Substance Use in Women of Reproductive Age.

Using anonymous exit questionnaires in a university OB/GYN clinic, of 165 pregnant women reporting on drinking prior to pregnancy, 26% screened positive for hazardous or harmful drinking. Among 153 non-pregnant women age 50 or younger, 39% screened positive. Of those, 85% had no plans to change their alcohol consumption, as most believed their drinking levels were not risky; 80% had a significant risk of becoming pregnant, but 85% believed pregnancy was unlikely.

Recumbent thunderclap headache in the postpartum period.

BACKGROUND: Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache and reversible cerebral vasoconstriction, with or without other neurologic signs and symptoms. CASE: A 33-year-old woman presented 13 days postpartum with a 4-day history of multiple thunderclap headaches while in the recumbent position, prompting her to attempt to sleep while standing or sitting. Cerebral angiogram demonstrated segmental cerebral artery vasoconstriction. Spinal fluid sampling excluded vasculitis, thereby confirming the diagnosis of reversible cerebral vasoconstriction syndrome. Treatment with a calcium channel antagonist rapidly attenuated her symptoms, and cerebral angiogram was normal at 3 months. CONCLUSION: Thunderclap headache during the postpartum period precipitated by valsalva or recumbent positioning may indicate reversible cerebral vasoconstriction syndrome, which, if untreated, places a patient at risk for serious neurologic injury.

Outcomes of a comprehensive nonsurgical approach to pelvic floor rehabilitation for urinary symptoms, defecatory dysfunction, and pelvic pain.

OBJECTIVE: The authors' intent was to determine the clinical efficacy of comprehensive pelvic floor rehabilitation among women with symptoms of pelvic floor dysfunction (PFD). METHODS: We performed a retrospective analysis of women referred to an academic female pelvic medicine and reconstructive surgery practice for PFD. Data were gathered from the records of 778 women referred for pelvic floor therapy for urinary, bowel, pelvic pain, and sexual symptoms over the course of 4 years. RESULTS: Patients who completed at least 5 therapy sessions reported a mean symptom improvement of 80% in each of the 3 main categories analyzed, namely, urinary incontinence, defecatory dysfunction, and pelvic pain. CONCLUSIONS: Comprehensive, nonoperative management of PFD including pelvic floor muscle training, biofeedback, electrogalvanic stimulation, constipation management, behavioral modification, incontinence devices, and pharmacotherapy including vaginal estrogen is effective in the treatment of women with PFD.

A simple device prevents hysterotomy extensions during cesarean delivery for failed second stage of labor.

BACKGROUND/AIMS: [corrected] During arrest of descent, maternal tissues conform to the fetal head, resulting in a suction-cup like effect during cesarean delivery. We hypothesize that breaking this suction might ease delivery. A novel device was designed for this purpose and tested in this series of 23 patients. METHODS: University-based retrospective cohort feasibility study. Term pregnant women with second-stage labor arrest (n = 23) provided written consent for use of the experimental device, inserted vaginally prior to cesarean delivery. Delivering obstetricians rated device effectiveness. Following case collection, the presence of hysterotomy extensions in study patients was retrospectively compared with controls (n = 49) from the same study period. RESULTS: On a 7-point Likert scale, consultant obstetricians rated overall device effectiveness as 6.0, and resident obstetricians rated it 6.3, consistent with a moderate improvement in ease of delivery. The device performed optimally at mid-pelvic stations (0 to +1), with no hysterotomy extensions (n = 0/17), which was significantly better than controls (n = 14/41, 34%, p < 0.01). CONCLUSION: A simple device prevented hysterotomy extension during second-stage cesarean delivery at 0 and +1 station. Obstetricians perceived that the device afforded a moderate improvement in delivery compared with previous deliveries in which the device was not used.

A novel and inexpensive vaginal hysterectomy simulator.

INTRODUCTION: The number of vaginal hysterectomy procedures performed by resident physicians in the United States is highly variable, with half of residency graduates completing 18 procedures or fewer as primary surgeon. Complex anatomy and technical challenge contribute to a steep learning curve for novice surgeons. Surgical simulation may be a useful adjunct to this surgical training, but a vaginal hysterectomy simulator is not currently available. METHODS: We describe the construction of a vaginal hysterectomy simulator that prioritizes low cost, wide availability of materials, and ease of assembly. Initial construction and per-use simulation costs were calculated. Per-use preparation time was recorded. Surgical learners who used the simulator (n = 12) completed a survey to determine its contribution to their learning. RESULTS: Total cost per simulation was US $1.83 after an initial US $103.79 investment in a resin bony pelvis and stand. All relevant major anatomic landmarks (ureter, bladder, uterus, cervix, vesicouterine fold, vagina, and posterior cul-de-sac) were represented. Of the 12 surveyed surgical learners, 9 (75%) responded. On a 10-point scale (10 = highest), respondents noted that the simulator positively contributed to knowledge of procedure steps (8.3), anatomic relationships (7.7), preprocedure confidence with the first vaginal hysterectomy as primary surgeon (8), and overall learning on how to perform a vaginal hysterectomy (8.3). CONCLUSIONS: This technical report details the construction of a vaginal hysterectomy simulator, the individual parts, the cost of each part, and the results of a blinded survey of resident physicians who used the simulator during their vaginal hysterectomy instruction.

The regulation of T-cell cytokine production by ICOS-B7H2 interactions at the human fetomaternal interface.

Although T cells are the most common decidual lymphocyte subset in late pregnancy, little is known about the mechanisms controlling their function. Costimulatory signaling, mediated by inducible costimulator (ICOS)-B7H2 interactions, is a known potent regulator of T-cell activation. We aimed to determine its role in fetomaternal immunity. T cells from matched peripheral blood and term decidua were assessed for ICOS, CD4/CD8, CD45RA/CD45RO and Foxp3 expression and for alterations in cytokine production upon ICOS-B7H2 ligation. We also assessed ICOS-B7H2 communication between T cells and a trophoblast cell line (JEG3). Strong ICOS expression was observed on CD4 and CD8 decidual (d)T cells, but not peripheral (p)T cells. Among dT cells, ICOS expression was higher on the predominant CD45RO(+) cell population compared with CD45RA(+) cells. Strong ICOS expression was also seen on CD4(+)Foxp3(+) regulatory T cells in the decidua. ICOS ligation enhanced T-cell secretion of interferon-gamma (IFN-γ) and interleukin-10 (IL-10), but not IL-2. The impact of ICOS stimulation was more remarkable in dT cells when compared with pT cells. T cells co-cultured with JEG3 cells promoted T-cell production of IFN-γ and IL-10, an effect blocked by antibody-specific masking of major histocompatibility class I or B7H2. These findings suggest that T-cell cytokine modulation by ICOS-B7H2 interactions is important in the delicate immune balance at the fetomaternal interface.

Immunology of endometriosis.

Endometriosis is a common condition with a varied phenotype. Symptomatic cases have been associated with progesterone resistance and dysregulated cytokine production in both ectopic and eutopic endometrium. In at least some cases, this seems to be associated with chronic local inflammation and antibody self-reactivity. Coexistence of endometriosis with autoimmune disease has been documented in a small number of cases, and the presence of autoreactive antibodies in the serum of some patients with endometriosis is commonly reported. This paper briefly reviews the association between endometriosis and autoimmune disease and describes the potential role of inflammation in the development of immunologic self-reactivity in these patients.

Human decidual stromal cells suppress cytokine secretion by allogenic CD4+ T cells via PD-1 ligand interactions.

BACKGROUND: Although previous reports suggest an antigen-presenting function for decidual stromal cells (DSCs), the relevance of cell-to-cell communication between DSCs and T cells at the human feto-maternal interface has not been fully elucidated. Therefore, we investigated the presence and function of human DSC-expressed B7-H1 and B7-DC co-stimulatory ligands. B7-H1 and B7-DC on peripheral antigen-presenting cells (APC) typically inhibit T cell activation after binding to their corresponding receptor, programmed death-1 (PD-1). METHODS: DSCs were isolated from human term decidua. The expression of B7-H1/B7-DC and HLA-DR and their alteration following IFN-gamma and/or TNF-alpha stimulation were assessed. DSCs with or without IFN-gamma pretreatment were co-cultured with allogenic CD4(+) T cells. The effect of PD-1:B7-H1/B7-DC and T cell receptor (TCR):HLA-DR interactions on T cell cytokine production was evaluated by adding blocking antibodies. RESULTS: DSCs constitutively expressed B7-H1 and B7-DC, as well as small amounts of HLA-DR. Exogenous IFN-gamma and TNF-alpha up-regulated the B7-H1/-DC expression on DSCs, whereas HLA-DR expression was increased only by IFN-gamma. IFN-gamma pretreatment of DSCs stimulated T cell cytokine production through HLA-DR up-regulation. B7-H1 blockade on DSCs strongly enhanced T cell cytokine production (IFN-gamma, TNF-alpha and IL-2), whereas B7-DC blockade had similar but more modest effects. Blockade of both B7-H1 and B7-DC resulted in additive effects. CONCLUSIONS: Our findings support the categorization of human DSCs as non-professional APCs and suggest that PD-1 ligands on DSCs, together with major histocompatibility complex class II, may play a crucial role in the regulation of decidual CD4(+) T cell cytokine production. This helps to maintain a balanced cytokine milieu at the feto-maternal interface.

The fetal allograft revisited: does the study of an ancient invertebrate species shed light on the role of natural killer cells at the maternal-fetal interface?

Human pregnancy poses a fundamental immunological problem because the placenta and fetus are genetically different from the host mother. Classical transplantation theory has not provided a plausible solution to this problem. Study of naturally occurring allogeneic chimeras in the colonial marine invertebrate, Botryllus schlosseri, has yielded fresh insight into the primitive development of allorecognition, especially regarding the role of natural killer (NK) cells. Uterine NK cells have a unique phenotype that appears to parallel aspects of the NK-like cells in the allorecognition system of B. schlosseri. Most notably, both cell types recognize and reject "missing self" and both are involved in the generation of a common vascular system between two individuals. Chimeric combination in B. schlosseri results in vascular fusion between two individual colonies; uterine NK cells appear essential to the establishment of adequate maternal-fetal circulation. Since human uterine NK cells appear to de-emphasize primary immunological function, it is proposed that they may share the same evolutionary roots as the B. schlosseri allorecognition system rather than a primary origin in immunity.

Catamenial appendicitis.

BACKGROUND: Reproductive-aged women undergoing appendectomy for suspected appendicitis have twice the rate of negative histology as age-matched men. The reason for this discrepancy is unknown. CASES: Three patients with peritoneal endometriosis and recurrent symptoms of acute appendicitis coincident with menses underwent resection of a noninflamed appendix with long-term symptom resolution. Standard pathological evaluation failed to demonstrate evidence of appendiceal endometriosis or appendicitis. Additional evaluation demonstrated a marked increase in number of mast cells in the appendiceal muscularis compared with normal appendices. CONCLUSION: The term "catamenial appendicitis" has been coined to describe these cases, and a mechanism of pathogenesis of right lower quadrant pain and nausea in patients with histologically confirmed endometriosis is proposed.

Characterization of spontaneous mammary gland carcinomas in female baboons.

Spontaneous mammary gland carcinomas occurred in five baboons during a 13-year period at Southwest Foundation for Biomedical Research. The affected baboons ranged in age from 21 to 33 years. Menopause in the baboon occurs at approximately 26 years of age. All five animals had typical invasive ductal carcinoma. Morphologically, the tumors were characterized by neoplastic cells arranged from pseudopapillary and cribiform to more poorly differentiated solid cellular growth patterns. Additional features included lack of tubule formation (4/5), marked nuclear pleomorphism (5/5), a high mitotic rate (4/5) and tumor necrosis (4/5). Applying a grading system used for breast cancer in women, four tumors were graded as poorly differentiated carcinomas and one was graded as moderately differentiated. Co-existent ductal carcinoma in situ (DCIS) was observed in three of the mammary tumors. Metastases to the regional lymph nodes were confirmed in two animals, both with histological evidence of lymphovascular invasion in the primary tumor. Distant metastases were observed in only one animal. Immunohistochemical staining for human therapeutic markers revealed 2/5 tumors strongly positive for estrogen receptor, 1/5 strongly positive for progesterone receptor and 4/4 negative for HER2 expression. Although the incidence appears to be low, these five cases of mammary carcinoma in female baboons suggest that when present baboon mammary carcinoma is usually of ductal origin and behaves similar to a human breast carcinoma.

External cephalic version of the term breech baboon (Papio sp.) fetus.

BACKGROUND: Breech presentation in baboons may be associated with head entrapment and stillbirth during vaginal delivery. For this reason, pregnant dams at our institution typically undergo cesarean delivery for known breech presentation, leading to problems with maternal-infant bonding and increased nursery utilization. METHODS: This paper describes a simple, non-invasive technique called external cephalic version (ECV) that effectively converts the baboon breech fetus into a cephalic presentation. RESULTS: ECV was successful in each of seven attempted cases, with the consistent development of contractions and vaginal bleeding leading to the delivery of a healthy liveborn infant within 72 hours. CONCLUSIONS: ECV may offer a safe and effective alternative to cesarean section for delivery of the breech baboon fetus.

Spontaneous adenomyosis in the chimpanzee (Pan troglodytes): a first report and review of the primate literature: case report.

Adenomyosis is a non-neoplastic condition characterized by the presence of ectopic endometrium in the myometrium with hyperplasia of adjacent smooth muscle. Common symptoms in women include debilitating pelvic pain and abnormal uterine bleeding, and the condition has been paradoxically associated with both multiparity and subfertility. Adenomyosis spontaneously occurs in humans and some non-human primates, including the baboon and macaque, where it has been associated with primary infertility and the presence of endometriosis. No cases of adenomyosis have been previously reported in Pongidae such as gorilla, orangutan or chimpanzee. We here describe two cases of naturally occurring adenomyosis in the chimpanzee (Pan troglodytes) and briefly review the literature regarding the presence of adenomyosis in non-human primate species.

Primary amenorrhea associated with ovarian leiomyoma in a baboon (Papio hamadryas).

A 6-y-old female baboon was examined due to absence of menstrual cycling and secondary sex characteristics and failure to reproduce. The mammary glands and vaginal introitus were hypoplastic, the clitoris was prominent, and the perineal skin was immature with lack of cyclic color alterations and sexual swelling. Evaluation of the reproductive tract revealed a hypoplastic uterus and rudimentary ovaries with the presence of an ovarian leiomyoma within the right ovary. Hormonal values (estradiol, progesterone) were low and comparable to those of adult males or ovariectomized females. Adrenal and pituitary hormones (dehydroepiandrosterone, luteinizing and follicular stimulating hormones) and pituitary structure were within normal limits for this species. The baboon had a normal 42,XX karyotype. These findings suggest primary amenorrhea due to ovarian dysgenesis. This is the first report of a case of primary amenorrhea due to ovarian dysgenesis with a normal karyotype associated with a unilateral ovarian leiomyoma in the baboon. Continued studies of noncycling female nonhuman primates in captive breeding colonies may lead to a greater understanding of the underlying causes of this condition.

Characterization of human leukocyte antigen-G (HLA-G) expression in endometrial adenocarcinoma.

OBJECTIVES: The current study sought to determine if endometrial adenocarcinomas express human leukocyte antigen-G (HLA-G), an immune-regulatory protein, and if degree of expression correlates with the stage of carcinoma. METHODS: Forty-four primary endometrial adenocarcinomas were tested using immunohistochemical staining with the 4H84 anti-HLA-G monoclonal antibody. Metastatic implants were not included. A subset of 10 samples was tested using RNA in situ hybridization to confirm the presence of HLA-G transcript. Results of staining were analyzed with respect to grade, tumor histology, and stage of disease. Spearman rank correlation was used to assess tumor grade, histology, and disease stage as a function of HLA-G protein staining. Receiver-operator characteristic (ROC) curve analysis was used to determine the feasibility of HLA-G protein staining as a clinical marker for advanced stage disease. RESULTS: Immunohistochemical staining for HLA-G protein was seen in 55% (24/44) of primary site endometrial adenocarcinomas and localized to glandular but not stromal epithelium. RNA in situ hybridization confirmed the presence of transcript in the majority of samples tested and also localized to glandular epithelium. A significant correlation was seen with increasing HLA-G protein staining and increasing stage of endometrial cancer, P < 0.01. HLA-G was found to be a fair discriminator as a test for metastatic disease with an area under the ROC curve of 0.75 for metastatic versus non-metastatic disease. CONCLUSIONS: HLA-G protein is expressed in a significant number of endometrial adenocarcinomas, in which it is localized to the glandular epithelium. HLA-G may serve as a clinical marker for the preoperative prediction of metastatic endometrial cancer.

Adenomyosis in the baboon is associated with primary infertility.

OBJECTIVE: To determine whether an association exists between the histopathologic diagnosis of adenomyosis and infertility in a population of captive baboons. DESIGN: Case-control study. SETTING: Southwest National Primate Research Center. ANIMAL(S): Necropsy records of 37 baboons diagnosed with adenomyosis uteri and 38 baboons with normal uterine histology. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Chi2 analysis of the association between adenomyosis, primary infertility, and the presence of coexisting endometriosis. RESULT(S): Endometriosis was associated with the presence of adenomyosis (OR = 31.5, 95% CI 4.2-1,348). There was a trend toward an association of endometriosis with the presence of lifelong infertility, but this correlation did not quite achieve statistical significance (OR = 3.6, 95% CI 0.9-15.8). Adenomyosis was associated with the presence of lifelong infertility (OR = 20.6, 95% CI 2.7-897). This association was maintained when cases of coexisting endometriosis (n = 17) were excluded (OR = 20.1, 95% CI 2.1-921). CONCLUSION(S): Adenomyosis is strongly associated with lifelong primary infertility in the baboon, even in the absence of coexisting endometriosis.

Efficacy of anti-tumor necrosis factor therapy in the treatment of spontaneous endometriosis in baboons.

OBJECTIVE: To determine the efficacy of anti-tumor necrosis factor therapy (etanercept) for treating endometriosis in baboons. DESIGN: A randomized, placebo-controlled, blinded study using the baboon endometriosis model. SETTING: Southwest National Primate Research Center. ANIMAL(S): Twelve female baboons with spontaneous peritoneal endometriosis. INTERVENTION(S): Etanercept (n = 8) or sterile water (n = 4) was administered subcutaneously three times per week. MAIN OUTCOME MEASURE(S): After 8 weeks, the number, color, and surface area of peritoneal lesions was evaluated. Revised American Society for Reproductive Medicine staging was used. RESULT(S): A statistically significant decrease in red lesion surface area in the treatment group was observed. A trend toward a decrease in the absolute number of red lesions was noted in the treatment group. White and black lesion number and total surface area slightly increased in both groups but failed to achieve statistical significance. Endometriosis was diagnosed in 60% of captive-born baboons with primary infertility. CONCLUSION(S): These results indicate that etanercept effectively reduces the amount of spontaneously occurring active endometriosis in the baboon.

Expression of soluble adhesion molecules in sera of women with stage III and IV endometriosis.

OBJECTIVE: To determine the effect of stage III and IV endometriosis on serum concentration of soluble intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin. METHODS: Sera from women with laparoscopically proven stage III and IV endometriosis were analyzed for the presence of soluble ICAM-1, VCAM-1, and E-selectin using enzyme-linked immunosorbent assays. Concentrations of these molecules were compared with those of laparoscopically proven disease-free controls. RESULTS: When compared with controls, women with stage III and IV endometriosis had higher serum concentrations of soluble VCAM-1, lower serum concentration of soluble ICAM-1, and no difference in serum concentration of soluble E-selectin. CONCLUSION: Significant aberrations in levels of circulating adhesion molecules were found in women with stage III and IV endometriosis. These findings might shed light on the pathogenesis of endometriosis and be useful in the development of biochemical markers for disease stage.