A rare exception to Haldane's rule: Are X chromosomes key to hybrid incompatibilities?

The prevalence of Haldane's rule suggests that sex chromosomes commonly have a key role in reproductive barriers and speciation. However, the majority of research on Haldane's rule has been conducted in species with conventional sex determination systems (XY and ZW) and exceptions to the rule have been understudied. Here we test the role of X-linked incompatibilities in a rare exception to Haldane's rule for female sterility in field cricket sister species (Teleogryllus oceanicus and T. commodus). Both have an XO sex determination system. Using three generations of crosses, we introgressed X chromosomes from each species onto different, mixed genomic backgrounds to test predictions about the fertility and viability of each cross type. We predicted that females with two different species X chromosomes would suffer reduced fertility and viability compared with females with two parental X chromosomes. However, we found no strong support for such X-linked incompatibilities. Our results preclude X-X incompatibilities and instead support an interchromosomal epistatic basis to hybrid female sterility. We discuss the broader implications of these findings, principally whether deviations from Haldane's rule might be more prevalent in species without dimorphic sex chromosomes.

How useful are the BSUG database outcome criteria: validation using the MESA questionnaire.

Urinary stress incontinence is common, but there is a wide range of prevalence which might account for variations in definition of incontinence and variations in study methodology. Our study assessed the validity and reliability of the British Society of Urogynaecology's (BSUG) database subjective outcome scores after the tension-free vaginal tape (TVT), by correlating these with the changes in the Medical Epidemiologic and Social Aspects of Ageing (MESA) questionnaire score. A total of 100 women with urodynamic stress incontinence underwent TVT, completed a MESA questionnaire preoperatively and at 6 months postoperatively. We also collected information about three outcome measures of the BSUG database, patients' global impression of outcome and stress and urge symptom analyses. Our study showed that the postoperative patients' global impression of outcome improved significantly in 85% of cases and had 73.89% reduction in mean MESA scores (p < 0.001). The outcome measures of the BSUG database relates well to symptom improvement, based on MESA scores and these subjective assessments currently used by the BSUG's database are a valid assessment of TVT outcome.

Regulation of HIV production by blood mononuclear cells from HIV-infected donors: I. Lack of correlation between HIV-1 production and T cell activation.

The relationship between production of HIV-1 by peripheral blood mononuclear cells (PBMCs) from HIV-1-infected donors and the level of T cell activation by various stimuli was examined. Stimulation of PBMCs with soluble anti-CD3 antibody or staphylococcal enterotoxin/superantigen (SAg) was found to be 100-1000 times more effective at inducing production of HIV-1 than was stimulation with immobilized anti-CD3 or various other T cell activating agents. However, proliferation of CD4+ T cells and lymphokine production following stimulation with soluble anti-CD3 were less than with immobilized anti-CD3. To determine whether immobilized anti-CD3 stimulated cells may produce a factor(s) that suppresses HIV production, dual-chamber coculture experiments were performed in which soluble and immobilized anti-CD3-stimulated CD8-depleted PBMCs were separated by porous membranes. Stimulation of cells by immobilized anti-CD3 suppressed HIV-1 production by soluble anti-CD3-stimulated cells in the inner chamber, suggesting that diffusible factor(s) are involved in suppressing HIV-1 production. Experiments in which exogenous cytokines were added to cells stimulated with soluble anti-CD3 did not reveal the suppressive factor(s) produced; however, IL-7 was found to markedly increase HIV-1 production. Both T cells and monocytes were found to be required for soluble anti-CD3 to induce high levels of HIV-1 production, suggesting a role for adhesion molecules. Our results thus show that (1) soluble anti-CD3 is a powerful stimulus for HIV production, (2) there is not an absolute correlation between the level of HIV-1 production and T cell activation following stimulation of PBMCs with T cell activating agents, (3) immobilized anti-CD3 stimulation produces a factor that decreases HIV replication, and (4) T cell monocyte interactions are important for production of HIV-1 following stimulation with soluble anti-CD3.

Regulation of HIV production by blood mononuclear cells from HIV-infected donors: II. HIV-1 production depends on T cell-monocyte interaction.

Cell-cell interactions induced between T cells and monocytes by certain soluble anti-CD3 monoclonal antibodies (MAbs) were previously shown to be required for high-level production of HIV-1 by peripheral blood mononuclear cells (PBMCs) from infected donors. Staphylococcal enterotoxin or superantigen (SAg) is another mitogen inducing monocytes-T cell interactions that exhibit potent induction of HIV-1 production. Antibodies to several adhesion molecules were used to test the requirements for T cell- and monocyte-associated adhesion molecules in HIV-1 production following activation with anti-CD3 or SAg. Blocking of either CD2-LFA-3, or CD18-ICAM-1, inhibited anti-CD3- or SAg-induced HIV-1 production by more than 90% without inhibiting CD4+ T cell proliferation. Inhibition of HIV production was observed when either the T cell or monocyte coreceptor was bound by MAbs to these adhesion molecules. Blocking of CD28-B7 interactions by soluble CTLA-4 fusion protein, a CD28 homolog, inhibited both HIV-1 production and CD4+ T cell proliferation. Fc binding was not required for HIV-1 inhibition by MAbs to CD2 and CD18, because Fab or F(ab')2 fragments of these MAbs inhibited HIV-1 production by more than 80%. A chimeric single-chain MAb to CD2 was produced, containing heavy and light chain variable regions from MAb 35.1 to CD2 linked to the constant regions of human IgG1 (CD2 SFv-Ig). This humanized CD2 SFv-Ig inhibited HIV-1 production by 30% to > 98%. These results thus indicate that simultaneous engagement of multiple adhesion pathways between T cells and monocytes are required for HIV production by patients PBMCs and may have implications for therapy of HIV infections.

THe changing seasonality of infant deaths in England and Wales 1912-78 and its relation to seasonal temperature.

Seasonal variation in the rates of stillbirth, and of deaths under the age of one year, were studied for England and Wales in order to examine (a) changes in the seasonal variation over the years and (b) the correlation between seasonal rates and seasonal temperatures. The quarterly rates of stillbirths were studied for the period 1928-78; and of deaths under the age of one year, in six different age groups, for the period 1912-78. A disappearance of seasonal variation in rates ('deseasonality') occurrred from stillbirths in about 1950, and for neonatal deaths in about 1965. For deaths at 1-2 months a trend towards deseasonality has been apparent since 1955, but there has been no such trends for deaths at 3-11 months of age. In the period before deseasonality, and for the first quarter of the year, there was a high negative correlation between the neonatal death rate and the mean temperature in England and Wales but this correlation fell as the seasonal variation in rates fell. The findings suggest that seasonal variation in the neonatal death rate was closely related to winter temperatures during the period 1921-60. For deaths at 1-11 months old, there has been and still is a relation between temperature and seasonal variation in rates, but the relation was less close than for the neonatal death rate.

An unusual cause of vaginal discharge following gender reassignment.

Neovaginal reconstruction is an important part of gender reassignment surgery. We report a case of stone formation at the apex of vaginal vault constructed with sigmoid colon segment. A 48-year-old woman presented with profuse vaginal discharge for 1 year. She had a history of gender reassignment surgery (male to female) in 1994, and the neovagina had been constructed with an isolated sigmoid colon. Vaginoscopy performed using a cystoscope revealed multiple calculi at the vaginal vault on the endoscopic gastrointestinal anastomosis staples that had been used to close the vault. Colon-vaginoplasty has the advantages of providing adequate lubrication, but excessive vaginal discharge could be a problem, as colon is a mucous membrane. Stone formation in the vaginal vault should be considered in cases of gender reassignment with persistent vaginal discharge. This case also highlights the use of cystoscope in visualising the upper vagina in difficult circumstances.

Outcome measures after TVT for mixed urinary incontinence.

This study assessed the outcome of tension-free vaginal tape (TVT) in the treatment of mixed incontinence using the Medical Epidemiologic and Social Aspects of Ageing (MESA) questionnaire and other outcome measures used by the British Society of Urogynaecology (BSUG) database. Forty women undergoing TVT completed a MESA questionnaire pre-operatively and at 6 months post-operatively. Information was also obtained about three outcome measures of the BSUG database-patients' global impression of outcome and stress and urge symptom analyses. Stress and urge incontinences were either cured or improved in 78 and 75 % of women, respectively, after TVT. The results of post-operative patients' global impression of outcome showed great or moderate improvement in 75% of cases and had 69% reduction in mean MESA scores (p value less than 0.001). Symptom improvement based on MESA scores relates well with the basic outcome measures for stress and urge incontinences used by the BSUG database.

Social relationships during the onset and remission of neurotic symptoms. A prospective community study.

In a prospective study of a community sample, we examined changes in social relationships accompanying the onset and remission of neurotic symptoms. For those who developed symptoms in the course of 12 months, no decrease was found in the availability or reported adequacy of either close or diffuse ties, compared to those who remained symptom-free. For those having a remission, an increase in the adequacy of social relationships and a decrease in rows was observed only in those who improved later on, at the 12-month interview. But with either the onset or remission of symptoms, the availability of relationships remained unchanged. These observations cannot establish the direction of causality, but suggest that neurotic symptoms are more associated with the perception of social relationships than with the structure of personal networks.

Raised parental age in psychiatric patients: evidence for the constitutional hypothesis.

In two series of psychiatric patients (numbering about 6,000 and 2,000 respectively), the mean age of the mothers at the time of the patients' birth was found to be very significantly above expectation from the general population, and this was so for each of the major diagnostic groups. In the second series, the age of the fathers was also found to be very significantly above that expected from a sample survey of the general population, and this was so for each diagnostic group. Fathers' age was raised more than mothers', and was highest for schizophrenia. The raised parental age could not be explained in terms of the patient's year of birth or his father's social class. The raised mothers' age could largely be accounted for by regression on the raised fathers' age. The present findings, and those of previous studies, seem best explained on the hypothesis of a constitutional parental trait leading to delayed marriage.

Parental age and birth order in homosexual patients: a replication of Slater's study.

Parental age (at patient's birth) and birth order were studied in 623 male and 89 female patients diagnosed as homosexual, who were born in England and Wales and first attended the Maudsley Hospital between the years 1961-1975. For male patients, mean parental ages were significantly higher than expectation, and mean birth order was significantly later. Regression analysis indicated that the raised fathers' age was probably of more aetiological importance than the raised mothers' age. The results confirm those of previous studies. The female patients did not show a raised parental age or late birth order.

Management of diabetic pregnancies in the United Kingdom.

The aim of this postal questionnaire survey was to identify facilities currently available for the care of pregnant diabetic women in the United Kingdom and determine how closely these reflect the standards recommended by The St Vincent Declaration Action Programme. A questionnaire was sent to a physician and an obstetrician in each of the 255 obstetric hospitals in the UK. Two hundred and forty-five (96.1%) hospitals replied, with most of these managing 20 or less insulin dependent diabetics per year. Of the hospitals, 58.4%, had a special combined diabetic antenatal clinic; 86.6% of the units had a single physician responsible for diabetic care, whilst more than one obstetrician was involved in 50.6% of the units. Prepregnancy counselling was provided in 87.4% of the hospitals. Home blood glucose monitoring was used in 97.9% of the units. Ideal mean pre- and postprandial blood glucose concentrations were 6.0 mmol/1 (SD 0.82) and 7.9 mmol/l (SD 0.91), respectively. Ultrasound was routinely used to assess fetal growth in 98.7% of the units. The mean gestational age for elective caesarean section was 38.2 weeks (SD 0.55), compared with 39.0 weeks (SD 0.35) for planned vaginal delivery. During labour, 98% of the units used a dextrose and insulin infusion, but only 53.7% of the units maintained an intrapartum maternal blood glucose of between 4 and 6 mmol/l. We conclude that there is widespread variation in the management of the pregnant diabetic patient, and much practice is suboptimal. Many of the recommendations of the St Vincent Declaration are not being met by current UK practice.

The utility of latent trait models in psychiatric epidemiology.

Latent trait modelling is a recent psychometric technique with great potential for the construction and refinement of psychiatric instruments. It provides a greater insight into the nature of measurement in psychiatry and the statistical machinery for improving it. This expository paper starts with a non-technical outline of the latent trait model, gives a detailed analysis of the 12-item General Health Questionnaire (GHQ) and examines points raised by the empirical analysis through computer stimulation. It is shown that the latent trait model can give a good representation of empirical data and uncover new aspects of a familiar instrument. It provides a precise methodology for evaluating the functioning of a questionnaire and for developing better short instruments. It highlights the need, and provides the means, to tailor instruments for different tasks, such as (a) screening, and (b) measuring over the whole range of the population. We examine scoring in the light of the model, and show that simple scoring is often adequate. While points for further methodological development are noted, it is argued that the method is already sufficiently developed for general application.

Urethral diverticula in pregnancy.

In 4 cases, the clinical presentation of urethral diverticulum (UD) during pregnancy was a paraurethral mass (3), urinary incontinence (2), irritative symptoms (2), urinary tract infection (1), urethral pain and discharge (1) and voiding difficulty (1). The diagnosis of UD during pregnancy was made by transvaginal ultrasonography (2), cystoscopy (1), and after pregnancy by a voiding cystourethrogram (1). Management during pregnancy involved antibiotics (2), diverticulum aspiration (2) and incision and drainage (1). Delivery was by the vaginal route in 2 women with diverticular aspiration being performed during the second stage to aid delivery in 1 woman. Caesarean section was performed in the other 2 women for reasons unrelated to the presence of the UD. Three women had diverticulectomy performed following pregnancy for persisting symptoms. Although uncommon, it is important to diagnose urethral diverticula given the associated morbidity and the potential for causing complications during pregnancy.

Urinary leakage during coitus in women.

During a 4-year period from 1993 to 1997, a total of 2153 women were referred to our urogynaecology clinic complaining of urinary incontinence. Of these women, 228 (10.6%) admitted to coital incontinence. Only 22 of these 228 women complained of this symptom without direct questioning. Urine loss occurred during penetration in 158 women, during orgasm in 45 women and during both in 25 women. Comparison of these groups showed few other differences in their presenting symptoms, examination findings, urodynamic data or diagnosis. Genuine stress incontinence was present in 79.8% of women with urinary leakage during penetration, in 93.2% with leak on orgasm and in 92.0% who leaked on both. Detrusor instability was uncommon. In most women who complain of urinary leakage during sexual intercourse, the underlying pathophysiological mechanism is urethral sphincter incompetence. Compared with women presenting with urinary incontinence in the absence of coital incontinence, women with coital leakage had a higher incidence of stress and urge incontinence, and a significantly greater incidence of anterior vaginal wall prolapse and demonstrable stress incontinence on examination.

Screening for gestational diabetes in the United Kingdom: a national survey.

To determine the attitudes of British obstetricians to screening for gestational diabetes a postal questionnaire survey was undertaken. A questionnaire was sent to a single obstetrician in each of 255 obstetric hospitals identified in the United Kingdom. Of the 189 (75%) units that replied, only 42.3% had a protocol for screening for gestational diabetes. Routine antenatal screening was performed by urinalysis and blood glucose tests in 89.4% and 32.8% of units respectively. Clinical risk factors were used as an indication for routine blood glucose testing in 91.5% units. Following a positive screening test 54.5% of units performed a 75 g oral glucose tolerance test (GTT) and of these 64% relied on the World Health Organisation diagnostic criteria to interpret the result. There currently appears to be widespread variation in the practice of screening for gestational diabetes in the United Kingdom.

Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSV type 2 glycoprotein subunit vaccine.

Studies were undertaken to determine whether immunization of humans with a herpes simplex virus type 2 (HSV-2) glycoprotein-subunit vaccine would result in the priming of both HSV-specific proliferating cells and cytotoxic T cells. Peripheral blood lymphocytes (PBL) from all eight vaccines studied responded by proliferating after stimulation with HSV-2, HSV-1, and glycoprotein gB-1. The PBL of five of these eight vaccines proliferated following stimulation with gD-2, whereas stimulation with gD-1 resulted in relatively low or no proliferative responses. T-cell clones were generated from HSV-2-stimulated PBL of three vaccinees who demonstrated strong proliferative responses to HSV-1 and HSV-2. Of 12 clones studied in lymphoproliferative assays, 9 were found to be cross-reactive for HSV-1 and HSV-2. Of the approximately 90 T-cell clones isolated, 14 demonstrated HSV-specific cytotoxic activity. Radioimmunoprecipitation-polyacrylamide gel electrophoresis analyses confirmed that the vaccinees had antibodies only to HSV glycoproteins, not to proteins which are absent in the subunit vaccine, indicating that these vaccinees had not become infected with HSV. Immunization of humans with an HSV-2 glycoprotein-subunit vaccine thus results in the priming of T cells that proliferate in response to stimulation with HSV and its glycoproteins and T cells that have cytotoxic activity against HSV-infected cells. Such HSV-specific memory T cells were detected as late as 2 years following the last boost with the subunit vaccine.

Herpes simplex virus (HSV)-specific human T-cell clones recognize HSV glycoprotein D expressed by a recombinant vaccinia virus.

Human cytotoxic T-cell (CTL) clones that lyse autologous cells infected with herpes simplex virus (HSV) type 1 or 2 were generated by stimulating lymphocytes with a recombinant vaccinia virus (recombinant vaccinia-gD-1 virus) that expresses HSV type 1 glycoprotein D (gD-1). Furthermore, CTL clones generated with HSV type 1 or with cloned gD-1 lysed autologous cells infected with the recombinant vaccinia-gD-1 virus. Our findings thus showed that gD serves as a target antigen for human CTLs and that a recombinant vaccinia-gD virus activates HSV-specific human CTL.

National audit of incontinence surgery in the United Kingdom.

The aim of the study was to describe the experience, current trends and management of incontinence surgery for urodynamic stress incontinence (USI) in the United Kingdom. The study was a postal questionnaire survey that was sent to a cohort of surgeons known to be performing continence surgery. The subjects addressed included the considered role of the surgeon, the total number and type of operations performed in the last year, urodynamics and physiotherapy prior to incontinence surgery, operative complications, postoperative advice and follow-up (lengths and methods). The response rate was 54%. Large variations were found in all areas. The survey provides evidence of the number of incontinence operations performed, potentially important trends and differences in the practice and management of incontinence in the United Kingdom. This survey may be helpful in making guidelines and standards for audit at regional, local and individual levels as well as recommendations for strategies to enhance professional expertise in urogynaecology in the United Kingdom.

Tension-free vaginal tape (TVT) in the United Kingdom.

Four hundred and twenty-six surgeons identified as performing TVT in the United Kingdom in the year ended 1 January 2002 were sent a postal questionnaire to identify the technique employed and the complications encountered. An 81% response rate was achieved. Over 7000 TVT operations were reported. Large numbers of surgeons perform a small number of operations each year. A variety of different surgical techniques and anaesthetics are used. Bladder perforations have been reported by 44% and de novo bladder overactivity by 37% of surgeons. Tape erosion is seen in 0.33%. Twenty-eight per cent of surgeons have seen voiding abnormalities that persist for more than 6 weeks. Fifty-seven per cent of surgeons perform short-term follow-up only. The operation is performed in a variety of different ways, by surgeons with variable experience and volumes of work. The different surgical techniques have not been evaluated prospectively and complications are seen more commonly than originally reported.