A primary Chlamydia trachomatis genital infection of rhesus macaques identifies new immunodominant B-cell antigens.

To identify immunodominant antigens that elicit a humoral immune response following a primary and a secondary genital infection, rhesus monkeys were inoculated cervically with Chlamydia trachomatis serovar D. Serum samples were collected and probed with a protein microarray expressing 864/894 (96.4%) of the open reading frames of the C. trachomatis serovar D genome. The antibody response to the primary infection was analyzed in 72 serum samples from 12 inoculated monkeys. The following criteria were utilized to identify immunodominant antigens: proteins found to be recognized by at least 75% (9/12) of the infected monkeys with at least 15% elevations in signal intensity from week 0 to week 8 post infection. All infected monkeys developed Chlamydia specific serum antibodies. Eight proteins satisfied the selection criteria for immunodominant antigens: CT242 (OmpH-like protein), CT541 (mip), CT681 (ompA), CT381 (artJ), CT443 (omcB), CT119 (incA), CT486 (fliY), and CT110 (groEL). Of these, three antigens, CT119, CT486 and CT381, were not previously identified as immunodominant antigens using non-human primate sera. Following the secondary infection, the antibody responses to the eight immunodominant antigens were analyzed and found to be quite different in intensity and duration to the primary infection. In conclusion, these eight immunodominant antigens can now be tested for their ability to identify individuals with a primary C. trachomatis genital infection and to design vaccine strategies to protect against a primary infection with this pathogen.

Hormonal, metabolic, and endometrial safety of testosterone vaginal cream versus estrogens for the treatment of vulvovaginal atrophy in postmenopausal women: a randomized, placebo-controlled study.

OBJECTIVE: The aim of the study was to evaluate the laboratory and endometrial safety of topical testosterone versus topical estrogen for the treatment of vaginal atrophy in postmenopausal women. METHODS: This was a randomized, placebo-controlled trial of 60 postmenopausal women aged 40 to 70 years at the Menopause Clinic of CAISM UNICAMP. Women were randomized into three vaginal treatment groups: estrogen, testosterone, or placebo. The treatment was applied 3 times a week for 12 weeks. Hormonal laboratory values of follicle-stimulating hormone, luteinizing hormone, estradiol, estrone, androstenedione, total testosterone, free testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin were assessed at baseline and at 6 and 12 weeks. Metabolic laboratory values of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase were also assessed at baseline and at 6 and 12 weeks. Endometrial safety was assessed using ultrasonography at baseline and at 12 weeks. RESULTS: After 12 weeks of treatment, there were no significant differences in hormonal or metabolic laboratory values among all three groups. Two participants in the estrogen group had increased serum estradiol after 12 weeks of treatment. No change in endometrial thickening was reported in all three groups. CONCLUSIONS: Twelve weeks of treatment with topical testosterone or estrogen in postmenopausal women with symptoms of vaginal atrophy demonstrated laboratory and endometrial safety when compared with placebo.

Transfusion support for transgender men of childbearing age.

BACKGROUND: To date, limited attention has been given to transgender recipients of blood components, particularly transgender men of childbearing age. Here, we highlight the essential information needed to provide transfusion support for this population. CASE REPORT: A 40-year-old transgender man, who retained his uterus and ovaries, presented with severe vaginal hemorrhage following biopsies for a cervical mass. He was admitted to the Gynecology unit and emergency blood was ordered. Because the patient was listed as male in the electronic health record (EHR), the transfusion service prepared uncrossmatched type O, RhD-positive red blood cells (RBC). After the sex/gender incongruence was recognized, the units were switched for Rh-negative. CONCLUSION: This case illustrates particular considerations when caring for transgender patients: gender/sex documentation, decision-making processes when gender/sex-specific care applies, and challenges to the pathology service.

Concentration range of serum sex steroids in normal postmenopausal women and those with diagnosis of vulvovaginal atrophy.

OBJECTIVE: The aim of the study was to determine the range of serum sex-related steroids in normal postmenopausal women and in women of the same age with a diagnosis of vulvovaginal atrophy (VVA). METHODS: Validated mass spectrometry-based assays coupled to gas or liquid chromatography were used over a 10-year period for steroid measurements. Serum samples were obtained in up to 1,512 women aged 55 to 65 years. RESULTS: Serum estrone sulfate (E1S) and androsterone glucuronide (ADT-G), the main metabolites of estrogens and androgens, respectively, were 16.9% (P = 0.005) and 16.1% (P = 0.001) higher in women not diagnosed with moderate/severe VVA than those diagnosed with VVA. Serum estrone (E1) was 14.5% (P < 0.0001) higher in women with no diagnosis of VVA, whereas the other steroids did not show meaningful differences. The limited biological significance of serum estradiol (E2) and testosterone is supported by the lack of statistical significance in the serum concentrations of these two steroids between the two groups. Most importantly, for the women without a diagnosis of VVA, the normal upper limit (95 centile) of serum E2 was 9.15 pg/mL (n = 364) and 10.7 pg/mL (n = 67) for a weighted average of 9.99 pg E2/mL. A limit of 10 pg E2/mL has recently been found by two other laboratories. When comparing 50- to 59-year-old and 70- to 79-year-old women, serum E2, E1S, ADT-G, and DHEA were, respectively, 24.4%, 22.6%, 27.0%, and 85.9% higher in the younger group. CONCLUSIONS: Somewhat higher values, namely, 16.9% and 16.1%, are observed in the serum concentrations of the estrogen (E1S) and androgen (ADT-G) metabolites in normal compared with women with a diagnosis of VVA. Such data indicating a lower estrogenic and androgenic global exposure in women diagnosed with VVA offers an opportunity for the local intravaginal administration of DHEA to replace the deficiency in endogenous DHEA.

V-Loc™ 180 suture in total laparoscopic hysterectomy: a retrospective study comparing Polysorb to barbed suture used for vaginal cuff closure.

OBJECTIVE: Sutures in laparoscopy have been extensively developed in recent years. In this study, we assessed differences between Polysorb™ braided absorbable suture (CL-914) and V-Loc™ barbed suture (V-Loc 180) used in vaginal cuff closure during laparoscopic hysterectomy from various aspects. STUDY DESIGN: This paper presented a prospective cohort study of 490 consecutive women underwent total laparoscopic hysterectomy (TLH) performed between January 2013 and September 2015 applying identical procedure technique, with cuff closure approaches selected by surgeons. Data collected included operative time, estimated blood loss, postoperative changes in body temperature, perioperative routine blood parameters changes, total average hospital stay, and postoperative hospital stay. In addition, short-term (at least 6 months) outcomes of vaginal cuff granulomatous (VCG) between the two suture approaches were compared. RESULTS: Between groups, statistical differences were detected in operative duration, estimated blood loss, total and postoperative hospital stay, WBC, neutrophil counts and Hb in postoperative routine blood parameters; while there were no significant differences in other data (all P>0.05). Postoperative routine blood parameters in each group: compared to preoperative baseline, in Group 1, WBC, N increased (P<0.05), while RBC, Hb decreased (P<0.05). In Group 2, same tendency in WBC, N and Hb was indicated, but RBC increased with no significant difference. In both groups, vaginal cuff healing was well, with no dehiscence. VCG occurred more often in women used CL-914 than women applied V-Loc 180. CONCLUSIONS: V-Loc barbed suture can be used for vaginal cuff closure during TLH due to advantages such as less operative duration and blood loss, shorter postoperative and total hospital stay, and reduced VCG formation six months after TLH.

Low-dose 17-ß-estradiol cream for vaginal atrophy in a cohort without prolapse: Serum levels and vaginal response including tissue biomarkers associated with tissue remodeling.

OBJECTIVES: Describe the effect of 50 mcg vaginal 17-ß-estradiol (E2) cream on vaginal maturation, serum estrogen levels, atrophic symptoms, and biomarkers of oxidative stress and tissue remodeling in postmenopausal women without prolapse. METHODS: Seventeen women, 65 years or older, applied intravaginal E2 cream nightly for eight weeks, then twice weekly for eight weeks. Vaginal biopsies, serial blood draws, and atrophic symptoms were obtained at baseline, eight, and sixteen weeks. Changes in atrophic symptoms, vaginal maturation indices (VMI), and serum E2 were measured. Immunohistochemical staining characterized levels of transforming growth factor-beta (TGF-ß), nuclear factor kappa B (NFKB), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and thrombospondin (TSP). RESULTS: Serum E2 levels (pg/ml) were unchanged from baseline (mean (SD)) 7.7 (3.3) to eight 9.7 (5.7) and sixteen 8.7 (5.8) (p=0.24) weeks. VMI (mean (SD)) improved from baseline 34.2 (18.3) to eight 56.7 (13.1) and sixteen 54.5 (11.3) (p<0.001) weeks with no difference between eight and sixteen weeks. Vaginal dryness (p=0.03) and itching (p=0.02) improved. Tissue biomarker levels did not change (TGF-ß p=0.35, NFKB p=0.74, eNOS p=0.80, iNOS p=0.24, TSP p=0.80). DISCUSSION: Vaginal E2 improved atrophic symptoms and VMI without elevating serum E2. Tissue remodeling biomarkers did not change.

Effect of one-month treatment with vaginal promestriene on serum estrone sulfate levels in cancer patients: a pilot study.

UNLABELLED: Vaginal promestriene was tested in gynecological cancer patients who suffered from severe vaginal dryness and dyspareunia. This form of estrogen has a low level of vaginal absorption and proved to be effective for vaginal atrophy. METHOD: 17 patients were treated with a 10mg soft vaginal suppository daily for one month. Plasma levels of estrone sulfate (E1S), used as the marker of overall estrogenicity, were measured by liquid chromatography in combination with mass spectrometry. RESULTS: Mean E1S levels changed from 533 (22-2920) to 374 (81-856) pg/ml (p=0.39). CONCLUSION: In highly symptomatic gynecological cancer patients the level of circulating estrone sulfate was not significantly affected by vaginal promestriene treatment overall, but a wide range of levels was noted pre and post treatment in individual patients.

Topical oxytocin reverses vaginal atrophy in postmenopausal women: a double-blind randomized pilot study.

INTRODUCTION: Oxytocin is a peptide hormone produced in the hypothalamus and it is best known for its role in labour and lactation. This double-blind, randomized study was performed at Huddinge Hospital of Karolinska Institutet, Stockholm in order to test the effectiveness of topical oxytocin gel in women with postmenopausal vaginal atrophy. METHODS: Twenty postmenopausal women (at least two years after menopause) with symptoms of vaginal atrophy such as vaginal dryness, pain, itching, discomfort and bleeding during intercourse were enrolled in the study when visual inspection of the vagina had confirmed that their mucosa was atrophic. The participants were randomized to intravaginal treatment with either oxytocin or placebo gel for seven days. Before and after treatment, a gynaecological examination and a visual and colposcopic inspection of the vagina were performed, biopsies from the vaginal mucosa were taken and blood samples were collected for analysis of circulating levels of estradiol and oxytocin. RESULTS: Prior to treatment, visual and colposcopic inspection showed that all of the 20 participants had an atrophic vaginal mucosa. After treatment with the oxytocin gel, the examination showed that the vaginal epithelium of seven of the 10 participants in the oxytocin group had become healthier and normalized. No change in these parameters was observed among the 10 participants in the placebo group. This difference between the oxytocin and placebo groups was significant (P= 0.003). Seven participants in the active group and four in the placebo group reported relief of symptoms of vaginal atrophy after seven days of applying the gel. The effect of oxytocin to normalize the morphological appearance of the vaginal mucosa was almost significant when compared with the placebo group (P= 0.07). There was no significant difference between the circulating levels of estradiol and oxytocin in both the oxytocin and placebo groups before and after treatment. None of the participants reported any side-effects. CONCLUSION: Topical treatment with oxytocin appears to improve vaginal atrophy in postmenopausal women. A limitation of this pilot study is that it was based on a small study population hence the results should be regarded with caution. Larger studies are in progress to establish the possibility of using oxytocin as a clinical treatment for vaginal atrophy.

Hormonal, biochemical, and hematological profiles in female camels (Camelus dromedarius) affected with reproductive disorders.

The aim of this study was to assess the blood profiles in female camels affected with common reproductive disorders. Estradiol-17beta (E(2)), progesterone (P(4)), thyroxin (T(4)), zinc (Zn), copper (Cu), calcium (Ca), phosphorus (P), magnesium (Mg), cholesterol, glucose, triglycerides, total protein, albumin, globulin, hematocrite, and total and differential white blood cell counts (WBC) were determined in blood of female camels affected with endometritis (n=15), vaginal adhesions (n=15), and ovarian cysts (n=15). Normal cyclic animals were used as controls (n=15). Diagnosis of reproductive disorders was based on transrectal palpation, ultrasonographic examination, and exploration of the vagina. Increased WBC counts (P=0.03) and a tendency for neutrophelia (P=0.05) were noted in female camels with vaginal adhesions. These animals were also characterized by having higher concentration of serum P(4) (P=0.0001), T(4) (P=0.001) and total protein (P=0.007), in comparison with female camels with endometritis, ovarian cysts, or controls. Animals having ovarian cysts with thin walls and homogenous hypoechogenic contents had greater serum E(2) (P=0.001) and P(4) (P=0.0001) than those having ovarian cysts with thick walls and non-homogenous echogenic contents. Animals with endometritis, vaginal adhesions, and ovarian cysts revealed lower serum Zn concentration than that of control group (P=0.003). Other blood parameters did not differ significantly compared to controls. In conclusion, this is the first report characterizing blood constituents in female camels with various reproductive disorders. These profiles may be valuable in clarifying the etio-pathogenesis of these disorders.

The use of local 17beta-oestradiol treatment for improving vaginal symptoms associated with post-menopausal oestrogen deficiency.

The effects of local 17beta-oestradiol therapy on the vaginal mucosa and endometrial thickness were studied in 35 post-menopausal women with symptoms of vaginal atrophy. Signs and symptoms of vaginal atrophy were measured by anamnesis, visual examination and the maturation index before and after 12 weeks' treatment with 17beta-oestradiol in the form of vaginal tablets. The maturation proportion on vaginal smear, endometrial thickness on transvaginal ultrasonography and plasma concentrations of follicle-stimulating hormone, luteinizing hormone and oestradiol were also determined. All vaginal atrophy signs and symptoms significantly improved and there was a significant increase in vaginal smear maturation with 17beta-oestradiol treatment. Endometrial thickness did not change significantly. It is concluded that 17beta-oestradiol improves the signs and symptoms of vaginal atrophy without causing endometrial stimulation and offers a safe and effective alternative to systemic hormone replacement therapy for the treatment of vaginal symptoms associated with post-menopausal oestrogen deficiency.

Aggregability and disaggregability of erythrocytes in women suffering from ovarian cancer: evidence for an increased disaggregation threshold.

In order to further characterize the alterations of erythrocyte aggregation described in ovarian cancer, we measured it with laser backscattering in eleven women suffering from ovarian cancer (mean age: 44.7 +/- 3.6, extreme values: 28-61 yr) compared with thirteen matched control women. Blood rheology exhibited a wide variability in cancer patients, with some unusually high values of plasma viscosity and/or RBC aggregation in individual cases. The only significant differences were found for the RBC disaggregation threshold which was higher in patients than in controls (78.06 +/- 10.14 vs 52.6 +/- 3.15 s(-1), p < 0.05), while hematocrit was lower (34.45 +/- 1.42 vs 38.23 +/- 0.75, p < 0.05). A negative correlation between hematocrit and corrected blood viscosity on the whole sample of subjects (r = 0.454, p < 0.05) indicates that hematocrit is decreased in subjects prone to high viscosity, resulting in similar values of apparent blood viscosity in controls and patients. Thus, a lower disaggregability of RBCs is evidenced in women with ovarian cancer, as well as a tendency to blood hyperviscosity compensated by a reduction of hematocrit which suggests that there may be some degree of 'viscoregulation'.

Protective efficacy of a parenterally administered MOMP-derived synthetic oligopeptide vaccine in a murine model of Chlamydia trachomatis genital tract infection: serum neutralizing IgG antibodies do not protect against chlamydial genital tract infection.

The protective efficacy of an alum-adsorbed, parenterally administered synthetic oligopeptide immunogen corresponding to antigenically common T-helper and neutralizing B-cell epitopes of the Chlamydia trachomatis major outer membrane protein was studied in a murine model of chlamydial genital tract infection. Mice produced high levels of anti-chlamydial serum IgG neutralizing antibodies following subcutaneous immunization with the alum-adsorbed oligopeptide. Lower but detectable levels of chlamydial specific IgG antibodies were found in vaginal washes. IgG1 was the predominant isotype present in sera and vaginal washes. Chlamydial-specific IgA was not present in either the sera or vaginal washes of immunized mice. Vaccinated and control mice were challenged intravaginally or intrauterinally with low, medium, or high doses of C. trachomatis serovar D challenge inocula. Protection was assessed by performing quantitative chlamydial cervico-vaginal cultures over the course of the infection period. There were no statistically significant differences between groups of immunized and control mice in either colonization, shedding, or duration of infection. These findings demonstrate that parenteral immunization with the oligopeptide (serum-neutralizing antibodies) is ineffective in preventing chlamydial genital tract infection. It is possible, since chlamydial infection is restricted to the genital tract mucosae, that a more accurate evaluation of the oligopeptide vaccine potential will require local rather than systemic immunization.

Human herpesvirus 6 infection of the female genital tract.

Four of the seven human herpesviruses are recognized to replicate in the female genital tract and may be transmissible to sexual partners and newborn infants. Several of these viruses have also been implicated in the etiology of various human cancers, including tumors of epithelial cell origin. Human herpesvirus 6 (HHV-6) is a newly identified herpesvirus that causes exanthem subitum. The pathogenicity of HHV-6 within the genital tract is largely unexplored. Acellular vaginal secretions from 29 women attending a sexually transmitted diseases clinic were examined for the presence of HHV-6 DNA sequences by polymerase chain reaction. Three samples (10%) were consistently positive for HHV-6 DNA. Since HHV-6 DNA is shed in the genital tract of some women, it is possible that infectious virus is transmissible through sexual contact and to newborn infants by perinatal spread.

Vaginal rings for continuous low-dose release of oestradiol in the treatment of urogenital atrophy.

Silicone vaginal rings for the continuous release of 17 beta-oestradiol (E2) with 2 constant in vitro release rates were used for the treatment of symptoms of urogenital atrophy in 2 groups of postmenopausal women. The very low dose of 7 micrograms/24 h was found to alleviate atrophic symptoms effectively and to induce significant maturation of vaginal and urethral epithelium. After a brief initial peak, the serum levels of E2 over 3 mth of treatment remained close to the detection limit. The 'undetectable' E2 release pattern was reflected only in increased levels of oestrone sulphate. There was no evidence of a systemic metabolic response and patient acceptance of the method was excellent. Continuous low-dose release of E2 via vaginal rings consequently offers an alternative means of administering local oestrogen therapy which may be particularly suitable for geriatric patients.

Vaginal rupture associated with herniation of abdominal viscera in pregnant ewes.

Seventeen cases of vaginal rupture with herniation of abdominal organs were examined. The injury consisted of a dorsal tear in the vagina and, most frequently, evisceration of the bowel. The tear was accompanied by extensive vaginal bleeding. Serum calcium concentrations were low in the affected cases and the concentrations of beta-hydroxybutyric acid and urea were high. The average age of the affected ewes was four years (range 3 to 6). They were generally in poor condition and carrying more than one fetus (2.7 lambs per ewe) although younger ewes and ewes in good condition were also affected. No primiparous ewes were affected. Ten of the 17 ewes were found dead and six were humanely destroyed; in one, the injury was repaired surgically but the ewe died 48 hours later.