Early preantral follicles of the domestic cat express gonadotropin and sex steroid signaling potential.

Key biomolecular processes, which regulate primordial ovarian follicle dormancy and early folliculogenesis in mammalian ovaries, are not fully understood. The domestic cat is a useful model to study ovarian folliculogenesis and is the most relevant for developing in vitro growth methods to be implemented in wild felid conservation breeding programs. Previously, RNA-sequencing of primordial (PrF), primary (PF), and secondary follicle (SF) samples from domestic cat implicated ovarian steroidogenesis and steroid reception during follicle development. Here, we aimed to identify which sex steroid biosynthesis and metabolism enzymes, gonadotropin receptors, and sex steroid receptors are present and may be potential regulators. Differential gene expression, functional annotation, and enrichment analyses were employed and protein localization was studied too. Gene transcripts for PGR, PGRMC1, AR (steroid receptors), CYP11A1, CYP17A1, HSD17B1 and HSD17B17 (steroidogenic enzymes), and STS (steroid metabolizing enzyme) were significantly differentially expressed (Q values of ≤0.05). Differential gene expression increased in all transcripts during follicle transitions apart from AR which decreased by the secondary stage. Immunohistochemistry localized FSHR and LHCGR to oocytes at each stage. PGRMC1 immunostaining was strongest in granulosa cells, whereas AR was strongest in oocytes throughout each stage. Protein signals for steroidogenic enzymes were only detectable in SFs. Products of these significantly differentially expressed genes may regulate domestic cat preantral folliculogenesis. In vitro growth could be optimized as all early follicles express gonadotropin and steroid receptors meaning hormone interaction and response may be possible. Protein expression analyses of early SFs supported its potential for producing sex steroids.

Effects of corn silage inclusion in preweaning calf diets.

The objective of this research was to evaluate the effects of corn silage inclusion in starter feed provided to calves after birth through weaning at 7 wk of age. Thirty-six heifer calves and 9 bull calves were individually housed in hutches. Calves in treatment groups received pasteurized milk with all calf starter, 25% calf starter and 75% corn silage, or all corn silage. Values were recorded daily for feed intake and health, which included fecal, respiratory, and attitude scores; and at wk 2, 4, and 8 for concentrations of serum protein, hematocrit, and serum ß-hydroxybutyrate. Body weight, withers height, and hip height were measured at wk 2, 4, 8, and 52. Nine bull calves (3/treatment) were killed at 8 wk of age for assessment of rumen and intestinal tissue morphology. Feed intake and average daily gain were not different among treatments. Least squares means of rumen papillae lengths were significantly different and decreased as corn silage inclusion increased. Crypt depths and total thickness of epithelium were reduced for the corn silage group. Least squares means of body weight, heart girth, hip height, withers height, serum protein, hematocrit, and ß-hydroxybutyrate concentrations did not differ among treatments. These data indicated that the mixture of corn silage and starter did not affect growth, feed intake, or intestinal morphology but did affect rumen wall morphology. Feeding solely corn silage as starter feed stunted the growth of rumen papillae and tended to impair intestinal morphology, indicating that only calf starter or a mixture of calf starter and corn silage is more appropriate.

The NICE classification for 'Ultra-radical (extensive) surgery for advanced ovarian cancer' guidance does not meaningfully predict postoperative complications: a cohort study.

OBJECTIVE: To determine which descriptors of cytoreductive surgical extent in advanced ovarian cancer (AOC) best predict postoperative morbidity. DESIGN: Retrospective notes review. SETTING: A gynaecological cancer centre in the UK. POPULATION: Six hundred and eight women operated on for AOC over a period of 114 months at a tertiary cancer centre, between 16 August 2007 and 16 February 2017. METHODS: Outcome data were analysed by six approaches to classify the extent of surgery: standard/ultra-radical surgery; standard/radical/supra-radical surgery; presence/absence of gastrointestinal resections; low/intermediate/high surgical complexity score (SCS); presence of bowel anastomoses and/or diaphragmatic surgery; and the presence/absence of multiple bowel resections. MAIN OUTCOME MEASURES: Major (grades 3-5) postoperative morbidity and mortality. RESULTS: Forty-three (7.1%) patients experienced major complications. Grade-5 complications occurred in six patients (1.0%). Patients who underwent multiple bowel resections had a relative risk (RR) of 7.73 (95% confidence interval, 95% CI 3.92-15.26), patients with a high SCS had an RR of 6.12 (95% CI 3.25-11.52), patients with diaphragmatic surgery and gastrointestinal anastomosis had an RR of 5.57 (95% CI 2.65-11.72), patients with 'any gastrointestinal resection' had an RR of 4.69 (95% CI 2.66-8.24), patients with ultra-radical surgery had an RR of 4.65 (95% CI 2.26-8.79), and patients with supra-radical surgery had an RR of 4.20 (95% CI 2.35-7.51) of grades 3-5 morbidity, compared with patients undergoing standard surgery as defined by the National Institute for Health and Care Excellence (NICE) in the UK. No significant difference was seen in the rate of major morbidity between standard (6/59, 10.2%) and ultra-radical (9/81, 11.1%) surgery within the cohort who had intermediate complex surgery (P > 0.05). CONCLUSIONS: The numbers of procedures performed significantly correlate with major morbidity. The number of procedures performed better predicted major postoperative morbidity than the performance of certain 'high risk' procedures. We recommend using SCS to define a higher risk operation. NICE should re-evaluate the use of the term 'ultra-radical' surgery. TWEETABLE ABSTRACT: Multiple bowel resection is the best predictor of morbidity and is more predictive than 'ultra-radical surgery'.

Adjacent Lichen Sclerosis predicts local recurrence and second field tumour in women with vulvar squamous cell carcinoma.

OBJECTIVE: In this study, we investigated if the presence of histologically abnormal epithelium adjacent to the primary tumour influenced the frequency, timing, and topography of local vulvar recurrences (LVR) following treatment for squamous cell carcinoma of the vulva (VSCC). METHODS: The study population comprised a cohort of 201 consecutive cases with incident VSCC. LVR were categorised as local relapses (LR) if they occurred <2cm from the tumour margins, and as second field tumours (SFT) when ≥2cm from these margins. Univariable and multivariable competing risk modelling was performed to identify the prognostic factors associated with local disease recurrence. RESULTS: The characterization of the epithelium adjacent to the invasive component was possible for 199 (99.0%) patients. Of these, 171 (85.9%) were found to have intraepithelial abnormalities found adjacent to the surgical specimen. Multivariable analyses revealed that, following adjustment, Lichen Sclerosis (LS) was associated with an increase in the incidence of LVR, LR and SFT (SHRs: 3.4, 2.7 and 4.4, respectively). Although the incidence of LR and SFT in women with LS associated VSCC was similar, the peak incidence of SFT occurred more than two years before that of LR. CONCLUSIONS: Women with VSCC arising in a field of LS may continue to have an increased risk of developing LR and SFT for many years after resection of their primary tumour. Our study suggests that these women should be followed up more regularly so that LVR can be detected earlier; unless a more robust surveillance programme or chemopreventative treatments become available.

Temporal analysis of dissolution by-products and genotoxic potential of spherical zinc-silicate bioglass: "imageable beads" for transarterial embolization.

Embolization of vascular tumors is an important tool in minimally invasive surgical intervention. Radiopaque, non-degradable, and non-deformable spherical zinc-silicate glass particles were produced in a range of 45-500 µm. Three size ranges (45-150, 150-300, and 300-500 µm) were used in the current study. The glass microspheres were eluted in polar (saline solution) and non-polar (dimethyl sulfoxide) medium, and ion release profiles were recorded using inductively coupled plasma atomic emission spectroscopy. Approximately 80% of Gaussian distribution was achieved by simple sieving. The ions released from the microspheres were dependent upon surface area to volume ratio as well as the nature of elution media. Greater ions were released from smaller particles (45-150 µm) having largest surface area in polar medium. For the genotoxicity bacterial mutation Ames assay, the concentrations of all the ions were well below their therapeutic concentration reported in the literature. No mutagenic effect was observed in the bacterial mutation Ames test. Hence, it can be concluded that the glass microspheres produced herein are non-mutagenic further supporting the materials potential as a suitable embolic agent.

Should pelvic exenteration for symptomatic relief in gynaecology malignancies be offered?

OBJECTIVE: To review the outcomes of pelvic exenterative surgery done with a palliative intent and evaluate its role in relapsed gynaecology malignancies. METHOD: This is a retrospective cohort study between April 2009 and May 2012 in Oxford Gynaecological Cancer Centre. Patients were identified from the oncology surgical database. RESULTS: 18 patients were identified with a mean age 54 (26-79) years, who underwent surgery for symptomatic recurrent cancer. All except one patient had radiotherapy prior to surgery. 12 patients had cervical cancer, five had vulval cancer and one had endometrial cancer. About half of the patients had major surgical complications; however, majority was patients satisfied with the outcome. CONCLUSION: Pelvic exenteration in this context carries considerable morbidity and in this series achieved good symptom control with a mean overall survival of 11 months. Careful patient selection, adequate counselling and ongoing support are imperative of successful outcome.

Novel adaptations to zinc-silicate glass polyalkenoate cements: the unexpected influences of germanium based glasses on handling characteristics and mechanical properties.

Aluminum-free glass polyalkenoate cements (GPC) have been hindered for use as injectable bone cements by their inability to balance handling characteristics with mechanical integrity. Currently, zinc-based, aluminum-free GPCs demonstrate compression strengths in excess of 60MPa, but set in c. 1-2 min. Previous efforts to extend the setting reaction have remained clinically insufficient and are typically accompanied by a significant drop in strength. This work synthesized novel glasses based on a zinc silicate composition with the inclusion of GeO2, ZrO2, and Na2O, and evaluated the setting reaction and mechanical properties of the resultant GPCs. Germanium based GPCs were found to have working times between 5 and 10 min, setting times between 14 and 36 min, and compression strengths in excess of 30 MPa for the first 30 days. The results of this investigation have shown that the inclusion of GeO2, ZrO2, and Na2O into the glass network have produced, for the first time, an aluminum-free GPC that is clinically viable as injectable bone cements with regards to handling characteristics and mechanical properties.

Characterization of PLGA based composite nerve guidance conduits: effect of F127 content on modulus over time in simulated physiological conditions.

PLGA/pluronic F127 based nerve guidance conduits (NGCs) for peripheral nerve regeneration offer excellent potential for clinical use. To date, little emphasis has been directed towards the effect of pluronic F127 on their subsequent mechanical properties as a function of degradation time or the physiological environment. This report was designed to redress the balance. This study synthesised 5 groups of 20wt% PLGA NGCs with varied additions of pluronic F127 (range 0-5wt%) to obtain Young's Moduli (E) in the range of 7-107MPa, depending on degradation conditions and pluronic F127 content.

FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy.

Several nerve guidance conduits (NGCs) and nerve protectant wraps are approved by the US Food and Drug Administration (FDA) for clinical use in peripheral nerve repair. These devices cover a wide range of natural and synthetic materials, which may or may not be resorbable. This review consolidates the data pertaining to all FDA approved materials into a single reference, which emphasizes material composition alongside pre-clinical and clinical safety and efficacy (where possible). This article also summarizes the key advantages and limitations for each material as noted in the literature (with respect to the indication considered). In this context, this review provides a comprehensive reference for clinicians which may facilitate optimal material/device selection for peripheral nerve repair. For materials scientists, this review highlights predicate devices and evaluation methodologies, offering an insight into current deficiencies associated with state-of-the-art materials and may help direct new technology developments and evaluation methodologies thereof.

Birth size and physical activity in a cohort of Indian children aged 6-10 years.

There is evidence of a reduction in children's physical activity in India in the last decade. Our objective was to assess whether size and body composition at birth are associated with physical activity in school-aged children. Children from a prospective observational cohort study born in Mysore, South India between 1997 and 1998 (n = 663) had neonatal anthropometric measurements made within 72 h of delivery [weight, mid-upper arm circumference (MUAC), chest, abdomen and head circumference, crown-heel, crown-buttock and leg length, triceps and subscapular skinfolds]. At 6-10 years, children (n = 449) were asked to wear AM7164 or GT1M Actigraph accelerometers for 7 days. Body composition was measured within 6 months of activity monitoring. Arm muscle area at birth and time of activity monitoring was calculated from MUAC and skinfold measurements. Activity outcome measures were: mean accelerometer counts per minute (cpm); counts per day and proportion of time spent in moderate and vigorous activity. The mean (S.D.) number of days with ≥500 min of recorded accelerometer data was 7.0 (1.1). Linear regression models showed no significant associations between any of the neonatal anthropometric measures and the activity variables. Body fat percentage at 7.5 years was negatively associated with all activity variables (B = -4.69, CI: -7.31, -2.07 for mean cpm). In conclusion, this study showed no associations between body size and skinfold thickness at birth and objectively measured physical activity in childhood.

Experimental composite guidance conduits for peripheral nerve repair: an evaluation of ion release.

Poly (lactide-co-glycolide) (PLGA) - Pluronic F127 - glass composites have demonstrated excellent potential, from the perspective of controlled mechanical properties and cytocompatibility, for peripheral nerve regeneration. In addition to controlling the mechanical properties and cytotoxicity for such composite devices, the glass component may mediate specific responses upon implantation via degradation in the physiological environment and release of constituent elements. However, research focused on quantifying the release levels of such therapeutic ions from these experimental medical devices has been limited. To redress the balance, this paper explores the ion release profiles for Si(4+), Ca(2+), Na(+), Zn(2+), and Ce(4+) from experimental composite nerve guidance conduits (CNGC) comprising PLGA (at 12.5, and 20 wt.%), F127 (at 0, 2.5 and 5 wt.%) and various loadings of Si-Ca-Na-Zn-Ce glass (at 20 and 40 wt.%) for incubation periods of up to 28 days. The concentration of each ion, at various time points, was determined using Inductively Coupled Plasma-Atomic Emission Spectrometry (Perkin Elmer Optima 3000). It was observed that the Si(4+), Na(+), Ca(2+), Zn(2+) release from CNGCs in this study ranged from 0.22 to 6.477 ppm, 2.307 to 3.277 ppm, 40 to 119 ppm, and 45 to 51 ppm, respectively. The Ce(4+) concentrations were under the minimum detection limits for the ICP instrument utilized. The results indicate that the ion release levels may be appropriate to mediate therapeutic effects with respect to peripheral nerve regeneration. The data generated in this paper provides requisite evidence to optimize composition for pre-clinical evaluation of the experimental composite.

Prediction of body-fat percentage from skinfold and bio-impedance measurements in Indian school children.

BACKGROUND/OBJECTIVES: Few equations for calculating body-fat percentage (BF%) from field methods have been developed in South-Asian children. The objective of this study was to assess agreement between BF% derived from primary reference methods and that from skinfold equations and bio-impedance analysis (BIA) in Indian children. SUBJECTS/METHODS: We measured BF% in two groups of Indian children. In Pune, 570 rural children aged 6-8 years underwent dual-energy X-ray absorptiometry (DXA) scans. In Mysore (18)O in doubly labeled water was administered to 59 urban children aged 7-9 years. We conducted BIA at 50 kHz and anthropometry, including sub-scapular and triceps skinfold thicknesses. We used the published equations of Wickramasinghe, Shaikh, Slaughter and Dezenburg to calculate BF% from anthropometric data and the manufacturer's equation for BIA measurements. We assessed agreement with values derived from DXA and doubly labeled water using Bland-Altman analysis. RESULTS: Children were light and thin on average compared with international standards. There was poor agreement between the reference BF% values and those from all equations. Assumptions for Bland-Altman analysis were not met for Wickramasinghe, Shaikh and Slaughter equations. The Dezenberg equations under-predicted BF% for most children (mean difference in Pune -13.4, LOA -22.7, -4.0 and in Mysore -7.9, LOA (-13.7 and -2.2). The mean bias for the BIA equation in Pune was +5.0% and in Mysore +1.95%, and the limits of agreement were wide; -5.0, 15.0 and -7.8, 11.7 respectively. CONCLUSIONS: Currently available skinfold equations do not accurately predict BF% in Indian children. We recommend development of BIA equations in this population using a four-compartment model.

Time-dependent evaluation of mechanical properties and in vitro cytocompatibility of experimental composite-based nerve guidance conduits.

The use of nerve guidance conduits to repair peripheral nerve discontinuities has attracted much attention from the biomaterials community, with many resorbable and non-resorbable materials in clinical use. However, a material with ideal biocompatibility, sufficient mechanical properties (to match that of the regenerating nerve) coupled with a suitable degradation rate, has yet to be realized. Recently, potential solutions (composite nerve guidance conduits) which support the emerging philosophy of allowing synthetic materials to establish key interactions with cells in ways that encourage self-repair (i.e. ionic mediators of repair such as those observed in hard tissue regeneration) have been proposed in the literature; such composites comprise specially designed bioactive phosphate-free glasses embedded in degradable polymeric matrices. Whilst much research has focussed on the optimization of such composites, there is no published literature on the performance of these experimental compositions under simulated physiological conditions. To address this key limitation, this paper explores the time-dependent variations in wet-state mechanical properties (tensile modulus and ultimate tensile strength) for NGC composites containing various compositions of PLGA (at 12.5, and 20 wt%), F127 (at 0, 2.5 and 5 wt%) and various loadings of Si-Na-Ca-Zn-Ce glass (at 0 and 20 wt%). It was observed that Young's modulus and ultimate tensile strength of these composites were in the range 5-203 MPa and 1-7 MPa respectively, indicating comparable mechanical performance to clinical materials. Furthermore, an analysis of the cytocompatibility of experimental compositions showed comparable (in some instances superior), compatibility when compared with the commercial product Neurolac(®). Based on current synthetic devices and the demands of the indication, the CNGCs examined in this work offer appropriate mechanical properties and compatibility to warrant enhanced development.

Composition-property relationships for an experimental composite nerve guidance conduit: evaluating cytotoxicity and initial tensile strength.

The objective of this work was to examine the main (individual), combined (interaction) and second-order (quadratic) effects of: (i) poly(D,L-lactide-co-glycolide) (PLGA), (ii) F127, and (iii) a zinc-silicate based bioactive glass, on the cytotoxicity and ultimate tensile strength of an experimental nerve guidance conduit (NGC). The experimental plan was carried out according to a Box-Behnken design matrix. The effects of each compositional factor were quantified using response surface methodology (RSM) techniques. Linear and quadratic polynomial equations were developed to examine cytotoxicity (after incubation at 3, 7 and 28 days) and initial ultimate tensile strength (UTS(0)). Multiple regression analyses showed that the developed models yielded a good prediction for each response examined. It was observed that the beneficial effects of PLGA and bioactive glass on controlling cytotoxicity appeared greater than that of F127. Furthermore, the experimental conduits (with the exception of CNGC-I and CNGC-K) generally showed superior cytocompatibility when compared with the comparable literature for the clinically used nerve guidance conduit Neurolac(®). In this investigation, optimal compositions for cell viability were obtained for the following composition: PLGA = 18.89 wt%/F127 = 0.52 wt%/glass = 12.71 wt%. The optimization of composition with respect to ultimate tensile strength was also established (desired UTS(0) being based on the properties of the control device Neurolac(®) whose UTS is c.20 MPa). The desired UTS(0) of ≤ 20 MPa was found for the composition: PLGA = 18.63 wt%/F127 = 0.77 wt%/glass = 5.54 wt%. A UTS(0) ≤ 30 MPa was recorded for the composition: PLGA = 18.34 wt%/F127 = 0.62 wt%/glass = 9.83 wt%, such tensile strengths are comparable to, reported values for Neurolac(®). Examination of the composition-property relationships with respect to combining cell viability and UTS(0) indicated preferred compositions in the range 17.97-19.90 wt% PLGA, 0.16-1.13 wt% F127 and between 5.54 and ≤ 20 wt% glass. This research demonstrates the value of a design of experiments approach for the design of novel nerve guidance conduits, and shows that the materials examined may have potential for the repair of peripheral nerve discontinuities.

Aggressive angiomyxoma: a case series and literature review.

BACKGROUND: Aggressive angiomyxoma was identified as a distinct clinicopathologic entity in 1983 and since then fewer than 250 cases of these rare tumors have been reported in world literature. These tumors usually arise in the pelvis and perineal regions, most often in women of the reproductive age group; however a few cases of its occurrence outside the pelvis have also been reported. PATIENTS AND METHODS: We report a series of 7 women treated in our institute in the last 8 years. Relevant literature on aggressive angiomyxoma was looked at and various management options reviewed. CONCLUSION: Aggressive angiomyxomas are locally aggressive, notorious for local recurrence and extremely rare to metastasize. While surgery remains the mainstay of treatment, there has been a definite shift towards less radical forms of excision, over the years. Various adjuvant treatment modalities have also been tried to reduce tumor recurrence.

The relationship of birthweight, muscle size at birth and post-natal growth to grip strength in 9-year-old Indian children: findings from the Mysore Parthenon study.

Foetal development may permanently affect muscle function. Indian newborns have a low mean birthweight, predominantly due to low lean tissue and muscle mass. We aimed to examine the relationship of birthweight, and arm muscle area (AMA) at birth and post-natal growth to handgrip strength in Indian children. Grip strength was measured in 574 children aged 9 years, who had detailed anthropometry at birth and every 6-12 months post-natally. Mean (standard deviation (s.d.)) birthweight was 2863 (446) g. At 9 years, the children were short (mean height s.d. -0.6) and light (mean weight s.d. -1.1) compared with the World Health Organization growth reference. Mean (s.d.) grip strength was 12.7 (2.2) kg (boys) and 11.0 (2.0) kg (girls). Weight, length and AMA at birth, but not skinfold measurements at birth, were positively related to 9-year grip strength (ß = 0.40 kg/s.d. increase in birthweight, P < 0.001; and ß = 0.41 kg/s.d. increase in AMA, P < 0.001). Grip strength was positively related to 9-year height, body mass index and AMA and to gains in these measurements from birth to 2 years, 2-5 years and 5-9 years (P < 0.001 for all). The associations between birth size and grip strength were attenuated but remained statistically significant for AMA after adjusting for 9-year size. We conclude that larger overall size and muscle mass at birth are associated with greater muscle strength in childhood, and that this is mediated mainly through greater post-natal size. Poorer muscle development in utero is associated with reduced childhood muscle strength.

Relationship between physical activity measured using accelerometers and energy expenditure measured using doubly labelled water in Indian children.

BACKGROUND/OBJECTIVES: To test the association between physical activity measured using accelerometer counts (Actigraph) and energy expenditure (EE) measured using the doubly labelled water (DLW) method in free-living children in India. The aim of this study was to explore the usefulness of Actigraphs in estimating EE. SUBJECTS/METHODS: Total EE (TEE) was measured in 58 children aged 8-9 years over a period of 2 weeks using the DLW technique. Physical activity level (PAL) was estimated from TEE, and the basal metabolic rate was predicted from weight. Physical activity was measured simultaneously using the Actigraph accelerometers (MTI AM7164 and GT1M). TEE was also calculated from the Actigraph counts using a published equation. RESULTS: TEE (mean: 6.6 vs 5.7 MJ, P=0.04) and Actigraph counts (counts/minute: 557 vs 465, P=0.02; total counts: 445 534 vs 354 748, P=0.004) were higher in boys than in girls. There were no significant correlations between either total Actigraph counts (r=0.15, P=0.3) or counts/minute (r=0.18, P=0.2), and TEE estimated using DLW. Similarly, there were no significant correlations between Actigraph counts and PAL (r=0.10, P=0.5; r=0.17, P=0.2, respectively). The Bland-Altman analysis showed poor agreement between TEE estimated using the DLW method and TEE derived from the Actigraph equation. CONCLUSIONS: Activity measured using Actigraph accelerometers was not related to TEE and PAL derived using the DLW technique in children in Mysore. Actigraphs may not be useful in predicting EE in this setting, but may be better used for judging activity patterns.

Bacterial delivery of a novel cytolysin to hypoxic areas of solid tumors.

The efficacy of current anti-cancer gene therapies is limited by the inability of gene vectors to penetrate the poorly vascularized, hypoxic regions of tumors, leaving these sites untreated. We describe a new approach for targeting gene therapy to these sites, which employs an attenuated strain of the non-pathogenic bacterium, Salmonella typhimurium, carrying an exogenous (that is, reporter or therapeutic) gene under the regulation of a new, highly hypoxia-inducible promoter (FF+20(*)). This bacterial vector was seen to rapidly migrate into, and thrive in, hypoxic areas of both mammary tumor spheroids grown in vitro and orthotopic mammary tumors after systemic injection. Using the reporter gene construct, FF+20(*)-lacZ, we show that bacterial expression of high levels of beta-galactosidase occurred only in hypoxic/necrotic sites of spheroids and tumors. We then replaced the reporter gene with one encoding a novel cytotoxic protein (HlyE) and showed that this was also expressed by bacteria only in hypoxic regions of murine mammary tumors. This resulted in a marked increase in tumor necrosis and reduced tumor growth. Our system represents a promising new strategy for delivering gene therapy to poorly vascularized regions of tumors and shows, for the first time, the efficacy of HlyE as an anti-tumor agent.

Endometrial atypical hyperplasia and subsequent diagnosis of endometrial cancer: a retrospective audit and literature review.

This study investigates the rate of endometrial carcinoma found at hysterectomy in women with a biopsy diagnosis of atypical endometrial hyperplasia, in the John Radcliffe Hospital, Oxford. The Gynecologic Oncology Group (GOG) recently reported a rate of 42.6% in a large prospective study in the USA (Trimble et al. 2006). This retrospective study has identified a similar rate of 45.9% at the John Radcliffe. There is much interest in conservative therapies for atypical endometrial hyperplasia, but with such a high incidence of endometrial carcinoma in cases of atypical endometrial hyperplasia diagnosed by endometrial biopsy, it would seem prudent to exercise caution when considering any conservative therapy.