Comparison of 68Ga-DOTANOC PET/CT with cardiac MRI in patients with clinical suspicion of cardiac sarcoidosis

Annals of Nuclear Medicine - 68Ga-DOTA-NaI-octreotide (DOTANOC) is a promising new alternative to 18F-fluorodeoxyglucose (FDG) for imaging inflammation in cardiac sarcoidosis. The aim of the study...     

Falsely low HbA1c value due to a rare variant of hemoglobin J-Baltimore

HbA1c values are heavily relied on to assess glycemic control. Hemoglobin variants may interfere with measurements of HbA1c resulting in falsely low values. We present the first report of a rare variant of Hb in a patient with type 2 diabetes, which lead to a falsely low HbA1c.     

Programmed death-1 expression in liver transplant recipients as a prognostic indicator of cytomegalovirus disease

Immunological parameters that distinguish solid-organ transplant (SOT) recipients at risk for life-threatening cytomegalovirus (CMV) disease are being actively pursued to aid posttransplant management. A candidate marker is programmed death (PD)-1 receptor, whose overexpression has been associated with disease progression during persistent viral infections. To determine whether levels of this negative regulator of T cell activity are altered in SOT recipients with symptoms of CMV disease, a comparative PD-1 expression analysis was done in healthy, CMV-positive individuals and in liver transplant recipients. PD-1 levels were measured among the total population of CD8(+) and CD8(+) T cells binding to CMV-specific major histocompatibility complex class I tetramers. Minimal PD-1 expression was found in the healthy, CMV-positive cohort, and symptomatic SOT recipients had significantly higher PD-1 levels. PD-1 up-regulation was significantly associated with incipient and overt CMV disease and with viremia. Our findings suggest that PD-1 could be developed as a prognostic tool to predict CMV disease and guide therapeutic interventions.     

Use of continuous subcutaneous insulin infusion pump in patients with type 2 diabetes mellitus

PURPOSE: In patients with type 2 diabetes, the control of hyperglycemia is often difficult despite full doses of oral hypoglycemic agents and extremely large doses of insulin. These patients pose a major management problem. The authors therefore investigated whether insulin given as a subcutaneous continuous infusion of insulin (CSII) would result in an improvement in glucose homeostasis. METHODS: Four patients with badly controlled type 2 diabetes, on treatment with extremely high doses of insulin and oral hypoglycemic agents, were started on CSII. RESULTS: All four patients had a marked improvement in plasma glucose concentrations with a corresponding fall in HbA1c levels. This improvement was associated with a marked fall in the insulin doses necessary to maintain adequate glucose homeostasis. CONCLUSIONS: Since HbA1c levels fell from levels that would be associated with diabetic complications to those at which complications are markedly reduced, we recommend that patients with type 2 diabetes uncontrolled on extremely high doses of insulin be given a trial of treatment with CSII.     

In Vitro Activity and Resistance Profile of Dasabuvir,a Nonnucleoside Hepatitis C Virus Polymerase Inhibitor

Dasabuvir (ABT-333) is a nonnucleoside inhibitor of the RNA-dependent RNA polymerase encoded by the hepatitis C virus (HCV) NS5B gene. Dasabuvir inhibited recombinant NS5B polymerases derived from HCV genotype 1a and 1b clinical isolates, with 50% inhibitory concentration (IC₅₀) values between 2.2 and 10.7 nM, and was at least 7,000-fold selective for the inhibition of HCV genotype 1 polymerases over human/mammalian polymerases. In the HCV subgenomic replicon system, dasabuvir inhibited genotype 1a (strain H77) and 1b (strain Con1) replicons with 50% effective concentration (EC₅₀) values of 7.7 and 1.8 nM, respectively, with a 13-fold decrease in inhibitory activity in the presence of 40% human plasma. This level of activity was retained against a panel of chimeric subgenomic replicons that contained HCV NS5B genes from 22 genotype 1 clinical isolates from treatment-naive patients, with EC₅₀s ranging between 0.15 and 8.57 nM. Maintenance of replicon-containing cells in medium containing dasabuvir at concentrations 10-fold or 100-fold greater than the EC₅₀ resulted in selection of resistant replicon clones. Sequencing of the NS5B coding regions from these clones revealed the presence of variants, including C316Y, M414T, Y448C, Y448H, and S556G, that are consistent with binding to the palm I site of HCV polymerase. Consequently, dasabuvir retained full activity against replicons known to confer resistance to other polymerase inhibitors, including the S282T variant in the nucleoside binding site and the M423T, P495A, P495S, and V499A single variants in the thumb domain. The use of dasabuvir in combination with inhibitors targeting HCV NS3/NS4A protease (ABT-450 with ritonavir) and NS5A (ombitasvir) is in development for the treatment of HCV genotype 1 infections.