Production of a monoclonal antibody,DF-5, that identifies cells at the epithelial-mesenchymal interface in normal human skin. APN/CD13 is an epithelial-mesenchymal marker in skin

Epithelial-mesenchymal interactions play a critical role in skin development and differentiation, and similar interactions may also regulate the day-to-day proliferation and differentiation events of the epidermis that occur in normal adult skin. This study was directed at identifying molecules that are selectively located at the dermal-epidermal junction in normal adult skin as they may be involved in regulating these homeostatic events. To this end, monoclonal antibodies were raised against the crude cell membrane fraction of cultured human dermal fibroblasts. Screening of antibodies that recognized cell surface antigen on cultured human dermal fibroblasts was followed by determining which of these antibodies selectively localized cells at sites of epithelial-mesenchymal interactions. Antibody DF-5 fit these criteria and was further characterized. This antibody was found to recognize the cell surface ectopeptidase aminopeptidase N (APN), a molecule homologous to the cluster differentiation antigen CD13. Antibody DF-5 and anti-CD13 antibodies both identified cells at sites of epithelial-mesenchymal interactions in fetal, neonatal, and adult human skin, and the APN/CD13 enzyme activity was also identified at these sites. A second ectopeptidase, dipeptidyl peptidase IV (DPPIV) or CD26, presented a significantly different immunohistochemical and histochemical pattern in skin samples, confirming the specificity of the APN/CD13 studies. The function of APN/CD13 in skin has yet to be determined. Its invariant localization at sites of epithelial-mesenchymal interactions argues for a role particular to this region. It may play a role in regulating the activity of neuropeptides or other signaling peptides that are released in this region of skin or it may have an as yet undefined role in mediating communication between dermal and epidermal cells.     

Quantifying the healthcare costs of treating severely bleeding major trauma patients: a national study for England

IntroductionSeverely bleeding trauma patients are a small proportion of the major trauma population but account for 40 % of all trauma deaths. Healthcare resource use and costs are likely to be substantial but have not been fully quantified. Knowledge of costs is essential for developing targeted cost reduction strategies, informing health policy, and ensuring the cost-effectiveness of interventions.MethodsIn collaboration with the Trauma Audit Research Network (TARN) detailed patient-level data on in-hospital resource use, extended care at hospital discharge, and readmissions up to 12 months post-injury were collected on 441 consecutive adult major trauma patients with severe bleeding presenting at 22 hospitals (21 in England and one in Wales). Resource use data were costed using national unit costs and mean costs estimated for the cohort and for clinically relevant subgroups. Using nationally available data on trauma presentations in England, patient-level cost estimates were up-scaled to a national level.ResultsThe mean (95 % confidence interval) total cost of initial hospital inpatient care was £19,770 (£18,177 to £21,364) per patient, of which 62 % was attributable to ventilation, intensive care, and ward stays, 16 % to surgery, and 12 % to blood component transfusion. Nursing home and rehabilitation unit care and re-admissions to hospital increased the cost to £20,591 (£18,924 to £22,257). Costs were significantly higher for more severely injured trauma patients (Injury Severity Score ≥15) and those with blunt injuries. Cost estimates for England were £148,300,000, with over a third of this cost attributable to patients aged 65 years and over.ConclusionsSeverely bleeding major trauma patients are a high cost subgroup of all major trauma patients, and the cost burden is projected to rise further as a consequence of an aging population and as evidence continues to emerge on the benefits of early and simultaneous administration of blood products in pre-specified ratios. The findings from this study provide a previously unreported baseline from which the potential impact of changes to service provision and/or treatment practice can begin to be evaluated. Further studies are still required to determine the full costs of post-discharge care requirements, which are also likely to be substantial.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0987-5) contains supplementary material, which is available to authorized users.     

Inconsistent Evidence: Analysis of Six National Guidelines for Vaginal Birth After Cesarean Section

Abstract: Background: Guidelines are increasingly used to direct clinical practice, with the expectation that they improve clinical outcomes and minimize health care expenditure. Several national guidelines for vaginal birth after cesarean section (VBAC) have been released or updated recently, and their range has created dilemmas for clinicians and women. The purpose of this study was to summarize the recommendations of existing guidelines and assess their quality using a standardized and validated instrument to determine which guidelines, if any, are best able to guide clinical practice. Methods: English language guidelines on VBAC were purposively selected from national and professional organizations in the United Kingdom, United States, Canada, New Zealand, and Australia. The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument was applied to each guideline, and each was analyzed to determine the range and level of evidence on which it was based and the recommendations made. Results: Six guidelines published or updated between 2004 and 2007 were examined. Only two of the six guidelines scored well overall using the AGREE instrument, and the evidence used demonstrated great variety. Most guidelines cited expert opinion and consensus as evidence for some recommendations. Reported success rates for VBAC ranged from 30 to 85 percent, and reported rates of uterine rupture ranged from 0 to 2.8 percent. Conclusions: VBAC guidelines are characterized by quasi‐experimental evidence and consensus‐based recommendations, which lead to wide variability in recommendations and undermine their usefulness in clinical practice. (BIRTH 37:1 March 2010)     

The effect of pre-existing medical conditions and age on mortality after injury

BACKGROUND: Pre-existing medical conditions (PMCs) have been shown to increase mortality after trauma even after adjustment for the effect of chronological aging. It has been suggested that there is an interaction between injury severity and physiologic reserve, such that diminished physiologic reserve will have an adverse effect on survival at lower injury severity, but that at higher levels of injury severity, physiologic reserve will have much less of an impact. METHODS: Records of 65,743 patients, admitted after trauma, were extracted from the database of the United Kingdom Trauma Network to explore the impacts of age, gender and PMCs on mortality, and modification of these effects by severity of injury. RESULTS: PMCs were categorized as absent (23%), present (23%), or unrecorded (54%). There was an increase in mortality with increasing age at all levels of injury severity. Presence of a PMC was associated with a marked increase in mortality of patients with minor injuries (odds ratio [OR] = 5.9, 95% confidence interval [CI] 4.4, 8.0) or moderate injuries (OR = 2.0, 95% CI 1.4, 2.9), but not in those with more severe injuries (OR = 1.1, 95% CI 0.9, 1.4). The impact of age and male gender were also somewhat more pronounced for patients with less severe injuries. CONCLUSION: These findings support the hypothesis of an interaction between physiologic reserve and injury severity, where PMCs are associated with increased mortality when combined with low to moderate severity injuries, but not when combined with more severe injuries.