A B S T R A C T Acetylation of platelet cyclooxygenase by oral aspirin is dose dependent and cumulative with repeated administration. However, no single dose of aspirin has been found to be completely selective of platelet thromboxane (TX) synthesis inhibition in man. We determined the dose dependence, cumulative nature and selectivity of aspirin effects on platelet TXB2 and renal prostaglandin (PG) and prostacyclin (PGI2) production. We measured, by radioimmunoassay, serum TXB2 levels after whole blood clotting and urinary excretion of PGE2, PGF2a, and 6-keto-PGF,a, before and after single or repeated oral aspirin doses given to 46 healthy subjects. Single doses of 6-100 mg aspirin resulted in a linear (r = 0.92, P < 0.01) inhibition of platelet TXB2 production, ranging from 12 to 95% after 24 h. A daily dose of 0.45 mg/kg given for 7 d produced a cumulative and virtually complete inhibition of platelet TXB2 production, without significantly reducing the urinary excretion of PGE2, PGF2a, and 6-keto-PGF,a in both healthy men and women. The platelet inhibitory effect of this regimen was maintained unaltered throughout 1 mo of therapy, with no evidence of cumulative inhibition of renal PGsynthesis. Moreover, furosemide-induced renal PGI2 synthesis and renin release were unaffected by chronic low-dose aspirin. Following cessation of aspirin therapy, platelet TXB2 production returned toward control values at a similar rate as after a single higher dose.We conclude that in healthy subjects: (a) aspirin causes a dose-dependent inhibition of platelet TXA2 production, with no obvious sex-related difference; (b) the inhibitory effect of daily low-dose aspirin is cumulative on platelet TXA2 but not on renal PG-synthesis; (c) during chronic low-dose aspirin therapy, renal PGI2-producing cells are readily activable by furosemide at a time of virtually complete suppression of platelet cyclooxygenase activity.

Nonsteroidal anti-inflammatory drugs and sulfinpyrazone compete dose-dependently with arachidonate for binding to platelet cyclooxygenase. Such a process closely follows systemic plasma drug concentrations and is reversible as a function of drug elimination. Peak inhibition and extent of its reversibility at 24 hr varies consistently with individual pharmacokinetic profile. Inhibition of platelet cyclooxygenase activity by these agents is associated with variable effects on prostaglandin (PG) synthesis in the gastric mucosa and the kidney. Aspirin acetylates platelet cyclooxygenase and permanently inhibits thromboxane (TX) A2 production in a dose-dependent fashion when single doses of 0.1 to 2.0 mg/kg are given. Acetylation of the enzyme by low-dose aspirin is cumulative on repeated dosing. The fractional dose of aspirin necessary to achieve a given level of acetylation by virtue of cumulative effects approximately equals the fractional daily platelet turnover. Serum TXB2 measurements obtained during long-term dosing with 0.11, 0.22, and 0.44 mg/kg aspirin in four healthy subjects could be fitted by a theoretical model assuming identical acetylation of platelet (irreversible) and megakaryocyte (reversible) cyclooxygenase. For a given dose within this range, both the rate at which cumulative acetylation occurs and its maximal extent largely depend upon the rate of platelet turnover. Continuous administration of low-dose aspirin (20 to 40 mg/day) has no statistically significant effect on urinary excretion of either 6-keto-PGF1 alpha or 2,3-dinor-6-keto-PGF1 alpha, i.e., indexes of renal and extrarenal PGI2 biosynthesis in vivo. Whether a selective sparing of extraplatelet cyclooxygenase activity by low-dose aspirin will result in increased antithrombotic efficacy, fewer toxic reactions, or both remains to be established in prospective clinical trials.

TUS is easily reproducible and we proved it to be a useful complementary diagnostic tool for the diagnosis and the follow-up of CAP.

Although numerous studies have been conducted on the use of ultrasonography (US) for the examination of thoracic structures, this procedure is not as widely accepted as abdominal US. The newer portable scanners can be used at the bedside to detect pleural malignancies and effusions, as well as peripheral lung nodules of the lung, even in seriously ill patients. Focal thickening of the pleura can be easily detected with US and further investigated with a US-guided biopsy. US guidance can also be used during percutaneous drainage of pleural effusion or transthoracic biopsy of peripheral lung lesions, thus reducing the incidence of procedure-related pneumothorax to almost zero. We review the current literature on thoracic US and present our clinical experience with the technique in large groups of patients with pleural and peripheral lung diseases.Sommario L'ecografia del torace non è ancora diffusa quanto quella addominale, nonostante una notevole quantità di studi ne attesti l'importanza. Le apparecchiature più recenti permettono di diagnosticare neoplasie, versamenti pleurici e noduli polmonari periferici al letto del paziente, anche nei casi più gravi. L'ispessimento pleurico focale è facilmente messo in luce dall'ecografia e può essere ulteriormente studiato tramite la biopsia ecoguidata. Questa può essere praticata anche su lesioni polmonari periferiche, riducendo quasi a zero il rischio di pneumotorace. In questo articolo esaminiamo la letteratura recente sull'ecografia del torace e presentiamo la nostra esperienza clinica su numerosi pazienti con patologia pleurica e della periferia polmonare. ª