Determination of albuminuria in the urine of diabetics for prevention and control of diabetic nephropathy

The issue: Diabetes has become the main cause of endstage renal disease. The costs for the treatment of diabetic patients with endstage renal disease have increased in the last years and have become a relevant economic topic of the health service. The first unspecific predictor of a diabetic nephropathy is an albuminuria. The screening for diabetic nephropathy uses microalbuminuria as a proof. Objectives: * What significance does the determination of albuminuria have on the precaution and course-control of the diabetic nephropathy? a) in type 1 diabetic patients, b) in type 2 diabetic patients * Which is an appropriate time to determine the albuminuria for the purpose of precaution and course-control of the diabetic nephropathy? a) in type 1 diabetic patients, b) in type 2 diabetic patients * Which method of testing is most effective concerning economic and medical aspects? Methods: Published literature from 1998 up to 2004 was identified by searching in the most important databases. Most of the guidelines were found by hand searching in the internet. Results: Of 2,792 citation titles and abstracts examined, 274 articles were retrieved for full-text review. Five metaanalyses and reviews, one review about clearing of guidelines (regarding 18 international guidelines) and four guidelines met the inclusion criteria for screening for microalbuminuria and type 1 diabetes. Seven metaanalyses, one HTA report, one review about clearing of guidelines (regarding 17 international guidelines), and seven guidelines met the inclusion criteria for screening for microalbuminuria and type 2 diabetes.At the moment, the determination of albuminuria still has a great significance because it is recommended in most published literature and guidelines. The time to determine the albuminuria depends on the age of the patients and their type of diabetes. Type 2 diabetic patients should start the determination when the diabetes is diagnosed whereas the determination is recommended five years later when type 1 diabetic patients are concerned. Most guidelines recommend a screening for microalbuminuria every year. Discussion and conclusion: All guidelines and most of the literature recommend this screening. However, these recommendations are only based on expert consensus. The specificity of this screening is rather low. False positive tests in type 2 diabetic patients will cause psychological problems. A positive test leads to the recommendation to achieve "normal blood pressure" and "normoglycaemia" - but this applies to each diabetic patient. Based on these facts, the screening for albuminuria in type 1 or type 2 diabetes patients cannot be recommended as long as benefit has not been demonstrated by large, clinical, controlled trials. Without an evidence of the benefit, this screening cannot be economic

Neue Ankergruppen für die enantioselektive kombinatorische Festphasensynthese

Within the scope of this work three new linkers for solid phase synthesis have been developed. Starting with functionalized amines these were diazotated and coupled onto a resin with secondary amine functionalities. This triazene-linker (T1-linker) allows the traceless cleavage of arenes. On the T1-linker Heck-reactions and based upon this several further derivatisations have been realized. Furthermore a linker system for the coupling of amines based on immobilized diazonium salts has been developed (T2-linker). On the T2-linker piperidone has successfully been immobilized, as a central building block for the sysnthesis of analgetics in cooperation with the Grünenthal-GmbH. On this building block Mannich-, Grignard- and Wittig-reactions have been realized, leading to precursors of the desired substances. In order to synthesize a "SAMP-resin", a trityl-protected precursor was synthesized from trans-4-Hydroxy-L-proline and linked to Merrifieldïs-resin. Deprotection, nitrosation and reduction lead to the "SAMP-resin". Hydrazones based on this "SAMP-resin" were used in alpha-alkylations at -100 øC leading to ee- values up to 86.3%. A library of 24 chiral ketones was synthesized at -72 øC. The purities of the products exeeded 99% and they showed moderate ee-values of up to 78.6%

Neue Ankergruppen für die enantioselektive kombinatorische Festphasensynthese

Within the scope of this work three new linkers for solid phase synthesis have been developed. Starting with functionalized amines these were diazotated and coupled onto a resin with secondary amine functionalities. This triazene-linker (T1-linker) allows the traceless cleavage of arenes. On the T1-linker Heck-reactions and based upon this several further derivatisations have been realized. Furthermore a linker system for the coupling of amines based on immobilized diazonium salts has been developed (T2-linker). On the T2-linker piperidone has successfully been immobilized, as a central building block for the sysnthesis of analgetics in cooperation with the Grünenthal-GmbH. On this building block Mannich-, Grignard- and Wittig-reactions have been realized, leading to precursors of the desired substances. In order to synthesize a "SAMP-resin", a trityl-protected precursor was synthesized from trans-4-Hydroxy-L-proline and linked to Merrifieldïs-resin. Deprotection, nitrosation and reduction lead to the "SAMP-resin". Hydrazones based on this "SAMP-resin" were used in alpha-alkylations at -100 øC leading to ee- values up to 86.3%. A library of 24 chiral ketones was synthesized at -72 øC. The purities of the products exeeded 99% and they showed moderate ee-values of up to 78.6%

A triazene-based new photolabile linker in solid phase chemistry

An extension of the T2 linker methodology by showing its applicability as a photocleavable linker is reported. Photocleavage was carried out with 355 nm UV laser irradiation (3Omega Nd-YAG) in methanol/diethyl ether and is suitable for protected amino acid derivatives, as well as simple small organic molecules including resin-bound biotin. The linker is stable under a wide range of conditions with the exception of strongly acidic medi

Complementary and alternative drug therapy versus science-oriented medicine

This opinion deals critically with the so-called complementary and alternative medical (CAM) therapy on the basis of current data. From the authors’ perspective, CAM prescriptions and most notably the extensive current endeavours to the “integration” of CAM into conventional patient care is problematic in several respects.Thus, several CAM measures are used, although no specific effects of medicines can be proved in clinical studies. It is extensively explained that the methods used in this regard are those of evidence-based medicine, which is one of the indispensable pillars of science-oriented medicine. This standard of proof of efficacy is fundamentally independent of the requirement of being able to explain efficacy of a therapy in a manner compatible with the insights of the natural sciences, which is also essential for medical progress. Numerous CAM treatments can however never conceivably satisfy this requirement; rather they are justified with pre-scientific or unscientific paradigms. The high attractiveness of CAM measures evidenced in patients and many doctors is based on a combination of positive expectations and experiences, among other things, which are at times unjustified, at times thoroughly justified, from a science-oriented view, but which are non-specific (context effects). With a view to the latter phenomenon, the authors consider the conscious use of CAM as unrevealed therapeutic placebos to be problematic. In addition, they advocate that academic medicine should again systematically endeavour to pay more attention to medical empathy and use context effects in the service of patients to the utmost.The subsequent opinion discusses the following after an introduction to medical history: the definition of CAM; the efficacy of most common CAM procedures; CAM utilisation and costs in Germany; characteristics of science-oriented medicine; awareness of placebo research; pro and contra arguments about the use of CAM, not least of all in terms of aspects related to medical ethics