Role of endothelial function and inflammation in patients with cardiovascular risk factors, with and without a history of myocardial infarction

BACKGROUND: Endothelial dysfunction and inflammation, in particular their lack of improvement after risk reduction, might better reflect advanced atherosclerosis than just the presence of risk factors. The aim of this study was to compare endothelial function and inflammatory parameters in high-risk patients who had no history of myocardial infarction and in patients in a stable phase after myocardial infarction. METHODS: We compared endothelial function of the brachial artery, measured using high-resolution ultrasound, in 45 patients with hyperlipidaemia (Group 1), and in 45 patients in a stable period after myocardial infarction (Group 2). Forty-five healthy individuals served as a control group (Group 3). RESULTS: Compared to patients with treated hyperlipidaemia, patients after myocardial infarction had lower values of total and LDL cholesterol (p = 0.015; 0.005) and homocysteine (p < 0.005), but marginally higher IL-6 levels (p = 0.1). Other measurements were comparable. However, flow-mediated dilation of the brachial artery was significantly diminished in patients after myocardial infarction (10.6 +/- 3.0; 5.9 +/- 4.0; 14.0 +/- 1.9% for Groups 1-3; ANOVA p = 0.0001; respectively). CONCLUSIONS: We found that patients with previous myocardial infarction have substantially lower endothelial function and increased some inflammatory parameters than patients with a similar level of atherosclerotic risk profile but without clinically evident coronary artery disease.     

Active breathing control (ABC): determination and reduction of breathing-induced organ motion in the chest

PURPOSE: Extensive radiotherapy volumes for tumors of the chest are partly caused by interfractional organ motion. We evaluated the feasibility of respiratory observation tools using the active breathing control (ABC) system and the effect on breathing cycle regularity and reproducibility. METHODS AND MATERIALS: Thirty-six patients with unresectable tumors of the chest were selected for evaluation of the ABC system. Computed tomography scans were performed at various respiratory phases starting at the same couch position without patient movement. Threshold levels were set at minimum and maximum volume during normal breathing cycles and at a volume defined as shallow breathing, reflecting the subjective maximal tolerable reduction of breath volume. To evaluate the extent of organ movement, 13 landmarks were considering using commercial software for image coregistration. In 4 patients, second examinations were performed during therapy. RESULTS: Investigating the differences in a normal breathing cycle versus shallow breathing, a statistically significant reduction of respiratory motion in the upper, middle, and lower regions of the chest could be detected, representing potential movement reduction achieved through reduced breath volume. Evaluating interfraction reproducibility, the mean displacement ranged between 0.24 mm (chest wall/tracheal bifurcation) to 3.5 mm (diaphragm) for expiration and shallow breathing and 0.24 mm (chest wall) to 5.25 mm (diaphragm) for normal inspiration. CONCLUSIONS: By modifying regularity of the respiratory cycle through reduction of breath volume, a significant and reproducible reduction of chest and diaphragm motion is possible, enabling reduction of treatment planning margins.     

Autoimmune blistering skin diseases in childhood

Autoimmune blistering skin disease in childhood are a heterogeneous group of diseases, which vary in presentation, clinical course, pathohistology, immunopathology and treatment. Although these diseases are rare, it is very important to make an accurate diagnosis based on a combination of clinical signs and laboratory findings. A short review is given of the most common childhood autoimmune bullous diseases according to the clinical, pathohistologic and immunopathologic picture and as well as treatment recommendations.     

Generalized regression neural networks in prediction of drug stability

This study had two aims. Firstly, we wanted to model the effects of the percentage of Eudragit RS PO and compression pressure as the most important process and formulation variables on the time course of drug release from extended-release matrix aspirin tablets. Secondly, we investigated the possibility of predicting drug stability and shelf-life using an artificial neural network (ANN). Ten types of matrix aspirin tablets were prepared as model formulations and were stored in stability chambers at 60 degrees C, 50 degrees C, 40 degrees C and 30 degrees C and controlled humidity. Samples were removed at predefined time points and analysed for acetylsalicylic acid (ASA) and salicylic acid (SA) content using stability-indicating HPLC. The decrease in aspirin content followed apparent zero-order kinetics. The amount of Eudragit RS PO and compression pressure were selected as causal factors. The apparent zero-order rate constants for each temperature were chosen as output variables for the ANN. A set of output parameters and causal factors were used as training data for the generalized regression neural network (GRNN). For two additional test formulations, Arrhenius plots were constructed from the experimentally observed and GRNN-predicted results. The slopes of experimentally observed and predicted Arrhenius plots were tested for significance using Student's t-test. For test formulations, the shelf life (t(95%)) was then calculated from experimentally observed values (t(95%) 82.90 weeks), as well as from GRNN-predicted values (t(95%) 81.88 weeks). These results demonstrate that GRNN networks can be used to predict ASA content and shelf life without stability testing for formulations in which the amount of polymer and tablet hardness are within the investigated range.     

Behandlungsassoziierte Spätfolgen nach Strahlentherapie maligner Erkrankungen im Kindes- und Jugendalter

BACKGROUND AND PURPOSE: Radiogenic late effects in children and adolescents have been evaluated retrospectively in most analyses, with small patient numbers. The German Group of Pediatric Radiation Oncology (APRO) has generated a concept for a prospective evaluation of radiation-associated late effects in childhood. The aim of this study was to evaluate the feasibility of a nationwide central database for the documentation of radiation parameters and side effects of all children treated within therapy protocols of the German Society of Pediatric Oncology and Hematology (GPOH). PATIENTS AND METHODS: A study center has been implemented in Muenster, the documentation has started in July 2001 in few centers in a pilot phase. Since February 2004 the documentation is done countrywide. Detailed documentation forms have been designed for treatment parameters and for doses applied at organs at risk. Furthermore, a uniform toxicity documentation, according to the RTOG/EORTC criteria, was chosen. Patients were reported from the study centers of the GPOH to the study center. All information was collected and analyzed in the study center. RESULTS: Till July 31, 2005, 438 documentations of radiation and 579 toxicity documentations of side effects have been collected in the study center. 46 centers for radiotherapy in Germany and one center each in Austria and in Switzerland took part in the documentation. The quality of documentation regarding completeness and plausibility fulfilled the expected criteria in most cases. This feasibility analysis showed that important information about organ dose levels and side effects was documented in a large number of patients (Figures 1 and 2). CONCLUSION: This prospective evaluation of radiotherapy and radiogenic side effects in children and adolescents will allow correlating doses at organs at risk and the incidence of acute and late sequelae in Germany. Further documentations and a longer follow-up are necessary to obtain powerful results.     

Characterisation of monoclonal antibodies to human factor X/Xa. Initial observations with a quantitative ELISA procedure

Monoclonal antibodies to human plasma factor X (FX) and factor Xa (FXa) have been developed using several modifications of previously described techniques. These include the use of footpad immunisation with a suspension of free and nitrocellulose-bound antigen with subsequent fusion of popliteal lymph node cells. From a panel of 17 reactive hybridomas to FX, 3 were selected for further characterisation. An additional hybridoma reactive to FXa but not FX was also selected. Two monoclonal antibodies designated FX52 and FX64 were specific for FX with no reactivity to FXa, while antibody FXa24 was specific for FXa. Another FX/FXa95 reacted with both FX and FXa. All selected antibodies were of the IgG isotype and reacted both with native antigen and antigen transferred to nitrocellulose by Western blotting. Initial observations suggest that Mab FX52 may be used to quantitate FX levels in plasma.     

Hematopoetic stem cell bank at Zagreb University Hospital Center, Zagreb, Croatia

At Zagreb University Hospital Center, the first cryopreservation of hematopoietic stem cells (HSC) was performed in 1989 at Department of Hematology. Since that time, more than 1000 products of HSC have been stored for autologous and related homologous use. In 2000, HSC Bank became organizational unit of the Department of Transfusion Medicine. The purpose of the Bank is to ensure quality in procurement, testing, processing, preservation, storage and distribution of HSC as well as transplantation traceability. Today, it serves as a central storage unit for two transplantation centers. At the moment, there are 587 HSC units on stock for 262 patients. In the future, we are planning to establish a public umbilical cord bank and laboratory for cell therapy.     

High prevalence of the CD14-159CC genotype in patients infected with severe acute respiratory syndrome-associated coronavirus

To investigate whether genetic factors of innate immunity might influence susceptibility and/or progression in individuals infected with SARS, we evaluated the CD14 gene polymorphism in 198 Hong Kong blood donors and 152 Hong Kong severe acute respiratory syndrome (SARS) patients who were previously genotyped for FcγRIIA polymorphisms. The prevalence of the CD14-159CC polymorphism was significantly higher in the patients with severe SARS than in the those with mild SARS or controls (31% versus 15% [mild SARS] or 20% [controls]; mild SARS: P = 0.029; odds ratio, 2.74; 95% confidence interval, 1.15 to 6.57; controls, P = 0.04; odds ratio, 2.41; 95% confidence interval, 1.05 to 5.54), and both CD14-159CC and FcγRIIA-RR131 are risk genotypes for severe SARS-CoV infection.