The Air Force Health Study: An Epidemiologic Retrospective

Buffler, Patricia A.; Ginevan, Michael E.; Mandel, Jack S.; Watkins, Deborah K.

doi:10.1016/j.annepidem.2011.02.001

Cited by 27 publications

(19 citation statements)

References 23 publications

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“…Recently, an air force health study with a 20-yearmatched cohort showed no cases of multiple myeloma in the Ranch Hand veterans-the most highly exposed Vietnam veterans to Agent Orange [6]. This further supports the finding of the present study.…”

supporting

confidence: 94%

No association between Agent Orange exposure and monoclonal gammopathies

Parikh

Pearlman

2011

Ann Hematol

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supporting

confidence: 94%

No association between Agent Orange exposure and monoclonal gammopathies

Parikh

Pearlman

2011

Ann Hematol

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“…Numerous human epidemiological studies of highly exposed communities and workers, however, have not observed similar effects as those reported in animal studies (Boffetta et al 2011; Buffler et al 2011). This discrepancy has created a need to identify useful human cell models to study the effects of dioxin-activated AhR of which primary hepatocytes are particularly well suited.…”

Section: Use Of In Vitro Systems For Predicting Liver Toxicitymentioning

confidence: 83%

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME

Hewitt²,

et al. 2013

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This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell–derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-013-1078-5) contains supplementary material, which is available to authorized users.

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“…13 Several studies have demonstrated nearly identical levels of TCDD in the serum of Vietnam-stationed and control US Army veterans and the general public. [13][14][15][16] Despite this strong evidence, surveys have shown between 25% to 55% of Vietnam veterans believe they were significantly exposed to herbicides during their service and many present to their physicians with concerns about Agent Orange and its possible contribution to their various health problems. 3,8,14 Several groups may be at higher risk including ORH and Army Chemical Corps members both of whom personally handled the liquid herbicides.…”

Section: Agent Orangementioning

confidence: 96%

“…[13][14][15][16] Despite this strong evidence, surveys have shown between 25% to 55% of Vietnam veterans believe they were significantly exposed to herbicides during their service and many present to their physicians with concerns about Agent Orange and its possible contribution to their various health problems. 3,8,14 Several groups may be at higher risk including ORH and Army Chemical Corps members both of whom personally handled the liquid herbicides. Compared with other Air Force personnel serving concurrently in Southeast Asia without direct Agent Orange exposure, this high-risk population has demonstrated a statistically significant increase in serum TCDD concentration with persistent elevations even 30 to 40 years postexposure in the Air Force Health Study (AFHS).…”

Section: Agent Orangementioning

confidence: 96%

Skin diseases associated with Agent Orange and other organochlorine exposures

Patterson

Kaffenberger

Keller

et al. 2016

Journal of the American Academy of Dermatology

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Organochlorine exposure is an important cause of cutaneous and systemic toxicity. Exposure has been associated with industrial accidents, intentional poisoning, and the use of defoliants, such as Agent Orange in the Vietnam War. Although long-term health effects are systematically reviewed by the Institute of Medicine, skin diseases are not comprehensively assessed. This represents an important practice gap as patients can present with cutaneous findings. This article provides a systematic review of the cutaneous manifestations of known mass organochlorine exposures in military and industrial settings with the goal of providing clinically useful recommendations for dermatologists seeing patients inquiring about organochlorine effects. Patients with a new diagnosis of chloracne, porphyria cutanea tarda, cutaneous lymphomas (non-Hodgkin lymphoma), and soft-tissue sarcomas including dermatofibrosarcoma protuberans and leiomyosarcomas should be screened for a history of Vietnam service or industrial exposure. Inconclusive evidence exists for an increased risk of other skin diseases in Vietnam veterans exposed to Agent Orange including benign fatty tumors, melanomas, nonmelanoma skin cancers, milia, eczema, dyschromias, disturbance of skin sensation, and rashes not otherwise specified. Affected veterans should be informed of the uncertain data in those cases. Referral to Department of Veterans Affairs for disability assessment is indicated for conditions with established associations.

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The Air Force Health Study: An Epidemiologic Retrospective

Cited by 27 publications

References 23 publications

No association between Agent Orange exposure and monoclonal gammopathies

No association between Agent Orange exposure and monoclonal gammopathies

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME

Skin diseases associated with Agent Orange and other organochlorine exposures

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