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PubMed1989

Sensitive detection of nucleic acids and protein of human papillomavirus type 6 in respiratory and genital tract papillomata.

We have developed a sensitive method to detect and localize HPV-6 viral DNA, mRNA and protein in biopsy specimens of genital and respiratory tract lesions by using in situ hybridization and immunoperoxidase assays on sections of plastic-embedded tissue. This modified in situ hybridization technique, using ultrathin sections and strand-specific 3H-labelled riboprobes, offers the advantages of superior morphological preservation and detection of viral genomes at low copy number with good resolution. This modified immunocytochemistry provides better sensitivity when compared to previous methods using paraffin-embedded materials. In respiratory tract lesions, immunoperoxidase assay detected only a few capsid antigen positive cells, while in the genital tract lesions, there were more capsid antigen positive cells. Southern transfer analyses and in situ hybridizations demonstrated the presence of more viral nucleic acids in genital tract papillomata than respiratory tract papillomata. Epithelial cells throughout the papillomata were infected by HPV-6 as evidenced by positive hybridization, with more viral DNA present in superficial cells. Our results suggest that genital tract epithelium is more permissive for HPV-6 replication than respiratory tract epithelium. Using stand-specific probes synthesized from subgenomic fragments of the HPV-6 genome in conjunction with nuclease digestions, we were able to demonstrate that HPV-6 transcripts specific to open reading frames (ORFs) E6, E7, E1, L1, and L2 occur in maturing superficial cells. In contrast, transcripts specific to ORFs E1, E2, E4, E5a, and E5b could be detected throughout the whole of the epithelium with more signals noted at the basal cell areas. In addition, the distribution of HPV-6 nucleic acids and protein in a carcinoma in situ of the larynx was analyzed. In comparison to benign respiratory tract papillomata, more viral DNA was found in the malignant lesion, but the pattern and distribution of transcription and capsid antigen was similar.

Antigens, Viral↗
PubMed1982

Anti-herpesvirus activity of adenine arabinoside analogues in tissue culture and a genital infection of mice and guinea pigs.

Four analogues of adenine arabinoside (ara-A) were compared for activity against herpes simplex virus (HSV) in tissue culture and in a genital infection of mice and guinea pigs. These analogues, 5'-monophosphate (ara-AMP), 5'-valerate ester (ara-AV), 2'3'-diacetate ester (ara-ADA), and 2',3',5'- triacetate ester (ara-ATA) have greater water and lipid solubility and resistance to deamination than ara-A. In mouse embryo fibroblast cells, similar viral inhibitory levels were noted with ara-A, AMP, and ara-Av, while ara-ADA and ara-ATA were 6-10 time less active. In mice infected intravaginally with HSV type 2 (HSV-2), intravaginal treatment with 10% concentrations of each of the compounds beginning 3 h after viral challenge, had no effect on infection rates, titers of virus in vaginal secretions, mortality rates or the mean day of death as compared with placebo-treated controls. In the HSV-2 genital infection of guinea pigs, treatment with 10% vaginal creams or placebo vehicle was initiated 6 or 24 h after viral inoculation. In animals treated at 6 h with ara-A, ara-AMP and ara-AV, there was complete inhibition of viral replication in the vaginal tract and development of external genital lesions. When treatment with these three drugs was delayed 24 h after infection, there was no effect on vaginal virus titers, but lesions severity was reduced by ara-A or ara-AMP therapy. Ara-ATA was ineffective whether begun at 6 or 24 h. The greater solubility in water and lipid as well as the resistance to deamination of ara-AMP and ara-AV did not appear to enhance their antiviral activity over that of ara-A. Additionally, ara-ADA and ara-ATA exhibited less activity both in tissue culture and in the experimental genital infections.

Administration, Topical↗
PubMed1983

Acyclovir treatment of experimental genital herpes simplex virus infections. I. Topical therapy of type 2 and type 1 infections of mice.

Intravaginal inoculation of mice with herpes simplex virus (HSV) provides a model infection of genital herpes to determine the effectiveness of potential antiviral agents. topical (intravaginal) treatment with 1% or 5% acyclovir (ACV) in an ointment of gel vehicle initiated 3, 6 or 24 h after inoculation with HSV type 2, significantly inhibited viral replication in the genital tract and usually reduced final mortality. Treatment with 5% ACV initiated 48 or 72 h after infection also reduced vaginal virus titers but did not alter final mortality. When mice were inoculated with HSV type 1 treatment with 5% ACV significantly reduced viral replication in the genital tract when begun as late as 72 h. In HSV-2 infected mice, treatment initiated 3 h but not 24 h after infection prevented the establishment of latent infection in sacral ganglie. These results suggest that topical ACV may be effective antiviral agent for primary genital herpes in humans.

Acyclovir↗
PubMed1992

Peptide histidine valine (PHV) is present and biologically active in the human female genital tract.

The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM) and peptide histidine valine (PHV) in the human female genital tract was studied by means of radioimmunoassay in combination with gel chromatography. In addition, the effect of PHV on genital smooth muscle activity was investigated in vitro and compared to that of VIP. Immunoreactive VIP, PHM and PHV were present in all regions of the human female genital tract, the highest concentrations being measured in the vagina and the uterine cervix. The peptides displayed similar regional distribution and as expected from the structure of the VIP precursor molecule in which the examined peptides are contained, the molar ratio of VIP to the total PHM/PHV immunoreactivity was close to 1:1. In all regions PHV constituted 50-70% of the total PHM/PHV immunoreactivity indicating that the dibasic conversion site after PHM was uncleaved. VIP and PHV were found to be equipotent relaxants of the smooth muscle from the Fallopian tube and the myometrium. The present study indicates that PHV like PHM and VIP may act as a neurotransmitter in the human female genital tract and thus participate in the local nervous control of the reproductive functions.

Adult↗
PubMed1991

Diabetic ketoacidosis precipitated by genital herpes infection.

Diabetic ketoacidosis is frequently precipitated by infections. We report three cases in which ketoacidosis was induced by genital herpes infection. There is good evidence that early treatment with systemic Acyclovir is effective in patients with a first attack of genital herpes. Therefore genital examination should be considered in patients with diabetic ketoacidosis particularly when there are symptoms of genital herpes. During episodes of recurrence, diabetic patients need to monitor their blood sugars more frequently and adjust insulin requirements accordingly. We believe that this is the first description of ketoacidosis being associated with this increasingly common and recurrent infection.

Acyclovir↗
PubMed1996

Expression patterns of developmental genes reveal segment and parasegment organization of D. melanogaster genital discs.

We have used the expression patterns of genes known to be important during early Drosophila development to determine the segment-parasegment organization of the genital discs and to localize the three primordia in the male and female genital discs, engrailed (en) and hedgehog (hh) were used to locate posterior compartments in A8-A10, while cubitus interrupts (ci) localized the anterior compartments for each segment, decapentaplegic (dpp) identified the anterior cells that abut en and hh at the anterior-posterior border. abdominal-A (abd-A) identified the anterior compartment for abdominal segment 8 (aA8) in females but was not detected in the repressed female primordium in male discs. Abdominal-B (Abd-B) was expressed throughout the discs except for a small area along the edge of the posterior lobes, leaving open the possibility that A11 may contribute to the genital discs, caudal (cad) was expressed segmentally in the anal primordium of A10, extending through the Abd-B unstained region, wingless (wg) and gooseberry (gsb) may have assumed an added role in the discs perhaps providing proximal-distal cues. Models are presented to show how the segments and parasegments may fuse together during embryogenesis to form the mature male and female genital discs.

Animals↗
PubMed2005

Prevalence and determinants of genital shedding of herpes simplex virus among women attending Italian colposcopy clinics.

OBJECTIVES: To determine the prevalence of herpes simplex virus (HSV) shedding among women attending Italian colposcopy clinics and describe their lifestyle, demographic characteristics, genital symptoms and signs. STUDY DESIGN: A cross-sectional study was performed to assess shedding of HSV among 4565 women requiring a gynecological consultation. An amplified enzyme immunoassay that detects an HSV type-common glycoprotein D was used to reveal HSV shedding in cervical specimens. Statistical analysis was performed using Chi-square test and Student's t test. RESULTS: A prevalence of 7.8% was found among colposcopy clinic patients. No significant differences regarding patients' average age, age at first sexual intercourse, contraceptive method used, and number of sexual partners in the previous year were found between subjects with and without viral shedding (P > 0.05). The detection of a concomitant genital infection with Trichomonas vaginalis as well as the report of previous episodes of genital herpes (GH) were significantly higher in the positive group (P < 0.01). Only 2.8% of the patients shedding HSV presented with vesicles and ulcers, with the majority of them being asymptomatic. CONCLUSION: This is the first Italian survey on genital herpes conducted among colposcopy clinic patients. Our data show that the prevalence of HSV shedding in this study population is high and confirms that the disease is often asymptomatic. The demographics and behavioural variables of women shedding HSV seem to differ from the ones assessed in high risk patients.

Adult↗
PubMed2004

Age-related effects on genital reflexes induced by paradoxical sleep deprivation and cocaine in rats.

Although sexual function often decreases with age, a recent study demonstrated that paradoxical sleep deprivation (PSD) was effective in inducing penile erection (PE) in 60% of 22-month-old PSD rats after acute cocaine injection, whereas this behavior was absent in non-PSD control rats. The present study sought to compare alterations in genital reflexes (PE and ejaculation-EJ) induced by PSD followed by acute cocaine or saline at different points in the life span of male rats. Rats of different ages (3, 6, 10, 12, 18, 22 and 28 months), were given a single injection of either saline or cocaine (7 mg/kg, i.p.) after a 4-day period of PSD, and then evaluated for genital reflexes. Results indicated that genital reflexes in PSD rats given saline become less frequent with age and disappear after the age of 18 months. However, cocaine potentiated and prolonged these behaviors until the age of 22 months. Although a number of factors are involved in such a complex phenomenon as PE, we suggest that the previously documented dopamine receptor supersensitivity induced by PSD may be an important contributor to the potentiation by cocaine of genital reflexes after sleep deprivation.

Aging↗
PubMed2005

Genital HIV-1 viral load is correlated with blood plasma HIV-1 viral load in Brazilian women and is reduced by antiretroviral therapy.

CONTEXT: Cervicovaginal secretions represent the primary vehicle in mother to infant and sexual HIV-1 transmission. Understanding the viral dynamics in this compartment is important to improve interventions to decrease HIV transmission. OBJECTIVES: To evaluate the correlation of HIV-1 blood plasma viral load and cervicovaginal HIV-1 viral load and the effect of antiretroviral therapy (ART) on cervicovaginal HIV-1 viral load. METHODS: A cross-sectional study among HIV-1 infected women recruited between February 2002 and January 2003 and a longitudinal study that included 11 women who initiated ART were performed. HIV-1 viral load was measured in the female genital tract and in blood plasma using the Nuclisens assay before and 1 month after ART introduction. RESULTS: HIV-1 viral load in cervicovaginal lavage was significantly correlated with HIV-1 blood plasma viral load (n = 27, Spearman rho = 0.73, p<0.001). In the longitudinal study, antiretroviral therapy was associated with a reduction of 1.44 log10 on genital HIV-1 viral load (95% CI = 0.57-2.30, p = 0.004, Student's t-test). CONCLUSIONS: HIV-1 viral load in female genital secretions is correlated with blood plasma HIV-1 viral load. Antiretroviral therapy substantially reduces HIV-1 viral load in the female genital tract.

Adult↗
PubMed2006

Hypercalciuria as a cause of genital bleeding in a 6-year-old girl.

STUDY OBJECTIVE: To document an unusual cause of genital bleeding in a 6-year-old girl. DESIGN: Case report. SETTING: Outpatient pediatric gynecology clinic in a tertiary care hospital. RESULTS: Clinical presentation of a case of genital bleeding secondary to hypercalciuria in a 6-year-old female. Gynecologic investigations were negative. There were hematuria on urinalysis and an elevated calcium-to-creatinine ratio on initial presentation; however, no evidence of urolithiasis was found on ultrasound. In the context of negative investigations and persistent episodes of bleeding, the hypercalciuria was treated with hydrochlorothiazide. Normalization of calciuria was associated with the end of genital bleeding episodes. CONCLUSION: Hypercalciuria with microcrystals and urethral irritation should be considered as part of the differential diagnosis for genital bleeding in girls.

Child↗
PubMed2004

T-cell-mediated mechanisms involved in resolution of genital herpes simplex virus type 2 (HSV-2) infection of mice.

Resolution of a HSV-2 infection of the female genital tract has been shown to be T-cell dependent. The T-cell populations and mechanisms involved in clearance of virus from the genital epithelium were examined in this study. T lymphocytes expressing either alphabeta or gammadelta T-cell receptors (TCR) have been detected in the vaginal epithelium of mice. The involvement of gammadelta T cells in HSV-2 clearance was tested by intravaginal (ivag) challenge of mice depleted of alphabeta T cells by administration of specific antibodies and of mice lacking gammadelta T cells due to specific deletion of the delta TCR gene. The results of these studies strongly suggest that gammadelta T cells are not required for or involved in clearance of HSV-2 from the genital epithelium. Mechanisms of virus clearance employed by alphabeta T cells were also examined. Although HSV-specific lytic activity could be demonstrated ex vivo in populations of vaginal exudate cells from HSV-infected mice, clearance of virus did not require either perforin- or Fas/Fas ligand (FasL)-dependent cytolytic pathways. In contrast, virus resolution was significantly impaired following neutralization of interferon-gamma (IFN-gamma), but not tumor necrosis factor-alpha (TNF-alpha). Together, these results suggest that non-lytic mechanisms mediated by alphabeta T cells were responsible for resolution of a genital HSV-2 infection.

Animals↗
PubMedDate not supplied

[Quality of life with genital herpes].

Health related quality of life (HRQOL) indicators take into account the personal perception of health, and are proposed as an alternative for efficacy indicators in medical and therapeutic decision-making. They provide, after elaboration and validation of a questionnaire, a standardized assessment of the health status perception. The authors had for aim to review of a variety of HRQOL instruments developed for patients presenting with genital herpes infection. Generic instruments are designed to be applicable in general population and disease-targeted instrument are potentially more sensitive to the characteristics of a specific population. Among HRQOL instruments, we found 4 specific disease-targeted questionnaires developed for patients presenting with genital herpes infection: Genital herpes questionnaire, Herpes research center questionnaire, quality of life with herpes (QLH) scale, and recurrent genital herpes quality of life (RGHQoL).

Attitude to Health↗
PubMed2006

Shape patterns of genital papillae in pinworms (Enterobiinae, Oxyurida, Nematoda) parasite of primates: a landmark analysis.

The Enterobiinae includes 47 species of pinworms parasite of primates. A previous cladistic analysis of this subfamily supported its monophyly and its subdivision into three genera. Based on morphological characters, this cladistic analysis excluded characters describing the shape of the genital papillae of male pinworms, because the corresponding patterns could not be described using discrete characters. In this study, the shape of the genital papillae of the males of 35 within the 47 species is analyzed using geometric morphometric approaches. The aims of this study are to investigate: (i) the relationships between the phylogeny and the shape patterns of the caudal bursa, (ii) the shape differences between and within monophyletic groups, and (iii) the functional implications of the shape patterns observed within the subfamily. Results demonstrate that different patterns of evolution of the caudal bursa, each one characterized by a particular spatial distribution of the phasmids and genital papillae may be recognized, which are consistent with the classification of the Enterobiinae into three groups. On the whole, these patterns may be related to particular mating behavior of the pinworms. When incongruence is observed between shape patterns distribution and species distribution into monophyletic groups, they are found to correspond to homoplasic events. This suggests that convergent selective pressures are involved in the evolution of the shape of the genital papillae. This analysis also confirms that morphometric shape patterns cannot be interpreted unequivocally without the support of a pre-existing phylogenetic framework.

Animals↗
PubMed2005

Treatment of genital prolapse by hammock using porcine skin collagen implant (Pelvicol).

INTRODUCTION: To assess the feasibility and efficacy of the hammock using a porcine skin collagen (Pelvicol) implant for the treatment of genital prolapse by the vaginal route. A total of 47 women with Stage III or IV genital prolapse underwent surgical treatment with porcine skin collagen implantation using anterior transobturator and posterior bilateral sacrospinous fixations. Genital prolapse treatment was combined with hysterectomy in 34 patients (72%). TECHNICAL CONSIDERATIONS: Porcine skin collagen implantation was feasible in every case. The surgical procedure lasted a median of 90 minutes (range 80 to 150). No vessel injuries, one bladder injury, and one rectal injury not requiring additional surgery occurred. One pararectal hematoma required a second procedure. The median follow-up was 24.6 +/- 8.5 months (range 6 to 42). No rejection of the porcine grafts occurred. Of the 47 women, 39 (83%) had optimal anatomic results, 5 had asymptomatic Stage I prolapse, and 2 had Stage II prolapse. The subjective cure rate was 93.6% (44 of 47 patients). The postoperative scores for lifestyle and urinary discomfort improved significantly after the procedure (P < 0.0001 and P < 0.0002, respectively). Of the 18 patients who were sexually active, an improvement in sexual discomfort occurred (P = 0.04). CONCLUSIONS: These short-term results suggest that hammock using porcine skin collagen implantation by the transobturator route and bilateral sacrospinous fixation is a safe and effective treatment for genital prolapse.

Aged↗
PubMed2005

Effects of paradoxical sleep deprivation on genital reflexes in five rat strains.

This study examined the effects of cocaine on genital reflexes in paradoxical sleep-deprived (PSD) male rats of five strains since it has been demonstrated that this drug enhances genital reflexes in Wistar PSD rats. At the end of a 4-day period of PSD or at the equivalent time-point to control animals, cocaine or saline was acutely administered to the animals and penile erection (PE) and ejaculation (EJ) were quantified. Results indicated that PSD induced genital reflexes in all strains, and cocaine potentiated these behaviors in Wistar and Long-Evans rats. Wistar PSD rats injected with cocaine performed significantly more PE than all the other PSD + cocaine strains. The number of Wistar and Long-Evans PSD + cocaine ejaculating was significantly higher than the respective PSD + saline and control, whereas a tendency of increase was seen in relation to other groups. Wistar PSD + cocaine rats showed the highest EJ frequency compared to F344, Sprague-Dawley and Wistar-Kyoto strains, and the Long-Evans displayed more EJ than Sprague-Dawley and Wistar-Kyoto. Analysis of testosterone concentrations revealed that after sleep deprivation, Wistar, Long-Evans, and F344 rats showed significantly lower testosterone concentrations than control rats. In F344, Sprague-Dawley and Wistar-Kyoto controls rats, testosterone was significantly lower than in the control Wistar and Long-Evans. Progesterone concentrations were significantly higher in Wistar and Long-Evans PSD rats than in respective control groups. In the other strains, this hormone was significantly lower compared to the Wistar and Long-Evans PSD. This study demonstrates that genital reflexes are differently influenced by PSD associated to cocaine in five rat strains.

Animals↗
PubMed2003

Genital mycoplasmas in women attending a family planning clinic in Guiné-Bissau and their susceptibility to antimicrobial agents.

A study on the prevalence of genital mycoplasmas and their susceptibility to the most common antimicrobial agents used for treating the infection was conducted on 94 women attending a family planning clinic in Guiné-Bissau. Fifty-four women (57.4%) were positive for Mycoplasma hominis and/or Ureaplasma urealyticum. M. hominis and U. urealyticum separately isolated from infected women yielded frequencies of 31.5 and 27.8%, respectively, the remainder were infected with both species. No strain was found to be resistant to all three commonly employed antibiotics for the management of these infections (erythromycin, tetracycline and ofloxacin), although multiple resistance to two antibiotics was frequent, especially when both genital mycoplasmas were present. Some 90.7 and 24.1% of all isolates were resistant to erythromycin and tetracycline, respectively. No resistance was observed to ofloxacin, although 50% of the strains had intermediate resistance. The high prevalence of genital mycoplasmas in women attending a family planning clinic in Guiné-Bissau, as demonstrated in this study, appears to be associated with trichomonosis and bacterial vaginosis. These infections were also found to be highly resistant to erythromycin and tetracycline and to have intermediate resistance to ofloxacin. However, further studies are necessary to establish the burden of infection due to antibiotic resistant genital mycoplasmas.

Adult↗
PubMed1992

The incidence of genital prolapse after the Burch colposuspension.

OBJECTIVE: Our objective was to determine the incidence of postoperative genital prolapse after the Burch colposuspension and to identify risk factors for the development of subsequent prolapse. STUDY DESIGN: The charts of 131 patients who had a Burch colposuspension performed by the senior author (S.L.S.) between 1977 and 1986 were reviewed at the Urodynamic Unit of St. George's Hospital, London. Emphasis was placed on the degree of genital prolapse on clinical examination and whether further surgery was required to correct the prolapse. RESULTS: Thirty-five patients (26.7%) required a total of 40 operations to correct genital prolapse after colposuspension. At 20 operations, more than one procedure was required to correct combined prolapse. The patient's age, weight, parity, menopausal status, and prior pelvic surgery did not affect the incidence of postoperative prolapse. The only preoperative risk factor identified was the presence of a large cystocele. CONCLUSION: Postoperative genital prolapse is a significant complication of the Burch colposuspension. It is unclear whether this is due to a disruption of the vaginal axis or to an intrinsic weakness of the pelvic floor in these women.

Adult↗
PubMed1994

Detection of tumor necrosis factor-alpha, interleukin-6, and fetal fibronectin in the lower genital tract during pregnancy: relation to outcome.

OBJECTIVE: Our purpose was to determine whether tumor necrosis factor-alpha, interleukin-6, and fetal fibronectin could be identified in the lower genital tract during pregnancy and whether their occurrence was associated with preterm delivery. STUDY DESIGN: A prospective cohort study was undertaken of 111 pregnant women in which cervicovaginal swabs were obtained at < 37 weeks' gestation. Seventy-three specimens were obtained from women during routine prenatal examination, whereas 38 specimens were obtained from women undergoing evaluation of preterm labor. Interleukin-6 and fetal fibronectin levels were determined by enzyme-linked immunosorbent assays, whereas tumor necrosis factor-alpha determinations were by bioassay. Urinary tract and lower genital tract samples were cultured for evidence of infection. The rates of maternal and neonatal complications were assessed. RESULTS: In patients undergoing evaluation for preterm labor the presence of tumor necrosis factor-alpha or fetal fibronectin was associated with an increased prevalence of preterm delivery. Women with tumor necrosis factor-alpha had a 6.19 greater risk (p < 0.005), whereas the presence of fetal fibronectin was associated with a 4.81 greater risk (p < 0.05), of preterm birth. This association was not evident in women who were sampled during routine prenatal examinations. In all women the presence of cytokines in the lower genital tract correlated with detection of fetal fibronectin. CONCLUSION: Localized inflammatory responses may lead to microscopic disruption in the amniotic membranes, leading to leakage of fibronectin. In patients being evaluated for preterm labor, the presence of tumor necrosis factor-alpha or fetal fibronectin in the lower genital tract is predictive of subsequent preterm delivery.

Adolescent↗