Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life.

Male sex hormones-androgens-regulate male physique development. Without androgen signaling, genetic males appear female. During puberty, increasing androgens harness the hair follicle's unique regenerative ability to replace many tiny vellus hairs with larger, darker terminal hairs ( e.g., beard). Follicle response is epigenetically varied: some remain unaffected ( e.g., eyelashes) or are inhibited, causing balding. How sex steroid hormones alter such developmental processes is unclear, despite high incidences of hormone-driven cancer, hirsutism, and alopecia. Unfortunately, existing development models are not androgen sensitive. Here, we use hair follicles to establish an androgen-responsive human organ culture model. We show that women's intermediate facial follicles respond to men's higher androgen levels by synthesizing more hair over several days, unlike donor-matched, androgen-insensitive, terminal follicles. We demonstrate that androgen receptors-androgen-activated gene transcription regulators-are required and are present in vivo within these follicles. This is the first human organ that involves multiple cell types that responds appropriately to hormones in prolonged culture, in a way which mirrors its natural behavior. Thus, intermediate hair follicles offer a hormone-switchable human model with exceptional, unique availability of genetically identical, but epigenetically hormone-insensitive, terminal follicles. This should enable advances in understanding sex steroid hormone signaling, gene regulation, and developmental and regenerative systems and facilitate better therapies for hormone-dependent disorders.-Miranda, B. H., Charlesworth, M. R., Tobin, D. J., Sharpe, D. T., Randall, V. A. Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life.

Analysis of outcomes achieved with squamous cell carcinomas of the anus in a single university hospital over the last two decades: Clinical response rate, relapse and survival of 190 patients.

BACKGROUND AND OBJECTIVES: We reviewed our series of anal squamous cell carcinomas (ASCC) treated over the last two decades. METHODS: ASCC patients undergoing treatment at the Leicester Royal Infirmary between 1998 and 2016 were selected. Age, gender, pathological tumor characteristics, treatment adopted, the overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) at 5-year follow-up were recorded and calculated. RESULTS: A total of 190 ASCC were reviewed, of these 64.2% (n = 122) received primary radical chemoradiotherapy. Complete response rate was 92.6% (n = 113) and four patients with residual disease underwent a salvage APER. Twenty-eight patients experienced recurrent disease (23.0%) either systemic (n = 8), local (n = 14), or both (n = 6); six had a salvage APER. Complete follow-up data are available for 63.1% patients (77/122). Overall, the locoregional failure rate of primary chemoradiotherapy (residual + recurrent disease) was present in 29 patients (29/122; 23.8%). OS was 41.6% CSS was 69.2% and DFS 60.0% at 5 years follow-up. CONCLUSIONS: In our series of ASCC primary chemoradiotherapy had achieved significant initial complete response rates, however, long term-follow ups still present systemic and local recurrences. APR is able to treat 30% of the pelvic recurrences (6/20), the others are either associated with systemic disease or locally inoperable masses.

Rectal cancers with microscopic circumferential resection margin involvement (R1 resections): Survivals, patterns of recurrence, and prognostic factors.

BACKGROUND AND OBJECTIVES: We have reviewed our series of rectal cancer patients with circumferential resection margin involvement (R1) with particular regard to survival and prognostic factors. METHODS: R1 rectal cancer patients undergoing surgery at the Leicester Royal Infirmary between 1998 and 2008. Age, gender, radiological, and pathological tumor characteristics, neoadjuvant and adjuvant therapies were examined as prognostic factors on the overall survival (OS) and disease-free survival (DFS) at 5-year follow-up. RESULTS: A total of 885 rectal cancers were reviewed. Six hundred ninety-nine patients underwent a mesorectal excision and 71 of them were R1 resections (12.9%). OS was 43.7% (CI95% 33.5-53.8%; median survival 39 months). DFS was 57.4% (CI95% 43.0-71.8%; median survival 31 months). Pelvic recurrence rate occurred in 16 patients (26.2%, CI95% 16.5-36.0%), systemic recurrence rate in 23 patients (37.7%, CI95% 25.5-49.9%). At Cox-regression LNR and adjuvant chemotherapy were associated with both OS and DFS. No significant association was found between OS or DFS and adjuvant radiotherapy. CONCLUSIONS: In our series of R1 patients, the rates of local recurrence and OS at 5 years were 26.2% and 43.7%, respectively. Factors influencing systemic recurrences (LNR, adjuvant chemotherapy) are more associated with OS and DFS than those potentially affecting locoregional recurrences (adjuvant radiotherapy). J. Surg. Oncol. 2016;114:642-648. © 2016 Wiley Periodicals, Inc.

Circumferential resection margins and perineal complications after neoadjuvant long-course chemoradiotherapy followed by extralevator abdominoperineal excision of the rectum: Five years of activity at a single institution.

BACKGROUND: Prone extralevator abdominoperineal excision of the rectum (ELAPE) has been introduced to improve the circumferential resection margins (CRM) compared with traditional APER. OBJECTIVE: We present short-term results achieved with prone ELAPE preceded by neoadjuvant chemoradiotherapy during the last 5 years of activity. DESIGN: A retrospective review was conducted. SETTINGS AND PATIENTS: Prone ELAPE operations performed between September 2010 and August 2014 at Leicester Royal Infirmary preceded by neoadjuvant chemoradiotherapy. INTERVENTIONS AND MAIN OUTCOME MEASURES: Data regarding demographics, staging, neoadjuvant therapies, intraoperative perforations, and perineal complications were collected. RESULTS: Seventy-two patients were included. Pretreatment radiological T4 were 25.0%, histological T4 2.8%. Intraoperative perforations occurred in 2.8%, CRM was involved in 11.1%. Perineal complications consisted of superficial wound infections (20.8%), full thickness dehiscences (16.7%), hematomas (9.7%), pelvic collections (6.9%), and perineal hernias (5.6%). CONCLUSIONS: In our experience, prone ELAPE preceded by long-course chemoradiotherapy has been successfully used in the last 5 years to resect low rectal tumors. Perineal wound complications rates are similar to those presented in series using direct perineal closures. J. Surg. Oncol. 2016;114:86-90. © 2016 Wiley Periodicals, Inc.

Sensitivity and specificity of the empirical lymphocyte genome sensitivity (LGS) assay: implications for improving cancer diagnostics.

Lymphocyte responses from 208 individuals: 20 with melanoma, 34 with colon cancer, and 4 with lung cancer (58), 18 with suspected melanoma, 28 with polyposis, and 10 with COPD (56), and 94 healthy volunteers were examined. The natural logarithm of the Olive tail moment (OTM) was plotted for exposure to UVA through 5 different agar depths (100 cell measurements/depth) and analyzed using a repeated measures regression model. Responses of patients with cancer plateaued after treatment with different UVA intensities, but returned toward control values for healthy volunteers. For precancerous conditions and suspected cancers, intermediate responses occurred. ROC analysis of mean log OTMs, for cancers plus precancerous/suspect conditions vs. controls, cancer vs. precancerous/suspect conditions plus controls, and cancer vs. controls, gave areas under the curve of 0.87, 0.89, and 0.93, respectively (P<0.001). Optimization allowed test sensitivity or specificity to approach 100% with acceptable complementary measures. This modified comet assay could represent a stand-alone test or an adjunct to other investigative procedures for detecting cancer.

Synthesis and properties of chemiluminescent acridinium ester labels with fluorous tags.

Acridinium dimethylphenyl esters are highly sensitive chemiluminescent labels that are used in clinical diagnostics. Light emission from these labels is triggered with alkaline peroxide in the presence of the cationic surfactant cetyltrimethylammonium chloride (CTAC). CTAC compresses emission times of these labels to <5 seconds and also increases overall light yield 3-4 fold. The observed enhancement in acridinium ester chemiluminescence (light yield) is quite sensitive to the polarity of the micellar interface. In the current study, we report the synthesis of new acridinium ester labels with fluorous tags of varying fluorine content and their chemiluminescence in the presence of cationic micelles of CTAC, anionic micelles of sodium perfluorooctanoate (SPFO) as well as mixed micelles of CTAC and SPFO. These studies indicate that in the presence of the mixed micelle system of CTAC and SPFO and at low mole fractions of SPFO, polarity of the mixed micelle interface is lower than that of CTAC leading to a greater enhancement of chemiluminescence for both fluorinated acridinium esters as well as a structurally analogous but non-fluorinated acridinium ester. Chemiluminescence stability of the fluorinated acridinium esters was either comparable to or better than the stability of the non-fluorinated acridinium ester. Non-specific binding to paramagnetic microparticles was higher for fluorinated acridinium esters requiring a surfactant wash to reduce their non-specific binding to the same extent as that observed for the non-fluorinated acridinium ester.

Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.

Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.

Synthesis and properties of differently charged chemiluminescent acridinium ester labels.

Chemiluminescent acridinium dimethylphenyl esters containing N-sulfopropyl groups in the acridinium ring are highly sensitive, hydrophilic labels that are used in automated immunoassays for clinical diagnostics. Light emission from these labels is triggered with alkaline peroxide in the presence of a cationic surfactant. At physiological pH, N-sulfopropyl acridinium esters exist as water adducts that are commonly referred to as pseudobases. Pseudobase formation, which results from addition of water to the zwitterionic N-sulfopropyl acridinium ring, neutralizes the positive charge on the acridinium nitrogen and imparts a net negative charge to the label due to the sulfonate moiety. As a consequence, N-sulfopropyl acridinium ester conjugates of small molecule haptens as well as large molecules such as proteins gain negative charges at neutral pH. In the current study, we describe the synthesis and properties of two new hydrophilic acridinium dimethylphenyl ester labels where the net charge in the labels was altered. In one label, the structure of the hydrophilic N-alkyl group attached to the acridinium ring was changed so that the pseudobase of the label contains no net charge. In the second acridinium ester, two additional negative charges in the form of sulfopropyl groups were added to the acridinium ring to make this label's pseudobase strongly anionic. Chemiluminescence measurements of these labels, as well as their conjugates of an antibody with a neutral pI, indicate that acridinium ester charge while having a modest effect on emission kinetics has little influence on light output. However, our results demonstrate that acridinium ester charge can affect protein pI, apparent chemiluminescence stability and non-specific binding of protein conjugates to microparticles. These results emphasize the need for careful consideration of acridinium ester charge in order to optimize reagent stability and performance in immunoassays. In the current study, we observed that for a neutral protein, an acridinium ester with a hydrophilic but charge-neutral N-alkyl group afforded faster light emission, lower non-specific binding and better chemiluminescence stability than an analogous label with an anionic N-alkyl group.

Chemiluminescence from alkoxy-substituted acridinium dimethylphenyl ester labels.

Chemiluminescent acridinium dimethylphenyl ester labels are used in automated immunoassays for clinical diagnostics. Light emission from these labels is triggered by alkaline peroxide in the presence of the cationic surfactant cetyltrimethylammonium chloride (CTAC). The surfactant plays a critical role in the chemiluminescence process of these labels by both accelerating their emission kinetics and increasing total light output enabling high throughout and improved assay sensitivity in automated immunoassays. Despite the surfactant's crucial role in the chemiluminescent reaction, no study has investigated how structural perturbations in the acridinium ring could impact the influence of the surfactant. We describe herein the synthesis and properties of three new alkoxy-substituted, acridinium dimethylphenyl esters where the nature of the alkoxy group in the acridinium ring was varied (hydrophobic or hydrophilic). Chemiluminescence measurements of these alkoxy-substituted labels indicate that hydrophilic functional groups in the acridinium ring, in particular sulfobetaine zwitterions, disrupt surfactant-mediated compression of emission times but not enhancement of light yield. These results support the hypothesis that surfactant-mediated effects require the binding of two different reaction intermediates to surfactant aggregates and, that surfactants influence light emission from acridinium esters by two separate mechanisms. Our studies also indicate that preservation of both surfactant effects on acridinium ester chemiluminescence and low non-specific binding of the label can be achieved with a relatively hydrophobic acridinium ring coupled to a hydrophilic phenolic ester leaving group.

Zwitterionic reagents for labeling, cross-linking and improving the performance of chemiluminescent immunoassays.

Improving reagent performance in immunoassays both to enhance assay sensitivity and to minimize interference are ongoing challenges in clinical diagnostics. We describe herein the syntheses of a new class of hydrophilic reagents containing sulfobetaine zwitterions and their applications. These zwitterionic reagents are potentially useful for improving the properties of immunoassay reagents. We demonstrate for the first time that zwitterion labeling is a general and viable strategy for reducing the non-specific binding of proteins to microparticles and, to improve the aqueous solubility of hydrophobic peptides. We also describe the synthesis of zwitterionic cross-linking reagents and demonstrate their utility for peptide conjugation. In automated, chemiluminescent immunoassays, improved assay performance was observed for a hydrophobic, small analyte (theophylline) using an acridinium ester conjugate with a zwitterionic sulfobetaine linker compared to a hexa(ethylene)glycol linker. Sandwich assay performance for a large analyte (thyroid stimulating hormone) was similar for the two acridinium ester labels. These results indicate that zwitterions are complementary to poly(ethylene)glycol in improving the aqueous solubility and reducing the non-specific binding of chemiluminescent acridinium ester conjugates.

Cost-Effectiveness of Monitoring Patients Post-Stroke With Mobile ECG During the Hospital Stay.

Background The effectiveness of a nurse-led in-hospital monitoring protocol with mobile ECG (iECG) was investigated for detecting atrial fibrillation in patients post-ischemic stroke or post-transient ischemic attack. The study aimed to assess the cost-effectiveness of using iECG during the initial hospital stay compared with standard 24-hour Holter monitoring. Methods and Results A Markov microsimulation model was constructed to simulate the lifetime health outcomes and costs. The rate of atrial fibrillation detection in iECG and Holter monitoring during the in-hospital phase and characteristics of modeled population (ie, age, sex, CHA2DS2-VASc) were informed by patient-level data. Costs related to recurrent stroke, stroke management, medications (new oral anticoagulants), and rehabilitation were included. The cost-effectiveness analysis outcome was calculated as an incremental cost per quality-adjusted life-year gained. As results, monitoring patients with iECG post-stroke during the index hospitalization was associated with marginally higher costs (A$31 196) and greater benefits (6.70 quality-adjusted life-years) compared with 24-hour Holter surveillance (A$31 095 and 6.66 quality-adjusted life-years) over a 20-year time horizon, with an incremental cost-effectiveness ratio of $3013/ quality-adjusted life-years. Monitoring patients with iECG also contributed to lower recurrence of stroke and stroke-related deaths (140 recurrent strokes and 20 deaths avoided per 10 000 patients). The probabilistic sensitivity analyses suggested iECG is highly likely to be a cost-effective intervention (100% probability). Conclusions A nurse-led iECG monitoring protocol during the acute hospital stay was found to improve the rate of atrial fibrillation detection and contributed to slightly increased costs and improved health outcomes. Using iECG to monitor patients post-stroke during initial hospitalization is recommended to complement routine care.

Effect of surfactants on the chemiluminescence of acridinium dimethylphenyl ester labels and their conjugates.

Chemiluminescent acridinium dimethylphenyl esters, containing two methyl groups flanking the phenolic ester bond, display excellent chemiluminescence stability and are used as labels in automated immunoassays for clinical diagnostics. Light emission from these labels is triggered with alkaline peroxide in the presence of the cationic surfactant cetyltrimethylammonium chloride. Under these conditions, light emission is rapid and is complete in <5 s. In the present study we examined the effect of various surfactants on light emission from acridinium dimethylphenyl ester labels and their conjugates containing hydrophilic linkers derived either from hexa(ethylene)glycol or a sulfobetaine zwitterion. Sulfobetaine zwitterions are very polar and incorporation of these functional groups in acridinium dimethyphenyl esters and their conjugates represents a new approach to improving the aqueous solubility of these chemiluminescent labels. Our results indicate that in general, surfactants affect light emission from these labels and their conjugates by two discrete mechanisms. Cationic surfactants, but not anionic or non-ionic surfactants, accelerate overall light emission kinetics and a more modest effect is observed with zwitterionic surfactants. Surfactants also enhance total light output and the magnitude of this enhancement is maximal for cationic surfactants and a sulfobetaine zwitterionic surfactant. These observations are the first to clearly delineate the role of the surfactant on the chemiluminescence reaction pathway of acridinium esters and can be rationalized based on known effects of surfactant aggregates on bimolecular and unimolecular reactions.

Impact of COVID-19 pandemic and lockdown on eye emergencies.

BACKGROUND: To characterise and compare ocular pathologies presenting to an emergency eye department (EED) during the COVID-19 pandemic in 2020 against an equivalent period in 2019. METHODS: Electronic patient records of 852 patients in 2020 and 1818 patients in 2019, attending the EED at a tertiary eye centre (University Hospitals of Leicester, UK) were analysed. Data was extracted over a 31-day period during: (study period 1 (SP1)) COVID-19 pandemic lockdown in UK (24th March 2020-23rd April 2020) and (study period 2 (SP2)) the equivalent 2019 period (24th March 2019-23rd April 2019). RESULTS: A 53% reduction in EED attendance was noted during lockdown. The top three pathologies accounting for >30% of the caseload were trauma-related, keratitis and uveitis in SP1 in comparison to conjunctivitis, trauma-related and blepharitis in SP2. The overall number of retinal tears and retinal detachments (RD) were lower in SP1, the proportion of macula-off RD's (84.6%) was significantly (p = 0.0099) higher in SP1 (vs 42.9% in SP2). CONCLUSION: COVID-19 pandemic related lockdown has had a significant impact on the range of presenting conditions to the EED. Measures to stop spread of COVID-19 such as awareness of hand hygiene practices, social distancing measures and school closures could have an indirect role in reducing spread of infective conjunctivitis. The higher proportion of macula-off RD and lower number of retinal tears raises possibility of delayed presentation in these cases. Going forward, we anticipate additional pressures on EED and other subspecialty services due to complications and associated morbidity from delayed presentations.

Enhanced immunoassay sensitivity using chemiluminescent acridinium esters with increased light output.

Chemiluminescent acridinium ester labels are widely used in clinical diagnostics especially in automated immunochemistry analyzers such as Siemens Healthcare Diagnostics' ADVIA Centaur systems. Although, chemiluminescence from acridinium compounds was discovered more than 50 years ago, details regarding the excitation process are still not well understood particularly in relation to acridinium structure and overall light output. Herein, we report an empirical study that correlates the presence of electron-donating methoxy groups at C-2 and/or C-7 in the acridinium ring with increased light output. We further demonstrate that these high light output labels can be combined with hydrophilic functional groups such as hexa(ethylene)glycol to generate unique acridinium esters that are stable and are useful in improving immunoassay sensitivity for both competitive and sandwich automated immunoassays.

Nurse Led Smartphone Electrographic Monitoring for Atrial Fibrillation after Ischemic Stroke: SPOT-AF.

BACKGROUND AND PURPOSE: Paroxysmal atrial fibrillation (PAF) underlying acute stroke frequently evades detection by standard practice, considered to be a combination of routine electrocardiogram (ECG) monitoring, and 24-hour Holter recordings. We hypothesized that nurse-led in-hospital intermittent monitoring approach would increase PAF detection rate. METHODS: We recruited patients hospitalised for stroke/transient ischemic attack, without history of atrial fibrillation (AF), in a prospective multi-centre observational study. Patients were monitored using a smartphone-enabled handheld ECG (iECG) during routine nursing observations, and underwent 24-hour Holter monitoring according to local practice. The primary outcome was comparison of AF detection by nurse-led iECG versus Holter monitoring in patients who received both tests: secondary outcome was oral anticoagulant commencement at 3-month following PAF detection. RESULTS: One thousand and seventy-nine patients underwent iECG monitoring: 294 had iECG and Holter monitoring. AF was detected in 25/294 (8.5%) by iECG, and 8/294 (2.8%) by 24-hour Holter recordings (P<0.001). Median duration from stroke onset to AF detection for iECG was 3 days (interquartile range [IQR], 2 to 6) compared with 7 days (IQR, 6 to 10) for Holter recordings (P=0.02). Of 25 patients with AF detected by iECG, 11 were commenced on oral anticoagulant, compared to 5/8 for Holter. AF was detected in 8.8% (69/785 patients) who underwent iECG recordings only (P=0.8 vs. those who had both iECG and 24-hour Holter). CONCLUSIONS: Nurse-led in-hospital iECG surveillance after stroke is feasible and effective and detects more PAF earlier and more frequently than routine 24-hour Holter recordings. Screening with iECG could be incorporated into routine post-stroke nursing observations to increase diagnosis of PAF, and facilitate institution of guideline-recommended anticoagulation.

Effects of oestrogen agonists on human dermal fibroblasts in an in vitro wounding assay.

Oestrogen and dehydroepiandrosterone (DHEA) improve wound healing, but circulating levels decline significantly with age. Recently, the selective oestrogen receptor modulators (SERMs) tamoxifen and raloxifene have been shown to improve age-associated impaired wound healing. Therefore, we have evaluated the effects of 17beta-oestradiol, ER alpha and ER beta agonists, tamoxifen, raloxifene and DHEA on human dermal fibroblasts using an in vitro wound assay. An ER alpha agonist, 17beta-oestradiol and DHEA all significantly accelerated cell migration; the DHEA effect was blocked with an aromatase inhibitor. Tamoxifen, raloxifene and DHEA all significantly increased DNA synthesis; the DHEA stimulatory effect was reversed by an aromatase inhibitor. This study demonstrates that 17beta-oestradiol, an ER alpha agonist, tamoxifen, raloxifene and DHEA (following conversion to oestrogen) all have significant effects on human fibroblasts, the key mesenchymal cell involved in the wound healing process. Further understanding of the mechanisms involved may have important implications for the management of age-related impaired wound healing.

Myasthenia gravis seven years after removal of an invasive thymoma.

This report describes a 59-year-old male who developed myasthenia gravis 92 months following excision of an invasive thymoma, in the absence of tumour recurrence. This report highlights the importance of prolonged clinical surveillance in post-thymectomy patients.

Differing responses of human follicular and nonfollicular scalp cells in an in vitro wound healing assay: effects of estrogen on vascular endothelial growth factor secretion.

Improved wound healing of hairy skin may involve mesenchymal hair follicle cells with stem cell potential and enhancement by estrogen therapy. How estrogen affects follicular dermal papilla (DP) and dermal sheath (DS) cells in wound healing is unknown. Therefore, a comparison of estradiol action on DP, DS, and corresponding interfollicular dermal fibroblasts (DF) in a scratch-wound assay was performed using matching primary cultures established from female temporo-occipital scalp. All three cell types expressed mRNA transcripts and protein for estrogen receptors alpha (ERalpha) and beta (ERbeta). DF ERalpha transcripts were half that of DP and one-third of DS cells, while DF ERbeta transcripts were two-thirds of DP and DS cells. In the scratch-wound assay all three cells types migrated at similar rates, but only the rate of DF was enhanced by estradiol. Mechanical wounding increased DNA synthesis rates of all three cell types and increased the secretion of collagen by DF and DS cells. All three secreted similar basal levels of vascular endothelial growth factor (VEGF), which was increased by wounding DF and DS cells, but not DP cells. DP cells required estradiol to increase VEGF secretion; by contrast VEGF secretion was decreased by estradiol in wounded DS cells. These results highlight differences in the responses of DF, DP, and DS cells to estradiol in a scratch-wound assay, providing further support for the dichotomy of cellular functions in the hair follicle. Further understanding of the role of estrogen in cutaneous wound healing may have important implications for the management of chronic wounds and scarring.

Epidemiology and outcome analysis of 208 children with burns attending an emergency department.

OBJECTIVE: The purpose of this study was to prospectively study all burns attending a single inner city emergency department (ED) to establish epidemiological burn patterns and final outcomes for thermal injuries affecting children. DESIGN AND SETTING: A 12-month prospective study of all burns involving children (ages, 0-16 years) presenting to a single ED serving approximately 500,000 people. RESULTS: Two hundred eight children with burns attended the ED. The average patient age was 5 years, with most cases involving infants and young children. Fifty one percent of injuries were scalds, and 36% were contact burns. Burn size varied from 1% body surface area to 23% body surface area. First aid had not been administered in one third of cases before attendance, and 87% of patients had received no analgesia. Final outcomes were as follows: 5% of patients were discharged from the ED with no further follow-up. Twenty three percent of patients were instructed to attend their general practitioner for follow-up, and 58% were instructed to attend the ED clinic for review. Four percent of patients were reviewed in the plastic surgery dressing clinic, 7% were admitted to the plastic surgery ward, and 3% of patients were transferred to a burn center. In total, 3% of patients required burn excision and skin grafting for their burns. There were no deaths. CONCLUSIONS: Many pediatric burns are appropriately managed in the ED without the need for burn center care. Although the mortality from burn injury in children may have fallen in recent decades, problems persist in terms of small burns that can be associated with long-standing morbidity. Education and prevention programs are still required at all levels to help address the problem of childhood burns.