Seroprevalence of human toxocariasis, Jamaica.

Seroprevalence of human toxocariasis was studied, based on 1544 samples selected from a total of 3524 submitted to the University of the West Indies in Kingston, Jamaica for diagnosis of dengue during an epidemic in 2010. The prevalence of anti-Toxocara IgG using the CELISA® (Cellabs) ELISA was 21.2% and males (24.4%) were significantly more likely to be exposed than females (17.5%) [χ2 =10.4; p=0.001]. No association was foundbetween exposure to Toxocara and area of residence (rural vs. urban) [χ2 =0.835; p = 0.409]. Prevalence of infection peaked in adolescents (10-19 years-old) and declined thereafter although a rise in prevalence was seen in older age classes. There was a high prevalence of toxocariasis in Jamaica with significant exposure among school age children with no predilection to either sex. The study will inform future work on elucidating the public health and clinical significance of toxocariasis in Jamaica.

Seroprevalence of human toxocariasis, Jamaica

Seroprevalence of human toxocariasis was studied, based on 1544 samples selected from a total of 3524 submitted to the University of the West Indies in Kingston, Jamaica for diagnosis of dengue during an epidemic in 2010. The prevalence of anti-Toxocara IgG using the CELISA® (Cellabs) ELISA was 21.2% and males (24.4%) were significantly more likely to be exposed than females (17.5%) [χ2 =10.4; p=0.001]. No association was foundbetween exposure to Toxocara and area of residence (rural vs. urban) [χ2 =0.835; p = 0.409]. Prevalence of infection peaked in adolescents (10-19 years-old) and declined thereafter although a rise in prevalence was seen in older age classes. There was a high prevalence of toxocariasis in Jamaica with significant exposure among school age children with no predilection to either sex. The study will inform future work on elucidating the public health and clinical significance of toxocariasis in Jamaica.

A rule-based expert system for chemical prioritization using effects-based chemical categories.

A rule-based expert system (ES) was developed to predict chemical binding to the estrogen receptor (ER) patterned on the research approaches championed by Gilman Veith to whom this article and journal issue are dedicated. The ERES was built to be mechanistically transparent and meet the needs of a specific application, i.e. predict for all chemicals within two well-defined inventories (industrial chemicals used as pesticide inerts and antimicrobial pesticides). These chemicals all lack structural features associated with high affinity binders and thus any binding should be low affinity. Similar to the high-quality fathead minnow database upon which Veith QSARs were built, the ERES was derived from what has been termed gold standard data, systematically collected in assays optimized to detect even low affinity binding and maximizing confidence in the negatives determinations. The resultant logic-based decision tree ERES, determined to be a robust model, contains seven major nodes with multiple effects-based chemicals categories within each. Predicted results are presented in the context of empirical data within local chemical structural groups facilitating informed decision-making. Even using optimized detection assays, the ERES applied to two inventories of >600 chemicals resulted in only ~5% of the chemicals predicted to bind ER.

Effects-based chemical category approach for prioritization of low affinity estrogenic chemicals.

Regulatory agencies are charged with addressing the endocrine disrupting potential of large numbers of chemicals for which there is often little or no data on which to make decisions. Prioritizing the chemicals of greatest concern for further screening for potential hazard to humans and wildlife is an initial step in the process. This paper presents the collection of in vitro data using assays optimized to detect low affinity estrogen receptor (ER) binding chemicals and the use of that data to build effects-based chemical categories following QSAR approaches and principles pioneered by Gilman Veith and colleagues for application to environmental regulatory challenges. Effects-based chemical categories were built using these QSAR principles focused on the types of chemicals in the specific regulatory domain of concern, i.e. non-steroidal industrial chemicals, and based upon a mechanistic hypothesis of how these non-steroidal chemicals of seemingly dissimilar structure to 17ß-estradiol (E2) could interact with the ER via two distinct binding types. Chemicals were also tested to solubility thereby minimizing false negatives and providing confidence in determination of chemicals as inactive. The high-quality data collected in this manner were used to build an ER expert system for chemical prioritization described in a companion article in this journal.

Emerging viral diseases and infectious disease risks.

New pathogens and antimicrobial-resistant forms of older pathogens continue to emerge, some with the potential for rapid, global spread and high morbidity and mortality. Pathogens can emerge either through introduction into a new population or when the interaction with the vector changes; emergence is also influenced by microbiological adaptation and change, global travel patterns, domestic and wild animal contact and other variants in human ecology and behaviour. Quick, decisive action to detect and control novel pathogens, and thereby contain outbreaks and prevent further transmission, is frequently hampered by incomplete or inadequate data about a new or re-emerging pathogen. Three examples of pathogens that are current causes for human health concern are avian influenza, West Nile virus (WNV) and the severe acute respiratory syndrome (SARS) coronavirus. Pathogens directly or indirectly transmitted by aerosolized droplets, such as avian influenza and SARS, pose considerable containment challenges. Rapid screening tests for other newly described pathogens such as WNV require time for development and may be <100% reliable. The importance of vigilance in the detection and control of newly recognized infectious threats cannot be overstressed. The presence of infectious agents in the blood supply could again have a significant impact on the safe use of both blood and blood-derived products in the care of patients with haemophilia, as did the human immunodeficiency virus in the 1980s. Emerging pathogens will continue to be a reality requiring the collaborative efforts of public health and individual healthcare providers worldwide to contain outbreaks and prevent transmission.

Discriminating redox cycling and arylation pathways of reactive chemical toxicity in trout hepatocytes.

The toxicity of four quinones, 2,3-dimethoxy-1,4-naphthoquinone (DMONQ), 2-methyl-1,4-naphthoquinone (MNQ), 1,4-naphthoquinone (NQ), and 1,4-benzoquinone (BQ), which redox cycle or arlyate in mammalian cells, was determined in isolated trout (Oncorhynchus mykiss) hepatocytes. More than 70% of cells died in 3 h when exposed to BQ or NQ; 50% died in 7 h when exposed to MNQ, with no mortality compared to controls after 7 h DMONQ exposure. A suite of biochemical parameters was assessed for ability to discriminate these reactivity pathways in fish. Rapid depletion of glutathione (GSH) with appearance of glutathione disulfide (GSSG) and increased dichlorofluoroscein fluorescence were used as indicators of redox cycling, noted with DMONQ, MNQ, and NQ. Depletion of GSH with no GSSG accumulation, and loss of free protein thiol (PrSH) groups (nonreducible) indicated direct arylation by BQ. All toxicants rapidly oxidized NADH, with changes in NADPH noted later (BQ, NQ, MNQ) or not at all (DMONQ). Biochemical measures including cellular energy status, cytotoxicity, and measures of reactive oxygen species, along with the key parameters of GSH and PrSH redox status, allowed differentiation of responses associated with lethality. Chemicals that arylate were more potent than redox cyclers. Toxic pathway discrimination is needed to group chemicals for potency predictions and identification of structural parameters associated with distinct types of reactive toxicity, a necessary step for development of mechanistically based quantitative structure-activity relationships (QSARs) to predict chemical toxic potential. The commonality of reactivity mechanisms between rodents and fish was also demonstrated, a step essential for species extrapolations.

Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States.

From October 4 to November 2, 2001, the first 10 confirmed cases of inhalational anthrax caused by intentional release of Bacillus anthracis were identified in the United States. Epidemiologic investigation indicated that the outbreak, in the District of Columbia, Florida, New Jersey, and New York, resulted from intentional delivery of B. anthracis spores through mailed letters or packages. We describe the clinical presentation and course of these cases of bioterrorism-related inhalational anthrax. The median age of patients was 56 years (range 43 to 73 years), 70% were male, and except for one, all were known or believed to have processed, handled, or received letters containing B. anthracis spores. The median incubation period from the time of exposure to onset of symptoms, when known (n=6), was 4 days (range 4 to 6 days). Symptoms at initial presentation included fever or chills (n=10), sweats (n=7), fatigue or malaise (n=10), minimal or nonproductive cough (n=9), dyspnea (n=8), and nausea or vomiting (n=9). The median white blood cell count was 9.8 X 10(3)/mm(3) (range 7.5 to 13.3), often with increased neutrophils and band forms. Nine patients had elevated serum transaminase levels, and six were hypoxic. All 10 patients had abnormal chest X-rays; abnormalities included infiltrates (n=7), pleural effusion (n=8), and mediastinal widening (seven patients). Computed tomography of the chest was performed on eight patients, and mediastinal lymphadenopathy was present in seven. With multidrug antibiotic regimens and supportive care, survival of patients (60%) was markedly higher (<15%) than previously reported.

Depletion of cellular protein thiols as an indicator of arylation in isolated trout hepatocytes exposed to 1,4-benzoquinone.

A method to measure protein thiols (PrSH), reduced and oxidized, was adapted to determine PrSH depletion in isolated rainbow trout hepatocytes exposed to arylating agent 1,4-benzoquinone (BQ). Toxicant analysis revealed rapid conversion of BQ to 1, 4-hydroquinone (HQ) upon addition to hepatocytes. Hepatocytes exposed to 200 microM BQ+HQ showed 80% decline in glutathione (GSH) (1 h), 30% loss of PrSH (6 h), and no loss of viability (24 h). Recoverable oxidized PrSH was detected only after 24 h (200 microM BQ+HQ). Exposure to 600 microM BQ+HQ caused rapid (10 min) loss of > 90% GSH and > 60% PrSH, with eventual cell death. Half of the PrSH depletion at 6 h observed in hepatocytes exposed to 600 microM BQ+HQ was recoverable by reduction with dithiothreitol. Following the loss of GSH in hepatocytes exposed to 600 microM BQ+HQ, cellular PrSH were susceptible to direct arylation and oxidation. Rainbow trout hepatocytes, which contained 10-fold less GSH than rat cells, had a GSH:PrSH ratio of 1:82 compared with rat ratios of 1:2 to 1:6. The methods reported are useful for further study and discrimination of reactive modes of action needed for prediction of aquatic organism susceptibility to these types of toxicants.

Optimization of a precision-cut trout liver tissue slice assay as a screen for vitellogenin induction: comparison of slice incubation techniques.

An in vitro male rainbow trout liver slice assay has been developed for long-term incubation of precision-cut slices for the detection of vitellogenin (VTG) protein induction in response to xenobiotic chemicals. The assay was optimized to allow 72 h of incubation of slices to maximize detection of VTG, while maintaining slice viability. Two methods of incubation frequently used with rat liver slices were compared: (1) slices were submerged in media (11 degrees C) and cultured in 12-well plates (PL) with continuous shaking; or (2) slices were floated onto titanium screens, placed into glass vials, and held under dynamic organ culture (DOC) conditions (11 degrees C). Slices (200 µm) in modified L-15 media were exposed to 1.0 µM 17beta-estradiol (E2) or diethylstilbestrol (DES). Protein from media and slice was sampled for Western blot analysis, using a polyclonal antibody to detect appearance of VTG protein. Maximum VTG was seen at 72 h, with detectable protein at 24 and 48 h in slices and media following PL incubation. In contrast, slices incubated in DOC showed little detectable VTG above background levels after 72 h. This difference was not attributable to protein loss to vial or plate surfaces. Standard viability assays did not reveal any differences between slices incubated in PL or DOC. However, histopathological examination revealed earlier and more severe vacuolization in slices incubated in DOC. Significantly more E2 uptake and conversion to water-soluble metabolites was noted in PL, compared with DOC, as well as more production of VTG in response to DES and E2, correlated with less histologic change. The in vitro assay described allows tissue-level assessment of estrogenicity in aquatic organisms, and will be useful for assessing not only comparative species receptor binding and transactivation, but also the role of tissue-specific activation factors in the estrogenic response of fish.

An 'anthropathology' of the 'American Negro': anthropology, genetics, and the new racial science, 1940-1952.

This essay documents how, in the 1940s and early 1950s, one scientifically discredited racialist assumption, namely the notion that 'hybridity', embodied by the 'American Negro', and linked to degeneration and disease, was re-authorized, again by science, through the discursive fusion of anthropology, medicine and genetics in the context of a particular disease--sickle cell anaemia. More specifically, I am concerned with the construction of what came to be called an 'anthropathology' of the 'American Negro', the discourse networks that situated it, its conditions of possibility and its consequences.

Tuberculosis control in health care.

This article describes the basic framework for developing a tuberculosis (TB) control program. We suggest how to assess the risk of TB in a healthcare delivery setting, how to prioritize control measures based on their effectiveness, and how to meet current regulatory requirements. In addition, we discuss some problematic issues, examples of how other hospitals have confronted these issues, and where to obtain additional information on nosocomial TB.

Reversible delirium in terminally ill patients.

Delirium is reported to be a common problem in terminally ill patients. The poor prognosis given to these patients may result in the failure to recognize the causes that are easily treated and may be reversible. We present four patients in whom a comprehensive assessment revealed a number of reversible causes of delirium, resulting in a treatment approach that significantly improved the patients' cognition and quality of life.

A perspective on the management of delirium in terminally ill patients on a palliative care unit.

This article outlines the approach to the management of delirium developed by the staff of the palliative care unit at the Edmonton General Hospital. Delirium occurs commonly in the terminally ill and is associated with a poor prognosis. Management requires a clear understanding of what delirium is, how to assess it, investigations for reversible causes, and the medical treatments that are most useful. If not well managed, delirium can be a very distressing symptom for the patient and family as well as having a very destructive impact on the functioning of a palliative care unit.

Blastomycosis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.

Interstitial pneumonitis associated with human herpesvirus-6 infection after marrow transplantation.

Severe interstitial pneumonitis in 2 marrow-transplant recipients was associated with human herpesvirus-6 (HHV-6) infection. The virus was repeatedly detected in respiratory specimens from 1 patient, and HHV-6-infected cells were shown in lung tissue from both patients by immunohistochemical staining. The infected cells were primarily intra-alveolar macrophages, although infected lymphocytes were seen. HHV-6 should be considered as a cause of unexplained lung disease in marrow-transplant recipients and other immunocompromised patients.

Pneumonitis associated with coinfection by human herpesvirus 6 and Legionella in an immunocompetent adult.

The authors report a case of pneumonitis in a young healthy man caused by coinfection with human herpesvirus 6 (HHV-6) and Legionella pneumophila. The patient's course was complicated by severe respiratory, renal, hepatic, and central nervous system dysfunctions, which were believed to be primarily the results of his Legionella infection. Aggressive antibiotic treatment produced no response, and Legionella remained isolatable from lung tissue throughout several weeks of antimicrobial therapy. Human herpesvirus 6 was isolated from a sample of peripheral blood during the acute stage of the patient's illness, and numerous HHV-6--infected macrophages and lymphocytes were detected by immunohistochemical staining of biopsy-derived lung tissue. Paradoxically treatment of the patient with high-dose corticosteroids resulted in dramatic improvement of his condition, including clearance of the Legionella infection. The demonstration that corticosteroids efficiently inhibit HHV-6 replication in vitro suggests that the virus may have contributed to the patient's pneumonitis by enhancing tissue inflammation, by compromising the function of pulmonary macrophages, and, perhaps, by destroying the patient's CD4+ T lymphocytes. Human herpesvirus 6 may be able to function as a synergistic cofactor in lung infections by Legionella and other pathogens.