Late pancreas retransplantation

Pancreas retransplantation, excluding immediate retransplantation for graft thrombosis, is a technically treacherous operation with the added challenges of adhesions from the prior transplant and difficulties identifying usable recipient vessels. The goal of this study was to review our single‐center experience with late pancreas retransplantation. Charts for all pancreas transplant recipients between 01/2003 and 04/2013 were reviewed for demographics, graft and patient survival, length of stay (LOS), readmissions, and technical complications. Of 473 pancreas transplants, there were 20 late pancreas retransplants compared to 441 first transplants. There were no significant differences in donor or recipient demographics. There was no significant difference in graft or patient survival. The mean and median lengths of stay were 22 and nine d, respectively (range 5–175 d), and 11 recipients required readmission within the first three months post‐transplant. Five patients were reexplored in the early postoperative period for an enteric leak at the site of the primary allograft (n = 1), complications of percutaneous gastrostomy tube placement (n = 1), hemorrhage (n = 1), and negative laparotomy for hyperglycemia (n = 2). Pancreas retransplantation is technically challenging but can be safely performed with graft and recipient survival comparable to primary transplants.     

Insight into the PrPC-->PrPSc conversion from the structures of antibody-bound ovine prion scrapie-susceptibility variants

Prion diseases are associated with the conversion of the alpha-helix rich prion protein (PrPC) into a beta-structure-rich insoluble conformer (PrPSc) that is thought to be infectious. The mechanism for the PrPC-->PrPSc conversion and its relationship with the pathological effects of prion diseases are poorly understood, partly because of our limited knowledge of the structure of PrPSc. In particular, the way in which mutations in the PRNP gene yield variants that confer different susceptibilities to disease needs to be clarified. We report here the 2.5-A-resolution crystal structures of three scrapie-susceptibility ovine PrP variants complexed with an antibody that binds to PrPC and to PrPSc; they identify two important features of the PrPC-->PrPSc conversion. First, the epitope of the antibody mainly consists of the last two turns of ovine PrP second alpha-helix. We show that this is a structural invariant in the PrPC-->PrPSc conversion; taken together with biochemical data, this leads to a model of the conformational change in which the two PrPC C-terminal alpha-helices are conserved in PrPSc, whereas secondary structure changes are located in the N-terminal alpha-helix. Second, comparison of the structures of scrapie-sensitivity variants defines local changes in distant parts of the protein that account for the observed differences of PrPC stability, resistant variants being destabilized compared with sensitive ones. Additive contributions of these sensitivity-modulating mutations to resistance suggest a possible causal relationship between scrapie resistance and lowered stability of the PrP protein.     

Adherence of low-income women to cancer screening recommendations

BACKGROUND: African-American and low-income women have lower rates of cancer screening and higher rates of late-stage disease than do their counterparts. OBJECTIVE: To examine the effects of primary care, health insurance, and HMO participation on adherence to regular breast, cervical, and colorectal cancer screening. DESIGN: Random-digit-dial and targeted household telephone survey of a population-based sample. SETTING: Washington, D.C. census tracts with > or =30% of households below 200% of federal poverty threshold. PARTICIPANTS: Included in the survey were 1,205 women over age 40, 82% of whom were African American. MAIN OUTCOME MEASURES: Adherence was defined as reported receipt of the last 2 screening tests within recommended intervals for age. RESULTS: The survey completion rate was 85%. Overall, 75% of respondents were adherent to regular Pap smears, 66% to clinical breast exams, 65% to mammography, and 29% to fecal occult blood test recommendations. Continuity with a single primary care practitioner, comprehensive service delivery, and higher patient satisfaction with the relationships with primary care practitioners were associated with higher adherence across the 4 screening tests, after considering other factors. Coordination of care also was associated with screening adherence for women age 65 and over, but not for the younger women. Compared with counterparts in non-HMO plans, women enrolled in health maintenance organizations were also more likely to be adherent to regular screening (e.g., Pap, odds ratio [OR] 1.89, 95% confidence interval [CI] 1.11 to 3.17; clinical breast exam, OR 2.04, 95% CI 1.21 to 3.44; mammogram, OR 1.95, 95% CI 1.15 to 3.31; fecal occult blood test, OR 1.70, 95% CI 1.01 to 2.83.) CONCLUSIONS: Organizing healthcare services to promote continuity with a specific primary care clinician, a comprehensive array of services available at the primary care delivery site, coordination among providers, and better patient-practitioner relationships are likely to improve inner-city, low-income women's adherence to cancer screening recommendations.     

Immune parameter analysis of children with sickle cell disease on hydroxycarbamide or chronic transfusion therapy

Sickle cell disease (SCD) is increasingly appreciated as an inflammatory condition associated with alterations in immune phenotype and function. In this cross‐sectional study we performed a multiparameter analysis of 18 immune markers in 114 paediatric SCD patients divided by treatment group [those receiving hydroxycrabamide (HC, previously termed hydroxyurea), chronic transfusion (CT), or no disease‐modifying therapy] and 29 age‐matched African American healthy controls. We found global elevation of most immune cell counts in SCD patients receiving no disease‐modifying therapy at steady state. Despite the decrease in percentage of haemoglobin S associated with CT therapy, the abnormal cellular immune phenotype persisted in patients on CT. In contrast, in both univariate and multivariate analysis, treatment with HC was associated with normalization of the vast majority of leucocyte populations. This study provides additional support for HC treatment in SCD, as it appears that HC decreases the abnormally elevated immune cell counts in patients with SCD.     

Ocular Syphilis: a Clinical Review

While ocular syphilis is not a new phenomenon, recent increased rates of new diagnoses, especially in human immunodeficiency virus (HIV)-infected persons and men who have sex with men, have sparked a new interest in an old disease. This article will review the clinical presentation, diagnosis, and treatment of ocular syphilis, and provide guidance on management.     

A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells

Tissue-derived adenosine, acting via the adenosine A(2A) receptor (A(2A)R), is emerging as an important negative regulator of T-cell function. In this report, we demonstrate that A(2A)R stimulation not only inhibits the generation of adaptive effector T cells but also promotes the induction of adaptive regulatory T cells. In vitro, antigen recognition in the setting of A(2A)R engagement induces T-cell anergy, even in the presence of costimulation. T cells initially stimulated in the presence of an A(2A)R agonist fail to proliferate and produce interleukin-2 and interferon (IFN)-gamma when rechallenged in the absence of A(2A)R stimulation. Likewise, in an in vivo model of autoimmunity, tissue-derived adenosine promotes anergy and abrogates tissue destruction. Indeed, A(2A)R stimulation inhibits interleukin-6 expression while enhancing the production of transforming growth factor-beta. Accordingly, treating mice with A(2A)R agonists not only inhibits Th1 and Th17 effector cell generation but also promotes the generation of Foxp3(+) and LAG-3(+) regulatory T cells. In this regard, A(2A)R agonists fail to prevent autoimmunity by LAG-3(-/-) clonotypic T cells, implicating an important role for LAG-3 in adenosine-mediated peripheral tolerance. Overall, our findings demonstrate that extracellular adenosine stimulates the A(2A)R to promote long-term T-cell anergy and the generation of adaptive regulatory T cells.     

Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

The 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB) have potent in vitro efficacies against Plasmodium falciparum, but susceptibility data for P. vivax are limited. The species- and stage-specific ex vivo activities of NQ and MB were assessed using a modified schizont maturation assay on clinical field isolates from Papua, Indonesia, where multidrug-resistant P. falciparum and P. vivax are prevalent. Both compounds were highly active against P. falciparum (median [range] 50% inhibitory concentration [IC₅₀]: NQ, 8.0 nM [2.6 to 71.8 nM]; and MB, 1.6 nM [0.2 to 7.0 nM]) and P. vivax (NQ, 7.8 nM [1.5 to 34.2 nM]; and MB, 1.2 nM [0.4 to 4.3 nM]). Stage-specific drug susceptibility assays revealed significantly greater IC₅₀s in parasites exposed at the trophozoite stage than at the ring stage for NQ in P. falciparum (26.5 versus 5.1 nM, P = 0.021) and P. vivax (341.6 versus 6.5 nM, P = 0.021) and for MB in P. vivax (10.1 versus 1.6 nM, P = 0.010). The excellent ex vivo activities of NQ and MB against both P. falciparum and P. vivax highlight their potential utility for the treatment of multidrug-resistant malaria in areas where both species are endemic.