Jenny Higham

Effect of ethnicity and gender on performance in undergraduate medical examinations

Objective  To assess the effect of ethnicity and gender on medical student examination performance.

Clinical associations with objective menstrual blood volume

OBJECTIVE To determine the association between simple clinical parameters and objective menstrual blood volume. STUDY DESIGN A cohort study, in a London teaching hospital. Women complaining of menorrhagia (207) and those who considered their menstruation to be normal (47) were studied. Those with no demonstrable gynaecological pathology had their menstrual blood loss measured using the alkaline haematin technique. RESULTS Only 49% of 207 women complaining of menorrhagia had a loss of 80 ml or more. There was an increasing incidence of objective menorrhagia with increasing duration of bleeding and use of more sanitary protection items. Increasing height, age and number of intrauterine pregnancies were all associated with increasing menstrual blood volume. Haemoglobin fell with increasing menstrual blood loss. CONCLUSIONS Despite these clinical associations it is difficult to establish the quantity of menstrual bleeding with certainty without an objective assessment.

Aromatase P450 messenger RNA expression in eutopic endometrium is not a specific marker for pelvic endometriosis

OBJECTIVE To determine whether expression of aromatase P450 mRNA in eutopic endometrium is predictive of the presence of pelvic endometriosis. DESIGN A prospective, multicenter, observational study. SETTING Four tertiary centers for reproductive medicine. PATIENT(S) Sixty subjects of reproductive age undergoing laparoscopy for subfertility exploration, pain assessment, or sterilization. INTERVENTION(S) Endometrial biopsy at time of laparoscopy. MAIN OUTCOME MEASURE(S) The expression of aromatase P450 mRNA in endometrial specimens was determined by single-tube reverse transcription-polymerase chain reaction (RT-PCR). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was amplified in parallel to exclude amplification failure. RESULT(S) The RT-PCR amplification was successful in 56 of the 60 biopsies (93%). Pelvic endometriosis was diagnosed in 34 patients (61%) and was strongly associated with aromatase P450 mRNA expression in eutopic endometrium. As a diagnostic marker for endometriosis, aromatase P450 mRNA expression yielded a sensitivity of 82%, a specificity of 59%, a positive predictive value of 76%, and a negative predictive value of 67%. If additional uterine pathology was taken in account, the sensitivity increased to 84%, the specificity to 72%, the positive predictive value to 87%, but the negative predictive value remained unchanged (67%). CONCLUSION(S) Although endometrial aromatase P450 gene expression is highly predictive of the presence of pelvic disease, the relative high incidence of false-negative results and lack of specificity is likely to impair clinical application.

Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis.

Pregnancy is dependent upon the endometrium acquiring a receptive phenotype that facilitates apposition, adhesion and invasion of a developmentally competent embryo. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry of mid-secretory endometrial biopsies revealed a 28 kDa protein peak that discriminated highly between samples obtained from women with recurrent implantation failure and fertile controls. Subsequent tandem mass spectroscopy unambiguously identified this peak as apolipoprotein A-I (apoA-I), a potent anti-inflammatory molecule. Total endometrial apoA-I levels were, however, comparable between the study and control group. Moreover, endometrial apoA-I mRNA expression was not cycle-dependent although there was partial loss of apoA-I immunoreactivity in luminal and glandular epithelium in mid-secretory compared with proliferative endometrial samples. Because of its putative anti-implantation properties, we examined whether endometrial apoA-I expression is regulated by embryonic signals. Human chorionic gonadotrophin (hCG) strongly inhibited apoA-I expression in differentiating explant cultures but not when established from eutopic endometrium from patients with endometriosis. Pelvic endometriosis was associated with elevated apoA-I mRNA levels, increased secretion by differentiating eutopic endometrial explant cultures and lack of hCG-dependent down-regulation. To corroborate these observations, we examined endometrial apoA-I expression and its regulation by hCG in a non-human primate model of endometriosis. As in humans, hCG strongly inhibited endometrial apoA-I mRNA expression in disease-free baboons, but this response was entirely lost upon induction of pelvic endometriosis. Together, these observations indicate that perturbations in endometrial apoA-I expression, modification or regulation by paracrine embryonic signals play a major role in implantation failure and infertility.

Endometrial bleeding in hormone replacement therapy users: preliminary findings regarding the role of matrix metalloproteinase 9 (MMP-9) and tissue inhibitors of MMPs.

OBJECTIVE To establish the effect of hormone replacement therapy (HRT) on the expression of matrix metalloproteinase 9 (MMP-9) and the tissue inhibitor of MMPs, TIMP-1, in the endometrium of postmenopausal and perimenopausal women. DESIGN Prospective observational study. SETTING United Kingdom teaching hospital. PATIENT(S) Thirty-one perimenopausal and postmenopausal HRT recipients, with a control group of eight postmenopausal women not undergoing HRT. INTERVENTION(S) Prospective record of bleeding patterns and endometrial biopsy. MAIN OUTCOME MEASURE(S) Endometrial histology, bleeding patterns, MMP-9, and TIMP-1 expression. RESULT(S) MMP-9 and TIMP-1 are expressed in benign postmenopausal endometrium. Expression of both molecules is reduced in HRT recipients compared with non-HRT recipients. CONCLUSION(S) Exposure to HRT appears to alter endometrial expression of MMP-9 and TIMP-1 and also the local balance between these molecules. This alteration may promote breakdown of the endometrial extracellular matrix and blood vessels and hence bleeding.

NADPH oxidase-derived reactive oxygen species mediate decidualization of human endometrial stromal cells in response to cyclic AMP signaling.

Differentiation of human endometrial stromal cells into specialized decidual cells is critical for embryo implantation and survival of the conceptus. Initiation of this differentiation process is strictly dependent on elevated cAMP levels, but the signal intermediates that control the expression of decidual marker genes, such as prolactin (PRL) and IGFBP1, remain poorly characterized. Here we show that cAMP-dependent decidualization can be attenuated or enhanced upon treatment of primary cultures with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (diphenylen iodonium) or activator (apocynin), respectively. Time-course analysis demonstrated that cAMP enhances endogenous reactive oxygen species production, apparent after 12 h of stimulation, which coincides with a dramatic increase in decidual PRL and IGFBP1 expression. Knockdown of the Rho GTPase RAC1, which disables activation of the NADPH oxidase homologs NADPH oxidase (NOX)-1, NOX-2, and NOX-3, had no effect on PRL or IGFBP1 expression. In contrast, silencing of NOX-4, or its cofactor p22(PHOX), inhibited the expression of both decidual markers. Finally, we show that the NOX-4/p22(PHOX) complex regulates the DNA-binding activity of CCAAT/enhancer binding protein-β, a key regulator of human endometrial stromal cell differentiation. Thus, NOX-4 activation and reactive oxygen species signaling play an integral role in initiating the endometrial decidual response in preparation of pregnancy.

Design and Delivery of Game-Based Learning for Virtual Patients in Second Life : Initial Findings

This chapter will present game-based learning activities developed for virtual patients based on the four-dimensional framework developed by De Freitas and Martin, as well as other design considerations that look at emergent narratives and modes of representation. This chapter will also present the interaction and call-management structure implemented between the Second LifeTM (SL) virtual world environment and the world wide web environment. This chapter also represents an overview of the finding of a recent trial aimed to explore attitude towards two e-learning delivery methods including the delivery of game-based learning for virtual patients in SL.

Key challenges in simulated patient programs: An international comparative case study

BackgroundThe literature on simulated or standardized patient (SP) methodology is expanding. However, at the level of the program, there are several gaps in the literature. We seek to fill this gap through documenting experiences from four programs in Australia, Canada, Switzerland and the United Kingdom. We focused on challenges in SP methodology, faculty, organisational structure and quality assurance.MethodsWe used a multiple case study method with cross-case synthesis. Over eighteen months during a series of informal and formal interactions (focused meetings and conference presentations) we documented key characteristics of programs and drew on secondary document sources.ResultsAlthough programs shared challenges in SP methodology they also experienced differences. Key challenges common to programs included systematic quality assurance and the opportunity for research. There were differences in the terminology used to describe SPs, in their recruitment and training. Other differences reflected local conditions and demands in organisational structure, funding relationships with the host institution and national trends, especially in assessments.ConclusionThis international case study reveals similarities and differences in SP methodology. Programs were highly contextualised and have emerged in response to local, institutional, profession/discipline and national conditions. Broader trends in healthcare education have also influenced development. Each of the programs experienced challenges in the same themes but the nature of the challenges often varied widely.

Defining responsibilities of simulated patients in medical education.

Background: Simulated patients (SPs) play a critical role in medical education. The development of SP methodology has resulted in wide ranging responsibilities. For SPs to work effectively, we believed it was important to clearly articulate their responsibilities, and that this would be best achieved by consultation with all stakeholders—SPs, students, tutors, and administrators. Methods: As part of a quality assurance initiative, we designed a questionnaire and focus group study to explore stakeholders’ perceptions of the responsibilities of SPs in teaching. Convenience and purposive sampling was used to recruit participants to questionnaires and focus groups, respectively. Data were analyzed thematically. Results: Eighty-six questionnaires were collected, and six focus groups were conducted. Five sets of guidelines on responsibilities were produced. In addition, guidelines were established for feedback that SPs and tutors could use to maximize impact. Discussion: The results highlight the complexity of SP-based teaching. Clarification of all stakeholders’ responsibilities demonstrates the importance of a team approach to SP-based teaching. Focusing attention on just one set of stakeholder’s responsibilities is unlikely to improve perception of quality. The process for developing the guidelines may be valuable for those who work with SPs. Stakeholder engagement is likely to ensure greater commitment than those developed by faculty.

Commentary: How can we make our medical students enthusiastic about a future in obstetrics and gynaecology?

Falling recruitment to obstetrics and gynaecology (O&G) among UK‐trained undergraduates is a pressing concern. The reasons for this are multifactorial and include the previous restriction on the number of postgraduate training places. Undergraduate placements are a key time to encourage potential recruits into the specialty. A recent survey demonstrated various changes within medical school attachments over the past 15 years that are having a mixed influence on the undergraduate O&G experience. These are explored in relation to their potential impact on recruitment.