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Biomedical subjects

U Julius

Publications and source records attributed to U Julius.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mutations of the human hepatic lipase gene in patients with combined hypertriglyceridemia/hyperalphalipoproteinemia and in patients with familial combined hyperlipidemia.

Hepatic lipase is an enzyme which hydrolyzes triglycerides from plasma lipoproteins and thus takes part in the metabolism of intermediate density lipoproteins and high-density lipoproteins. The search described here concentrated on mutations of the HL gene in 129 patients with combined hypertriglyceridemia/hyperalphalipoproteinemia and in 184 members of 19 families with familial combined hyperlipidemia. Controls were 100 subjects with favorable lipid values (age 46-51 years). Mutation screening and analysis were performed by temperature-gradient gel electrophoresis, allele-specific restriction genotyping, and sequencing. Six different missense mutations and four different silent mutations were found in the HL gene. The alleles Phe-267 and Gln-343 were detected only once in the patient group with hypertriglyceridemia and hyperalphalipoproteinemia and were not detected in the control group. The allele Met-383 was rare in both patients and controls. We found 9.3% of the patients and only 3.0% of controls to be carrying the Val-73-Met missense mutation. The allele Phe-334 was found in 5.43% of patients and in 2.0% of controls. The difference between the frequencies of these alleles was significant between male patients and male controls (Met-73 P=0.044; Phe-334 P=0.047). Also, the summarized odds ratio of 3.28 (95% confidence interval 1.23-8.73) demonstrates that mutation carriers are significantly more prevalent in the patients. Fifteen carriers of the Met-73 allele were found in six families of the familial combined hyperlipidemia group. Furthermore, six carriers of the Phe-334 allele were found in three families of the same group. In comparison to the controls the summarized odds ratio of 2.45 (95% confidence interval 0.89-6.71) barely missed the level of significance. The linkage between genotype and phenotype was incomplete. These results show an association of the missense mutations Val-73-Met and Leu-334-Phe as susceptibility alleles for combined forms of hyperlipidemia.

Adolescent↗
PubMed1998

DALI-the first human whole-blood low-density lipoprotein and lipoprotein (a) apheresis system in clinical use: procedure and clinical results.

BACKGROUND: The DALI low-density lipoprotein (LDL) apheresis system is the first whole-blood apheresis system in regular clinical use. DALI stands for direct adsorption of lipoproteins, which describes the basic principle of operation of this newly developed LDL apheresis procedure. METHODS: The selective removal of LDLs and lipoprotein (a) [Lp(a)] is performed in human whole blood by adsorption onto polyacrylate-coated polyacrylamide beads in an adsorber. This article describes the results of the first open multicentre clinical trial in 14 patients in whom the safety and the efficacy of the system were tested. All patients were treated on average 17 times on a weekly basis. In total, 238 sessions were carried out during the study without severe side-effects. On average, 7675 mL of the patients' whole blood was processed in about 2 h. Anticoagulation in the extracorporeal system was carried out by first giving a heparin bolus followed by continuous addition of an acid citrate dextrose (ACD-A) infusion during the treatment. RESULTS: The processing of nearly 1.6 times the patient blood volumes resulted in a reduction in the median LDL-cholesterol level by 66-77% (dependent on the system configuration). The Lp(a) concentrations were reduced by 59-73% (dependent on the system configuration). HDL-cholesterol, blood cell count and the other clinical parameters were not significantly affected. CONCLUSION: Based on this short-term evaluation, the DALI apheresis system is a well-tolerated, effective and simple way of reducing LDL and Lp(a) in human whole blood. The system has been introduced to clinical practice. However, to use the DALI apheresis system in clinical routine, further evaluation of long-term effects is required.

Adult↗
PubMed1998

In vivo evidence for increased apolipoprotein A-I catabolism in subjects with impaired glucose tolerance.

The in vivo kinetics of the HDL apolipoproteins (apo) A-I and A-II were studied in six subjects with impaired glucose tolerance (IGT) and six control subjects with normal glucose tolerance (NGT), using a stable isotope approach. During a 12-h primed constant infusion of L-[ring-13C6]-phenylalanine, tracer enrichment was determined in apoA-I and apoA-II from ultracentrifugally isolated HDL. The rates of HDL apoA-I and apoA-II production and catabolism were estimated using a one-compartment model-based analysis. Triglycerides were higher in IGT subjects (1.33 +/- 0.21 vs. 0.84 +/- 0.27 mmol/l, P < 0.05), but were within the normal range. HDL cholesterol and apoA-I levels were significantly lower in subjects with IGT (1.07 +/- 0.15 vs. 1.36 +/- 0.14 mmol/l, P < 0.05; 0.94 +/- 0.10 vs. 1.34 +/- 0.07 g/l, P < 0.01). In IGT subjects, HDL composition was significantly altered, characterized by an increase in HDL triglycerides (4.9 +/- 1.9 vs. 3.2 +/- 1.0%, P < 0.05) and HDL phospholipids (34.7 +/- 2.6 vs. 27.5 +/- 5.8%, P < 0.05) and a decrease in HDL cholesteryl esters (10.1 +/- 2.0 vs. 12.7 +/- 2.9%, P < 0.05) and HDL apoA-I (31.5 +/- 4.4 vs. 43.2 +/- 2.4%, P < 0.05). The mean fractional catabolic rate (FCR) of HDL apoA-I was significantly higher in IGT subjects (0.34 +/- 0.05 vs. 0.26 +/- 0.03 day(-1), P < 0.01), while the HDL apoA-I production rate (PR), as well as the PR and FCR of HDL apoA-II, showed no differences between the two groups. There were significant correlations between HDL apoA-I FCR and the following parameters: HDL apoA-I (r = -0.902, P < 0.001), HDL cholesterol (r = -0.797, P = 0.001), plasma triglycerides (r = 0.743, P < 0.01), HDL triglycerides (r = 0.696, P < 0.01), and cholesterol ester transfer protein activity (r = 0.646, P < 0.01). We observed a strong positive association between increased apoA-I catabolism and insulin (r = 0.765, P < 0.01) and proinsulin (r = 0.797, P < 0.01) concentrations. These data support the hypothesis that the decrease in HDL cholesterol and apoA-I levels in IGT is principally the result of an enhanced apoA-I catabolism. The latter seems to be an early metabolic finding in IGT even when other lipid parameters, especially plasma triglycerides, still appear to be not or only weakly affected.

Adult↗
PubMed1997

[Immune thrombocytopenia, anemia and leukopenia during pregnancy. Successful therapy with extracorporeal immunoadsorption].

HISTORY AND CLINICAL FINDINGS: A 28-year-old woman in her fourth pregnancy had a positive direct Race-Coombs test in her 14th week of pregnancy. About 6 weeks later she developed marked anaemia, severe thrombocytopenia and leukopenia with nose-bleeds as well as petechiae over the lower abdomen and the inguinal regions. INVESTIGATIONS: Platelet count was 7000/microliter, haemoglobin concentration 4.8 mmol/l (7.73 g/dl) and WBC count 2600/microliter). Bleeding time was markedly prolonged. Erythrocyte-attached immunoglobulin G and complement components as well as antithrombocyte and antigranulocyte antibodies were demonstrated. Haemoblastosis or aplastic anaemia was excluded by bone marrow examination. TREATMENT AND COURSE: The pancytopenia with immune thrombocytopenia, autohaemolytic anaemia and associated leukopenia were classified as Evans syndrome. Administration of glucocorticoids and of immunoglobulins intravenously for 5 days failed to improve the blood picture significantly. But platelet count rose significantly on immunoadsorption (Ig Therasorb columns), allowing the pregnancy to proceed. CONCLUSION: In life-threatening states Ig immunoadsorption can achieve well tolerated, effective and specific elimination of pathogenetically relevant antibodies against blood cells and can also be applied in pregnant women.

Adult↗
PubMed1997

Stable isotope ratio analysis of amino acids: the use of N(O,S)-ethoxycarbonyl trifluoroethyl ester derivatives and gas chromatography/mass spectrometry.

N(O,S)-Ethoxycarbonyl trifluoroethyl amino acid esters are formed by the reaction of amino acids with ethylchloroformate plus trifluoroethanol plus pyridine. The use of these derivatives for a rapid and sensitive determination of specific enrichment of stable isotopically labeled tracer amino acids in blood plasma and protein hydrolysates, by using gas chromatography/electron impact mass spectrometry, is discussed.

Amino Acids↗
PubMed1997

[Postmenopausal hormone substitution and its effects on the climacteric syndrome, body weight and blood pressure].

The effect of 0.6 mg conjugated equine estrogens in combination with sequential medrogestone (5 mg from day 11 to 21) on climacteric symptoms, blood pressure and weight were investigated in 46 postmenopausal women. The climacteric symptoms were quantified by a modified Kuppermann-Index. After a 3 months' treatment the index decreased from 20.58 to 8.47 (p < 0.001). 28 patients (65%) showed a 50% and more reduction of climacteric symptoms. 40 patients (93%) reported an improvement of their complaints. The body weight remained stable. One patient had to interrupt the treatment due to a cerebral ischemic disease (PRIND). The systolic blood pressure was decreased by 7% and the diastolic by 16% under treatment (p < 0.001). 11 patients with borderline or not treated hypertension returned to normal ranges. 3 of the 4 patients treated with antihypertensiva came off the medicines.

Blood Pressure↗
PubMed1996

Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up.

The Diabetes Intervention Study (DIS) is a prospective population-based multicentre trial of newly detected cases of non-insulin-dependent diabetes mellitus (NIDDM). This report analyses the risk factors for subsequent coronary heart disease and all-cause death during the 11-year follow-up. The prognostic significance of the categories of the NIDDM Policy Group was validated with respect to the incidence of coronary heart disease and mortality. At baseline 1139 subjects, aged 30-55 years at the time of diabetes detection and classified as diet controlled after a 6-week screening phase, were included. Of the patients 112 (15.2%) suffered from myocardial infarction, 197 (19.82%) of 994 had died. The odds ratio for all-cause mortality compared to the general population for males at the age of 36-45 years was 5.1 and for females 7.0. In multivariate analysis age, blood pressure and smoking were independent risk factors for myocardial infarction and male sex, age, blood pressure, triglycerides, postprandial blood glucose and smoking for death, respectively. The categories of the NIDDM Policy Group target parameters for blood glucose, triglycerides and blood pressure were significant predictors of both CHD and death. Thus, it appears that in NIDDM good control of blood glucose, blood pressure and triglycerides is associated with a lower incidence of coronary heart disease and death rate respectively.

Adult↗
PubMed1996

Determinants for coronary heart disease in non-insulin-dependent diabetes mellitus: lessons from the diabetes intervention study.

In NIDDM a clustering of established coronary risk factors, e.g. the metabolic syndrome is responsible for excessive incidence of myocardial infarction. The harmful effects of these risk factors are aggravated by poor glucose control. Hyperinsulinaemia is associated with a higher level of risk factors for coronary heart disease. Individuals with subsequent myocardial infarction exhibit higher levels of serum insulin at entry. However, insulin in multivariate analysis was no independent risk factor. Perfect control of blood glucose, triglycerides and blood pressure was associated with a lower incidence of coronary heart disease. By extrapolation an integrated approach to correct the anomalies of the metabolic syndrome seems to be necessary to prevent macroangiopathy and improve life expectancy.

Clinical Trials as Topic↗
PubMed1996

Increased clearance of low density lipoprotein precursors in patients with heterozygous familial defective apolipoprotein B-100: a stable isotope approach.

In familial defective apolipoprotein B-100 (FDB) the presence of a mutant apolipoprotein (apo) B-100 (FDB3500Q/W) in LDL markedly reduces their affinity for the LDL receptor, leading to elevated LDL cholesterol levels. However, the hypercholesterolemia in most FDB patients is relatively mild when compared with, e.g., familial hypercholesterolemia (FH). In order to study mechanisms that may partly alleviate the clinical consequences of FDB, we investigated the in vivo kinetics of apoB-100-containing lipoproteins in five FDB heterozygotes (total cholesterol: 7.84 +/- 1.37 mmol/I; total apoB: 1.68 +/- 0.37 g/l; mean +/- SD) and six normolipidemic controls (4.61 +/- 0.62 mmol/l; 0.98 +/- 0.12 g/l) using a stable isotope approach. During and after a 10-12 h primed, constant infusion of either [13C6]phenylalanine or [2H3]leucine, tracer enrichment was determined in apoB-100 from ultracentrifugally isolated VLDL1 (Sf 60-400), VLDL2 (Sf 20-60), IDL (Sf 12-20), LDL1 (Sf 7-12), and LDL2 (Sf 0-7). The rates of apoB-100 production, catabolism, and transfer were estimated by model-based compartmental analysis. The overall fractional catabolic rate (FCR) of IDL apoB-100 in FDB was substantially increased (2.99 +/- 0.68 pools/day vs. 1.70 +/- 0.23 pools/day in controls, P < 0.01). The fractional rate of apoB-100 transfer from IDL to LDL in FDB was decreased (0.97 +/- 0.13 pools/day vs. 1.24 +/- 0.10 pools/day, P < 0.05). The FCR of LDL apoB-100 in FDB was decreased (0.18 +/- 0.07 pools/day vs. 0.56 +/- 0.05 pools/, P < 0.01). Finally, the input rate of LDL apoB-100 in FDB was markedly decreased (9.45 +/- 2.96 mg/kg day1 vs. 15.54 +/- 1.70 mg/kg day1, P < 0.05). Our data suggest that the relatively small increase of LDL concentrations in FDB is due to an increased clearance of LDL precursor particles via the LDL-receptor and apoE-receptors as well as a decreased conversion of IDL to LDL - two mechanisms that distinguish FDB from FH.

Adult↗
PubMed1995

[Blood coagulation/fibrinolytic disorders in diabetic patients].

In many diabetic patients, disturbances of components of the coagulation/fibrinolysis system have been observed. These disturbances have been studied extensively due to their interrelations with the development of atherosclerotic vascular lesions. A thrombophilia (increased tendency to form thrombi) is regarded as a part of the presently widely discussed Metabolic Syndrome. In diabetic patients, increases of the fibrinogen concentration, of the factor VII activity and of the von Willebrand factor, of the concentration and activity of the plasminogen activator inhibitor as well as a raised platelet reactivity have been measured. Probably, further disturbances exist in the complexly regulated subsystems of hemostasis. Not only the hyperglycemia, but also dyslipidemias and a number of other factors do modify the individual situation. First of all, the therapeutic approach to reduce the atherosclerotic risk in the diabetic patients focuses on the optimization of these factors. In this context, a fat-modified diet, physical activity and eumetabolisation in a broader sense are especially important. In high-risk patients, especially within the framework of the secondary prevention of atherosclerotic lesions, the use of fibrates and of inhibitors of platelet aggregation are to be taken into consideration.

Blood Coagulation Tests↗
PubMed1994

Impact of hormone replacement therapy on postprandial lipoproteins and lipoprotein(a) in normolipidemic postmenopausal women.

In 43 normolipidemic postmenopausal women we studied fasting and postprandial (oral fat load with 50 g fat per square meter; blood sampling for 5 h) lipoprotein components and lipoprotein(a) levels before and with the administration of conjugated equine estrogens opposed by medrogestone (on days 11-21). Data was compared intraindividually; the second testing was performed during the last 5 days of the combined estrogen/progestogen phase of the third cycle. Fasting low-density lipoprotein (LDL) and total cholesterol concentrations decreased significantly; high-density lipoprotein (HDL) cholesterol, including subfractions HDL2 and HDL3, was not changed. Fasting triglyceride concentrations increased. All lipoprotein fractions measured showed a postprandial elevation with the exception of chylomicron cholesterol concentrations. There was a significant effect of hormone replacement therapy on the postprandial course of total cholesterol (decrease; P < 0.001), VLDL cholesterol (increase; P = 0.025), and the triglyceride proportion in the LDL plus HDL fraction (increase; P < 0.001). With hormone replacement therapy the postprandial curve of total triglycerides was increased only 1 h after the fat load while chylomicron triglyceride concentrations were lowered after 5 h. VLDL triglycerides were not influenced. In all patients with lipoprotein(a) levels above 10 mg/dl, this parameter decreased (about 25%). Although increasing fasting triglyceride concentrations, hormone replacement therapy does not bring about an exaggerated postprandial increase in triglycerides. Postprandial chylomicron clearance is evidently promoted. Hormone replacement therapy leads to a small increase in triglycerides in the LDL plus HDL fraction by inhibiting hepatic lipase activity. Moreover, the decrease in lipoprotein(a) levels may contribute to the antiatherosclerotic effect.

Dietary Fats↗
PubMed1994

Recovery of cholesterol and triacylglycerol in very-fast ultracentrifugation of human lipoproteins in a large range of concentrations.

Very-fast ultracentrifugation using a benchtop ultracentrifuge was applied to the analysis of lipoproteins in 0.5 ml of human plasma. VLDL, IDL and LDL were flotated at densities of 1.006, 1.019 and 1.063 kg/l in runs lasting 30, 100 and 100 minutes. Chylomicrons, if present, were flotated in a separate run. HDL were isolated by precipitation of the apolipoprotein B-containing lipoproteins from total plasma using polyethylene glycol. Three series of separations were routinely performed: 1. VLDL run alone (632 samples), 2. VLDL run + LDL run (122 samples), and 3. Chylomicron separation + VLDL run + IDL run (92 samples). The concentrations of cholesterol and triacylglycerol were obtained for plasma, chylomicrons, VLDL, IDL, LDL and HDL. Plasma values ranged from 1.8 to 37.1 mmol/l cholesterol and 0.26 to 50.2 mmol/l triacylglycerol. The plasma triacylglycerol concentrations were corrected for free glycerol by 3% (for triacylglycerols < 2.5 mmol/l) and by 2% (for triacylglycerols > or = 2.5 mmol/l). The recovery rate of lipids after ultracentrifugation was determined by comparing the concentrations in lipoproteins and in plasma. It was near to 100% and decreased for samples with extremely high lipid concentrations.

Cholesterol↗
PubMed1993

Work absenteeism in type 2 diabetes mellitus: results of the prospective Diabetes Intervention Study.

Newly diagnosed mild Type 2 diabetic patients, aged 30-55 years, were included in the prospective, multi-centre Diabetes Intervention Study. They were randomly allotted to either an intervention group receiving intensified health education or to a control group on usual care. This paper reports the incidence, duration of and causes for absence from work due to any disease in the patients who were working during the first 5-year follow-up. Data from 817 patients could be taken into account. 14.5% of the intervention patients and 17.3% of the control patients had never been on the sick list. Those patients who had undergone intensified health education were listed sick less often. Women showed a higher work absenteeism in either group; they had higher blood pressure and higher body mass index at entry. Cardiovascular diseases and musculo-skeletal disorders were major reasons for absence from work. However, when compared to the general population, these Type 2-diabetic patients were approximately four times more often on the sick list. Thus, the health education programme of the Diabetes Intervention Study was shown to be effective with respect to work absenteeism. Teaching patients is recommended as an important part of the therapeutic regimen.

Absenteeism↗
PubMed1992

[Different effects of fibrates on the lipoprotein profile. Comparison of the effectiveness of gemfibrozil and bezafibrate in various types of hyperlipoproteinemia].

AIMS: To compare the efficacy and tolerability of Gemfibrozil and Bezafibrate in patients with hyperlipoproteinemia, types IIa, IIb and IV. METHOD: In an open, randomized parallel study, the tolerability and efficacy of Gemfibrozil (G) and Bezafibrate (B) were investigated over a period of 12 weeks in 178 hyperlipidemic (HLP) patients first submitted to an 8-week "wash-out" (diet only) phase. In HLP type IIa patients, LDL cholesterol was lowered (G: -13%, B: -10%). In HLP type IIb, a decrease in triglyceride (TG) levels (G: -41%, B: -31%), an increase in HDL-cholesterol (G: +19%, B: +5%), and a decrease in the total cholesterol/HDL cholesterol ratio (G: -32%, B: -9%) predominated. Patients with type IV HLP responded to both fibrates with an appreciable reduction in TG levels (G: -45%, B: -42%). The effects of the preparations differed significantly with respect to the elevation of HDL cholesterol and a decrease in the total cholesterol/HDL cholesterol ratio in HLP type IIb patients. The respective lipid baseline concentration appeared to be of importance for the sense and extent of the changes induced.

Adult↗
PubMed1991

Diabetes Intervention Study. Multi-intervention trial in newly diagnosed NIDDM.

OBJECTIVE: In a randomized 5-yr multi-intervention trial, we tested the efficacy of intensified health education (IHE) in improving metabolic control and reducing the level of coronary risk factors and incidence of ischemic heart disease (IHD). RESEARCH DESIGN AND METHODS: Within the intervention group, the benefit of clofibric acid was evaluated in a double-blind study. One thousand one hundred thirty-nine newly diagnosed middle-aged (30- to 55-yr-old) patients with non-insulin-dependent diabetes mellitus (NIDDM) entered the study. They were classified as diet controlled after a 6-wk screening phase with conventional dietary treatment. During the follow-up, the control group (n = 378) was cared for at different diabetes outpatient clinics with a standardized surveillance. The intervention group (n = 761) had a structured IHE that included dietary advice, antismoking and antialcohol education, and ways to enhance physical activity. RESULTS: Randomly, 379 of the IHE patients received 1.6 g clofibric acid/day, and the others received placebo. IHE resulted in improved glucose control (adjusted fasting blood glucose) levels after 5 yr (control subjects 9.27 mM, IHE group 8.71 mM, and IHE plus clofibric acid group 8.60 mM, P less than 0.01). The better glycemic control was achieved with fewer antidiabetic drugs. After 5 yr, antidiabetic drugs were prescribed to 47% of the control subjects, 28% of the IHE group, and 34% of the IHE plus clofibric acid group (cutoff limit for drug application was postprandial blood glucose of greater than or equal to 13.87 mM). The ratio of polyunsaturated to saturated fatty acids (0.26 vs. 0.40, P less than 0.01) and physical activity (174 vs. 327 scores, P less than 0.01) were increased, and blood pressure, tobacco, and alcohol consumption were significantly reduced by IHE. However, IHE had no effect on calorie intake, percentage of fat in the diet (45%), and body weight. The most important finding was the significant increase of blood cholesterol in all three groups (+0.47, +0.36, and +0.34 mM, respectively). Clofibric acid only prevented the increase of triglyceride levels (+0.56, +0.24, and +0.05 mM, respectively). The incidence rate per 1000 for myocardial infarction was 30.3 for control subjects, 53.6 for the IHE group, and 55.6 for the IHE plus clofibric acid group. The corresponding rates for IHD incidence were 90.9, 97.8, and 98.8, respectively. Men suffered more frequently from myocardial infarction, whereas women developed ECG criteria for IHD more frequently. Among the 35 cases of death, besides cardiovascular diseases, liver cirrhosis and neoplasia were the predominant causes. The death rate per 1000 in control subjects was 46.2, 30.6 in the IHE group, and 27 among patients with IHE plus clofibric acid. CONCLUSIONS: IHE was of substantial benefit for the control of glycemia, significantly diminished the need for antidiabetic drugs, and reduced a cluster of risk factors but had no effect on the control of blood lipids. This could be one major reason for the failure of IHE, effective lowering of blood pressure, and clofibric acid to prevent cardiovascular complications. Clofibric acid was only effective in reducing triglycerides.

Adult↗