Transmission of hepatitis C virus during myocardial perfusion imaging in an outpatient clinic

Reports of health care--associated viral hepatitis transmission have been increasing in the United States. Transmission due to poor infection control practices during myocardial perfusion imaging (MPI) has not previously been reported. The aim of this study was to identify the source of incident hepatitis C virus (HCV) infection in a patient without identified risk factors who had undergone MPI 6 weeks before diagnosis. Practices at the cardiology clinic and nuclear pharmacy were evaluated, and HCV testing was performed in patients with shared potential exposures. Clinical and epidemiologic information was obtained for patients with HCV infection, and molecular testing was performed to assess viral relatedness. Evidence of HCV transmission among patients who had undergone MPI at the cardiology clinic on 2 separate dates was found, involving 2 potential source patients and a total of 5 newly infected patients. Molecular testing identified a high degree of genetic homology among viruses from patients with common procedure dates. The nuclear medicine technologist routinely drew up flush from multidose vials of saline solution using the same needle and syringe that had been used to administer radiopharmaceutical doses. Multipatient use of vials was not observed, but a review of purchasing invoices and interviews with staff members suggested that this had occurred. No evidence of transmission via contamination of radiopharmaceuticals at the nuclear pharmacy was found. In conclusion, transmission of HCV occurred because of unsafe injection practices during MPI. Cardiologists should carefully review their infection control practices and the practices of other staff members involved with these procedures.     

Dose range evaluation of Mycograb C28Y variant, a human recombinant antibody fragment to heat shock protein 90, in combination with amphotericin B-desoxycholate for treatment of murine systemic candidiasis

Systemic candidiasis causes significant mortality in patients despite amphotericin B (AMB) therapy. Mycograb C28Y variant, a human recombinant antibody fragment to heat shock protein 90, is closely related to Mycograb, which showed a survival advantage in combination with AMB in a phase III human trial. The Mycograb C28Y variant could potentially increase the antifungal effect of AMB. In our study, the interaction between AMB-desoxycholate (DAMB) and the Mycograb C28Y variant was characterized in vitro by using a checkerboard method. Quantitative cultures of kidneys, livers, and spleens of neutropenic mice with systemic Candida albicans infections were used to assess the in vivo interaction between 1.4 mg/kg of body weight/day of DAMB and 0.15, 1.5, and 15 mg/kg/day of the Mycograb C28Y variant after 1, 3, and 5 days of therapy. DAMB and Mycograb C28Y variant monotherapies, vehicle, and a no-treatment arm served as controls. Also, single- and multidose pharmacokinetics for the Mycograb C28Y variant were determined. Indifference or synergy between DAMB and the Mycograb C28Y variant was seen in two trials by the checkerboard method. The pharmacokinetics of the Mycograb C28Y variant was best described by a 2-compartment model with a median serum t(1/2)(α) of ~0.198 h and a t(1/2)(β) of ~1.77 h. In mice, DAMB together with the Mycograb C28Y variant was no more effective than AMB alone (P > 0.05 by analysis of variance). The Mycograb C28Y variant alone had no antifungal activity. We therefore conclude that the Mycograb C28Y variant in combination with DAMB offered no benefit over DAMB monotherapy in a neutropenic murine model of systemic candidiasis.     

Autoantigen signalling through chemokine receptors

PURPOSE OF REVIEW: Recent studies have shown that disease-associated self-antigens activate chemokine receptors. This review focuses on the mechanics of autoantigen interaction with select chemokine receptors, how these migratory signals are amplified and discusses the possibility that chemokine receptors can be valuable therapeutic targets in the prevention and treatment of autoimmune disease. RECENT FINDINGS: We have recently shown that most autoantigens are chemotactic for immature dendritic cells, suggesting that autoantigens have the potential to bridge the innate and adaptive immune systems. Autoantigens also induce other leukocytes expressing their responsive chemokine receptor to migrate. These newly recruited leukocytes, in response to proinflammatory mediators, simulate the surrounding tissues to release chemokines. Several groups have reported increases in both select chemokines and chemokine receptors in inflamed tissues. Taken together, these studies suggest that autoantigens initiate leukocyte migration into damaged and inflamed tissue that leads to the subsequent amplification of the inflammatory response. SUMMARY: Most autoantigens induce chemokine receptor mediated cell migration, therefore targeting chemokine receptors for either prevention or therapy has great potential to limit autoimmune diseases.     

Physiological day-to-day variability of select hormones at rest in exercise-trained men

The purpose was to determine the day-to-day variability of total testosterone (tT), total T4 (tT4), total 3,5,3'-T3 (tT3), and cortisol (C) levels in exercise-trained men [no.=63, 24+/-4 yr (X+/-SD)]. Resting blood samples were collected at the same time of day (morning) over 3 consecutive days, 24 h apart, under controlled conditions. Subjects were instructed to minimize mental stress and physical activity and to maintain a consistent diet, and sleep patterns during the period of blood collections. Radioimmunoassay procedures were used to measure all hormones. Repeated measures analysis of variances were used to test for differences within each hormone across days, and intra-class correlations (ICC) and typical error were used to assess reliability of hormone concentrations across days. Results revealed resting hormonal values were within accepted clinical ranges. No significant mean differences (p>0.05) from day-to-day were found in any of the hormones. Furthermore, each hormone displayed highly significant (p<0.01) ICC values; tT 0.891, tT4 0.861, tT3 0.705, C 0.886, and consistent daily typical errors. These findings suggest resting tT, tT4, tT3, and C concentrations are not highly variable and appear reliable from day-to-day in exercise-trained men. If researchers measure any of these hormones at rest, before and after (ie, 24-48 h later) an experimental exercise treatment, they can presume that any changes seen at the 24-48 h point (that exceed the typical error appropriately) are due to their treatment and not an artifact of day-to-day variability.     

T lineage differentiation from human embryonic stem cells

Harnessing the ability of genetically manipulated human embryonic stem cells (hESC) to differentiate into appropriate lineages could revolutionize medical practice. These cells have the theoretical potential to develop into all mature cell types; however, the actual ability to develop into all hematopoietic lineages has not been demonstrated. Using sequential in vitro coculture on murine bone marrow stromal cells, and engraftment into human thymic tissues in immunodeficient mice, we demonstrate that hESC can differentiate through the T lymphoid lineage. Stable transgene expression was maintained at high levels throughout differentiation, suggesting that genetically manipulated hESC hold potential to treat several T cell disorders.     

Dendritic cells as a pharmacological target of traditional Chinese medicine

Dendritic cells （DCs） represent a heterogeneous population of professional antigen-presenting cells （APCs） that play a central role in the initiation and regulation of immune responses. There is considerable evidence that DCs can be used as therapeutic targets for pharmacological modulation of immune responses. Traditional Chinese medicine （TCM） has a long-standing history of using herbal medicine in the treatment of variety of human diseases. Many of the clinical effects of TCM have reportedly been attributed to the up- or down-regulation of immune responses. Accumulating evidence indicates that TCM and its components can interfere with immune responses at the earliest stage by targeting key functions of DCs. Here, we review those published studies of TCM with respect to their effects on immunobiological functions of DCs. Investigations based on both chemical entities derived from TCM as well as TCM herbal mixtures are presented. These studies suggest that various TCM herbal medicines have the capacity to inhibit or promote major functions of DCs, such as differentiation, maturation, cytokine production, survival, antigen uptake and presentation as well as trafficking. These studies have revealed novel biological effects of TCM and documented the utility of this approach to discover novel biological modifier of DC functions derived from natural sources.