Effects of fenofibrate on angiographically examined coronary atherosclerosis and left ventricular function in hypercholesterolemic patients.

Within the framework of a prospective lipid-lowering intervention study 44 patients were treated over a period of 3 years with a lipid-lowering diet and 200-400 mg fenofibrate daily. The intervention led to statistically significant decreases in total cholesterol (Chol), low density lipoprotein cholesterol (LDL-Chol) and triglycerides levels, and to a significant increase in high density lipoprotein cholesterol (HDL-Chol) levels. Despite intervention, in 8 patients the HDL-Chol levels decreased by up to 20 mg/dl, where these were mainly patients with high initial values. Likewise, the triglycerides of 4 patients whose initial levels were relatively low increased (up to 49 mg/dl) and the LDL-Chol levels of 8 patients whose initial levels were also low increased (up to 49 mg/dl). Only minor success was achieved through the 6-week diet, but this was still slightly significant for Chol and LDL-Chol levels. A total of 21 patients underwent repeat angiography within 3 years for clinical reasons. For the evaluation of the angiographic progress a total of 98 minor and moderate stenoses was measured using digital image processing and automatic contour finding. The change in the angiographic parameters 'percent diameter reduction' (%DR) and 'percent plaque area' (%PA) correlated with on-treatment LDL-Chol levels (%DR change with LDL-Chol: r = 0.67, P = 0.0005; %DR change with Chol: r = 0.61, P = 0.002; %PA change with LDL-Chol: r = 0.40, P = 0.037; %PA change with Chol: r = 0.38, P = 0.044), while for HDL-Chol and triglycerides no influence on the angiographic progress could be demonstrated. On the basis of the reproducibility of the measuring methods the patients were classified in the categories 'regression', 'unchanged' and 'progression'. The patients classified as 'regression' (parameter: %DR change) showed an LDL-Chol mean value of 162 +/- 9 mg/dl, whereas those classified as 'unchanged' or 'progression' showed values of 189 +/- 25 mg/dl and 199 +/- 21 mg/dl, respectively (P = 0.014). A negative correlation appeared between the angiographic progress parameters and the initial degree of stenosis. The left ventricular ejection fraction in the second angiography showed relationships to lipoprotein levels and angiographic progress parameters.

Progression and regression of minor coronary arterial narrowings by quantitative angiography after fenofibrate therapy.

To study the effects of fenofibrate, a lipid-lowering medication, on patients with coronary artery disease, 191 minor coronary narrowings in 42 patients with coronary artery disease were analyzed by quantitative coronary angiography using computer-assisted contour detection. Computed parameters were percent diameter reduction and percent plaque area. A prospectively formed intervention group of 21 patients treated with special diet and fenofibrate (200 to 400 mg/day) was checked every 6 weeks with regard to risk factors. After a mean interval of 21 months, coronary angiography was repeated, using the same x-ray system and nearly identical projections. The intervention group was angiographically compared at follow-up with an untreated comparison group, also comprising 21 patients. Both groups had high initial serum cholesterol (mean 311 mg/dl) and low-density lipoprotein (LDL) cholesterol levels (mean 235 mg/dl). Only among the treated patients did lipid levels change significantly: cholesterol, -19%; LDL cholesterol, -20%; high-density lipoprotein cholesterol, +19%; and triglycerides, -30%. At angiographic follow-up, the changes in percent diameter reduction and percent plaque area correlated positively with the mean serum and LDL cholesterol levels of the intervention group. Significant differences were found in the change in percent plaque area between both groups. The intervention subgroup with angiographic regressions (11 patients) had significantly lower serum and LDL cholesterol levels than the intervention subgroup with angiographic progressions (10 patients). These results indicate the beneficial effect of fenofibrate on minor coronary narrowings. Because of its high reproducibility in measuring minor narrowings, quantitative coronary angiography proved to be a suitable method for angiographic follow-up.

Effects of high-dose aprotinin on renal function in aortocoronary bypass grafting.

BACKGROUND: To reduce blood consumption in cardiac surgery, aprotinin has been widely used for years. Because aprotinin is metabolized in the kidney, damage of the renal system has been discussed. METHODS: To study these possibly unfavorable effects of aprotinin, a prospective, randomized, placebo-controlled study of 20 patients undergoing aortocoronary bypass operations was performed. A placebo group P was compared with group A, in which patients received high-dose aprotinin according to the "Hammersmith" regimen. Renal function was assessed for 5 postoperative days using sodium dodecyl sulfate gel electrophoresis and quantitative protein analysis of the urine. RESULTS: During and after the operation, temporary renal dysfunction was found in all patients, with a substantial increase of all investigated indices. The alpha 1-microglobulin level in the urine was significantly increased in the aprotinin group for 5 days in comparison with the placebo group, with a maximum on the third postoperative day (64.8 +/- 13.7 versus 21.0 +/- 6.5 mg/L; p < 0.05). Similarly, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the bands of proteins filtrated in the renal tubular system were almost tripled in the aprotinin group 5 days postoperatively (5.0 +/- 0.8 versus 2.1 +/- 0.2; p < 0.05). Although urine production was significantly increased in group A (4789 +/- 580 versus 3653 +/- 492 mL/24 h postoperatively; p < 0.05), no relevant changes in serum or urine creatinine levels could be observed in either group. CONCLUSIONS: Patients undergoing aortocoronary bypass operations demonstrate a temporary renal dysfunction. Aprotinin impairs renal function in addition by overloading the tubular reabsorption mechanisms. Patients with normal renal function preoperatively--as were included in this study--are able to compensate for both the perioperative renal dysfunction caused by the extracorporeal circulation and the additional tubular damage due to aprotinin.

Elevated serum CK-BB levels in patients with cerebral transtentorial herniation after ischemic stroke.

We examined the time course of CK and its isoenzymes in 15 patients with severe ischemic stroke. Patients with cerebral transtentorial herniation (n = 7) had the highest CK-BB activity during herniation (1.54 +/- 0.6 U/L, mean +/- SD; range: 1.0-2.6 U/L). These values were distinctly above the values of a control group of 20 patients with non-neurological diseases (0.39 +/- 0.2 U/L, mean +/- SD). In patients with smaller lesions without herniation (n = 8) the maximum CK-BB increase was lower (0.56 +/- 0.26 U/L, mean +/- SD).

LDL-apheresis in two patients with extremely elevated lipoprotein (a) levels.

Hyperlipidemia and elevated lipoprotein (a) [Lp(a)] levels have been linked to the development and progression of premature atherosclerosis. Two male caucasian patients (36 and 42 years old) with heterozygous familial hypercholesterolemia and extremely elevated Lp(a) concentrations, resistant to diet regimen and lipid lowering drugs, were treated with LDL-apheresis for 55 months (liposorber system, Kaneka, Japan) and 15 months (immunoadsorption system, special Lp(a) columns, Lipopak, Pocard, Russia). Lp(a) dropped on average by 50%, total cholesterol by 27%, LDL-cholesterol by 42%, triglycerides by 43% and the fibrinogen concentration by 16%. Prior to treatment, both patients had suffered three myocardial infarctions. Four and six coronary angiographies with two and four percutaneous transluminal angioplasties (PTCA) were necessary. Since the treatment with LDL-apheresis neither myocardial infarctions nor cardiac complaints have been observed, and both patients have reported better performance. Available data suggest that LDL-apheresis may be effective in the treatment of patients with extremely high Lp(a) concentration.

Clinical chemical methods for the routine assessment of the vitamin status in human populations. Part III: The apoenzyme stimulation tests for vitamin B1, B2 and B6 adapted to the Cobas-Bio analyzer.

The programming of the Cobas-Bio centrifugal analyzer for kinetic tests of transketolase, glutathione reductase and aspartate amino-transferase is described. The results obtained in a population of 200 healthy people of both sexes are reported.

Simultaneous determination of retinol, tocopherols, carotenes and lycopene in plasma by means of high-performance liquid chromatography on reversed phase.

The determination of the vitamins A and E as well as of carotenes and lycopene is important for studies of cardiovascular diseases and cancer. A method for laboratory routine is reported to separate simultaneously retinol, tocopherols, alpha- and beta-carotene, lycopene and beta-cryptoxanthin in human plasma or serum by HPLC on reversed phase starting from one extract. Two detectors with programmable wavelength are used sequentially, a spectrophotometer for the detection of the carotenoids in the visible region and a fluorometer for the assay of retinol and the tocopherols.

Clinical chemical methods for the routine assessment of the vitamin status in human populations. Part II: The water-soluble vitamins B1, B2 and B6.

Simple and proven techniques for the assay of the coenzyme stimulation of the erythrocyte enzymes transketolase, glutathione reductase and glutamate oxaloacetate aminotransferase are described. The results found in a cohort of 150 blood donors and their comparison with the values for total thiamine in whole blood and pyridoxal phosphate in erythrocytes are presented.

Clinical chemical methods for the routine assessment of the vitamin status in human populations. Part I: The fat-soluble vitamins A and E, and beta-carotene.

Reliable HPLC methods for the routine determination of vitamin A (only retinol, not the ester) of beta-carotene and of vitamin E in plasma are described. The results found in 150 blood donors are reported; the correlation of the concentrations of vitamin A with retinol-binding protein and of vitamin E with beta-lipoproteins are calculated.

Contrast enhancement in light microscopy.

The optical microscope is a fundamental component of an image cytometry system. Electronic imaging has both greatly enhanced the capabilities of light microscopes and placed ever-increasing demands on their optical performance. This unit covers the basic concepts of light microscopy, including Köhler illumination, resolution, contrast, and numerical aperture, and reviews the many types of instruments and techniques for contrast enhancement.

Thyroid iodine concentration and total thyroid iodine in normal subjects and in endemic goitre subjects.

Thyroid iodine concentration and total thyroid iodine were determined by an automated technique by means of the ceric arsenious acid reaction in 42 males and 13 females. The thyroids were taken from autopsy material in a region with a low dietary intake. The accuracy of the method to estimate iodine was checked by neutron activation analysis. There was an excellent correlation between the iodine contents of thyroid specimens, when measured by chemical or by activation analysis. The mean iodine concentration was 1.86 mg/g dry weight and was found to be lower than in non-goitrous regions. In goitres, the mean iodine concentration was significantly lower, and the mean total thyroid of normal weight. There was no significant difference in iodine concentration and total iodine between males and females. The thyroid iodine concentration did not depend upon age in adults. The data were log normally distributed. It was established that mean iodine concentrations under 2 mg/g dry weight or 0.45 mg/g fresh weight are to be regarded as an important index of iodine deficiency.

[Enzyme determination in the urine for the evaluation of kidney tolerance of the water-soluble roentgen contrast medium iopamidol]. / Enzymbestimmungen im Harn zur Beurteilung der Nierenverträglichkeit des wasserlöslichen Röntgen-Kontrastmittels Iopamidol.

The renal toxicity of the ionic, very hyperosmolaric megluminamidotrizoate was compared with the toxicity of the non-ionic, slightly hypertonic iopamidol after intravenous injection of 0.7 ml/kg body weight (i.e. about 300 mg iodine/ml) in a randomized study of 20 individuals with normal kidneys. Quantitative measurements of the excretion of the enzymes, lactate dehydrogenase (LDH), alkaline phosphatase (AP), and N-acetylglucosaminidase (NAG) in 24-h urine samples, serum creatinine, and the endogeneous creatine clearance were conducted to determine the possible renal damage. All 20 subjects tolerated both contrast mediums well. Reduced renal function as measured by the creatinine blood level and the endogeneous clearance did not occur. The ionic, hyperosmolaric megluminamidotrizoate++ caused significantly elevated enzymuria of NAG, AP, and LDH (P less than 0.01) following tubular irrigation, whereas iopamidol showed no significant enzymuria. Therefore, it appears that the non-ionic contrast medium, iopamidol, is less toxic for kidneys than the ionic megluminamidotrizoate.

[The effect of methotrexate pharmacokinetics and of leucovorin rescue on the prognosis of osteosarcoma]. / Einfluss der Methotrexatpharmakokinetik und des Leukovorinrescues auf die Prognose des Osteosarkoms.

A total of 129 high-dosage methotrexate therapies performed in 19 patients with osteosarcoma were retrospectively analyzed. Serum methotrexate peak concentrations were found to vary widely, both inter-individually as well as in the same patient. The measured MTX peak concentrations correlated closely with pharmacokinetic data such as area under the curve and total body clearance. No correlations were found between the serum MTX correlations and different times after methotrexate administration. Increase in leucovorin rescue or low MTX peak concentrations were associated with poor prognosis. High-dosage methotrexate therapies with leucovorin rescue need to be further optimized in accordance with biochemical knowledge of the mode of action and the individual pharmacokinetic data of methotrexate. Such optimization may be expected to improve the prognosis for osteosarcoma. Serum methotrexate concentrations should be determined not only 24, 48, and 72 hours after methotrexate administration, in order to avoid elevated toxicity of the therapy, but also at the start of methotrexate infusion, in order to influence MTX peak concentrations at an early stage if necessary. Measurement of L-leucovorin in serum will be necessary, to enable a restrictive leucovorin rescue to be performed safely.

[Subendocardial jeopardy of the hypertrophied myocardium]. / Zur Innenschichtgefährdung des hypertrophierten Myokards.

In moderate hypertrophy (+35%) of the canine left ventricle (LV), resting myocardial blood flow (MBF, tracer microspheres) was not significantly altered when compared with controls. The endo/epi flow ratio of the LV was, however, significantly smaller (0.82-0.9) than in controls (1.02-1.17). After coronary dilatation with dipyridamole, coronary flow reserve was smaller in hypertrophied hearts. This became particularly obvious when acute coronary constriction (70%) was induced. There was, however, no indication that after coronary constriction in early hypertrophy the subendocardium was more jeopardized than in controls.