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.     

Utility of scintigraphic methods in patients with fever of unknown origin

BACKGROUND: We assessed the utility of scintigraphy with indium 111-labeled polyclonal human IgG scintigraphy in patients with fever of unknown origin that fulfilled the criteria of temperature of 38.3 degrees C or more for at least 3 weeks and no diagnosis during 1 week of hospital admission. We compared the utility of this technique with results of scintigraphic techniques reported in the literature. METHODS: Data for all patients seen at our university hospital in whom 111In-IgG scanning was performed were analyzed and checked for the criteria for fever of unknown origin. The literature on the utility of scintigraphic techniques in patients with fever of unknown origin was reviewed. RESULTS: We studied 24 patients with fever of unknown origin. In 13 patients, focal 111In-IgG accumulation was observed. In nine (38%) of those, the positive 111In-IgG scintigram led to the final diagnosis; in the other four patients (17%), the scintigraphic findings were not helpful. In the 11 patients with negative 111In-IgG scans, extensive diagnostic workup produced no infection as the final diagnosis in nine patients (38%), one had an abscess in a renal cyst that was detected several months later, and in the other the cause of fever was an infected intravenous line. The overall sensitivity and specificity of 111In-IgG scintigraphy were 81% and 69%, respectively. The positive predictive value was 69% and the negative predictive value was 82%. CONCLUSIONS: Our results show that 111In-IgG scintigraphy significantly contributed to the diagnostic process in patients with fever of unknown origin. A positive scan increased the likelihood of finding the cause of the fever, and a negative scan ruled out an inflammatory component with a high degree of certainty. These data compare favorably with data in the literature concerning other radiopharmaceuticals; a larger prospective evaluation of this technique is indicated.