A Case of Silicone and Sarcoid Granulomas in a Patient with "Highly Cohesive" Silicone Breast Implants: A Histopathologic and Laser Raman Microprobe Analysis.

Foreign body giant cell (FBGC) reaction to silicone material in the lymph nodes of patients with silicone breast implants has been documented in the literature, with a number of case reports dating back to 1978. Many of these case reports describe histologic features of silicone lymphadenopathy in regional lymph nodes from patients with multiple sets of different types of implants, including single lumen smooth surface gel, single lumen textured surface gel, single lumen with polyethylene terephthalate patch, single lumen with polyurethane coating, and double lumen smooth surface. Only one other case report described a patient with highly-cohesive breast implants and silicone granulomas of the skin.

Spectroscopic and Spectrometric Approaches for Assessing the Composition of Embedded Metals in Tissues.

Many medical devices contain metals that interface with the body. Additionally, embedded metal fragments from military wounds are typically not removed, to avoid the risk of morbidity associated with invasive surgery. The long-term health consequences of many of these materials are not thoroughly understood.

Semen Uranium Concentrations in Depleted Uranium Exposed Gulf War Veterans: Correlations with Other Body Fluid Matrices.

Environmental metal exposure, as well as dietary metals, may adversely affect semen quality even as others play an essential role in normal spermatogenesis and fertility. Measures of seminal fluid metals have therefore been of high interest in the last several decades but have shown inconsistent results in correlations with some semen quality parameters. As well, environmental metal measures across various body fluid matrices have not been consistently correlated contrary to what one might hypothesize based on a systemic body burden of metal.

Cerebrospinal Fluid-Directed rAAV9-rsATP7A Plus Subcutaneous Copper Histidinate Advance Survival and Outcomes in a Menkes Disease Mouse Model.

Menkes disease is a lethal neurodegenerative disorder of copper metabolism caused by mutations in an evolutionarily conserved copper transporter, ATP7A. Based on our prior clinical and animal studies, we seek to develop a therapeutic approach suitable for application in affected human subjects, using the () mouse model that closely mimics the Menkes disease biochemical and clinical phenotypes. Here, we evaluate the efficacy of low-, intermediate-, and high-dose recombinant adeno-associated virus serotype 9 (rAAV9)-ATP7A delivered to the cerebrospinal fluid (CSF), in combination with subcutaneous administration of clinical-grade copper histidinate (sc CuHis, IND #34,166).

Public Regulatory Databases as a Source of Insight for Neuromodulation Devices Stimulation Parameters.

Objective: The Shannon model is often used to define an expected boundary between non-damaging and damaging modes of electrical neurostimulation. Numerous preclinical studies have been performed by manufacturers of neuromodulation devices using different animal models and a broad range of stimulation parameters while developing devices for clinical use. These studies are mostly absent from peer-reviewed literature, which may lead to this information being overlooked by the scientific community.

Metal Exposure in Veterans With Embedded Fragments From War-Related Injuries: Early Findings From Surveillance Efforts.

Objective: To characterize systemic metal exposures from retained fragments in a cohort of war-injured US Veterans enrolled in the Department of Veterans Affairs' Embedded Fragment Registry.

Methods: Five hundred seventy nine registry-enrolled Veterans submitted an exposure questionnaire and urine sample for analyses of 14 metals often found in fragments. Urine metal results were compared with reference values of unexposed populations to identify elevations.

The U.S. Department of Veterans' Affairs depleted uranium exposed cohort at 25 Years: Longitudinal surveillance results.

Background: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored for health changes in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994.

Methods: During the spring of 2015, an in-patient clinical surveillance protocol was performed on 36 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes.

Results: On-going mobilization of U from embedded fragments is evidenced by elevated urine U concentrations.

Mobilization of Metal From Retained Embedded Fragments in a Blast-Injured Iraq War Veteran.

A frequent comorbidity of traumatic injury due to a blast or explosion, commonly reported in Iraq and Afghanistan veterans, is that of retained embedded fragments typically of unknown content. Because of concerns over both local and systemic health effects related to both the physical presence of and mobilization of materials from embedded fragments, the Department of Veterans Affairs established a surveillance program for this group of veterans. We present here the case of a surveillance-enrolled veteran who submitted: (1) three surgically removed fragments for content analyses, (2) tissue adhered to the fragments for histology and metal concentration evaluation, and (3) pre- and postfragment removal urine samples to assess concentrations of various metals often found in fragments.

Biologic monitoring and surveillance results for the department of veterans affairs' depleted uranium cohort: Lessons learned from sustained exposure over two decades.

Background: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly fire incidents have been monitored in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994.

Methods: An in-patient clinical surveillance protocol was performed on 35 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes.

Results: Although urine U concentrations continue to be elevated in this group, illustrating on-going in situ mobilization of U from embedded fragments, no consistent U-related health effects have been observed.

Molecular and biochemical characterization of Mottled-dappled, an embryonic lethal Menkes disease mouse model.

Mottled-dappled (Mo-dp) is a mouse model of Menkes disease caused by a large, previously uncharacterized deletion in the 5' region of Atp7a, the mouse ortholog of ATP7A. Affected mutants die in utero at embryonic day 17, and show bending and thickening of the ribs and distortion of the pectoral and pelvic girdles and limbs. To characterize this allele, we designed a custom 4x180K microarray on the mouse X chromosome and performed comparative genomic hybridization using extracted DNA from normal and carrier Mo-dp females, and identified an approximately 9 kb deletion.

Chapter 4 embedded metal fragments.

The continued evolution of military munitions and armor on the battlefield, as well as the insurgent use of improvised explosive devices, has led to embedded fragment wounds containing metal and metal mixtures whose long-term toxicologic and carcinogenic properties are not as yet known. Advances in medical care have greatly increased the survival from these types of injuries. Standard surgical guidelines suggest leaving embedded fragments in place, thus individuals may carry these retained metal fragments for the rest of their lives.

Embedded fragments from U.S. military personnel--chemical analysis and potential health implications.

Background: The majority of modern war wounds are characterized by high-energy blast injuries containing a wide range of retained foreign materials of a metallic or composite nature. Health effects of retained fragments range from local or systemic toxicities to foreign body reactions or malignancies, and dependent on the chemical composition and corrosiveness of the fragments in vivo. Information obtained by chemical analysis of excised fragments can be used to guide clinical decisions regarding the need for fragment removal, to develop therapeutic interventions, and to better anticipate future medical problems from retained fragment related injuries.

Assessment of geographical variation in the respiratory toxicity of desert dust particles.

The health consequences of sand particle inhalation are incompletely understood. This project evaluated the respiratory toxicity of sand particles collected at military bases near Fort Irwin USA, in Iraq (Camp Victory, Taji and Talil), and Khost Afghanistan. Our primary focus was on assessing the role of soluble metals in the respiratory toxicity of the sand particles using in vitro and in vivo methods.

Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague-Dawley rats.

Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats.

Uranium quantification in semen by inductively coupled plasma mass spectrometry.

In this study we report uranium analysis for human semen samples. Uranium quantification was performed by inductively coupled plasma mass spectrometry. No additives, such as chymotrypsin or bovine serum albumin, were used for semen liquefaction, as they showed significant uranium content.

In utero copper treatment for Menkes disease associated with a severe ATP7A mutation.

Menkes disease is a lethal X-linked recessive neurodegenerative disorder of copper transport caused by mutations in ATP7A, which encodes a copper-transporting ATPase. Early postnatal treatment with copper injections often improves clinical outcomes in affected infants. While Menkes disease newborns appear normal neurologically, analyses of fetal tissues including placenta indicate abnormal copper distribution and suggest a prenatal onset of the metal transport defect.

Arsenic-induced health crisis in peri-urban Moyna and Ardebok villages, West Bengal, India: an exposure assessment study.

Drinking of arsenic (As)-contaminated groundwater has adverse effects on health of millions of people worldwide. This study aimed to determine the degree of severity of As exposure from drinking water in peri-urban Moyna and Ardebok villages, West Bengal, India. Arsenic concentrations in hair, nail and urine samp les of the individuals were determined.

Surveillance for long-term health effects associated with depleted uranium exposure and retained embedded fragments in US veterans.

Objective: To ensure that all veterans with retained embedded fragments are properly monitored for potential health effects of embedded materials.

Methods: Urine biomonitoring and health surveillance programs were developed to gather information about health risks associated with chemicals released from embedded fragments.

Results: Elevated systemic exposure to depleted uranium (DU) that continues to occur in veterans with DU fragments remains a concern, although no clinically significant DU-related health effects have been observed to date.

Biological responses in rats exposed to cigarette smoke and Middle East sand (dust).

Respiratory symptoms are frequently reported in personnel deployed to the Middle East. This project characterized the respiratory toxicity of inhaled Iraqi sand (IS). Adult rats underwent a 6-wk inhalation to air or mainstream cigarette smoke (MSCS) (3 h/d, 5 d/wk) that included exposure to IS or crystalline silica (1 mg/m(3), 19 h/d, 7 d/wk) or air during the last 2 weeks.

ATP7A gene addition to the choroid plexus results in long-term rescue of the lethal copper transport defect in a Menkes disease mouse model.

Menkes disease is a lethal infantile neurodegenerative disorder of copper metabolism caused by mutations in a P-type ATPase, ATP7A. Currently available treatment (daily subcutaneous copper injections) is not entirely effective in the majority of affected individuals. The mottled-brindled (mo-br) mouse recapitulates the Menkes phenotype, including abnormal copper transport to the brain owing to mutation in the murine homolog, Atp7a, and dies by 14 days of age.

Biomarkers of mercury exposure in two eastern Ukraine cities.

This study evaluates biomarkers of mercury exposure among residents of Horlivka, a city in eastern Ukraine located in an area with geologic and industrial sources of environmental mercury, and residents of Artemivsk, a nearby comparison city outside the mercury-enriched area. Samples of urine, blood, hair, and nails were collected from study participants, and a questionnaire was administered to obtain data on age, gender, occupational history, smoking, alcohol consumption, fish consumption, tattoos, dental amalgams, home heating system, education, source of drinking water, and family employment in mines. Median biomarker mercury concentrations in Artemivsk were 0.

Tissue distribution of tungsten in mice following oral exposure to sodium tungstate.

Heavy metal tungsten alloys have replaced lead and depleted uranium in many munitions applications, due to public perception of these elements as environmentally unsafe. Tungsten materials left in the environment may become bioaccessible as tungstate, which might lead to population exposure through water and soil contamination. Although tungsten had been considered a relatively inert and toxicologically safe material, recent research findings have raised concerns about possible deleterious health effects after acute and chronic exposure to this metal.

Spatial mapping of mineralization with manganese-enhanced magnetic resonance imaging.

Paramagnetic manganese can be employed as a calcium surrogate to sensitize the magnetic resonance imaging (MRI) technique to the processing of calcium during the bone formation process. At low doses, after just 48h of exposure, osteoblasts take up sufficient quantities of manganese to cause marked reductions in the water proton T1 values compared with untreated cells. After just 24h of exposure, 25μM MnCl(2) had no significant effect on cell viability.

Prostate cancer outcome and tissue levels of metal ions.

Background: There are several studies examining prostate cancer and exposure to cadmium, iron, selenium, and zinc. Less data are available on the possible influence of these metal ions on prostate cancer outcome. This study measured levels of these ions in prostatectomy samples in order to examine possible associations between metal concentrations and disease outcome.