B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS)

OBJECTIVES: In this B-mode ultrasound study we assessed pravastatin treatment effects on carotid and femoral artery walls and investigated the correlations between the state and evolution of peripheral and coronary atherosclerosis. BACKGROUND: The Regression Growth Evaluation Statin Study (REGRESS) was an 11-center, 2-year, double-blind, placebo-controlled, prospective study of 885 men with coronary artery disease (CAD) (total cholesterol 4 to 8 mmol/liter). The study primarily investigated pravastatin treatment effects on the coronary lumen. This report focuses on the 255 patients who participated in the REGRESS ultrasound study. METHODS: Carotid and femoral artery walls were imaged at baseline and at 6, 12, 18 and 24 months. Pravastatin treatment effect was defined as the difference in progression of the combined intima-media thicknesses (IMT) between treatment groups. RESULTS: Pravastatin treatment effects were highly significant (combined IMT: p = 0.0085; combined far wall IMT: p < 0.0001; common femoral artery far wall IMT: p = 0.004). Correlations between the IMTs of the arterial wall segments ranged from -0.17 to 0.81. Baseline correlations between IMT and percent coronary lumen stenoses ranged from 0.23 to 0.36. Baseline IMT correlated with the mean coronary segment diameter (r = -0.32, p = 0.001) and minimal coronary obstruction diameter (r = -0.27, p = 0.005). There were no individual correlations between IMT and coronary lumen variables (p > 0.30). CONCLUSIONS: Pravastatin treatment effects on carotid and femoral artery walls were observed. B-mode ultrasound imaging studies of peripheral arterial walls could not describe the state and evolution of the coronary lumen in the individual patient, but proved to be a highly suitable tool for the assessment of antiatherosclerotic properties of agents.     

Detection of apoptosis in human and rat ovarian follicles

OBJECTIVE: The purpose of this study was to determine whether cells acquired from individual human preovulatory follicles undergo apoptosis (physiologic cell death) and, if so, to correlate the degree of apoptosis with characteristics of the follicles or the oocytes derived from the follicles. METHODS: We devised a sensitive nonradioactive method for detecting apoptotic DNA fragmentation in small numbers of cells derived from rat atretic follicles and follicular aspirates of patients undergoing assisted reproductive technologies. RESULTS: Using this method, apoptotic DNA was detected in rat atretic follicles, with optimal detection at 10-100 ng. Furthermore, apoptotic DNA was detected in some, but not all individual human follicular aspirates from several patients, and was found in follicles that produced oocytes that fertilized and developed into embryos. CONCLUSION: Apoptosis occurs in cells from human ovarian preovulatory follicles and may be a normal physiologic process of the follicle during luteinization.     

Lipidemic effect of methanol

The effect of methanol on some of the lipid components in serum was studied in rats. Methanol was administered by stomach tube in doses of 2 and 6 ml/kg b.wt daily for 21 and 6 days, respectively. Methanol was found to accumulate lipids; thus, cholesterol, phospholipids and triglycerides increased significantly. Concurrently, modification of the lipoid content of organs has been considered. It was concluded that methanol and not only formate, is toxic to rats, inspite of the alleged difference in routes of its metabolism in primates and rodents.     

Expression and rapid purification of recombinant rat calretinin: similarity to native rat calretinin

Therapeutic fast neutrons are densely ionizing particles, with a high relative biological effectiveness relative to 60Co gamma rays (RBE) and a low oxygen enhancement ratio (OER). The molecular basis of their properties is not yet entirely understood. In a previous work, we have shown that neutrons induce a different number of DNA frank strand breaks as compared to gamma photons, and we have revealed the presence of breaks due to the direct effects of neutrons. In the present work, we searched for eventual differences in the chemical nature of the attacked sites in DNA irradiated in oxygenated diluted solution. We compare our results with neutrons to those previously reported by other authors using gamma- or X-rays. Using sequencing gel electrophoresis of short natural DNA restriction fragments, or synthetic oligonucleotides, we have shown that, in the case of neutrons, the attack occurs with almost the same probability, at each nucleotide, as reported for gamma- and X-rays. The doubling of bands in the bottom of gels shows the presence of two types of termini, the 3'-phosphate and the 3'-phosphoglycolate. Upon neutron irradiation, the 3'-phosphate end appears with a higher yield than the 3'-phosphoglycolate, whereas equal amounts were obtained with gamma- or X-rays.     

Crystal structure of NMC-4 fab anti-von Willebrand factor A1 domain

We have solved the crystal structure of the Fab fragment of NMC-4, a mouse monoclonal antibody that binds to the A1 domain of von Willebrand factor (vWF). Two Asp and three Tyr residues in the complementarity determining regions 1 and 3 of the heavy chain exhibited a spatial orientation suggestive of a dominant role in establishing contact with the antigen. A cluster of Asp and Tyr residues occurs also in a region of the platelet glycoprotein (GP) Ib alpha amino terminal domain known to be critically involved in vWF binding. Thus, the structural information obtained with NMC-4 may prove relevant to understand the stereochemical bases of the GP Ib alpha-vWF interaction essential for thrombus formation at sites of vascular lesion.     

Analysis of vagal effects on ventricular rhythm in patients with atrial fibrillation

1. Animal studies suggest that the heart-rate-lowering effect of vagal stimulation during atrial fibrillation is due to: (1) a direct depressant effect on atrioventricular node conductivity, (2) enhancement of concealed atrioventricular nodal conduction of atrial impulses through augmenting fibrillatory activity, thereby indirectly prolonging atrioventricular nodal refractoriness. The purpose of the present study was to analyse these effects in man. 2. Sixteen patients with chronic atrial fibrillation were studied. After administration of propranolol (0.2 mg/kg intravenously) baseline ventricular rhythm was recorded (500 R-R intervals). Recordings were repeated after methylatropine (0.02 mg/kg intravenously). The shortest R-R interval was taken to represent atrioventricular nodal refractoriness. The ratio of the longest to the shortest R-R interval and the coefficient of variation of R-R intervals were used as parameters of concealed conduction. 3. Methylatropine foremost shortened long R-R intervals: values for the mean, shortest and longest R-R intervals decreased from 834 to 685 ms (-18%) (P < 0.001), 573 to 498 ms (-13%) (P < 0.001) and 1228 to 924 ms (-25%) (P < 0.001), respectively. Accordingly, the ratio of the longest to the shortest R-R interval decreased: 2.12 to 1.89 (-11%) (P < 0.05). Also, the coefficient of variation decreased: 0.24 to 0.20 (-17%) (P < 0.05). 4. This study supports the contention that vagal stimulation lowers ventricular rate during atrial fibrillation both by exerting a direct effect on the atrioventricular node and by augmenting concealed conduction.     

A new method for strengthening palatal closure defects of the hard palate

Closure of minor defects in the hard palate can be done with local flaps. There is often a risk of perforation of the reconstructed area. In the case reported this complication was obvious due to a large, thin, flap-covered area. In strengthening the reconstruction fascia lata and Surgicel was used. The postoperative result was excellent and the rehabilitation of the patient was without complications.