[Obligation to operate splenic injuries in polytrauma patients using MS-CT criteria]. / Operationspflichtigkeit von Milzverletzungen bei Polytraumapatienten nach MSCT-Kriterien.

PURPOSE: The aim of this study is to evaluate the validity of multi-slice computed tomography (MS-CT) in predicting the need to operate on spleen injuries in polytrauma patients using selected grading systems; the Thompson screening test (TST) and the extended TST (ETST). PATIENTS AND METHODS: A retrospective evaluation of 2791 patients who presented spleen injuries in polytrauma MS-CTs in the period between 12/2002 and 06/2010 was undertaken. On the basis of CT morphology, and by using the above mentioned grading systems, the probability of the need to operate on a splenic injury was defined. RESULTS: From a sample of 2791 patients, an MS-CT polytrauma scan was used to identify 139 splenic injuries. In correlation with the actual interventions carried out on the spleen, the applied grading systems showed sensitivities of 91 % (TST) and 69 % (ETST) as well as specificities of 78 % (TST) and 93 % (ETST). Regarding interventions on a splenic injury, positive predictive values were 57 % (TST) and 76 % (ETST), and the accordant negative predictive values were 96 % (TST) and 91 % (ETST). Thereby we ascertained significantly lower results than Thompson et al. CONCLUSION: The applied grading systems based on the findings of MS-CT do not reliably predict the need to operate on spleen injuries in polytrauma patients.

Prehospital anaesthesia: a survey of current practice in the UK.

AIM: To establish the national picture of prehospital anaesthesia in the UK and to reference practice against the Association of prior to Anaesthetists of Great Britain and Ireland safety guideline on prehospital anaesthesia. METHODS: Lead clinicians were identified for all prehospital services in the UK that could potentially be performing prehospital anaesthesia and invited to complete a detailed online survey. The survey requested details on team structure, the process for prehospital anaesthesia, drugs and equipment used and training and governance arrangements. RESULTS: 55 responses were received from 63 invitations sent (87.3%) yielding usable data for 47 services. 31 of the 47 services (70%) responded that they performed prehospital anaesthesia. All services performing prehospital anaesthesia utilised a doctor but only 18 services (58%) always utilised a trained assistant. 28 services (90%) maintained a database and over half of services (55%) performed less than 20 prehospital anaesthetics annually. 23 services (74%) had a designated lead clinician for prehospital anaesthesia and 25 (81%) had a written difficult airway plan. 19 services (61%) had mandatory continual training requirements. CONCLUSIONS: The majority of services are currently complying with the recommendations in the Association of prior to Anaesthetists of Great Britain and Ireland safety guideline. There are still areas of concern, particularly with regard to ongoing training and the high numbers of services that do not use a trained assistant for the process of prehospital anaesthesia.

A generic consensus assessment of undergraduate competence in forceps exodontia in the United Kingdom.

UNLABELLED: The assessment of competence in clinical skills has become more frequent in published healthcare curricula and syllabuses recently. There are agreed mechanisms for the assessment of competence in the post-graduate environment, but no consensus within the undergraduate curriculum. This paper seeks to develop an agreed generic checklist for the assessment of competence in forceps exodontia. MATERIALS AND METHODS: A modified Delphi process was undertaken with representatives from all UK dental schools (n = 13) to develop a generic checklist for the assessment of competence in forceps exodontia. A content analysis of the assessments employed by each school was used to help discussion and inform the Delphi process. RESULTS: Seven schools currently employ a summative assessment of competence in forceps exodontia, with the majority employing a structured clinical objective test (n = 6). From the seven assessments, there were a total of 29 putative items and 10 putative domains identified for a generic checklist. These were reduced to five domains and 19 items through the content analysis and Delphi process, and a generic overarching checklist was created. CONCLUSION: Using this generic checklist, it may now be possible to pool data inter-institution to perform more powerful analyses on how our students obtain, or fail to obtain competence in forceps exodontia.

Plasmodesmal targeting and intercellular movement of potato mop-top pomovirus is mediated by a membrane anchored tyrosine-based motif on the lumenal side of the endoplasmic reticulum and the C-terminal transmembrane domain in the TGB3 movement protein.

Live-cell fluorescence microscopy was used to investigate the third triple gene block protein (TGB3) of potato mop-top pomovirus and its role in assisted targeting of TGB2 to plasmodesmata (PD). Wild-type and mutant TGB3 proteins were expressed under the control of the 35S promoter or from a virus reporter clone. Assisted targeting of TGB2 to PD was optimal when the proteins were expressed from a bicistronic plasmid in the relative ratios expected in a virus infection, suggesting that excess TGB3 inhibited PD localisation. Contrary to the generally accepted view, bimolecular fluorescence complementation showed that the TGB3 N terminus is located in the cytosol. Mutational analysis to dissect TGB3 sub domain functions showed that PD targeting was mediated by a composite signal comprising an ER-lumenal tyrosine-based motif and the C-terminal transmembrane domain. Mutation of either of these domains also abolished cell-to-cell movement of the virus. The results are discussed in the context of TGB3 membrane topology.

Germ cell differentiation in the marmoset (Callithrix jacchus) during fetal and neonatal life closely parallels that in the human.

BACKGROUND: Testicular germ cell tumours (TGCT) are thought to originate from fetal germ cells that fail to differentiate normally, but no animal model for these events has been described. We evaluated the marmoset (Callithrix jacchus) as a model by comparing perinatal germ cell differentiation with that in humans. METHODS: Immunohistochemical profiling was used to investigate germ cell differentiation (OCT4, NANOG, AP-2gamma, MAGE-A4, VASA, NANOS-1) and proliferation (Ki67) in fetal and neonatal marmoset testes in comparison with the human and, to a lesser extent, the rat. RESULTS: In marmosets and humans, differentiation of gonocytes into spermatogonia is associated with the gradual loss of pluripotency markers such as OCT4 and NANOG, and the expression of germ cell-specific proteins such as VASA. This differentiation occurs asynchronously within individual cords during fetal and early postnatal life. This contrasts with rapid and synchronous germ cell differentiation within and between cords in the rat. Similarly, germ cell proliferation in the marmoset and human occurs throughout perinatal life, in contrast to rats in which proliferation ceases during this period. CONCLUSIONS: The marmoset provides a good model for normal human germ cell differentiation and proliferation. The perinatal marmoset may be a useful model in which to establish factors that lead to failure of normal germ cell differentiation and the origins of TGCT.

UK national curriculum for undergraduate oral surgery subgroup for teaching of the Association of British Academic Oral and Maxillofacial Surgeons.

This article describes a curriculum in oral surgery for undergraduate dental education in the United Kingdom prepared by the Education Subgroup of The British Academic Oral and Maxillofacial Surgeons. This group is made up of representatives from each of the 13 UK Dental Schools, one Irish Dental School and one Post-graduate Institute. The document represents a group consensus of an undergraduate UK oral surgery curriculum that is founded on the frameworks outlined by the General Dental Council, the Quality Assurance Agency for Higher Education and the Association for Dental Education in Europe. Our curriculum document is more prescriptive than the information available in the aforementioned documents. It is based on UK undergraduate oral surgery experience and thus attempts to set achievable core competencies and, in a few areas, challenges the available curriculum and related documentation.

Regulatory requirements for vaccine authorisation.

Vaccines are one of the most important tools available in the prevention and control of diseases in animals. It is therefore of the utmost importance that when vaccines are used, such use should meet with the requirements of the World Organisation for Animal Health Terrestrial Animal Health Code and must be authorised by the recognised licensing body in the country/region where the vaccines are to be used, in accordance with the three key criteria of quality, safety and efficacy. This article provides a comprehensive and comparative description of the regulatory requirements in place for veterinary vaccines in major regions of the world, highlighting the similarities and pointing out also where there are differences. Recent advances in harmonisation of such testing requirements achieved through the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) are also described. The contents will provide a valuable guide to those engaged in the research and development of vaccines globally, and reassure those involved in the prevention and control of animal diseases that veterinary vaccines, when fully authorised and used according to the label instructions, are safe and efficacious.

Facing up to binge drinking: reducing binge drinking in adolescent males.

OBJECTIVE: To evaluate the effectiveness of an orofacial trauma-based brief intervention, designed to raise adolescent males' awareness about the immediate dangers of binge drinking. DESIGN: Non-randomised controlled exploratory trial. SETTING: Secondary level schools. MATERIALS & METHODS: Pre, post and follow up validated questionnaires were used to assess a variety of descriptive data and changes in behaviour. Sixty Year 12 students were recruited in the pilot study and 182 in the definitive study. INTERVENTION: A brief visual presentation containing salient information and anonymised photographs relating to orofacial injuries. MAIN OUTCOME MEASURES: Intention to binge drink. RESULTS: The majority of participants obtained alcohol from off-licence or licenced premises. At the commencement of the study, 68% of the participants were regular drinkers. Whilst there was no change in drinking behaviour, the intervention group reported that it was significantly more likely (compared to the control group) that they would reduce their drinking to less than binge levels. CONCLUSION: The intervention resulted in participants reporting a more negative attitude towards binge drinking and increased their intention to disengage from binge drinking.

Barley stripe mosaic virus-encoded proteins triple-gene block 2 and gammab localize to chloroplasts in virus-infected monocot and dicot plants, revealing hitherto-unknown roles in virus replication.

Replication of Barley stripe mosaic virus (BSMV), genus Hordeivirus, is thought to be associated with vesicles in proplastids and chloroplasts, but the molecular details of the process and identity of virus proteins involved in establishing the virus replication complexes are unknown. In addition, BSMV encodes a triple-gene block of movement proteins (TGBs) that putatively share functional roles with their counterparts in other hordei-, pomo- and pecluviruses, but detailed information on the intracellular locations of the individual TGBs is lacking. Here, the subcellular localizations of BSMV-encoded proteins TGB2 and gammab fused to green or red fluorescent proteins were examined in epidermal cells of Nicotiana benthamiana and barley (Hordeum vulgare 'Black Hulless'). The fusion proteins were expressed from a BSMV vector or under the control of the cauliflower mosaic virus 35S promoter. The subcellular localizations were studied by confocal laser-scanning microscopy (CLSM). CLSM studies showed that both proteins were recruited to chloroplasts in the presence of viral RNA and that virus RNA, coat protein and gammab protein were detected in plastid preparations from infected leaves. Electron microscope images of thin sections of virus-infected leaves revealed abnormal chloroplasts with cytoplasmic inclusions containing virus-like particles. In addition, cellular localizations of BSMV TGB2 suggest subtle differences in function between the hordei-like TGB2 proteins. The results indicate that TGB2 and gammab proteins play a previously unknown functional role at the site of virus replication.

Pneumolysin-mediated activation of NFkappaB in human neutrophils is antagonized by docosahexaenoic acid.

This study was designed to investigate the relationship between influx of extracellular Ca(2+), activation of NFkappaB and synthesis of interleukin-8 (IL-8) following exposure of human neutrophils to subcytolytic concentrations (8.37 and 41.75 ng/ml) of the pneumococcal toxin, pneumolysin, as well as the potential of the omega-3 polyunsaturated fatty acid, docosahexaenoic acid, to antagonize these events. Activation and translocation of NFkappaB were measured using a radiometric electrophoretic mobility shift assay, while influx of extracellular Ca(2+) and synthesis of IL-8 were determined using a radioassay and an ELISA procedure, respectively. Exposure of neutrophils to pneumolysin was accompanied by influx of Ca(2+), activation of NFkappaB, and synthesis of IL-8, all of which were eliminated by inclusion of the Ca(2+)-chelating agent, EGTA (10 m m), in the cell-suspending medium, as well as by pretreatment of the cells with docosahexaenoic acid (5 and 10 microg/ml). The antagonistic effects of docosahexaenoic acid on these pro-inflammatory interactions of pneumolysin with neutrophils were not attributable to inactivation of the toxin, and required the continuous presence of the fatty acid. These observations demonstrate that activation of NFkappaB and synthesis of IL-8, following exposure of neutrophils to pneumolysin are dependent on toxin-mediated influx of Ca(2+) and that these potentially harmful activities of the toxin are antagonized by docosahexaenoic acid.

Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults.

PURPOSE: Hyperinsulinemia is a common feature of many obesity syndromes. We investigated whether suppression of insulin secretion, without dietary or exercise intervention, could promote weight loss and alter food intake and preference in obese adults. METHODS: Suppression of insulin secretion was achieved using octreotide-LAR 40 mg IM q28d for 24 weeks in 44 severely obese adults (89% female, 39% minority). Oral glucose tolerance testing was performed before and after treatment, indices of beta-cell activity (CIRgp), insulin sensitivity (CISI), and clearance (CP/I AUC) were computed, and leptin levels, 3-day food records and carbohydrate-craving measurements were obtained. DEXA evaluations were performed pre- and post-therapy in an evaluable subgroup. RESULTS: For the entire cohort, significant insulin suppression was achieved with simultaneous improvements in insulin sensitivity, weight loss, and body mass index (BMI). Leptin, fat mass, total caloric intake, and carbohydrate craving significantly decreased. When grouped by BMI response, high responders (HR; DeltaBMI<-3 kg/m(2)) and low responders (LR; DeltaBMI between -3 and -0.5) exhibited higher suppression of CIRgp and IAUC than nonresponders (NR; DeltaBMI-0.5). CISI improved and significant declines in leptin and fat mass occurred only in HR and LR. Conversely, both leptin and fat mass increased in NR. Carbohydrate intake was markedly suppressed in HR only, while carbohydrate-craving scores decreased in HR and LR. For the entire cohort, DeltaBMI correlated with DeltaCISI, Deltafat mass, and Deltaleptin. DeltaFat mass also correlated with DeltaIAUC and DeltaCISI. CONCLUSIONS: In a subcohort of obese adults, suppression of insulin secretion was associated with loss of body weight and fat mass and with concomitant modulation of caloric intake and macronutrient preference.

Comparison of PGE2, prostacyclin and leptin release by human adipocytes versus explants of adipose tissue in primary culture.

The present studies were designed to investigate the sites of PGE(2), prostacyclin and leptin formation in human adipose tissue. Most of the PGE(2) and prostacyclin formation by adipose tissue explants from obese humans after 48 h in primary culture was due to blood vessels and other tissues not digested by collagenase. However, there was appreciable PGE(2) formation by adipocytes over a 48 h incubation and leptin formation was only seen in adipocytes. An increase in COX-2 immunoreactive protein was also seen after incubation of isolated human adipocytes for 48 h. The release of PGE(2) by adipocytes incubated for 48 h was about 4% that by intact adipose tissue explants while the release of prostacyclin was about 1.5% that by tissue. However, in a different experimental design where PGE(2) formation was measured over 2 h in the presence of 20 microM arachidonic acid the formation of PGE(2) by adipocytes after 48 h prior incubation in primary culture was 38% of that by tissue explants. Dexamethasone enhanced leptin release by adipocytes while inhibiting PGE(2) release and COX-2 up-regulation. The mechanisms involved in up-regulation of COX-2 activity during primary culture of adipocytes and the inhibition of this by dexamethasone do not appear to involve p38 MAPK or p42-44 MAPK. Interleukin I(beta) further enhanced PGE(2) formation by adipocytes but did not affect leptin formation. In conclusion, these data indicate that leptin release is exclusively a function of adipocytes while prostanoids are made by both adipocytes and the other cells present in human adipose tissue

Subcellular localisation, protein interactions, and RNA binding of Potato mop-top virus triple gene block proteins.

Subcellular localisation, protein interactions, and RNA binding of the triple gene block proteins (TGBp) of Potato mop-top virus (PMTV) were studied. The 13-kDa (TGBp2) and 21-kDa (TGBp3) proteins with or without green fluorescent protein fused to their N-terminus, and the 51-kDa protein (TGBp1) were expressed individually from a recombinant Tobacco mosaic virus (TMV) vector. Fluorescent images and Western immunoblotting experiments of recombinant TMV-infected Nicotiana benthamiana cells suggested that TGBp2 and TGBp3 were associated with cellular endomembranes and that TGBp3 was associated with the cell wall, possibly located close to plasmodesmata. In Western blots, TGBp1 was detected in fractions containing the cell wall and those enriched for organelles and membranous structures. Self-interactions were demonstrated with all three proteins in yeast two-hybrid experiments, and a heterologous interaction was found between TGBp2 and TGBp3. No additional heterologous interactions were discovered between the different TGBp and none were detected in an in vitro binding assay. TGBp1 and TGBp2 but not TGBp3 were shown to bind ssRNA in a sequence nonspecific manner. The results support the model where TGBp2 and TGBp3 facilitate delivery and localisation of the ribonucleoprotein complex to the plasmodesmata. However, the process is facilitated by RNA-protein rather than protein:protein interactions between the TGBp1 in complex with viral RNA and membrane-localised TGBp2.

Assessment of the effects of a taped cognitive behavior message on postoperative complications (therapeutic suggestions under anesthesia).

BACKGROUND: The authors studied whether playing a taped cognitive-behavior message during and immediately following bariatric surgery will improve performance of a postoperative regimen designed to enhance recovery. METHODS: The double-blinded placebo-controlled study consisted of 27 morbidly obese bariatric surgical patients randomly assigned to listen to either a blank (Controls) or a positive therapeutic message audiotape (Tape). A Postoperative Regimen Checklist (PRC) quantified different parts of the postoperative recovery regimen. RESULTS: The data showed that patients in the Tape group, compared to the Controls: 1) achieved better scores at most PRC assessment points (p < 0.05), 2) required less encouragement to perform tasks (p < 0.05), and 3) were discharged from the hospital a mean of 1.6 days earlier. CONCLUSIONS: A taped cognitive-behavioral message, played to patients repetitively during and immediately following bariatric surgery, is effective in enhancing postoperative compliance and reducing in-patient length of stay.

Stimulation of leptin release by arachidonic acid and prostaglandin E(2) in adipose tissue from obese humans.

The purpose of this study was to examine the effect of arachidonic acid and its metabolites on leptin formation by explants of human adipose tissue over a 48-hour incubation in primary culture. We found that arachidonic acid or prostaglandin E(2) (PGE(2)) stimulated leptin release by explants of subcutaneous adipose tissue from obese humans. The stimulatory effect of arachidonic acid on leptin formation was blocked by NS-398, a cyclooxygenase-2 (COX-2) inhibitor. There was appreciable release of PGE(2) to the medium over 48 hours, and this was inhibited by 99% in the presence of 200 nmol/L dexamethasone or 5 micromol/L NS-398. The increase in PGE(2) release correlated with induction of COX-2 activity during the 48-hour incubation. The increase in COX-2 activity was blocked by 200nmol/L dexamethasone. The level of leptin mRNA at 48 hours was reduced by 28% if PGE(2) was added in the absence of dexamethasone, while in the presence of dexamethasone, the amount of leptin mRNA was enhanced by 156%. These data suggest that when upregulation of COX-2 is blocked by dexamethasone, exogenous PGE(2) enhances both leptin release and leptin mRNA accumulation by explants of human adipose tissue in primary culture.

Influence of body fat distribution on oxygen uptake and pulmonary performance in morbidly obese females during exercise.

OBJECTIVE: The aim of this study was to determine the effects of fat distribution on aerobic and ventilatory response to exercise testing in morbidly obese (MO) females. METHODOLOGY: The study population consisted of 164 MO females, 55% (n = 90) with upper body or abdominal adiposity (UBD), as defined by waist-hip circumference ratio (WHR) > or = 0.80, and 45% (n = 74) with lower body fat distribution (LBD) (WHR < 0.80). An incremental exercise testing on cycle ergometer was performed to determine the effect of exercise on oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), tidal volume (VT), respiratory rate (fb) and heart rate (HR). RESULTS: Upper body adiposity individuals had significantly higher VO2 and VCO2 than LBD subjects (P < 0.05) from 0 watt (W) of pedalling up to their anaerobic threshold (AT) and maximal exercise. VE was significantly higher in UBD subjects compared with LBD subjects, from 20 W during exercise up to AT and peak work levels (P < 0.05). Upper body adiposity group also had a significantly higher fb than the LBD group at rest, after each workload and at AT and peak exercise work rates (P < 0.05). VT was lower in UBD subjects at free pedalling and up to AT and peak workload with significant difference at 60 and 80 W (P < 0.05). The anaerobic threshold, expressed as work rate, was significantly lower in the UBD subjects (P < 0.05) and peak workload achieved did not differ significantly between the two groups. CONCLUSIONS: Upper body adiposity subjects had higher oxygen requirement, more rapid and shallow breathing, higher ventilatory demand, but lower anaerobic threshold than the LBD individuals during progressive exercise. It suggests that the cardiopulmonary endurance to exercise in MO patients with upper body fat distribution is lower than in those with lower body fat distribution.

Regulation of leptin release by troglitazone in human adipose tissue.

In pieces of human subcutaneous adipose tissue incubated in primary culture for 48 hours, the release of leptin was stimulated by 50% in the presence of 3.3 micromol/L troglitazone. Insulin (0.1 nmol/L) and dexamethasone (200 nmol/L) stimulated leptin release by 30% and 300%, respectively. Troglitazone in combination with either insulin or dexamethasone had no effect on leptin release. Instead, troglitazone inhibited leptin release in the presence of both dexamethasone and insulin. The stimulatory effect of troglitazone on leptin release was also mimicked by 1 micromol/L 15-deoxy-delta(12-14)prostaglandin J2 (dPGJ2). However, if the concentration of dPGJ2 was increased to 10 micromol/L in the presence of dexamethasone, there was a decrease in leptin release, as well as of lactate formation and lipolysis. These data indicate that both stimulatory and inhibitory effects of troglitazone and dPGJ2 can be seen on leptin release by human adipose tissue.

Intravenous immunoglobulin therapy for children with Stevens-Johnson syndrome.

OBJECTIVE: To review the experience with intravenous immunoglobulin (IVIG) therapy in patients with Stevens-Johnson syndrome (SJS) in our institution. METHODS: All charts of patients with SJS admitted to Children's Hospital between November 1988 and June 1998 were reviewed. RESULTS: Twelve patients with SJS were detected. There were 8 males and 4 females, with a mean age 6 years (range 10 mo to 17 yrs). All patients presented with high fever and cutaneous and mucous membrane changes, and the diagnosis SJS was confirmed by a dermatologist. Of the 12 patients with SJS, 7 were treated with IVIG, 2 with corticosteroids, and 3 with supportive care. IVIG was administered in a single infusion at 1.5-2 g/kg, and was given on an average of hospital day 3 (range 1-8 days). The average duration of fever was 8 days (range 3-14) in the IVIG treated patients compared to 14 days (range 6-20) in the non-IVIG treated group (p = 0.06). The mean hospital stay was 12 days (range 4-22) for the patients treated with IVIG and 15 days (range 6-25) for the non-IVIG treated group (p = 0.5). No toxicity was observed with IVIG therapy. CONCLUSION: Duration of fever was shortened in patients treated with IVIG, although statistical significance was marginal. The hospital stay was slightly shortened in patients treated with IVIG; however, statistical significance was not reached. Prospective and controlled, multicenter studies are needed to further investigate these preliminary findings.

Synergism between insulin and low concentrations of isoproterenol in the stimulation of leptin release by cultured human adipose tissue.

The release of leptin by pieces of human adipose tissue incubated in primary culture for 24 or 48 hours in the presence of dexamethasone was reduced by isoproterenol. An inhibition of leptin release was observed at 24 hours in the presence of isoproterenol and was mediated by beta1-adrenergic receptors, since it was blocked by the specific beta1-adrenoceptor antagonist CGP-20712A. The inhibitory effect of 33 nmol/L isoproterenol on leptin release was reversed in the presence of 0.1 nmol/L insulin to a 2-fold stimulation of leptin release. These data suggest that the primary mechanism by which insulin stimulates leptin release is to blunt the inhibitory effects of beta1-adrenergic receptor agonists, and low concentrations of catecholamines actually enhance the stimulation of leptin release by insulin.