Mutations in the iduronate-2-sulfatase gene in five Norwegians with Hunter syndrome

OBJECTIVES: Adolescents with human immunodeficiency virus (HIV) infection are at increased risk for tuberculosis (TB), underscoring the importance of early identification of TB infection. The goals of this study were to assess the factors associated with the completion of evaluations for TB in a cohort of HIV-positive adolescents and young adults and to describe the prevalence of Mycobacterium tuberculosis infection and adherence to antituberculous treatment regimens. METHODS: A retrospective chart review was done for all HIV-positive adolescents and young adults, ages 13 to 21 years (n = 49), seen in a comprehensive care program from January 1991 through December 1992. Data collected included CD4 cell count, HIV clinical status, living situation, substance use history, and the completion of an annual evaluation for TB infection. The evaluation consisted of a tuberculin skin test (Mantoux test), using an intraepidermal injection of 0.1 mL of 5 tuberculin units of purified protein derivative (PPD) and a simultaneous Merieux multitest anergy panel. Chi-square analysis was used to assess the association between the completion of the evaluation for TB and both living status and substance use. RESULTS: Thirty-one (63%) of 49 patients completed evaluations for TB. Of the 31 completed evaluations, 18 were assessed by clinic staff on site, and 13 were assessed by other medical or trained nonmedical observers through community networking efforts. Neither homelessness nor illicit substance use were factors in the completion of the evaluation. Six (19%) of the 31 patients had positive PPD skin test results. Three had medical histories and chest radiographs suggesting active TB, and all were hospitalized for at least 2 weeks. Two had positive cultures for M tuberculosis, although the third also responded clinically to antituberculous therapy. All three were otherwise asymptomatic for HIV infection, with only moderately depressed CD4 cell counts. All three were homeless and used crack cocaine. After the initial treatment as inpatients, none completed treatment within the prescribed time period. CONCLUSIONS: The completions of the evaluations for TB were greatly facilitated by community networking, but innovative strategies to enhance both screening and treatment programs, such as training youth service providers in the community to read PPD skin tests, expansion of directly observed therapy services, and youth-centered programs for housing and substance use, need further development. The high prevalence of TB in the cohort underscores the need for providers to increase efforts to identify cases of TB infection among adolescents and young adults and to incorporate HIV risk assessment, counseling, and testing into their practices routinely.     

Exposure assessment and risk characterization for perfluorooctanoate in selected consumer articles

An exposure assessment and risk characterization was conducted to better understand the potential human health significance of trace levels of perfluorooctanoate (PFO) detected in certain consumer articles. PFO is the anion of perfluorooctanoic acid (PFOA). Concentrations of PFO in the consumer articles were determined from extraction tests and product formulation information. Potential exposures during consumer use of the articles were quantified based on an assessment of behavior patterns and regulatory guidance. Health benchmarks were developed and then compared to the exposure estimates to yield margins of exposure (MOEs). A simple one-compartment model was also developed to estimate contributions of potential consumer exposures to PFO concentrations in serum. While there are considerable uncertainties in this assessment, it indicates that exposures to PFO during consumer use of the articles evaluated in this study are not expected to cause adverse human health effects in infants, children, adolescents, adult residents, or professionals nor result in quantifiable levels of PFO in human serum.     

Crossregulation between T helper cell (Th)1 and Th2: inhibition of Th2 proliferation by IFN-gamma involves interference with IL-1

The Th1-derived cytokine IFN-gamma inhibits the proliferation of Th2 lymphocytes, but the mechanism of inhibition is not known. Under certain disease conditions, an established Th2-mediated immune response is undesirable and a Th1-mediated response is beneficial. However, established Th2 cells appear to be phenotypically stable. Thus, learning more about cytokine-mediated regulation of established Th2 cells is important if deleterious immune responses are to be altered. We studied the effects of IFN-gamma on a panel of recently derived Th2 lines and clones, as well as a previously established Th2 clone, 13.26. Inhibition by IFN-gamma was observed only when there was a concomitant response to IL-1, a known costimulator of Th2. Clone 13.26 was particularly sensitive to both IL-1 and IFN-gamma, so it was studied in greater detail. We examined cytokine responses using stimulation by anti-TCR mAb-coated plates, or Ag presented by APC populations that do or do not produce IL-1. All IL-1-mediated proliferative responses of 13.26 were inhibited by IFN-gamma, whereas IL-1-independent (IL-4-associated) responses were unaffected. Our data suggest that IFN-gamma inhibits Th2 proliferation through an IL-1-dependent mechanism, and furthermore, that the costimulatory pathways used by APCs may be critical for subsequent Th cell responses to cytokines.