Review of current classifications for diverticular disease and a translation into clinical practice

Introduction  

Diverticular disease of the sigmoid colon prevails in Western society. Its presentation may vary greatly per individual patient, from symptomatic diverticulosis to perforated diverticulitis. Since publication of the original Hinchey classification, several modifications and new grading systems have been developed. Yet, new insights in the natural history of the disease, the emergence of the computed tomography scan, and new treatment modalities plead for evolving classifications.     

APOE1 mutation in a patient with type III hyperlipoproteinaemia: detailed genetic analysis required

We present the case of a patient with clinical features of familial dysbetalipoproteinaemia (FD) including high levels of total cholesterol, hypertriglyceridaemia and the presence of palmar xanthomas. Whereas genotype analysis identified the APOE3E3 isoform, sequence analysis revealed the presence of one APOE1 allele due to a mutation, p.Lys164Glu, which leads to loss of function of apolipoprotein E (ApoE), a rare cause of dominant FD.     

Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis

The pronounced daily variation in the release of adrenal hormones has been at the heart of the deciphering and understanding of the circadian timing system. Indeed, the first demonstration of an endocrine day/night rhythm was provided by Pincus (1943), by showing a daily pattern of 17-keto-steroid excretion in the urine of 7 healthy males. Twenty years later the adrenal gland was one of the very first organs to show, in vitro, that circadian rhythmicity was maintained. In the seventies, experimental manipulation of the daily corticosterone rhythm served as evidence for the identification of respectively the light- and food-entrainable oscillator. Another 20 years later the hypothalamo-pituitary-adrenal (HPA)-axis was key in furthering our understanding of the way in which rhythmic signals generated by the central pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) are forwarded to the rest of the brain and to the organism as a whole. To date, the adrenal gland is still of prime importance for understanding how the oscillations of clock genes in peripheral tissues result in functional rhythms of these tissues, whereas it has become even more evident that adrenal glucocorticoids are key in the resetting of the circadian system after a phase-shift. The HPA-axis thus still is an excellent model for studying the transmission of circadian information in the body.     

Treatment with high-dose simvastatin inhibits geranylgeranylation in AML blast cells in a subset of AML patients

It is currently unknown whether the in?vitro effects observed with statins in acute myeloid leukemia (AML) cells, including lowering of cholesterol, inhibition of isoprenylation, and sensitization to chemotherapy, also occur in?vivo. Therefore, AML mononuclear cells (MNCs) were isolated from 12 patients before and after 7 days of high-dose (7.5-15 mg/kg/day) simvastatin treatment. Parallel mouse studies were performed to have, in addition to AML cells, access to liver tissue, a major target of statins. Serum cholesterol levels were lowered by simvastatin in all patients, however, only limited changes in the messenger RNA expression of cholesterol metabolism genes were seen in patient and mouse MNCs compared to murine liver cells. Still, two out of seven patients displayed an increased in?vitro chemosensitivity of their AML cells upon simvastatin treatment. Gene set enrichment analysis on microarray data of AML patient cells and Western blot analysis for the isoprenylated proteins DnaJ and Rap1 on murine and AML patient MNCs demonstrated that in?vivo simvastatin treatment resulted in inhibition of geranylgeranylation in murine MNCs and in a subset of patient AML MNCs. In summary, our data demonstrate that simvastatin treatment results in chemosensitization and inhibition of geranylgeranylation in AML cells of a subset of patients.     

A giant aneurysm of the popliteal vein

Popliteal vein aneurysm is a rare diagnosis, associated with a 70 % risk of pulmonary embolism, sometimes even with fatal evolution. Surgery dramatically reduces the risk of pulmonary embolism. We report a case of a 66-year-old man with recurrent pulmonary embolism and a giant popliteal venous aneurysm (9.3 × 4 × 4 cm) presenting at our dermatological clinic.