[Lipid intervention and coronary heart disease in men less than 56 years of age. The Coronary Intervention Study: CIS]. / Lipid-Intervention und koronare Herzkrankheit bei Männern unter 56 Jahren. Die Coronare Interventions-Studie: CIS.

UNLABELLED: The CIS was undertaken with the aim to evaluate the effects of lipid modifications on angiographic progression and regression of CAD in patients with CAD and hypercholesterolemia. The design included a multicenter randomized, double-blind, parallel, placebo-controlled comparison, with target and safety limits for adjusting the trial medication depending on the LDL cholesterol level (LDL-C) achieved, i.e., up to 40 mg of simvastatin (S) or placebo (P) daily, add-on medication (up to 3 x 4 g Colestyramin), and diet counselling. Male patients, average age 49 (< or = 56) years, were included with angiographic CAD and a screening total cholesterol of 207-350 mg/dl, who were not due to undergo coronary bypass surgery or PTCA, who did not suffer from serious other disease (e.g., diabetes mellitus), and who had not undergone coronary bypass surgery previously. RESULTS: All baseline variables were comparable in the treatment groups, with 129 patients taking S and 125 taking P. Of these 254 patients 217 had their final study visit and 207 underwent a second angiography after an average treatment time of 2.3 years under an average daily dose of 37 mg S. 205 pairs of films were available for analysis. Vital information was obtained of all patients until closure of the data bank, half a year after the last study angiography. Five deaths occurred within the study period, 12 through March 15, 1995 (S: 1/6, P: 4/6). 37 patients (S: 18, P: 19) discontinued trial drug and protocol. Concomitant CAD medication was comparable in both groups, except lipid-lowering add-on medication which was significantly higher in the P group (38% versus 13%). Significant changes in lipid levels, on treatment, were observed in the S group amounting to a mean difference in LDL-C of -35%, in Apo-Protein B (ApoB) of -30%, in VLDL-C of -37%, and in triglycerides (TG) of -27%, and in HDL-C of +6%, in comparison to the control group; these differences were even greater in 137 fully compliant patients: -41, -36, -39, -31, and +7%, respectively. Progression in the S group was significantly less, as defined by the two primary target criteria: 1) the minimum obstruction diameter (MOD), determined by quantitative coronary angiography (QCA), decreased about five times less in comparison to the control group (S: by -0.017; P: -0.0954 mm), and 2) the standardized visual global change score (GCS) deteriorated almost three times less in the S group (by +0.20) than in the P group (+0.58). Of the secondary target criteria, the mean lumen diameter (QCA) also developed a significant difference (S: -0.20; P: +0.23 mm; p = 0.0006) with a trend toward regression in the S group. The QCA-%-stenosis deteriorated three- to four-times less in the S group as compared to the control group (S: by 0.69%; P: by 2.73%; p = 0.0022), and the number of patients with angiographic progression was nearly halved (S: 30%; P: 56%; p < 0.0000). These differences were determined by intention to treat analysis (ITT), and they were obtained in spite of lipid lowering add-on medication in 38% of the P patients; they turned out to be more pronounced in 137 fully compliant patients, in an analysis "as treated". The mean decrease in LDL-C serum level caused by S was significantly correlated to the decrease in progression, and multivariate regression analysis of both treatment groups identified LDL-C (or ApoB) and TG as independent predictors of progression. Progression appeared to be most pronounced in low and medium sized lesions, and the beneficial effect of lipid intervention dominated in lesions with 12-56% QCA stenosis severity. A small fraction of patients who suffered from exercise-induced angina, with ST-segment-depression at the beginning of the study, experienced a significant improvement under S as compared to P treatment. Although the study was not designed to show differences in clinical events, the combined number of all major cardiovascular events tended to be less frequent in the S than in the C gr

Development of antibodies reactive in antibody-dependent cellular cytotoxicity in infectious mononucleosis.

Serial sera from patients with infectious mononucleosis were examined for the emergence of antibodies reactive in antibody-dependent cellular cytotoxicity tests, using Epstein-Barr virus-superinfected Raji cells as targets. For this specific purpose, the antibody-dependent cellular cytotoxicity test proved to be of limited sensitivity because only relatively high serum dilutions can be tested dependably, due to prozone effects at low serum concentrations, and because antibody-dependent cellular cytotoxicity reactions at the 5% level are not always statistically significant. Under the conditions of the test, antibody-dependent cellular cytotoxicity-reactive antibodies were not measurable, or only barely measurable, in early-acute-phase sera, but they became detectable during convalescence and increased thereafter, gradually over many months to the range of titers seen in healthy persons after long-past-primary Epstein-Barr virus infections. The percentages of antibody-dependent cellular cytotoxicity ultimately attained were on the order of 20% in most patients and healthy individuals, but in others did not exceed 10%. The likely identity of the antibodies reactive in the test with antibodies to late Epstein-Barr virus-determined cell membrane antigens has been discussed.

Measurement of antibodies to herpesvirus types 1 and 2 in human sera by microradioimmunoassay.

The binding of 125I-labelled anti-human antibodies against the fc IgG fragment to unlabelled antiviral immunoglobulins in the surface of infected cells was used to quantitate antibodies against herpes simplex virus type (HSV-1) and type 2 (HSV-2) in sera from patients with cervix carcinoma. The microradioimmunoassay technique (micro-RIA) proved to be 5-10 times more sensitive than the microneutralization test. Antibody titres determined by micro-RIA correlated with neutralizing antibody titres to both HSV-1 and HSV-2. The relative antibody titres to HSV-1 and HSV-2, as determined by micro-RIA, could be used to distinguish persons previously infected with HSV-2 by means of II/I indices.

[Carcinoma of the uterine cervix and herpes simplex virus type 2. Investigations on the causal relationship (author's transl)]. / Zervixkarzinom und Herpes-simplex-Virus Typ 2. Untersuchungen zur Frage eines Kausalzusammenhangs

Epidemiological serological studies have shown that women with carcinoma of the uterine cervix show a higher incidence of Herpes Simplex Virus Type 2 (HSV 2) than controls. The attempt to demonstrate the genomic DNS of the HSV 2 in cells of carcinoma of the cervix by experiments of hybridization is reported. The investigations were carried out directly on material from carcinoma of the cervix and also on cell cultures from tumor material. The majority of the cultures grew fibroblasts but some cultures grew cells with the characteristics of malignant cells. The hybridization of DNS from portions of carcinoma or of DNS from cell cultures with complementary HSV 2 radioactive RNS showed in no case HSV-2-DNS in a quantity of one or one half genomic equivalent per cell. These investigations suggest that a casual relationship between carcinoma of the uterine cervix and an infection with HSV 2 is unlikely. However, it cannot be excluded that carcinoma of the uterine cervix has different quantitative proportions than the Burkitt-lymphoma and that only a fraction of the genomic material of the virus (smaller than 1/10) is incorporated into the malignant cell.