Folic acid supplementation in postmenopausal women with hot flushes: phase III randomised double-blind placebo-controlled trial.

OBJECTIVE: To assess whether folic acid supplementation ameliorates hot flushes. DESIGN: Double-blind, placebo-controlled randomised trial. SETTING: Nine hospitals in England. POPULATION: Postmenopausal women experiencing ≥50 hot flushes weekly. METHODS: Women (n = 164) were randomly assigned in a 1:1 ratio to receive folic acid 5 mg tablet or placebo daily for 12 weeks. Participants recorded frequency and severity of hot flushes in a Sloan Diary daily and completed Greene Climacteric and Utian Quality of Life (UQoL) Scales at 4-week intervals. MAIN OUTCOME MEASURES: The change in daily Hot Flush Score at week 12 from randomisation based on Sloan Diary Composite Score B calculation. RESULTS: Data of 143 (87%) women were available for the primary outcome. The mean change (SD) in Hot Flush Score at week 12 was -6.98 (10.30) and -4.57 (9.46) for folic acid and placebo group, respectively. The difference between groups in the mean change was -2.41 (95% CI -5.68 to 0.87) (P = 0.149) and in the adjusted mean change -2.61 (95% CI -5.72 to 0.49) (P = 0.098). Analysis of secondary outcomes indicated an increased benefit in the folic acid group regarding changes in total and emotional UQoL scores at week 8 when compared with placebo. The difference in the mean change from baseline was 5.22 (95% CI 1.16-9.28) and 1.88 (95% CI 0.23-3.52) for total and emotional score, respectively. CONCLUSIONS: The study was not able to demonstrate that folic acid had a statistically significant greater benefit in reducing Hot Flush Score over 12 weeks in postmenopausal women when compared with placebo. TWEETABLE ABSTRACT: Folic acid may ameliorate hot flushes in postmenopausal women but confirmation is required from a larger study.

A new measure of sexual function in women with pelvic floor disorders (PFD): the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR).

INTRODUCTION AND HYPOTHESIS: The objective of this study was to create a valid, reliable, and responsive sexual function measure in women with pelvic floor disorders (PFDs) for both sexually active (SA) and inactive (NSA) women. METHODS: Expert review identified concept gaps and generated items evaluated with cognitive interviews. Women underwent Pelvic Organ Prolapse Quantification (POPQ) exams and completed the Incontinence Severity Index (ISI), a prolapse question from the Epidemiology of Prolapse and Incontinence Questionnaire (ISI scores), the Pelvic Floor Distress Inventory-20 (PFDI-20), and the Female Sexual Function Index (FSFI). Principle components and orthogonal varimax rotation and principle factor analysis with oblique rotation identified item grouping. Cronbach's alpha measured internal consistency. Factor correlations evaluated criterion validation. Change scores compared to change scores in other measures evaluated responsiveness among women who underwent surgery. RESULTS: A total of 589 women gave baseline data, 200 returned surveys after treatment, and 147 provided test-retest data. For SA women, 3 subscales each in 2 domains (21 items) and for NSA women 2 subscales in each of 2 domains (12 items) emerged with robust psychometric properties. Cronbach's alpha ranged from .63 to .91. For SA women, correlations were in the anticipated direction with PFDI-20, ISI, and FSFI scores, POPQ, and EPIQ question #35 (all p < .05). PFDI-20, ISI, and FSFI subscale change scores correlated with Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire International Urogynecological Association-revised (PISQ-IR) factor change scores and with mean change scores in women who underwent surgery (all p < .05). For NSA women, PISQ-IR scores correlated with PFDI-20, ISI scores, and with EPIQ question #35 (all p < .05). No items demonstrated differences between test and retest (all p ≥ .05), indicating stability over time. CONCLUSIONS: The PISQ-IR is a valid, reliable, and responsive measure of sexual function.

Psychosocial adjustment in women with premature menopause: a cross-sectional survey.

OBJECTIVES: Previous studies have found that women with premature menopause often report fertility problems, menopause symptoms and negative experiences of medical services. This study aims to measure the prevalence of these problems and explore whether they have negative impacts on psychosocial adjustment (symptom experience and quality of life). METHODS: A cross-sectional survey was mailed to women who had been diagnosed with premature menopause, recruited from hospital clinics in West London and from a patient support website (the Daisy Network). The survey measured participant characteristics, fertility problems, hot flushes and night sweats, experience of diagnosis, patient satisfaction with medical services, the Women's Health Questionnaire and the General Health Survey SF-36. Responses were described and multiple linear regressions were used to explore predictors of psychosocial functioning and quality of life. RESULTS: A total of 136 women were included in the analysis. Psychosocial functioning was relatively poor compared to typical aged menopausal women. Fertility concerns were prevalent (reported by 71% of the sample), 35% reported experiencing hot flushes and/or nights sweats, and, on average, women were neither satisfied nor unsatisfied with medical services (mean =3.00, standard deviation =0.98). Age, experiencing hot flushes and/or night sweats and patient satisfaction predicted psychosocial functioning, but only explained a small amount of the variance (3-11%). CONCLUSIONS: Women with premature menopause would benefit from interventions that improve psychosocial functioning and quality of life, including improving patient experience and effective treatment of menopause symptoms. Assumptions about treatment needs could not reliably be made based on patient characteristics, suggesting that individually tailored treatments may be more effective.

The silent grief: psychosocial aspects of premature ovarian failure.

OBJECTIVE: Premature ovarian failure in women under 40 years is uncommon, but not rare (1-3%), with up to 2.5% of adolescents affected. This study aims to investigate women's experiences of diagnosis, perception of cause, treatment, main concerns, long-term consequences and impact on self-esteem, sexual functioning and health-related quality of life. DESIGN: This was a cross-sectional study, using a single-group design, including quantitative and qualitative measures. Two hundred and twenty questionnaires were sent to women recruited from the databases of two London specialist multidisciplinary clinics and from a national premature menopause self-help website. The questionnaire included the Rosenberg's Self Esteem Questionnaire, SF 36 Health Survey (quality of life), the Sexual Personal Experiences Questionnaire and the Young Menopause Assessment questionnaire, following a pilot to assess acceptability and feasibility. RESULTS: The response rate was 62% in women aged 19-61 years. The majority of women felt that they had been offered inadequate information; 53% did not know the reason for their condition, 30% obtained a diagnosis within 6 months, and the diagnosis for 22% took up to 3 years. Fertility and bone health were main concerns, followed by emotional well-being. Libido and vaginal dryness were perceived as the main long-term effects by 79% of the women. The internet was the main source of information. The majority requested more information targeted to their age group and 49% requested psychological support, citing a negative impact on their self-esteem. CONCLUSIONS: This study examined women's perceptions of premature ovarian failure, its impact and the services they received. The results can be used to inform service reconfiguration and improvement.

Menopause and urogynaecology service standards: a UK consultant-based questionnaire survey of RCOG recommendations.

A postal questionnaire of UK consultant obstetricians and gynaecologists was performed to evaluate the number of hospitals which met the Royal College of Obstetricians and Gynaecologists recommended standards for urogynaecology and menopause services. A total of 359 responses were analysed. Sixty-four percent of the consultants worked in units with direct referral systems from primary care continence services, while 63% of the consultants worked in units without a dedicated menopause clinic integrated with other women's health facilities. Most of the criteria assessed for clinical service standards in these fields are not met.

Double bubble, double trouble.

Duodenal atresia (DA) is not uncommon, either as an isolated anomaly or associated with trisomy 21, malrotation, or cardiac anomalies. It may be diagnosed on antenatal ultrasound by a "double-bubble" sign, which typically persists after birth on a plain abdominal radiograph. DA as a familial association is rare but has been reported with or without other associated anomalies. We report DA in two siblings of nonconsanguineous parents, one case occurring with an annular pancreas in association with gestational diabetes. These two cases suggest possible genetic and environmental components in the aetiology of this anomaly.

Compliance with estrogen replacement therapy: current issues.

Compliance is now considered to be a major issue in the clinical arena of the menopause and hormone replacement management. Recently, the terminology has evolved to intimate a closer working relationship between the woman and her clinician, but still varies from country to country, as do uptake and continuation rates. The literature is conflicting, some papers demonstrating an improvement in the situation in recent years, others striking a more pessimistic note. Certainly, trends can be identified. Factors are emerging that will positively influence long-term adherence, and most studies are consistent in the reasons women quote for cessation of therapy. The gulf between medical and feminist literature is wide, but we should examine women's viewpoints to enhance the profession's understanding of why the perception is one of unnecessary medicalization. Market research allows an insight into women's requirements and we should learn from other countries, cultures and professions. There is an increasing emphasis on communication skills. Counselling and information-giving have been recognized to be the key to developing a working relationship with the patient, but education for the physician is also necessary if accurate, individualized risk-benefit assessments and patient profiling are to be effective. Finally, a wider range of treatment options enhance individualization for the woman.

Bacterial vaginosis in climacteric and menopausal women.

The objective was to determine how frequently an abnormal vaginal flora occurred in women attending a menopause clinic and whether any abnormality might be related to a particular risk factor. Women completed a questionnaire on their gynaecological, sexual and medical history. Whether they were perimenopausal or postmenopausal was determined on the basis of symptomatology, duration of amenorrhoea and on a follicle-stimulating hormone (FSH) assay when clinically indicated. A speculum examination of the vagina was undertaken, at which time a smear of vaginal secretion was Gram stained and the bacterial flora graded as follows: grade 1, normal; grade 2, intermediate, and grade 3, bacterial vaginosis (BV). Of 100 women examined, 44 had grade 1 flora, 17 had grade 2 flora and 18 had BV. An apparent absence of, or very scanty, vaginal bacteria in which grading was not possible was found in 21 women. Women with BV had had more sexual partners than the others, but otherwise there were no discernible factors associated with the occurrence of BV. Women with vaginal atrophy were more likely to have an apparent absence of vaginal bacteria, but a few had BV.

Intraoperative fibreoptic bronchoscopy during neonatal tracheo-oesophageal fistula ligation and oesophageal atresia repair.

Maintenance of adequate ventilation under anaesthesia can be difficult during identification and ligation of congenital tracheo-oesophageal fistula with repair of oesophageal atresia. Anaesthesia may also be complicated by problems associated with prematurity, pre-existing aspiration pneumonitis, and difficulty positioning the endotracheal tube to prevent inflation of the stomach with increased risk of aspiration and diaphragmatic splinting. Even intubation of the fistula and gastric rupture may occur. Two neonatal cases are presented where use of a 2.2 mm neonatal bronchoscope passed through a 3.0 mm ID tracheal tube facilitated surgical identification of the fistula, diagnosis of fistula intubation and other airway problems intraoperatively.

Small bowel injuries in children.

OBJECTIVE: To determine the common features of small bowel injury (SBI) in childhood and the consequences of delayed diagnosis. METHODOLOGY: A retrospective case review was performed of children with traumatic SBI between January 1988 and November 1999. RESULTS: Twenty-eight patients were identified with SBI. Road trauma accounted for 71% of them. Tachycardia was present on admission in 82% of patients with SBI including all but one of the intestinal perforations. SBI was associated with a Chance fracture of the lumbar spine in three patients (11%). An abdominal computed tomography scan with intravenous contrast was abnormal in all patients with a perforation or mesenteric tear. Diagnosis was delayed in six patients, one of whom died as a result of sepsis from a small bowel perforation. CONCLUSIONS: Persistent tachycardia with an appropriate mechanism of injury following blunt abdominal trauma requires active exclusion of SBI. Delayed diagnosis is associated with significant morbidity and mortality.

Cloning and expression of the S-adenosylmethionine decarboxylase gene of Neurospora crassa and processing of its product.

S-adenosylmethionine decarboxylase (AdoMetDC) catalyzes the formation of decarboxylated AdoMetDC, a precursor of the polyamines spermidine and spermine. The enzyme is derived from a proenzyme by autocatalytic cleavage. We report the cloning and regulation of the gene for AdoMetDC in Neurospora crassa, spe-2, and the effect of putrescine on enzyme maturation and activity. The gene was cloned from a genomic library by complementation of a spe-2 mutant. Like other AdoMetDCs, that of Neurospora is derived by cleavage of a proenzyme. The deduced sequence of the Neurospora proenzyme (503 codons) is over 100 codons longer than any other AdoMetDC sequence available in genomic databases. The additional amino acids are found only in the AdoMetDC of another fungus, Aspergillus nidulans, a cDNA for which we also sequenced. Despite the conserved processing site and four acidic residues required for putrescine stimulation of human proenzyme processing, putrescine has no effect on the rate (t0.5 approximately 10 min) of processing of the Neurospora gene product. However, putrescine is absolutely required for activity of the Neurospora enzyme (K0.5 approximately 100 microM). The abundance of spe-2 mRNA and enzyme activity is regulated 2- to 4-fold by spermidine.

Reduced virulence caused by meiotic instability of the TOX2 chromosome of the maize pathogen Cochliobolus carbonum.

The mechanisms by which pathogenic fungi evolve are poorly understood. Production of the host-selective cyclic peptide HC-toxin is controlled by a complex locus, TOX2, in the plant pathogen Cochliobolus carbonum. Crosses between toxin-producing (Tox2+) and toxin-nonproducing (Tox2-) isolates, as well as crosses between isolates in which the TOX2 genes were on chromosomes of different size, yielded progeny that had lost one or more copies of one or more of the TOX2 genes. Of approximately 200 progeny analyzed, eight (4%) had lost at least one TOX2 gene. All of them still had at least one functional copy of all of the known genes required for HC-toxin production (HTS1, TOXA, TOXC, and TOXE). Most deletion strains could be explained by simple chromosome breaks resulting in the loss of major contiguous portions (0.8 to 1.4 Mb) of the 3.5-Mb TOX2 chromosome, whereas others had more complicated patterns. All deletion strains had normal growth and were fertile, indicating that the 1.4 Mb of DNA contained no essential housekeeping genes. Most strains were also still virulent (Tox2+), but two had a novel phenotype of reduced virulence (RV), characterized by smaller lesions that expanded at a reduced rate and an inability to colonize plants systemically. Although the RV strains made no detectable HC-toxin in culture, the RV phenotype was dependent on the presence of a functional copy of HTS1, which encodes the central enzyme in HC-toxin biosynthesis. We propose that the RV strains still make a low level of HC-toxin, at least in planta, and that this is due to the loss of one or more genes that contribute to, but are not absolutely required for, HC-toxin synthesis.

British-Asian women's views on and attitudes towards menopause and hormone replacement therapy.

OBJECTIVE: To establish an understanding of the views and values of Asian women living in the UK but of Indian subcontinent origin, in relation to the menopause and hormone replacement therapy (HRT): hopefully this will allow the development of strategies for increasing HRT uptake and long-term adherence. METHOD: This was a postal, structured questionnaire survey, completed anonymously by British-Asian women who expressed their opinions and knowledge about the menopause and HRT, including their views on service provision. RESULTS: Some 70% of women were in the age range 40-59 years; 74.5% had some education. In all 82% declared that they understood the menopause, and 77% thought that the menopause was a natural phenomenon. Over 75% were interested in seeking a medical opinion for management of the menopause. Of the women surveyed, 33% (n = 88) felt happy about and 46% (n = 123) felt frightened by the menopause. CONCLUSIONS: The results suggest an overwhelming demand for information and the need for special clinics run by female doctors who can communicate in the women's own language. Fears and concerns are similar to those of the Caucasian population.

Adverse outcome of congenital diaphragmatic hernia is determined by diaphragmatic agenesis, not by antenatal diagnosis.

BACKGROUND/PURPOSE: The authors studied their congenital diaphragmatic hernia (CDH) cases retrospectively to ascertain if classical CDH and diaphragmatic agenesis (DA) have separate clinical manifestations, whether antenatally diagnosed cases behave differently from those not diagnosed antenatally, and if antenatal diagnosis before 25 weeks carries a worse prognosis. METHODS: The authors performed a retrospective review of 23 infants with CDH treated at their institution between January 1996 and March 1999. The patients were divided into 3 groups that were analyzed: DA and classical CDH, antenatally diagnosed and nonantenatally diagnosed, and antenatally diagnosed before 25 weeks and after 25 weeks. RESULTS: There were 8 cases of DA and 11 cases of classical CDH. Four infants died without operation and could not be classified. Neonates with DA had significantly longer mean duration of preoperative stabilization compared with classical CDH (5.25+/-2.76 days v 1.36+/-1.0 days) and postoperative mechanical ventilatory support (15.7+/-3.0 days v 4.9+/-3.0 days). Fifty percent of DA patients died; all classical CDH patients survived. Twelve cases were diagnosed antenatally, 6 before 25 weeks' gestation. Antenatally diagnosed cases had no statistically significant difference in mortality rates from those not diagnosed antenatally; 50% of those diagnosed before 25 weeks survived. CONCLUSIONS: DA cases require more preoperative preparation and postoperative ventilation and have a bad prognosis compared with classical CDH. Antenatal diagnosis of CDH does not convey a different prognosis. Fifty percent of CDH patients with antenatal diagnosis before 25 weeks survive.

EXG1p, a novel exo-beta1,3-glucanase from the fungus Cochliobolus carbonum, contains a repeated motif present in other proteins that interact with polysaccharides.

Genomic and cDNA copies of EXG1, a gene encoding an exo-beta1, 3-glucanase from the plant pathogenic fungus Cochliobolus carbonum, were isolated. The gene contains two introns of 50 and 53 bp, and the mRNA has a 5'-untranslated region of 90 nt and a 3'-untranslated region of 159 nt. The deduced protein product, EXG1p, has a predicted signal peptide of 17 amino acids, but based on the known N-terminus of the mature protein is further processed to remove an additional 25 amino acids. The sequence of EXG1p is not closely related to any other known protein, but has a low similarity (29% overall amino acid identity) to BGN13.1, an endo-beta1,3-glucanase from the mycoparasitic fungus Trichoderma harzianum. EXG1p contains two imperfect copies of a 23-amino acid motif that is found in several other proteins that interact with polysaccharides, including plant and bacterial polygalacturonases, phage neck appendage protein, phage endoneuramidase, and bacterial mannuronan epimerase.

Recurrent necrotizing enterocolitis associated with episodes of supraventricular tachycardia.

The case of a 5-month-old baby with congenital heart disease and recurrent episodes of refractory supraventricular tachycardia (SVT) is presented. Severe segmental necrotizing enterocolitis (NEC) developed in the patient after one prolonged episode of SVT that required a limited right hemicolectomy. Further episodes of SVT were associated with recurrence of NEC requiring multiple laparotomies. The pathogenesis and therapeutic implications of this process are discussed in view of the potentially multiple pathological processes involved.

Behaviour of children associated with parental participation during induction of general anaesthesia.

OBJECTIVE: To evaluate children's behaviour during induction of general anaesthesia with parental participation. METHODS: A descriptive observational study in which the behaviour of the children was assessed using a Global Mood Scoring system before and during the induction of general anaesthesia, with their parents participating at induction. RESULTS: Parental participation in anaesthetic induction was beneficial in avoiding distress at parental separation without the use of preoperative sedation. Negative effects of parental participation were not encountered. CONCLUSIONS: Parental participation in anaesthetic induction of children can reduce distress at parental separation without any negative consequences. With proper preparation and education, parents should be encouraged to be present during the induction of general anaesthesia.