouabain. To determine if the rate of transepithelial transport affected the rate of lactate oxidation, lactate oxidation was measured in proximal straight tubules after the lumen had been opened by perfusion with Ringer's containing 10 mM polyethylene glycol. No difference in lactate oxidation rate was observed between tubules with patent lumina and nonperfused tubules. These results suggest that the various segments of the renal proximal tubule have different metabolic characteristics, and that the rate of substrate oxidation is related to the activity of the Na+, K+-ATPase.

Autonomic failure with postprandial hypotension: case report.

A case of severe symptomatic postprandial hypotension associated with idiopathic autonomic neuropathy and endogenous hyperinsulinaemia is described. The possible mechanisms of the blood pressure changes are discussed. Attempts at treatment included dietary change; the use of vasodilators with salt and fludrocortisone; elastic stockings, antigravity suit; diazoxide and bromocriptine.

Rat thymic dihydrotestosterone receptor: preparation, location and physiochemical properties.

Castration in the male rat has been shown to produce enlargement of the thymus gland while treatment with dihydrotestosterone (DHT) results in a decrease in thymic size in these animals. To determine if these changes might be receptor mediated, thymus tissue from castrate male rats was removed and homogenized in buffer and centrifuged to produce cytosol. By Scatchard plot analysis, it was shown that a specific DHT receptor was present at a concentration of 0.24 +/- 0.02 pmoles/g tissue and it possessed a KA of 2.51 +/- 0.45 x 10(9)M-1. This thymic DHT receptor sedimented on 5--20% sucrose gradients in the 8s region. By competition analysis it was found that testosterone only partially competed (25%) for this receptor, with virtually no binding noted for estradiol, progesterone, and cortisol. The receptor was found to be localized in the reticuloepithelial matrix of the thymus and was not present in the thymic lymphocyte fraction.

Anticonvulsant-induced osteomalacia.

Four cases of osteomalacia associated with the long term consumption of phenytoin (Dilantin) were admitted to a geriatric unit in a two-month period. No other cause for their disease was found. The diagnosis was made on biochemical data and no bone biopsy was obtained. Radiographic evidence was found in two cases only.

The in-vitro and in-vito effects of diethylstilbestrol on testicular synthesis of testosterone.

The effect of diethylstilbestrol (DES) on the percent conversion of a 14C-progesterone (14C-P) substrate to 14C-testosterone (14C-T) when added to incubates fo rat testicular homogenates has been measured. Similarly the effect of DES administered parenterally to intact adult rats at 9 dose regimens on such conversion has been evaluated. In addition, in the latter group serum luteinizing hormone (LH) levels were assessed simultaneously. DES added in-vitro significantly reduced T formation at every level. Only the large parenteral dose of DES affected T synthesis after 24 hours, while every parenteral dose significantly reduced T synthesis with 4 and 8 day regimens. Mean serum LH levels failed to reflect a significant decrease at the 1 and 4 day dose level, but did decrease significantly in 2 of 3 groups on the 8 day regimen. These results suggest that there is a direct effect of DES at a testicular level inhibiting T synthesis not associated with a simultaneous drop in mean serum LH levels. A measurable decrease in LH concentration does occur with continued treatment.

PIP: The effect of diethylstilbestrol (DES) on the conversion of carbon-14-progesterone to carbon-14-testosterone in incubates of rat testicular homogenates was studied, as well as the in vivo effect of DES, administered parenterally, on the conversion of the hormones and levels of luteinizing hormone (LH). In vitro, DES significantly diminished testosterone formation at every dose level (p.01). DES, administered in repeated daily doses for 4 or 8 days, caused a markedly decreasing conversion to testosterone. The 1- and 4-day dose levels of DES did not produce significant changes in LH levels (p .1), though an 8-day regimen of 5 mg and 50 mg DES significantly decreased LH values (p .02, p .02, respectively). It is suggested that DES has a direct effect, at the testicular level, in inhibiting the synthesis of testosterone, which is not associated with a drop in serum LH levels.