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Context: While uncommon, spinal cord injuries most frequently occur in adolescent and young adult males. Established treatment options are limited and focused on supportive care. Therapeutic systemic hypothermia is an emerging experimental treatment currently undergoing clinical trials in adults. Findings: Here we report a case of a 13-year-old male with an American Spinal Injury Association Impairment Scale grade C traumatic cervical spinal cord injury treated with 48 hours of therapeutic systemic hypothermia who made a complete neurological recovery. To our knowledge, this is the youngest such case report. Clinical relevance: This case suggests that consideration should be given to including pediatric patients in future clinical trials of therapeutic hypothermia for spinal cord injury.

Introduction: North Carolina (NC) is home to more than 30 species of indigenous venomous and nonvenomous snakes. Snakebites can cause debilitating and potentially fatal injuries. However, there is a lack of current information available describing the incidence of snakebites in NC. Therefore, we performed this study of snakebites treated in NC emergency departments (EDs) using the statewide syndromic surveillance system, the North Carolina Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT)., Methods: This was a descriptive epidemiologic study characterizing NC ED visits collected by NC DETECT between October 1, 2013 and September 30, 2015 with an assigned International Classification of Diseases, 9th Revision, Clinical Modification code or keyword indicating a snakebite., Results: Over the 2-year period, the absolute count of snakebite-related ED visits was 2080 visits with an incidence rate of 10.4 visits per 100 000 person-years (95% confidence interval: 10.0-10.9). The frequency of snakebite was highest during the summer months and evening hours. Men had higher incidence rates of snakebite-related ED visits than women, and residents of the Coastal Plain geographic region of NC had higher incidence rates than persons in other regions., Conclusions: The current study indicated that snakebites are common injuries treated at NC EDs, with a strong seasonal and geographic component. Additional research is needed to further characterize the circumstances associated with snakebites for the development of preventive measures and public health education., (Copyright © 2018 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to describe discharge instructions given to school-aged patients evaluated in a children's emergency department (ED) following concussion., Methods: This was a retrospective cohort study of children 6 to 18 years evaluated in a dedicated children's ED at a level I trauma center in 2008 following acute head trauma regardless of mechanism, identified by any of 27 International Classification of Disease, Ninth Revision diagnoses for head injury, concussion, or skull fracture. Included were those presentations consistent with the Zurich definition for concussion. Excluded were hospital admission, death before admission, evidence of intoxication, or structural abnormality on imaging. Univariate and multivariate analyses determined adjusted odds ratios (ORs) for receipt of concussion-specific discharge instructions and activity restrictions., Results: Of 350 eligible patients, the 218 included patients were mostly male (68%) with mean age 12.8 (SD, 3.4) years. Injury characteristics included sports-related, 42%; fall, 23%; loss of consciousness, 33%; headache, 75%; dizziness, 29%; amnesia, 25%; and vomiting, 19%. Most patients underwent imaging (81%). Discharge characteristics included concussion stated in final diagnosis, 31%; concussion-specific instructions, 62%; and activity restrictions, 34%. Concussion-specific discharge instructions were more likely for loss of consciousness (OR, 1.7; 95% confidence interval [CI], 1.22-2.36), and activity restrictions were more likely for sport-related injury (OR, 1.31; 95% CI, 1.02-1.76) and amnesia (OR, 1.42; 95% CI, 1.01-1.98)., Conclusions: Most children meeting diagnostic criteria for concussion were discharged without concussion-specific diagnoses or activity restrictions. Given the risks associated with untimely return to both physical and cognitive activity after concussion, improved awareness and standardization of disposition are imperative for the management of these young patients in the ED.

Introduction: The role of laparoscopic lymphadenectomy in the management of gynaecological cancers has been established over the last two decades, having been first described in Dargent and Selvat (L'envahissement ganglionnaire pelvin. Medsi-Mcgraw Hill, Paris, 1989). It has been shown that laparoscopic lymphadenectomy can be performed in the majority of patients and is associated with a low complication rate. However, the technique continues to be undertaken in only a relatively small number of Gynaecological Cancer Centres in the UK owing to the long learning curve and wide variations in training., Materials and Methods: At the Royal Wolverhampton NHS Trust Gynaecological Cancer Centre in the Greater Midlands Cancer Network laparoscopic lymphadenectomy has been performed since 1999 in the management of early cervical and high grade endometrial cancers. We have undertaken a retrospective audit (1999-2009) of these 42 cases to assess the feasibility of the procedure as well as to assess the complication rate., Conclusion: We are presenting the first reported series of exclusive laparoscopic transperitoneal lymphadenectomies from a Gynaecological Cancer Centre in the UK.

Purpose: To determine the effects of training with low muscle glycogen on exercise performance, substrate metabolism, and skeletal muscle adaptation., Methods: Fourteen well-trained cyclists were pair-matched and randomly assigned to HIGH- or LOW-glycogen training groups. Subjects performed nine aerobic training (AT; 90 min at 70% VO2max) and nine high-intensity interval training sessions (HIT; 8 × 5-min efforts, 1-min recovery) during a 3-wk period. HIGH trained once daily, alternating between AT on day 1 and HIT the following day, whereas LOW trained twice every second day, first performing AT and then, 1 h later, performing HIT. Pretraining and posttraining measures were a resting muscle biopsy, metabolic measures during steady-state cycling, and a time trial., Results: Power output during HIT was 297 ± 8 W in LOW compared with 323 ± 9 W in HIGH (P < 0.05); however, time trial performance improved by ∼10% in both groups (P < 0.05). Fat oxidation during steady-state cycling increased after training in LOW (from 26 ± 2 to 34 ± 2 μmol·kg−¹·min−¹, P < 0.01). Plasma free fatty acid oxidation was similar before and after training in both groups, but muscle-derived triacylglycerol oxidation increased after training in LOW (from 16 ± 1 to 23 ± 1 μmol·kg−¹·min−¹, P < 0.05). Training with low muscle glycogen also increased β-hydroxyacyl-CoA-dehydrogenase protein content (P < 0.01)., Conclusions: Training with low muscle glycogen reduced training intensity and, in performance, was no more effective than training with high muscle glycogen. However, fat oxidation was increased after training with low muscle glycogen, which may have been due to the enhanced metabolic adaptations in skeletal muscle.

Objective: To explore the role of long-standing hormone replacement therapy (HRT) in the malignant transformation of endometriosis., Design: Short case series. Three cases of women with pelvic clearance receiving long-standing HRT studied in detail., Setting: Teaching hospital in the United Kingdom (Gynaecological Cancer Centre) (Institutional Review Board approval was not obtained as it was not deemed necessary, this being a case series)., Patient(s): Women with a history of pelvic clearance for endometriosis and longstanding HRT., Intervention(s): HRT., Main Outcome Measure(s): Malignant transformation of endometriosis., Result(s): Long-standing HRT in all three women with pelvic clearance for endometriosis resulted in malignant transformation of residual endometriosis many years after the initial surgery. All cases presented with a new pelvic lesion., Conclusion(s): The diagnosis of malignant transformation needs to be considered in women with a history of endometriosis and with long-term HRT use in whom a new pelvic lesion is detected. The risk of malignant transformation in women with endometriosis after pelvic clearance receiving HRT needs to be explored further. Surveillance with CA-125 and imaging in such cases to predict recurrence or malignant transformation needs to be studied further in a research setting.

Purpose: To evaluate the efficacy of using combined glucose and fructose (GF) ingestion as a means to stimulate short-term (4 h) postexercise muscle glycogen synthesis compared to glucose only (G)., Methods: On two separate occasions, six endurance-trained men performed an exhaustive glycogen-depleting exercise bout followed by a 4-h recovery period. Muscle biopsy samples were obtained from the vastus lateralis muscle at 0, 1, and 4 h after exercise. Subjects ingested carbohydrate solutions containing G (90 g x h(-1)) or GF (G = 60 g x h(-1); F = 30 g x h(-1)) commencing immediately after exercise and every 30 min thereafter., Results: Immediate postexercise muscle glycogen concentrations were similar in both trials (G = 128 +/- 25 mmol x kg(-1) dry muscle (dm) vs GF = 112 +/- 16 mmol x kg(-1) dm; P > 0.05). Total glycogen storage during the 4-h recovery period was 176 +/- 33 and 155 +/- 31 mmol x kg(-1) dm for G and GF, respectively (G vs GF, P > 0.05). Hence, mean muscle glycogen synthesis rates during the 4-h recovery period did not differ between the two conditions (G = 44 +/- 8 mmol x kg(-1) dm x h(-1) vs GF = 39 +/- 8 mmol x kg(-1) dm x h(-1), P > 0.05). Plasma glucose and serum insulin responses during the recovery period were similar in both conditions, although plasma lactate concentrations were significantly elevated during GF compared to G (by approximately 0.8 mmol x L(-1), P < 0.05)., Conclusions: Glucose and glucose/fructose (2:1 ratio) solutions, ingested at a rate of 90 g x h(-1), are equally effective at restoring muscle glycogen in exercised muscles during the recovery from exhaustive exercise.

Objectives: Endometriosis is a long term, disabling condition, and a common cause of chronic pelvic pain. Symptomatic disease is usually characterised by pelvic and abdominal pain, lower back pain, and dyspareunia, all of which may be severe and debilitating. Yet the time between onset of symptoms and diagnosis is frequently a number of years, and many women report negative experience within the primary care setting. This paper explores the experience of women with endometriosis in the primary care setting., Study Design: A qualitative research design was considered appropriate to elicit the experience of endometriosis and the impact on women's lives. Semi-structured interviews were conducted with 30 women who suffer with endometriosis. The sample was recruited via a dedicated endometriosis clinic in the English Midlands, and participants had all been diagnosed laparoscopically with endometriosis., Results: Participants described diverse experiences within the primary care setting. Although some women reported a positive relationship with their general practitioner, over half had had negative experiences, which they felt had contributed to delays in them receiving a diagnosis of endometriosis., Conclusion: The delay in diagnosis can be reduced and perceived attitudes of general practitioners towards women presenting with endometriosis can be improved by being alert to certain symptomology, and by detailed and sensitive history taking.

Background: The lymph node status of a patient is a key determinate in staging, prognosis and adjuvant treatment of endometrial cancer. Despite this, the potential additional morbidity associated with lymphadenectomy makes its role controversial. This study systematically reviews the accuracy literature on sentinel node biopsy; ultra sound scanning, magnetic resonance imaging (MRI) and computer tomography (CT) for determining lymph node status in endometrial cancer., Methods: Relevant articles were identified form MEDLINE (1966-2006), EMBASE (1980-2006), MEDION, the Cochrane library, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 18 relevant primary studies (693 women). Data was extracted for study characteristics and quality. Bivariate random-effect model meta-analysis was used to estimate diagnostic accuracy of the various index tests., Results: MRI (pooled positive LR 26.7, 95% CI 10.6 - 67.6 and negative LR 0.29 95% CI 0.17 - 0.49) and successful sentinel node biopsy (pooled positive LR 18.9 95% CI 6.7 - 53.2 and negative LR 0.22, 95% CI 0.1 - 0.48) were the most accurate tests. CT was not as accurate a test (pooled positive LR 3.8, 95% CI 2.0 - 7.3 and negative LR of 0.62, 95% CI 0.45 - 0.86. There was only one study that reported the use of ultrasound scanning., Conclusion: MRI and sentinel node biopsy have shown similar diagnostic accuracy in confirming lymph node status among women with primary endometrial cancer than CT scanning, although the comparisons made are indirect and hence subject to bias. MRI should be used in preference, in light of the ASTEC trial, because of its non invasive nature.

Endometriosis is the presence of endometrial glands and stroma outside the endometrial cavity and is the most common known cause of pelvic pain. The number of women being diagnosed with the disease is increasing, but this may be reflective of improved diagnostic techniques. The aetiology is unknown, although the theory of retrograde menstruation remains dominant. Although pain around menstruation is the most frequently experienced symptom, dyspareunia, dyschezia, cyclical dysuria and extreme fatigue are all common. The 'gold standard' diagnostic technique is laparoscopic visualization, and the Royal College of Obstetricians and Gynaecologists (2006) recommends that surgical removal of all endometriotic lesions is the ideal. The experience of endometriosis can negatively affect all aspects of a woman's life and relationships, and this is consistently reported in research studies. This article discusses the aetiology and clinical aspects of endometriosis as well as giving an overview of empirical literature surrounding the experience of the disease. It provides nurses with the knowledge to be alert to the possibility of endometriosis as a diagnosis in women with a certain set of symptoms, in whatever healthcare setting they work.

Background and Methodology: Endometriosis is a chronic condition in which endometrial glands and stroma are present outside of the uterus. Whereas chronic pelvic pain is the most commonly experienced pain of endometriosis, many women also suffer from deep dyspareunia. In order to determine how much of an impact endometriosis-associated dyspareunia has on the lives and relationships of women a qualitative study using semi-structured interviews, supplemented with quantitative data on the extent of dyspareunia, was conducted in a dedicated endometriosis clinic in the West Midlands, UK with 30 women aged from 19 to 44 years., Results: The main outcome measures were the extent of dyspareunia within the sample of women, and the impact of dyspareunia on quality of life. The experience of dyspareunia was found to be higher than in previous research. Three main themes emerged. The experience of pain was found to limit sexual activity for the majority of the sample, with a minority ceasing to be sexually active. Lack of sexual activity resulted in a lowering of self-esteem and a negative effect on relationships with partners, although the experience differed between younger and older women., Discussion and Conclusions: The experience of dyspareunia is a significant factor in the quality of life and relationships for women living with endometriosis. For most of the women in the study it was very severe and resulted in their reducing or curtailing sexual activity. Qualitative research can produce salient data that highlight the impact of dyspareunia on self-esteem and sexual relationships.

Background: Guidelines exist for the management of endometriosis. Validated and reliable appraisal tools exist to assess the quality of guidelines., Objectives: To systematically appraise the quality of guidelines for the management of pelvic pain associated with endometriosis., Search Strategy: Guidelines were identified using a prospective protocol through a systematic search of MEDLINE (1951-2005), EMBASE (1974-2005), the Cochrane Library (2005, issue 2), known guideline websites and the World Wide Web., Selection Criteria: Type of document: guideline, consensus statement, care protocol or healthcare technology assessment produced by national or international professional organisations and societies or governmental agencies; subject: management of pelvic pain associated with endometriosis., Data Collection and Analysis: Two validated appraisal tools, Cluzeau and The Appraisal of Guidelines and Research and Evaluation (AGREE), were used to quantitatively assess the quality of guidelines. Areas evaluated included 'rigour of development', 'context and content' and 'application.', Main Results: Eight of 596 potentially relevant citations identified met our inclusion criteria. The Cluzeau instrument quality score were the following: rigour of development, 53% (range 5-65%); context and content, 69% (range 29-79%) and application 20% (range 0-20%). The application dimension achieved significantly lower quality scores (P = 0.026 versus rigour of development and P = 0.017 versus context and content). The AGREE instrument quality scores were the following: scope and purpose, 68% (range 17-89%); stakeholder involvement, 33% (range 13-63%); rigour of development, 49% (range 10-81%); clarity of presentation, 55% (range 42-67%); applicability, 14% (range 0-28%) and editorial independence, 28% (range 8-67%). The applicability domain achieved significantly lower quality scores (P = 0.001 versus scope and purpose and P = 0.009 versus rigour of development)., Author's Conclusions: Guidelines for the management of pelvic pain associated with endometriosis do not comply with the recommendations for high-quality standards.

The purposes of this study were: 1) to obtain a measure of exogenous carbohydrate (CHO(Exo)) oxidation and plasma glucose kinetics during 5 h of exercise; and 2) to compare CHO(Exo) following the ingestion of a glucose solution (Glu) or a glucose + fructose solution (2:1 ratio, Glu+Fru) during ultraendurance exercise. Eight well-trained subjects exercised three times for 5 h at 58% maximum O2 consumption while ingesting either Glu or Glu+Fru (both delivering 1.5 g/min CHO) or water. The CHO used had a naturally high 13C enrichment, and five subjects received a primed continuous intravenous [6,6-2H2]glucose infusion. CHO(Exo) rates following the ingestion of Glu leveled off after 120 min and peaked at 1.24 +/- 0.04 g/min. The ingestion of Glu+Fru resulted in a significantly higher peak rate of CHO(Exo) (1.40 +/- 0.08 g/min), a faster rate of increase in CHO(Exo), and an increase in the percentage of CHO(Exo) oxidized (65-77%). However, the rate of appearance and disappearance of Glu continued to increase during exercise, with no differences between trials. These data suggest an important role for gluconeogenesis during the later stages of exercise. Following the ingestion of Glu+Fru, cadence (rpm) was maintained, and the perception of stomach fullness was reduced relative to Glu. The ingestion of Glu+Fru increases CHO(Exo) compared with the ingestion of Glu alone, potentially through the oxidation of CHO(Exo) in the liver or through the conversion to, and oxidation of, lactate.

Objective: To determine the efficacy of laparoscopic excision of visually diagnosed endometriosis in the treatment of chronic pelvic pain., Study Design: Sixty-two women with chronic pelvic pain and who underwent laparoscopic excision of visually diagnosed peritoneal lesions suggestive of endometriosis returned postal questionnaires. The main outcomes measures were change in pelvic pain symptoms measured on a continuous and ordinal scale and patient satisfaction following treatment. Secondary outcomes were quality of life, time off work and use of health service resources., Results: 42/62 (68%) women with an average follow up time of 13 months (range 6-38 months) returned completed outcome questionnaires. The mean amount of pelvic pain was reduced following surgery compared to immediately prior to treatment, regardless of the nature of the pain (P<0.05). Overall, 67% (95% CI 50-80%) of women reported improvement in pain symptoms and 71% (95% CI 55-84%) were satisfied with the results of treatment. Satisfaction with treatment was comparable whether the visual diagnosis of peritoneal endometriosis was confirmed histologically or not (62% versus 64%, P=1.0)., Conclusion: Laparoscopic excision of visually diagnosed endometriosis appears to be efficacious in the treatment of women with chronic pelvic pain. The launch of a long-term randomised controlled trial to confirm these provisional results is now required.

The first purpose of this study was to investigate whether a glucose (GLU)+fructose (FRUC) beverage would result in a higher exogenous carbohydrate (CHO) oxidation rate and a higher fluid availability during exercise in the heat compared with an isoenergetic GLU beverage. A second aim of the study was to examine whether ingestion of GLU at a rate of 1.5 g/min during exercise in the heat would lead to a reduced muscle glycogen oxidation rate compared with ingestion of water (WAT). Eight trained male cyclists (maximal oxygen uptake: 64+/-1 ml.kg-1.min-1) cycled on three different occasions for 120 min at 50% maximum power output at an ambient temperature of 31.9+/-0.1 degrees C. Subjects received, in random order, a solution providing either 1.5 g/min of GLU, 1.0 g/min of GLU+0.5 g/min of FRUC, or WAT. Exogenous CHO oxidation during the last hour of exercise was approximately 36% higher (P<0.05) in GLU+FRUC compared with GLU, and peak oxidation rates were 1.14+/-0.05 and 0.77+/-0.08 g/min, respectively. Endogenous CHO oxidation was significantly lower (P<0.05) in GLU+FRUC compared with WAT. Muscle glycogen oxidation was not different after ingestion of GLU or WAT. Plasma deuterium enrichments were significantly higher (P<0.05) in WAT and GLU+FRUC compared with GLU. Furthermore, at 60 and 75 min of exercise, plasma deuterium enrichments were higher (P<0.05) in WAT compared with GLU+FRUC. Ingestion of GLU+FRUC during exercise in the heat resulted in higher exogenous CHO oxidation rates and fluid availability compared with ingestion of GLU and reduced endogenous CHO oxidation compared with ingestion of WAT.

Objective: To determine the accuracy of minimally and non-invasive tests to assess the groin node status in squamous cell vulvar cancer., Methods: A systematic review of published research from 1979 to 2004 that compares the results of tests to determine groin node status with histology at inguinofemoral lymphadenectomy was made. Studies included in the review were those that compared the index test to the standard surgical intervention of inguinofemoral lymphadenectomy and allowed the construction of two-by-two tables. From these tables, sensitivity, specificity, and the likelihood ratios (with 95% confidence intervals) were reported and, where feasible, meta-analysis was used to pool results for each test separately. Sentinel node biopsy using technetium-99m-labelled nanocolloid ((99m)Tc) had a pooled sensitivity and negative LR of 97% (91-100 95% CI) and 0.12 (0.053-0.28 95% CI), respectively, and was the most accurate test reviewed., Conclusion: Five diagnostic tests were identified in a total of 29 studies (961 groins). Although the studies were small and the design often poor, this represents the best summary of the data to date. Sentinel node identification using (99m)Tc appeared to be the most promising test for accurately excluding lymph node metastases in squamous cell vulvar cancer and potentially reducing the radicality of surgery. Its efficacy as a tool in reducing the need for radical surgery and associated patient morbidity without reducing survival needs further assessment probably in a randomised control trial.

Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease.

Radical hysterectomy and pelvic lymphadenectomy is the standard surgical treatment for early stage cervical cancer. This operation is well recognised as having a higher morbidity and mortality rate than a simple hysterectomy. We studied the histology results of 131 patients who had standard surgery for cervical cancer to ascertain if a radical hysterectomy was required for adequate treatment. Of 110 (84%) patients with negative pelvic lymphadenopathy, only 9 (8%) had positive parametrial histology and all required adjuvant therapy independent of their parametrial histology. This study confirms that a less radical hysterectomy and pelvic lymphadenectomy provides adequate treatment and allows us to consider a more conservative, minimal access approach to the management of these patients.

Purpose and Methods: To investigate the effect of glucose infusion on glucose kinetics and performance, six endurance cyclists (VO2max = 61.7 +/- 2.0 (mean +/- SE) mL x kg(-1) x min(-1)) completed two performance trials in which they had to accomplish a set amount of work as quickly as possible (991 +/- 41 kJ). Subjects were infused with either glucose (20% in saline; carbohydrate (CHO)) at a rate of 1 g x min(-1) or saline (0.9% saline; placebo (PLA)). It was hypothesized that time trial performance would be unaffected by the infusion of glucose, as endogenous stores of CHO would not be limiting in the PLA trial., Results: Plasma glucose concentration increased from 4.8 +/- 0.1 mmol x L(-1) to 5.9 +/- 0.3 mmol x L(-1) during the PLA trial and from 4.9 +/- 0.1 mmol x L(-1) at rest to 12.4 +/- 1.1 mmol x L(-1) during the CHO trial. These values were significantly higher at all time points during the CHO trial compared with PLA (P < 0.001). In the final stages of the time trial, Rd in the PLA trial was 49 +/- 5 micromol x kg(-1) x min(-1) compared with 88 +/- 7 micromol x kg(-1) x min(-1) in the CHO trial (P < 0.05). Despite these differences, there was no difference in performance time between PLA and CHO (60.04 +/- 1.47 min, PLA, vs 59.90 +/- 1.49 min, CHO, respectively). Infused carbohydrate oxidation in the last 25% of the CHO trial was at least 675 +/- 120 micromol x kg(-1) and contributed 17 +/- 4% to total carbohydrate oxidation., Conclusion: The results demonstrate that glucose infusion had no effect on 1-h cycle time-trial performance, despite an increased availability of plasma glucose for oxidation and evidence of increased glucose uptake into the tissues.

Human papillomavirus (HPV)-associated vulvar intraepithelial neoplasia (VIN) has serious sequelae for the sufferer. Current treatments are associated with poor response and high relapse rates. The development of HPV-specific T cell immunotherapies offers a new approach to treatment. This will require a detailed understanding of the spectrum of T cell responses induced by HPV antigens, and how effectively viral antigens can be accessed by the immune system. We have investigated the frequency and spectrum of HPV16-specific CD8+ T cell responses to three HPV16 antigens in 9 women with high grade VIN (VIN3). CD4-depleted populations of responder cells were screened against overlapping 30-35mer peptides covering the sequences of HPV16 E6, E7 and E4 using ELISPOT assays of IFN-gamma release. We demonstrated CD8+ T cell reactivity to one or more of the proteins in 6 of 9 patient samples. All 6 of these responders recognised peptides covering the E7 protein, 3 of 9 women responded to E6 peptides, but no reactivity was seen to E4. Our results suggest that HPV16-specific cytotoxic T cells (CTLs) are relatively common in women with persistent VIN3. The HPV-specific CTL response, however, seems to be ineffective. There is some evidence that there are problems associated with the processing and presentation of HPV antigens by the infected vulvar epithelium. It will be crucial to address this in the design of any T cell based therapy for HPV-associated VIN and vulval cancer., (Copyright 2003 Wiley-Liss, Inc.)

Objective: To develop a simple but sensitive instrument to evaluate and document symptoms of both bowel and urinary dysfunction in women., Design: A 22-item questionnaire covering a range of bowel and urinary symptoms was developed and underwent rigorous psychometric testing., Setting: The gynaecology departments of three hospitals, a urogynaecology clinic, a functional bowel clinic and a general practice., Population: Six hundred and thirty women, comprising four groups: 1. women awaiting hysterectomy (n = 379), 2. women following hysterectomy (n = 45), 3. women referred with functional bowel and/or urinary symptoms (n = 65), 4. asymptomatic controls (n = 141)., Main Outcome Measures: The content, construct and criterion validity, internal consistency, reliability and responsiveness of the questionnaire were measured. RESULTS Peer and patient reports and missing data patterns supported face and content validity. Factor analysis showed a clinically relevant four-factor structure with low content replication able to distinguish between patient groups, indicating good internal structure. Comparison with clinical, anorectal physiological, videoproctographic, transit time and urodynamic test results provide provisional indication of criterion validity. Key domain question analysis and Cronbach's alphas showed internal consistency. Kappa values demonstrated good test-retest reliability and key question correlation over time proved responsiveness., Conclusions: Our findings support the suitability, clinical validity, reliability and responsiveness of a simple questionnaire, which is sensitive to the constraints of clinical practice. The authors recommend its use in health care evaluation research assessing the effects of pelvic surgery and as a useful tool in comparing treatment efficacy.

Objective: To determine the accuracy of outpatient endometrial biopsy in diagnosing endometrial cancer in women with abnormal uterine bleeding., Design: A systematic quantitative review of published research., Methods: Studies were selected if accuracy of outpatient endometrial biopsy was estimated compared with a reference standard. Diagnostic accuracy was determined by pooled likelihood ratios for positive and negative test results. There were 1013 subjects in 13 diagnostic evaluations reported in 11 primary studies., Results: A positive test result on outpatient biopsy diagnosed endometrial cancer with a pooled likelihood ratio of 66.48 (95% CI 30.04-147.13) while a negative test result had a pooled likelihood ratio of 0.14 (95% CI 0.08-0.27). The post test probability of endometrial cancer was 81.7% (95% CI 59.7%-92.9%) for a positive test and 0.9% (95% CI 0.4%-2.4%) for a negative test., Conclusion: Outpatient endometrial biopsy has a high overall accuracy in diagnosing endometrial cancer when an adequate specimen is obtained. A positive test result is more accurate for ruling in disease than a negative test result is for ruling it out. Therefore, in cases of abnormal uterine bleeding where symptoms persist despite negative biopsy, further evaluation will be warranted.

Background: To determine the accuracy of outpatient endometrial biopsy in diagnosing endometrial hyperplasia in women with abnormal uterine bleeding., Design: Systematic quantitative review of published medical literature., Data Sources: Relevant papers were identified through electronic scanning of MEDLINE (1980-1999) and EMBASE (1980-1999), manual searching of bibliography of known primary and review articles and contact with manufacturers., Review Methods: Studies were selected if accuracy of outpatient endometrial biopsy, in women with abnormal pre or postmenopausal uterine bleeding, was estimated compared to a reference standard, which was endometrial histology obtained by tissue sampling under anesthesia. Quality assessment and data extraction were performed in duplicate. Diagnostic accuracy was determined by pooled likelihood ratios (LR) for positive and negative test results for endometrial hyperplasia., Results: There were 881 subjects in 8 diagnostic evaluations reported in 6 primary studies. Postmenopausal women represented 25% of the participants studied. There were 43 patients in whom outpatient sampling was inadequate. A positive test result on outpatient biopsy diagnosed endometrial hyperplasia with a pooled LR of 12.0 (95% CI 7.8-18.6) while a negative test result had a pooled LR of 0.2 (95% CI 0.1-0.3). With a positive test result, the posttest probability of endometrial hyperplasia was 57.7% (95% CI 41.1%-72.7%) while it was 2.2% (95% CI 0.9%-4.1%) with a negative test., Conclusion: Outpatient endometrial biopsy has modest accuracy in diagnosing endometrial hyperplasia. Therefore, additional endometrial assessment should be undertaken, especially if symptoms persist or intrauterine structural abnormalities are suspected.

Ingestion of a protein-amino acid mixture (Pro; wheat protein hydrolysate, leucine, and phenylalanine) in combination with carbohydrate (CHO; 0.8 g x kg(-1) x h(-1)) has been shown to increase muscle glycogen synthesis after exercise compared with the same amount of CHO without Pro. The aim of this study was to investigate whether coingestion of Pro also increases muscle glycogen synthesis when 1.2 g CHO. kg(-1). h(-1) is ingested. Eight male cyclists performed two experimental trials separated by 1 wk. After glycogen-depleting exercise, subjects received either CHO (1.2 g x kg(-1) x h(-1)) or CHO+Pro (1.2 g CHO x kg(-1) x h(-1) + 0.4 g Pro x kg(-1) x h(-1)) during a 3-h recovery period. Muscle biopsies were obtained immediately, 1 h, and 3 h after exercise. Blood samples were collected immediately after the exercise bout and every 30 min thereafter. Plasma insulin was significantly higher in the CHO+Pro trial compared with the CHO trial (P < 0.05). No difference was found in plasma glucose or in rate of muscle glycogen synthesis between the CHO and the CHO+Pro trials. Although coingestion of a protein amino acid mixture in combination with a large CHO intake (1.2 g x kg(-1) x h(-1)) increases insulin levels, this does not result in increased muscle glycogen synthesis.

Objectives: To develop an evidence based protocol for the follow up of women with low grade cervical abnormalities for whom treatment is not immediately indicated., Design: Population outcome study., Setting: Colposcopy clinic of an inner city teaching hospital., Participants: 566 women with low grade cytological abnormalities who were not treated at a first visit to the colposcopy clinic, followed up for a total of 881 years., Main Outcome Measures: Resolution of abnormalities, persistence of disease, and treated disease., Results: Abnormalities resolved in 306 (54.1%) women, whereas 138 (24.4%) had persistent disease and 122 (21.5%) were subsequently treated. Colposcopic opinion, smear test results, age, smoking history, and number of pregnancies were all significantly related to outcome. Logistic regression analysis produced a model that correctly identified 70% of women whose abnormalities resolved. Only 23 of 295 women (7.8%) with a normal cervix on colposcopy and a smear without dyskaryosis at a first visit were treated by the end of the observation period., Conclusions: Women referred with low grade cytological abnormalities who have a normal cervix on colposcopy and a negative or borderline repeat smear test result may be discharged from the colposcopy clinic. We propose a follow up protocol that could safely avoid unnecessary visits to a clinic.