Standardized findings in echocardiography using WWW: EchoBefundSystem

As a non-invasive imaging system, ultrasound echocardiography has a very high impact on modern diagnosis and is widely used in clinical routine but without any structured and standardized documentation of the results. Thus, quality management (QM), statistics and comparison of the results are difficult. Therefore, a working group of the German Cardiac Society issued a consensus proposal. For evaluation and wide public distribution, we have developed the first internet-based application covering the full proposal: EchoBefundSystem. The EchoBefundSystem is a web based client-server application for standardized documentation of echocardiography results right at the workplace. The software leads the examiner by means of a user interface design and stored medical knowledge. The level of detail is scaled automatically to the ongoing examination. Every day clinical routine is performed on only two pages, one for general patient data and a second one covering the complete minimal data set called "minimum finding" in the standard. As the examiner discovers more and more special findings or might even enter a complete medical study, the interface offers more and more fields and checkboxes. One data set can contain up to 600 values and findings. The structured user interface reflects the organ structure as well as examination methods familiar to the examiner. Automatically calculated fields speed up the examination. Judgements, diagnoses, values and ranges are interrelated. If there is a difference between the entered data and the medical knowledge base, a warning will be issued but the doctor's decision is authoritative. Some values may be gathered by different methods and even different units are converted automatically. The final doctor's letter is generated automatically in clear text but still editable and can be given out to the patient right after the examination without any further delay. Beside the minimal data set, all abnormal findings will appear and findings will be summarized wherever possible. The report is intended for the referring general practitioner, your own documentation, expert witness as well as clinical studies. Interested examiners may test the full version online at http://echo.ma.uni-heidelberg.de     

Regulatory effects of a fermented food concentrate on immune function parameters in healthy volunteers

ObjectiveNutrition is known to influence the immune system and can thereby modulate resistance to infection. The objective of this clinical trial was to assess the influence of a cascade-fermented food consisting of fruits, nuts, and vegetables rich in polyphenols (Regulat) on the immune system in healthy volunteers.MethodsThe clinical trial was double-blinded and placebo-controlled. In total, 48 healthy men 20–48 y of age with a body mass index of 20–28 kg/m² were enrolled in the clinical trial. The group was characterized according to lifestyle parameters and only men with regular low to moderate intake of fruit and vegetables were enrolled. The intervention lasted for a period of 4 wk. Volunteers received Regulat twice daily or a placebo product (essence of vinegar).ResultsThe intake of Regulat significantly enhanced intracellular glutathione content in lymphocytes (P < 0.05), monocytes (P < 0.05), and natural killer cells (P < 0.01). Furthermore, activation of natural killer cell cytotoxicity in response to interleukin-2 stimulation (P < 0.05), a reduction of total lipid peroxidation, and a reduction of soluble vascular cell adhesion molecule-1 (P < 0.01) and soluble intercellular adhesion molecule-1 (P < 0.05) as inflammatory blood markers were found in the Regulat but not in the placebo group.ConclusionIn summary, the results from this intervention study demonstrate promising physiologic effects of immune regulation on the innate immune system and antioxidative and anti-inflammatory parameters after Regulat supplementation. However, these promising results need to be confirmed in more volunteers with a more prolonged application to ensure significant beneficial effects of Regulat in the general population.     

Toxicology and pharmacokinetics of 1-methyl-d-tryptophan: absence of toxicity due to saturating absorption.

1-methyl-d-tryptophan (D-1MT) reverses the immunosuppressive effect of indoleamine 2,3-dioxygenase (IDO), and it is currently being developed both as a vaccine adjuvant and as an immunotherapeutic agent for combination with chemotherapy. The present study examined the pharmacokinetics and toxicity of D-1MT in preparation for clinical trials. Incubation of D-1MT in rat plasma for 24h produced no significant degradation, with <15% of D-1MT being bound to plasma protein. Following oral administration, D-1MT exhibited a larger AUC and V(d), longer elimination t(1/2), and slower clearance in rats than in dogs. When oral doses of D-1MT exceeded levels of 600 mg/m(2)/day in rats, or 1200 mg/m(2)/day in dogs, the C(max) and AUC values decreased, resulting in a corresponding decrease in oral bioavailability. Thus, the doses were indicative of the lowest saturating doses in dogs and rats corresponding with an elimination t(1/2) of 6.0 h and 28.7 h, a T(max) of 1h and 8h, and a bioavailability of 47% and 92%, respectively. Tissue concentrations of D-1MT in mice were highest in the kidney, followed by the liver, muscle, heart, lung, and spleen, respectively; 48 h post dosing, D-1MT was excreted in the urine (35.1%) and feces (13.5%). Oral administration of D-1MT in rats from 150 to 3000 mg/m(2)/day (25-500 mg/kg/day) and in dogs from 600 to 1200 mg/m(2)/day (30 and 60 mg/kg/day) for 28 consecutive days did not lead to mortality, adverse events, histopathological lesions, or significant changes in hematology, clinical chemistry, and body weight. These results suggested that 3000 and 1200 mg/m(2)/day were the no-observed-adverse-effect levels in rats and dogs, respectively. Mean plasma concentrations of D-1MT (600 and 1200 mg/m(2)/day) in dogs 1h post dosing were 54.4 and 69.5 microg/ml on Day 1, respectively, and 53.1 and 66.6 microg/ml on Day 28, respectively; thus, indicating no increase in plasma D-1MT with a change in dose. In conclusion, D-1MT has little toxicity when administered orally to rats and dogs. Exceeding the saturating dose of D-1MT is unlikely to cause systemic toxicity, since any further increase in D-1MT plasma levels would be minimal.     

Preclinical pharmacokinetic,toxicological and biomarker evaluation of SR16157, a novel dual-acting steroid sulfatase inhibitor and selective estrogen receptor modulator

Purpose  

SR16157 is a novel dual-acting inhibitor of estrogen action that irreversibly inhibits the estrogen biosynthetic enzyme steroid sulfatase (STS) and releases the selective estrogen receptor modulator SR16137, which blocks the estrogen receptor. SR16157 is a promising agent for the endocrine therapy of breast cancer. We conducted preclinical in vivo toxicity evaluations to determine the maximum-tolerated dose (MTD), target organ(s) of toxicity, reversibility, dose-limiting toxicity, no observable adverse effect level (NOAEL), and toxicokinetics (TK) and to investigate a potential biomarker for use in SR16157 clinical trials.     

New perspectives on the use of Geographical Information Systems (GIS) in environmental health sciences

At first glance, the domain of health is no typical area to applicate Geographical Information Systems (GIS). Nevertheless, the recent development clearly shows that also within the domains of environmental health, disease ecology and public health GIS have become an indispensable tool for processing, analysing and visualising spatial data. In the field of geographical epidemiology, GIS are used for drawing up disease maps and for ecological analysis. The striking advantages of GIS for the disease mapping process are the considerably simplified generation and variation of maps as well as a broader variety in terms of determining a real units. In the frame of ecological analysis, GIS can significantly assist with the assessment of the distribution of health-relevant environmental factors via interpolation and modelling. On the other hand, the GIS-supported methods for the detection of striking spatial patterns of disease distribution need to be much improved. An important topic in this respect is the integration of the time dimension. The increasing use of remote sensing as well as the integration into internet functionalities will stimulate the application of GIS in the field of Environmental Health Sciences (EHS). In future, the integration and analysis of health-relevant data in one single data system will open up many new research opportunities.     

Relationship of cardiac troponin T and procoagulant activity in unstable angina

OBJECTIVE: The present study sought to determine the incidence of increased procoagulant activity in patients with unstable angina (UAP), and to evaluate the relationship between cardiac troponin T (cTnT) and molecular markers of hemostatic activation. Method. We studied 44 patients with UAP further classified by plasma cTnT levels. All patients received an antithrombotic therapy consisting of therapeutic doses of unfractionated heparin and acetylsalicylic acid. Quantitative levels of cTnT and plasma concentrations of fibrin monomers (FM), prothrombin fragments F1+2, thrombin antithrombin III complexes (TAT), plasminogen and alpha2-antiplasmin were sampled serially within the first 48 h. RESULTS: Increased plasma concentrations of FM were detected in 45.5% of patients and were more frequently present among those with cTnT concentrations > or =0.1 ng/ml (13 of 18 vs 7 of 26 patients, p = 0.003). In these patients, mean plasma concentrations of FM were significantly higher than in patients with cTnT <0.1 ng/ml (7.93 +/- 2.3 vs 3.12 +/- 0.6 microg/ml, p = 0.02). There was a close relationship between plasma levels of cTnT and FM (r = 0.74, p <0.004), prothrombin fragments F1+2 (r = 0.71, p = 0.046) and a trend to significance was noted for TAT (r = 0.42, p = 0.055). No significant correlation was observed with markers of the fibrinolytic system (plasminogen and alpha2-anti-plasmin). Plasma levels of cTnT > or =0.1 ng/ml identified a concomitant increase of hemostatic markers with a sensitivity, specificity and positive predictive value of 65, 79, and 72% for FM, 63, 76, and 67% for prothrombin fragments F1+2, and 58, 66, and 39% for TAT, respectively. CONCLUSIONS: In patients with UAP, cTnT identifies patients with increased procoagulant activity and is closely related to plasma levels of molecular markers of hemostatic activation. Therefore, cTnT alone or in combination with one of these markers may be helpful to identify patients requiring more potent antithrombin or antiplatelet therapy.