Environmental relative moldiness index and associations with home characteristics and infant wheeze.

Possible relationships between mold contamination, as described by the Environmental Relative Moldiness Index (ERMI), home characteristics, and the development of wheeze in the first year of life were evaluated among a cohort of urban infants (n = 103) in Syracuse, New York. Pregnant women with a history of asthma were recruited in 2001-2002 for the "Assessment of Urban Dwellings for Indoor Toxics" (AUDIT) study. When the infants were approximately 3 months of age, a home inspection was carried out and indoor environmental samples collected, including vacuumed house dust. ERMI levels in the Syracuse cohort homes were higher than the U.S. average, with an overall mean of 11.4. ERMI levels were significantly higher in homes with visible water problems (p = 0.023) and visible mold (p = 0.023). ERMI levels in apartments were significantly lower than the values measured in houses (p = 0.0003). While infants experiencing wheeze (38%) tended to live in homes with higher ERMI values than those without wheeze (ERMI values of 12.3 and 10.9, respectively), the differences did not reach statistical significance. A subset analysis limited to infants with living room samples who remained in the same home during the study (n = 25) was suggestive of an association between higher ERMI values and wheeze (p = 0.10). In summary, the ERMI is a standardized metric which allows for comparison of moldiness levels in homes across studies and regions in the United States. ERMI levels in Syracuse homes were skewed to the high end of the national scale. Higher ERMI levels were indicators of water problems, mold, and type of housing.

Quantification and micron-scale imaging of spatial distribution of trace beryllium in shrapnel fragments and metallurgic samples with correlative fluorescence detection method and secondary ion mass spectrometry (SIMS).

Recently, a report raised the possibility of shrapnel-induced chronic beryllium disease from long-term exposure to the surface of retained aluminum shrapnel fragments in the body. Since the shrapnel fragments contained trace beryllium, methodological developments were needed for beryllium quantification and to study its spatial distribution in relation to other matrix elements, such as aluminum and iron, in metallurgic samples. In this work, we developed methodology for quantification of trace beryllium in samples of shrapnel fragments and other metallurgic sample-types with main matrix of aluminum (aluminum cans from soda, beer, carbonated water and aluminum foil). Sample preparation procedures were developed for dissolving beryllium for its quantification with the fluorescence detection method for homogenized measurements. The spatial distribution of trace beryllium on the sample surface and in 3D was imaged with a dynamic secondary ion mass spectrometry instrument, CAMECA IMS 3f secondary ion mass spectrometry ion microscope. The beryllium content of shrapnel (∼100 ppb) was the same as the trace quantities of beryllium found in aluminum cans. The beryllium content of aluminum foil (∼25 ppb) was significantly lower than cans. SIMS imaging analysis revealed beryllium to be distributed in the form of low micron-sized particles and clusters distributed randomly in X-Y- and Z dimensions, and often in association with iron, in the main aluminum matrix of cans. These observations indicate a plausible formation of Be-Fe or Al-Be alloy in the matrix of cans. Further observations were made on fluids (carbonated water) for understanding if trace beryllium in cans leached out and contaminated the food product. A direct comparison of carbonated water in aluminum cans and plastic bottles revealed that beryllium was below the detection limits of the fluorescence detection method (∼0.01 ppb). These observations indicate that beryllium present in aluminum matrix was either present in an immobile form or its mobilization into the food product was prevented by a polymer coating on the inside of cans, a practice used in food industry to prevent contamination of food products. The lack of such coating in retained shrapnel fragments renders their surface a possible source of contamination for long-term exposure of tissues and fluids and induction of disease, as characterized in a recent study. Methodological developments reported here can be extended to studies of beryllium in electronics devices and components.

Chest wall shrapnel-induced beryllium-sensitization and associated pulmonary disease.

Chronic beryllium disease (CBD) is an exposure-related granulomatous disease mimicking sarcoidosis. Beryllium exposure-associated disease occurs mainly via inhalation, but skin may also be a source of sensitization. A 65-year-old male with a history of war-related shrapnel wounds was initially diagnosed with pulmonary sarcoidosis. Twenty years later, the possibility of a metal-related etiology for the lung disease was raised. A beryllium lymphocyte proliferation test, elemental analysis of removed shrapnel, and genetic studies were consistent with a diagnosis of CBD. This case demonstrates that retained beryllium-containing foreign bodies can be linked to a pathophysiologic response in the lung consistent with CBD.

Levels of household particulate matter and environmental tobacco smoke exposure in the first year of life for a cohort at risk for asthma in urban Syracuse, NY.

The Syracuse, NY, AUDIT (Assessment of Urban Dwellings for Indoor Toxics) study was designed to quantify asthma agent levels in the inner-city homes of a birth cohort whose mothers had a diagnosis of asthma. Risk of exposure to particulate matter (PM), particle number and tobacco smoke was assessed in 103 infants' homes. Repeat measurements were made in 44% of the homes. Infants also were examined on a quarterly basis during the first year of life to monitor their respiratory health and urine cotinine levels. Overall geometric mean (GM) values for PM(2.5) of 21.2 µg/m(3) and for PM(10) of 31.8 µg/m(3) were recorded in homes at visit 1. GM values for PM(2.5) and PM(10) in smoking homes were higher at 26.3 and 37.7 µg/m(3), while values in non-smoking homes were 12.7 and 21.2 µg/m(3) respectively. Fifty-four percent of mothers (55/103) smoked at some point in pregnancy (39% smoked throughout pregnancy). Environmental tobacco smoke (ETS) exposure occurred in 68% of homes during the infants' first year. Significant to this study was the size- and time-resolved monitoring of PM at 140 home visits and the classification of PM count data. PM number counts ranged from continuously low levels (little indoor activity) to continuously high counts (constant indoor activity), and recorded apparent instances of prolonged repeated cigarette smoking. Wheezing in the first year of life was recorded for 38% of the infants (39/103). Adjusted logistic regression modeling demonstrated that elevated levels of indoor PM(2.5) (≥ 15 µg/m(3)) were a significant risk factor for infant wheezing after controlling for infant gender, mothers' age and education level, season of home visit and presence of carpeting (OR 4.21; 95% CI 1.36-13.03; p=0.013). An elevated level of the nicotine metabolite cotinine in infant urine also was associated with infant wheezing after adjusting for infant gender, mothers' age and education level (OR 5.10; 95% CI 0.96-27.24; p=0.057). ETS exposure was pervasive in the AUDIT cohort and a risk for developing infants in this urban population.

Applying definitions of "asbestos" to environmental and "low-dose" exposure levels and health effects, particularly malignant mesothelioma.

Although asbestos research has been ongoing for decades, this increased knowledge has not led to consensus in many areas of the field. Two such areas of controversy include the specific definitions of asbestos, and limitations in understanding exposure-response relationships for various asbestos types and exposure levels and disease. This document reviews the current regulatory and mineralogical definitions and how variability in these definitions has led to difficulties in the discussion and comparison of both experimental laboratory and human epidemiological studies for asbestos. This review also examines the issues of exposure measurement in both animal and human studies, and discusses the impact of these issues on determination of cause for asbestos-related diseases. Limitations include the lack of detailed characterization and limited quantification of the fibers in most studies. Associated data gaps and research needs are also enumerated in this review.

Synchrotron X-ray analyses demonstrate phosphate-bound gadolinium in skin in nephrogenic systemic fibrosis.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is an incurable, debilitating disease found exclusively in patients with decreased kidney function and comprises a fibrosing disorder of the skin and systemic tissues. The disease is associated with exposure to gadolinium (Gd)-based contrast agents (GBCA) used in magnetic resonance imaging (MRI). Tissue samples from many patients with NSF contain micron-sized insoluble Gd-containing deposits. However, the precise composition and chemical nature of these particles is unclear. OBJECTIVES: To clarify the precise chemical structure of the Gd-containing deposits in NSF tissues. METHODS: Autopsy skin tissues from a patient with NSF were examined in situ using synchrotron X-ray fluorescence (SXRF) microscopy and extended X-ray absorption fine structure (EXAFS) spectroscopy and in correlation with light microscopy and the results of scanning electron microscopy /energy dispersive spectroscopy analyses. RESULTS: The insoluble Gd deposits were shown to contain Gd no longer coordinated by GBCA chelator molecules but rather in a sodium calcium phosphate material. SXRF microscopy shows a clear correlation between Gd, Ca and P. EXAFS spectroscopy shows a very different spectrum from the GBCAs, with Gd­P distances at 3·11 A and 3·11 A as well as Gd­Gd distances at an average of 4·05 A, consistent with a GdPO4 structure. CONCLUSIONS: This is the first direct evidence for the chemical release of Gd from GBCA in human tissue. This supports the physical­chemical, clinical and epidemiological data indicating a link between stability and dose of GBCA to the development of NSF.

Gadolinium-induced nephrogenic systemic fibrosis in a patient with an acute and transient kidney injury.

Nephrogenic systemic fibrosis (NSF) describes a characteristic fibrosing disorder which typically presents with indurated plaques on the trunk and extremities of patients with advanced renal disease. We present a case of biopsy-confirmed NSF in a patient with severe acute kidney injury with no prior history of renal disease. A 64-year-old man with an acute and severe decrease in glomerular filtration rate underwent magnetic resonance imaging studies with gadolinium contrast (Omniscan) and subsequently developed NSF. His renal disease had normalized at the time his skin disease developed. Skin biopsies revealed findings of NSF and scanning electron microscopy with energy-dispersive X-ray spectroscopy confirmed insoluble gadolinium within lesional tissue.

Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis.

BACKGROUND: Gadolinium (Gd)-based magnetic resonance contrast agents (GBMCA), including gadodiamide, have been identified as the probable causative agents of the serious disease, nephrogenic systemic fibrosis (NSF). OBJECTIVES: To investigate retained Gd-containing deposits in skin biopsies from patients with NSF and to determine their relative concentrations over time from administration of GBMCA. METHODS: An investigator-blinded retrospective study, analysing 43 skin biopsies from 20 patients with gadodiamide-related NSF and one NSF-negative gadodiamide-exposed dialysis patient, ranging from 16 days to 1991 days after Gd contrast dose. Utilizing automated quantitative scanning electron microscopy/energy-dispersive X-ray spectroscopy we determined the concentration of Gd and associated elements present as insoluble deposits in situ in the tissues. RESULTS: We detected Gd in skin lesions of all 20 patients with NSF, whereas Gd was undetectable in the NSF-negative patient. Gd concentration increased over time in 60% of patients with multiple sequential biopsies (n=10), decreasing only when the initial sampling time was >23 months after first gadodiamide dose. All Gd-containing deposits contained phosphorus, calcium and sodium. The ratio of Gd to calcium in tissue deposits correlated positively with the gadodiamide dose and with serum ionized calcium at the time of Gd exposure. CONCLUSIONS: These findings demonstrate the in vivo release (through transmetallation) of the toxic free Gd3+ from gadodiamide, and its retention in apatite-like deposits. We suggest that Gd may be mobilized over time from bone stores, explaining variably delayed onset of NSF and increasing skin concentration over time in patients with NSF.

Inorganic dust exposure causes pulmonary fibrosis in smokers: analysis using light microscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy.

Smoking is alleged to cause pulmonary fibrosis, but the role of inorganic dust particulates has not been adequately examined. The authors hypothesize that inorganic dust exposure is an independent risk factor for the development of fibrosis in smokers. They studied a prospective series of 34 subjects with open lung biopsies, 18 of whom had adequate lung parenchyma for evaluation. They also examined the relationships between smoking (pack-years), respiratory bronchiolitis (RB), inorganic dusts, and interstitial fibrosis. They graded RB, fibrosis, and particulate dust by means of light microscopy. They performed a semiquantitative analysis of dust burden by using scanning electron microscopy with energy-dispersive X-ray spectroscopy. A logistic regression analysis demonstrated a significant association between smoking and RB (p = .03), but not between smoking and fibrosis or between RB and fibrosis. Fibrosis was significantly associated with silica (p = .004) and titanium (p = .0006) concentrations. The results support the authors' hypothesis.

Traumatic osmium tetroxide inoculation.

Osmium tetroxide is a highly oxidizing, corrosive compound commonly found in electron microscopy laboratories. Although osmium tetroxide is known to cause rapid damage to organic tissue, its cutaneous effects have not been well studied. We report a case of traumatic inoculation from a broken vial of 4% osmium tetroxide. Electron microscopy and energy dispersive x-ray spectroscopy confirmed the presence of osmium in the tissue specimen. The lesion was treated by simple excision.

Mercury exposure and cutaneous disease.

Human contact with mercury has been ongoing for centuries and was previously considered a legitimate means of treating different cutaneous and systemic conditions. Toxicity from this heavy metal may occur from exposure to elemental, inorganic, and organic forms of mercury. This article outlines the signs and symptoms of mercury poisoning and the different clinical conditions with assorted cutaneous findings.

Evaluation of workers exposed to dust containing hard metals and aluminum oxide.

BACKGROUND: Fourteen worker exposed to hard metals and aluminum oxide were evaluated. METHODS: Six heavily exposed workers underwent bronchoscopy and bronchoalveolar lavage, and five workers underwent transbronchial biopsy. RESULTS: Microchemical analysis of transbronchial biopsies showed a high lung burden of exogenous particles, especially metal related to their hard metals exposure. Lung tissue and cellular changes, which were associated with exposure to hard metal and aluminum oxide, corresponded well with the microanalytic test results. CONCLUSIONS: Three workers had at biopsy diffuse interstitial inflammatory changes: two of them were asymptomatic with normal chest X-ray films, and one had clinically evident disease with severe giant cell inflammation. Two other workers showed focal inflammation. The worker showing clinical disease and one asymptomatic worker with interstitial inflammatory changes had evaluated bronchoalveolar lavage fluid-eosinophilia counts. These two were father (with clinical disease) and son (asymptomatic).

Cirsoid arteriovenous malformation of kidney presenting as a mass suggestive of malignancy.

This paper reports a rare case of cirsoid renal arteriovenous malformation (AVM) that showed radiological characteristics of a renal malignancy. Using only conventional procedures such as computerized tomography, the present case was misdiagnosed as a solid tumor mass and therefore radical nephrectomy was indicated. Angiographic analysis is expected to improve the accuracy of diagnosis of AVM, thus reducing the need to resort to invasive techniques.

Potato gun ocular injury.

PURPOSE: This study aimed to identify a dangerous new weapon capable of causing damage to the ocular and periocular regions. METHODS: The authors report two patients who had penetrating ocular injury in the past year because of homemade recreational potato guns. RESULTS: In one 14-year-old boy, projectiles from the firing of a potato gun resulted in orbital and cranial injuries that were life threatening with widespread fractures, marked disruption of facial structures, a cerebrospinal fluid fistula requiring bifrontal surgical repair, and loss of one eye. In a separate accident with a different potato gun, a 14-year-old boy who was wearing glasses at the time of injury had a sight-threatening perforating corneal laceration. CONCLUSION: Practitioners must be aware of the existence of these new, homemade unregulated devices. Information about the use and construction of these guns is widespread on the Internet, but no injuries resulting from these guns currently are documented in the medical literature.

Silicate and metal dust in lungs of Greyhounds.

OBJECTIVES: To determine whether the amount of opaque dust in lung specimens increases with age, the composition of that dust, and whether the composition is similar for Greyhounds and pet dogs. DESIGN: Quantification of lung particulate dust burdens. ANIMALS: 192 Greyhounds and 5 pet dogs. PROCEDURE: Lung specimens of 192 Greyhounds and 5 pet dogs were examined for dust accumulation, using light microscopy. Lung specimens from Greyhounds and the 5 pet dogs were analyzed, using scanning electron microscopy and energy dispersive x-ray spectroscopy to quantify the lung burden of inorganic particles. RESULTS: Lung dust burden increased linearly with age. Pulmonary dust was composed of aluminum silicates, silica, and 18 metals. Silicate and metal particulate burdens were higher in Greyhounds than in the pet dogs. The 3 most common metals were iron, titanium, and chromium. CONCLUSIONS AND CLINICAL RELEVANCE: Amount of opaque dust increased with age. The higher pulmonary dust burden in Greyhounds than in pet dogs suggests that environmental exposure is important.