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Biomedical subjects

W Herrmann

Publications and source records attributed to W Herrmann.

At least 55 records · Page 3Linked to original sources

Mutation analysis of exon 3 of the LDL receptor gene in patients with severe hypercholesterolemia.

Single-strand conformation polymorphism analysis was used to screen for mutations in exon 3 of the low density lipoprotein receptor gene in a group of 218 unrelated patients with severe hypercholesterolemia (low density lipoprotein cholesterol > 6.7 mmol/l) living in the Cologne area of Germany. Including the complementary primers the fragment studied had a length of 176 bp. An abnormal single-strand conformation polymorphism pattern was observed in eight patients, four of whom had an identical abnormal fragment pattern indicating that five different mutations were present. By direct DNA sequencing, the underlying mutations could be confirmed (Cys54-->Tyr, Trp66-->Gly, Glu80-->Lys, 2 bp insertion (AT between codon 44 and 45, 9 bp deletion (codons 65 to 67)). The analysis of the pathogenicity indicates that all mutations were causative for the low density lipoprotein cholesterol elevation. The Trp66-->Gly and Glu80-->Lys mutations were previously described in a French-Canadian population and in an English population, respectively. The 2 bp insertion was detected in four unrelated patients and is one of the most frequent mutations detected up to now in the German population.

Base Sequence↗

Reference standardization and triglyceride interference of a new homogeneous HDL-cholesterol assay compared with a former chemical precipitation assay.

A homogeneous HDL-c assay (HDL-H), which uses polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin, was assessed for precision, accuracy, and cholesterol and triglyceride interference. In addition, its analytical performance was compared with that of a phosphotungstic acid (PTA)/MgCl2 precipitation method (HDL-P). Within-run CVs were < or = 1.87%; total CVs were < or = 3.08%. Accuracy was evaluated in fresh normotriglyceridemic sera using the Designated Comparison Method (HDL-H = 1.037 Designated Comparison Method + 4 mg/L; n = 63) and in moderately hypertriglyceridemic sera by using the Reference Method (HDL-H = 1.068 Reference Method - 17 mg/L; n = 41). Mean biases were 4.5% and 2.2%, respectively. In hypertriglyceridemic sera (n = 85), HDL-H concentrations were increasingly positively biased with increasing triglyceride concentrations. The method comparison between HDL-H and HDL-P yielded the following equation: HDL-H = 1.037 HDL-P + 15 mg/L; n = 478. We conclude that HDL-H amply meets the 1998 NCEP recommendations for total error; its precision is superior compared with that of HDL-P, and its average bias remains below +/-5% as long as triglyceride concentrations are < or = 10 g/L and in case of moderate hypercholesterolemia.

Chemical Precipitation↗

Effects of bunazosin and atenolol on serum lipids and apolipoproteins in a randomised trial.

The effects of bunazosin and atenolol on serum lipids and lipoproteins after 6 months of treatment were compared in this multicentric, double-blind, randomised trial. A total of 174 patients with mild to moderate essential hypertension from 15 hospitals in Germany and Poland was included in the study. Eighty-seven were treated with the alpha-receptor blocker bunazosin and the same number with the beta-blocker atenolol. Systolic and diastolic blood pressure decreased significantly in both groups, whereas only atenolol decreased pulse rate. In the bunazosin group HDL-cholesterol was significantly increased after 6 months of treatment, whereas all other analysed parameters remained unchanged. In the atenolol group total cholesterol, LDL-cholesterol, total triglycerides, apolipoprotein E, VLDL-cholesterol and VLDL-triglycerides were significantly increased after 6 months of therapy. There was a significant difference between bunazosin and atenolol for total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, triglycerides, VLDL-triglycerides and apolipoprotein B levels. As a consequence, there was a significant difference in the atherogenic index of both groups. We conclude that bunazosin is favorable in the treatment of high blood pressure, because the coronary risk is not negatively influenced as shown for atenolol.

Adrenergic alpha-Antagonists↗

Comparison of effects of N-3 to N-6 fatty acids on serum level of lipoprotein(a) in patients with coronary artery disease.

The influence of dietary supplementation with n-3 versus n-6 fatty acids on plasma lipoprotein(a) (Lp[a]) levels was studied. Thirty-five male hospitalized patients with coronary artery disease were treated for 4 weeks with 12 g/day of fish oil (approximately 8.5 g of n-3 fatty acids) in combination with a 5,000 kilojoule, 30% fat diet and moderate exercise. Eighteen control patients given the same dietary and training program were treated with 12 g/day of rapeseed oil. Plasma Lp(a), in addition to several lipids and lipoproteins, blood clotting factors, and platelet reactivity, were measured before and at the end of therapy. Results can be summarized as follows: total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels decreased significantly in both the rapeseed oil (-14.4%, -20.3%, -15.2%, respectively) and fish oil (-12.2%, -16.0%, and -14.2%, respectively) groups. Triglycerides decreased (-20.3%) and high-density lipoprotein cholesterol increased (+8.3%) significantly only in patients treated with fish oil. Plasma Lp(a) levels were reduced by 14% in the fish oil group, but unaffected in the rapeseed oil group. Patients treated with fish oil could be categorized into 2 subgroups: "responders," with a reduction in Lp(a) by 24% and "nonresponders," with a small nonsignificant increase in serum Lp(a). Responders and nonresponders exhibited a marked reduction in cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and triglycerides, and an increase in high-density lipoprotein3 cholesterol. There was a large reduction in tissue plasminogen activator in the fish oil group, which correlated significantly with reduction in Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins B↗

The influence of apolipoprotein E polymorphism on plasma concentrations of apolipoprotein B and A-I during the first year of life.

Apolipoprotein (apo)E polymorphism has been shown to be associated with different serum levels of cholesterol, apoB, and apoE. In clarifying the degree of influence of the apoE isoforms, investigations in an early stage of life are useful. The aim of the study was to investigate the plasma levels of apoB and apoA-I as structural proteins of low and high density lipoproteins, in relation to apoE phenotypes during the first year of life. Conclusions about the relationship between apoE phenotype and the development of the lipoprotein patterns can be drawn. The concentrations of apoB and apoA-I in capillary plasma as well as the apoE phenotype were estimated in 199 newborns (7 days old) and in follow-up investigations of a subgroup of 45 at 1, 4, 12, 24, and 52 weeks. The phenotype frequencies were as follows: 70% apoE 3/3, 16% apoE 3/4, 10% apoE 2/3, 2.5% apoE 2/2, and 1.5% apoE 4/2. The plasma concentrations of apoB and apoA-I in the newborns (7 days old) averaged 55% of the adult value and increased toward the end of the first year of life up to approximately 85%. The course of the plasma concentrations of apoB and apoA-I in relation to the apoE phenotype showed that, beginning at 24 weeks, the apoB levels were significantly lower for the phenotype E 2/2 and in tendency also for the phenotype E 2/3 in comparison with E 3/3. At the end of the first year of life, the apoB levels in infants with apoE phenotype 2/2 increased only by 50% and yielded 0.59 g/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗

[Classification of hyperlipoproteinemias and interpretation of laboratory parameters].

Hyperlipidemias are grouped according to their lipid levels in hypercholesterolemia, hypertriglyceridemias, and mixed hyperlipidemias. Among these, hypercholesterolemia has the strongest correlation to the risk for coronary heart disease. Based on the results from epidemiologic studies and intervention trials several expert panels have defined cholesterol values with low and high cardiovascular risk and cholesterol target levels for treatment. In the presence of hyperlipidemia additional parameters like LDL cholesterol, HDL cholesterol, and Lp(a) may be determined depending on the individual patient's risk profile. For classification of familial lipid disorders, analysis of relatives and the determination of special parameters may be necessary. These include apolipoproteins (concentration, isoforms, mutants), enzyme activities (lipases, LCAT), LDL receptor activity, oratypical lipoproteins.

Apolipoproteins↗

[Effect of fish oil concentrate on the lipoprotein profile of patients with type II diabetes mellitus].

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with increased very-low-density lipoprotein (VLDL) and triglyceride concentrations as abnormalities of low-density lipoprotein (LDL) composition. Because fish oil has a strong triglyceride lowering effect in case of normolipemic subjects, we investigated the influence of supplementary fish oil diet in patients suffering from NIDDM (n = 19), who until now were not treated by drugs but only by diet. The study was started with a placebo-run-in-period for four weeks (phase I, 6 g rape seed oil capsules/d), followed by a verum period for twelve weeks (phase II, 6 g fish oil concentrate capsules/d), and a wash-out-period for four weeks (phase III, 6 g rape seed oil capsules/d). The fish oil supplementation contained at least 3 g eicosapentenoic and docosahexenoic acid. The lipoproteins, apolipoproteins, blood glucose, and insulin level (fasting and after load test) were checked at the beginning and at the end of each phase. In comparison to the placebo rape seed oil supplementation, the fish oil diet effected a decrease of serum triglycerides by 29%. LDL-cholesterol increased by 9%, HDL-cholesterol by 9% (especially HDL2-cholesterol), and apolipoprotein B by 4%. Apolipoprotein A-I was reduced by 9%. The fasting blood glucose and the glucose load test as the insulin level (fasting and after load test) showed no significant changes at the end of the verum period in comparison to the run-in-phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol, HDL↗

Preservation of cartilage matrix proteoglycans using cationic dyes chemically related to ruthenium hexaammine trichloride.

We tested various cationic dyes chemically related to ruthenium hexaammine trichloride (RHT) [i.e., the RHT-cyclohexanedione complex (RHT-CC), pentaamine ruthenium N-dimethylphenylenediimine trichloride (PRT), tris-(bipyridyl)ruthenium (II) chloride (TRC), tris (bipyridyl) iron (II) chloride (TIC), and cobalt hexaammine trichloride (CHT)] for their effectiveness in precipitating cartilage matrix proteoglycans in situ. Dyes were introduced into media at the onset of processing and were present throughout both aldehyde fixation and osmium tetroxide post-fixation. Contrary to expectation, most of the dye-proteoglycan complexes generated and stable under aldehyde fixation conditions were found to be unstable during post-fixation despite the continuing presence of the dye. A similar phenomenon was also found for the cationic dyes commonly used for precipitation of proteoglycans in cartilage tissue sections (such as Acridine Orange, Alcian Blue, Azure A, Methylene Blue, and Ruthenium Red). Only two dyes, i.e., RHT and the newly tested RHT-CC, formed proteoglycan precipitates sufficiently stable to resist disruption and extraction during osmium tetroxide post-fixation. The latter may be particularly useful in semiquantitative analyses of proteoglycan content in unstained tissue sections owing to its intense brown-black color. For applications in which the osmium tetroxide post-fixation step may be omitted, TRC and PRT may also be valuable for semiquantitative histochemistry by virtue of their stable fluorescence and intense violet color signals, respectively.

Animals↗

Co-dergocrine plasma concentrations and blood pressure changes in hypertensive patients during therapy with slow-release co-dergocrine mesylate.

In a placebo controlled trial in 20 patients (mean age 38 years) with mild/moderate essential hypertension 4.5 mg slow-release co-dergocrine mesylate was administered once daily for 6 weeks and antihypertensive effects and plasma co-dergocrine concentrations determined 9 hours post-dose. Mean plasma co-dergocrine concentrations were 299 pg/ml, 357 pg/ml and 331 pg/ml measured after 2-, 4-, and 6-weeks administration respectively. Despite these relatively low concentrations there were statistically significant reductions in supine (-6/-6 mmHg), standing (-9/-8 mmHg) and exercise (-8/-5 mmHg) systolic and diastolic blood pressure. Blood glucose fell progressively and was 10% lower (p less than 0.02) after 6 weeks medication. Clinical and laboratory parameters showed that slow-release co-dergocrine mesylate was well tolerated with negligible adverse reactions.

Adolescent↗

[Therapy of mild to moderate hypertension. Efficacy and tolerance of Amlodipine in comparison with the combination nifedipine/mefruside].

Earlier clinical trials demonstrated the anti-hypertensive effect of amlodipine, a new calcium channel blocker of the dihydropyridine type. In the present comparative study, we investigated the anti-hypertensive effect of amlodipine in comparison with a combination of nifedipine and mefruside. In both groups, the anti-hypertensive effect was comparable. Normalization of the supine diastolic blood pressure was observed in 72.3% of patients treated with amlodipine and in 66.6% of those patients in the combination group. Both drugs were generally well tolerated, with a somewhat higher incidence of side effects being observed in the combination group. The study shows that amlodipine monotherapy in mild-to-moderate hypertension is equally as effective as combination therapy with nifedipine/mefruside, with amlodipine being superior in terms of tolerability.

Adult↗

[Real-time sonography in deep thrombosis of the pelvic and leg veins. A prospective comparison to phlebography].

Real-time B mode ultrasound is a well accepted diagnostic procedure in the non-invasive vascular examination. In a prospective study we examined 101 patients with clinical suspected deep vein thrombosis of the pelvis or leg using ultrasound and contrast venography within 24 hours and we compared the results of both examinations. All veins of the pelvis and lower extremities were scanned in transverse and longitudinal planes. 113 venograms were obtained; they demonstrated the presence of isolated proximal vein thrombosis in seven patients, seven isolated calf vein thromboses and 43 thromboses of both proximal and calf veins. The sensitivity of ultrasonography for detecting deep vein thrombosis in the proximal veins of the lower extremity was 98%, the specificity was also 98%. In the veins of the pelvis the sensitivity was 78%, the specificity 98% and in calf veins 60% and 97% respectively. The sensitivity for the detection of isolated calf vein thrombosis was only 14%. We conclude that ultrasonography has a very good sensitivity for detecting proximal vein thrombosis of the lower extremity and thrombosis of the pelvic veins. Phlebography remains the better method in detecting isolated calf vein thrombosis because of the difficult visualisation of the small calf veins by ultrasonography.

Adolescent↗

[Modification of selected lipoproteins and blood pressure by different dosages of n-3-fatty acids].

125 male patients with cardiovascular diseases (51.0 +/- 5.1 years) were treated with supplementary fish oil diet (gelatin capsules 2 g or 6 g PUFA/a day) and arachis oil gelatin capsules, respectively, as well as simultaneous fat- and energy-reduced diet at a moderate body-training during a four-week cure. N-3 PUFA-rich fish oil diet caused a significant decrease of the triglycerides and the Apo B with increase of the HDL2 cholesterol. By addition of reduction diet the effect became clearer by additional ascertained decrease of total and LDL-cholesterol. The blood pressure-reducing effect of n-3 PUFA, but not n-6 PUFA, at test as well as on exertion was present with 2 g and 6 g/a day, however, it was more conspicuous with the higher dosage.

Angina Pectoris↗

Is longitudinal bone growth influenced by diurnal variation in the mitotic activity of chondrocytes of the growth plate?

The diurnal variations in the mitotic index, height, and rate of linear bone growth were determined and correlations between these parameters examined. Young, unweaned, female Wistar rats were housed under standardized conditions, labeled with a fluorochrome 60 h before sacrifice, and killed at intervals throughout a 24-h period, specifically 0600, 1200, 1800, and 2400. The proximal tibial epiphyseal growth plates were collected and processed, and the mitotic index, growth plate height, and the rate of linear bone growth were measured. The mitotic index measured at 0600 was significantly higher than that measured at 1800 and 2400. Growth plates of rats sacrificed at 1200 were taller than those of rats sacrificed at 1800, but there was no difference between heights of growth plates from rats sacrificed at other times. Daily growth rate for all rats averaged 283.9 microns/day and there were no statistically significant differences between daily growth rates measured at any time period. Our findings imply that in comparative, quantitative structural studies of animal groups, sacrifice should be carried out at identical times of the day, since, given a constant speed of vascular ingrowth and diurnal variation in width, relative diurnal accumulation and depletions of cells may take place. We also suggest that the daily growth rate and mitotic index be measured directly and not be considered a function of the height of the growth plate.

Animals↗