Pair distribution function X-ray analysis explains dissolution characteristics of felodipine melt extrusion products.

Solid solutions of felodipine with EUDRAGIT E and EUDRAGIT E/NE were shown to dramatically increase the dissolution rate of felodipine in biorelevant media. Of the two polymer systems, extrudates containing 5% EUDRAGIT NE showed a faster dissolution rate and less recrystallization (no precipitation within 2 h). Although differential scanning calorimetry (DSC) and conventional X-ray powder diffraction (XRPD) were able to verify the amorphous state of the drug after melt extrusion, it was not possible to differentiate the two extrudate compositions further with these methods. We then applied pair distribution function (PDF) analysis to investigate extrudates. It was possible to more closely characterize the solid state of the amorphous extrudates in terms of local structural order: PDF analysis revealed that addition of minor amounts of EUDRAGIT NE to the main component EUDRAGIT E during extrusion changed the local structure of EUDRAGIT E in a nonadditive way. We conclude that local ordering can be important to the release characteristics of extrudates, even when the components are present in the amorphous state.

[Socioeconomic class as a risk factor for cardiovascular diseases]. / Soziale Schicht als kardiovaskulärer Risikofaktor.

It's been known for a long time, that certain diseases are more frequent in lower socioeconomic classes. But knowledge about the nature of this association, its main risk factors and how to improve health outcomes in lower social groups is still limited. Social class has been defined by different indicators by e.g. occupation and job position or the highest school qualification achieved. For international comparisons different classifications such as "The Registrar General's Social Class Classification " or the "International Standard Classification of Education" have been used. Several European Studies show a higher prevalence of cardiovascular diseases and cardiovascular risk factors including smoking, obesity, physical inactivity, hypertension and hypercholesterolemia in lower socioeconomic classes. But this studies also show that all socioeconomic groups have access to medical services. The Data from the Swiss Health Survey show the distribution of cardiovascular risk factors and diseases by three levels of education: Behaviouralfactors such as smoking, obesity and physical inactivity are more commonly present in the lower socioeconomic groups. People with a lower educational level visit their GP more often, whereas people with a higher level of educational consult specialists more frequently. Medical services are often used to check of blood pressure, blood sugar and cholesterol. An indication of state of health may be shown by medication and treatment for cardiovascular disease which is more prevalent in lower socioeconomic groups. The present discussion of explanations of the poorer state of health in lower socioeconomic groups goes beyond the classical risk factors for cardiovascular disease. Studies have shown that after the correction for risk factors a correlation remains between social class and state of health. It is believed, that psychosocial factors such as self-esteem, control in the workplace or coping-strategies play an additional important role in staying healthy. Therefore prevention of cardiovascular disease should not be restricted to minimisation of risk factors or to the measurement of certain blood-values and treatments. Efforts must also go into creating the conditions for a healthier life and promote possibilities for healthier behaviour in all socioeconomic classes.

[Differential gene expression signatures in well differentiated thyroid carcinomas]. / Differentielle Genexpression in gut differenzierten Schilddrüsenkarzinomen.

Despite their common origin from follicular epithelial cells, papillary and follicular thyroid carcinomas differ in their histology and clinical course. In this study the transcriptional profiles of these tumors in comparison with normal thyroid tissue were established. The aim was the development of a molecular tool providing additional information to current histopathological diagnosis and allowing further insight into tumorigenesis. Genome wide expression profiling was performed using Human Unigene Set--RZPD 2 high density cDNA macroarrays comprising 76,000 genes as probes and radioactively labeled cDNA targets retrotranscribed from the isolated RNA of three papillary and three follicular thyroid carcinomas as well as three normal thyroid tissues. 8600 genes differing in their expression between the three groups were selected and printed onto subarrays. Radioactively labeled cDNA targets obtained from 16 papillary carcinomas, 13 follicular carcinomas and 17 normal thyroid tissues were hybridized to these subarrays. 200 genes exhibited a statistically significant expression difference between the two tumor types (p <0.01). In a hierarchical cluster analysis of 124 of these genes (46 known genes and 78 ESTs) the algorythm divided the tumor samples into two groups corresponding to the papillary and follicular thyroid carcinomas. The clearcut diagnostic potential of this method has to be corroborated in a prospective study. Several of the differentiallly expressed genes are known to play a role in tumor development and metastasis. Some of the genes up- or down-regulated in both tumor types are members of known oncogenic pathways in thyroid carcinomas. The complete understanding of complex genome wide expression profiles however awaits a longstanding advancement of hypothesis driven research.

Feasibility and potential of MR-Colonography for evaluating colorectal cancer.

BACKGROUND: MR-Colonography (MRC) based on MR-imaging is a relatively new diagnostic modality for diagnosing colorectal polyps. The aim of this experimental study was to evaluate its performance in detecting and staging colorectal cancer. METHOD: 23 patients with proven colorectal cancer underwent MR-Colonography one day prior to operation after standard bowel preparation. The colon was filled with a diluted gadolinium enema. Coronal sections were acquired in prone and supine. Virtual colonoscopy (VC) was processed from the acquired 3D data sets and MRC was interactively analysed together with VC. The findings were correlated with colonoscopic and pathology results. RESULTS: A complete MRC was achieved in 21 patients (92%), two patients (8%) could not be conclusively evaluated due to insufficient bowel preparation or technical problems. No complications were observed. Compared to colonoscopy all 23 carcinomas were detected. No lesion > or = 8 mm was missed. In one patient a synchronous carcinoma was newly diagnosed. This lesion was missed by colonoscopy since the distal tumour was endoscopically unpassable. In total eight (33%) colonoscopies were incomplete. CONCLUSION: MRC offers a new and promising diagnostic tool for colorectal cancer. It is particularly valuable when colonoscopy is incomplete. It improves preoperative planning and it holds the potential as an all-in-one investigation including local and liver staging in combination with conventional MRI.