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.

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.

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.

A prospective evaluation of the pathogenesis of detrusor instability in women, using electron microscopy and immunohistochemistry.

OBJECTIVE: To characterize the types of detrusor smooth muscle junctions in the bladders of women with detrusor instability and in a control group without, and to assess whether there are differences in the cell junctions between these groups. PATIENTS AND METHODS: The study included 13 women with detrusor instability (median age 57 years, range 32-86) and 11 control women (median age 50 years, range 33-62). Bladder biopsies were taken from each participant, processed for electron microscopy and immunohistochemistry (using a labelled antibody to vinculin) and analysed by investigators who were unaware of the patients' diagnoses. RESULTS: Adherens (intermediate) junctions in classic and rudimentary forms were present in all biopsies from patients and controls. Adherens junctions and dense plaques occupied almost the complete cell border in most samples. Complete immunohistochemistry was possible in seven patients and five controls. In almost every detrusor smooth muscle cell studied, there was staining of the entire cell border with labelled antibody to vinculin in all biopsies. CONCLUSIONS: This study provides evidence against an ultrastructural basis for idiopathic detrusor instability based on possible differences in detrusor smooth muscle intercellular junctions. Virtually the entire cell membrane of detrusor smooth muscle fibres is occupied by adherens junctions in classic and rudimentary forms, and with dense plaques present in samples from women with an unstable bladder and from controls. There was no junction detected in those with instability that was not present in the control group. The adherens junctions in the bladder facilitate mechanical coupling between cells.

Tension-free vaginal tape for primary genuine stress incontinence: a two-centre follow-up study.

OBJECTIVE: To assess the safety and efficacy of the tension-free vaginal tape procedure in the treatment of primary genuine stress incontinence. PATIENTS AND METHODS: A two-centre follow-up study was conducted on 40 women with urodynamically confirmed primary genuine stress incontinence who had a tension-free vaginal tape inserted under local anaesthesia with sedation. Operative details were recorded and all patients followed up both subjectively, and objectively with repeat urodynamic studies and pad testing. RESULTS: The mean (range) age of the women was 51.1 (33-86) years, the median parity 2 (0-4) and mean body mass index 25.1 (19-35). The mean anaesthesia and operative duration was 42 (25-65) min; 93% of the women resumed immediate spontaneous voiding with no need for catheterization. The mean inpatient stay was 2.2 (2-4) days (where 2 days is equivalent to one night in hospital). The follow-up was conducted at a mean interval of 12.3 (6-24) months. Subjectively, 80% of women were cured and 17.5% significantly improved; objectively, genuine stress incontinence was cured in 95%. Symptomatic postoperative detrusor instability was found in 15% of women and symptoms of voiding dysfunction identified in 5% of women. There were no defects in healing or tape rejection. CONCLUSION: The tension-free vaginal tape procedure is a promising new technique that, in this short-term analysis, appears to be safe and effective. Intra-operative complications are uncommon and both hospital stay and recovery are short. Voiding complications are rare but symptomatic postoperative detrusor instability had an incidence of 15%.

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.

Colposuspension or sling for low urethral pressure stress incontinence?

The aim of this study was to compare Burch colposuspension with the pubovaginal sling in the management of low urethral pressure urinary stress incontinence. Forty-five women with low urethral pressure stress incontinence were retrospectively reviewed: 21 underwent colposuspension and 24 a pubovaginal sling. The subjective success rate of the Burch colposuspension and the pubovaginal sling was 90% and 71% (P = 0.12), respectively; the objective success rate was 67% and 50% (P = 0.26), respectively. The incidence of postoperative complications, including de novo detrusor instability and symptomatic voiding dysfunction following the colposuspension, was 5% compared to 25% following the pubovaginal sling (P = 0.06). Colposuspension should be considered in the management of women undergoing surgical correction of low urethral pressure stress incontinence. In a clinically similar group of women, the Burch colposuspension had a superior subjective and objective success rate with a lower incidence of complications than did the pubovaginal sling. Although these differences failed to reach statistical significance, colposuspension can be safely considered in the management of women with low urethral pressure GSI.

Oral methotrexate in the management of refractory interstitial cystitis.

To establish the safety and efficacy of low-dose oral methotrexate in treating refractory interstitial cystitis, 9 women who fulfilled internationally accepted criteria for the diagnosis of interstitial cystitis were enrolled in a prospective study. All had proven unresponsive to conventional treatment modalities. Assessment by pain score and frequency volume charts was performed pretreatment and up to 6 months during therapy. No significant adverse side effects were noted. At the end of follow-up, 4 women had noted a subjective improvement in bladder pain and wished to continue on methotrexate, 4 women noted little change and 1 woman reported a worsening of symptoms. Overall there was a significant reduction in pain score (p = 0.047) posttreatment. However, there was no significant difference in urinary frequency per 24 hours (p = 0.40), maximum voided volume (p = 0.089) or mean voided volume (p = 0.59). Methotrexate significantly improved bladder pain in women with interstitial cystitis, although no significant change was found in voiding pattern.

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.

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.

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.

Inhibition of virus production in peripheral blood mononuclear cells from human immunodeficiency virus (HIV) type 1-seropositive donors by treatment with recombinant HIV-like particles.

We have previously reported on the assembly of recombinant human immunodeficiency virus (HIV)-like particles that contain gag structural proteins and present env glycoproteins gp120 and gp41 on their surfaces (O. Haffar,. J. Garriques, B. Travis, P. Moran, J. Zarling, and S.-L. Hu, J. Virol. 64:2653-2659, 1990). On the basis of their structures, we hypothesized that the recombinant particles would interfere with virus infection and tested our hypothesis in vitro by using peripheral blood mononuclear cells (PBMC) from HIV type 1-seropositive donors. Addition of the recombinant particles to PBMC concomitant with stimulation by anti-CD3 inhibited virus production, as determined by reduced levels of p24 in the culture supernatants. This inhibition of p24 production correlated with lower levels of cell-associated viral DNA. Several lines of evidence suggested that the recombinant particles exerted their antiviral effects primarily by inhibiting virus production from latently infected cells and not by inhibiting subsequent virus spread. Importantly, CD4+ T-cell stimulation by specific antigen or by anti-CD3 was not inhibited by treatment with the recombinant particles. This apparent selective inhibition of virus replication in infected PBMC represents a novel property of the recombinant HIV-like particles.

HIV-specific humoral and cellular immunity in rabbits vaccinated with recombinant human immunodeficiency virus-like gag-env particles.

Recombinant human immunodeficiency virus type-1 (HIV-1)-like gag-env particles produced in mammalian cells were inoculated into two New Zealand white rabbits. In parallel, two control rabbits were inoculated with the homologous HIV-1 virions inactivated by ultra violet light (uv) and psoralen treatments. The humoral and cellular immune responses to HIV-1 were evaluated for both groups of animals. Recombinant particles elicited humoral immunity that was specific for all the viral structural proteins. The antibodies recognized both denatured and nondenatured proteins. Moreover, the sera neutralized the in vitro infectivity of the homologous virus in CEM cells. Importantly, the recombinant particles also generated a T helper response by priming with the HIV proteins. Similar results were observed with inactivated virus immunization. Therefore, our results suggest that the recombinant HIV-like particles elicit functional humoral immunity as well as cellular immunity and represent a novel vaccine candidate for AIDS.

Inhibition of HIV-1 replication in seropositive patients' CD4+ T-cells by pokeweed antiviral protein-monoclonal antibody conjugates.

Pokeweed antiviral protein (PAP) inhibits HIV-1 replication in HIV-1 infected CD4+ cells and PAP targeted to CD4+T-cells by conjugation with monoclonal antibodies (mAb) against CD4 is approximately 1000 times more potent than non-conjugated PAP. Furthermore, PAP-antiCD4 inhibits HIV-1 production in seropositive patients' CD4+ T-cells activated with mAb to CD3 which was found to be the most potent means to activate HIV-1 production. These findings, together with previous observations that PAP-mAb conjugates have an in vivo plasma half-life of about 30 times that of non-conjugated PAP, suggest that PAP-antiCD4 may be a useful therapy in HIV-infected humans. Additionally, because PAP is known to have antiviral activity against several other human viruses, PAP-mAb conjugates may also have clinical potential for treating other viral diseases.