Trends in Liver and Skin Tumor Prevalence in Brown Bullhead ( Ameiurus nebulosus) from the Anacostia River, Washington, DC, and Nearby Waters.

The prevalence of liver and skin tumors in brown bullhead ( Ameiurus nebulosus) from the Anacostia River (Washington, DC) and nearby areas was determined in 2014, 2015, and 2016. The objectives were to (1) compare tumor prevalence across space and time; (2) analyze the 1992-2016 Chesapeake Bay Tumor Database to identify reference locations and test age, length, weight, and sex as covariates; and (3) explore whether changes in bullhead exposure to contaminants can explain the observed trends. With logistic regression, we reported large statistically significant decreases in liver tumor probabilities in bullheads from the Anacostia CSX Bridge (ANAC) area between 1996 and 2001 (merged: female, 77.8%; male, 48.6%), 2009 to 2011 (female, 42.5%; male, 16.6%), and 2014 to 2016 (female, 18.0%; male, 5.7%). Skin tumors decreased by a factor of six in both females and males. Polycyclic aromatic compounds (PAC) initiate liver neoplasms and polychlorinated biphenyls (PCBs) and DDT compounds are promoters. The causes of skin tumors in bullhead are uncertain. Biomarker and tissue data show decreases in PAC-DNA adducts and PCB and DDT contamination in ANAC bullheads. It is likely that the decreased liver tumor prevalence is associated with decreased exposure to these contaminants.

Tumor prevalence and biomarkers of genotoxicity in brown bullhead (Ameiurus nebulosus) in Chesapeake Bay tributaries.

We surveyed four Chesapeake Bay tributaries for skin and liver tumors in brown bullhead (Ameiurus nebulosus). We focused on the South River, where the highest skin tumor prevalence (53%) in the Bay watershed had been reported. The objectives were to 1) compare tumor prevalence with nearby rivers (Severn and Rhode) and a more remote river (Choptank); 2) investigate associations between tumor prevalence and polynuclear aromatic hydrocarbons (PAHs) and alkylating agents; and 3) statistically analyze Chesapeake Bay bullhead tumor data from 1992 through 2008. All four South River collections exhibited high skin tumor prevalence (19% to 58%), whereas skin tumor prevalence was 2%, 10%, and 52% in the three Severn collections; 0% and 2% in the Choptank collections; and 5.6% in the Rhode collection. Liver tumor prevalence was 0% to 6% in all but one South River collection (20%) and 0% to 6% in the three other rivers. In a subset of samples, PAH-like biliary metabolites and (32)P-DNA adducts were used as biomarkers of exposure and response to polycyclic aromatic compounds (PACs). Adducts from alkylating agents were detected as O6-methyl-2'-deoxyguanosine (O6Me-dG) and O6-ethyl-2'-deoxyguanosine (O6Et-dG) modified DNA. Bullheads from the contaminated Anacostia River were used as a positive control for DNA adducts. (32)P-DNA adduct concentrations were significantly higher in Anacostia bullhead livers compared with the other rivers. We identified alkyl DNA adducts in bullhead livers from the South and Anacostia, but not the Choptank. Neither the PAH-like bile metabolite data, sediment PAH data, nor the DNA adduct data suggest an association between liver or skin tumor prevalence and exposure to PACs or alkylating agents in the South, Choptank, Severn, or Rhode rivers. Logistic regression analysis of the Chesapeake Bay database revealed that sex and length were significant covariates for liver tumors and length was a significant covariate for skin tumors.

Tumors in brown bullheads in the Chesapeake Bay watershed: analysis of survey data from 1992 through 2006.

Liver and skin tumor prevalences in brown bullheads Ameiurus nebulosus have been used in the North American Great Lakes to designate highly contaminated areas of concern and monitor their recovery. Here we interpret the results of six surveys conducted in the Chesapeake Bay watershed between 1992 and 2006, with data for 647 fish. The objective has been to develop an adequate database to critically evaluate the use of tumor prevalence as a habitat quality indicator within the watershed. Surveys featured randomized fish collection; recording of sex, length, weight, and age; and histopathology of all livers and all raised skin lesions. The Bayes information criterion was used to analyze all possible combinations of age, gender, length, and weight as covariates for logistic regression. Length and gender were the covariates that best described liver tumor prevalence. There were no covariates in the model for skin tumor prevalence. In some surveys, biomarkers, such as biliary polynuclear aromatic hydrocarbon (PAH)-like metabolites, hepatic cytochrome P450 activity, and hepatic DNA adducts, were used with sediment and tissue chemistry data to evaluate classes of chemicals as likely contributors to tumor prevalence. We highlight two surveys of the Anacostia River, Washington, D.C. (average = 55% liver tumors, 23% skin tumors), where sediment PAHs, biliary PAH-like metabolites, and hepatic DNA adducts were high, suggesting that PAHs play a major role. We show that logistic regression is an appropriate procedure for comparing "contaminated" versus "reference" locations, and we evaluate the utility of tumor surveys as an environmental indicator for the Chesapeake Bay watershed.

A multicenter, randomized, open study to evaluate the impact of an electronic data capture system on the care of patients with rheumatoid arthritis.

OBJECTIVE: To examine the impact of an electronic data capture system on patient satisfaction and patient-physician interactions in a rheumatology clinical setting. STUDY DESIGN: In this multicenter study, 1079 patients with rheumatoid arthritis completed questionnaires quarterly about their health and satisfaction with care using a computer. At 6 months, 901 eligible patients were randomized 2:1 to receive or not to receive graphical summarized health information or Health Tracker (HT) reports. Data collected at each visit included patient satisfaction with care; patient-physician interaction assessments; a 56-joint self-assessment for patients; a 28-joint assessment for physicians; patient pain, fatigue, and global assessments (visual analogue scale, physician global assessment, Health Assessment Questionnaire, and Short Form-12) all of which were cumulatively recorded in the HT report. RESULTS: Patient demographics at baseline were similar between groups. Changes from baseline to 1 year showed that patients in the HT-viewers group were significantly more satisfied with their care (p < 0.001) than those in the HT-nonviewers group (p = 0.131). Physicians reported improved interactions with patients at 1 year in both the HT-viewers (p < 0.001) and HT-nonviewers groups (p = 0.002); however, the improvement was significantly larger for the HT-viewers group than for the HT-nonviewers group (p < 0.001). Adverse events were comparable between groups. CONCLUSIONS: Patient access to systematically collected patient data reports promoted self-involvement and improved patient satisfaction and patient-physician interactions more in the HT-viewers than in HT-nonviewers groups at 1 year (p < 0.001). This was an open, observational study; no formal hypothesis testing was conducted. The HT system was not validated and some bias may have existed with respect to patient comfort level with a computer, user error, and timing of data entry of the physicians' assessments.

Germinoma in razor clam Ensis arcuatus (Jeffreys, 1865) in Galicia (NW Spain).

Germinoma is a gonadal neoplasm originating from progenitor cells in germinal epithelium. Over the last four decades it has been diagnosed in several species of marine bivalve molluscs but most consistently in some populations of Mercenaria mercenaria and Mya arenaria in North America. Tissue sections of gonads from Ensis arcuatus (family Pharidae--superfamily Solenacea), collected in Ría de Vigo (Galicia-NW Spain), revealed germinoma in both males and females. Proliferating, undifferentiated, germ cells, with no evidence of maturation, had formed discrete masses in the walls and lumens of gonadal follicles. This is the first report of germinoma in superfamily Solenacea.

Tumor Prevalence in Mummichogs from the Delaware Estuary Watershed.

Mummichogs Fundulus heteroclitus were collected in 2002-2004 from six locations within the Delaware Estuary watershed and examined histopathologically. The objective was to compare the prevalence of skin and liver tumors in fish from locations with a range of sediment polynuclear aromatic hydrocarbons (PAHs) based on available data. Fish were collected from (1) three locations within the industrialized Christina River subwatershed (Hershey Run, Newport Marsh (upriver and downriver)); (2) one location in the Motiva Enterprises refinery discharge canal to the Delaware River; (3) one location in the St. Jones River; and (4) one location in Blackbird Creek. Adult mummichogs (≥70 mm; n = 21-30 fish per location) were seined and held for necropsy. No neoplastic skin lesions were diagnosed in any fish. No liver tumors were diagnosed in the St. Jones, Motiva, Newport Marsh upriver, or Newport Marsh downriver collections. One of 30 Blackbird Creek mummichogs had foci of hepatocellular alteration (a putative preneoplastic lesion) and one had hepatocellular carcinoma. There was a significant difference in hepatocellular carcinoma prevalence in Hershey Run mummichogs in 2002 (9 of 21 fish, or 43%) and in 2003 (3 of 29 fish, or 10%) compared with all other locations pooled (1 of 145 fish, or 0.7%). Hershey Run is contaminated with creosote from an adjacent Superfund site, where sediments were frequently reported to have total PAH concentrations greater than 100 mg of total PAH/kg and a maximum of 13,300 mg/kg. No other locations had reports of total PAHs higher than 11 mg/kg. In conclusion, liver neoplasia was associated with exposure to sediment containing high concentrations of PAHs derived from creosote. Studies that include tumor prevalence, biomarkers (e.g., DNA adducts and PAH metabolites in bile), and sediment and/or tissue chemistry are recommended to develop a weight of evidence for specific chemical classes.

Morphometry of hepatic neoplasms and altered foci in the mummichog, Fundulus heteroclitus.

The goal of this study was to intensively sample a small number of livers from a population of mummichog exposed to PAH-contaminated sediments and evaluate them for lesion pathology, distribution, shape, and volume, and the number of histological sections needed to adequately describe the extent of various lesions. Volumetric data for each lesion type from each step section was derived from digitized section images. The total number of hepatic alterations ranged from 10-125 per fish. Alterations included: eosinophilic, basophilic, and clear cell foci; hepatocellular carcinomas; hemangiopericytomas; and cholangiomas. Lesion volumes ranged from 0.00012-64 mm3 and represented 0.21%-67% of total liver volume. There was a tendency for the lesions to be more dorsal-ventrally compressed than spherical or ropelike when observed from longitudinal sections. Periodic subsampling of the data indicated that. on average, 6 evenly spaced, longitudinal histological sections were required to accurately estimate lesion volume and extent in our model population. These data provide a formulation for histological sampling techniques and methodological support for piscine and other cancer study models that observe lesion volume changes over time. Further, this study fosters the development of early quantitative endpoints. rather than using a large number of animals and waiting for tumor progression or death to occur.

Tumor prevalence and biomarkers of exposure and response in brown bullhead (Ameiurus nebulosus) from the Anacostia River, Washington, DC and Tuckahoe River, Maryland, USA.

We evaluated liver and skin tumor prevalence and biomarkers of exposure and response in brown bullhead (Ameiurus nebulosus) from three locations in the Anacostia River (Washington, DC, USA), a Chesapeake Bay region of concern. The Tuckahoe River (Maryland, USA) served as a reference. Each river was sampled in fall 2000 and spring 2001. In the Anacostia, prevalence of liver tumors was 50 to 68%, and prevalence of skin tumors was 13 to 23% in large (> or = 260 mm, age > or = 3 years) bullheads. Liver and skin tumor prevalence was 10 to 17% and 0%, respectively, in small (150-225 mm, age 1-2 years) bullheads. Tuckahoe bullhead liver tumor prevalence was 0 to 3% (large) and 0% (small); none had skin tumors. Biliary polynuclear aromatic hydrocarbon (PAH)-like fluorescent metabolites and liver DNA adduct concentrations were elevated in large and small Anacostia bullheads. Mean adduct concentrations were 16 to 28 times higher than those in Tuckahoe fish. Chromatograms revealed a diagonal radioactive zone, indicating polycyclic aromatic compound (PAC)-DNA adducts. The biomarker data and the 10 to 17% liver tumor prevalence at ages 1 to 2 suggest that these year classes are likely to have a high prevalence as they reach age 3 and older. This study provides the strongest evidence to date of the role of PAHs in tumor development in Anacostia bullheads.

Open label study to assess infliximab safety and timing of onset of clinical benefit among patients with rheumatoid arthritis.

OBJECTIVE: To assess the timing of onset of clinical benefit following the initial infusion of infliximab and to obtain additional safety experience of infliximab when given in an office setting to patients with rheumatoid arthritis (RA). In addition, the safety of reducing the infusion time from 2 hours to 1 hour was evaluated. METHODS: Patients (n = 553) with active RA despite receiving methotrexate (MTX) were treated with infliximab 3 mg/kg given over 2 h at baseline (Week 0), and Weeks 2, 6, and 14 in this multicenter open-label trial. Patients continued to receive a stable dose of MTX (> or = 7.5 mg/wk). At selected sites, patients tolerating the first 4 infusions were eligible to receive 2 additional infusions at twice the usual infusion rate (given over 1 h). Patients returned for efficacy assessments at 48 h following the initial infusion and several times throughout study participation. RESULTS: By 48 h following the first infusion, significant (p < 0.001) improvements were observed in duration of morning stiffness (34% mean improvement), physician's global disease assessment scores (30%), patient's global disease assessment scores (25%), and patient's pain assessment scores (30%). By Week 16, 52 to 63% mean improvements in these efficacy variables were observed (p < 0.001), the significant improvement was maintained through the end of study participation in the subset of patients who received the additional 1 h infliximab infusions. Through 16 weeks, 10% (54/553) of patients reported an adverse event associated with at least 1 of the 4 infusion procedures; the majority were mild and transient in nature. In the subset of 197 patients who received 2 additional infusions over 1 h, no increase in the frequency or severity of infusion-related adverse events was observed compared to the 2 h infusion. CONCLUSION: Infliximab administered to patients with RA in an outpatient setting resulted in significant clinical improvement within 48 h that was sustained with additional infusions. Approximately 10% of patients experienced an infusion reaction, highlighting the need for direct supervision over patient treatment. Patients who tolerated infliximab infusions given over 2 h also tolerated a 1 h infusion.

Health of lake whitefish (Coregonus clupeaformis) with elevated tissue levels of environmental contaminants.

Lake whitefish (Coregonus clupeaformis) were collected in 1996 from the St. Lawrence River, Quebec, Canada. Histologic examination was performed on major organs of 497 specimens and on the liver of 48 additional individuals. Preneoplastic and neoplastic hepatic changes consisted of vacuolated cell (n = 65), clear cell (n = 17), and acidophilic (n = 16) foci of altered hepatocyte, hepatocellular carcinoma (n = 12), cholangioma (n = 5), and cholangiocarcinoma (n = 28). Six fish were intersexes (1.2%), and 11.7% of the ovaries (26/223) had ducts containing spermatogonia or more differentiated cells of the male germ cell line. Asynchronous nodular maturation of the testes was present in 8.2% of the male fish (22/267). The mean hepatic concentrations of various contaminants, including polychlorinated biphenyls (PCBs), chlorobenzenes, pesticides, and trace metals, were 6 to 8 times higher in lake whitefish than in three other fish species (Ictalurus punctatus, Catostomus commersoni, and Stizostedion vitreum) collected at the same site. Condition factor of lake whitefish from this study was lower than that previously reported 40 to 50 years ago at this site and from contemporary pristine sites in the Great Lakes, USA. The presence of liver neoplasms, gonadal lesions, and a decreased condition factor in lake whitefish from the St. Lawrence River may be etiologically related to elevated tissue concentrations of toxic chemical contaminants.