[2010 Love Parade in Duisburg: clinical experiences in planning and treatment]. / Loveparade 2010 Duisburg - klinische Erfahrungen in Vorbereitung und Versorgung.

BACKGROUND: Tragic incidents at the 2010 Love Parade attracted significant public attention. As the frequency of similar events increases, more hospitals and practitioners will face the necessities of planning and response to unforeseeable occurrences. Obligatory guidelines for physicians do not exist, so that essential aspects are repeatedly discussed for each new event. This paper summarizes the experience of hospitals and emergency departments and draws conclusions, allowing recommendations for reasonable proposals for hospitals and practitioners. METHODS AND MATERIAL: A structured analysis of data concerning planning, patient flow and injury statistics led to a profile determining personnel, rooms and material which have to be provided by the hospitals. In a consensus conference afterwards and personal interviews with clinical coordinators the preparation of hospitals was evaluated to separate reasonable from needless efforts. RESULTS: We describe various measures concerning staff, logistics and rooms from the viewpoint of actual application. Reasonable measures for preparation and management of mass panic are analysed and described in detail. Problems are explained and solutions discussed. The result is a qualitative catalogue, which supports the organization of future events. CONCLUSION: Knowledge and reflection on the experience of the 2010 Love Parade optimizes local emergency guidelines and planning for similar events. A coordinated cooperation of all involved is essential.

Different persistence on initial basal supported oral therapy in Type 2 diabetics is associated with unequal distributions of insulin treatment regimens under real-life conditions in Germany.

OBJECTIVES: Results from a representative German database and from two German health services research studies revealed an unequal distribution between basal supported oral therapy (BOT) and basal-bolus therapy (ICT) regimens in Type 2 diabetics treated with either insulin glargine (GLA) or human insulin (Neutral Protamine Hagedorn; NPH). This study assesses whether this unequal distribution could be caused by a different persistence on the initial BOT regimen. METHODS: A Markov model was developed simulating the transition from BOT to ICT during a treatment course of 10 years. Data on persistence with BOT were obtained from the IMS® Disease Analyzer database. The model cohort consisted of German statutorily insured Type 2 diabetics starting a BOT either with insulin glargine or NPH insulin at a ratio of 1 : 1. RESULTS: The number of Type 2 diabetics who switched from BOT to ICT differed between the two groups: After 2 years, 53% of glargine-treated patients and 31% of NPH-treated patients continued the BOT. After 6.5 years, all NPH-treated patients had switched to ICT. However, complete transition to ICT of glargine-treated patients occurred 1.75 years later. In the first quarter of Year 3, the model simulation resulted in BOT : ICT ratios comparable to those found in the real-world settings for GLA- and NPH-treated patients. CONCLUSIONS: The simulation indicates that the persistence on the initial basal supported oral therapy is associated with the resulting BOT : ICT ratio. Therefore, the unequal distribution between BOT and ICT of Type 2 diabetics treated with either insulin glargine or NPH insulin might be caused by different persistence on the initial BOT regimen.

Impaired flow-mediated vasodilation in type 2 diabetes: lack of relation to microvascular dysfunction.

A reduced availability of nitric oxide (NO) is an important feature of endothelial dysfunction occurring early in the course of type 2 diabetes. The measurement of flow-mediated dilation (FMD) of the brachial artery after forearm ischemia is supposed to be a non-invasive method to assess endothelial production and release of NO. The impairment of reactive hyperemia due to microvascular dysfunction in diabetes might cause an insufficient increase in shear stress stimulating the endothelial NO release, thus leading to an underestimation of FMD. Therefore, the aim of the present study was to investigate the relationship between microcirculatory disturbances and the impairment of FMD in type 2 diabetic patients. 63 type 2 diabetic patients and 44 non-diabetic control subjects were investigated. Capillary blood cell velocity (CBV) was assessed at the dorsal middle phalangeal area of the left ring finger. Lumen diameter of the brachial artery was measured by high-resolution ultrasound. Patients were investigated at rest and after 5-min suprasystolic arterial compression. Percentage change of CBV during reactive hyperemia (CBV%) and flow-mediated dilation (FMD%) of the brachial artery relative to the baseline measurement were calculated. CBV% (63.4+/-10.7% vs. 124.0+/-18.5%; p<0.01) and FMD% (3.8+/-0.8% vs. 6.9+/-0.9%; p<0.01) were reduced in the diabetic patients compared to their control subjects. FMD% was not related to CBV% (r=0.14; p=0.139). The lack of an association between the reduction of endothelium-dependent vasodilation of the brachial artery and the impairment of postocclusive microvascular hyperemia observed in the present study contradicts the assumption that a reduced FMD is only the consequence of an impaired reactive hyperemia due to microvascular dysfunction. It also lends support to the suggestion that endothelial dysfunction in conduit vessels and impaired cutaneous microvascular responses to reactive hyperemia might at least partly develop independently due to several differences in their pathogenesis.

Influence of the duration of type 2 diabetes on early functional and morphological markers of atherosclerosis compared to the impact of coexisting classic cardiovascular risk factors.

AIM: The increased incidence of atherosclerotic macrovascular disease in type 2 diabetic patients is associated both with diabetes specific factors and coexisting classic cardiovascular risk factors as components of the metabolic syndrome. The aim of this study was to investigate the association between the duration of diabetes and early functional and morphological markers of atherosclerosis compared to the impact of coexisting cardiovascular risk factors such as hypertension, dyslipoproteinemia and cigarette smoking. METHODS: 63 type 2 diabetic patients and 25 non-diabetic control subjects were investigated. Lumen diameter of the brachial artery was measured by high-resolution ultrasound at rest and after 5-min suprasystolic arterial compression. Endothelium-independent dilatation of the brachial artery was measured 4 min after sublingual administration of 400 mug of glycerol trinitrate (GTN). Percentage change of arterial lumen diameter during reactive hyperemia (FMD%) and after GTN administration (GTN%) relative to the baseline measurements were calculated. The intima-media thickness (IMT) of the common carotid artery was measured bilaterally and averages were calculated. RESULTS: FMD% (3.8+/-0.8% vs. 6.9+/-0.9%; p<0.01) and GTN% (5.6+/-0.7% vs. 14.9+/-1.7%; p<0.01) were reduced in the diabetic patients compared to their control subjects. IMT was increased in diabetic patients compared to their controls (0.82+/-0.02 mm vs. 0.62+/-0.02 mm; p<0.01). The age-adjusted diabetes duration was inversely related to FMD% (r=-0.27; p=0.016). On multiple regression analysis including packyears, hypertension, hypercholesterolemia, and hypertriglyceridemia, only diabetes duration remained a significant independent determinant of FMD. GTN% and IMT were not associated with diabetes duration, packyears, hypertension, hypercholesterolemia, and hypertriglyceridemia when all variables were taken into account. CONCLUSION: The present data lend support to the suggestion that diabetic specific factors compared to coexisting cardiovascular risk factors such as hypertension, hyperlipoproteinemia, and smoking are of major importance for the pathogenesis of endothelial dysfunction in type 2 diabetes, because only the diabetes duration was shown to be related to endothelium-dependent vasodilation when all variables were taken into account.

Dry shear aligning: a simple and versatile method to smooth and align the surfaces of carbon nanotube thin films.

We show that the application of lateral shear force on a randomly oriented thin film of carbon nanotubes, in the dry state, causes significant reordering of the nanotubes at the film surface. This new technique of dry shear aligning is applicable to carbon nanotube thin films produced by many of the established methods.

Correction: Dry shear aligning: a simple and versatile method to smooth and align the surfaces of carbon nanotube thin films.

Correction for 'Dry shear aligning: a simple and versatile method to smooth and align the surfaces of carbon nanotube thin films' by D. D. Tune et al., Nanoscale, 2016, DOI: 10.1039/c5nr08784h.

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.

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.

Healing times and prediction of wound healing in neuropathic diabetic foot ulcers: a prospective study.

Time line of wound healing and prediction of healing times in diabetic foot ulcers is an important issue. Usually, the percentage of wounds healed within a defined period is used for characterization of wound healing. R=sqrtA/pi (R, radius; A, planimetric wound area; pi, constant 3.14), and the wound radius reduction was 0.39 mm/week which was previously established. The initial average wound area was 96.9+/-13.1 mm2 (mean+/-SEM), and 3.61+/-1.6 mm 2 after ten weeks with an average healing time of 75.9 (95 %-CI 71-81) days. Using the equation mentioned above and the calculated weekly wound radius reduction, the predicted healing time in the test group was 86.9 (95 %-CI 73-101) days. The predicted and the observed healing times were significantly correlated with each other (r=0.55, p=0.0002). Providing standard care, the time needed for wound healing can reliably be predicted in neuropathic diabetic foot ulcers. This may be a useful tool in daily clinical practice to predict wound healing and recognize ulcers who do not respond adequately to the treatment.

Early detection of microcirculatory impairment in diabetic patients with foot at risk.

OBJECTIVE: To assess microcirculatory impairment and alterations of the skin oxygen supply in diabetic patients with foot at risk. RESEARCH DESIGN AND METHODS: This study evaluated skin blood flow in 21 type 2 diabetic patients with a foot at risk (defined as a foot with neuropathy but without ulceration or previous ulcerations), 20 type 2 diabetic patients without foot lesions or neuropathy, and 21 normal subjects as a control group. The skin blood flow was determined by measuring the transcutaneous oxygen pressure (TcPO(2)) at the dorsum of the foot in supine and sitting position. The clinical assessment included standard measures of peripheral and autonomic neuropathy, but peripheral vascular disease was excluded by Doppler ultrasound. RESULTS: In supine position, TcPO(2) was significantly reduced (means +/- SE) in diabetic patients with foot at risk (6.04 +/- 0.52 kPa) compared with diabetic (7.14 +/- 0.43 kPa, P = 0.035) and nondiabetic (8.10 +/- 0.44 kPa, P = 0.01) control subjects. The sitting/supine TcPO(2) difference was higher in diabetic subjects with foot at risk (3.13 +/- 0.27 kPa) compared with both diabetic (2.00 +/- 0.18, P = 0.004) and nondiabetic (1.77 +/- 0.15 kPa, P = 0.0003) control subjects. The mean sitting/supine ratio was 1.70 +/- 0.12 in diabetic patients with foot at risk, 1.32 +/- 0.04 in diabetic control subjects, and 1.25 +/- 0.03 in nondiabetic control subjects (P = 0.007). The sitting/supine TcPO(2) ratio was negatively correlated with the heart rate variation coefficient at rest (r = -0.32, P = 0.044) and at deep respiration (r = -0.31, P = 0.046). CONCLUSIONS: Our data indicate that skin oxygen supply is reduced in type 2 diabetic patients with foot at risk. This is probably due to an impaired neurogenic blood flow regulation and may contribute to capillary hypertension, followed by disturbed endothelial function leading to edema and skin damage of the foot. The determination of TcPO(2) appears to be a useful tool in screening type 2 diabetic patients for foot at risk.

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.

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.

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.

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.

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.

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.

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.

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.

Strategies for the prevention of type 2 diabetes.

Type 2 diabetes is a common chronic disease affecting more than 100 millions of people world-wide, and is a major cause of premature morbidity and mortality. Macrovascular disease and its risk factors are often already present in individuals at risk for type 2 diabetes, and some of the risk factors for the development of type 2 diabetes, such as obesity, physical inactivity, and high-fat diet, can potentially be modified. Because some of the metabolic abnormalities, such as insulin resistance or impaired glucose tolerance, that indicate a risk for diabetes can be improved by lifestyle modification and drug treatment, strategies for the prevention of type 2 diabetes appear to be necessary for affected individuals. Several clinical trials have addressed the hypothesis that type 2 diabetes can be prevented by dietary modification, physical activity, or drug treatment. Although some of these studies indicate a protective effect of these measures against the development of type 2 diabetes in people at risk, many of their conclusions are limited with respect to randomisation, sample size, or intensity of the intervention. In the large prospective Da Qing study (1997), both dietary and physical activity interventions reduced the incidence of type 2 diabetes considerably in a Chinese population. Whether this is also achievable in other ethnic populations at high risk for developing type 2 diabetes, and whether additional pharmacological measures are useful, is currently under investigation.

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.