Augmentation vaginoplasty with buccal mucosa for the surgical revision of postreconstructive vaginal stenosis: a case series.

BACKGROUND: Vaginal stenosis is a common consequence of vaginal reconstruction in childhood. Significant scarring can make dilation ineffective, and there maybe a paucity of skin to create perineal skin flaps. Numerous vaginoplasty techniques exist, including perineal skin flaps for distal stenosis and intestinal vaginoplasty requiring laparotomy and bowel anastomosis. Buccal mucosa graft is widely used in urethroplasty and has been reported in neovaginal construction. It is easily accessible with minimal graft site morbidity and provides a close functional replica to vaginal mucosa. AIM: The aim was to describe the use of buccal mucosa grafts for the surgical revision of postreconstructive vaginal stenosis. METHOD: The study setting was a tertiary centre for congenital gynaecological anomalies. Buccal mucosa grafting was provided to women with vaginal stenosis unsuitable for perineal skin flaps and in whom intestinal vaginoplasty was the next option. Four cases have been performed, and the medical notes were reviewed for clinical data. RESULTS: Mean age at buccal mucosa vaginoplasty was 21 years (range 18-26 years). Two patients had a cloacal anomaly, one had mosaic Turner syndrome and one had postradiation vaginal stenosis. All four had undergone previous vaginal reconstruction. In all cases, there was a tight band of vaginal stenosis either too proximal or with insufficient perineal tissue to allow a perineal flap vaginoplasty. There were no immediate complications. Mean clinic follow-up was 16 months (3 months-4 years). Two patients were able to have penetrative sexual intercourse, and two were using vaginal dilators successfully. Patients have an email contact for the team nurse specialist and therefore are able to contact before clinical review if they develop concerns. DISCUSSION: The use of buccal mucosal grafts for vaginoplasty is increasingly reported. This is the first detailed case series describing its use for augmentation vaginoplasty with postreconstructive/stenosis. CONCLUSIONS: All patients had a successful outcome with a normal capacity vagina, and two were able to have penetrative intercourse. This suggests that buccal mucosal graft vaginoplasty is a safe and effective alternative for women with previous vaginal reconstruction requiring surgery for vaginal stenosis.

Dissociable roles for histone acetyltransferases p300 and PCAF in hippocampus and perirhinal cortex-mediated object memory.

The importance of histone acetylation for certain types of memory is now well established. However, the specific contributions of the various histone acetyltransferases to distinct memory functions remain to be determined; therefore, we employed selective histone acetyltransferase protein inhibitors and short-interference RNAs to evaluate the roles of CREB-binding protein (CBP), E1A-binding protein (p300) and p300/CBP-associated factor (PCAF) in hippocampus and perirhinal cortex (PRh)-mediated object memory. Rats were tested for short- (STM) and long-term memory (LTM) in the object-in-place task, which relies on the hippocampus and PRh for spatial memory and object identity processing, respectively. Selective inhibition of these histone acetyltransferases by small-interfering RNA and pharmacological inhibitors targeting the HAT domain produced dissociable effects. In the hippocampus, CBP or p300 inhibition impaired long-term but not short-term object memory, while inhibition of PCAF impaired memory at both delays. In PRh, HAT inhibition did not impair STM, and only CBP and PCAF inhibition disrupted LTM; p300 inhibition had no effects. Messenger RNA analyses revealed findings consistent with the pattern of behavioral effects, as all three enzymes were upregulated in the hippocampus (dentate gyrus) following learning, whereas only CBP and PCAF were upregulated in PRh. These results demonstrate, for the first time, the necessity of histone acetyltransferase activity for PRh-mediated object memory and indicate that the specific mnemonic roles of distinctive histone acetyltransferases can be dissociated according to specific brain regions and memory timeframe.

Transverse vaginal septae: management and long-term outcomes.

OBJECTIVE: To examine the management and long-term outcomes of transverse vaginal septae. DESIGN: Observational study with cross-sectional and retrospective arms. SETTING: Tertiary referral centre specialising in Müllerian anomalies. POPULATION: Forty-six girls and women with a transverse vaginal septum. METHODS: Data from medical records of all cases (1998-2013) of transverse vaginal septae were collected and reviewed. Patients over 16 years of age also completed a questionnaire. MAIN OUTCOME MEASURES: Presentation, examination findings, investigations, surgery, and long-term reproductive outcomes. RESULTS: The septae in the study were described as follows: 61% (95% CI 0.46-0.74) were imperforate, and presented with obstructed menstruation; 39% (95% CI 0.26-0.54) were perforate, and presented with a variety of concerns; 72% (95% CI 0.57-0.83) were low, 22% (95% CI 0.12-0.36) were mid-vaginal, and 6% (95% CI 0.02-0.18) were high; 33% were managed via an abdominoperineal approach, 59% were managed via a vaginal approach, and 6% had laparoscopic resection (one patient did not have surgery); 11% (95% CI 0.05-0.23) of patients presented with reobstruction, all following abdominoperineal vaginoplasty; 7% presented with vaginal stenosis, two following vaginal resection and one following the abdominoperineal approach; 61% of questionnaires were returned. These results showed that 22/23 patients were menstruating and one had a hysterectomy, 74% had been sexually active, 35% had dyspareunia, and 36% complained of dysmenorrhoea. There were seven pregnancies, with one termination and six live births, all following the vaginal excision of a transverse vaginal septum. CONCLUSIONS: Transverse vaginal septae resected vaginally or laparoscopically have low complication rates and good long-term outcomes. Complex septae require more extensive surgery, with an increased risk of complications.

Experiences of surgical continence management approaches for cloacal anomalies: a qualitative analysis based on 6 women.

STUDY OBJECTIVE: The aim of this qualitative study was to gain insight into health care experiences of young women diagnosed with cloacal anomalies, with a special focus on continence management. DESIGN: Qualitative analysis of one-to-one interviews. SETTING: A tertiary center for congenital anomalies of the urogenital tract in London. PARTICIPANTS: Six women aged 16 to 24 with cloacal anomalies. INTERVENTIONS: Tape-recorded one-to-one semi-stuctured interviews with a skilled interviewer. MAIN OUTCOME MEASURE(S): The taped interviews were transcribed and analyzed verbatim using interpretative phenomenological analysis according to the research question. Organizing themes across all of the accounts were identified. RESULTS: Two organizing themes concerning our research interests are summarized. The first theme Personal Agency in the Hands of Experts focuses on the interviewees' appreciation of their life-saving surgical care and their involvement in treatment decisions. The second theme Compromises and Trade-Offs focuses on what it was like to live with the more traditional versus the more advanced continence methods. Reliability emerged as a key priority in terms of continence treatment outcome. Gratitude may have interfered with the women's honest communications during treatment decision and evaluation consultations. CONCLUSIONS: A more developed approach to communication about the complex interventions proposed, founded on a nuanced understanding of users perspectives, can enhance informed decision making about continence management approaches. Despite these specific gaps, the interviewees were appreciative of their care and optimistic about life.

The normal vulva in medical textbooks.

When a healthy woman expresses concerns about her vulva, the doctor's response should be informed by clinical knowledge. For many doctors, accumulation of such knowledge would have begun with undergraduate teaching and medical textbooks. The aim of this study is to examine the information on female genital morphology in medical textbooks. A total of 59 gynaecology and anatomy textbooks were searched for information on the dimensions of vulval constitutent parts. No textbook gave measurements for all vulval structures. Vaginal length was reported in 21/59 textbooks, clitoral size in 15/59 and labia minora in 1/59. Where measurements appear, they suggest narrower ranges than recent reports. Information of vulval morphology is scanty and inaccurate in medical textbooks. The general lack of professional resources means that doctors may consciously or non-consciously rely upon personal experiences and popular culture to form their opinions, as do their patients.

Quality of obstetric and midwifery care for pregnant women who have undergone female genital mutilation.

Despite the availability of professional guidelines for the pregnancy management of women affected by female genital mutilation (FGM), this study demonstrated major deficits in identification, management and safeguarding.

The c.7409G>A (p.Cys2470Tyr) Variant of FBN1: Phenotypic Variability across Three Generations.

Marfan syndrome is an autosomal dominant connective tissue disorder caused by mutations in the fibrillin gene FBN1, which encodes an extracellular matrix glycoprotein. Major features of Marfan syndrome occur in the ocular, cardiovascular, and skeletal systems as well as in the dura mater. Approximately 60% of known disease-causing mutations are missense mutations of single amino acid residues. Effects on the cardiovascular system are classically associated with mutations in exons 24-32 of the 65 FBN1 exons and many, though not all, reports associate missense mutations in exons 59-65 with a mild cardiovascular phenotype. Here we present 5 related individuals among whom a c.7409G>A (p.Cys2470Tyr) missense variant in exon 59 of FBN1 is associated with significant cardiovascular features. The index case also had an apparently de novo 46,XX,del(5)(q33.1q33.3) deletion on chromosome 5. This family demonstrates skeletal, dermatological and neurological features consistent with Marfan syndrome but lacks significant ophthalmological findings to date. These findings suggest that FBN1 C-terminal missense mutations may not confer the ophthalmological features of Marfan syndrome, but they also confer a more significant risk for cardiovascular pathology than that suggested by previous studies. Furthermore, clinical data from this family supports the previously reported association of dural ectasia with C-terminal mutations.

Persistent unexplained congenital clitoromegaly in females born extremely prematurely.

OBJECTIVE: Unexplained clitoromegaly is a rare but well recognised feature in girls born premature. Although detected at birth, girls may re-present during childhood to paediatric urologists and gynaecologists who should be aware of this condition. The aim of the study was to describe the clinical findings and management of a series of girls presenting with persistent congenital clitoromegaly associated with prematurity. MATERIALS AND METHODS: This was a retrospective notes review set in a tertiary referral centre for Paediatric and Adolescent Gynaecology (PAG). RESULTS: Eight girls with a mean age of 6 years were seen over an eight year period. In all cases a Disorder of Sex Development (DSD) had been previously excluded. The main symptoms were discomfort or concern about appearance. On examination five girls had excess skin over the clitoris and three had enlarged corporal tissue. Management included reassurance and simple measures to ease discomfort. In two cases the parents requested referral to a paediatric urologist to consider clitoral surgery. CONCLUSION: As survival rates for extreme prematurity improve, paediatric urologists and gynaecologists are likely to see more of these cases. Clinicians must be familiar with this condition to ensure children are managed appropriately.

Adult recall of childhood female genital cutting and perceptions of its effects: a pilot study for service improvement and research feasibility.

This study aimed to gather information from service users of an African Women's Clinic for the purposes of planning service improvement and estimating research feasibility. The report is based on 17 interviews with Somali speaking women who had experienced female genital cutting in childhood. With language barriers removed, a high percentage of clinic attendees responded positively to the invitation to participate in research. They willingly discussed their experiences of FGM and expressed their negative viewpoints about the practice of FGM, suggesting that psychosocial and psychosexual research may be feasibly carried out in specialist contexts. The results also point to the need for psychological and educational input for service improvement.

Providing predictive testing for Huntington disease via telehealth: results of a pilot study in British Columbia, Canada.

Predictive testing (PT) for Huntington disease (HD) usually requires several in-person appointments which acts as a barrier to testing for those from remote regions. This pilot study reports the use of telehealth PT to examine whether such telehealth testing improves access to HD PT while maintaining quality of care and support. Individuals underwent PT via the telehealth protocol or standard in-person protocol and were asked to complete surveys regarding their experience. Results reveal no significant differences between the in-person-tested and telehealth-tested groups with respect to quality of care, information, counselling and support. The majority of participants in both groups stated that pre-test counselling had provided them with sufficient knowledge about the advantages and disadvantages of undergoing testing, the opportunity to ask questions, and the ability to make an informed decision. The majority of participants in both groups were satisfied by the manner in which results were delivered and stated they had received sufficient information regarding the implications of these results. This study reveals that telehealth PT improves access while maintaining quality of care and support.

A comparison of genital sensory and motor innervation in women with pelvic organ prolapse and normal controls including a pilot study on the effect of vaginal prolapse surgery on genital sensation: a prospective study.

OBJECTIVE: To study genital sensory and motor innervation in women with pelvic organ prolapse and to determine the effect of vaginal prolapse surgery on genital sensation. DESIGN: A prospective observational study. SETTING: A tertiary referral unit in northwest England. POPULATION: Twenty women complaining of prolapse symptoms (including seven undergoing vaginal prolapse repair) and a control group of ten healthy women. METHODS: Women attended a research clinic where genital sensory thresholds were determined by quantitative sensory testing and motor innervation was assessed by concentric needle electromyography (EMG) of the pelvic floor muscles. Women undergoing surgery were assessed preoperatively and postoperatively at 6 months. MAIN OUTCOME MEASURES: Primary outcome measure was change in genital vibration threshold and the percentage of polyphasic potentials on EMG. RESULTS: Healthy control women had normal vibration detection thresholds at the vagina and clitoris. Thresholds in the majority of women with prolapse were abnormal and in all women with prolapse over the age of 50 years. Women with prolapse had a significantly larger percentage of polyphasic potentials of the left pubococcygeus but not the right. There was no significant change in genital sensory thresholds at 6 months postoperatively following vaginal repair. CONCLUSIONS: The majority of women with prolapse have abnormal genital vibration detection, which is particularly evident after the age of 50 years. Impaired sensory function does not correlate with EMG markers of partial motor denervation. In women with abnormal sensory thresholds, no additional effect was detected following vaginal prolapse repair.

Developing a comprehensive, effective patient-friendly website to enhance decision making in predictive testing for Huntington disease.

PURPOSE: Predictive testing for Huntington disease is a complex decision, requiring in-depth counseling, education, and evaluation. Despite the growth in Web-based decision aids and educational resources, such tools for those considering Huntington disease testing are not available. The main objective of this project was to develop a patient-friendly, comprehensive, accessible Web-based tool to provide accurate information about testing for Huntington disease. METHODS: A semistructured interview study was conducted to determine the informational, educational, and support needs of those considering Huntington disease testing. A dedicated predictive testing website was subsequently developed and pilot tested. RESULTS: The interview study revealed that an effective website should include interactive diagrams, video documentaries, and personal stories of others who had considered testing. The pilot test revealed that the multidimensional site was easy to navigate and understand and provided an accurate, unbiased overview of the important factors to be considered before undergoing predictive testing. CONCLUSION: This project demonstrates the use of a mixed-method approach to develop the first tailored website dedicated to predictive testing for Huntington disease. Such an approach enabled the development of a comprehensive, accurate, and effective educational tool that supports informed decision making for people considering predictive testing for Huntington disease in an accessible, nonthreatening manner.

False-positive pregnancy tests following enterocystoplasty.

People with major congenital urological or neurological malformations invariably require bladder reconstruction with enterocystoplasty in early childhood. The improvement of the surgical management of these children has reflected significantly on their life expectancy. As a result, more young people with enterocystoplasty are being transitioned to adolescent clinics where they receive the usual counselling about sexual health and pregnancy risks. However, the possibility of false-positive urinary pregnancy tests in these young women remains an overlooked but essential message. The lack of awareness about this fact can result in significant patient anxiety and the potential for unnecessary interventions as exemplified by the three cases we have encountered.

Testing the fathers: carrying out HIV and STI tests on partners of pregnant women.

OBJECTIVES: Opt out antenatal HIV testing has significantly reduced mother to child transmission of HIV, but seroconversion during pregnancy from undiagnosed HIV positive male partners remains a risk. The authors report on a pilot initiative for sexual health and HIV screening for male partners of women attending antenatal ultrasound examination at Homerton Hospital, London. METHODS: Men attending with their female partners for routine ultrasound examination between 1 August 2010 and 31 January 2011 were offered on-site serology for HIV, syphilis, hepatitis B and hepatitis C and urine testing for Neiserria gonorrhoeae and Chlamydia trachomatis. RESULTS: were followed up through the genitourinary medicine service. Referral pathways were established for men with positive results. RESULTS: 1243 male partners of 2400 women attended ultrasound examinations, of whom 430 accepted testing (acceptance rate 35% and coverage rate 18%). Median age was 32 years (range 19-52). 112/430 (26%) male partners were of black ethnicity. 41% had previously had a HIV test. There was no difference in prior HIV testing between whites and non-whites. 16 infections were diagnosed, including two cases of hepatitis C, eight cases of hepatitis B and six cases of C trachomatis. No HIV diagnoses were made. CONCLUSIONS: The authors have shown that it is acceptable and feasible to engage heterosexual men for testing in this setting. Of those men who accepted HIV testing, more than half had never been previously tested. 4% of men tested had an infection, which had the potential to affect the outcome of the pregnancy.

Clinical characteristics of well women seeking labial reduction surgery: a prospective study.

OBJECTIVE: To assess clinical characteristics and expectations in well women requesting elective labial reduction surgery. DESIGN: Prospective study of women attending an outpatient gynaecology clinic. SETTING: General gynaecology clinic at a Central London teaching hospital. SAMPLE: Women requesting labial reduction surgery and referred by their general practitioner. METHODS: The labia minora width and length were measured for all participants for comparison with published normal values. The presenting complaint was recorded, along with demographic details, expectations of surgery and sources of information regarding appearance of the labia. MAIN OUTCOME MEASURES: Labial measurements, reported symptoms and expectations of surgery. RESULTS: The labia of all participants were within normal published limits, with a mean (SD) of 26.9 (12.8) mm (right labia), and 24.8 (13.1) mm (left labia). The majority of complaints were regarding appearance or discomfort. Expectations were to alter the appearance with surgery. CONCLUSIONS: All women seeking surgery had normal-sized labia minora. Clear guidance is needed for clinicians on how best to care for the worried well woman seeking surgery.

Androgen-dependent measurements of female genitalia in women with complete androgen insensitivity syndrome.

Measurements of clitoral length and clitoral to urethral distance were made and analysed for a relationship in a group of 19 women with complete androgen insensitivity syndrome (CAIS)attending a specialist clinic for adult women with disorders of sexual development. These were compared with a control group of 50 women attending hospital for a gynaecological procedure.There was a positive correlation between clitoral length and clitoral to urethral distance for women with CAIS. In contrast, a negative correlation was seen between clitoral length and clitoral to urethral distance for women in the control group. Women with CAIS had a reduced mean clitoral length compared with controls(P = 0.001), but no difference was observed for the clitoral to urethral distance between the two groups (P = 0.116).

Magnetic resonance spectroscopy biomarkers in premanifest and early Huntington disease.

OBJECTIVES: To evaluate in vivo brain metabolite differences in control subjects, individuals with premanifest Huntington disease (pre-HD), and individuals with early HD using ¹H magnetic resonance spectroscopy (MRS) and to assess their relationship with motor performance. METHODS: Eighty-five participants (30 controls, 25 pre-HD, and 30 early HD) were recruited as part of the TRACK-HD study. Eighty-four were scanned at 3 T with single-voxel spectroscopy in the left putamen. Disease burden score was >220 among pre-HD individuals. Subjects underwent TRACK-HD motor assessment including Unified Huntington's Disease Rating Scale (UHDRS) motor scoring and a novel quantitative motor battery. Statistical analyses included linear regression and one-way analysis of variance. RESULTS: Total N-acetylaspartate (tNAA), a neuronal integrity marker, was lower in early HD (∼15%) vs controls (p < 0.001). N-acetylaspartate (NAA), a constituent of tNAA, was lower in pre-HD (∼8%) and early HD (∼17%) vs controls (p < 0.05). The glial cell marker, myo-inositol (mI), was 50% higher in early HD vs pre-HD (p < 0.01). In early HD, mI correlated with UHDRS motor score (R² = 0.23, p < 0.05). Across pre-HD and early HD, tNAA correlated with performance on a tongue pressure task (R² = 0.30, p < 0.0001) and with disease burden score (R² = 0.17, p < 0.005). CONCLUSIONS: We demonstrate lower putaminal tNAA in early HD compared to controls in a cross-section of subjects. A novel biomarker role for mI in early HD was also identified. These findings resolve disagreement in the literature about the role of MRS as an HD biomarker. We conclude that putaminal MRS measurements of NAA and mI are promising potential biomarkers of HD onset and progression.

Management of vaginal hypoplasia in disorders of sexual development: surgical and non-surgical options.

Patients with disorders of sexual development (DSD) requiring vaginal reconstruction are complex and varied in their presentation. Enlargement procedures for vaginal hypoplasia include self-dilation therapy or surgical vaginoplasty. There are many vaginoplasty techniques described, and each method has different risks and benefits. Reviewing the literature on management options for vaginal hypoplasia, the results show a number of techniques available for the creation of a neovagina. Studies are difficult to compare due to their heterogeneity, and the indications for surgery are not always clear. Psychological support improves outcomes. There is a paucity of evidence to inform management regarding the optimum surgical technique to use, and long-term data on success is lacking, particularly with respect to sexual function. In conclusion, vaginal dilators remain the cornerstone of treatment of women with vaginal hypoplasia and should be used as the first-line technique. Surgical vaginoplasty has a role in complex patients with previous failed dilation and surgical intervention, particularly those cases where there is significant scarring from previous surgery. Regardless of the vaginal reconstruction technique, patients should be managed in a multidisciplinary team where there is adequate emotional and psychological support available.

Labial surgery for well women: a review of the literature.

This review investigates the quality and content of published reports relating to labial surgery for well women. Electronic databases were searched for relevant articles between 1950 and April 2009. Forty articles were identified, 18 of which included patient data. The specification of the study design was unavailable in 15 of the 18 papers; the remaining three were retrospective reports. No prospective, randomised or controlled studies were found. All reports claimed high levels of patient satisfaction and contained anecdotes pertaining to success. Medically nonessential surgery to the labia minora is being promoted as an effective treatment for women's complaints, but no data on clinical effectiveness exist.