Biomedical subjects

M Pfohl

Publications and source records attributed to M Pfohl.

At least 37 records · Page 2Linked to original sources

PubMed2000

Spot glucose measurement in epidermal interstitial fluid--an alternative to capillary blood glucose estimation?

Capillary blood glucose estimation is an essential but inconvenient prerequisite in the current management of diabetes mellitus. Spot glucose measurement in epidermal interstitial fluid appears to be a promising alternative to capillary blood glucose estimation, and due to its near non-invasive properties it might be a tool for improving the lives of people with diabetes in the near future. The present status of epidermal interstitial fluid glucose determination, the first clinical results, and some open questions regarding this new technology are reviewed here.

Blood Glucose↗

PubMed2000

Acute improvement of peripheral endothelial function in postmenopausal women with coronary artery disease after single oral intake of 17beta-estradiol valerate.

Chronic estrogen supplementation is known to improve endothelial function in postmenopausal women. We studied the acute effect of a single dose of orally administered 17beta-estradiol valerate (E2) on the peripheral endothelial dependent and independent vasodilatation in postmenopausal women with coronary artery disease (CAD). 20 postmenopausal women (age: 64.9 (7.2) y, height: 1.61 (0.04) m. weight: 68.6 (10.6) kg) with angiographically confirmed CAD were randomly examined for flow-associated vasodilatation (= FAD%, a marker for endothelial dependent vasodilatation) and for glyceryltrinitrate (400 microg, p.o.) induced vasodilatation (= GTN%, representing endothelial independent vasodilatation) two hours after placebo controlled, randomized crossover intake of 4 mg E2 p.o. After placebo FAD% was impaired (3.5 (1.7)%) compared to historic controls. After the oral intake of 4 mg E2, FAD% improved to 5.0 (2.8)% (P=0.02). GTN% was not significantly influenced by the oral E2 (E2: 12.6 (5.7) v placebo: 11.2 (6.9)%, P=0.14). Endothelial dysfunction can partially be restored by a single oral dose of 4 mg E2. This indicates an acute vasoprotective effect of E2 beyond its genomic and lipid modifying actions. It remains to be investigated if estrogen might play a beneficial role in the acute treatment of symptomatic coronary artery disease such as angina pectoris or preinfarct syndrome.

Aged↗

PubMed1999

[The ultrasonic measurement of the endothelial function of the brachial artery in suspected coronary heart disease].

BACKGROUND AND OBJECTIVE: A positive correlation between the presence of coronary artery disease (CAD) and peripheral endothelial dysfunction (ED) of the brachial artery has been shown in several studies. Aim of the present study was to evaluate whether the non-invasive determination of ED could also be used as a screening test in patients suspected of having CAD. PATIENTS AND METHODS: 122 patients were included. 112 had an exercise-ECG before hospital admission. Preceding coronary angiography, FMD% was measured by high-resolution ultrasound (13 Mhz). Longitudinal scans of the brachial artery were done at rest, during reactive hyperemia and after the sublingual administration of nitroglycerin. RESULTS: In 101 of the 122 patients the presence of CAD was diagnosed by angiography, whereas 21 patients had normal coronary arteries. The extent of the vasodilation (FMD%) was found to be largely independent of the resting vessel diameters (FMD%/vessel diameter at rest: r = -0.32767 p = 0.0002). FMD% was significantly higher in patient without CAD than in the CAD group (7.01 +/- 3.5% vs. 3.73 +/- 4.11%, p < 0.001). Comparison of sensitivity and specificity to predict the presence of CAD between FMD% [sensitivity 71.3%, specificity 81%] and exercise-ECG [sensitivity 82.4%, specificity 57.1%] gave similar results. No correlation was found between the degree of the impairment of FMD% and the severely of CAD. CONCLUSION: The determination of peripheral ED was found to be a sensitive and specific measure for predicting the presence of CAD in our cohort. Since this approach is non-invasive, non-radioactive and cost-effective it warrants further evaluation of its role as an additional screening test in patients clinically suspected of having CAD.

Aged↗

PubMed1999

Noninvasive determination of endothelium-mediated vasodilation as a screening test for coronary artery disease: pilot study to assess the predictive value in comparison with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging.

BACKGROUND: Peripheral endothelial dysfunction (ED) quantified by the determination of flow-mediated dilation (FMD%) of the brachial artery with the use of high-resolution ultrasound is an early marker of atherosclerosis. Although a positive correlation with coronary artery disease (CAD) has been reported, the unanswered clinical question is the validity of FMD% as a screening test in patients with clinical suspicion of CAD. Thus the aim of this study was to determine the predictive value of FMD% compared with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging. METHODS AND RESULTS: In this pilot study, we measured ED in 122 patients scheduled for coronary angiography by using high-resolution ultrasound (13 MHz). We defined ED as FMD% </=4.5%. The presence of CAD was defined as angiographically detectable atherosclerotic vessel alterations of any degree. Exercise electrocardiography and myocardial perfusion imaging had been performed on an outpatient basis. Statistical analysis was conducted by analysis of variance and Mantel-Haenszel chi-square test. Patients with CAD (n = 101) had a significantly lower FMD% than patients without CAD (n = 21; 3.7% +/- 4.1% vs 7.01% +/- 3.5%, P <.001). A sensitivity of 71%, a specificity of 81% with a positive predictive value of 0.95 (72 of 76), and a negative predictive value of 0.41 (17 of 46) was calculated. In comparison to angina pectoris (sensitivity 95%, specificity 47.6%), exercise electrocardiography (sensitivity 82.4%, specificity 57.1%) and myocardial perfusion imaging (sensitivity in our study group 100%) had the best specificity, and a high sensitivity for FMD% was found. CONCLUSIONS: The determination of ED was found to be a sensitive and specific screening test to predict the presence of CAD. Because this is a noninvasive, nonradioactive, and cost-effective approach, it warrants further evaluation to determine its value in daily clinical practice as an additional screening test in the diagnosis of CAD.

Angina Pectoris↗

PubMed1999

Upregulation of cholesterol synthesis after acute myocardial infarction--is cholesterol a positive acute phase reactant?

Acute myocardial infarction is associated with profound alterations in the plasma lipoprotein profile. The mechanism of these alterations is not clear, and both cholesterol biosynthesis up- and downregulation could possibly be a consequence of acute myocardial infarction. We determined plasma lipids, lipoproteins, apolipoproteins, and lathosterol-which is regarded as an estimate of whole body cholesterol biosynthesis in humans-concentrations in 34 patients (age 68+/-10 years, 24 male, 10 female) admitted to our hospital with acute MI and with onset of symptoms within the last 12 h. Samples were taken immediately after admission to the hospital, and 1, 2, and 10 days after admission. On the first day after admission there was a decrease in total cholesterol (C) by 14.1%, (P = 0.01), in LDL-C by 14.4% (P = 0.03), in HDL-C by 9.3% (NS), and in triglycerides by 19.5% (NS). Apolipoprotein B100 was reduced by 18.3% (P = 0.008), and apolipoprotein AI by 12.3% (NS). The lathosterol/cholesterol ratio was increased by 23.1% after 1 day, and by 28.7% after 2 days (P = 0.05). After 10 days, all variables except the apolipoproteins had essentially returned to baseline values. In conclusion, the changes in the plasma lipid profile after acute myocardial infarction are associated with a profound increase of whole body cholesterol biosynthesis as judged by the lathosterol/cholesterol ratio. These changes may possibly enhance the delivery of cholesterol to cells involved in tissue repair mechanisms after acute myocardial infarction.

Acute-Phase Reaction↗

PubMed1999

Angiotensin I-converting enzyme gene polymorphism, coronary artery disease and myocardial infarction. An angiographically controlled study.

OBJECTIVES: We investigated the association between insertion/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene, the presence and extent of coronary artery disease, and myocardial infarction. BACKGROUND: The D allele of the ACE gene has been associated with coronary artery disease and myocardial infarction, but this association has been challenged in epidemiological studies. METHODS: Nine hundred and sixty-nine men and 341 women undergoing coronary angiography were studied. The ACE genotypes were assessed by polymerase chain reaction from genomic deoxyribonucleic acid, homozygosity for the D allele was controlled using an insertion-specific primer. Coronary artery disease was defined by angiographic criteria, the extent of coronary artery disease by the number of coronary arteries with >/=50% lumen narrowing. RESULTS: The ACE genotypes did not differ in terms of age, sex, body mass index, blood pressure, plasma lipids or lipoproteins. We found no association between the ACE genotypes and coronary artery disease (odds ratio, 95% confidence interval in DD genotypes for coronary artery disease in men 0.97, 0.70-1.36; in women 1.56, 0.95-2.57), extent of coronary artery disease (men 1.17, 0.85-1.61; women 1.24, 0.65-2.34), or myocardial infarction among the patients with coronary artery disease (men 1.07, 0.78-1.48; women 0.95, 0.50-1.76). The ACE genotype was not associated with coronary artery disease or myocardial infarction in hypertensives (n=771; odds ratio for coronary artery disease 0.93, 0.65-1.34; odds ratio for myocardial infarction 0.94, 0.66-1.33), or in patients </=60 years (n=649; odds ratio for coronary artery disease 1.05, 0.72-1.52; odds ratio for myocardial infarction 0.96, 0.63-1.47). CONCLUSION: ACE insertion/deletion gene polymorphism is associated neither with the prevalence nor the extent of coronary artery disease, nor with myocardial infarction in this relatively large sample of Caucasian men and women. Genotyping for ACE insertion/deletion polymorphism is not useful in assessing the individual risk of coronary artery disease or myocardial infarction.

Age Factors↗

PubMed1999

Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes.

Paraoxonase is an HDL-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. Its biallelic gene polymorphism at codon 192 (glutamine/arginine) has been associated with coronary artery disease (CAD). To further evaluate the role of this paraoxonase gene polymorphism for CAD in type 2 diabetes, we determined the paraoxonase genotype in 288 type 2 diabetic patients (170 with and 118 without angiographically documented CAD). The paraoxonase 192 Gln/Arg genotype was assessed using polymerase chain reaction followed by AlwI digestion. The frequency of the Gln allele was 0.656 in the CAD patients and 0.746 in the controls (chi2 = 5.36, P = 0.02). Compared with the Gln/Gln genotypes, the age-adjusted odds ratio for CAD was 1.78 (95% CI 1.08-2.96, P = 0.02) in subjects carrying at least one Arg allele. In the multivariate analysis, this association was even stronger after correction for the possible confounders age, sex, smoking history, and hypertension. Among current and former smokers, the odds ratio (OR) for having CAD among patients with at least one Arg allele was 3.58 (1.45-9.53, P < 0.01). The paraoxonase Arg allele was not associated with the history of myocardial infarction (OR 1.20 [0.73-1.99, NS]), but was with the extent of CAD (OR for three-vessel disease 1.92 [1.15-3.27, P = 0.01]). Our data indicate that the 192 Arg allele of the human paraoxonase gene is a risk factor for CAD but not myocardial infarction in type 2 diabetic patients, a risk factor further modified by cigarette smoking. This risk could possibly be explained by a reduced ability of the paraoxonase Arg isoform to protect lipoproteins against peroxidation.

Arginine↗

PubMed1998

Downregulation of beta-adrenergic receptors by low density lipoproteins and its prevention by beta-adrenergic receptor antagonists.

OBJECTIVE: Vasodilation by beta-adrenergic receptors of smooth muscle cells appears to be impaired early after the onset of hypercholesteremia. The aim of this study was to analyze the modulation of beta-adrenergic receptor density and adenylyl cyclase activity in the presence of moderately elevated concentrations of LDL. The effects of beta 1- and beta 2-adrenergic receptor antagonists on LDL-induced receptor changes were studied. METHODS AND RESULTS: Media explants of porcine coronary arteries were incubated with moderately elevated LDL concentrations (0.7-3.9 mmol/l). The density of beta-adrenergic receptors was determined in plasma membranes using the radioligand [125I]iodocyanopinodolol. LDL (3.9 mmol/l) resulted in a decrease of beta-adrenergic receptor density (control 137 +/- 5 vs. 89 +/- 7 fmol/mg protein, P < 0.01). After removal of LDL and cultivation for an additional 3 days beta-adrenergic receptors increased to 129 +/- 5 fmol/mg. In the presence of the beta 1- or beta 2-adrenergic receptor antagonists the LDL-mediated decrease was inhibited. Addition of metoprolol after 3 days of LDL incubation caused a restoration of receptor density. The basal, isoproterenol- and forskolin-stimulated adenylyl cyclase activities were increased after LDL incubation by 180, 110 or 80%, respectively. CONCLUSION: Moderately elevated LDL levels decreased beta-adrenergic receptor density while adenylyl cyclase activity was simultaneously increased. beta 1- or beta 2-adrenergic receptor antagonists prevented this receptor decrease and might preserve the beta-adrenergic receptor density in the presence of moderately elevated LDL levels.

Adenylyl Cyclases↗

PubMed1998

Association between angiotensin I-converting enzyme genotypes, extracranial artery stenosis, and stroke.

The insertion(I)/deletion(D) polymorphism of the angiotensin-converting-enzyme (ACE) gene has been associated with an increased risk of myocardial infarction, lacunar stroke, and with an increased intimal-medial thickness in several populations. The aim of this study was to evaluate whether the ACE I/D genotype is associated with stenosis of extracranial arteries and stroke in middle-aged and aged men and women. We studied 388 patients (247 male, 141 female) using Doppler and Duplex ultrasound of the extracranial arteries. Patients' history was obtained by standard questionnaire and by the hospital case records. Genomic DNA was analyzed by polymerase chain reaction (PCR) to identify the I/D polymorphism, with a second insertion specific PCR in samples classified as homozygous DD genotypes to prevent mistyping. The ACE genotype groups (DD 132, ID 164, II 92) were well matched for the basic characteristics. The DD genotype was more common in patients with extracranial artery stenosis > or = 50%, compared with patients without stenosis (59/147 versus 73/241, odds ratio 1.54, 95%-CI 1.01-2.37), but was not associated with a history of stroke (30/91 versus 102/297, odds ratio 0.94, 95%-CI 0.57-1.54). The association of the DD genotype with extracranial artery stenosis was also present in hypertensive subjects (n = 206, odds ratio 1.76, 95%-CI 0.99-3.17). In the whole group multiple logistic regression analysis revealed that the association of the DD genotype with extracranial artery stenosis was independent of age, gender, hypertension, hyperlipidemia, and diabetes. In conclusion, the ACE DD genotype is a weak risk factor for hemodynamically relevant stenosis of extracranial arteries, but not for stroke.

Adult↗

PubMed1998

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene is associated with coronary artery plaque calcification as assessed by intravascular ultrasound.

OBJECTIVES: We evaluated the influence of the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene on coronary plaque morphology and calcification in patients with angiographically documented coronary artery disease (CAD). BACKGROUND: The ACE I/D polymorphism has been associated with an increased risk of myocardial infarction in patients with the DD genotype but not with the presence of native CAD. METHODS: We studied 146 patients undergoing percutaneous transluminal coronary angioplasty for stable angina pectoris by means of preinterventional intravascular ultrasound (IVUS). Qualitative and quantitative criteria were used to classify the target lesions as poorly or highly echoreflective or as calcified. Genomic deoxyribonucleic acid was analyzed by polymerase chain reaction (PCR) to identify the I/D polymorphism, with a second insertion-specific PCR in DD genotypes to prevent mistyping. RESULTS: The ACE genotype groups (DD 46, ID 68, II 32) were well matched for the basic characteristics. Patients with the DD genotype had significantly more calcified lesions (DD 80%, ID 57%, II 66%; unadjusted odds ratio [OR] 2.88, 95% confidence interval [CI] 1.30 to 6.92, p = 0.008) and more calcifications >180 degrees of the vessel circumference (DD 22%, ID 10%, II 6%; OR 2.80, 95% CI 1.05 to 7.63, p = 0.03). The prevalence of myocardial infarction was not significantly associated with coronary calcification (OR 1.44, 95% CI 0.72 to 2.88, p = 0.31). CONCLUSIONS: Patients with CAD and the ACE DD genotype have a significantly higher incidence and greater extent of coronary lesion calcification, as determined by IVUS. This finding indicates that the ACE I/D gene polymorphism is related to the development or progression of atherosclerotic plaque calcification.

Aged↗

PubMed1998

Use of cholesterol precursors to assess changes in cholesterol synthesis under non-steady-state conditions.

BACKGROUND: Quantification of plasma levels of an early and late intermediate on the cholesterol pathway, mevalonic acid (MVA) and lathosterol respectively, provides a useful method of estimating cholesterol synthesis in humans. The aim of this study was to assess further their roles as indices of cholesterol synthesis under non-steady-state conditions. METHODS: The short-term effects of pharmacological inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase on both variables were determined in four normolipidaemic subjects during and after treatment with simvastatin 20 mg daily. Plasma MVA was measured using gas chromatography-mass spectrometry, and lathosterol using gas chromatography. RESULTS: A single dose of 20 mg of simvastatin decreased plasma MVA after 2 h and decreased the lathosterol-cholesterol (L/C) ratio after 4 h. Treatment with simvastatin 20 mg daily for 9 days decreased both variables by approximately 50%, the nadir of plasma MVA occurring on the second day and of the L/C ratio on the fifth day, and resulted in a 39% reduction in low-density lipoprotein (LDL)-cholesterol. After discontinuing simvastatin, there were rebounds in plasma MVA and the L/C ratio to above basal levels but not in LDL cholesterol or apolipoprotein B (apoB), the latter continuing to decrease for a further 2 days. CONCLUSION: These results suggest that simvastatin rapidly down-regulates cholesterol synthesis, which is then up-regulated when the drug is withdrawn.

Acyl Coenzyme A↗

PubMed1998

[Early detection of atherosclerosis with high resolution ultrasound exemplified by type II diabetic patients].

AIM: Endothelial Dysfunction (ED) is an early functional marker and Intima-Media-Thickness (IMT) an early morphological parameter of atherogenesis. Is there a simple, non-invasive routine method for the identification of atherosclerosis including the detection of the early functional endothelial impairment seen for example in Type 2 diabetic patients? METHODS: Using high resolution ultrasound we studied peripheral endothelial function expressed as flow-associated dilation (FAD %) and endothelial independent vasodilation after administration of 400 micrograms glycerol trinitrate (postnitro %) of the brachial artery as well as IMT of the common carotid artery in 25 Type 2 diabetic patients and their matched controls. RESULTS: (mean +/- SD): The diabetic patients showed a remarkable ED (FAD%: 3.8 +/- 3.3 vs. 6.9 +/- 4.4%, p = 0.01) and an already increased IMT (0.72 +/- 0.14 vs. 0.62 +/- 0.10 mm, p < 0.01). The similar postnitro % in diabetic patients and controls suggests normal dilating capacity of the studied vessels in the diabetic patients (postnitro %: 14.3 +/- 9.4 vs. 14.9 +/- 8.5%, p = ns). CONCLUSION: With a combination of these three sonomorphological parameters it is possible to document the stage of atherosclerosis including endothelial dysfunction in Type 2 diabetic patients.

Adult↗

PubMed1998

Lack of association between the insertion/deletion polymorphism of the angiotensin-converting-enzyme gene and diabetic nephropathy in IDDM patients.

The insertion/deletion (I/D) polymorphism of the angiotensin-converting-enzyme (ACE) gene has been reported to be associated with diabetic nephropathy in IDDM. We studied the relationship between this polymorphism and diabetic nephropathy in 210 IDDM patients. Their DNA was analyzed by polymerase chain reaction to type for the presence (I) or absence (D) of the 287 bp fragment in intron 16 of the ACE gene. The relative frequency of the different genotypes was 33.8% (DD), 43.8% (ID), and 22.4% (II). There were no significant differences between the genotypes in age, body-mass-index, blood pressure, plasma total cholesterol and triglycerides. The prevalence of microalbuminuria or nephropathy was 23.9% in the DD, 16.3% in the ID, and 17% in the II genotypes. The higher percentage of microalbuminuria or nephropathy in the DD genotypes was due to an increasing frequency of DD genotypes in the IDDM patients with long diabetes duration. After matching for diabetic retinopathy, gender, and diabetes duration, there was no association between the ACEI/D polymorphism and diabetic nephropathy. In conclusion, these results suggest that the ACE DD genotype cannot be regarded as a risk factor for diabetic nephropathy, but may even be associated with diabetes duration and thus longevity in IDDM patients.

Adult↗

PubMed1998

Comparison of peripheral endothelial dysfunction and intimal media thickness in patients with suspected coronary artery disease.

OBJECTIVE: Flow associated dilatation (FAD%) and intimal media thickness are established markers of early atherosclerosis. This study aimed to compare the ability of the non-invasive measurements FAD% and intimal media thickness to predict coronary artery disease. METHODS: FAD% and intimal media thickness were determined using high resolution ultrasound in 122 patients with clinically suspected coronary artery disease before coronary angiography. Results are given as mean (SD). RESULTS: Patients with coronary artery disease had reduced FAD% compared with those with angiographically normal coronary vessels (3.7 (4.1) v 7.0 (3.5)%, p < 0.001), whereas intimal media thickness tended to be increased in patients with coronary artery disease (0.58 (0.35) v 0.47 (0.11)mm, p = 0.054). There was a negative correlation between FAD% and intimal media thickness (R = -0.317, p = 0.0004). Receiver operating characteristic analysis showed that FAD% < or = 4.5% predicted coronary artery disease with a sensitivity of 0.71 (95% confidence interval 0.61 to 0.80) and a specificity of 0.81 (0.58 to 0.95). In contrast, intimal media thickness showed a positive correlation with the extent of coronary artery disease (number of vessels with a lesion > or = 50%) (R = 0.324, p = 0.0003), without a clear cut off point. CONCLUSIONS: In patients with clinically suspected coronary artery disease, FAD% discriminates between the presence or absence of coronary artery disease, whereas intimal media thickness is associated more with the extent of coronary artery disease.

Adult↗

PubMed1998

Preserved endothelial function in IDDM patients, but not in NIDDM patients, compared with healthy subjects.

OBJECTIVE: To examine endothelial function (EF) noninvasively in IDDM and NIDDM patients with long diabetes duration. RESEARCH DESIGN AND METHODS: We studied EF in 17 IDDM patients without diabetic complications and in 25 NIDDM patients with comparable glycemic control and with diabetic complications and compared both with nondiabetic control subjects matched for age, sex, and lumen diameter. Using high-resolution ultrasound, we measured the endothelial-dependent (FAD%) and independent vasodilation (GTN%); the blood flow at rest, postocclusive, and after application of 400 micrograms glyceroltrinitrate of the branchial artery; and the intima media thickness (IMT) of the common carotid artery. RESULTS: In the IDDM patients, neither FAD% (8.2 +/- 4.6 vs. 7.6 +/- 4.2%), GTN% (16.3 +/- 4.9 vs. 18.4 +/- 6.4%), nor postocclusive blood flow (40.6 +/- 19.1 vs. 39.3 +/- 23.6 cm/s) differed from the control subjects. IMT (0.59 +/- 0.10 vs. 0.55 +/- 0.14 mm) was slightly, but not significantly, elevated. In contrast, the NIDDM patients showed an impaired FAD% (3.8 +/- 3.3 vs. 6.9 +/- 4.4%, P < 0.01), no difference in GTN%, and a decreased postocclusive blood flow (18.5 +/- 13.8 vs. 32.7 +/- 20.0 cm/s, P < 0.01). IMT was significantly increased in NIDDM patients (0.77 +/- 0.14 vs. 0.62 +/- 0.10 mm, P < 0.001). CONCLUSIONS: In contrast to NIDDM patients with cardiovascular complications, IDDM patients with long diabetes duration and good long-term metabolic control do not have impaired EF compared with control subjects.

Adult↗

PubMed1998

Evaluation of the insertion/deletion ACE gene polymorphism as a risk factor for carotid artery intima-media thickening and hypertension in young type 1 diabetic patients.

OBJECTIVE: To study the distribution of the insertion/deletion polymorphism of the ACE gene in young type 1 diabetic patients and to evaluate possible associations between the ACE genotype, arterial hypertension, and intima-media thickness (IMT) of the common carotid artery. RESEARCH DESIGN AND METHODS: Study participants were 148 type 1 diabetic patients (56 men and 92 women), aged 14-44 years, with a diabetes duration of > or = 2 years. HbA1c, albuminuria, and lipid status were assessed by standard laboratory techniques; the ACE genotypes were assessed by polymerase chain reaction. The patients were categorized according to the presence or absence of hypertension, nephropathy, and retinopathy. The IMT, which can be used to estimate early stages of atherosclerosis, was measured by high-resolution ultrasonography. RESULTS: The ACE genotypes were distributed as follows: 21% II, 37% ID, 42% DD. The IMT values did not differ among patients with various ACE genotypes (0.63 +/- 0.15 mm), but the prevalence of hypertension was significantly higher in patients with DD (odds ratio, 4.26 versus II + ID; 95% CI, 1.64-11.06). Multiple linear regression analysis showed that only age, hypertension, and sex were determinants for the IMT. CONCLUSIONS: Our results suggest a relationship between the prevalence of hypertension and the deletion polymorphism of the ACE gene in young type 1 diabetic patients, but we could not find an association between carotid artery IMT and ACE genotype in this population.

Adolescent↗

PubMed1997

Upregulation of cholesterol synthesis after acute reduction of low density lipoprotein by apheresis in normocholesterolaemic subjects: evidence for a threshold effect.

The influence of low density lipoproteins (LDL) in the plasma on the regulation of cholesterol biosynthesis is not clear. We studied the changes in plasma mevalonic acid (MVA) concentration and the lathosterol/cholesterol (L/C) ratio, which are well established indices of whole body cholesterol synthesis, in four normocholesterolaemic subjects after each had undergone LDL apheresis on two occasions. LDL apheresis of 75% of the calculated plasma volume reduced LDL-cholesterol by 44% to 1.5 +/- 0.2 mmol/l without changing plasma MVA levels or L/C ratios. Apheresis of 125% of the calculated plasma volume decreased plasma LDL-cholesterol by 69% to 0.9 +/- 0.2 mmol/l, with significant increases in plasma MVA and L/C ratio on the day after the procedure. These results imply that LDL-cholesterol is an integral part of the sterol regulatory pool and suggest that plasma levels cannot be lowered below 1-1.4 mmol/l in normal subjects without upregulating cholesterol biosynthesis.

Adult↗

PubMed1996

Screening and identification of familial defective apolipoprotein B-100 in clinical samples by capillary gel electrophoresis.

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder. It is characterized by a decreased affinity of low density lipoprotein (LDL) for the LDL receptor, as a consequence of a substitution of adenine by guanine in exon 26 of the apolipoprotein B-100 gene, coding for the putative LDL receptor-binding domain of the mature protein. This disorder is associated with a strikingly high incidence of arteriosclerosis and tends to cause disease and premature death. In this communication we describe a rapid capillary gel electrophoretic method in combination with molecular biology techniques to facilitate the diagnosis of FDB. Mutation screening for FDB is performed by an allele-specific amplification followed by capillary gel electrophoresis (CGE). For the combined polymerase chain reaction (PCR)-CGE method, a total analysis time of only 3 h is needed, a period that is normally necessary for the run and for staining of the gel only, not including the time for PCR, gel casting, etc. In our pilot study 4 of 43 hypercholesterolemic patients were found to have the predominant apoB 3500 codon mutation. The verification is demonstrated by DNA-sequencing. This pilot study will be followed by a large cohort analysis of the south-west German population to determine the frequency of FDB in this area. The PCR-CGE method on the Dionex capillary electrophoresis system (CES I) allows rapid, fully automated detection of the mutation resulting in the unequivocal diagnosis of FDB.

Adult↗