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Background: Inflammatory biomarkers are useful in detecting patients with sepsis. The prognostic role of resistin and myeloperoxidase (MPO) has been investigated in sepsis., Materials and Methods: Plasma resistin and MPO were measured on days 1, 2 and 7 in 957 patients enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. The association between resistin and MPO levels on day 1, 2 and 7 and 90-day mortality was assessed., Results: Plasma resistin and MPO concentrations were higher at day 1 and decreased until day 7. Both biomarkers were positively correlated with each other and with physiological parameters. Higher levels of resistin and MPO on day 1 were associated with the development of new organ failures. Patients experiencing death at 90 days showed higher levels of resistin and MPO compared with survivors. At day 1, only MPO in the 4th quartile (Q4), but not resistin, was found to predict 90-day death (adjusted hazard ratio [aHR] 1.55 vs Q1). At day 2, resistin in the Q3 and Q4 predicted a > 40% increase in mortality as also did MPO in the Q4. On day 7, Q4 resistin was able to predict 90-day mortality, while all quartiles of MPO were not., Conclusions: High levels of MPO, but not of resistin, on day 1 were able to predict 90-day mortality. These findings may either suggest that early hyper-activation of neutrophils is detrimental in patients with sepsis or reflect the burden of the inflammatory process caused by sepsis. Further studies are warranted to deepen these aspects (ALBIOS ClinicalTrials.gov Identifier: NCT00707122)., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cangrelor administered as an intravenous bolus plus a continuous infusion in healthy volunteers. Twenty-two healthy volunteers are randomized to receive 1 of 2 intravenous cangrelor dosing regimens: a 15-microg/kg bolus followed by a 2-microg/kg/min infusion or a 30-microg/kg bolus followed by a 4-microg/kg/min infusion. The infusion is continued for 60 minutes, and serial blood samples are obtained for evaluation of pharmacokinetic and pharmacodynamic parameters. Administration of an intravenous bolus followed by a continuous infusion rapidly achieves maximum concentrations of cangrelor that are associated with extensive platelet inhibition within 2 minutes. Moreover, extensive platelet inhibition is maintained throughout the infusion period with near-full recovery of platelet function within 60 to 90 minutes of terminating the infusion. The effect of high-dose cangrelor is more consistent and demonstrates a greater level of inhibition on adenosine diphosphate-induced P-selectin expression; how ever, no significant differences are observed between the 2 dosing regimens with regard to platelet aggregation or time to recovery of platelet function. Cangrelor administered as an intravenous bolus followed by a continuous infusion in healthy volunteers offers rapid and reversible inhibition of platelet function.

In 1975, dihydropteridine reductase (DHPR) deficiency was first recognized as a cause of tetrahydrobiopterin (BH(4)) deficiency, leading to hyperphenylalaninemia (HPA) and impaired biogenic amine deficiency. So far, more than 150 patients scattered worldwide have been reported and major progresses have been made in the understanding of physiopathology, screening, diagnosis, treatment, and molecular genetics of this inherited disease. Present knowledge on different aspects of DHPR deficiency, largely derived from authors' personal experience, is traced in this article., (Copyright 2003 Wiley Periodicals, Inc.)

Background: In hyperthyroidism-complicated pregnancies, medical therapy is necessary to reach an euthyroid condition, and propylthiouracil (PTU) or methimazole (MMI) are used. These drugs are equally effective, but may cause fetal and neonatal hypothyroidism because they freely cross the placenta. Although PTU has not been significantly associated with embryo-fetal anomalies, it has been suggested that MMI might be responsible for a specific embryopathy., Case(s): Two cases of major congenital anomalies after MMI exposure during pregnancy are reported., Conclusions: PTU should be the drug of choice, and the use of MMI should be restricted to cases with allergic reactions, intolerance, or poor response to PTU., (Copyright 2003 Wiley-Liss, Inc.)