Das Endothel als Thromboregulator

The endothelium provides an anti-thrombotic surface which is an absolute requirement for intact circulation. It also has the ability to effectively support coagulation. Insufficient support of thrombus formation can have fatal consequences in the event of severe injury or damage to the vessel wall resulting in loss of the container function of the endothelium. However, thrombus formation needs to be strictly limited and controlled to avoid severe clinical consequences as a result of disturbed blood flow. Newer observations suggest that the endothelium might change from an anti- to a pro-thrombotic state even in the absence of any morphologically detectable lesion. It is assumed that such a change in the endothelium’s properties is caused by an “endothelial dysfunction” or “activation” of the endothelium as a consequence of on-going inflammatory processes, metabolic stress such as hyperglycaemia and hypoxia, cyto- and chemokines. The underlying mechanisms have not yet been elucidated in detail, but there is growing evidence that the formation of reactive oxygen species may trigger the expression of pro-thrombotic activities on the endothelial surface which require particular therapeutic attention.     

Das Parkinson-Syndrom als Modellerkrankung verschiedener Obstipationsformen

Constipation is a common problem in patients suffering from Parkinson’s disease. In Parkinson’s disease, the degenerative process may include both the nucleus of the vagal nerve in the brainstem and Onuf’s nucleus in the sacral spinal cord. Reduced vagal tone may inhibit gastrointestinal motility up to the left colonic flexure. Degeneration of the sacral parasympathetic neurons may reduce motility of the remaining segment of colon and sigmoid. In addition, degeneration of the myenteric and submucosal plexus may lead to intestinal atony. Disease-related immobility as well as the administration of anti-Parkinsonian medication contribute to constipation. The extrapyramidal disorder of anismus is another cause of outlet constipation. As all modes of dysfunction are also observed in non-Parkinsonian patients. Parkinson’s disease can be regarded a model disease for various types of constipation. The study of constipation in Parkinsonian patients is therefore highly suitable to evaluate novel diagnostic or therapeutic strategies.     

Das Renin-Angiotensin-Aldosteron-System als Zentraler Mediator der Progression der Niereninsuffizienz

The complex renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of renal insufficiency. Renin and aldosterone can contribute independently of ANG II to renal fibrosis via the induction of TGFβ synthesis. Genetic polymorphisms involving the components of RAAS, agonistic antibodies against the AT₁ receptor as well as AT₁ receptor dimers can all contribute further to deterioration in renal function. ACE inhibitors and AT₁ receptor antagonists in standard dosages incompletely inhibit intrarenal RAAS. To control blood pressure and proteinuria, ACE inhibitors or AT₁ receptor antagonists should be prescribed up to the recommended dose. Double blockade should be considered for patients with chronic renal failure and a proteinuria of more than 1 g/day. Recommendations for the additional use of aldosterone antagonists can currently not be made due to lack of data from clinical studies. Renin inhibitors are not yet licensed for the German market.     

Das Pankreaskarzinom

Zum Thema In jüngster Zeit konnte mit Hilfe der Molekularbiologie Licht in die Pathogenese des Pankreaskarzinoms und seiner Vorl?uferl?sionen, der duktalen pankreatischen intraepithelialen Neoplasien gebracht werden. Die Detektion des K-ras-Onkogens, z. B. hat zu einer deutlichen Erh?hung der Sensitivit?t der Diagnostik in Kombination mit den etablierten Verfahren geführt. Interessanterweise lassen sich bei der famili?ren Pankreatitis und beim Pankreaskarzinom spezifische Gendefekte finden. Daher ist bereits abzusehen, dass auf der Grundlage tumorbiologischer Erkenntnisse neue Therapiestrategien für das Pankreaskarzinom entwickelt werden.     

Das Lynch-Syndrom

Purpose

Lynch syndrome as the most common hereditary colorectal cancer syndrome and the most common cause of hereditary endometrial cancer is characterized by an autosomal dominant inheritance with a penetrance of 85–90%. The molecular genetic underlying mechanism is a mutation in one of the mismatch repair genes.

Methods

In order to identify patients with Lynch syndrome, a nuclear family history should be ascertained and matched with the Amsterdam criteria. A different approach for identification is the adherence to Bethesda criteria and subsequent testing for microsatellite instability. In patients with unstable tumors as an indicator for mismatch repair deficiency, genetic counseling and mutation analysis are warranted. For families fulfilling the Amsterdam criteria, intensified screening is recommended, even if a pathogenic mutation is not identified.

Results

Individuals from families with a proven pathogenic mutation that are tested negative are at normal population risk for cancers and may be dismissed from intensified surveillance. Prophylactic surgery in high-risk individuals without neoplasia is not generally recommended. At the time of a colon primary, however, extended surgery should be discussed in the light of a high rate of metachronous cancers. The worries of impairing functional results have now been evaluated in the light of quality of life in a large international cohort. Interestingly, extended (prophylactic) surgery does not lead to inferior quality of life with equal perioperative risks.

Conclusions

Therefore, taking the risk reduction into account, extended surgery at the time of the first colon primary should at least be discussed, if not recommended. Also, prophylactic hysterectomy and bilateral oophorectomy at the time of a colorectal primary should be recommended if family planning has been completed.