Diphenylene iodonium, an inhibitor of free radical formation, inhibits platelet aggregation.

Diphenylene iodonium is an inhibitor of the enzyme NADPH-oxidase and prevents the generation of oxygen-derived free radicals in neutrophils (Cross and Jones, 1986). Here we show that diphenylene iodonium (0.25-2 microM) inhibited, according to the dose, thrombin-induced platelet-aggregation in human washed platelets and ADP-induced platelet aggregation in platelet-rich plasma. At the concentrations which inhibited platelet aggregation diphenylene iodonium did not alter platelet concentrations of cAMP or cGMP but enhanced the anti-platelet activity of iloprost, sodium nitroprusside or cultured endothelial cells. These findings highlight the importance of free radicals as platelet pro-aggregatory agents.     

Retrograde left atrial catheterization

Catheterization of the left atrium can provide valuable information about both congenital and acquired heart disease. The traditional approach to examination of the left atrium has been the transseptal route, which has occasionally been associated with serious complications. A method of retrograde left atrial catheterization has been developed that is performed with a modified standard catheter. The technique was tested in five dogs and was easy and safe to perform.     

Equilibrium of medical and radiology services in Manitoba

Diagnostic imaging policy for the one million people of Manitoba was reviewed. Four complete data collections of diagnostic imaging activity, physician claims, vital statistics, and disease incidence from existing registries were assembled. Mammography, Hodgkin disease, and regional enteritis were analyzed briefly. Studies of protocols for patient access to computed tomography, imaging in head injury, and actions by society indicated that new technology and procedures can be accommodated at manageable public expense. To overcome emerging problems, several initiatives have been considered, including a proposed Canadian Health Council to moderate policy, a personal health identification number to link information, and imaging investigation directed by radiologists.     

Duodenitis: endoscopic-radiologic correlation in 272 patients

Potential radiologic findings of duodenitis were investigated in 272 patients, 157 with endoscopically diagnosed duodenitis and 115 endoscopically normal controls. The study assessed the value of four signs: folds more than 4 mm thick, mucosal nodules, bulbar deformity, and erosions. The most sensitive signs were thickened folds (72.0%) and nodularity (48.4%), while demonstration of erosions was the least sensitive (10.8%). Overall sensitivity (77.7%) approximated that for the radiologic diagnosis of peptic ulcer or esophagitis. Radiologic specificity (76.5%) was in the same range.     

Clinical pharmacology of deoxycoformycin

Deoxycoformycin (DCF) is an inhibitor of adenosine deaminase (ADA). Twenty-one courses of DCF were administered to 13 patients ranging in age from 15 to 78 yr. Eight patients had T-cell disorders, and five patients had non-T-cell malignancies. The i.v. bolus dose was escalated from 5 to 30 mg/sq m/day, and the duration of the courses ranged from 1 to 5 days. The DCF plasma half-life ranged from 4.9 to 6.2 hr and was independent of dose. The dose-limiting toxicities involved the central nervous system (CNS) and the kidneys. Other toxicities included bronchitis, decreases in hematocrit, arthralgias, and myalgias. Mortality was encountered in three patients. These toxic effects may have been secondary to the accumulation of the metabolites adenosine and deoxyadenosine. Deoxyadenosine and adenosine were both detectable in plasma (10(-6) M) and in urine (10(-3) M). Two partial remissions were observed: one in a patient with T-cell ALL and another in a patient with mycosis fungoides. Minimal responses characterized by either declines in peripheral blast counts or partial resolution of adenopathy were observed in five other patients. No responses were observed in six patients. These observations suggest that DCF is effective in the treatment of T-cell lymphoid malignancies.     

Cytokine-mediated induction of cyclo-oxygenase-2 by activation of tyrosine kinase in bovine endothelial cells stimulated by bacterial lipopolysaccharide.

1. The induction of cyclo-oxygenase-2 (COX-2) afforded by bacterial lipopolysaccharide (LPS, endotoxin) in bovine aortic endothelial cells (BAEC) is mediated by tyrosine kinase. LPS also causes the generation of several cytokines including interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). This study investigates whether endogenous IL-1 beta, TNF-alpha, EGF or PDGF contribute to the induction of COX-2 elicited by LPS in BAEC and if their action is due to activation of tyrosine kinase. Furthermore, we have studied the induction of COX-2 by exogenous cytokines. 2. Accumulation of 6-oxo-prostaglandin (PG) F1 alpha in cultures of BAEC was measured by radioimmunoassay at 24 h after addition of either LPS (1 microgram ml-1) alone or LPS together with a polyclonal antibody to one of the various cytokines. In experiments designed to measure 'COX activity', 6-oxo-PGF1 alpha generated by BAEC activated with recombinant human IL-1 beta, TNF-alpha, EGF or PDGF for 12 h was measured after incubation of washed cells with exogenous arachidonic acid (30 microM for 15 min). Western blot analysis determined the expression of COX-2 protein in BAEC. 3. The accumulation of 6-oxo-PGF1 alpha caused by LPS in BAEC was attenuated by co-incubation with one of the polyclonal antibodies, anti-IL-1 beta, anti-TNF-alpha, anti-EGF, anti-PDGF or with the IL-1 receptor antagonist, in a dose-dependent manner. Exogenous IL-1 beta, TNF-alpha or EGF also caused an increase in COX activity, while PDGF was ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)     

Citrate anticoagulants for plateletpheresis

In 112 plateletphereses done by the Haemonetics blood processor, the comparative effectiveness of ACD formula A, ACD formula B, and 2 per cent citrate in saline was evaluated. With respect to yields of platelets and white blood cells (e.g., lymphocytes), ACD-B was significantly better than the other two. Both ACD-B and 2 per cent citrate gave a much lower incidence of citrate reactions in the donors than were encountered with ACD-A.