The clinicopathologic spectrum of segmental membranous glomerulopathy

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The influence of body size on the pharmacodynamic and pharmacokinetic response to clopidogrel and prasugrel: A retrospective analysis of the FEATHER study

Introduction

Patients treated with clopidogrel who have higher body size exhibit greater platelet reactivity than patients with lower body size. In a retrospective analysis of the FEATHER trial, we examined the relationship between platelet response to thienopyridines clopidogrel 75 mg (Clop-75), prasugrel 5 mg (Pras-5), and prasugrel 10 mg (Pras-10) using 3 body size indices: body weight (BW), body mass index (BMI), and body surface area (BSA). Relationships were assessed as continuous variables and as 4 incremental body size groups.

Materials and Methods

Aspirin-treated patients with stable coronary artery disease (N = 72) and a BW range of 45-134 kg received Clop-75, Pras-5, and Pras-10 in a 3-period, blinded, cross-over study. Platelet assays included maximum platelet aggregation (MPA) to 20 μM ADP by light transmission aggregometry, VerifyNow-P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation platelet reactivity index (PRI). Exposure to active metabolites (AMs) was also assessed.

Results

Body size was a determinant of AM exposure and residual platelet reactivity regardless of type and dose of thienopyridine. BW and BSA demonstrated marginally stronger correlations with platelet reactivity; VASP-PRI demonstrated a stronger correlation with the body size than the other tests. Correlation coefficients ranged from a high of 0.64 (BW vs. PRI on Pras-5) to a low of 0.34 (BMI vs. MPA on Pras-10), but all were statistically significant (p < 0.01).

Conclusions

Using a comprehensive selection of body size indices, AM exposures, platelet function tests, and thienopyridine doses, we demonstrated a consistent inverse relationship between body size and response to clopidogrel and prasugrel.     

Diagnosis of Latent Mycobacterium tuberculosis Infection in the Era of Interferon Gamma Release Assays

Mycobacterium tuberculosis (MTB), an acid-fast bacterium, is a leading cause of respiratory illness and death worldwide. Individuals can be latently infected and can harbor the organism without clinical evidence of disease for years. Screening and treatment of numerous populations, including health care workers, recent contacts of actively infected individuals, immunocompromised individuals, children, and immigrants from countries where MTB is endemic, is essential to eradicate the infection by 2050, as the World Health Organization envisions. Detection of active and latent infection historically has utilized tuberculin skin tests and other clinical findings. Interferon gamma release assays can test whether a patient has had MTB exposure with improved sensitivity and specificity over tuberculin skin testing. This article reviews the history of MTB testing, compares available interferon gamma release assays, and discusses the new developments related to latent-MTB infection testing.     

Comparative In Vitro Activity of Newer Cephalosporins Against Anaerobic Bacteria

The in vitro susceptibilities of 408 recent clinical isolates of anaerobic bacteria against cefaclor, cephalexin, cephalothin, cefazolin, cefamandole, and cefoxitin were compared by an agar dilution technique. Against gram-positive bacteria, especially peptococci, peptostreptococci, and propionibacteria, cephalexin and cefaclor were significantly less active than cephalothin (P < 0.05). Cephalexin was also less active than cephalothin against clostridia and lactobacillus (P < 0.05). Against gram-negative bacteria, major differences were observed primarily with Bacteroides fragilis, against which cephalexin, cefazolin and cefoxitin were all significantly more active than cephalothin (P < 0.001). At concentrations of 16 μg per ml, however, all cephalosporins showed high in vitro activity, except against Lactobacillus species and B. fragilis. Cephalothin, cefazolin and cefamandole were considerably more active against the former, whereas cefoxitin was distinctly more active against the latter.