Correlation between clinical course and quantitative analysis of the ischemia related artery in patients with unstable angina pectoris, refractory to medical treatment. Results of two randomized trials. The European Cooperative Study Group

Patients with unstable angina, refractory to intensive medical therapy, are at high risk for developing thrombotic complications, such as recurrent ischemia, myocardial infarction and coronary occlusion during coronary angioplasty. As both platelet aggregation and/or thrombus formation play an important role in this ongoing ischemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) or thrombolytic therapy (alteplase) might be able to modify the clinical course and underlying coronary lesion morphology. To evaluate whether alteplase or c7E3 could influence the incidence of complications, we randomized 36 and 60 patients, respectively to alteplase or placebo, or c7E3 or placebo. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite maximal tolerated medical therapy. Patients were randomized in both studies after initial angiography had demonstrated a culprit lesion amenable for angioplasty. After study drug infusion quantitative angiography was repeated and angioplasty performed. Recurrent ischemia during study drug infusion occurred in 5, 6, 9 and 16 patients from the alteplase, placebo, c7E3 and placebo group, respectively. Major events defined as death, myocardial infarction or urgent intervention occurred in 7, 3, 1 and 7 patients, respectively. Two patients died: one in the alteplase group and one in the placebo group from the c7E3 study. The first patient due to retroperitoneal hemorrhage, the second as a result of recurrent infarction. Qualitative angiography showed resolution of clots in the c7E3 group only, while the same group of patients showed in 20% an improvement in TIMI flow grade, without deterioration in any patient from this group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relative involvement of protein kinase C and of the estrogen receptor in the cytotoxic action of a population of triphenylethylenes on MCF7 cells as revealed by correspondence factorial (CF) analysis

A multivariate statistical method, correspondence factorial (CF) analysis, was used to examine the correlations among the protein binding and cell proliferation effects of a series of 36 di- and triphenylethylenes (DPEs and TPEs). The analysis was applied to a study which measured their competition for estradiol binding to cytosol estrogen receptor (ER), their influence on protein kinase C (PKC) activity under different conditions of enzyme activation, their ability to promote the growth of a breast cancer cell line and to inhibit growth at high concentrations (cytotoxicity). The CF analysis revealed several levels of correlation. First, it distinguished those molecules within the population that stimulated rather than inhibited PKC activity. Second, it made apparent a strong correlation between cytotoxicity and inhibition of Ca++ and phosphatidylserine-dependent PKC activity, which was most marked when the enzyme had been activated by diacylglycerol indicating that PKC inhibition under physiological conditions might contribute to the overall cytotoxicity of these compounds. Third, a lower level of correlation was established between competition for ER binding and cytotoxicity. Taken together, the results suggest that MCF7 cells might be most sensitive to a cytotoxic effect of TPEs (via PKC and other targets) when they at the same time decrease estrogen-stimulated proliferation via an ER-mediated antiestrogenic effect.     

Prospective study of carotid endarterectomy and contralateral carotid occlusion

A total of 700 patients who had carotid endarterectomy (CEA) in the UK and Ireland during a 6-month interval between March and August 1994 were studied prospectively. Some 108 patients (15.4 per cent) had a contralateral internal carotid artery occlusion. Previous reports have shown an associated stroke rate of about 10 per cent in these patients. This study assessed complications and outcome for patients undergoing CEA with contralateral internal carotid artery occlusion compared with those without. The indications for surgery were comparable between the two groups although the patients with occlusion had a slightly higher incidence of arrhythmia and stroke. Intraoperative shunts were used in a significantly higher proportion of those with occlusion (83.3 versus 64.7 per cent, P = 0.0001). The combined death and stroke rate for patients with occlusion was 5.6 per cent compared with 2.4 per cent for the remainder (P not significant). On the basis of the present data, CEA with a contralateral carotid artery occlusion carries only a slight increase in the rate of postoperative stroke and death. This increase was not statistically significant and is lower than that reported previously.     

The water purification system for the low background counting test facility of the Borexino experiment at Gran Sasso

The Borexino experiment, for the study of solar neutrino physics, requires radiopurity at the level of 5 × 10⁻¹⁶ g/g ²³⁸U equivalent (or 6 × 10⁻⁹ Bq/kg) on a detector mass of many tons of scintillator. Feasibility studies are performed in a counting test facility now operating at LNGS, which consists of 4 t of liquid scintillator viewed by 100 photomultipliers and shielded by 100 t of water. The accomplishment of this goal requires the shielding liquid, water, to be at the 10⁻¹³ g/g contamination level (1.2 × 10⁻⁶ Bq/kg) or better. This paper describes the water purification system; it consists of a combination of several purification processes to remove particulate, radioactive ions, dissolved gases and other impurities. Residual contaminations are measured by analytical or direct-counting techniques. For radon measurement, particularly challenging at this low activity levels, a low background counting method has been developed.     

Use of subunit-specific antisense oligodeoxynucleotides to define developmental changes in the properties of N-methyl-D-aspartate receptors

Antisense oligodeoxynucleotides were used to determine whether alterations in the expression of N-methyl-D-aspartate (NMDA) receptor subunit mRNA are responsible for developmental changes in the sensitivity of receptors to agonists and antagonists. Xenopus laevis oocytes were injected with mRNA prepared from neonatal and adult rat cerebral cortex, and the effects of agonists and antagonists were determined under voltage-clamp conditions. Glycine-site antagonists like 7-chlorokynurenate and glutamate-site antagonists like CGP-39653 were more potent at NMDA receptors expressed from mRNA from adult rat cerebral cortex than those expressed from mRNA from 1-day-old rat. NMDA receptors from 1-day-old rat cerebral cortex were more sensitive to activation by glycine than were receptors from adult rat cerebral cortex. 7-Chlorokynurenate and CGP-39653 were more potent inhibitors of responses seen with heteromeric NR1/NR2A receptors than with NR1/ NR2B receptors. Conversely, heteromeric NR1/NR2B receptors were more sensitive to activation by glycine than were NR1/NR2A receptors. We previously described a delay in the expression of the NR2A subunit in developing rat brain. Anti-sense oligodeoxynucleotides were used to determine whether the delayed expression of the NR2A subunit underlies changes in pharmacological properties observed during development. The properties of receptors seen when adult brain mRNA was coinjected with antisense oligodeoxynucleotides against the NR2A subunit were similar to those found in receptors from 1-day-old rat brain. These data suggest that changes in the sensitivity of NMDA receptors to antagonists and to glycine seen during development are a result of alterations in the expression of different species of NR2 subunit mRNA.