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Biomedical subjects

W F Riesen

Publications and source records attributed to W F Riesen.

At least 55 records · Page 3Linked to original sources

[Swiss simvastatin multicenter study: 1. Efficacy of 10 mg simvastatin daily in patients with primary hypercholesterolemia].

In a Swiss multicenter study with determination of lipid and lipoprotein parameters in a central laboratory, the efficacy of simvastatin, MSD, was evaluated in patients with primary hypercholesterolemia. Lipid and lipoprotein values were determined in 109 patients before and after 6 weeks' therapy with 10 mg simvastatin per day. A significant decrease in total cholesterol, LDL-cholesterol and apo B, of 21.1, 25.8 and 24.1% respectively, was observed. No influence of simvastatin on apo A-II was found, but HDL-cholesterol and apo A-I were slightly increased (+6.1 and 4.4% respectively). The data show that HMG-CoA reductase inhibitors constitute a new class of effective drugs for the treatment of hypercholesterolemia.

Adult↗

[Selective elimination of atherogenic lipoproteins using dextran-sulfate cellulose. Experiences in 2 patients with heterozygote familial hypercholesterolemia].

Extracorporeal elimination of atherogenic lipoproteins with dextran-sulfate-cellulose for lowering of plasma cholesterol levels was tested in 2 patients with familial heterozygous hypercholesterolemia (untreated cholesterol values 12.9 +/- 1.5 and 12.5 +/- 1.2 respectively) in a longterm experiment. One patient was treated weekly for a period of 36 weeks and the other at fourteen days' intervals with simultaneous administration of 40 mg/day Simvastatin (synvinolin, MSD) for 8 weeks. The mean reduction in total cholesterol concentration was 41% in the first case and 54% in the second (combination with Simvastatin). The therapy was well tolerated without side effects.

Adult↗

Effects of simvastatin and fenofibrate on serum lipoproteins and apolipoproteins in primary hypercholesterolaemia.

Sixteen patients with primary hypercholesterolaemia received double-blind either fenofibrate (n = 8; 200 mg bid) or the HMG-CoA reductase inhibitor simvastatin (n = 8; 20 mg q.p.m. [corrected] or 40 mg q.p.m. [corrected] if LDL-cholesterol did not fall below 3.6 mmol.l-1 after 4 weeks of treatment). Simvastatin reduced total cholesterol from 9.7 to 7.0 mmol.l-1 after 10 weeks (-28%), and fenofibrate reduced it from 9.2 to 7.7 mmol.l-1 (-15%). The decrease was less during fenofibrate than during simvastatin treatment (time x drug: p = 0.02). Serum LDL-cholesterol fell from 8.3 to 5.3 mmol.l-1 (-36%) during simvastatin and from 7.2 to 6.0 mmol.l-1 (-16%) during fenofibrate administration. Again, the effect of simvastatin was more pronounced than that of fenofibrate (time x drug: p = 0.03). HDL-cholesterol increased significantly from 1.1 to 1.2 mmol.l-1 (+13%) during fenofibrate administration and it did not change significantly during simvastatin. Serum triglycerides fell from 1.3 to 1.1 mmol.l-1 (-16%) during simvastatin, and even more significantly from 2.2 to 1.1 mmol.l-1 (-51%) during fenofibrate (time x drug: p = 0.002). Apolipoprotein B fell on simvastatin from 1.9 to 1.4 g.l-1 (-24%) and from 1.8 to 1.4 g.l-1 (-22%) during fenofibrate. Both drugs were well tolerated and had no significant adverse effects. Simvastatin lowered total and LDL-cholesterol concentrations more than fenofibrate, while the latter had more effect on triglycerides, suggesting specific indications for the two drugs in the treatment of hyperlipoproteinaemias.

Adult↗

Anthropometric and lifestyle correlates of serum lipoprotein and apolipoprotein levels among normal non-smoking men and women.

The relationship between serologic predictors of coronary risk and anthropometric as well as lifestyle characteristics was investigated in 61 men (37.5 +/- 8.5 yrs) and 33 women (40.1 +/- 9.0 yrs). All subjects were healthy non-smokers, mostly middle-class bank employees. In bivariate analysis, among both genders the ratio of waist-to-hip circumference (WHR) was the single best predictor of levels of serum LDL-cholesterol, apolipoprotein B, VLDL-cholesterol and triglycerides (positive association) as well as HDL-cholesterol and apolipoprotein A-I (inverse association). In men, body fat as estimated from bioelectrical impedance measurement was the second best predictor of lipoprotein and apoprotein concentrations, whereas in women it was the body mass index (BMI). The additional independent predictive power of WHR and body fat for the lipid profile was tested in multivariate analysis by adding WHR and body fat sequentially to regression models containing already BMI, endurance capacity, exercise, alcohol consumption and age. For example, explained variance of triglyceride distribution rose from 26.3 to 35.1% (P = 0.01 for increase) when body fat was entered into the regression equation, or inclusion of WHR into a model already containing age, the behavioral variables, BMI, and body fat increased the explained variance of LDL/HDL-cholesterol ratio from 20.9 to 27.6% (P = 0.04 for increase). In women, the same regression models were even slightly more predictive for the serum lipid profile. Endurance capacity was related to a low atherogenic risk lipid profile in bivariate analysis but lost much of its predictive power in multivariate analysis, which confirms that the effect of fitness on lipid levels is probably mediated in part by a low body fat content. It is concluded from this cross-sectional investigation that studies which focus on associations between lifestyle and serologic predictors of atherogenic risk should possibly include the WHR and a measure of body fat, since the latter two appear to be closer correlates of serum lipoprotein and apolipoprotein levels than BMI or single behavioral factors, at least among male non-smokers.

Adipose Tissue↗

Lipoprotein changes in familial hypercholesterolemia after extracorporeal immunoadsorption of low density lipoproteins.

The effects of extracorporeal immunoadsorption of LDL on the lipoprotein metabolism in two patients with familial hypercholesterolemia are reported. The immunoadsorbent consisted of F(ab')2 fragments of sheep anti-LDL antibodies, which had been coupled to Sepharose CL 4B. Within a time period of 3 to 3.5 hours a mean reduction of the level of total cholesterol by 76 +/- 4 p. cent could be obtained. The level of LDL cholesterol was reduced by 78 +/- 4 p. cent and the level of apo. B by 84 +/- 5 p. cent. Both LDL and VLDL were bound to the immunoadsorbent, while HDL was predominantly lowered by the plasma-dilution, which was in the order of 20 p. cent. The same was true for other serum proteins, not related to LDL or VLDL. The relative distribution of the different lipoprotein classes was again reached 3 days after the treatment, the initial lipid and apolipoprotein levels two to three weeks after the treatment. In a long-term therapy consisting of 45 treatments with a mean interval of 18 days between two treatments a mean cholesterol lowering of 42 p. cent could be achieved. No adverse effects and no sensitization to be heterologous protein were observed.

Adult↗

The proliferative response of human peripheral blood lymphocytes to group A streptococcal vaccine.

The proliferative response of human peripheral blood mononuclear cells to group A streptococcal vaccine (strain J17A4) was assessed by measurement of [3H]thymidine incorporation. This was maximal after 7 days in cultures containing 1 X 10(5) lymphocytes. Cells from 33 out of 38 adult donors (87%) yielded stimulation indices between 2.0 and 81. Responding cells were predominantly of the OKT4+, Ia+, Tac+ phenotype expressed by activated helper T lymphocytes. In contrast, no response was observed in 10 out of 12 samples of cord blood lymphocytes. Addition of conventional rabbit or monoclonal murine anti-Ia (HLA-DR) antibodies to the culture medium abrogated the vaccine-induced proliferative response. Frequencies of responding cells estimated by limiting dilution analysis were between 1 in 2370 and 1 in 4580 lymphocytes. The results suggest that lymphocyte stimulations induced with streptococcal group A vaccine represented an in vitro anamnestic cellular immune response.

Antibody-Producing Cells↗

Quantitation of apolipoprotein C-III in normal and in hyperlipaemic serum samples by enzyme-linked immunosorbent assay.

A specific and sensitive Sandwich enzyme-linked immunosorbent assay (ELISA) for the quantitative determination of apolipoprotein C-III, a major apolipoprotein of human very low density lipoproteins is described. The assay is non-competitive and it uses the same affinity isolated sheep antibody both for coating the wells and as conjugate with alkaline phosphatase. Total serum apo C-III was determined in a normal population of 24 men and 21 women. The difference was not statistically significant. In both sexes apo C-III concentration correlated positively with the serum triglyceride levels. In patients with hyperlipoproteinemia, apo C-III levels were increased.

Apolipoprotein C-III↗

Quantitation of apolipoprotein B by polyclonal and monoclonal antibodies.

A non-competitive sandwich enzyme linked immunosorbent assay for the quantitation of apolipoprotein B with polyclonal and monoclonal antibodies was developed. Polyclonal antibodies were used as 'coater'. In the assay with polyclonal antibodies, the same antibody was used as conjugate with alkaline phosphatase. For studies with monoclonal antibodies, enzyme conjugated anti-mouse immunoglobulin had to be used, since monoclonal antibodies lost their reactivity upon enzyme conjugation. Two murine monoclonal antibodies were employed: MAB B-1 with specificity for apolipoproteins (Apo) B-48 and B-100 and MAB B-5 with specificity for B-100 (Radioimmunoassay Inc.). In a reference group Apo B values of 0.82 +/- 0.20 g/l were measured with polyclonal antibodies, 0.68 +/- 0.19 g/l and 0.95 +/- 0.33 g/l with MAB B-1 and MAB B-5. In pure hypercholesterolemia, a similar increase was found with all three antibodies, while in combined hyperlipoproteinemia MAB B-5 gave greater than 40% lower values. Differences were also found with respect to the correlation between Apo B and cholesterol or triglycerides.

Antibodies↗

[Management of hypercholesteremia by extracorporeal immune adsorption].

Reduction of plasma cholesterol by extracorporeal immune elimination of low density lipoproteins (LDL) as an efficient approach to the treatment of familial hypercholesterolemia is described. LDL was removed from the plasma by immune adsorption on Sepharose-bound sheep antibodies against apo B, the protein fraction of LDL. To prevent the possibility of sensitization by the sheep antibodies, F(ab')2 fragments were used and the antibody containing Sepharose was underlaid by LDL containing Sepharose. Within a treatment time of 4 1/2-5 hours a reduction of the total plasma cholesterol by 70-80% was obtained. The mean reduction of the cholesterol concentration was more than 40% with a 14-day interval between two treatments. The concentration of other plasma proteins was not affected. The 11 treatments achieved so far were well tolerated and no side effects could be observed.

Adult↗

Enzyme-linked immunosorbent assay for apolipoprotein C-I.

A non-competitive sandwich enzyme-linked immunosorbent assay for apolipoprotein C-I was developed. Sheep antibody to this apolipoprotein C-I, purified by affinity chromatography, was used for coating the wells of a microtiter plate and as a conjugate with alkaline phosphatase. The linear range of the assay was from 80 ng to 15 ng. It was sensitive down to 5 ng. The intra-assay variation coefficient was 2.8%, and the inter-assay variation coefficient 5.3%. The mean concentration of apolipoprotein C-I was 61 +/- 20 mg/l in healthy normal males, and 65 +/- 19 mg/l in females. Apolipoprotein C-I levels were positively correlated with the total cholesterol concentration in both sexes (p less than 0.002). A significant correlation with triacylglycerol was only observed in males (p less than 0.05). A significant increase of apolipoprotein C-I was observed in type V hyperlipoproteinaemia, and in the only studied case of type III.

Apolipoprotein C-I↗

Long-term cimetidine in children with cystic fibrosis: a randomized double-blind study.

A prospective, randomized double-blind study of 38 children with cystic fibrosis (CF) was designed to evaluate the effectiveness of cimetidine in improving fat absorption and clinical condition. The treatment consisted of cimetidine or placebo, 600 mg/m2 body surface/day, over a 4-mo period. Clinical state, weight, height, skinfold thickness, lung function tests, para-aminobenzoic acid (PABA) peptide test, and plasma lipid and lipoprotein determinations were performed before and after the treatment period. Compared with age-matched healthy children, patients showed decreased cholesterol (150.2 +/- 31.2 mg/dl, mean +/- SD), decreased high density lipoprotein cholesterol (44.1 +/- 11.8 mg/dl), and decreased low density lipoprotein cholesterol (84.1 +/- 25.5 mg/dl) whereas the triglycerides and the very low density lipoprotein triglycerides were slightly elevated (118.2 +/- 33.0 mg/dl and 60.5 +/- 17.5 mg/dl, respectively). Apoprotein B and AI were slightly reduced and Apoprotein AII was in the normal range. After the 4-mo treatment no significant change in clinical condition, weight, or lipoprotein patterns could be detected between the two groups. The total PABA recovery in urine also did not change significantly (36.6 +/- 19.4% of the dosage given before versus 28.7 +/- 12.9% after 4 mo in the cimetidine group). Cimetidine gave rise to bronchoconstriction as shown by an increase in airway resistance (mean increase 14.8%) whereas the placebo group had a decreased Raw with a mean of 8.3%. Patients with CF have a dyslipoproteinemia that was not influenced by cimetidine. We conclude that cimetidine does not improve fat absorption and has, therefore, no place and no benefit in the treatment of children with CF.

Adolescent↗

Idiotypic and structural analysis of monoclonal human immunoglobulins with anti-streptolysin O activity.

The class, subclass and light chain distribution of eight myeloma proteins with anti-streptolysin O activity (ASO) in sera studied by our group and in cases from the literature indicates a predominance of the IgG1 kappa subclass and type of immunoglobulins. Three IgG myeloma proteins (O.I., L.F. and A.S.) were further characterized with respect to idiotypic cross-reaction and variable region subgroup. The anti-idiotypic antibodies (anti-Id) against protein O.I. and against protein L.F. both indicated idiotypic cross-reaction between O.I. and L.F. While in the case of anti-IdL.F. this cross-reaction was in the order of 5% it was much weaker when studied with anti-IdO.I.. The reaction between O.I. and anti-IdO.I. could be inhibited to 95% by the antigen streptolysin O, indicating that the idiotypic determinants are associated with the combining site. N-terminal amino acid sequence analysis showed that all three light chains fall in the V kappa III variable region subgroup. The heavy chains of proteins O.I. and L.F. with idiotypic similarities both have blocked N-termini, indicating the presence of the VHI or VHII subgroup while protein A.S. belongs to the VHIII subgroup.

Amino Acid Sequence↗

Studies on retinal microangiopathy and coronary macroangiopathy in rats with streptozotocin-induced diabetes.

Diabetes mellitus was induced in male rats by streptozotocin injection. After 4, 8 and 12 months, retinal and coronary vessels were prepared and their structure was studied. An age-dependent increase in thickness of the capillary basement membrane of retinal vessels was found both in controls and diabetics. Furthermore, diabetics had an added 20%, disease-related thickening, present after 4 months and thereafter. No significant change in coronary arteries was found. After 8 and 12 months, plasma lipids, triiodothyronin and thyroxin were measured. In diabetics, triglycerides were higher at both time intervals, high density lipoprotein was slightly increased and thyroxin was reduced after 8 months, and triiodothyronin was reduced after both 8 and 12 months. Diabetes of 12 months duration appears insufficient to induce significant arteriosclerotic changes in rats.

Animals↗

Apoproteins and lipids as discriminators of severity of coronary heart disease.

Serum apoprotein and lipid concentrations were measured in 63 patients undergoing coronary angiography. Thirty-eight patients had 50% or higher grade stenoses, 25 had chest pain, but no significant stenoses. Among the patients with higher grade stenoses 71% had hyperlipoproteinemias as opposed to 12% in patients without stenoses. As compared to suitable normal controls, patients with angiographically documented coronary heart disease showed significant changes in all lipid and apoprotein concentrations under study. However, differences between the two patients groups were also noted. Among these, apo A-I, A-II and B, total cholesterol and LDL cholesterol were statistically significant. These results indicate that apoprotein A and B levels, total cholesterol and LDL cholesterol are good discriminators of the severity of coronary heart disease, while HDL cholesterol is a more suitable parameter for epidemiological studies.

Adult↗