Young child with fever of unknown origin in the 'post Haemophilus influenzae era']

A 2.5-year-old boy and a 2-month-old girl presented with fever without an apparent source. Additional laboratory tests were requested due to alarming signs for the presence of a serious bacterial infection. Pneumonia and viral meningitis respectively were diagnosed, and adequate therapy led to a quick and complete recovery. Due to changing prospects following the near eradication of invasive Haemophilus influenzae type b (Hib) infections by vaccination, there are no suitable guidelines at present concerning fever without an apparent source in children. A selection of patients at risk can first of all be made based on patient history and a physical examination and secondly by carrying out additional laboratory tests. Furthermore, careful evaluation, clinical acumen, well-informed parents and observation are all important elements in the treatment of these patients.     

乳酸脱氢酶实验检测细胞新陈代谢的实验研究

目的 探索LDH实验检测细胞活力的可行性。方法 原代培养骨髓细胞和软骨细胞，用LDH实验测定上述两组细胞的活力，并与镜下活体观察到细胞的生长状况相比较。与目前比较成熟的测定细胞活力的MTS实验的测得的值相比较。结果 LDH实验对上述两组细胞的活力的测定结果与镜下活体观察到的结果相符合。与MTS实验的测得的结果经统计学处理无显著差异。结论 LDH实验可用于细胞活力的直接测定，而对活细胞的生存、繁殖无影响。     

Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism

Parathyroid hormone secretion is negatively regulated by a 7- transmembrane domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation. We also identified a de novo, missense Ca(2+)-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor. The other mutations involved the transmembrane region. Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations. Their greater hypercalciuria presumably reflected activation of Ca(2+)-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption. This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy.      

Preserved contribution of nitric oxide to baseline vascular tone in deconditioned human skeletal muscle

Deconditioning is a risk factor for cardiovascular disease. Exercise reduces this risk, possibly by improving the vascular endothelial nitric oxide (NO) pathway. The effect of deconditioning on the NO pathway is largely unknown. This study was designed to assess baseline NO availability in the leg vascular bed after extreme, long-term deconditioning (spinal cord-injured individuals, SCI) as well as after moderate, short-term deconditioning (4 weeks of unilateral lower limb suspension, ULLS). For this purpose, seven SCI were compared with seven matched controls. Additionally, seven healthy subjects were studied pre- and post-ULLS. Leg blood flow was measured by venous occlusion plethysmography at baseline and during infusion of 5 incremental dosages of N ^G-monomethyl- l -arginine ( l -NMMA) into the femoral artery. Sodium nitroprusside (SNP) was infused to test vascular responsiveness to NO. Baseline leg vascular resistance tended to be higher in SCI compared with controls (37 ± 4 versus 31 ± 2 arbitrary units (AU), P = 0.06). Deconditioning altered neither the vasoconstrictor response to l -NMMA (increase in resistance in SCI versus controls: 102 ± 33% versus 69 ± 9%; pre- versus post-ULLS: 95 ± 18% versus 119 ± 15%), nor the vascular responsiveness to NO. In conclusion, two human in vivo models of deconditioning show a preserved baseline NO availability in the leg skeletal muscle vascular bed.     

Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung

Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic hydrocarbon, is the most potent carcinogen ever tested in mouse skin and rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction, tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in strain A/J mouse lung. Groups of mice received a single i.p. injection of 0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment, DNA adducts were measured at times between 1 and 28 days, while tumors were counted at 250 days and analyzed for the occurrence of point mutations in codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung induced six major and four minor DNA adducts. Maximal levels of adduction occurred between 5 and 10 days after injection followed by a gradual decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti- and syn-11,12- dihydroxy-13,14-epoxy- 11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed by cochromatography. The major adduct was identified as a product of the reaction of an anti-DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced significant numbers of lung adenomas in a dose- dependent manner, with the highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based on the administered dose, DB[a,l]P was more active than other environmental carcinogens including benzo[a]pyrene. As a function of time-integrated DNA adduct levels, DB[a,l]P induced lung adenomas with about the same potency as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar in carcinogenic potency to other PAHs in the strain A/J mouse lung model. Analysis of the Ki- ras mutation spectrum in DB[a,l]P-induced lung tumors revealed the predominant mutations to be G-->T transversions in the first base of codon 12, A-->G transitions in the second base of codon 12, and A-->T transversions in the second or third base of codon 61, concordant with the DNA adduct profile.      

Considerations on the EU definition of a nanomaterial: Science to support policy making

In recent years, an increasing number of applications and products containing or using nanomaterials have become available. This has raised concerns that some of these materials may introduce new risks for humans or the environment. A clear definition to discriminate nanomaterials from other materials is prerequisite to include provisions for nanomaterials in legislation. In October 2011 the European Commission published the ‘Recommendation on the definition of a nanomaterial’, primarily intended to provide unambiguous criteria to identify materials for which special regulatory provisions might apply, but also to promote consistency on the interpretation of the term ‘nanomaterial’. In this paper, the current status of various regulatory frameworks of the European Union with regard to nanomaterials is described, and major issues relevant for regulation of nanomaterials are discussed. This will contribute to better understanding the implications of the choices policy makers have to make in further regulation of nanomaterials. Potential issues that need to be addressed and areas of research in which science can contribute are indicated. These issues include awareness on situations in which nano-related risks may occur for materials that fall outside the definition, guidance and further development of measurement techniques, and dealing with changes during the life cycle.     

Mythos OP-Minute

The economic situation in German Hospitals is tense and needs the implementation of differentiated controlling instruments. Accordingly, parameters of revenue development of different organizational units within a hospital are needed. This is particularly necessary in the revenue and cost-intensive operating theater field. So far there are only barely established productivity data for the control of operating room (OR) revenues during the year available. This article describes a valid method for the calculation of case-related revenues per OR minute conform to the diagnosis-related groups (DRG).