A toxicogenomic approach for identifying biomarkers for myelosuppressive anemia in rats

Myelosuppressive anemia is a serious side effect associated with several drugs. Thus, there is an increasing demand for sensitive biomarkers for the early detection of myelosuppressive anemia during toxicological studies. We applied a toxicogenomic approach to identify useful biomarker genes reflecting myelosuppressive anemia in the rat liver. Expression of the hemoglobin beta chain complex (Hbb), aminolevulinic acid synthase 2 (Alas2), and cell division cycle 25 homolog B (Cdc25b) genes changed as a result of anemia induced by the myelosuppressive agents linezolid, cisplatin, and carboplatin, suggesting that these genes may be suitable biomarkers. Moreover, evaluation of perfused and unperfused livers indicated that changes in the expression of these genes originate in circulating reticulocytes in the liver. Erythroid differentiation-associated changes in expression of the Hbb, Alas2, and Cdc25b genes were confirmed in vitro using Friend leukemia cells. In conclusion, our current research provides novel evidence that gene expression in circulating reticulocytes contained in the liver changes dramatically under myelosuppressive conditions. While further large-scale validation studies are needed, our results indicate that the genes we identified might be useful biomarkers for the sensitive detection of myelosuppressive anemia in rats.     

Effect of linezolid against postneurosurgical meningitis caused by methicillin-resistant <Emphasis Type="Italic">Staphylococcus epidermidis</Emphasis>: case report

A 67-year-old man who had twice previously undergone operations for a tuberculum sellae meningioma was admitted to hospital for further treatment. After the third surgical intervention, the patient developed persistent low-grade fever and impaired consciousness. Computed tomography, 1 week after surgery, showed postsurgical hydrocephalus. Cerebrospinal fluid (CSF) studies revealed high intracranial pressure (above 30 cm H₂O), and increased cell count (1232/3). One week after the ventricular drainage, coagulase-negative Staphylococcus epidermidis was recovered from his CSF, and antimicrobial susceptibility results indicated that the organism was methicillin-resistant. After 14 days of intravenous vancomycin (VCM) administration failed, linezolid (LZD) was initialized intravenously, resulting in a resolution of the meningitis. After a ventriculoperitoneal shunt procedure was performed, LZD was continued orally, which resulted in a cure. CSF penetration by VCM is reported to be poor, i.e., approximately 10% of serum concentration, which may explain its lack of efficacy. In this case, the penetration of LZD into the CSF was 58.9% of the peak value and 133% of the trough value of serum concentrations. LZD must be considered one of the first-line treatments against surgical-site infection in neurosurgery caused by methicillin-resistant Staphylococci.     

Undifferentiated Nasopharyngeal Carcinoma in Children: a report of four cases

Abstract

Nasopharyngeal carcinoma in early stages in children is a highly curable neoplasm. The major cause of treatment failure is the development of distant metastases, predominantly in advanced stages. This paper reports about four young patients with undifferentiated nasopharyngeal carcinoma treated with preradiation chemotherapy, locoregional radiotherapy and maintenance chemotherapy up to a total period of two years. Treating these four children, we noticed that preradiation chemotherapy caused satisfactory regression of the primary tumor. Three patients are still without signs of disease after 28 to 88 months and one died due to tumor progression. Further studies have to confirm our observations and support research in designing the optimal combination of effective chemotherapeutic agents and radiotherapy.     

Antimicrobial susceptibility testing of Mycobacteroides (Mycobacterium) abscessus complex,Mycolicibacterium (Mycobacterium) fortuitum,and Mycobacteroides (Mycobacterium) chelonae

The drug susceptibility of rapidly growing mycobacteria (RGM) varies among isolates. Treatment strategies similarly differ depending on the isolate, and for some, no clear strategy has been identified. This complicates clinical management of RGM. Following Clinical and Laboratory Standards Institute standard M24-A2, we assessed the susceptibility of 140 RGM isolates to 14 different antimicrobial drugs by measuring their minimal inhibitory concentrations (MICs). We also investigated the correlation of clarithromycin (CAM) MICs with the erm(41) and rrl gene mutations in the Mycobacteroides (Mycobacterium) abscessus complex, the rrl mutation in Mycobacteroides (Mycobacterium) chelonae, and the erm(39) mutation in Mycolicibacterium (Mycobacterium) fortuitum to determine the contribution of these mutations to CAM susceptibility. The five species and subspecies examined included 48 M. abscessus subsp. abscessus isolates (34.3%), 35 (25.0%) being M. abscessus subsp. massiliense, and two (1.4%) being M. abscessus subsp. bolletii. The M. abscessus complex accounted for 85 isolates (60.7%) in total, whereas 43 isolates (30.7%) were M. fortuitum, and 12 (8.6%) were M. chelonae. Our results demonstrated species-specific susceptibility to antimicrobials. In most cases, susceptibility to CAM could be predicted based on genetic pattern, but since one isolate did not fit that pattern, MIC values needed to be measured. Some isolates also exhibited rates of resistance to other drugs that differed from those previously reported in other locations, indicating that accurate identification of the bacterial isolate and use of the correct method for determining MIC are both important for the diagnosis of RGM.