Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation.

Mutations in MECP2 cause Rett syndrome, a severe neurological disorder with autism-like features. Duplication of MECP2 also causes severe neuropathology. Both diseases display immunological abnormalities that suggest a role for MECP2 in controlling immune and inflammatory responses. Here, we used mecp2-null zebrafish to study the potential function of Mecp2 as an immunological regulator. Mecp2 deficiency resulted in an increase in neutrophil infiltration and upregulated expression of the pro- and anti-inflammatory cytokines Il1b and Il10 as a secondary response to disturbances in tissue homeostasis. By contrast, expression of the proinflammatory cytokine tumor necrosis factor alpha (Tnfa) was consistently downregulated in mecp2-null animals during development, representing the earliest developmental phenotype described for MECP2 deficiency to date. Expression of tnfa was unresponsive to inflammatory stimulation, and was partially restored by re-expression of functional mecp2 Thus, Mecp2 is required for tnfa expression during zebrafish development and inflammation. Finally, RNA sequencing of mecp2-null embryos revealed dysregulated processes predictive for Rett syndrome phenotypes.

[Dementia care in Germany]. / Dementiezorg in Duitsland.

In Germany there are approximately 1.6 million people with dementia. A quarter of them live in a care home, often alongside residents who have a physical condition. The quality of nursing for physical conditions is good; although specialised dementia care is less developed, this lag is slowly being addressed. Medical care in German care homes is delivered by GPs. Preservation of life is the norm. Due to the lack of both advance care planning and a non-resuscitation policy, many care home residents with dementia undergo life-extending measures. Through the use of an advance health care directive, people can protect themselves from such a situation occurring.

Clinical relevance of advanced glycation endproducts for vascular surgery.

Atherosclerosis is the main contributor to cardiovascular disease and leads to intimal plaque formation, which may progress to plaque rupture with subsequent thromboembolic events and/or occlusion of the arterial lumen. There is increasing evidence that the development or progression of atherosclerosis is associated with advanced glycation endproducts (AGEs). AGEs are a heterogeneous group of compounds formed by the non-enzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. An increased understanding of the mechanisms of formation and interaction of AGEs has allowed the development of several potential anti-AGE strategies. This review summarizes AGE formation and biochemistry, the pathogeneic role of AGEs in cardiovascular disease, anti-AGE therapies and clinical relevance to vascular surgery.

Application of PET/SPECT imaging in vascular disease.

BACKGROUND: Nuclear medicine imaging differs from other imaging modalities by showing physiological processes instead of anatomical details. OBJECTIVE: To describe the current applications of positron emission tomography (PET) and single photon emission computed tomography (SPECT) as a diagnostic tool for vascular disease as relevant to vascular surgeons. METHODS: A literature search identified articles focussing on vascular disease and PET or SPECT using the Pubmed database. Manual cross referencing was also performed. RESULTS: PET and SPECT may be used to assess plaque vulnerability, biology of aneurysm progression, prosthetic graft infection, and vasculitis. The ability to combine computerized tomography scanning or magnetic resonance imaging with PET or SPECT adds detailed anatomical information and enhances the potential of nuclear medicine imaging in the investigation of vascular disease. DISCUSSION: Considerable further information will be needed to define whether and where PET or SPECT will fit in a clinical strategy. The necessary validation studies represent an exciting challenge for the future but also may require the development of interdisciplinary imaging groups to integrate expertise and optimize nuclear diagnostic potential.

Rectal carcinoma treated with short-term preoperative radiotherapy followed by abdominoperineal resection. Significantly more presacral abscesses with absence of local recurrence.

BACKGROUND: Treatment of choice for rectal carcinoma is short-term preoperative radiotherapy (5 x 5 Gy) followed by a total mesorectal excision (TME) of the rectum. This treatment has led to a reduction in local recurrence 2 years after surgery from 8.2 to 2.4%. Side effects of this treatment seem to be marginal and of no consequence. After introduction of short-term preoperative radiotherapy we noticed a rise in the postoperative presacral abscess formation which is difficult to treat and results in readmissions and prolonged hospital stay. Research was needed to investigate whether short-term preoperative radiotherapy can be held accountable for the presumed rise in presacral abscess formation in the treatment of rectal carcinoma. METHODS: A retrospective study was performed over the period January 2000-October 2004. Two groups were formed. Group 1 existed of 30 patients who underwent a TME of the rectum without short-term preoperative radiotherapy. Group two existed of 35 patients who underwent a TME of the rectum with short-term preoperative radiotherapy. RESULTS: Statistical analysis showed a significant increase in presacral abscess formation (13 vs. 40%) after introduction of short-term preoperative radiotherapy. Radiotherapy proved to be an important risk factor. Reduction in incidence of local recurrence was not evident. CONCLUSION: We found a significant increase in presacral abscess formation strongly suggestive due to the introduction of short-term preoperative radiotherapy in the treatment of rectal carcinoma. We noticed no reduction in incidence of local recurrence. We advocate that additional research is needed in order to formulate extra patient selection criteria for the use of preoperative radiotherapy in the treatment of rectal cancer.