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Association of lower genital tract inflammation with objective evidence of endometritis.

The purpose of this report is to evaluate the association between lower genital tract inflammation and objectively diagnosed endometritis. We analyzed the first 157 patients enrolled in the PEACH study, a multicenter randomized clinical trial designed to compare the effectiveness of outpatient and inpatient therapy for PID. Women less than 38 years of age, who presented with a history of pelvic discomfort for 30 days or less and who were found to have pelvic organ tenderness (uterine or adnexal tenderness) on bimanual examination, were initially invited to participate. After recruitment of the first 58 patients (group 1) we added the presence of leukorrhea, mucopurulent cervicitis, or untreated positive test for N. gonorrhoeae or C. trachomatis to the inclusion criteria (group 2, N = 99). We compared rates of endometritis in the two groups and calculated the sensitivity, specificity, and predicted values of the presence of white blood cells in the vaginal wet preparation. The rate of upper genital tract infection in group 1 was 46.5% (27/58) compared to 49.5% (49/99) in group 2. Microbiologic evidence of either N. gonorrhoeae or C. trachomatis increased from 22.4% in group 1 to 38.3% in group 2. The presence of vaginal white blood cells or mucopus has a high sensitivity (88.9%), but a low specificity (19.4%) for the diagnosis of upper genital-tract infection. Assessment of the lower genital tract for evidence of infection or inflammation is a valuable component of the diagnostic evaluation of pelvic inflammatory disease. The presence of either mucopus or vaginal white blood cells is a highly sensitive test for endometritis in patients with pelvic pain and tenderness.

Adolescent↗

Efficacy of azithromycin in reducing lower genital Ureaplasma urealyticum colonization in women at risk for preterm delivery.

OBJECTIVE: The purpose of this study was to determine if azithromycin is effective in reducing lower genital colonization of Ureaplasma urealyticum in women with preterm labor or preterm premature rupture of membranes (PROM). METHODS: A randomized, double-blinded, placebo-controlled prospective study of 60 pregnancies was carried out between 22 and 34 weeks. Genital mycoplasma cultures were performed at the time of admission. Patients were randomized to receive either a single dose of azithromycin (four 250 mg capsules) or a placebo in addition to prophylactic intravenous ampicillin. Repeat cultures were done on undelivered patients 7 days after enrollment. The study had power to detect a 50% decrease in colonization. RESULTS: Overall, lower genital colonization was 47/59 (79.7%) for U. urealyticum. Seven days after enrollment, U. urealyticum was isolated in 14/15 (93.3%) of the azithromycin-treated cases and in 11/14 (78.6%) of the controls (RR = 1.19, 95% CI = 0.88-1.61). Vertical transmission of U. urealyticum was 3/15 (20%) in the azithromycin-treated cases and 5/10 (50%) for the controls (RR = 0.40, 95%, CI = 0.12-1.31). CONCLUSION: These data suggests that a single 1 g dose of azithromycin is ineffective in reducing lower genital colonization with U. urealyticum.

Adult↗

Viruses and cancer of the lower genital tract.

The importance of viruses as oncogenic agents in animals is well established. Recent work suggests that viruses may also be etiologically related to some human cancers. Herpes simplex virus type 2 (HSV-2) and the genital wart virus are prime suspects in carcinomas involving the female lower genital tract. In particular, a close association has been found between HSV-2 infection and cervical neoplasia in cytohistopathologic and seroepidemiologic studies. Preliminary results of prospective studies show further that women with genital herpetic infection are at increased risk of developing cervical neoplasia. Additional studies are also in progress on animal models, including subhuman primates, and efforts continue in the attempt to confirm the presence of viral genetic material or its expression in human cervical cancer cells. The possibility that human wart viruses have an oncogenic potential is suggested by clinicopathologic and electron microscopic observations. Further research is needed to ascertain the precise role of viruses in genital cancer.

Adenoviridae↗

Perinatal implications of the lower genital tract flora.

In a longitudinal study of the microflora of the lower genital tract at three stages in pregnancy and once postnatally, 20 different groups or genera of microorganisms were isolated. No substantial change was demonstrated in the flora as pregnancy progressed, although there was a fall in the rate of isolation of organisms after delivery. Few infants acquired organisms from their mother's lower genital tract. Caucasian mothers colonized by genital ureaplasmas gave birth to infants with a higher mean birth weight for length of gestation than the infants of ureaplasma-negative mothers. There was no correlation between birth weight and maternal genital colonization with ureaplasmas in the infants of Asian mothers. Group B streptococci were recovered from the ano-rectum more frequently than from the posterior vaginal fornix during pregnancy and strains recovered from these sites in individual patients were indistinguishable by serotyping and phage typing, suggesting that the ano-rectum or bowel is the probable source of the organism. Group B streptococci were never recovered from Asian patients (16% of the study population). Sera of women colonized with group B streptococci and cord sera from their infants had higher levels of type-specific IgG antibody than non-colonized controls and their neonates.

Antibodies, Bacterial↗

Human and pig SRY 5' flanking sequences can direct reporter transgene expression to the genital ridge and to migrating neural crest cells.

Mechanisms for sex determination vary greatly between animal groups, and include chromosome dosage and haploid-diploid mechanisms as seen in insects, temperature and environmental cues as seen in fish and reptiles, and gene-based mechanisms as seen in birds and mammals. In eutherian mammals, sex determination is genetic, and SRY is the Y chromosome located gene representing the dominant testes determining factor. How SRY took over this function from ancestral mechanisms is not known, nor is it known what those ancestral mechanisms were. What is known is that SRY is haploid and thus poorly protected from mutations, and consequently is poorly conserved between mammalian species. To functionally compare SRY promoter sequences, we have generated transgenic mice with fluorescent reporter genes under the control of various lengths of human and pig SRY 5' flanking sequences. Human SRY 5' flanking sequences (5 Kb) supported reporter transgene expression within the genital ridge of male embryos at the time of sex determination and also supported expression within migrating truncal neural crest cells of both male and female embryos. The 4.6 Kb of pig SRY 5' flanking sequences supported reporter transgene expression within the male genital ridge but not within the neural crest; however, 2.6 Kb and 1.6 Kb of pig SRY 5' flanking sequences retained male genital ridge expression and now supported extensive expression within cells of the neural crest in embryos of both sexes. When 2 Kb of mouse SRY 5' flanking sequences (-3 to -1 Kb) were placed in front of the 1.6 Kb of pig SRY 5' flanking sequences and this transgene was introduced into mice, reporter transgene expression within the male genital ridge was retained but neural crest expression was lost. These observations suggest that SRY 5' flanking sequences from at least two mammalian species contain elements that can support transgene expression within cells of the migrating neural crest and that additional SRY 5' flanking sequences can extinguish this expression.

5' Flanking Region↗

Identification of genital human papillomaviruses in cervical biopsy specimens: segregation of specific virus types in specific clinicopathologic lesions.

We have established a critical identification method for the full spectrum of genital human papillomaviruses (HPVs) in clinical specimens. It was based on the recognition of PstI, BanI and MspI cleavage patterns of HPV DNA detected by blot hybridization with HPV 58 DNA probe at Tm -40 degrees C. By this method, we identified 24 different types of genital HPV including 5 novel types (HPV 59, 61, 62, 64 and 67) in the specimens collected at one hospital and found almost all the HPVs with the authentic cleavage patterns of their respective prototypes. In 235 cervical biopsy specimens, HPV 6 or 11 was found in exophytic condyloma acuminatum (15/15) but not in any cervical intraepithelial neoplasia (CIN) specimens. In contrast, HPV 18, 30, 43, 54, 56, 59, 62, 66 and 67 were identified in CIN I (28/71) or II (4/56) but not in CIN III, while HPV 16, 31, 33, 35, 39, 51, 52 and 58 were identified in CIN III (83/93) as well as in CIN I (34/71) and II (47/56). The result indicates that heterogeneous genital HPVs prevail all over the world. In addition, HPV 6 and 11 are etiologic agents only of exophytic condyloma, whereas the other HPVs are etiologic agents of CIN with the segregation of specific HPVs in CIN III. We propose a new clinicopathologic grouping of genital HPVs founded on nucleotide homology of the HPV genome.

Biopsy↗

Risk of lung cancer in pre- and post-menopausal women with ano-genital malignancies.

Women diagnosed during the period 1943-1990 and reported to the Danish Cancer Registry with invasive squamous-cell carcinomas of the uterine cervix, vulva, vagina or anus, together with those having pre-cancerous lesions (CIN III or carcinoma in situ) of the uterine cervix diagnosed in the period 1958-1990, were followed for the occurrence of subsequent lung cancer over 762,000 person-years. Overall, these patients developed 2 to 2 1/2 times more lung cancers than women in the general Danish population. Women in whom cervical cancer was diagnosed recently, and before the age of 45 years, had a 4.6 times elevated risk of developing lung cancer, while young women with vulvar or vaginal cancer were at a 4.0-fold elevated risk. Similarly, women in whom anal cancer was diagnosed before the age of 60 years were at a 3.5-fold increased risk of developing lung cancer. The present study supports the hypothesis that smoking is involved in the aetiology of ano-genital malignancies. The particularly high risk of developing subsequent lung cancers seen in women who were pre-menopausal (< 45 years) at the time of the ano-genital cancer diagnosis suggests that the effect of smoking in ano-genital carcinogenesis might be partly mediated through alterations in oestrogen metabolism. Alternatively, patients who developed their initial ano-genital cancer at a young age might harbour some genetic susceptibility which could explain their excess lung-cancer risk.

Adult↗

Development of the genital ducts in Telmatodrilinae (Tubificidae, Clitellata).

In Tubificidae, the male genital duct comprises a funnel in the testes segment, followed by a vas deferens, an atrium, and, frequently, a copulatory structure in the adjacent ovarian segment. There may also be a diffuse or compact prostate gland in association with the duct. The morphology and position of the genital ducts are important for the classification of the oligochaetous Clitellata. Different parts of the male duct, however, have been named without regard to whether they are homologous or not. One way to establish better hypotheses of homology is to study the detailed morphology and/or the development of the genital ducts. The morphogenesis of the genital ducts in Alexandrovia onegensis (Telmatodrilinae) is described. The male funnel originates by multiplication of peritoneal (mesodermal) cells in the posterior septum in the testes segment. A cord of these cells breaks through the septum and grows backwards into the next segment, where it connects to the epidermis. This cord gives rise to the vas deferens, and is therefore mesodermal in origin. The atrium in A. onegensis develops from a primary epidermal (ectodermal) invagination. The vas deferens and atrium connect and a continuous duct from the testes segment to the exterior is formed. Several compact prostate glands develop along the atrium, each being formed from cells in the atrial epithelium. The spermatheca develops from an invagination of the epidermis in the testes segment. The female duct is formed from peritoneal (mesodermal) cells in the posterior septum in the ovarian segment. These developmental findings strengthen the hypothesis about a closer relationship between the Telmatodrilinae and Tubificinae (both Tubificidae).

Animals↗

Genital herpes: natural history and treatment of acute episodes.

Genital herpes is a common, distressing infection whose incidence has been underestimated. Recent serological surveys, employing type-specific antibody assays, show a rising prevalence of previous herpes simplex virus (HSV) type 2 infections in post-adolescent populations in developed countries; many of these infections have been asymptomatic. In some geographical locations, HSV-1 infections are a common cause of first episodes. They may occur in stable, monogamous relationships and are less likely to recur than genital infections caused by HSV-2. The clinical features of first episode genital herpes show marked individual variation in severity; they tend to be more severe in women than in men. Local and distant complications are common in immunocompetent individuals and may be life-threatening in those who are immunocompromised. The psychological and social consequences which result from the life-long infection and its risks of transmission to new sexual partners often prove more disabling to affected individuals than do the milder physical symptoms associated with recurrent episodes. Counselling, support, and patient education are essential components of management. Acyclovir is clearly established as the first choice therapy in both first and recurrent episodes of genital herpes. This drug has potent antiviral effect and provides significant clinical benefit in first episodes. Systemic therapy for initial episodes does not prevent either the establishment of latency or the development of future recurrences even when used in high or prolonged dosage. Episodic treatment of recurrences, with either oral or topical acyclovir, requires early patient initiation of therapy to provide significant clinical benefit.

Acute Disease↗

Reduced genital sensitivity in female patients with multiple system atrophy of parkinsonian type.

According to the consensus statement on the diagnosis of multiple system atrophy (MSA), erectile dysfunction is required for male patients to fulfil the urinary incontinence criterion. However, there is no equivalent item for female patients. We questioned 19 female patients with MSA of the parkinsonian type (MSA-P), 28 female patients with Parkinson's disease (PD), and 27 healthy controls on their genital sensitivity. A total of 47% of the MSA patients but only 4% of the PD patients and 4% of the control group admitted to reduced genital sensitivity, a highly significant difference (P < 0.001). Moreover, the appearance of reduced genital sensitivity in female MSA patients showed a close temporal relation to the onset of the disease. If these preliminary results can be confirmed and further specified in a larger sample, a historical item of reduced genital sensitivity in female patients might become a diagnostic feature for MSA, comparable to erectile dysfunction in male patients.

Aged↗

Association of prenatal phenobarbital and phenytoin exposure with genital anomalies and menstrual disorders.

BACKGROUND: Animal studies demonstrated that early exposure to phenobarbital decreases reproductive function. This study investigates whether prenatal exposure to these anticonvulsants affects human genital tract development. METHODS: Genital anomalies at birth were studied retrospectively in 90 phenobarbital-exposed, 108 phenobarbital plus phenytoin-exposed, and 198 matched control infants. Of this group, 72 drug-exposed males, 75 drug-exposed females, and 147 matched control subjects participated in a follow-up and were interviewed at age 19-35. Differences between groups were tested by chi-square and t-tests. RESULTS: A total of 15% of the phenobarbital-exposed boys versus 2.8% control boys had undescended testes at birth. More anticonvulsant-exposed (24%) than control males (11%) had received medical treatment for genital anomalies. Anticonvulsant-exposed females more often had irregularities in menstrual cycles (31% vs. 17%) and bleeding (15% vs. 3%) and reported more problems during pregnancy. CONCLUSIONS: Prenatal exposure to anticonvulsants seems to induce minor genital anomalies and may affect reproductive function.

Adult↗

Mucosal melanoma of the female genital tract is a multifocal disorder.

OBJECTIVE: This is a retrospective analysis of malignant melanoma of the female genital tract, focusing on the high local recurrence rate of this tumor. METHODS: All women treated for malignant melanoma of the genital tract were identified through the archives of the Hadassah University Hospital. The medical records and the pathological specimens were reviewed and reevaluated. RESULTS: From 1986 to 2002, nine cases were diagnosed and treated at Hadassah. Seven had vulvar melanoma and two had vaginal melanoma. Sixty-six percent (6/9) of the patients had more than one focus of melanoma, either apparent at their initial diagnosis (3/9) or developed during follow up (3/9). Most of the recurring lesions were melanoma in situ. In one patient multiple nodular melanomas were detected. Atypical melanocytic hyperplasia was found in an otherwise normal mucosa in four patients. Three had experienced multiple recurrences. All patients were treated by radical local excisions with (3/9) or without (6/9) elective groin lymph node dissection. Three patients with locally recurring melanoma within the genital tract required two to five sessions of repeated surgical excisions. CONCLUSION: It is suggested that melanoma of the genital tract is the result of a multifocal disorder of the melanocytes within the mucosa. The increased local recurrence rate reflects an inherent abnormality of melanocytes. It is not attributed to surgical failure in controlling the disease. Insistent and even radical surgical excision is recommended, especially for patients whose prospects for prolonged survival are improved.

Adult↗

Comparative study on E6 and E7 genes of some cutaneous and genital papillomaviruses of human origin for their ability to transform 3Y1 cells.

E6 (or E7) genes of some genital and cutaneous human papillomaviruses (HPVs) were compared for their ability to transform cells of a rat fibroblastic line (3Y1) by using recombinant retroviruses. The E6 gene of genital cancer-associated HPV 16 or 18 was found to induce a characteristic morphological change, i.e., densely packed arrays of elongated cells forming swirl patterns. This change is the same as that induced by the E6 gene of cutaneous cancer-associated HPV 5, 8, or 47, which we described previously. The E6 gene of HPV 1 or 11, associated with benign tumor of cutaneous or genital tissue, respectively, induced no such change. The E6 genes of all these cutaneous and genital HPVs enhanced anchorage-independent growth of the target cells induced by E7 gene of HPV 16 or 18, and this enhancing activity of HPVs 16, 18, and 47 was stronger than that of HPVs 1 and 11. A distinct type of morphological transformation of 3Y1 cells, i.e., rounded miniaturized cells that were densely packed without forming any distinctive arrays, was found to be induced strongly by E7 genes of HPVs 16 and 18, weakly by E7 of HPVs 1 and 11, and not at all by E7 of HPV 47. The results suggest that the intensity of the morphological change induced by E6 genes, rather than E7 genes, is correlated to the risk of malignant conversion of the lesion with which the corresponding HPVs are associated.

Cell Line↗

Rabbit oral papillomavirus complete genome sequence and immunity following genital infection.

Rabbit oral papillomavirus (ROPV) infects mucosal tissues of domestic rabbits. The viral genomic sequence has been determined and the most related papillomavirus type was the cutaneous cottontail rabbit papillomavirus (CRPV). Homologies between the open reading frames (ORFs) of ROPV and CRPV, however, ranged from 68% amino acid identity for L1 to only 23% identity for E4. Shared features unique to the two rabbit viruses included a large E6 ORF and a small E8 ORF that overlapped the E6 ORF. Serological responses to ROPV L1 viruslike particles (VLPs) were detected in rabbits infected at either the genital or oral mucosa with ROPV. The antibody response was specific to intact ROPV L1 VLP antigen, was first detected at the time of late regression, and persisted at high levels for several months after complete regression. Both oral and genital lesions regressed spontaneously, accompanied by a heavy infiltrate of lymphocytes. ROPV infection of rabbit genital mucosa is a useful model to study host immunological responses to genital papillomavirus infections.

Animals↗

Decreased vaginal disease in J-chain-deficient mice following herpes simplex type 2 genital infection.

J-chain-deficient (Jch(-/-)) mice were used to study the role of polymeric IgA (pIgA) in primary disease and protective immunity following genital herpes simplex type 2 (HSV-2) infection. Vaginal IgA in the Jch(-/-) mice was composed primarily of monomeric IgA and was not associated with secretory component (SC). In contrast, vaginal IgA in wild-type (WT) mice was predominantly polymeric and bound to SC. Following HSV-2 genital infection, the Jch(-/-) mice consistently exhibited fewer vaginal symptoms (P = 0.010) and mortality (P = 0.075) than did the WT mice. The variation in disease expression could not be explained by differences in local viral replication, since titers in vaginal wash fluid were comparable. To assess the effect of J chain deficiency on protective immunity, WT and Jch(-/-) mice were immunized intravaginally with attenuated HSV-2, challenged intravaginally with wild-type virus 5 weeks later, and evaluated for vaginal infection and neurological disease. Although the Jch(-/-) mice had reduced vaginal HSV-specific IgA and IgG levels following immunization, both WT and Jch(-/-) mice were protected from symptoms following wild-type virus challenge. We conclude that pIgA is not required for protective immunity against genital HSV-2 disease and that J chain deficiency offers some protection against symptoms following primary HSV-2 genital infection.

Animals↗

The efferent innervation of the genital chamber by an identified serotonergic neuron in the female cricket Acheta domestica.

The serotonergic innervation of the genital chamber of the female cricket, Acheta domestica, has been investigated applying anti-serotonin (5-HT) immunocytochemistry at both light- and electron-microscopic levels as well as using conventional electron microscopy. Whole mount and pre-embedding chopper techniques of immunocytochemistry reveal a dense 5-HT-immunoreactive network of varicose fibers in the musculature of the genital chamber. All of these immunoreactive fibers originate from the efferent serotonergic neuron projecting through the nerve 8v to the genital chamber (Hustert and Topel 1986; Elekes et al. 1987). At the electron-microscopic level, 5-HT-immunoreactive nerve terminals, which contain small (50-60 nm) and large (approximately 100 nm) agranular vesicles as well as granular vesicles (approximately 100 nm), contact the muscle fibers or the sarcoplasmic processes without establishing specialized neuromuscular connections. In addition to the 5-HT-immunoreactive axons, two types of immunonegative axons can also be found in the musculature. By use of conventional electron microscopy, three ultrastructurally distinct types of axon processes can be observed, one of which resembles 5-HT-immunoreactive axons. While the majority of the varicosities do not synapse on the muscle fibers, terminals containing small (50-60 nm) agranular vesicles occasionally form specialized neuromuscular contacts. It is suggested that the 5-HTergic innervation plays a non-synaptic modulatory role in the regulation circular musculature in the genital chamber of the cricket, while the musculature as a whole may be influenced by both synaptic and modulatory mechanisms.

Animals↗

Women's sexual arousal concurrently assessed by three genital measures.

The relationship among three objective measures of genital vasocongestion in women was evaluated both during and after an erotic film using simultaneous recording of both vaginal pressure pulse and vaginal blood volume responses by means of photoplethysmography and of labial temperature change by means of a thermistor clip. During the film each of the genital measures increased for most subjects, resulting in highly significant positive correlations between measures. However, following the erotic film presentation there was considerably less direct correspondence among the three measures; although the genital reactions of most subjects subsided to some extent following the film, none of the three measures consistently returned to prestimulation levels. Periodic estimates of subjective levels of sexual arousal were significantly correlated with each of the genital measures during the erotic film but were not significantly correlated with any after the film.

Adult↗

Expression of c-erbB-2 protein and epidermal growth factor receptor in normal tissues of the female genital tract and in the placenta.

The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor receptor that has molecular homology with the epidermal growth factor receptor (EGFR). To investigate the relationship between the expression of c-erbB-2 protein and EGFR in the tissues of the human female genital tract and in the placenta, we examined the immunohistochemical reactivity of monoclonal antibodies against both of these proteins. In the müllerian-derived genital tract, epithelial cells of the fallopian tube, endometrium, and endocervix showed reactivity for c-erbB-2 protein, whereas reactivity for EGFR was distributed mainly in the stromal cells throughout the menstrual cycle and during pregnancy. In addition, the staining intensity for EGFR in the endometrial stroma increased with its decidualization. In the exocervical squamous epithelium, basal cells were c-erbB-2 protein-negative and EGFR-positive, but the more differentiated squamous cells of the intermediate layer were c-erbB-2 protein-positive and EGFR-negative. In the placental tissues, cytotrophoblasts and syncytiotrophoblasts of the chorionic villi were c-erbB-2 protein-negative and EGFR-positive. In contrast, intermediate trophoblasts in the extravillous space were c-erbB-2 protein-positive and EGFR-negative. Thus, there is an inverse relationship between the expression of c-erbB-2 protein and EGFR in the tissues of the female genital tract and in the placenta. This suggests that there may be a regulatory mechanism(s) for the expression of both proteins that is associated with the differentiation and/or function of cells in the female genital tract and the placenta.

ErbB Receptors↗