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A specific and automated method was developed to quantitate the aminoglycosides amikacin, gentamicin, kanamycin, neomycin, paromomycin, and tobramycin simultaneously in human serum. Samples were prepared with an automated solid phase extraction (SPE). The hydrophilic interaction chromatography (HILIC) was used for separation of analytes from endogenous compounds and baseline separation. The aminoglycosides were detected with electrospray ionisation tandem mass spectrometry (ESI-MS-MS). Using a volume of 500 microl biological sample the lower limits of quantification were 100 ng/ml or better. The described HILIC-MS-MS method is suitable for therapeutic drug monitoring and for clinical and pharmcokinetical investigations of the aminoglycosides.

There have only been few investigations comparing total fluoride intake and the fluoride proportion excreted in urine in pre–school children. In addition, the results of available studies are conflicting. Total fluoride intake was assessed in 11 healthy children aged 3–6 years on 2 consecutive days and urinary fluoride excretion was determined. The duplicate–diet approach was used for the assessment of fluoride intake from solid and liquid foods. Fluoride intake from toothbrushing was calculated as the difference between the amount of fluoride in the paste put on the toothbrush and the drinking water (fluoride concentration 0.25 mg/l) used for rinsing vs. the fluoride amounts recovered in the toothpaste spat out and in the rinsing water. Use of fluoridated domestic salt and/or fluoride tablets was recorded. The children’s intake of fluoride from food averaged 202.5±116.2 µg F/day. They swallowed an average amount of 273.9±175.6 µg F/day when brushing their teeth. Daily fluoride ingestion from all sources totalled 930.7±391.5 µg or 53.0±21.4 µg/kg body weight. On average 51.5% of the fluoride ingested was excreted in urine. The wide interindividual variation makes it necessary to evaluate the urinary excretion rate for fluoride in larger study populations with varied fluoride exposure.

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ObjectiveThe intestinal epithelium is a rapidly renewing tissue which plays central roles in nutrient uptake, barrier function and the prevention of intestinal inflammation. Control of epithelial differentiation is essential to these processes and is dependent on cell type-specific activity of transcription factors which bind to accessible chromatin. Here, we studied the role of SET Domain Bifurcated Histone Lysine Methyltransferase 1, also known as ESET (SETDB1), a histone H3K9 methyltransferase, in intestinal epithelial homeostasis and IBD.DesignWe investigated mice with constitutive and inducible intestinal epithelial deletion of Setdb1, studied the expression of SETDB1 in patients with IBD and mouse models of IBD, and investigated the abundance of SETDB1 variants in healthy individuals and patients with IBD.ResultsDeletion of intestinal epithelial Setdb1 in mice was associated with defects in intestinal epithelial differentiation, barrier disruption, inflammation and mortality. Mechanistic studies showed that loss of SETDB1 leads to de-silencing of endogenous retroviruses, DNA damage and intestinal epithelial cell death. Predicted loss-of-function variants in human SETDB1 were considerably less frequently observed than expected, consistent with a critical role of SETDB1 in human biology. While the vast majority of patients with IBD showed unimpaired mucosal SETDB1 expression, comparison of IBD and non-IBD exomes revealed over-representation of individual rare missense variants in SETDB1 in IBD, some of which are predicted to be associated with loss of function and may contribute to the pathogenesis of intestinal inflammation.ConclusionSETDB1 plays an essential role in intestinal epithelial homeostasis. Future work is required to investigate whether rare variants in SETDB1 contribute to the pathogenesis of IBD.

Cerebral involvement of systemic mastocytosis and intracranial sarcoma of myelogenic origin are well known entities. An 8-year-old girl with an isolated cerebral mast cell tumor is presented. Specific histopathologic stains were used to confirm the diagnosis detecting immunophenotype and proliferative activity. Treatment with irradiation, intrathecal cytarabine, and interferon-alpha2b did not induce regression whereas polychemotherapy did. Systemic combination chemotherapy led to marked transient tumor regression in this proliferating mast cell sarcoma in an unusual intracranial location.

The data suggest that allergic sensitization to GCR is less frequent in asthmatics from Dresden, Germany than in US cities. The data indicate that GCR sensitization is not an independent risk factor for asthma and other atopic diseases in 5-11-year-olds from this city.

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