Pre-oxygenation using high-flow nasal oxygen vs. tight facemask during rapid sequence induction.

Pre-oxygenation using high-flow nasal oxygen can decrease the risk of desaturation during rapid sequence induction in patients undergoing emergency surgery. Previous studies were single-centre and often in limited settings. This randomised, international, multicentre trial compared high-flow nasal oxygen with standard facemask pre-oxygenation for rapid sequence induction in emergency surgery at all hours of the day and night. A total of 350 adult patients from six centres in Sweden and one in Switzerland undergoing emergency surgery where rapid sequence induction was required were included and randomly allocated to pre-oxygenation with 100% oxygen using high-flow nasal oxygen or a standard tight-fitting facemask. The primary outcome was the number of patients developing oxygen saturations <93% from the start of pre-oxygenation until 1 min after tracheal intubation. Data from 349 of 350 patients who entered the study were analysed (174 in the high-flow nasal oxygen group and 175 in the facemask group). No difference was detected in the number of patients desaturating <93%, five (2.9%) vs. six (3.4%) patients in the high-flow nasal oxygen and facemask group, respectively (p = 0.77). The risk of desaturation was not increased during on-call hours. No difference was seen in end-tidal carbon dioxide levels in the first breath after tracheal intubation or in the number of patients with signs of regurgitation between groups. These results confirm that high-flow nasal oxygen maintains adequate oxygen levels during pre-oxygenation for rapid sequence induction.

Multisensory enhancement of attention depends on whether you are already paying attention.

Multisensory stimuli are argued to capture attention more effectively than unisensory stimuli due to their ability to elicit a super-additive neuronal response. However, behavioural evidence for enhanced multisensory attentional capture is mixed. Furthermore, the notion of multisensory enhancement of attention conflicts with findings suggesting that multisensory integration may itself be dependent upon top-down attention. The present research resolves this discrepancy by examining how both endogenous attentional settings and the availability of attentional capacity modulate capture by multisensory stimuli. Across a series of four studies, two measures of attentional capture were used which vary in their reliance on endogenous attention: facilitation and distraction. Perceptual load was additionally manipulated to determine whether multisensory stimuli are still able to capture attention when attention is occupied by a demanding primary task. Multisensory stimuli presented as search targets were consistently detected faster than unisensory stimuli regardless of perceptual load, although they are nevertheless subject to load modulation. In contrast, task irrelevant multisensory stimuli did not cause greater distraction than unisensory stimuli, suggesting that the enhanced attentional status of multisensory stimuli may be mediated by the availability of endogenous attention. Implications for multisensory alerts in practical settings such as driving and aviation are discussed, namely that these may be advantageous during demanding tasks, but may be less suitable to signaling unexpected events.

The influence of humic substances on the speciation and bioavailability of dissolved mercury and methylmercury, measured as uptake by Chaoborus larvae and loss by volatilization.

The influence of dissolved humic substances (HS) on the bioavailability of dissolved inorganic and methyl mercury (Hg) was quantified by measuring the direct uptake of 203Hg in Chaoborus larvae using laboratory microcosms containing artificial freshwater. The animals were exposed individually in triplicate aquaria at 10 different concentrations of HS covering the whole range found in natural freshwaters (0-110 mg C l(-1)). Mercury-203 concentrations were monitored repeatedly in the same individuals and in their ambient water during up to 10 days. Near-steady state Hg concentrations in Chaoborus were usually reached within 5 days. The bioconcentration factor (BCF, direct uptake only) for the larvae in the absence of HS was 0.55+/-0.09 (S.E.) ml individual(-1) for inorganic Hg and 5.3+/-0.7 ml individual(-1) for methyl Hg, thus showing a 10-fold difference. Normalizing to the organic carbon content of the larvae yields a BCF(OC) in the absence of HS of 2.8+/-0.4 x 10(3) ml (gC)(-1) for inorganic Hg and 2.7+/-0.3 x 10(4) ml (gC)(-1) for methyl Hg. The uptake of both inorganic and methyl Hg decreased markedly with increasing concentration of HS. For inorganic Hg, the decrease in uptake was most pronounced at HS concentrations below 0.2 mg C l(-1). For methyl Hg, the relationship between uptake and log([HS]) was sigmoid, showing a reduction by > 90% when increasing HS concentrations from 1 to 50 mg C l(-1). Similar patterns were observed for losses of Hg from the water phase, mainly through volatilization. These results have implications for both the biouptake and the abiotic cycling of Hg in natural ecosystems and suggest that most dissolved inorganic Hg is bound to dissolved organic matter in most natural freshwaters, whereas dissolved methyl Hg is bound only in humic waters. Assuming that only free aqueous Hg is taken up by the organisms, the rather simple methodology employed here can be used for estimating distribution coefficients (K(OC)) for Hg between HS and water. In this study, the K(OC) values were 2.5+/-0.7 (S.E.) x 10(7) ml (gC)(-1) for inorganic Hg and 1.5+/-0.6 x 10(5) ml (gC)(-1) for methyl Hg. Values of similar magnitude were derived from observed losses of Hg from the water phase, supporting the assumption of an immobilization of both inorganic and methyl Hg by HS. The strong negative influence of dissolved HS on the bioavailability of both inorganic and methyl Hg in freshwater suggests that the high Hg levels often found in fish from humic lakes in the boreal forest zone cannot be explained alone by direct uptake of methyl Hg from the water phase into biota at low trophic levels.

An ATF/CRE element mediates both EBNA2-dependent and EBNA2-independent activation of the Epstein-Barr virus LMP1 gene promoter.

The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is a viral oncogene whose expression is regulated by both viral and cellular factors. EBV nuclear antigen 2 (EBNA2) is a potent transactivator of LMP1 expression in human B cells, and several EBNA2 response elements have been identified in the promoter regulatory sequence (LRS). We have previously shown that an activating transcription factor/cyclic AMP response element (ATF/CRE) site in LRS is involved in EBNA2 responsiveness. We now establish the importance of the ATF/CRE element by mutational analysis and show that both EBNA2-dependent activation and EBNA2-independent activation of the promoter occur via this site but are mediated by separate sets of factors. An electrophoretic mobility shift assay (EMSA) with specific antibodies showed that the ATF-1, CREB-1, ATF-2 and c-Jun factors bind to the site as ATF-1/CREB-1 and ATF-2/c-Jun heterodimers whereas the Sp1 and Sp3 factors bind to an adjacent Sp site. Overexpression of ATF-1 and CREB-1 in the cells by expression vectors demonstrated that homodimeric as well as heterodimeric forms of the factors transactivate the LMP1 promoter in an EBNA2-independent manner. The homodimers of ATF-2 and c-Jun did not significantly stimulate promoter activity. In contrast, the ATF-2/c-Jun heterodimer had only a minor stimulatory effect in the absence of EBNA2 but induced a strong transactivation of the LMP1 promoter when coexpressed with this protein. Evidence for a direct interaction between the ATF-2/c-Jun heterodimeric complex and EBNA2 was obtained by EMSA and coimmunoprecipitation experiments. Thus, our results suggest that EBNA2-induced transactivation via the ATF/CRE site occurs through a direct contact between EBNA2 and an ATF-2/c-Jun heterodimer. EBNA2-independent promoter activation via this site, on the other hand, is mediated by a heterodimeric complex between the ATF-1 and CREB-1 factors.

Interexaminer reliability in physical examination of patients with low back pain.

STUDY DESIGN: Seventy-one patients with low back pain were examined by two physiotherapists (50 patients) and two physicians (21 patients). The two physiotherapists had worked together for many years, but the two physicians had not. The interexaminer reliability of the clinical tests included in the physical examination was evaluated. OBJECTIVES: To evaluate the interexaminer reliability of clinical tests used in the physical examination of patients with low back pain under ideal circumstances, which was the case for the physiotherapists. SUMMARY OF BACKGROUND DATA: Numerous clinical tests are used in the evaluation of patients with low back pain. To reach the correct diagnosis, only tests with an acceptable validity and reliability should be used. Previous studies have mainly shown low reliability. It is important that clinical tests not be rejected because of low reliability caused by differences between examiners in performance of the examination and in their definition of normal results. METHODS: Two examiners, either two physiotherapists or two physicians, independently examined patients with low back pain. RESULTS: In approximately half of the clinical tests studied, an acceptable reliability was demonstrated. CONCLUSION: On the basis of the physiotherapists series, the reliability was acceptable for a number of clinical tests that are used in the evaluation of patients with low back pain. The results suggest that clinical tests should be standardized to a much higher degree than they are today.

Erysipelas: clinical and bacteriologic spectrum and serological aspects.

The bacteriologic, serological, and clinical characteristics of 229 patients with erysipelas diagnosed during a 2-year period at a university hospital for infectious diseases in Sweden are presented. Beta-Hemolytic streptococci were detected in 34% of these patients. Group A was the dominant serogroup, but group G streptococci were found in about half as many cases. Bacteremia was present in 5%. A serological response with antistreptolysin O (ASO) and antideoxyribonuclease B (ADNase B) was seen primarily in patients harboring group A streptococci but also in those from whom no pathogen was isolated. ASO was also found in high titers in some patients with Group G streptococcal infection. The clinical course was usually benign, with few complications, but recurrences were common (occurring in 21% of the patients). No cases of streptococcal toxic shock were seen. Culture of skin biopsy specimens had low sensitivity; Beta-hemolytic were isolated from only two of 15 patients.

PU box-binding transcription factors and a POU domain protein cooperate in the Epstein-Barr virus (EBV) nuclear antigen 2-induced transactivation of the EBV latent membrane protein 1 promoter.

Expression of the Epstein-Barr virus (EBV) latent membrane protein (LMP1) is regulated by virus- and host cell-specific factors. The EBV nuclear antigen 2 (EBNA2) has been shown to transactivate a number of viral and cellular gene promoters including the promoter for the LMP1 gene. EBNA2 is targeted to at least some of these promoters by interacting with a cellular DNA binding protein, RBP-J kappa. In the present report we confirm and extend our previous observation that the LMP1 promoter can be activated by EBNA2 in the absence of the RBP-J kappa-binding sequence in the LMP1 promoter regulatory region (LRS). We show that two distinct LRS regions, -106 to +40 and -176 to -136, contribute to EBNA2 responsiveness. Site-directed mutagenesis analysis of the upstream -176/-136 EBNA2 responsive element revealed that two critical cis-acting elements are required for full promoter function. These same elements analysed by electrophoretic mobility shift assays define two binding sites recognized by nuclear factors derived from B cells. An octamer-like sequence (-147 to -139) contained overlapping binding sites for an unidentified transcriptional repressor on the one hand and a factor(s) belonging to the POU domain family but distinct from Oct-1 and Oct-2 on the other. An adjacent purine tract (-171 to -155) held a PU.1 binding site, which was also recognized by a related factor. The results suggest that the POU domain protein and either of two PU box-binding factors bind simultaneously to LRS, creating a ternary complex that might be in part responsible for mediating the transactivation of the LMP1 promoter by EBNA2. There were no qualitative differences between EBV-negative and EBV-positive cells with regard to transcription factor binding to the octamer-like sequence and the PU.1 recognition site, as revealed by electrophoretic mobility shift assays.

Domains of the Epstein-Barr virus nuclear antigen 2 (EBNA2) involved in the transactivation of the latent membrane protein 1 and the EBNA Cp promoters.

The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) is one of the first EBV-encoded gene products expressed after infection of primary B lymphocytes. EBNA2 is essential for the growth-transforming potential of the virus and it functions as a transcriptional activator of a set of viral and cellular genes. Sequence-specific DNA-binding by EBNA2 has not been demonstrated but the molecule is targeted to specific DNA regions by a cellular protein, RBP-J kappa, which recognizes the GTGGGAA sequence present in the regulatory region of all EBNA2-responsive promoters defined so far. We have determined the contribution of a RBP-J kappa recognition sequence, an adjacent interferon-stimulated response element (ISRE) motif and a PU.1-binding site in the LMP1 regulatory sequence (LRS) to EBNA2-induced transactivation of the promoter by site-directed mutagenesis of LRS-carrying reporter plasmids. EBNA2 responsiveness was reduced by approximately twofold when either or both of the RBP-J kappa-binding and ISRE sequences were mutated. ISRE seemed to function as an EBNA2-independent positive element. On the other hand, mutation of the PU box resulted in a drastic reduction of EBNA2 responsiveness, irrespective of whether the RBP-J kappa site or the ISRE motif was present. A comparative study by deletion mutation identified regions of EBV B95-8 EBNA2 involved in the transactivation of the LMP1 and the EBNA Cp promoters. Two domains of EBNA2 defined by deletion of amino acids 247-337 and 437-476 were found to be important for the activation of both promoters, while two different domains corresponding to residues 4-18 and 118-198 were required solely for the LMP1 promoter. Thus, EBNA2 must activate the LMP1 and Cp promoters by different mechanisms. All deletions involved in transcriptional activation of the two promoters contained regions that are conserved in EBNA2 of B95-8 EBV (type 1), AG876 EBV (type 2) and herpesvirus papio origin.

Vision related daily life problems in patients waiting for a cataract extraction.

Problems in daily life activities caused by bad vision were studied in 150 patients with cataract before and 6 months after a cataract extraction. A relation was found between binocular visual acuity before surgery and the number of problems experienced (p < 0.001). After cataract extraction a reduction in problems was closely associated with an increase in visual acuity (p < 0.001) and also, in the patients' opinion, a better life situation (p < 0.001). Six questions to be answered when considering surgery are given.

Antibiotic prophylaxis in recurrent erysipelas.

Recurrences of erysipelas are especially prevalent in patients suffering from local impairment of circulation and intervention might thus be of benefit. Therefore a prospective, randomized, open study was undertaken to evaluate whether daily antibiotic prophylaxis would reduce the risk of recurrence. Patients with venous insufficiency or lymphatic congestion who had suffered two or more episodes of erysipelas during the previous 3 years and were admitted to the Infectious Disease Department at Roslagstull Hospital, Stockholm, Sweden, between November 1988 and November 1991 were included. Fourty patients, 20 on prophylaxis and 20 controls were followed according to a life table analysis during a median time of 15 months. Phenoxymethylpenicillin was prescribed as daily prophylaxis (while erythromycin was given to patients allergic to penicillin). Recurrences of erysipelas appeared to be reduced by daily antibiotic prophylaxis but the effect was not dramatic (p = 0.06). Only in patients with a high recurrence rate continuous antibiotic prophylaxis against erysipelas is indicated.

Cell phenotype-dependent control of Epstein-Barr virus latent membrane protein 1 gene regulatory sequences.

Growth transformation-associated Epstein-Barr virus-encoded genes are differentially regulated depending on the host cell phenotype. We have previously identified an LMP1 regulatory region (LRS) 5' of the LMP1 gene (+40 to -634) and analyzed its role in transcription initiation in the EBV-negative Burkitt's lymphoma line DG 75 (Fåhraeus et al., 1990a). In order to investigate the cell phenotype dependence of LMP1 gene regulation we have now compared the activity of positive and negative cis-acting LRS elements in cell lines of B lymphoid and epithelial cell origin in the presence and absence of the virus-encoded nuclear antigen EBNA2. Our results show that reporter plasmids that contain only the -54/+40 region of LRS are active in all tested cell lines. Furthermore, the previously identified negative cis-elements in the -144/-54 region were found to suppress promoter activity independent of the cell phenotype. EBNA2 was able to override the effect of the negative elements in all lines of B-cell origin, whereas it had no effect in epithelial lines. The positive effect of EBNA2 was mediated by cis-acting elements in the -214/-144-bp region. In all six tested cell lines of epithelial origin, reporter plasmids that carried the full-length LRS were active, independent of EBNA2. The LMP1 promoter in these constructs was activated by the concerted action of EBNA2-independent, positive elements in the -214/-144 and -324/-214 positions that counteracted the effect of the negative LRS elements.

Viral and cellular factors influence the activity of the Epstein-Barr virus BCR2 and BWR1 promoters in cells of different phenotype.

Transformation of B-lymphocytes by Epstein-Barr virus (EBV) is characterized by the expression of six viral nuclear antigens (EBNA1 to EBNA6) which are encoded by messages derived from long primary transcripts initiated at one of two promoters located in the BamHI C (BCR2) and BamHI W (BWR1) regions of the viral genome. The BWR1 promoter is preferentially utilized during the initial phases of EBV infection, whereas the BCR2 promoter is almost invariably used in transformed lymphoblastoid cell lines (LCLs). In order to gain some insight into the molecular mechanisms underlying promoter usage we have analyzed the activity of reporter plasmids carrying different parts of the BWR1 and BCR2 regulatory sequences in EBV-negative and EBV-carrying B cell lines that, on the basis of their surface marker expression, are representative of different stages of B cell activation/differentiation. We show that: (i) there is an inverse correlation between the activity of BWR1 and oriP-containing BCR2 reporter plasmids in cell lines expressing a BL group I versus a group III phenotype, the BWR1 promoter being virtually inactive in group III cells; (ii) BCR2 reporter plasmids devoid of the oriP region are active in EBV-negative cell lines and EBV-positive cells expressing a group I or group II phenotype and virtually inactive in BL group III cells and LCLs, suggesting that cellular factors are required for activation of BCR2 promoter elements. These factors are lost upon progression to a group III phenotype); (iii) expression of EBNA2 is sufficient to activate reporter plasmids containing the proximal part of the BCR2 promoter in EBV negative cells, whereas coexpression of EBNA2 and EBNA1 is required to activate the promoter in oriP-containing plasmids; (iv) the 30-bp repeat region of oriP acts as a negative cis-element on downstream promoters but is transformed into a transcriptional enhancer by the concerted action of EBNA1 and cellular factors. There was a poor correlation between the activity of exogenous reporter plasmids and endogenous BWR1 and BCR2 promoters in phenotypically different EBV-positive cell lines. The presence of the appropriate trans-acting factors was not sufficient to activate the endogenous BWR1 and BCR2 promoters in BL cells expressing a group I phenotype.

Virulence properties of erysipelas-associated group A streptococci.

Group A streptococcal isolates (n = 53) recovered from 38 erysipelas patients in 1988 and 1990 in Sweden were analysed with respect to serotype, erythrogenic toxin production and polymorphism in the emm gene region. Serotype determination showed a dominance of type T1M1 (28.6% of the strains), but T type 8 was also prevalent (14.3%). In the majority of the strains only a low production of erythrogenic toxin A was demonstrated, while both toxin B and C production were high. Polymorphism was detected in the emm gene region of T1M1 strains at a frequency of 64%. These erysipelas associated group A streptococci were more heterogenic with respect to serotype distribution and polymorphism in the emm gene region compared to previously studied group A streptococci isolated during an outbreak of serious streptococcal infections in Sweden in 1988/1989. The material included isolates from two cases of recurrence, and typing of the isolates indicated that the patients had been infected by the same serotype as in the primary infection.

Skin concentrations of phenoxymethylpenicillin in patients with erysipelas.

In 45 patients hospitalized with febrile erysipelas that had been treated with oral penicillin, punch biopsies of infected skin were performed and analysed for phenoxymethylpenicillin (pcV) concentrations. The curves for the concurrent serum and tissue levels followed the same course, indicating a rapid diffusion of pcV from serum into tissue. Penicillin concentrations in infected skin exceeded the minimal inhibitory concentrations (MIC) of the streptococci isolated for the first 4 h after tablet ingestion. Venous insufficiency was highly prevalent and pcV concentrations in affected patients were slightly but not significantly higher. A theoretical basis for the successful treatment of erysipelas with oral penicillin is therefore at hand.

Epstein-Barr virus-encoded nuclear antigen 2 activates the viral latent membrane protein promoter by modulating the activity of a negative regulatory element.

Previous studies suggest that the Epstein-Barr virus nuclear antigen EBNA2 participates in the regulation of the expression of the viral latent membrane protein (LMP). We have used reporter plasmids containing DNA fragments of the 5' flanking region of the LMP gene in cotransfection experiments to analyze the effect of EBNA2 on the activity of the LMP promoter. The results show that the LMP promoter is controlled by positive and negative transcription elements in a DNA fragment that contains the LMP transcription initiation site and 634 base pairs of upstream sequences. The promoter is activated by EBNA2. The region between position -54 and +40 relative to the mRNA cap site contains a positive transcription element that is constitutively active in DG75 cells and independent of EBNA2. The -106 to -54 region contains a negative regulatory element that prevents adjacent positive elements from functioning in the absence of EBNA2. Regulatory sequences between -324 and -144 participate in maintaining a high level of transcription of the LMP promoter after induction with EBNA2. The regulatory elements in the -634 to -54 promoter region have the characteristics of an inducible enhancer, including orientation independence and ability to regulate a heterologous promoter.

Form distortion in narrow beam rotation radiography.

The distortion of morphologic object elements, for distortion, at the exposure of a panoramic image has been determined mathematically and experimentally. As models the square, the circle, the rhomb, and the equilateral triangle were used. The general characteristics of the form distortion in narrow beam rotation radiography are analysed and described.