Otoacoustic emissions as a screening test for hearing impairment in children

Transient evoked otoacoustic emissions (TEOAEs) are low amplitude sound waves produced by the healthy cochlea. They can be recorded with a microphone in the external ear. TEOAEs are abolished by hearing losses of 30 dB or more. The feasibility of using TEOAEs as a screening test for hearing loss in children was studied. TEOAE recordings were attempted in 56 children attending an audiology clinic. Recordings were possible from both ears in 52 children; of these 104 ears, 32 had hearing deficits of 30 dB or more. Hearing status was compared with the results of six TEOAE screening criteria. All criteria had a sensitivity of 1.00. Four standard TEOAE criteria yielded specificities of 0.46-0.58. Two new criteria derived from analysis of limited frequencies from the TEOAE waveform gave specificities of 0.76 and 0.82. It can be concluded that, when appropriate pass/fail criteria are employed, TEOAEs are a feasible screening test in children.     

Bacterial and mammalian DNA alkyltransferases sensitize Escherichia coli to the lethal and mutagenic effects of dibromoalkanes

Here we confirm and extend our previous studies demonstrating that the mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is markedly enhanced (not prevented) in bacteria expressing the O6- alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli ogt gene. We demonstrate that, in close parallel with mutagenesis, the Ogt ATase sensitizes the bacteria to the lethal effects of these carcinogens, suggesting that one or more of the potentially mutagenic lesions induced by DBE and DBM in the presence of Ogt has additional lethal capacity. We further demonstrate that the sensitization to both lethality and mutagenesis by DBE and DBM is a property shared by other DNA alkyltransferases. This objective was accomplished by quantifying the induction of mutations and lethal events in ogt- ada- E. coli expressing an exogenous bacterial or mammalian ATase from a multicopy plasmid. Mammalian recombinant ATases enhanced the lethal and mutagenic actions of DBE and suppressed the lack of sensitivity of the vector- transformed bacteria to DBM. In most cases the order of effectiveness of the ATases ranked: murine > human > Ogt > rat. Further comparisons included the full-length Ada ATase from E. coli and a truncated Ada version (T-ada) that retains the O6-methylguanine binding domain of the protein. The full-length Ada ATase was effective in enhancing the lethality but not the mutagenicity induced by DBE and DBM. The T-ada ATase provided less sensitization than Ada to lethality by DBE, but of the three bacterial ATases T-ada yielded the highest sensitization to mutagenesis by this compound. T-ada and Ada ATases were in general less effective than the mammalian versions, with the exception of the rat recombinant ATase. The effectiveness of the different mammalian and bacterial ATases in promoting the deleterious actions of dibromoalkanes was compared with the effectiveness of these proteins in suppressing the lethal and mutagenic effects induced by N-nitroso-N-methylurea. The ability to sensitize E. coli to the lethal and mutagenic effects of DBE and DBM seems restricted to DNA alkyltransferase, since overexpression of thioredoxin (Trx) or glutaredoxin (Grx1) in ogt- ada- cells showed no effect, in spite of the reported potential of bioactive dihaloethane- derived species to alkylate Trx.      

Sensitivity of Escherichia coli (MutT) and human (MTH1) 8-oxo-dGTPases to in vitro inhibition by the carcinogenic metals, nickel(II), copper(II), cobalt(II) and cadmium(II)

The toxicity of Ni(II), Co(II) and Cu(II) in animals, and that of Cd(II) in cultured cells, has been associated with generation of the promutagenic lesion 8-oxo-7,8-dihydroguanine (8-oxoguanine) in DNA, among other effects. One possible source of this base may be 8-oxo-7,8- dihydro-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP), a product of oxidative damage to the nucleotide pool, from which it is incorporated into DNA. To promote such incorporation, the metals would have to inhibit specific cellular 8-oxo-dGTPases that eliminate 8-oxo-dGTP from the nucleotide pool. The present study was designed to test such inhibition in vitro on 8-oxo-dGTPases from two different species, the human MTH1 protein and Escherichia coli MutT protein. In the presence of Mg(II), the natural activator of 8-oxo-dGTPases, all four metals were found to inhibit both enzymes. For MTH1, the IC50 values (+/- SE; n = 3-4) were 17 +/- 2 microM for Cu(II), 30 +/- 8 microM for Cd(II), 376 +/- 71 microM for Co(II) and 801 +/- 97 microM for Ni(II). For MutT, they were 60 +/- 6 microM for Cd(II), 102 +/- 8 microM for Cu(II), 1461 +/- 96 microM for Ni(II) and 8788 +/- 1003 microM for Co(II). Thus, Cu(II) and Cd(II) emerged as much stronger inhibitors than Ni(II) and Co(II), and MTH1 appeared to be generally more sensitive to metal inhibition than MutT. Interestingly, in the absence of Mg(II), the activity of the enzymes could be restored by Co(II) to 73% of that with Mg(II) alone for MutT, and 34% for MTH1, the other metals being much less or non-effective. The difference in sensitivity to metal inhibition between the two enzymes may reflect the differences in the amino acid ligands, especially the cysteine ligand, outside their evolutionarily conserved Mg(II)-binding active sites, which might indicate predominantly non-competitive or uncompetitive mechanism of the inhibition. The overall results suggest that inhibition of 8-oxo- dGTPases may be involved in the mechanisms of induction of the 8- oxoguanine lesion in DNA by the metal ions studied, especially the non- redox-active Cd(II) cation.      

Selective reduction of bone blood flow by short-term treatment with high-dose methylprednisolone. An experimental study in pigs

Treatment with corticosteroids is a risk factor for non-traumatic avascular necrosis of the femoral head, but the pathological mechanism is poorly understood. Short-term treatment with high doses of methylprednisolone is used in severe neurotrauma and after kidney and heart transplantation. We investigated the effect of such treatment on the pattern of perfusion of the femoral head and of bone in general in the pig. We allocated 15 immature pigs to treatment with high-dose methylprednisolone (20 mg/kg per day intramuscularly for three days, followed by 10 mg/kg intramuscularly for a further 11 days) and 15 to a control group. Perfusion of the systematically subdivided femoral head, proximal femur, acetabulum, humerus, and soft tissues was determined by the microsphere technique. Blood flow in bone was severely reduced in the steroid-treated group. The reduction of flow affected all the segments and the entire epiphysis of the femoral head. No changes in flow were found in non-osseous tissue. Short-term treatment with high-dose methylprednisolone causes reduction of osseous blood flow which may be the pathogenetic factor in the early stage of steroid-induced osteonecrosis.     

Hyperbilirubinemia, hypocarbia and periventricular leukomalacia in preterm infants: relationship to cerebral palsy

This study comprised 103 preterm infants with a gestational age less than 33 weeks who were born in Tampere University Hospital and who were followed up to two years of age. Sixty-four perinatal variables were compared to ultrasound findings in the neonatal period and neurologic handicap at the age of two years. Duration of hypocarbia (PCO2 < or = 30 mmHg) during the first 72 h and hyperbilirubinemia (the mean level of serum total bilirubin) at three days of age were independently and significantly related to periventricular leukomalacia, but not directly to cerebral palsy. The only perinatal variables related independently and significantly to cerebral palsy at two years of age were periventricular leukomalacia and ventriculomegaly. According to these results, periventricular leukomalacia was the main predictor of cerebral palsy in preterm infants. In addition to hypocarbia, hyperbilirubinemia may also be involved in the pathogenesis of extensive (severe cystic) periventricular leukomalacia.     

Diffusion-weighted MR imaging after angioplasty or angioplasty plus stenting of arteries supplying the brain

BACKGROUND AND PURPOSE: There has been concern regarding the safety of revascularization procedures of vessels supplying the brain vessels because of the risk of cerebral embolization during the procedure. We have observed a high incidence of hyperintense lesions on diffusion-weighted MR images of the brain after stenting at the carotid bifurcation. The hypothesis of this study is that diffusion-weighted MR imaging of the brain can reveal new diffusion abnormalities after angioplasty or angioplasty plus stenting of arteries supplying the brain, other than at the carotid bifurcation. Therefore, we prospectively obtained diffusion-weighted MR images of the brain before and after such revascularization procedures. METHODS: Thirty-seven revascularization procedures were performed in 32 patients. Eleven interventions were performed at the distal internal carotid artery, two at the external carotid artery, two at the common carotid artery, five at the innominate artery, five at the vertebral artery, and 12 at the proximal subclavian artery. Diffusion-weighted MR imaging of the brain was performed before and 24 hours after the procedures. RESULTS: After eight (22%) of 37 procedures, new hyperintensities were visible on the diffusion-weighted MR images. With six of these eight procedures, the hyperintensities occurred in the vascular territory supplied by the treated vessel. In total, 35 new cerebral lesions could be seen, 33 (94%) of which occurred in the vascular territory supplied by the treated vessel. None of the patients in whom new diffusion abnormalities were found had new neurologic symptoms or deficits. No new lesions could be seen after procedures at the subclavian artery. CONCLUSION: Revascularization procedures of arteries supplying the brain were associated with new lesions on the diffusion-weighted MR images of the brain after 22% of the procedures, provided that MR imaging could be performed, indicating the occurrence of cerebral microemboli during such procedures. Diffusion-weighted MR imaging of the brain can be used as a tool to assess the impact of modifications of procedural technique and/or the use of cerebral protection devices on the occurrence of such lesions.     

Materialtechnische Besonderheiten orthodontischer Nickel-Titan-Drähte

Zusammenfassung Seit ihrer Einführung 1971 finden Nickel-Titan-Legierungen in großem Umfang Anwendung in der Kieferorthopädie. Heute existiert ein breites Angebot weiterentwickelter Legierungen, deren besondere Eigenschaften beschrieben werden. Orthodontische NiTi-Drähte gehören zu den Formgedächtnislegierungen. Neben dem Memory-Effekt zeichnen sie sich durch besondere Elastizitätseigenschaften aus, die durch niedriges Elastizitätsmodul, sehr hohes Deflektionsvermögen und Pseudoelastizität gekennzeichnet sind. Diese Merkmale basieren auf der Tatsache, daß diese Legierungen in Abhängigkeit von Temperatur und mechanischer Spannung in zwei Kristallstrukturen vorliegen: Martensit und Austenit. Der Übergang zwischen diesen Phasen, die martensitische Transformation, ist verantwortlich für den Memoryeffekt, bei dem ein Einweg- und ein Zweiwegeffekt unterschieden werden kann. Die für kieferorthopädische Anwendungen besonders günstig erscheinende Eigenschaft der Pseudoelastizität (Superelastizität) beruht auf der Erzeugung spannungsinduzierten Martensits. Die verfügbaren Drähte können in die Kategorien aufgehärteter Martensit und pseudoelastische Legierung eingeordnet werden. NiTi-Legierungen besitzen eine gute Biokompatibilität, die sie auch als Implantatmaterial geeignet erscheinen läßt.

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Summary Since their introduction in 1971 nickel-titanium wires have been widely used in orthodontics. Today, there is a multitude of new NiTi-alloys, whose properties are described. Beside the memory effect, these alloys have particular elastic properties, which can be characterized by a low modulus of elasticity, excellent springback, and pseudoelasticity (superelasticity). These properties are a consequence of the fact that depending on temperature and mechanical stress NiTi-alloys have two crystalline structures: martensite and austenite. The transition between these two phases, called martensitic transformation, is responsible for the memory effect, where a one way and a two way effect can be distinguished. For orthodontic applications pseudoelasticity is regarded as a highly favourable property. Pseudoelastic behavior is caused by stress induced martensite. Analysing the elastic properties of the available wires two categories can be distinguished: work hardended martensite and pseudoelastic alloy. The biocompatibility of NiTi is sufficient, it can be used as an implant material.

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Diese Arbeit wurde gefördert durch die Deutsche Forschungsgemeinschaft (Dr 196/1).