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“The purpose of the present study was to evaluate in a novel manner the arsenic exposure of humans living in two towns in Northeastern Chile. Residents of one town drink water containing 593 microg As/l. Those in the control town drink water containing 21 microg As/l. Our hypothesis was that the administration of the chelating agent, 2,3-dimercaptopropane-1-sulfonic acid, Na salt (DMPS, DIMAVAL) would increase the urinary excretion of arsenic, alter the urinary profile of arsenic species and thus result in a better indication of the body load of arsenic and a better biomarker for arsenic exposure. The method used to evaluate these subjects was to give them 300 mg DMPS by mouth, after an overnight fast, and collect urine at specified time periods. The urine samples were analyzed for inorganic arsenic, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and total arsenic by hydride generation and atomic absorption spectrophotometry. The results indicated that: 1) During the 2-hr period after DMPS administration, MMA represented 42%, inorganic As, 20 to 22% and DMA, 37 to 38% of the total urinary arsenic. The usual range of the MMA percentage in human urine has been 10 to 20%. The % MMA increased almost equally for both the arsenic-exposed and control subjects. 2) The exposed subjects had a greater urinary excretion of total arsenic, before and after DMPS administration, than the control subjects. 3) Although buccal cells were obtained only from a few subjects, the prevalence of mononucleated buccal cells, an indication of genotoxicity, was 5-fold greater for those who consumed drinking water with the higher arsenic content than among control subjects. Our conclusions are that 1) DMPS has a highly specific effect in humans on MMA metabolism and/or urinary excretion; 2) the human body stores substantial amounts of arsenic; and 3) the urinary arsenic concentration after DMPS administration may be more indicative of the body burden of arsenic because it was greater than that found before DMPS was given.”

In 31 patients with osteonecrosis (primarily of the hip), 74% had 1 or more primary coagulation disorders. In 18 patients, 15 (83%) who had coagulation disorders, the osteonecrosis was initially identified as idiopathic and was not associated with known underlying drugs (glucocorticoids) or diseases (alcoholism, sickle cell disease, Gaucher’s disease). In 13 patients, 8 (62 %) who had coagulation disorders, the osteonecrosis was initially identified as secondary, and was associated with glucocorticoids in 12 patients, and with alcoholism in 1. The coagulation disorders included thrombhophilia (increased tendency to intravascular thrombosis) and hypofibrinolysis (reduced ability to lyse thrombi). Of the 18 patients initially thought to have idiopathic osteonecrosis, thrombophilia alone was found in 12% (resistance to activated protein C in 6%, low protein C in 6%), hypofibrinolysis alone was found in 50% (high lipoprotein(a) in 44%, low stimulated tissue plasminogen activator activity was found in 6%), and mixed thrombophilia hypofibrinolysis was found in 22%. Resistance to activated protein C was more common in these 18 patients than in healthy controls (11% versus 0%), as was high lipoprotein(a) (67% versus 20%). Of the 13 patients with secondary osteonecrosis, thrombophilia alone was found in 8% (low protein C), hypofibrinolysis alone was found in 30% (high Lp(a) in 15%, low tissue plasminogen activator activity in 15%), and mixed thrombophilia hypofibrinolysis was found in 23%. Low tissue plasminogen activator activity was more common in the 13 patients with secondary osteonecrosis than in controls (27% versus 7%), as was low protein C (23% versus 0%). In aggregate, these findings lead us to the speculation that primary, heritable thrombophilia or hypofibrinolysis causes thrombotic venous occlusion in the head of the femur, leading to venous hypertension and hypoxic death of bone (osteonecrosis).

“Concerns have been expressed regarding the health risks posed by chemical exposures from dental restorative materials. Dental materials are exempted from the pre?market review provisions for medical devices in Canada and, therefore, information on the risks of potential chemical exposures arising from such materials is lacking. An assessment of components and degradation products of the class of dental materials known as composite resins was undertaken to provide such chemical exposure and risk information.

A probabilistic assessment was undertaken of adult exposures to two principal components of composite resins – silica, bisphenol-A glycidylmethacrylate (BIS-GMA) — and two degradation products of BIS-GMA — formaldehyde and methacrylic acid. Assuming that the Canadian adult population with fillings had only composite resin materials, results indicated that average exposures to formaldehyde and methacrylic acid were 10,000 times and 1,600,000 times lower, respectively, than relevant reference doses. Worst case exposures were also well below applicable reference levels. Risks posed by exposures to BIS-GMA and silica could not be assessed due to a lack of published ingestion reference doses for these substances.

Gaps in the data base relating to the risks posed by composite resin dental materials were discussed, particularly in reference to the recently reported estrogenic potential of other degradation products of BIS-GMA.”

In a case-control study, we investigated the possible etiologic relevance to Parkinson’s disease (PD) of rural factors such as farming activity, pesticide exposures, well-water drinking, and animal contacts; toxicologic exposures such as wood preservatives, heavy metals, and solvents; general anesthesia; head trauma; and differences in the intrauterine environment. We recruited 380 patients in nine German clinics, 379 neighborhood control subjects, and 376 regional control subjects in the largest case-control study investigating such factors and collected data in structured personal interviews using conditional logistic regression to control for educational status and cigarette smoking. The latter was strongly inversely associated with PD. There were significantly elevated odds ratios (OR) for pesticide use, in particular, for organochlorines and alkylated phosphates, but no association was present between PD and other rural factors. A significantly elevated OR was present for exposure to wood preservatives. Subjective assessment by the probands indicated that exposure to some heavy metals, solvents, exhaust fumes, and carbon monoxide was significantly more frequent among patients than control subjects, but this was not confirmed by a parallel assessment of job histories according to a job exposure matrix. Patients had undergone general anesthesia and suffered severe head trauma more often than control subjects, but a dose-response gradient was not present. Patients reported a significantly larger number of amalgam-filled teeth before their illness than control subjects. The frequency of premature births and birth order did not differ between patients and control subjects. Patients reported significantly more relatives affected with PD than control subjects. These results support a role for environmental and genetic factors in the etiology of PD.

A 67-year-old man with a 12-year history of trigeminal neuralgia experienced multiple fainting episodes preceded by right facial pain. One episode resulted in cardiac arrest with successful resuscitation. Pacemaker insertion prevented further episodes of syncope despite the occurrence of pain. The fainting episodes and cardiac arrest are believed to be unusual manifestations of trigeminal neuralgia.

“Ethylene oxide is a gas used in some dental offices to sterilize equipment. In pregnant laboratory animals, ethylene oxide increases malformations and feral loss. Increased gestation length has also been reported. In humans, two studies have reported increased spontaneous abortions among ethylene oxide-exposed women, but few other data exist. We sent questionnaires to 7,000 dental assistants, age 18-39 years, registered in California in 1987; 4,856 responded (69%). We based our analysis on 1,320 women whose most recent pregnancy was conceived while working full-time. Thirty-two women reported exposure to ethylene oxide; unexposed dental assistants comprised the comparison group. We estimated relative risks of spontaneous abortion and preterm birth using a person-week model. We estimated relative risks of postterm birth (> or = 42 weeks) and a combined adverse outcomes model using logistic regression. Among exposed women, the age-adjusted relative risk of spontaneous abortion was 2.5 [95% confidence interval (CI) = 1.0-6.3], for preterm birth 2.7 (95% CI = 0.8-8.8), and for postterm birth 2.1 (95% CI = 0.7-5.9). The estimated relative risk of any of these adverse outcomes among exposed women was 2.5 (95% CI = 1.0-6.1) after adjusting for age, nitrous oxide, and number of mercury amalgams prepared. These data further implicate ethylene oxide as a possible reproductive toxicant in humans.”

Sevoflurane administration can result in increased serum inorganic fluoride ion concentrations, which have been associated with inhibition of renal concentrating ability. We measured serum fluoride levels, renal function, and recovery variables as a function of time in ASA grade I-III patients administered general anesthesia with isoflurane or sevoflurane for at least 1 h. Fifty patients were exposed to sevoflurane (< or = 2.4% inspired concentration) or isoflurane (< or = 1.9% inspired concentration) for maintenance of anesthesia as part of a multicenter trial. Blood was collected for determination of serum fluoride ion concentration, electrolytes, blood urea nitrogen, and creatinine at various time points pre- and postoperatively. Mean serum fluoride levels were significantly increased in sevoflurane versus isoflurane groups at all time points; the mean peak serum levels were 28.2 +/- 14 mumol/L at 1 h for sevoflurane and 5.08 +/- 4.35 mumol/L at 12 h for isoflurane. Sevoflurane-mediated increases in serum fluoride levels peaked at 1 h and, in general, decreased rapidly after discontinuation of the anesthesia. Three of 24 patients exposed to sevoflurane had one or more fluoride levels > 50 mumol/L. One of these patients had a serum inorganic fluoride ion level > 50 mumol/L at 12 h after sevoflurane, and an additional patient had fluoride levels > 33 mumol/L for up to 24 h after sevoflurane discontinuation. Those two patients also demonstrated an increase in serum blood urea nitrogen and creatinine at 24 h after sevoflurane administration compared with baseline. The elimination half-life of serum fluoride ion was 21.6 h. The results of this study suggest the possibility of sevoflurane induced nephrotoxicity.

“A recent report from Health Canada (Richardson 1995), regarding mercury exposure and risks from dental amalgam, has raised questions regarding the potential risks posed by all dental restorative materials. Dental materials used to repair carious teeth are exempted from the pre-market review provisions for medical devices, published under the Canadian Food and Drugs Act (HC 1996). As a result, there are no Canadian regulatory requirements for the safety evaluation of dental restorative materials. In Canada, these materials are reviewed by a dental materials committee of the Canadian Dental Association. As well, certification is provided by the Standards Council of Canada, in the form of CSA® approval. However, these review procedures do not include a formal evaluation of potential health risks posed by exposures to the components and degradation products of dental materials.”

On the basis of the findings of nine of our patients and our review of previously reported cases of diffuse sclerosing osteomyelitis and chronic recurrent multifocal osteomyelitis, we discuss the similarity of these two entities. Our nine patients had initially been given diagnoses of diffuse sclerosing osteomyelitis on the basis of their clinicopathologic findings. However, technetium 99m-MDP bone scans performed on four of them revealed multiple bone lesions leading to the diagnosis of chronic recurrent multifocal osteomyelitis. Furthermore, no clear difference between clinical features in the patients with multiple bone lesions and those in the patients with diffuse sclerosing osteomyelitis was found. We conclude that diffuse sclerosing osteomyelitis is an expression of chronic recurrent multifocal osteomyelitis.