Search

Previous population investigation of perfluoroalkyl substances (PFAS) features associations with lipids in a number of populations; these investigations have seldom included consideration of apolipoproteins. Apolipoprotein B (Apo B) fractions were considered in this descriptive analysis because they are essential to the assembly, transport, and cellular uptake of lipid classes associated with poorer health outcomes, and they are associated with incident and prevalent disease. Regression models stratified by diabetes and lipid lowering medication (LLM) status for data from National Health and Nutrition Examination Survey for 2007–2014 were fitted to interrogate associations between selected PFAS and Apo B for US adults aged ≥ 20 years. Adjusted concentrations of Apo B were positively associated with perfluorooctanoic acid (PFOA β = 0.03878, p

OBJECTIVE Perfluoroalkyl substances (PFAS) and liver function biomarkers were reexamined for relatively lower serum concentrations of PFAS observed in recent years. METHODS National Health and Nutrition Examination Survey 2011 to 2014 data were analyzed for obese and nonobese participants for serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA) as well as four liver function biomarkers in risk-adjusted analysis. RESULTS Among obese participants only, alanine aminotransferase (ALT) was positively associated with PFOA (β = 0.07065, P

Respiratory exposure to multiwalled carbon nanotubes (MWCNT) or asbestos results in fibrosis; however, the mechanisms to reach this end point may be different. A previous study by our group identified pulmonary effects and significantly altered messenger RNA (mRNA) signaling pathways following exposure to 1, 10, 40, and 80 µg MWCNT and 120 µg crocidolite asbestos on mouse lungs over time at 1-month, 6-month, and 1-year postexposure following pulmonary aspiration. As a continuation to the above study, this current study took an in-depth look at the signaling pathways involved in fibrosis development at a single time point, 1 year, and exposure, 40 µg MWCNT, the lowest exposure at which fibrosis was pathologically evident. The 120 µg asbestos exposure was included to compare MWCNT-induced fibrosis with asbestos-induced fibrosis. A previously validated computational model was used to identify mRNAs with expression profiles matching the fibrosis pathology patterns from exposed mouse lungs. mRNAs that matched the pathology patterns were then input into ingenuity pathway analysis to determine potential signaling pathways and physiological disease functions inherent to MWCNT and asbestos exposure. Both MWCNT and asbestos exposure induced changes in mouse lungs regarding gene expression, cell proliferation, and survival, while MWCNT uniquely induced alterations in pathways involved in oxidative phosphorylation, mitochondrial dysfunction, and transcription. Asbestos exposure produced unique alterations in pathways involved in sustained inflammation. Although typically considered similar due to scale and fiber-like appearance, the different compositional properties inherent to either MWCNT or asbestos may play a role in their ability to induce fibrosis after pulmonary exposure.

Context.— Human papillomavirus (HPV) is implicated in the development of oropharyngeal squamous cell carcinomas (OPC), particularly those cancers developing in tonsillar tissue. Objectives.— To review the prevalence, subtypes, and methods of detecting HPV in OPC and to review the epidemiology, histology, staging, management, and prevention of these cancers. Data Sources.— The study comprised a review of the literature. Conclusions.— The incidence of HPV-OPC is rising globally and in the United States, but rates of HPV-positivity vary with the anatomic site(s) and the population studied, as well as the method of detecting HPV infection. These tumors are more common in men. In contrast to HPV− OPC, the rates of smoking and alcohol abuse are lower. The HPV 16 subtype is predominant, and immunohistochemistry staining for p16 and in situ hybridization are the most widely used methods clinically to detect transcriptionally active HPV. Moreover, HPV-OPC has a unique tumor phenotype with predominantly nonkeratinizing morphology and a variety of patterns. These cancers often present with cystic lymph node metastases. The prognosis for HPV-OPC is significantly better than HPV− OPC and has led to differences in grading, staging, and management. Although there are similarities to cervical cancer, there are challenges in preventing such cancers.

Introduction/Objective Capillary inflammation (capillaritis) is rarely the primary pathologic cause of pulmonary hemorrhage. It may coexist with vasculitis. The aim of this study is to investigate the specificity of five histologic features of pulmonary capillaritis previously described by Mark and Ramirez (discussed below). They are usually treated with corticosteroids and cyclophosphamide or azathioprine. Methods A retrospective review of patients with a pathologic diagnosis of capillaritis in open lung biopsies was done. The diagnosis was confirmed by two expert pulmonary pathologists. The slides were reviewed and compared to a control group, who also underwent open lung biopsies for clinical suggestion of pulmonary hemorrhage and no pathologic diagnosis of capillaritis. Cases with malignant neoplasms, large and medium size vasculitis syndromes, and diffuse alveolar damage (DAD) were excluded. The five pathologic features of capillaritis were evaluated and scored as negative (0), focal (1+) and moderate to diffuse (2+) in both groups. Results Five cases of pulmonary capillaritis and five cases in control group were identified. The etiology of pulmonary capillaritis in the five identified cases included autoimmune diseases, pulmonary hypertension, non-specific interstitial pneumonia, and idiopathic capillaritis. The average score for the morphologic features of capillaritis versus the control group were as follows: Interstitial erythrocytes and/or hemosiderin (2+ vs 2+), fibrinoid necrosis of capillary walls (2+vs 0), intraalveolar septal capillary occlusion by fibrin thrombi (1+ vs 0), neutrophils and nuclear dust in the interstitium, in the fibrin, and in the adjacent alveolar spaces (2+ vs 1+), and fibrin clots attached to interalveolar septa in a sessile manner (2+ vs 1+). Conclusion In this small study, we can conclude that fibrinous necrosis is the most specific finding for pulmonary capillaritis while interstitial erythrocytes and/or hemosiderin is least specific. Therefore, in the presence of fibrinous necrosis; in addition to other supporting features; a pathologist is more inclined to communicate a diagnosis of pulmonary capillaritis to the clinicians.

Associations between selected perfluoroalkyl acids (PFAAs) and biomarkers of renal function were evaluated for US adult aged ≥ 20 years (N = 8220) in the National Health and Nutrition Examination Survey for 2005–2014. Glomerular filtration (GF) stage-stratified regression models were classified by estimated glomerular filtration rate (eGFR) with GF-1 (eGFR > 90 mL/min/1.73 m2), GF-2 (eGFR 60–89 mL/min/1.73 m2), GF-3A (45–59 mL/min/1.73 m2), and GF-3B/4 (15–44 mL/min/1.73 m2). For GF-1, PFOA, PFOS, and PFHxS were positively and significantly associated with serum creatinine. Serum albumin levels were positively associated with the PFAA considered at all stages and most associations were significant. Further, PFAS serum concentration associations to serum albumin were about 2–3 times stronger at GF-3B/4 than at GF-1. In contrast, urine albumin was negatively and significantly associated with PFOA and PFHxS serum concentrations at all stages of renal function, while, PFOS and PFNA were negatively and significantly associated to urine albumin at GF-3A and GF-3B/4. Urine albumin/creatinine ratios were negatively and significantly associated with PFOA, PFOS, and, and PFHxS serum concentrations at all stages of renal function, as well as with PFNA and PFDA at GF-3A and GF-3B/4. Recent work revealed that serum PFAAs have an inverted U-shaped association to the calculated stages of renal failure based on eGFR; this work adds that albuminuria makes additional negative contributions to already existing negative associations of PFAA to eGFR in advancing stages of renal failure. We hypothesize that both progressive renal failure per se and especially renal failure with albuminuria cause the kidneys to reabsorb less and to excrete more of the PFAAs studied. We suspect this finding may generalize to some other perfluoroalkyl substances (PFAS). The findings also imply study design considerations for evaluating associations to diseases and biomarkers associated with renal failure, such as diabetes.

National Health and Nutrition Examination Survey 2007-2014 data (N = 6844) for adults aged ≥ 20 years were analyzed to estimate associations of perfluoroalkyl substances (PFAS), namely, PFOA, PFOS, PFDA, PFHxS, and PFNA with uric acid across stages of declining glomerular function. The population was stratified by the estimated glomerular filtration rates (eGFR) stages accompanying kidney disease: GF-1 with eGFR > 90 mL/min/1.73 m2; GF-2 with eGFR 60-89 mL/min/1.73 m2; GF-3A with eGFR 45-59 mL/min/1.73 m2; and GF-3B/4 with eGFR 15-44 mL/min/1.73 m2. Adjusted and unadjusted geometric means of uric acid increased from GF-1 to GF-3B/4 for males and females. Adjusted geometric means for uric acid were higher for males by 1.38, 1.03, and 0.62 mg/dL for GF-1, GF2, and GF-3 respectively but for GF-3B/4, females had higher adjusted geometric means than males by 0.16 mg/dL, revealing narrowing of sex differences in uric acid as glomerular function declines. The direction of association between PFAS and uric acid was positive for GF-1 and GF-2 for males and for every PFAS except PFDA for females. For males for GF-3B/4, association between every PFAS except PFHxS and uric acid was found to be negative (p < 0.01). For females, only PFHxS actually reverses its relationship with increasing stages of renal disease. Uric acid associations with PFAS reverse in males with advanced renal failure. An implication is that previously reported association of PFAS exposure with uric acid is not due to renal failure. Understanding of other biomarkers associated with both PFAS exposure and renal failure may benefit from similar evaluation.

Exposures to perfluoroalkyl substances (PFAS) including perfluoroalkyl acids (PFAAs) are associated with increased liver enzymes in cohort studies including the C8 Health Study. In animal models, PFAAs disrupt hepatic lipid metabolism and induce apoptosis to cause nonalcoholic fatty liver disease (NAFLD). PFAAs are immunotoxic and inhibit pro-inflammatory cytokine release from stimulated leukocytes in vitro. This cross-sectional study tests the hypothesis that environmental PFAAs are associated with increased hepatocyte apoptosis and decreased pro-inflammatory cytokines in serum. Biomarkers previously associated with PFAS exposures and/or NAFLD were evaluated as secondary endpoints. Two hundred adult C8 Health Study participants were included. Measured serum biomarkers included: perfluorohexane sulfonate (PFHxS); perfluorooctanoic acid (PFOA); perfluorooctane sulfonate (PFOS); perfluorononanoic acid (PFNA); cytokeratin 18 M30 (CK18 M30, hepatocyte apoptosis); adipocytokines; insulin; and cleaved complement 3 (C3a). Confounder-adjusted linear regression models determined associations between PFAS and disease biomarkers with cut-offs determined by classification and regression tree analysis. CK18 M30 was positively associated with PFHxS (β = 0.889, p = 0.042); PFOA (β = 2.1, p = 0.005); and PFNA (β = 0.567, p = 0.03). Tumor necrosis factor α (TNFα) was inversely associated with PFHxS (β = -0.799, p = 0.001); PFOA (β = - 1.242, p = 0.001); and PFOS (β = -0.704, p 0.001). Interleukin 8 was inversely associated with PFOS and PFNA. PFAAs were also associated with sexually dimorphic adipocytokine and C3a responses. Overall, PFAA exposures were associated with the novel combination of increased biomarkers of hepatocyte apoptosis and decreased serum TNFα. These data support previous findings from cohorts and experimental systems that PFAAs may cause liver injury while downregulated some aspects of the immune response. Further studies of PFAAs in NAFLD are warranted and should evaluate sex differences.

Data (N = 6844) from National Health and Nutrition Examination Survey for US adults aged ≥ 20 years for the years 2007–2014 were analyzed to evaluate distributional characteristics of selected perfluoroalkyl substances (PFAS) - perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonate (PFHxS) and perfluorononanoic acid (PFNA) with declining glomerular function. The population was stratified according to the estimated glomerular filtration rates (eGFR) that accompany the stages of kidney disease, designated as glomerular function-1 (GF-1, eGFR>90 mL/min/1.73 m2); GF-2 (eGFR 60–89 mL/min/1.73 m2), GF-3A (eGFR 45–59 mL/min/1.73 m2), and GF-3B and 4 combined (eGFR 15–44 mL/min/1.73 m2). Unadjusted as well as adjusted geometric means for serum PFOA, PFDA, PFHxS, and PFNA increased as expected through stage GF-3A but decreased below the concentrations associated with GF-1 for those who were in GF-3B/4. For example, unadjusted geometric means for PFOA were 2.59, 3.02, 3.01, and 2.22 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Adjusted geometric means for PFOA were 2.34, 2.83, 2.83, and 1.81 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Thus, PFAS were found to follow inverted U-shaped distributions across different stages of glomerular function. For females, decreases in adjusted PFAS serum levels were initiated at GF-3A, while decreases for males began as early as GF-2. Usually, females are known to have lower levels of PFAS but when in GF-3A and GF-3B/4, females were found to have higher levels of PFAS than males. Thus, inverted U-shaped curves for males and females intersected between GF-2 and GF-3A for PFOA and PFHxS and at GF-3A for PFOS and PFNA. Associations between PFAS and biomarkers of kidney function may be modified in both magnitude and even in direction as kidney function deteriorates. These findings have implications for studies that evaluate associations between PFAS and disease states that affect kidney function, as well as outcome biomarkers known to be affected by kidney function.

Types 16 and 18 are the most widely studied high-risk types of human papillomavirus (HPV). However, other high-risk HPV types (HPV non-16/18) also play a significant role in cervical neoplasia. Currently, screening and management algorithms separate out HPV 16/18 from all other HPV non-16/18 types. In addition, most of the previously vaccinated population has only been vaccinated for these high-risk types, so many women are still vulnerable to HPV non-16/18 infections.- To review the prevalence and role of HPV non-16/18 neoplasia and to review current surveillance, management, and vaccination strategies in view of these findings.- The study comprised a review of the literature.- Although HPV non-16/18 types are less frequently associated with cervical intraepithelial neoplasia and cancer, they are nonetheless a significant cause of disease. Further stratification of higher-risk HPV non-16/18 may be necessary to improve prevention and management, however, regional prevalence differences may make a unified approach difficult. As HPV 16/18 infections decrease owing to vaccination of at-risk women, the relative frequency of HPV non-16/18 will increase, although the latest vaccine covers several more high-risk types.

Purpose 1) To determine SUVs and PET/CT characteristics of Warthin's tumors in patients presenting to a head and neck cancer clinic. 2) To analyze the impact of PET/CT on the clinical course of these patients. Materials and methods This is a single-institution retrospective analysis of patients with proven Warthin’s tumors who underwent PET/CT done at or near the time of diagnosis and presented to a head and neck cancer practice. Data were obtained from the electronic medical records of these patients and the imaging and pathology databases. Results Six patients with Warthin's tumor met the criteria for and form the study cohort. Three patients had bilateral tumors. The SUVs for Warthin's varied from 3.4 to 16.1 in these patients, with an average of 7.8 and these SUVs were higher for Warthin's than for the cancers. These findings on PET/CT in this group required additional workup of all patients and required FNA, surgery or SPECT-CT to confirm the diagnosis. Conclusion Although it is known that Warthin's tumor may be hypermetabolic on PET, this finding in the parotid or neck on PET/CT alters the evaluation and treatment of head and neck cancer patients and patients with cancers outside the head and neck by raising the concern about metastatic disease or multiple primary cancers. In other patients, PET/CT obtained for other reasons may prompt concern about incidental malignancy. This series specifically characterizes clinical features, SPECT-CT and FNA findings that can help reinforce the diagnosis of Warthin's and facilitate management.

Purpose To inform questions raised by inconsistent findings regarding an association between perfluoroalkyl acids (PFAAs) and prostate cancer by assessing the relationship of PFAAs in human serum to prostate-specific antigen (PSA). Materials and methods Using 2005 to 2006 survey data from a large survey population, we compared serum PFAA concentrations in adult males with PSA concentrations adjusted for risk factors including age, body mass index, smoking status, and socioeconomic status. Results Perfluoroalkyl acids are not consistently associated with PSA concentration in general, or with PSA more than 4.0. Discussion These findings do not provide evidence that PFAA exposure is associated with PSA.

We investigated the influence of pathology data to improve patient outcomes in the treatment of high-grade cervical neoplasia in a joint pathology and gynecology collaboration. Two of us (B.S.D. and M.D.) reviewed all cytology, colposcopy and surgical pathology results, patient history, and pregnancy outcomes from all patients with loop electrosurgical excision procedure specimens for a 33-month period (January 2011-September 2013). We used this to determine compliance to 2006 consensus guidelines for the performance of loop electrosurgical excision procedure and shared this information in 2 interprofessional and interdisciplinary educational interventions with Obstetrics/Gynecology and Pathology faculty at the end of September 2013. We simultaneously emphasized the new 2013 guidelines. During the postintervention period, we continued to provide follow-up using the parameters previously collected. Our postintervention data include 90 cases from a 27-month period (October 2013-December 2015). Our preintervention data include 331 cases in 33 months (average 10.0 per month) with 76% adherence to guidelines. Postintervention, there were 90 cases in 27 months (average 3.4 per month) and 96% adherence to the 2013 (more conservative) guidelines (P < .0001, χ2 test). Preintervention, the rate of high-grade squamous intraepithelial lesion in loop electrosurgical excision procedures was 44%, whereas postintervention, there was a 60% high-grade squamous intraepithelial lesion rate on loop electrosurgical excision procedure (P < .0087 by 2-tailed Fisher exact test). The duration between diagnosis of low-grade squamous intraepithelial lesion and loop electrosurgical excision procedure also increased significantly from a median 25.5 months preintervention to 54 months postintervention (P < .0073; Wilcoxon Kruskal-Wallis test). Postintervention, there was a marked decrease of loop electrosurgical excision procedure cases as well as better patient outcomes. We infer improved patient safety, and higher value can be achieved by providing performance-based pathologic data.

Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure to E-cig vapor on vascular function. The purpose of this study was to determine the cardiovascular consequences of chronic E-cig exposure. Female mice (C57BL/6 background strain) were randomly assigned to chronic daily exposure to E-cig vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group). Respective whole body exposures consisted of four 1-h-exposure time blocks, separated by 30-min intervals of fresh air breaks, resulting in intermittent daily exposure for a total of 4 h/day, 5 days/wk for 8 mo. Noninvasive ultrasonography was used to assess cardiac function and aortic arterial stiffness (AS), measured as pulse wave velocity, at three times points (before, during, and after chronic exposure). Upon completion of the 8-mo exposure, ex vivo wire tension myography and force transduction were used to measure changes in thoracic aortic tension in response to vasoactive-inducing compounds. AS increased 2.5- and 2.8-fold in E-cig- and 3R4F-exposed mice, respectively, compared with air-exposed control mice ( P < 0.05). The maximal aortic relaxation to methacholine was 24% and 33% lower in E-cig- and 3R4F-exposed mice, respectively, than in controls ( P < 0.05). No differences were noted in sodium nitroprusside dilation between the groups. 3R4F exposure altered cardiac function by reducing fractional shortening and ejection fraction after 8 mo ( P < 0.05). A similar, although not statistically significant, tendency was also observed with E-cig exposure ( P < 0.10). Histological and respiratory function data support emphysema-associated changes in 3R4F-exposed, but not E-cig-exposed, mice. Chronic exposure to E-cig vapor accelerates AS, significantly impairs aortic endothelial function, and may lead to impaired cardiac function. The clinical implication from this study is that chronic use of E-cigs, even at relatively low exposure levels, induces cardiovascular dysfunction. NEW & NOTEWORTHY Electronic cigarettes (E-cigs) are marketed as safe, but there has been insufficient long-term exposure to humans to justify these claims. This is the first study to report the long-term in vivo vascular consequences of 8 mo of exposure to E-cig vapor in mice (equivalent to ~25 yr of exposure in humans). We report that E-cig exposure increases arterial stiffness and impairs normal vascular reactivity responses, similar to other risk factors, including cigarette smoking, which contribute to the development of cardiovascular disease.

Aims Diabetes is linked with decreases in lung elasticity and in capacity to transfer carbon monoxide. Systemic inflammation, a common concern with diabetes, may contribute to airflow obstruction. We examined the association of self-reported diabetes with self-reported respiratory diseases (RDs) among 53,146 adults from the C8 Health Project. Methods Participants were categorized into three groups: Type 1 (T1D, n = 781), Type 2 (T2D, n = 4277), or no diabetes (n = 48,088). ORs (95% CIs) for the association of diabetes with four RDs were computed: emphysema, chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), and asthma. Covariates controlled for were age, sex, estimated glomerular filtration rate, C-reactive protein, smoking history, BMI, and perfluorooctonaoic acid (C8). Results RDs were present in 26%, 21% and 13% of persons with T1D, T2D, and no diabetes, respectively. In multivariable analyses, persons with T1D were 62% more likely to have any RD (OR: 1.62, CI: (1.36–1.93)), while those with T2D were 1.3 times as likely (OR: 1.26, CI: 1.15–1.37)). Compared to those without diabetes, in those with T1D and T2D diabetes respectively, ORs (CIs) for COPD were 1.89 (1.38–2.57), 1.45 (1.23–1.71), asthma: 1.51 (1.21–1.87), 1.38 (1.24–1.53), CB: 1.96 (1.57–2.45), 1.35 (1.20–1.52) and emphysema: 1.25 (0.85–1.82), 1.31 (1.10–1.56). Population attributable risks for any RDs associated with a history of smoking were 19%, 30%, and 26% for those with Type 1, Type 2, and no diabetes respectively. Conclusions Diabetes, more so in T1D, appears to increase RD risk. Smoking is an important risk factor, but not as informative in Type 1 diabetes.

Objective The aim of the current study is to investigate the association of polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants, with diabetes mellitus. Animal studies link PAHs to inflammation and subsequent development of diabetes mellitus. In addition, occupational studies suggest that exposure to other aromatic hydrocarbons such as dioxins may be associated with diabetes risk in humans. Design We examined participants from the merged National Health and Nutrition Examination Survey 2001–2002, 2003–2004 and 2005–2006. Exposures of interest were eight urinary monohydroxy-PAHs. Our outcome was diabetes mellitus defined as a glycohemoglobin level (HbA1c) ≥6.5%, a self-reported physician diagnosis of diabetes or use of oral hypoglycaemic medication or insulin. Analyses were adjusted for age, sex, body mass index, race, alcohol consumption, poverty–income ratio, total cholesterol and serum cotinine. Results We observed a positive association between urinary biomarkers of 1 and 2-hydroxynapthol, 2-hydroxyphenanthrene and summed low molecular weight (LMW) PAH biomarkers, and diabetes mellitus. Compared with participants with summed LMW PAH biomarkers in the lowest quartile, the multivariable-adjusted OR of diabetes mellitus among those in the highest quartile was 3.1 (95% CI 1.6 to 5.8). Conclusions Urinary biomarkers of 1 and 2-hydroxynapthol, 2-hydroxyphenanthrene and summed LMW PAH biomarkers are associated with diabetes mellitus in US adults 20–65 years of age. The association of a one-time biomarker of PAH exposure has limitations commonly associated with cross-sectional studies, yet is consistent with experimental animal data and is worthy of additional consideration.

Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration and lactate dehydrogenase (LDH) activity and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 month, 6 months, and 1 year post-exposure. As MWCNT are often structurally compared to asbestos, a 120 μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all 3 post-exposure times. Asbestos exposure elevated LDH activity at all 3 post-exposure times and PMN infiltration at 1- and 6 months post-exposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 year post-exposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, we determined up- and down-regulated gene expression in lung tissue at 1 year post-exposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological changes similar to crocidolite asbestos, but may reach these endpoints by different mechanisms.

Chronic kidney disease (CKD) is a major public health problem. Identifying novel risk factors for CKD, including widely prevalent environmental exposures, is therefore important. Perfluoroalkyl chemicals (PFCs), including perfluorooctanoic acid and perfluorooctane sulfonate, are manmade chemicals that have been detected in the blood of more than 98% of the US population. Results from experimental animal studies have suggested that an association between PFCs and CKD is plausible. However, in humans, the relation between serum PFCs and CKD has not been examined. The authors examined the relation of serum PFCs and CKD in 4,587 adult participants (51.1% women) from the combined 1999-2000 and 2003-2008 cycles of the National Health and Nutritional Examination Survey for whom PFC measurements were available. The main outcome was CKD, defined as a glomerular filtration rate of less than 60 mL/minute/1.73 m(2). The authors found that serum levels of PFCs, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with CKD. This association was independent of confounders such as age, sex, race/ethnicity, body mass index, diabetes, hypertension, and serum cholesterol level. Compared with subjects in quartile 1 (referent), the multivariable odds ratio for CKD among subjects in quartile 4 was 1.73 (95% confidence interval: 1.04, 2.88; P for trend = 0.015) for perfluorooctanoic acid and 1.82 (95% confidence interval: 1.01, 3.27; P for trend = 0.019) for perfluorooctane sulfonate. The present results suggest that elevated PFC levels are associated with CKD.

Perfluorocarbons (PFC) are man-made chemicals used in numerous household products. They have a long half-life in humans and complex animal toxicity, and accumulating evidence points toward associations with multiple human health endpoints.Our objective was to investigate whether PFC are associated with endocrine disruption in women.Cross-sectional analyses were made between quintiles of serum PFC, serum estradiol, and menopause onset.The C8 Health Project, with cohort of 69,030 adults and children, was conducted due to PFC contamination of drinking water from six water districts in two states.Participants included 25,957 women aged 18-65 yr.Serum estradiol levels and onset of menopause were assessed. The survey was the result of a class action suit, and survey designers (an independent corporation) had no a priori hypotheses. All hypotheses have been formulated by other investigators after data collection.After excluding women who reported hysterectomy and adjusting for age within the group, smoking, alcohol consumption, body mass index, and exercise, the odds of having experienced menopause were significantly higher in the highest quintile relative to the lowest quintile of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in the perimenopausal [PFOS odds = 1.4, confidence interval (CI) = 1.1-1.8; PFOA odds =1.4, CI = 1.1-1.8] and menopausal age groups (PFOS odds = 2.1, CI=1.6-2.8; PFOA odds = 1.7, CI = 1.3-2.3). After appropriate exclusions and adjustment for covariates, there was a significant inverse association between PFOS and estradiol in perimenopausal (β = -3.65; P0.0001) and menopausal age groups (β = -0.83; P = 0.007) but not between PFOA and estradiol.These data suggest that PFC are associated with endocrine disruption in women and that further research on mechanisms is warranted.

Background/Aim: Serum γ-glutamyltransferase (GGT), a biomarker of oxidative stress, is associated with an increased risk of diabetes and hypertension. However, it is not known whether higher serum GGT is independently associated with chronic kidney disease (CKD). Therefore, we examined the association between serum GGT levels and CKD in a representative sample of US adults. Methods: We conducted a cross-sectional study of 9,516 National Health and Nutrition Examination Survey 1999–2002 participants ≧18 years of age (52.40% women). Serum GGT was categorized into quartiles for the analysis. CKD (n = 622) was defined as an estimated glomerular filtration rate of 2. Results and Conclusion: Higher serum GGT levels were not associated with CKD after adjusting for age, sex, race/ethnicity, education levels, smoking, alcohol intake, body mass index (BMI), diabetes, hypertension and serum cholesterol. Compared to quartile 1 of GGT, the odds ratio (95% confidence interval) of CKD associated with quartile 4 was 1.02 (0.81–1.28); p trend = 0.377. Subgroup analyses that examined the relation between GGT and CKD by gender, alcohol intake, and BMI categories also showed a consistent null association. In summary, there was no association between increasing levels of serum GGT and CKD in a sample of US adults.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are compounds that do not occur in nature but have been widely used since World War II and persist indefinitely in the environment. They are present in the serum of Americans with median levels of 4 ng/mL and 21 ng/mL, respectively. PFOA has been positively associated with cholesterol in several studies of workers. A cross-sectional study of lipids and PFOA and PFOS was conducted among 46,294 community residents aged 18 years or above, who drank water contaminated with PFOA from a chemical plant in West Virginia. The mean levels of serum PFOA and PFOS in 2005-2006 were 80 ng/mL (median, 27 ng/mL) and 22 ng/mL (median, 20 ng/mL), respectively. All lipid outcomes except high density lipoprotein cholesterol showed significant increasing trends by increasing decile of either compound; high density lipoprotein cholesterol showed no association. The predicted increase in cholesterol from lowest to highest decile for either compound was 11-12 mg/dL. The odds ratios for high cholesterol (>/=240 mg/dL), by increasing quartile of PFOA, were 1.00, 1.21 (95% confidence interval (CI): 1.12, 1.31), 1.33 (95% CI: 1.23, 1.43), and 1.40 (95% CI: 1.29, 1.51) and were similar for PFOS quartiles. Because these data are cross-sectional, causal inference is limited. Nonetheless, the associations between these compounds and lipids raise concerns, given their common presence in the general population.

Serum gamma-glutamyl transferase (GGT), a marker of oxidative stress, has been shown to be associated with diabetes mellitus in some population-based studies, but not all. Also, it is not clear if there is a continuous dose-response relationship in this association, or if this association is evident only beyond a particular threshold level of GGT. We examined the association between serum GGT and diabetes mellitus in a representative sample of US adults agedor = 20 years, in a cross-sectional study involving 7,976 National Health and Nutrition Examination Survey 1999-2002 participants. Diabetes mellitus was defined as a fasting glucoseor = 126 mg/dl, nonfasting glucoseor = 200 mg/dl, or use of oral hypoglycemic medication or insulin (n = 805). Higher serum GGT levels were positively associated with diabetes mellitus, independent of, alcohol consumption, body mass index, hypertension and other confounders. Multivariable odds ratio (95% confidence interval) comparing quartile 4 of GGT (33 U/L) to quartile 1 (15 U/L) was 2.33 (1.59-3.41), P-trend0.0001. This association persisted in separate analysis among men and women. In nonparametric models, the positive association between serum GGT and diabetes appeared to be present across the full range of GGT, without any threshold effect. Higher serum GGT levels are positively associated with diabetes mellitus.

To investigate evidence that lymph node silicosis can precede parenchymal silicosis.The study population was comprised of 264 deceased male uranium miners for whom two or more of four pathologists agreed on the presence or absence of silicosis in lymph nodes and lung parenchyma. We had work histories and silica exposure estimates.Twenty percent of the miners had lymph node silicosis only, 4% had parenchymal silicosis only, and 39% had both. Silica exposure was lower for miners with lymph node silicosis only than for those with both lymph node and parenchymal silicosis. Lymph node silicosis was associated with parenchymal silicosis after adjustment for silica exposure.Our results are consistent with silicosis potentially occurring in lymph nodes before the parenchyma. Lymph node damage could impair silica clearance and increase the risk for parenchymal silicosis.

Aims: To determine whether Src homology phosphotyrosyl phosphatase 2 (SHP2) is up-regulated in breast cancer and, if so, to determine whether its up-regulation has any relationship with clinical variables of breast cancer. Methods and results: Immunoblotting, immunohistochemistry and immunofluorescence microscopy were used to assess the state of SHP2 expression in breast cancer cells and in infiltrating ductal carcinoma (IDC) of breast. The possible role of SHP2 in breast cancer cell transformation was determined by dominant-negative expression and anchorage-independent growth assays. All of the breast cancer cell lines tested and 72% of IDC breast tumours analysed had increased amounts of the SHP2 protein. In support of its positive role, dominant-negative SHP2 blocked anchorage-independent growth of breast cancer cells. Furthermore, overexpression of SHP2 seemed to have a positive relationship to HER2 overexpression, nuclear accumulation of hormone receptors, higher tumour grade and lymph node metastasis, but not to age of breast cancer patients. Conclusion: SHP2 is a widely overexpressed signalling protein in IDC breast tumours. Given SHP2’s positive role in cell growth, transformation and stem cell survival, the positive relationship of its overexpression to lymph node metastasis, nuclear accumulation of hormone receptors and higher tumour grade suggests that SHP2 promotes breast oncogenesis.

Atypical fibroxanthoma (AFX), a benign lesion, and pleomorphic malignant fibrous histiocytoma (MFH) are thought to represent points along the same neoplastic spectrum but with different prognoses and treatments. Diagnosis based on histology and clinical parameters alone is sometimes difficult, and a reliable cost-effective immunohistochemical marker to help distinguish these lesions would be beneficial. The diagnosis of AFX or MFH was based upon published clinical and microscopic criteria. Formalin-fixed, paraffin-embedded tissues of 17 cases of AFX and 26 cases of MFH were immunostained with monoclonal antibody to CD99. For all cases, CD99 expression was scored on a four-tiered scale: negative, weak (1+), moderate (2+), or strong (3+). Two pathologists blinded to tumor diagnoses and type of immunostain evaluated each case independently. The interobserver correlation coefficient was calculated. Seventeen patients with AFX (16 males and one female; mean age = 79) and 26 patients with MFH (16 males and 10 females; mean age = 60) were included. AFX lesions were from the head and the face, mean size = 1.5 cm, and MFH lesions were from the head, the neck, the trunk, and the upper/lower extremities, mean size = 5.2 cm. The 17 cases of AFX demonstrated moderate or strong (2 to 3+) immunoreactivity with CD99, compared to nine of 26 (35%) MFH cases (chi-square = 18.38; p < 0.001; interobserver correlation coefficient = 0.83). Of these, 16 of 17 (94%) AFX cases stained diffusely with CD99, while only four of 26 (15%) MFH cases stained diffusely. Control slides were adequate. Our study demonstrated that CD99 can help distinguish AFX from MFH, in addition to other immunohistochemistry as well as clinical and histologic criteria.

Carcinosarcomas and carcinoma ex pleomorphic adenoma of the salivary glands are rare tumors that fit into the broader category of malignant mixed tumors. Although most evidence has suggested that the different morphologic components arise from a common clonal origin, there are very few studies that have provided molecular evidence for this clonality. In this study, we examined a set of seven carcinosarcomas and four carcinomas ex pleomorphic adenoma for tumor suppressor gene loss of heterozygosity, in order to assess the clonal patterns in the varying components. Microdissection was performed to obtain each morphological component and tumor suppressor gene loci on 3p, 5q, 9p, 17p, 17q, and 18q were analyzed. The fractional allelic loss (FAL) was calculated for each area, and the different targets were compared for their molecular profile. The overall mean FAL of the malignant targets was 42%. In carcinosarcomas, the sarcomatous targets had a higher mean FAL than the carcinomatous targets (68 vs 46%, respectively) and in carcinomas ex pleomorphic adenoma, the mean FAL in the benign component was 11 vs 46% seen in the carcinomatous component. The most frequently lost genetic loci were p53 (17p13, 73%), nm23-H1 (17q21, 55%), and DCC (18q21, 50%). Loss of heterozygosity of 17q21 and 9p21 only occurred in carcinosarcomas and not in carcinomas ex pleomorphic adenoma. Within the carcinosarcomas, the mutational profiles were conserved between epithelial and sarcomatous areas. In carcinomas ex pleomorphic adenoma, loss of heterozygosity was uncommon in the benign component, but the mutations were conserved in the corresponding malignant areas. These results support the hypothesis that the carcinomatous and sarcomatous components of carcinosarcomas are clonally related. Furthermore, these data support prior studies that suggest a common clonal origin for the benign and malignant components of carcinomas ex pleomorphic adenoma.

We have previously demonstrated the accuracy and reproducibility of a probabilistic/categorical approach for reporting breast fine-needle aspiration (FNA). However, the interobserver agreement in the application of this approach has not been assessed. Twenty breast FNA cases (each on one ThinPrep slide) were pulled from the cytology files of Beth Israel Deaconess Medical Center. The cases included benign epithelial proliferative lesions (6), DCIS (4), and infiltrating carcinoma (10), as shown by subsequent histology. Six pathologists with 14-25 yr of experience in interpreting breast FNA and 0-8 yr of experience with ThinPrep preparations rendered diagnoses according to the probabilistic approach. The kappa statistic for the unremarkable/proliferative, atypical, suspicious, and positive categories were 0.64, 0.08, 0.43, and 0.75, respectively (P < 0.001 for all except for the atypical category [P = 0.09]). Spearman's rho correlating the individual pathologist's diagnosis and the histologic diagnosis ranged from 0.51 (P = 0.02) to 0.78 (P < 0.0001). This was not correlated with the pathologists' years of experience interpreting breast FNA (P = 1.0) or with their years using ThinPrep preparations for breast FNA (P = 0.96). In conclusion, the interobserver agreement was excellent for the positive category in the probabilistic approach, poor for the atypical category, and fair to good for the other categories. The specific level of experience interpreting breast FNA or using ThinPrep among experienced pathologists did not seem to influence their accuracy in reporting the cases in our study.

Little data exist that defines the consequences of occupational injuries in children. Traditional assessment of work-related injury is coupled with disability payments based on salary, which give little insight into etiology and severity. The authors hypothesize that the risk and pattern of occupational injuries in young workers are different then adults.Claims from 1996 through 2000 were analyzed from the West Virginia Bureau of Workers Compensation. To define the significance of an injury, child and adult groups were subdivided into injuries that required surgery (ie, serious injuries). Current Procedural Terminology (CPT) codes for anesthesia and surgical procedures were cross referenced with the claims to ensure group designation. Relative risks (RR) were used to compare groups.Between 1996 and 2000, 364,063 claims were submitted, 14,093 in workersor =19 years of age. Two hundred seventy claims in children required surgery. Serious injuries in children occur more often in boys 2.2x mainly in the (16 to 24 hours) evening (48% v 23.13%; P.05) and in July/August (26.5 v 18.4; P.001). Falls were the main mechanism of injury. Proportionately fingers (1.70x) and hands (1.64x, 1.6 to 1.7) were injured in children. Lacerations (3.4x), fractures (1.4x), and amputations (3.75x) frequently resulted in general anesthetic procedures, and the RR of these injuries were increased versus adults. Service, manufacturing, construction, and agriculture were the main injury-related occupations in children.For any job category, injuries in children have unique features, tend to be more serious, and require a surgical intervention proportionately more frequently than adults.

Background The estimation of incidence and evaluation of risk factors associated with nonfatal occupational assault injuries have rarely been documented in a statewide population context. A state-managed workers’ compensation system can provide estimates of incidence of such injuries and allow evaluation of risk factors. Methods Using claims data from the state-managed West Virginia Workers’ Compensation, the incidence rates of workplace injuries resulting from physical assault were estimated for the period 1997–1999. Data on potential risk factors were obtained from the claim-related electronic data files, and the risk associated with each factor was assessed using proportional injury ratios (PIRs). Results During the study period, 2122 compensated injuries were associated with workplace violence. The incidence of assault injuries was 108.2 cases per 100,000 employee years. Women sustained a higher incidence than men. Healthcare workers, public safety workers, and teachers accounted for almost 75% of all assault injuries. Workers in these occupations also differed from each other with regard to seasonality and timing of assault, perpetrator–victim relationship, and types of injury. Evidence of gender–occupation interaction indicated higher risk of assault injury in men compared to women across the three leading occupations. Nighttime work shifts were associated with greater risk of assault for female healthcare workers (PIR=1.8; 95% confidence interval, 1.09–2.87). Conclusion The healthcare sector sustained the bulk of assault injuries in West Virginia. Although the majority of healthcare-sector employees were women, the risk of assault injuries was higher in male employees. Risk factors and injury characteristics identified in this study, particularly for three high-risk occupations, should help develop strategies for preventing workplace violence. Protecting female healthcare workers on night-shift duty, especially in nursing home settings, appears to be an important target for intervention.

Objectives/Hypothesis: Interleukin-10 (IL-10) is an immunosuppressive cytokine with numerous, well-described effects on the human cellular and humoral immune response. The oncogenic potential of IL-10 has been previously investigated in bronchogenic carcinoma, nasopharyngeal carcinoma, Waldeyer's ring carcinoma, and serum supernatants of patients with squamous cell carcinoma of the head and neck (SCCHN). The purpose of the study was to determine the prevalence and cellular localization of IL-10 in human SCCHN. Study Design: Immunohistochemistry of archival tissues. Methods: Paraffin-embedded archival tissues were retrospectively obtained from 98 patients with oral and pharyngeal squamous cell carcinoma. Using a standard immunohistochemical technique, these specimens were stained with a polyclonal antibody to IL-10. Results: Using these methods, we found specific localization of antigenic IL-10 to individual tumor cells in 65% of tumors studied. Intensity of staining was significantly, but inversely, related to tumor grade and N stage; there also existed a significant staining predisposition for oral cavity lesions when samples from this site were compared with tissues derived from elsewhere in the pharynx. Furthermore, IL-10 was not localized to normal epithelial keratinocytes or inflammatory cells at the level of sensitivity achieved by the immunohistochemical methods used in the study. Conclusions: The findings demonstrate that IL-10 can be specifically localized to human oral and pharyngeal cancer cells. These data also suggest an inverse association for both tumor grade and N stage with specific tumor marker staining. Future studies should investigate the role of this cytokine in the pathogenesis of human SCCHN.

Recent data suggests that intradermal (ID) injection for sentinel lymph node (SLN) mapping and biopsy in breast cancer is as effective and reproducible as intraparenchymal (IP) injection. The aim of this study was to review our initial experience with IP and ID injection for SLN mapping and biopsy at our rural-based university medical center.From January 4, 1999 to January 5, 2001, 113 of 165 patients with breast cancer underwent attempted SLN mapping and biopsy by either IP (n=63) or ID (n=50) injection. Selection of the IP versus ID injection route was non-randomized and based on surgeon preference. Success of SLN localization was examined.SLN localization was successful in 82% of IP and 100% of ID for radioisotope (p=0.001), 69% of IP and 92% of ID for blue dye (p=0.002), and 90% of IP and 100% of ID (p=0.024) for radioisotope and blue dye. Identical comparisons made after excluding the first 10 cases, 20 cases, and 30 cases from each injection group showed that the percentage of cases in each group in which the SLN localized changed minimally; however, some of the resultant p values eventually lost statistical significance.SLN localization was more successful by ID injection than by IP injection, thus favoring utilization of the ID injection route. The eventual loss of statistical power in some of the comparisons with increasing numbers of initial cases excluded may reflect differential learning curves of the two injection techniques; however, this may simply be a reflection of decreasing sample size used in each subsequent analysis. A prospective randomized trial comparing the IP and ID injection route may be warranted.

Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns. For 687 patients, 13.8% developed metastases to bone (n=42) or visceral sites (n=53). Metastases to viscera occurred within five years, a latent period which was shorter than that for bone (P=0.042). More women with visceral metastasis presented with grade 3 tumors compared with the bone and nonmetastatic groups (P=0.0002). There were 135/574 women (23.5%) with triple-negative breast cancer, who presented with lymph node involvement and visceral metastases (68.2% versus 24.3%;P=0.033). Triple-negative tumors that metastasized to visceral sites were larger (P=0.007). Developing a visceral metastasis within 10 years was higher among women with triple-negative tumors. Across all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. The excess risk of metastatic spread to visceral organs in triple-negative breast cancers, even in the absence of positive nodes, was combined with the burden of larger and more advanced tumors.

BACKGROUND The presence of tumor cells in peritoneal washing cytology specimens taken during surgery affects the staging of many gynecologic malignancies. Peritoneal washings are often collected routinely, even in cases of presumed benign disease. This study was designed to address whether evaluation of these specimens is justified. METHODS We reviewed diagnostic reports from all peritoneal washings and the corresponding surgical pathology specimens from patients undergoing gynecologic surgery during a 1-year period in one institution and a 20-month period in the other. Cases were divided into benign and malignant categories based on the surgical pathology diagnosis. RESULTS Three hundred forty-six patients had peritoneal washings collected during the study period. The proportion of cases with malignancy was 30% in one institution and 49% in the other. Of these, 119 had an endometrial or ovarian malignancy, including 16 ovarian tumors of low malignant potential. Malignant cells were detected in 19 cases. In 10 of these 19, grossly apparent peritoneal tumor implants were present at the time of surgery. The remaining 227 were found to have benign disease, and the peritoneal washing cytology diagnosis was negative in all cases. Potential savings of $13,000 to $17,000 based on current insurance reimbursement could have been realized for these 227 patients without compromising patient care. CONCLUSIONS These data suggest that peritoneal washing cytology specimens collected at the time of gynecologic surgery for presumed benign disease can be held and processed later if an unsuspected malignancy is discovered. This practice can result in cost savings without compromising patient care. Cancer (Cancer Cytopathol) 1999;87:259–62. © 1999 American Cancer Society.

OBJECTIVE: To develop a classification scheme for reporting the results of fine needle aspiration (FNA) cytology of a breast lesion according to its likelihood of being a carcinoma. STUDY DESIGN: To verify the validity of this scheme, we studied a total of 267 FNAs that were prospectively classified according to predefined criteria as positive (76), suspicious (41), proliferative with atypia (66), proliferative without atypia (48) and unremarkable (36), and compared these results with the final histology. RESULTS : The percentages of patients who had carcinoma on histology were 100% (76), 93% (38), 35% (23), 6% (3) and 31% (11) of cases diagnosed as positive, suspicious, atypical proliferative, proliferative without atypia and unremarkable on cytology, respectively. However, if only invasive carcinoma is considered, then the percentage of carcinoma was 99% (75), 93% (38), 23% (15), 2% (1) and 11% (4), respectively. The only invasive carcinoma in the proliferative-without-atypia category was a tubular carcinoma and represented a false negative diagnosis. All four invasive carcinomas with an unremarkable cytologic diagnosis were due to sampling errors. Definitive, surgery after FNA was common in cases with positive (65%) and suspicious (42%) cytologic diagnosis, whereas all but one patient with atypical, proliferative and unremarkable diagnoses had a biopsy initially. CONCLUSION: This scheme of reporting breast FNA results with defined criteria according to the probability of identifying carcinoma provides a rational basis for guidelines for the management of breast lesions.

Although results from some epidemiologic studies indicate an association between silicosis and lung cancer, other investigations have not confirmed these findings. The discrepancies may be related to methodologic problems. These include the lack of autopsy confirmation for the presence of silicosis or of information on the histologic lung cancer type, and unavailable or uncertain estimates of exposures to silica and to known carcinogens that may interact with silica or silicosis. This study will be designed to avoid the above weaknesses and reconcile observations in humans with results from animal studies, which show a carcinogenic effect for silica. We have formulated a series of testable hypotheses based on plausible mechanisms of carcinogenesis. These hypotheses suggest that silica interacts with known carcinogens (e.g., radon or cigarette smoke), and that only specific types of lung cancer are associated with silica or silicosis: (1) if silica or silicosis of lung parenchyma causes proliferat...

Objectives Despite the wide use of the International Labor Organization (ILO) system for reading chest radiographs, little information is available regarding the prevalence of abnormalities in populations unexposed to dusts. Prevalence studies of radiographic changes consistent with dust inhalation, as classified by the system, would be more meaningful if there were better understanding regarding the extent of abnormalities in unexposed populations. Design To determine small opacity prevalence in unexposed populations, a review of articles published since 1970 that used the ILO system to classify radiographs of the unexposed, either as subjects or control subjects, was performed. Criteria for inclusion in this review included ascertainment of the lack of exposure of subjects to occupational dusts, and independent reading of radiographs by at least two readers certified in the ILO system (B readers) or experienced in its use. A total of eight published articles presenting data on nine study populations were included in this study. Results The prevalence of small opacities graded 1/0 or greater varied widely, with a range from 0.21 to 11.7%. A meta-analysis of the published data yielded a population prevalence of 5.3% (95% confidence interval [CI]=2.9 to 7.7%). The prevalence was significantly greater in Europe than in North America (Europe, 11.3%; 95% CI=10.1 to 12.5%; North America, 1.6%; 95% CI=0.6 to 2.6%). A subset of the studies contained information on gender that showed greater prevalence of lung opacities in male subjects than female subjects (male subjects, 5.5%; 95% CI=3.4 to 7.6%; female subjects, 3.5%; 95% CI=1.3 to 5.8%). Based on estimated age information, the studies were divided into two strata (mean age Conclusions These results indicate that a background level of opacities consistent with the radiographic appearance of pneumoconiosis exists in populations considered to be free of occupational dust exposure. Environmental and unaccounted occupational exposures, as well as reader variability, all may play a role in the determination of small opacity prevalence in these subjects and may explain the large differences between Europe and North America. Thorough ascertainments of occupational and environmental exposures are essential to determine the true significance of opacities in populations who are not exposed to dust.

Perfluoroalkyl substances are manmade chem- icals used in many consumer products and have become ubiquitous in the environment. Animal studies and a limited number of human studies have demonstrated developmental effects in offspring exposed to perfluoroalkyl substances in utero, but the implications of timing of in utero exposure have not been systematically investigated. The present study investigated variation in perfluorocarbon levels of 9952 women of childbearing age who had been exposed to perfluorooctanoic acid (PFOA) in drinking water contaminated by industrial waste. An analysis of variance with contrast was performed to compare the levels of PFOA and perfluoroocta- nesulfonic acid (PFOS) in pregnant and nonpregnant women overall and during each trimester of pregnancy. We found that pregnant women had lower circulating PFOA and PFOS concentrations in peripheral blood than nonpregnant women and that PFOA levels were consistently lower throughout all trimesters for pregnancy, suggesting transfer to the fetus at an early stage of gestation. These results are discussed in the context of the endocrine-disrupting properties of perfluoroalkyl substances that have been characterized in animal and human studies. Our conclusion is that further, systematic study of the potential implications of intrauterine perfluorocarbon exposure during critical periods of fetal development is urgently needed.

Purpose/objectives To examine how routine laboratory biomarkers and clinical parameters available within medical records related to overall survival in patients with non-small cell lung cancer (NSCLC). Design Retrospective chart review. Setting University-based cancer center in rural West Virginia. Sample 110 patients from the U.S. Appalachian region with a primary diagnosis of NSCLC at initial hospitalization. Methods Electronic medical records were reviewed for one year after discharge or until death. The Kaplan-Meier method was used to compare survival curves for each prognostic factor. Cox proportional hazards model was used for multivariate analyses. Main research variables Total white blood cell, neutrophil, lymphocyte, and platelet counts; hemoglobin level; body mass index (BMI); performance status; and cancer stage. Findings Low BMI (lower than 18.5 lb/in2), advanced cancer stage (IIIB or IV), and elevated neutrophil (higher than 8 x 103/mcl) and platelet (300-826 x 1012/L) counts were significant, independent prognostic factors for shorter survival time in NSCLC. BMI (hazard ratio [HR] = 2.15, 95% confidence interval [CI] [0.94, 4.9]) and neutrophil (HR = 2.93, 95% CI [1.53, 5.59]) and platelet (HR = 2.65, 95% CI [1.25, 5.62]) counts were overall prognostic predictors for patients with advanced NSCLC and remained in the multivariate survival model. Conclusions This study detected two known clinical parameters, cancer stage and nutritional status (i.e., BMI and neutrophil and platelet counts), as having independent prognostic significance for shorter survival in NSCLC. Research on survival in patients with NSCLC should include those identified laboratory biomarkers and clinical parameters for screening patients at risk for shorter survival time following hospitalization. Investigation of whether treatments tailored to address neutrophil and platelet counts and BMI can improve survival outcomes also is warranted. Implications for nursing Attention to common biomarkers recorded in patient charts (e.g., neutrophil and platelet counts) as well as BMI could allow nurses to identify patients at risk for low survival. Interventions should be identified and initiated. Longitudinal studies in clinical settings that follow the survival of patients with NSCLC are essential.

Background Cardiovascular disease (CVD) is a major public health problem. Identifying novel risk factors for CVD, including widely prevalent environmental exposures, is therefore important. Perfluorooctanoic acid (PFOA) is a manmade chemical used in the manufacture of common household consumer products. Biomonitoring surveys have shown that PFOA is detectable in the blood of more than 98% of the US population. Experimental animal studies suggest that an association between PFOA and CVD is plausible. However, this association in humans has not been previously examined. We therefore examined the independent relationship between serum PFOA levels and CVD outcomes in a representative sample of Americans. Methods We examined 1216 subjects (51.2% women) from the 1999-2003 National Health and Nutritional Examination Survey. Serum PFOA levels were examined in quartiles. The main outcomes of interest were self-reported CVD, including coronary heart disease and stroke, and objectively measured peripheral arterial disease (PAD), defined as an ankle-brachial blood pressure index of less than 0.9. Results We found that increasing serum PFOA levels are positively associated with CVD and PAD, independent of confounders such as age, sex, race/ethnicity, smoking status, body mass index, diabetes mellitus, hypertension, and serum cholesterol level. Compared with quartile 1 (reference) of PFOA level, the multivariable odds ratio (95% CI) among subjects in quartile 4 was 2.01 (1.12-3.60; P = .01 for trend) for CVD and 1.78 (1.03-3.08; P = .04 for trend) for PAD. Conclusion Exposure to PFOA is associated with CVD and PAD, independent of traditional cardiovascular risk factors.

Background Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the development and progression of colorectal cancer (CRC). However, the link between these compounds and CRC remains unknown. In this cross-sectional study, we investigated the association of CRC diagnosis to PFOA and PFOS blood levels in a large Appalachian population. Methods Participants were 47,359 adults ≥ 21 years of age and residing in six PFOA-contaminated water districts in the mid-Ohio Valley (N = 47,151 cancer-free adults, 208 cases of primary CRC). All participants completed a comprehensive health survey between 2005 and 2006; serum levels of PFOA, PFOS, and a range of other blood markers were also measured. Medical history was assessed via self report and cancer diagnosis confirmed via chart review. Results CRC showed a strong inverse, dose–response association with PFOS serum levels (odds ratio (OR) adjusted for potential confounders = 0.2, 95% confidence interval (CI) 0.2,0.3) for highest vs. lowest quartile of PFOS, P-trend

The increasing prevalence of childhood obesity has been well documented & is predictive of increased severity in obesity-related CVD risk factors & metabolic disorders, such as systemic inflammation & oxidative stress. While the poor long-term vascular consequences of these conditions are better understood in adults, the consequences of these obesity-associated metabolic disturbances are less studied in children. This study utilized the 12,476 children (

A stress-induced myocardial perfusion abnormality (MPS), in the absence of angiographically significant epicardial coronary artery disease, is considered a "false-positive" test result. We hypothesized that echocardiography would provide complementary prognostic and pathophysiologic data relevant to the management of patients with MPS and normal coronary angiograms. Accordingly, left atrial volume index (LAVi) was assessed by echocardiography in 38 patients with false positive MPS as defined by normal coronary angiograms and 26 patients with true negative MPS from a total of 1,356 patients stressed from July 2006-May 2008. Pathologically abnormal elevation of LAVi (≥ 32 mL/m(2)) was observed in 16 of 19 women (84%) and 11 of 19 men (58%) in the false positive MPS (FPMPS) group while none of the patients in the true negative MPS (TNMPS) group had elevated LAVi. In the FPMPS group mean LAVi was significantly higher in women than men (40.64 ± 11.4 mL/m(2) versus 32.6 ± 10.5 mL/m(2), P = 0.01). The mean LAVi in the FPMPS group was significantly different from the TNMPS group (36.6 ± 11.6 versus 21 ± 7 mL/m(2), P = 0.000). A stepwise logistic regression determined BSA, LAV and LAVi as useful in predicting false positive and true negative MPS. All three were significant predictors (P < 0.01) and the area under the ROC curve was 0.91. Our findings in this relatively small cohort suggest that patients with false positive MPS have a greater increased LAVi.

Context.—In 2006, the first gynecologic cytology proficiency tests were offered by the College of American Pathologists. Four years of data are now available using field-validated slides, including conventional and liquid-based Papanicolaou tests.Objective.—To characterize the pattern of error types that resulted in initial proficiency-test failure for cytotechnologists, primary screening pathologists, and secondary pathologists (those whose slides are prescreened by cytotechnologists).Design.—The results of 37 029 initial College of American Pathologists Papanicolaou proficiency tests were reviewed from 4 slide-set modules: conventional, ThinPrep, SurePath, or a module containing all 3 slide types.Results.—During this 4-year period, cytotechnologists were least likely to fail the initial test (3.4%; 614 of 18 264), followed by secondary pathologists (ie, those reviewing slides already screened by a cytotechnologist) with a failure rate of 4.2% (728 of 17 346), and primary pathologists (ie, those screening their own slides) having the highest level of failure (13.7%; 194 of 1419). Failure rates have fallen for all 3 groups over time. Pathologists are graded more stringently on proficiency tests, and more primary pathologists would have passed if they had been graded as cytotechnologists. There were no significant differences among performances using different types of slide sets. False-positive errors were common for both primary (63.9%; 124 of 194 errors) and secondary (55.6%; 405 of 728 errors) pathologists, whereas automatic failures were most common for cytotechnologists (75.7%; 465 of 614 errors).Conclusions.—The failure rate is decreasing for all participants. The failures for primary pathologist screeners are due to false-positive responses. Primary screening cytotechnologists and secondary pathologists have automatic failures more often than do primary screening pathologists.

Anoop Shankar, Jie Xiao, Alan DucatmanDepartment of Community Medicine, West Virginia University School of Medicine, Morgantown, WV, USABackground: Perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, are man-made chemicals that have been detected in the blood of over 98% of the US population. Serum uric acid is a novel biomarker, even mild elevations of which has been implicated in the development of hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. We examined the relationship of serum perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, and elevated uric acid levels in a representative sample of US adults.Methods: We examined 3883 participants from the 1999–2000 and 2003–2006 National Health and Nutritional Examination Surveys,a representative, multiethnic population-based survey of noninstitutionalized US adults. Serum perfluorooctanoic acid and perfluorooctane sulfonate were analyzed as quartiles. The main outcome was hyperuricemia.Results: We found that serum levels of perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with hyperuricemia. This association appeared to be independent of confounders such as age, gender, race-ethnicity, body mass index, diabetes, hypertension, and serum cholesterol. Compared with subjects in quartile 1 (referent), the multivariate odds ratio for hyperuricemia among subjects in quartile 4 was 1.97 (95% confidence interval 1.44–2.70, P < 0.0001) for perfluorooctanoic acid and 1.48% (95% confidence interval 0.99–2.22, P = 0.0433) for perfluorooctane sulfonate. This observed association persisted in subgroup analysis by gender and body mass index.Conclusion: Our results demonstrate that elevated levels of perfluoroalkyl chemicals are associated with hyperuricemia even at low perfluoroalkyl chemical exposure levels as seen in the US general population.Keywords: perfluoroalkyl chemicals, perfluorooctanoic acid, perfluorooctane sulfonate, uric acid

Perfluorocarbons from common household products such as food containers, stain- resistant protection for clothing, furniture and carpets, paints, and fire-fighting foams are found in soil, water, plants, animal and human serum worldwide. Previous research has shown a significant association between these chemicals and thyroid disease in women. The present data from the C8 Health Project assessed thyroid function in a cross-sectional analysis of 52,296 adults with a year or more of exposure to perfluorooctanoate (PFOA) from drinking water. Outcomes were: thyroxine, T3 uptake, and thyroid stimulating hormone (TSH). Analyses were stratified by gender and age group (20 -50 years and50). Both PFOA and perfluorooctane sulfonate (PFOS) were associated with significant elevations in serum thyroxine and a significant reduction in T3 uptake in all participants. There were also significant gender/PFOS interactions for T3( )uptake and thyroxine, as well as gender/PFOA interactions for T3 uptake. Results provide evidence for disruption of thyroid function related to these common chemicals and possible mechanisms are discussed.

Objective: The primary objective of this project is to determine if circulating tumor cells (CTCs) are identifiable in peripheral blood from patients with advanced head and neck squamous cell carcinoma using a commercially available semi-automated technique.Method: Prior to treatment, adult patients with advanced Head and Neck Squmous Cell Carcinoma had whole peripheral blood drawn and analyzed using the CellSearch Epithelial CTC kit. The target molecules of the system include EpCAM and cytokeratins 8, 18, and 19.Results: There was a total of 18 patients with additional positive and negative controls. The average age was 65 years and 61% of the population was female. Primary tumor sites were varied with 39% laryngeal, 33% pharyngeal, 22% oral cavity, and 6% cutaneous. The majority of patients, 78%, had stage IV disease at the time of evaluation. The positive control, SCC-1483, identified over 305 CTCs. There were no CTCs identified in clinical samples.Conclusion: HNSCC cells are detectable using the CellS...

Objectives The authors compared rates of tooth loss between adult residents of Appalachian coal-mining areas and other areas of the nation before and after control for covariate risks. Methods The authors conducted a cross-sectional secondary data analysis that merged 2006 national Behavioral Risk Factor Surveillance System data (BRFSS) (N = 242 184) with county coal-mining data and other county characteristics. The hypothesis tested was that adult tooth loss would be greater in Appalachian mining areas after control for other risks. Primary independent variables included main effects for coal-mining present (yes/no) residence in Appalachia (yes/no), and their interaction. Data were weighted using the BRFSS final weights and analyzed using SUDAAN Proc Multilog to account for the multilevel complex sampling structure. The odds of two measures of tooth loss were examined controlling for age, race\ethnicity, drinking, smoking, income, education, supply of dentists, receipt of dental care, fluoridation rate, and other variables. Results After covariate adjustment, the interaction variable for the residents of Appalachian coal-mining counties showed a significantly elevated odds for any tooth loss [odds ratio (OR) = 1.19, 95% CI = 1.02, 1.38], and greater tooth loss measured by a 4-level edentulism scale (OR = 1.20, 95% CI = 1.05, 1.36). The main effect for Appalachia was also significant for both measures, but the main effect for coal mining was not. Conclusions Greater risk of tooth loss among adult residents of Appalachian coal-mining areas is present and is not explained by differences in reported receipt of dental care, fluoridation rates, supply of dentists or other behavioral or socioeconomic risks. Possible contributing factors include mining-specific disparities related to access, behavior or environmental exposures.

Background.An increased risk of lung cancer has been observed at exposure to certain industrial chemicals in occupational settings; however, less is known about their carcinogenic potential to the general population when those agents are released into the environment.Methods.We used the Toxics Release Inventory (TRI) database and Surveillance, Epidemiology, and End Results (SEER) data to conduct an ecological study at the county level. We used multiple linear regression to assess the association of age-adjusted lung cancer incidence with the quantities of on-site air and water releases of six selected industrial chemicals including arsenic, 1,3 butadiene, cadmium, chromium, formaldehyde, and nickel after controlling for other risk variables.Results.Overall, we observed a significantly increased risk of lung cancer incidence associated with releases of chromium, formaldehyde, and nickel. The links were present for both males and females. Significant effects were present in nonmetropolitan but not metropolitan counties. Releases of arsenic, 1,3 butadiene, and cadmium were reported by small numbers of facilities, and no relationships to lung cancer incidence were detected.Conclusions.Our results suggest that environmental exposure to chromium, formaldehyde, and nickel from TRI sites may increase population risk of lung cancer. These findings need to be confirmed in individual-level studies, but in congruence with the precautionary principle in environmental science, support prudent efforts to limit release of these agents into the environment.

Hürthle cells may be found in fine-needle aspirates of the thyroid (FNATs) from Hürthle cell tumors (HCTs) and nonneoplastic Hürthle cell lesions, including Hashimoto's thyroiditis and goiter. To differentiate the characteristic cytomorphologic features from these lesions, the authors studied 38 surgically excised Hürthle cell lesions of the thyroid. Preoperative FNATs were reviewed for a number of architectural and cytologic features. The chi-squared and Fisher's exact tests were used for statistical analysis. There were many statistically significant cytologic differences between HCTs and nonneoplastic Hürthle cell lesions. Statistically significant features indicating an HCT versus nonneoplastic Hürthle cell lesion included the following: a high percentage (90%) of Hürthle cells, single Hürthle cells (10%), cellular dyshesion, large nucleoli, significant nuclear pleomorphism, significant nuclear enlargement, absence of macrophages, absence of plasma cells, and absence of or few lymphocytes. The architecture of cell groups, cellularity, amount of colloid, and multinucleation appeared to be of no value. The presence of a high percentage of dyshesive Hürthle cells with large nucleoli, with some cells showing significant nuclear enlargement and pleomorphism, associated with a lack of lymphoplasmacytic inflammatory cells, appears statistically predictive of an HCT and should enable the differentiation of an HCT from a nonneoplastic Hürthle cell lesion.

Background. Fine-needle aspiration has been less valuable in the diagnosis of follicular lesions than for other neoplasms of the thyroid. It has been observed that follicular carcinoma is found in microfollicular, but not macrofollicular lesions, and this has served as a guide to management for many surgeons. The authors attempted to determine what cytologic parameters might usefully distinguish these types of follicular lesion. Methods. The histologic findings and cytology of 56 thyroid lobectomies for follicular lesions that had adequate preoperative fine-needle aspiration of the thyroid (FNAT) were reviewed. Histologic specimens were classified into macrofollicular, mixed, and microfollicular groups. Cytologic features examined included the presence of colloid, irregularity of cell arrangements within groups, the presence and size of flat and folded cell sheets, three-dimensional clusters, and microfollicles and macrofollicles. Results. Of the histologic specimens, 15 were preponderantly (≥ 70%) microfollicular, 19 were mixed, and 22 were predominantly (≥ 70%) macrofollicular. Three cytologic features were useful in their distinction: none of the predominantly microfollicular but 24% of the mixed and predominantly macrofollicular had abundant colloid (P = 0.048). Likewise, none of the predominantly microfollicular but 27% of the mixed and predominantly macrofollicular had large follicles (P = 0.026). Finally, 73% of the predominantly microfollicular but only 37% of the mixed and predominantly macrofollicular showed irregularity or crowding of cells in groups (P = 0.018). Conclusions. Used in combination, abundant colloid, regular spacing, and large follicles are helpful in distinguishing macrofollicular and mixed lesions from microfollicular ones, which have a higher malignant potential.