Uno Erikson

The effect of probucol on femoral atherosclerosis: the Probucol Quantitative Regression Swedish Trial (PQRST).

The Probucol Quantitative Regression Swedish Trial tested whether treatment of hypercholesterolemic persons with probucol for 3 years affected femoral atherosclerosis. The primary end point was the change in atheroma volume estimated as change in lumen volume of the femoral artery assessed by quantitative arteriography. Three hundred three patients with visible atherosclerosis were randomized to probucol 0.5 g, twice daily, or to placebo. All patients were given diet and cholestyramine, 8 to 16 g/day. Twenty-nine patients were excluded because of inadequate primary end point measurements. The mean age of the remaining 274 subjects (158 were men) was 55 years. Seventeen percent had intermittent claudication and 24% had angina pectoris. After 3 years, the probucol-treated patients had 17% lower serum cholesterol, 12% lower low-density lipoprotein cholesterol, 24% lower total high-density lipoprotein cholesterol, and 34% lower high-density lipoprotein2 cholesterol levels than control subjects. All lipoprotein differences between the treatment groups remained highly significant during the trial. There was no statistically significant change in lumen volume between the probucol and the control group. Furthermore, there was no difference between the treatment groups with regard to change in arterial edge roughness or amount of aorto-femoral atherosclerosis; neither were there any differences between the treatment groups with regard to change in ST-segment depressions on exercise tests or ankle/arm blood pressure (secondary end points). In the control group, lumen volume increased (p < 0.001) and roughness of the femoral artery decreased (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Lowering of HDL2b by Probucol Partly Explains the Failure of the Drug to Affect Femoral Atherosclerosis in Subjects With Hypercholesterolemia : A Probucol Quantitative Regression Swedish Trial (PQRST) Report

The aim of the Probucol Quantitative Regression Swedish Trial (PQRST) (n = 303) was to investigate whether probucol (0.5 g BID) added to diet and cholestyramine (8 g BID) could retard progression or induce regression of femoral atherosclerosis in hypercholesterolemic (> 6.86 mmol/L) subjects. Probucol did not induce regression over the 3-year trial period as estimated by change in lumen volume on quantitative arteriography of a 20-cm segment of the femoral artery. In this report we studied in a representative subgroup (n = 72) whether the reduction in HDL concentrations induced by probucol could explain the failure of the drug to be effective. We analyzed the effects of treatment on HDL particle size subclasses. Probucol lowered the relative level of HDL2b, comprising the largest HDL particles, by 53% and the protein concentration of HDL2b by 67%. The protein reduction in HDL was mainly confined to the apolipoprotein A-I moiety. The change in lumen volume correlated significantly with change in HDL, ie, HDL cholesterol (r = .34, P < .01), HDL2 cholesterol (r = .37, P < .01), HDL2b protein (r = .44, P < .001), and the relative HDL2b value (r = .51, P < .001). The corresponding values for relative HDL2b, distribution calculated on the active (n = 35) and placebo (n = 37) groups separately were also significant (r = .39 and .32, respectively; both P < .05). The correlation between drug-induced change in the relative HDL2b concentration and change in atherosclerosis was independent of the alteration in triglyceride concentration and could not be explained by treatment interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Intravenous Contrast Media on Cortical and Medullary Blood Flow in the Rat Kidney

The effect of slow intravenous infusion of contrast medium (CM) (1600 mg I/kg body weight) on cortical blood flow (BF) and medullary BF in rat kidneys was investigated by laser-Doppler flowmetry on either renal cortex or exposed renal papillas (inner medulla). The effect on cortical BF was evaluated after infusion of either ioxaglate, iohexol, or ioxithalamate. Mannitol and Ringers solution were used as control substances. The effect on medullary BF was examined after infusion of either ioxaglate, iohexol, iopamidol, ioxithalamate, or mannitol. BF was measured continuously during a 30-minute control period and a 60-minute experimental period, starting with the CM infusion. Cortical BF was unchanged in the ioxaglate group and significantly increased in the iohexol, ioxithalamate, and mannitol groups (P less than .05). Medullary BF was moderately increased in the ioxaglate group (P less than .05) but moderately decreased in the groups that received iohexol, iopamidol, ioxithalamate, or mannitol (P less than .05). The reduction in medullary BF following infusion of the ratio 3.0 nonionic CM and of the ratio 1.5 ionic CM might be one contributory mechanism to the pathogenesis of CM nephropathy, especially in the presence of microangiopathy in the kidney.

Two-dimensional tortuosity of the superficial femoral artery in early atherosclerosis.

Tortuosity of an artery can disturb fluid mechanics and cause flow separation, which might in turn promote atherogenesis. This study discusses theoretically several quantitative measures of arterial tortuosity and curvature in two dimensions and tests them with computations from digitized femoral arteriograms. When reproducibility, sensitivity to scaling and computational procedure, and agreement between the measures were all taken into account, the total curvature and distance factor were considered the most suitable measures. Significant correlations were found between tortuosity and atherosclerosis measures, but the interpretation of this finding is not straightforward.

Influence of Contrast Media on Single Nephron Glomerular Filtration Rate in Rat Kidney: A comparison between diatrizoate, iohexol, ioxaglate, and iotrolan

The effects of slow (10 min) i.v. infusions of contrast media (CM, 1 600 mg I/kg b.w.) on single nephron glomerular filtration rate (SNGFR) in the rat kidney were investigated using a micropuncture technique. Diatrizoate, iohexol, or ioxaglate did not change SNGFR, although a tendency towards a transient suppression was seen during the infusion phase. Iotrolan infusion, however, decreased SNGFR (p < 0.05) and the value still remained below the control value 25 min after the start of infusion. Iotrolan is a nonionic dimeric CM and has a lower osmotic effect in the tubules than the ionic dimeric CM and the monomeric CM when given in iodine equivalent doses. These characteristics of iotrolan have probably some influence on the depression of SNGFR after iotrolan injection.

Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: Probucol quantitative regression Swedish trial (PQRST): A status report

The Probucol Quantitative Regression Swedish Trial is being performed to investigate the effects of probucol on atherosclerosis in the femoral artery. Probucol is combined with cholestyramine and dietary management in hypercholesterolemic patients, and the effects of atheroma developing in the femoral artery will be followed by a quantitative angiographic technique. A randomly selected control group is also being managed by dietary therapy and cholestyramine, but receives placebo instead of probucol. The treatment time in this double-blind trial is 3 years, and femoral angiography is performed yearly. Detailed lipoprotein and apolipoprotein analysis are performed at monthly intervals. The basic study design is described here, and some results from the open prerandomization phase of the study are presented.

Complications of Percutaneous Pericardiocentesis under Fluoroscopic Guidance

Complications in 352 cases of fluoroscopy-guided percutaneous pericardiocentesis accomplished through an indwelling catheter were reviewed following surgery and non-surgery. Thirteen major complications were found, namely 3 cardiac perforations, 2 cardiac arrhythmias, 4 cases of arterial bleeding, 2 cases of pneumothorax in children, one infection, and one major vagal reaction. No significant difference in complications was found between pericardiocenteses for pericardial effusions after cardiac surgery (n = 208) and those for effusions of non-surgical (n = 144) origin. Fluoroscopy-guided pericardiocentesis by the subxiphoid approach with placement of an indwelling catheter is a safe method for achieving pericardial drainage in both surgical and non-surgical effusions. Accidental cardiac perforation with a fine needle is a minor complication as long as the needle is directed towards the anterior diaphragmatic border of the right ventricle and drainage is achieved with a reliable indwelling catheter.

New Observations on Tissue Changes Along the Pathway of the Current in an Electrical Injury

This case reprot describes an electrical injury to a 43-year-old man in whom a high voltage alternating current had passed from one hand to the other. Since the extent of damage under the intact skin surface is always difficult to asses, the authors have studied the main arteries with repeated arteriograms, and the morphological changes of muscles and vessels in the immediate vicinity of the contact burns as well as those proximal to these points and under intact skin.

Predilection of atherosclerosis for the inner curvature in the femoral artery. A digitized angiography study.

The degree of atherosclerosis in the inner and outer curvature of the femoral artery was studied by using digitized angiography and edge-roughness calculations in 301 hyperlipidemic patients. When the two edges of the vessel were compared no significant difference was seen, but when the local curvature was taken into account, inner curves were found to be more atherosclerotic than outer curves, and both inner and outer curves were more affected than straight segments. The same pattern was encountered in subpopulations defined by clinical or blood lipid criteria. The suggested explanation is that flow disturbances such as low shear rates or separated flow, which tend to arise along the inner curvature, promote the development of atherosclerosis.

Effect of furosemide or mannitol before injection of a non-ionic contrast medium on intrarenal oxygen tension.

Oxygen tension (pO2) in rat renal cortex and outer medulla was studied after an intravenous injection of mannitol or furosemide, followed 10 minutes later by an intravenous injection of the non-ionic X-ray contrast medium (CM) iopromide (370 mg iodine/ml). Ten minutes after mannitol injection, before injection of CM, pO2 in the medulla had decreased from a control level of 32 +/- 3 to 28 +/- 4 mm Hg. The addition of CM caused a further decrease, to 24 +/- 5 mm Hg, which was a significant reduction. Ten minutes after furosemide injection the pO2 in the medulla had increased significantly, from a control value of 32 +/- 2 to 44 +/- 4 mm Hg. Injection of CM caused a significant decrease in pO2 to 37 +/- 3 mm. Ringers solution (n = 6) caused no changes. We conclude that pretreatment with mannitol or furosemide does not prevent the CM-induced decrease in pO2 in the outer medulla.