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Byline: A.S. Zinkernagel (1), R. Gmur (2), L. Fenner (1), A. Schaffner (1), G. Schoedon (1), M. Schneemann (1) Abstract: Background: DNA of Tropheryma whipplei, the etiologic agent of Whipple's disease, has recently been detected in the saliva of healthy subjects. In this pilot study we searched for the habitat of T. whipplei within the oral cavity. Materials and Methods: Samples from different oral sites were obtained from periodontically healthy volunteers, patients with progressive periodontitis and Chinese subjects with necrotizing ulcerative gingivitis or gingivitis. Quantitative real-time PCR was performed using T. whippleispecific primers, human [beta]-globin-specific primers to control for tissue DNA extraction and PCR reaction and broad-range eubacterial primers to control for bacterial DNA extraction. T. whipplei specificity of multiple amplicons was confirmed by sequencing. The detection limit of the method was 10 ag of T. whipplei DNA, corresponding to one to five bacteria under reference assay conditions. Results: T. whipplei was found in the oral cavity of four out of ten healthy individuals from hospital staff and in three out of nine periodontitis patients, but in none of the individuals from China. All positive samples derived from subgingival and gingival sulcus plaque containing between 10.sup.3 and 5 x 10.sup.5 cells ml.sup.-1 of plaque suspension, whereas saliva, smooth surface plaque and samples from the tongue or cheeks were negative. Conclusion: Our results suggest that T. whipplei colonizes the human body via the oral cavity and that bacterial plaques of the gingival crevice and the gingival sulcus/pocket may serve as a natural primary habitat. Author Affiliation: (1) Dept. of Medicine, University Hospital, Ramistrasse 100, CH-8091 Zurich, Switzerland. markus.schneemann@dim.usz.ch, CH (2) Institute of Oral Microbiology and General Immunology, Center for Dental and Oral Medicine and Maxillofacial Surgery, University of Zurich, Switzerland, CH Article note: Received: June 11, 2002 * Revision accepted: October 6, 2002 M. Schneemann (corresponding author)

Purpose: Hyperkalaemia due to potassium-increasing drug-drug interactions (DDIs) is a clinically important adverse drug event. The purpose of this study was to identify patient- and physician-related risk factors for the development of hyperkalaemia., Methods: The risk for adult patients hospitalised in the University Hospital Zurich between 1 December 2009 and 31 December 2011 of developing hyperkalaemia was correlated with patient characteristics, number, type and duration of potassium-increasing DDIs and frequency of serum potassium monitoring., Results: The 76,467 patients included in this study were prescribed 8,413 potentially severe potassium-increasing DDIs. Patient-related characteristics associated with the development of hyperkalaemia were pulmonary allograft [relative risk (RR) 5.1; p < 0.0001), impaired renal function (RR 2.7; p < 0.0001), diabetes mellitus (RR 1.6; p = 0.002) and female gender (RR 1.5; p = 0.007). Risk factors associated with medication were number of concurrently administered potassium-increasing drugs (RR 3.3 per additional drug; p < 0.0001) and longer duration of the DDI (RR 4.9 for duration ≥6 days; p < 0.0001). Physician-related factors associated with the development of hyperkalaemia were undetermined or elevated serum potassium level before treatment initiation (RR 2.2; p < 0.001) and infrequent monitoring of serum potassium during a DDI (interval >48 h: RR 1.6; p < 0.01)., Conclusion: Strategies for reducing the risk of hyperkalaemia during potassium-increasing DDIs should consider both patient- and physician-related risk factors.

In the study presented here a LightCycler real-time PCR system was used for the diagnosis of fungal infections from clinical tissue samples. Nine specimens were investigated from six patients with suspected or proven invasive fungal infections. Seven of nine samples were positive in a broad-range fungal PCR assay. In four samples, Aspergillus fumigatus was detected both by a species-specific hybridization assay as well as by sequencing of amplification products. In addition, the broad-range fungal PCR assay and PCR sequencing detected and identified, respectively, the following organisms in the specimens noted: Candida albicans in a culture-negative liver biopsy, Histoplasma capsulatum in a bone marrow sample, and Conidiobolus coronatus in a facial soft tissue specimen. Real-time PCR is a promising tool for the diagnosis of invasive fungal infections in human tissue samples and offers some advantages over culture methods, such as rapid analysis and increased sensitivity.

This report describes a 57-year-old female patient with chronic lumbago, who died from the sequelae of acute liver failure induced by nimesulide medication. Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclo-oxygenase 2 and has been associated with a total of 13 reported cases of severe liver injury including our case. On the basis of the literature reports, the following features of nimesulide-associated hepatotoxicity were identified: female sex (84% of cases), age (mean age 62 years), jaundice as a primary manifestation (90%) and the absence of peripheral blood eosinophilia. The average duration of therapy of the published cases was 62 days (range 7-180 days). Based on spontaneous reports to the World Health Organization, nimesulide induces a high proportion of severe adverse hepatic reactions compared with other NSAIDs registered in Switzerland. Hepatotoxicity thus represents an important risk factor of nimesulide usage.