[The role of cardiovascular magnetic resonance imaging in the diagnosis and prognosis of patients with heart failure]. / Die Rolle der Kardio-MRT bei Diagnose und Prognosebeurteilung der Herzinsuffizienz.

Cardiovascular magnetic resonance (CMR) imaging is a tomographic technique, which allows three-dimensional slice orientation without limitations from acoustic windows inherent to echocardiography. Further advantages of CMR are its high temporal and spatial resolution, its excellent soft tissue resolution and its high blood-to-tissue contrast. Cardiovascular magnetic resonance is currently the only imaging technique, which provides a comprehensive study of both structure and function of the heart as well as myocardial perfusion and viability. Moreover, post-processing of CMR images does not require any geometric assumptions as in echocardiography to determine ventricular dimensions. This is particularly important when evaluating ventricles of patients with chronic heart failure with severely altered morphology that may have regional variations in wall thickness and contractility at least in ischemic cardiomyopathy. The highly reproducible results of CMR imaging have turned this technique into a reference standard for the non-invasive assessment of ventricular dimensions, mass and function. In cases with indeterminate results of clinical, electrocardiographic and particularly echocardiographic findings CMR should be used early in the process of diagnosis of patients with heart failure. Not only can altered structure and degree of ventricular and valvular dysfunctions be accurately assessed but also regional perfusion deficits and/or myocardial scars are easily detected. For therapeutic and prognostic reasons a simple differentiation between ischemic and non-ischemic cardiomyopathy should be achieved as the first diagnostic step. In addition, the type and localization of the late gadolinium enhancement (LGE) phenomenon may aid in non-invasively differentiating the etiology of non-ischemic cardiomyopathy. CMR may also improve the assessment and extent of interventricular and intraventricular dyssynchrony in patients to be selected for cardiac resynchronization therapy (CRT). Lastly, the LGE phenomenon may provide independent prognostic information in patients with a CRT system implanted, as well as in patients with ischemic and non-ischemic cardiomyopathy. Thus, CMR imaging should be implemented early in the diagnostic process of patients with heart failure to significantly improve the speed and accuracy of diagnostic procedures, to control the effect of therapeutic measures, and to select patients with a limited prognosis by assessing the degree of ventricular dysfunction and the extent of myocardial scarring.

Signalling processes involved in C-peptide-induced chemotaxis of CD4-positive lymphocytes.

Previous data from our group demonstrated that C-peptide induces chemotaxis of CD4-positive lymphocytes in-vitro, mediated by activation of G-protein and PI 3-kinase gamma, but additional signalling pathways involved in this process remained unexplored. In the present study we further analyze intracellular signalling pathways which lead to C-peptide-induced CD4-positive lymphocyte migration. We provide evidence that C-peptide-induced chemotaxis of CD4-positive lymphocytes is critically dependent on activation of Src-kinase and RhoA, Rac-1 and Cdc42 GTPases. Furthermore, C-peptide stimulates phosphorylation of PAK, LIMK and cofilin downstream of Rac-1 and Cdc42, leading to cofilin inactivation and actin filament stabilization. In addition, C-peptide induces ROCK kinase activity and MLC phosphorylation downstream of RhoA, thereby stimulating myosin mediated cell contraction. In contrast, C-peptide does not activate ERK1/2, p38 or Akt in CD4-positive lymphocytes. Our data support an active role of C-peptide in CD4-positive lymphocyte chemotaxis and elucidate molecular mechanisms in C-peptide-induced cell migration.

Integrated FDG PET-CT imaging improves staging in malignant pleural mesothelioma.

UNLABELLED: AIM of this study was to investigate, how often TNM staging is changed in patients with malignant pleural mesothelioma (MPM) by the application of integrated PET-CT compared to computed tomography alone and how often these changes are clinically relevant. PATIENTS, METHODS: We studied 17 patients (68 +/- 6 years, 8 women) with MPM. Integrated PET-CT scan and histological confirmation were performed in all patients. RESULTS: Final histological diagnosis confirmed 9 epithelial type, 2 sarcomatoid type and 6 biphasic type MPM. Mean standardized uptake value (SUV) was 5.9 +/- 1.9 in epithelial MPM and 15.1 +/- 10.2 in sarcomatoid MPM. CT and PET-CT revealed discordances in 8/17 (47%) patients in TNM classification with 4/8 (50%) being clinically relevant. PET-CT led to downstaging in 5 (29%) and upstaging in 3 (18%) patients. Mean survival time tended to be higher in the subgroup of patients with lower mean SUV. CONCLUSIONS: PET-CT seems to be a valuable tool in staging of MPM and leads to discordant findings in almost every second patient compared to CT alone. In many cases these differences are clinically relevant and have therapeutic consequences.

Patients with in-stent restenoses: comparison of intracoronary beta-brachytherapy using a rhenium-188 filled balloon catheter with the polymer-based paclitaxel-eluting taxus-express stent.

AIMS: We compared the intracoronary beta-brachytherapy using a liquid rhenium-188 filled balloon with the slow-release, polymer-based, paclitaxel-eluting Taxus-Express stent for treatment of in-stent restenoses. PATIENTS, METHODS: During the same study period, patients with restenoses in bare-metal stents were either treated with Taxus-Express stents (n = 50) or beta-brachytherapy after successful angioplasty (n = 51). For brachytherapy 30 Gy in 0.5 mm tissue depth were administered. The irradiated segment exceeded the traumatized segment 7.5 mm on both sides. Primary endpoint was the minimal lumen diameter (MLD) at the target lesion at six months follow-up. Angiographic follow-up was available in 78% (n = 79/101) and clinical follow-up in all patients. RESULTS: Baseline parameters did not differ statistically. The Taxus-Express stent resulted in a significantly larger MLD and a significantly lower percent diameter stenosis post intervention compared to beta-brachytherapy, which both maintained until angiographic follow-up (primary endpoint 2.44 +/- 0.74 mm versus 1.73 +/- 0.74 mm, p < 0.0001). Therefore, Taxus-Express stents were associated with a lower angiographic restenosis rate compared with beta-brachytherapy, both for the target lesion (6.1% versus 17.4%) and the total segment (9.1% versus 23.9%). Moreover, use of Taxus-stent was associated with a clinical benefit based on a significantly lower MACE rate compared with beta-brachytherapy (p < 0.05). CONCLUSIONS: Paclitaxel-eluting Taxus-Express stents resulted in superior clinical and angiographic outcomes compared to intracoronary beta-brachytherapy with a liquid (188)Re filled balloon for treatment of restenosis within a bare-metal stent.

Pericardial synovial sarcoma mimicking pericarditis in findings of cardiac magnetic resonance imaging.

We report a case of a 64-year-old woman with increasing shortness of breath due to massive pericardial effusion. Cardiac magnetic resonance imaging (CMRI) identified typical findings for pericarditis. Pericardectomy was needed due to suspicion of pericardial abscess formation. Histological examination of the resected tissue revealed an undifferentiated primary pericardial synovial sarcoma. The present case illustrates that pericardial tumours could be an important differential diagnosis to pericarditis, even if typical findings of pericarditis were present in CMRI.

Improved non-invasive T-Staging in non-small cell lung cancer by integrated 18F-FDG PET/CT.

AIM: In this prospective study, reliability of integrated (18)F-FDG PET/CT for staging of NSCLC was evaluated and compared to MDCT or PET alone. PATIENTS, METHODS: 240 patients (pts) with suspected NSCLC were examined using PET/CT. Of those patients 112 underwent surgery comprising 80 patients with NSCLC (T1 n = 26, T2 n = 37, T3 n = 11, T4 n = 6). Imaging modalities were evaluated independently. RESULTS: MDCT, PET and PET/CT diagnosed the correct T-stage in 40/80 pts (50%; CI: 0.39-0.61), 40/80 pts (50%; CI: 0.39-0.61) and 51/80 pts (64%; CI: 0.52-0.74), respectively, whereas equivocal T-stage was found in 15/80 pts (19%; CI: 0.11-0.19), 12/80 pts (15%; CI: 0.08-0.25) and 4/80 pts (5%; CI: 0.01-0.12), respectively. With PET/CT, T-stage was more frequently correct compared to MDCT (p = 0.003) or PET (p = 0.019). Pooling stages T1/T2, T-stage was correctly diagnosed with MDCT, PET and PET/CT in 54/80 pts (68%; CI: 0.56-0.78), 56/80 pts (70%; CI: 0.59-0.80) and 65/80 pts (81%; CI: 0.71-0.89). T3 stage was most difficult to diagnose. T3 tumors were correctly diagnosed with MDCT in 2/11 pts (18%; CI: 0.02-0.52) versus 0/11 pts (0%; CI: 0.00-0.28) with PET and 5/11 pts (45%; CI: 0.17-0.77) with PET/CT. In all imaging modalities, there were no equivocal findings for T4 tumors. Of these, MDCT found the correct tumor stage in 4/6 pts (67%; CI: 0.22-0.95), PET in 3/6 pts (50%; CI: 0.12-0.88) and PET/CT in 5/6 pts (83%; CI: 0.36-0.99). CONCLUSION: Integrated PET/CT was significantly more accurate for T-staging of NSCLC compared to MDCT or PET alone. The advantages of PET/CT are especially pronounced combining T1- and T2-stage as well as in advanced tumors.

Comparison of the slow-release polymer-based paclitaxel-eluting Taxus-Express stent with the bare-metal Express stent for saphenous vein graft interventions.

BACKGROUND: The paclitaxel-eluting Taxus-Express stent is superior regarding angiographic and clinical outcome compared with its bare-metal platform for lesions in native coronary arteries. We studied the potential impact of the Taxus-Express stent in comparison with its bare-metal counterpart for treatment of lesions in saphenous vein grafts (SVGs). Furthermore, a meta-analysis was performed regarding use of drug-eluting (DES) vs bare-metal stents (BMS) in SVG lesions. METHODS: We analyzed 13 consecutive patients who underwent percutaneous revascularization in SVG lesions using the slow-release, paclitaxel-eluting Taxus-Express stent. These lesions were balanced with 26 patients with SVG lesions treated with the bare-metal Express stent (BMS) in the preceding period. Angiographic follow-up was performed after 6 months, clinical follow-up after 6 and 12 months. RESULTS: There were no statistically significant differences regarding clinical, procedural and angiographic parameters pre and post intervention. Binary restenoses occurred significantly less in the Taxus group compared with the BMS group (0% vs 34.6%; p=0.016). This translated into a significantly lower occurrence of major adverse cardiac events (death, Q-wave myocardial infarction, repeat target vessel revascularization) in the Taxus group compared with the BMS group at the 6-month (0% vs 26.9%, p=0.039) and 12-month follow-up (7.7% vs 38.5%, p=0.045). Multivariate predictors for freedom of binary restenosis were the reference diameter pre intervention and treatment with Taxus stents. Meta-analysis including 280 DES and 256 BMS patients revealed an odds ratio of 0.34 (95% confidence interval 0.21-0.54) for MACE and 0.26 (95% confidence interval 0.16-0.44) for target vessel revascularizations, both favoring DES. CONCLUSIONS: We conclude that the use of the slow-release Taxus-Express stent has the potential to be superior regarding angiographic and clinical outcome compared with its bare-metal counterpart for treatment of SVG lesions within a 12-month follow-up. A large, randomized trial including a long follow-up period is now required to prove the results of the meta-analysis.

Use of integrated FDG PET/CT imaging in pulmonary carcinoid tumours.

BACKGROUND: Integrated positron emission tomography (PET)/computed tomography (CT) scanners have been recently introduced in the diagnostic work-up of suspected pulmonary malignancy and demonstrate encouraging results in the staging of nonsmall-cell lung cancer. OBJECTIVE: To evaluate the usefulness of integrated FDG PET/CT in pulmonary carcinoid tumours. SETTING: University hospital. METHODS: We studied 13 patients (mean age +/- 1 SD, 57 +/- 11 years) with pulmonary carcinoid tumours. All patients demonstrated a single pulmonary lesion. Integrated PET/CT scan and surgical resection were performed in all patients. RESULTS: The pulmonary lesion size ranged from 1.1 to 5.0 cm. Final histological diagnosis confirmed 12 typical and one atypical pulmonary carcinoid. Mean proliferation rate of the typical carcinoids was 1.7 +/- 1.4%. None of the patients had recurrent carcinoid disease or died during follow-up (864 +/- 218 days). Mean standardized uptake value (SUV) of (18)F-fluorodeoxyglucose (FDG) in typical carcinoids was 3.0 +/- 1.5 (range 1.2 - 6.6); SUV in the atypical carcinoid was remarkably high with a value of 8.5. The SUV was lower than 2.5 in 6 of 12 patients (50%). Mediastinal lymph node metastases or extrathoracic metastases were not detected in any patient. CONCLUSIONS: (18)F-fluorodeoxyglucose PET/CT imaging improves accurate localization of metabolic activity and thus the interpretation of pulmonary lesions on CT. FDG uptake in pulmonary carcinoid tumours is often lower than expected for malignant tumours. Therefore, surgical resection or biopsy of lesions suspected to be carcinoids should be mandatory, even if they show no hypermetabolism on FDG PET images.

Labeling of adult stem cells for in vivo-application in the human heart.

Tissue regeneration with human hematopoietic or mesenchymal stem cells has become a fashionable research topic. In cardiology, intracoronary injection of adult stem cells has already been used for the treatment of human myocardial infarction and ischemic cardiomyopathy. The experimental background of such therapies, however, i.e. the potential of adult stem cells to regenerate myocardium through "transdifferentiation" of hematopoietic or mesenchymal stem cells into cardiomyocytes described in animal models, has recently been challenged by other experimental data. Nonetheless, clinical trials are continuing. This may be due to the fact that, in open-labeled pilot trials, a benefit of intracoronary injection of adult stem cells for the treatment of myocardial infarction has been described. As pilot trials may overemphasize the beneficial effects of intracoronary injection of bone marrow stem cells, controlled double-blinded randomised multicenter studies are warranted. Furthermore, a careful characterization of the cells involved in the proposed cardiac repair as well as in vivo-monitoring of such cells following intracoronary injection in humans might help to answer many essential questions linked to this important research topic. The latter requires biocompatible labeling. This review focuses on the technologies available for stem cell labeling and summarizes the arguments and contra-arguments to use these labeling technologies for application in humans.

A new strategy for easy volume conductor modelling in magnetocardiography.

Modelling the electromagnetic properties of the thorax in magnetocardiographic (MCG) studies is usually performed by the Boundary Element Method (BEM). Magnetic Resonance Imaging (MRI) scans are generally used as the basis for extracting the coordinates for BEM. As MRI is a (time) expensive technique and scanners have a high use demand, in this work a strategy is presented that reduces the costs and the need for additional MRI images. This strategy is based on the use of low resolution and incomplete MRI image sets of the thorax.

Assessment of left ventricular function with steady-state-free-precession magnetic resonance imaging. Reference values and a comparison to left ventriculography.

UNLABELLED: Ejection fraction (EF) and end-diastolic and end-systolic volume index (EDVI/ ESVI) derived from ventriculography are important prognostic parameters. Cine magnetic resonance imaging (MRI) using a steady-state, free-precession sequence (SSFP) offers excellent delineation of the endocardial borders and highly reproducible and accurate results for cardiac volumes. We evaluated MRI volumetry against routine x-ray ventriculography. In 200 patients EF, EDVI and ESVI were measured with MRI volumetry and x-ray ventriculography. The same MRI protocol was applied to 102 healthy persons in order to establish reference values. In healthy subjects mean EF was 68.8% +/- 5.4% (range 59-84%), mean EDVI 69 +/- 10 (43-90) and mean ESVI 22 +/- 5.8 (10-35 ml). In the patients, overall correlation (Spearman's R) of MRI with ventriculography was 0.86 for EF, 0.77 for EDVI and 0.88 for ESVI. For postextrasystolic beats (38% of the measurements), R was 0.73/0.65/0.73 for EF/EDVI/ESVI. MRI correlated best with biplane ventriculography during sinus rhythm (0.96/0.85/0.93); the worst correlation (0.78/0.81/0.83) resulted from patients with wall motion abnormalities in comparison to monoplane x-ray ventriculography. CONCLUSION: Contemporary MRI volumetry compares well to invasive data obtained under optimal conditions. In view of the known limitations of single plane ventriculography, MRI seems to allow exact volumetry independent from regional wall motion abnormalities.

Analysis of the ST-segment in terms of principal components: application on multichannel magnetocardiographic recordings.

Parameterization of the ST-segment is used as a tool for risk stratification for patients to suffer from ventricular tachycardia. This parameterization is performed in terms of Principal Component Analysis (PCA) applied on multichannel magnetocardiographic (MCG) recordings. 55-channel MCG was recorded from 14 normal persons, 10 patients with CHD, 14 patients with MI, and six patients with VT. We found a significantly (p < 0.05) lower PCA-score in patients with MI compared to normals. The lowest PCA-score was found in VT patients. Significant differences can be found between VT patients and normals and also between VT patients and CHD patients.

Pulmonary hemodynamics in obstructive sleep apnea: frequency and causes of pulmonary hypertension.

The association between nocturnal apneas and transient pulmonary hypertension (PHT) has been well documented. However, there is controversy over the frequency and pathophysiological mechanisms of daytime pulmonary hypertension in patients with obstructive sleep apnea (OSAS). The present study sought to evaluate frequency and mechanisms of pulmonary hypertension in patients with OSAS. It included 49 consecutive patients with polysomnographically proven OSAS without pathological lung function testing. All patients performed daytime measurements of pulmonary hemodynamics at rest and during exercise (50-75W). Six patients (12%) had resting PHT mean pulmonary of artery pressure (PAPM) of >20 mmHg), whereas 39 patients (80%) showed PHT during exercise (PAPM >30 mmHg). Multiple regression analysis revealed 3 independent contributing factors for mean pulmonary artery pressure during exercise (PAPMmax): body mass index, age and total lung capacity % of predicted. Twenty-five of the 39 patients with pathologically high PAPMmax (64%) showed elevated pulmonary capillary wedge pressures (PCWPmax > 20 mmHg), whereas no patient had elevated pulmonary vascular resistance (PVRmax > 120 dynes x s x cm(-5)). In conclusion, daytime PHT during exercise is frequently seen in patients with OSAS and normal lung function testing and is mainly caused by abnormally high PCWP, whereas PVR seems to play a minor role.

C-reactive protein and atherosclerosis. Is there a causal link?

C-reactive protein (CRP) is a powerful cardiovascular risk marker. Evidence suggests that this may be due to its direct proatherogenic properties. Because of different biological functions of CRP in different species, an appropriate animal model for the study of its role in atherogenesis is difficult to set up. Binding to low density lipoprotein (LDL), activation of the complement system and interaction with monocyte/macrophages are rigorously defined pathogenic properties of CRP which might contribute to an active role of the molecule in human atherogenesis. Furthermore, direct effects on arterial wall cells, i.e. endothelial cells and smooth muscle cells, have been reported. The molecular basis of CRP interaction with these cells, however, remains unclear. Should CRP indeed be actively involved in human atherogenesis, the molecule may become a target for therapy. Pharmaceutical companies develop CRP-inhibitors.

Inhibition of MMP-9 expression by PPARgamma activators in human bronchial epithelial cells.

BACKGROUND: The release of matrix degrading enzymes such as matrix metalloproteinase 9 (MMP-9) from bronchial epithelial cells is critically involved in airway wall remodelling in chronic inflammatory processes of the respiratory system. MMP-9 expression is induced by inflammatory mediators such as tumour necrosis factor (TNF)-alpha, but to date nothing is known about the mechanisms of inhibition of MMP-9 expression in these cells. METHODS: A study was undertaken to examine whether activators of the nuclear transcription factor peroxisome proliferator activated receptor gamma (PPARgamma) might modulate MMP-9 expression in two different bronchial epithelial cell lines. RESULTS: PPARgamma was expressed and was functionally active in NL20 and BEAS cells. Activation of PPARgamma by rosiglitazone or pioglitazone significantly reduced TNF-alpha and PMA induced MMP-9 gelatinolytic activity in a concentration dependent manner in both cell lines, but did not alter the expression of tissue inhibitor of MMPs type 1 (TIMP-1), the local inhibitor of MMP-9. Northern blot analysis revealed a decrease in MMP-9 mRNA expression following treatment with PPARgamma which resulted from the inhibition of NF-kappaB activation in these cells, as determined by transient transfection assays and electromobility shift assays. CONCLUSION: Activation of PPARgamma in human bronchial epithelial cells limits the expression of matrix degrading MMP-9. This might have therapeutic applications in chronic inflammatory processes of the respiratory system.

[Effect of molsidomine on rheological parameters and the incidence of cardiovascular events]. / Einfluss von Molsidomin auf rheologische Parameter und die Inzidenz kardiovaskulärer Ereignisse.

BACKGROUND AND OBJECTIVE: In-vitro studies revealed that nitric oxide (NO) may affect rheological parameters. We studied the effect of highly-dosed NO-donor molsidomine on blood rheology and the impact of rheological parameters on the incidence of severe cardiovascular events. PATIENTS AND METHODS: In this randomized, placebo-controlled and double-blind trial 166 patients (60 +/- 10 years) with stable angina pectoris and coronary intervention received molsidomine 3 x 8 mg t. i. d. (controlled release tablets) or placebo for 6 months. Patients with inflammatory/neoplastic disorders or elevated values of C-reactive protein were excluded from analysis. A rheological profile (plasma viscosity, blood viscosity, aggregation and flexibility of erythrocytes, filtrability of leukocytes, fibrinogen levels) was done initially and after 6 months. Adverse cardiovascular events (death, myocardial infarction, stroke, coronary/peripheral revascularization) were recorded during 12 months. Furthermore, the impact of rheological parameters regarding the occurrence of severe cardiovascular events (death, myocardial infarction, stroke) was evaluated during a follow-up of median 38 months. RESULTS: The data of 137 patients (n = 71 placebo, n = 66 molsidomine) were analysed. The difference of rheological parameters between the two measurements did not vary between the two groups. Analysis of event-free survival with Kaplan-Meier technique revealed no difference between the two groups. Multivariate Cox regression analysis with adjustment for diabetes mellitus, smoking and therapy with statin showed a significant association of fibrinogen and plasma viscosity with the occurrence of severe cardiovascular events. CONCLUSION: Treatment with molsidomine 3 x 8 mg/day for 6 months does not improve blood rheology or reduce cardiovascular events. But elevated levels of fibrinogen and plasma viscosity were associated with the occurrence of severe cardiovascular events.

On the variability of QRS time-duration in magnetocardiographic recordings.

High resolution electrocardiography (HRECG) recordings have already shown an increased beat-to-beat microvariability of the QRS duration of the terminal QRS in patients with a history of ventricular tachycardia (VT). The purpose of this study is to detect QRS-duration microvariability with magnetocardiographic (MCG) recordings in normals, patients with coronary heart disease (CHD), patients with a history of myocardial infarction (MI), and VT patients. QRS microvariability is calculated as the variance of time-shifts of single beats respectively to the average of all beats. The average over all channels of the MCG is performed. QRS microvariability was evaluated from 55-channel MCG in 15 normal persons, in 12 patients with CHD, in 13 patients with MI, and in 10 patients with VT. We found a significantly higher microvariability in patients with MI compared to normals. The highest microvariability was found in VT patients.

Temperature changes in chicken embryos exposed to a continuous-wave 1.25 GHz radiofrequency electromagnetic field.

A total of 550 fertile chicken eggs (White Leghorn) were exposed to a radiofrequency (RF) electromagnetic field of 1.25 GHz (continuous wave) at six different power flux densities in the range of 9.0-0.75 mW/cm(2). The eggs were exposed either continuously throughout the whole 21 days of incubation (long-term exposure) or in a short-term exposure (1-2 h/day). The temperatures of the embryonic tissue and the amniotic fluid, respectively, were measured with inserted temperature probes. This study was designed to investigate the relationship between exposure and temperature changes in exposed tissues, without considering biological and medical effects. This knowledge is of general interest for studies of nonthermic teratological or embryo-lethal effects of exposure to electromagnetic fields (EMFs). Throughout the entire 21 days of embryonic development, the mean temperature increases in the eggs during the exposure were found to be up to 0.25 degrees C for a power flux density of 1.25 mW/cm(2) and increased to 2.3 degrees C for 9.0 mW/cm(2). The corresponding maximum whole-body SARs for the embryos over the 21 days of embryonic development were 1.45 and 10.44 W/kg, respectively. At 0.75 mW/cm(2) (0.87 W/kg) the extent of the RF-field induced hyperthermia was within the measurement accuracy (+/-0.1 degrees C) of the temperature probes used in the tests. The field-induced temperature increase was greatest in the first week of incubation and was less pronounced in the last (third) week before hatching. In both the short- and the long-term exposures, the temperature of the exposed tissue and the amniotic fluid, respectively, reached its maximum (asymptotic) approximately 40-50 min after the RF field was switched on. After the field was switched off, the temperature inside the exposed eggs returned to its initial value within 40-50 min.

Microvascular permeability is increased in both types of diabetes and correlates differentially with serum levels of insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF).

Vascular endothelial growth factor (VEGF) and insulin-like growth factor-I (IGF-I) both play a pivotal role in diabetic microangiopathy. This study assessed the relationship between capillary permeability as a marker of endothelial dysfunction and serum VEGF and IGF-I levels in normotensive diabetics. Subjects were 10 Type 1 (6/4, male/female, age: 30 [mean] +/- 5 [SD] years, HbA1c: 7.5 +/- 1.1 %), 13 Type 2 diabetics (9/4, m/f; 63 +/- 7 years, 8.3 +/- 1.8 %), and 24 age- and sex-matched control subjects. We determined nailfold capillary permeability by intravital fluorescence videomicroscopy after intravenous injection of sodium-fluorescein. Serum VEGF, free and total IGF-I, IGF binding protein (IGFBP)-1, IGFBP-3, and insulin levels were measured by specific immunoassays. Capillary permeability was increased in both types of diabetes patients compared to age- and sex-matched controls. In Type 1 diabetics, fluorescence light intensities increased over time, reaching significance 30 minutes after dye injection. Type 2 diabetics already revealed an early onset of elevated fluorescence light intensities after one minute. Capillary permeability showed a significant positive correlation with VEGF levels in Type 1 diabetics, (r = 0.76, p < 0.05; 20 min after dye injection) but with free IGF-I levels in type 2 diabetics (r = 0.65, p < 0.05; 5 min after dye injection). IGFBP-3 correlated negatively with capillary permeability in both diabetes types, whereas IGFBP-1 levels correlated positively in Type 2 patients. In conclusion, capillary permeability is increased in both types of diabetes mellitus. However, VEGF and IGF-I may differentially affect microvascular permeability depending on the diabetes type.