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.

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.

Molecular microanalysis of pathological specimens in situ with a laser-Raman microprobe.

A laser-Raman microprobe has been used to identify microscopic inclusions of silicone polymer in standard paraffin sections of lymph node. This example of organic chemical microanalysis in situ in pathological tissue represents an extension of microanalytical capabilities from elemental analysis, performed with electron and ion microprobes, to compound-specific molecular microanalysis.

Silicon identification in prosthesis-associated fibrous capsules.

The use of correlated microscopic techniques, including the scanning electron microscopic modes of backscattered electron imaging and energy dispersive x-ray analysis, aid in defining the process of dispersion of silicon-containing material around silicone rubber (polydimethylsiloxane) prosthetic devices.

Zirconium compound-induced pulmonary fibrosis.

Despite suspicion that inhalation of zirconium should be capable of causing human pulmonary disease, documentation of zirconium pneumoconiosis in humans has been lacking. We studied a likely case of zirconium compound-induced pulmonary fibrosis. The diagnosis was based on the following: (1) a history of gradual increase in symptoms and slowly progressing pulmonary fibrosis by chest roentgenogram compatible with a pneumoconiosis; (2) an appropriate history of exposure and a latency period of about 15 years before the onset of dyspnea and of roentgenographic changes; (3) analysis of open lung biopsy material revealing end-stage fibrosis and honeycombing, a moderate number of birefringent particles, and extremely high levels of a variety of zirconium compounds; and (4) no other potential cause of fibrosis. We conclude that zirconium should be considered a likely cause of pneumoconiosis and that appropriate precautions should be taken in the workplace.

Angiosarcoma of the lung with fatal pulmonary hemorrhage.

A patient with fatal pulmonary hemorrhage was found to have angiosarcoma of the lung at postmortem examination. This case, occurring in a man with a prior history of industrial exposure in South African copper mines, is the third well-described primary occurrence of this tumor in the lung.

Cysticercosis of the fallopian tube: histology and microanalysis.

The authors identified a degenerated, focally calcified cestode larva (cysticercus) in the fallopian tube of a 50-year-old woman with endometriosis. The physiologic reaction to the larva was minimal, with some focal granulomatous salpingitis. No other focus of infection was detected. The differential diagnosis included trophoblastic tissue, foreign material, and parasites. Scanning electron microscopy and x-ray microanalysis of the organism revealed concentration of iodine in the subcuticular connective tissue of the larva and confirmed the calcium phosphate composition of the calcareous corpuscles. The presumed source of the iodine was the continued exposure of the larva to an environment rich in iodide secreted by the epithelium of the fallopian tube.

Silicone granulomas: report of three cases and review of the literature.

Since silicone is rapidly becoming one of the most commonly used biomaterials in modern medicine, pathologists will be observing increasing numbers of cases of silicone-related disease. Although numerous case reports have established that silicone elicits a characteristic response in tissues, the varying tissue reactions to silicone gels, liquids, and elastomers (rubber) have not been emphasized. Three cases are reported, and the literature is reviewed to illustrate the varying features of tissue reaction to silicone in its different forms. The first case is an example of silicone lymphadenopathy in an inguinal lymph node. This case demonstrates exuberant foreign body granuloma formation in response to particles of silicone elastomer. The second case involves a patient who had facial subcutaneous liquid silicone injections, and the third case is that of a woman in whom breast carcinoma developed 13 years after mammary augmentation with liquid silicone injections. These two cases illustrate the characteristic reaction to silicone liquid, with numerous cystic spaces and vacuoles in the soft tissues but minimal or no foreign body giant cell reaction. Scanning electron microscopy and energy dispersive x-ray analysis were performed in the first two cases, confirming the presence of silicon. Silicone migration and the clinical significance of various silicone-induced lesions are discussed.

Pulmonary alveolar proteinosis in a painter with elevated pulmonary concentrations of titanium.

We present the case of a professional painter who developed pulmonary alveolar proteinosis (PAP) with severe respiratory failure. He required total bilateral pulmonary lavage on two separate occasions, 3 months apart. Quantitative analysis of particles found in lung tissues obtained by open lung biopsies demonstrated the presence of titanium (60-129 million particles of titanium per cm3 of lung tissue). This report extends previous results from animal studies that demonstrated development of alveolar proteinosis in rats following exposure to titanium. It has been proposed that the overwhelming impairment of the normal clearance mechanisms of the lung by particles of titanium is one of the possible mechanisms responsible for the development of this lung disease. We suggest that a similar mechanism occurred in our patient and that titanium should be recognized as a potential cause of PAP in humans.

Uptake of iodinated contrast material by the ischemically damaged myocardial cell.

Computerized transmission tomography has shown differential contrast enhancement of the area of ischemic damage after intravenous administration of iodinated contrast material. The current study performed in normal dogs and dogs with two-day-old and 30-day-old myocardial infarctions was intended to determine if the iodine accumulation is intracellular. Scanning electron microscopy with energy dispersive x-ray analysis detected iodine peaks associated with the cells in areas of ischemic damage, while iodine peaks were not detected in normal myocardium. Energy spectra in the area of ischemic damage showed a significant increase in the Na+ -K+ ratio compared to normal myocardium, consistent with the loss of cellular membrane integrity in this region. Results were similar for both two- and 30-day-old infarcts. These results indicate that iodinated contrast material attaches to the membrane of enters the ischemically damaged cell, but is virtually excluded from the normal myocardial cell. It may serve as a marker of myocardial cells which have lost cellular membrane integrity after an ischemic insult.

Identification and quantitative analysis of tissue particulate burden.

The analysis of particles in tissue samples, especially in lung tissue samples, has been of great use diagnostically and in the search for more precise information on the etiology of occupational/environmental diseases. There is a strong need for an interdisciplinary approach involving patients, epidemiologists, clinicians, pathologists, toxicologists, and microscopists if advancement in the recognition, diagnosis, and prevention of disease is to proceed.

Pulmonary hypertension. Its association with hepatic cirrhosis and iron accumulation.

A 62-year-old white woman was found to have pulmonary hypertension; a short time later hepatic insufficiency developed. At the time of autopsy, hepatic cirrhosis, "primary" pulmonary hypertension, and evidence of increased iron absorption and storage were found. Pulmonary hypertension is an unusual complication of portal hypertension that is being reported increasingly often.

Silicone-induced endocarditis. A complication of transvenous cardiac pacing catheterization.

We report a case of silicone-induced endocarditis as a newly recognized complication of transvenous cardiac pacing catheterization. Silicone was found embedded in thrombotic vegetations on the tricuspid valve of a patient who had a long-standing pacing catheter in the right side of his heart. Scanning electron microscopy and energy-dispersive x-ray analysis confirmed the presence of silicone in the vegetations and in the catheter tip.

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.

Arc Welders' pneumoconiosis: application of advanced scanning electron microscopy.

Study of lung tissue from necropsy of a 58-year-old arc welder with arc welders' pneumoconiosis, confirmed by history, chest radiography, and pathology, demonstrates the versatility and usefulness of new techniques in scanning electron microscopy (SEM). Secondary electron imaging, the most familiar SEM mode, showed heavy cellular infiltrates in alveoli, the interstitium, and within the interstices of loose whorled fibrotic nodules. Backscattered electron imaging, in which contrast is proportional to elemental atomic number, revealed intracellular metal particles not otherwise visible. Microprobe analysis, energy-dispersive x-ray spectrometry, mapped elemeental iron over the particle image and identified traces of silicon in the whorled nodules. Arc welders' pneumoconiosis appears to be more than a benign siderosis resulting from particulate iron deposition. Simultaneous exposure to other components of welding fumes may alter the pathologic picture, inducing a more complicated fibrotic reaction. The more recently developed advanced techniques of SEM are well suited to the study of pneumoconioses and other problems of heterogenous tissue and mixed chemical systems.

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.