Reclassification of Treatment Strategy With Instantaneous Wave-Free Ratio and Fractional Flow Reserve: A Substudy From the iFR-SWEDEHEART Trial

Objectives

The authors sought to compare reclassification of treatment strategy following instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR).

Polychlorinated biphenyls induce arachidonic acid release in human platelets in a tamoxifen sensitive manner via activation of group IVA cytosolic phospholipase A2-alpha

Polychlorinated biphenyls (PCBs) are stable compounds commonly found in nature as environmental pollutants. PCBs can affect the endocrine function of hormones such as steroid-hormones. Also, PCBs are known to be inducers of arachidonic acid release in various cells. We report, here, the effects of PCBs on eicosanoid formation, arachidonic acid release and cytosolic phospholipase A2-alpha (cPLA2-alpha) activation in human platelets. Ortho-substituted PCBs induced a time and dose-dependent release of arachidonic acid and the concomitant formation of 12(S)-hydroxy-5,8-cis-10-trans-14-cis-eicosatetraenoic acid (12-HETE) and 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid (12-HHT) in human platelets. The release of arachidonic acid and the formation of 12-HETE was completely blocked by the cPLA2-alpha inhibitors AACOCF3 or pyrrolidine-1. PCB-treatment of platelets demonstrated that the cPLA2-alpha protein as well as PLA2 activity translocated to the membrane fraction, independent of a rise in intracellular Ca2+. Furthermore, electrophoretic gel mobility shift analysis of cPLA2-alpha on SDS-PAGE demonstrated a PCB-dependent phosphorylation of cPLA2-alpha. The effects of 17beta-estradiol and two structurally unrelated anti-estrogens, nafoxidin and tamoxifen on PCB-induced arachidonic acid release in platelets were also investigated. Both nafoxidin and tamoxifen inhibited PCB-induced arachidonic acid release as well as 12-HETE and 12-HHT formation. Interestingly, platelets incubated with PCBs did not aggregate despite the fact that robust release of arachidonic acid was observed. In summary, these results demonstrate that certain PCBs induce activation of cPLA2-alpha independent of a rise in intracellular calcium and a robust release of arachidonic acid release with resulting eicosanoid formation in human platelets.     

Sinusitis of odontogenic origin: pathophysiological implications of early treatment

Although sinusitis is a common condition its pathogenesis is not clearly understood and there is lack of consensus concerning its treatment and prevention. Sinusitis is regarded as being primarily rhinogenous in origin, and oral/dental infections are considered to be predisposing factors. A review of the literature suggests that many cases of recurrent acute sinusitis are due to secondary rhinogenous bacterial colonization of antral mucosa that have been weakened and degenerated by chronic dental infection/inflammation. Unless the underlying dental condition, which may be asymptomatic or mildly symptomatic, is diagnosed and treated, the value of antibiotic treatment in such cases is questionable. In order to halt disease progression and avoid excessive antibiotic treatment, early intervention (both preventive and therapeutic) is necessary. Further research is required to establish the sequence of events by which infection of odontogenic origin initiates degenerative changes in the antral mucosa, culminating eventually in sinusitis.     

Urachal adenocarcinoma

The authors report a case of mucinous adenocarcinoma of the urachus treated with partial cystectomy. The urachal cancer is an uncommon clinicopathologic entity associated with a poor prognosis. Anatomical considerations, clinical features and treatment are discussed.     

The size of the mastoid air cell system among black and white children with middle ear effusion

The incidence of middle ear disease among black American children is lower than among white children. Many factors may contribute to this difference. The possibility of an anatomical variation regarding the cellularity of the mastoid process was investigated. The size of the mastoid air cell system was measured in black and white children with and without middle ear effusion. A significantly smaller mastoid air cell system was found in the groups with middle ear disease compared to those without disease. No difference between white and black children in diseased as well as non-diseased ears could be demonstrated.     

The effect of process variables on the degradation and physical properties of spray dried insulin intended for inhalation

The aim of this study was to investigate the effect of process variables on the degradation and physical properties of spray dried insulin intended for inhalation. A 2(4) full factorial experimentally designed study was performed to investigate the influence of the following independent spray drying variables: feed flow rate, nozzle gas flow rate, inlet air temperature and aspirator capacity (drying gas flow rate). Human insulin (biosynthetic and Ph.Eur. quality) was dissolved in distilled water to concentrations of 5 mg/ml. The solutions were spray dried in a Mini Spray Dryer Büchi and the dry powders produced were characterized by high performance liquid chromatography, size exclusion chromatography, laser diffraction, thermo gravimetric analysis, scanning electron microscopy and weighing. The degradation of insulin was found to be affected mainly by the process variables that determine the outlet air temperature, i.e.: inlet air temperature, aspirator capacity and feed flow rate. The outlet air temperature should be kept below 120 degrees C to avoid degradation. A statistical optimization of the spray drying variables was performed, and found to recommend an experiment with an outlet air temperature of 61+/-4 degrees C. This experiment ought to generate a yield of 54+/-7% by weight of particles with a mass median diameter 2.9+/-0.4 microm, moisture content 3.9+/-0.5% by weight, content of high molecular weight proteins 0.3+/-0.1% by area, A-21 desamido insulin 0.3+/-0.05% by area and other insulin related compounds 0.3+/-0.1% by area.