Group A Streptococcus (GAS; Streptococcus pyogenes) is a facultative gram-positive coccus, uncommonly colonizing parturient genitalia, where its presence can potentially lead to a life-threatening invasive infection after delivery. GAS infection typically occurs within the first 4 days post-partum and is characterized by high fever, chills, flashing, abdominal pain, and uterine tenderness. Nonetheless, patients with GAS puerperal sepsis may have an unusual presentation, when fever is absent, and the symptoms and signs can be mild, non-specific, and not indicative of the severity of infection. This unusual presentation may lead to a delayed diagnosis and increase the risk for severe puerperal sepsis. Therefore, in these cases, a high index of suspicion and prompt early antibiotic and surgical treatment is crucial to saving the parturient's life.
Cutaneous metastases originating from a primary solid visceral organ are an uncommon phenomenon, seen in 0.3% to 9% of patients [1]. Cutaneous metastases from a urinary origin are especially rare, reported in only 1.1% of urologic malignancies [1]. Although urothelial carcinoma is the third most prevalent malignancy in adults [2], cutaneous metastases from a genitourinary origin account for only 10.4% of cutaneous metastases. The current report provides a detailed description of a case with this rare condition.
The vulvar vestibule is the tissue located between the vagina and the vulva, comprising the vaginal introitus. It is mainly considered in the context of localized provoked vestibulodynia, a pain condition causing dyspareunia in 8–16% of women. To describe the vulvar vestibule’s unique properties, which may have a role in the development of vestibular tenderness and dyspareunia. The vestibule displays different neural features when compared with neighboring organs. It is an immunologically diverse tissue that exhibits highly localized and tissue-specific pro-inflammatory responses. Systemic, as well as local hormonal-associated processes regarding estrogen, androgens, and usage of hormonal contraception apear to influence the pain threshold in the vestibule. The vestibule, emerging from the embryonic endoderm, exhibits unique features regarding innervation, inflammation, and hormonal stimuli. A better understanding of these mechanisms is required in order to advance our understanding of introital dyspareunia.
BACKGROUND:Serum amyloid A (SAA) is an acute phase protein expressed primarily in the liver in response to various injuries and inflammatory stimuli and is recognized as a modulator of inflammation. Ovarian reproductive functions including folliculogenesis and ovulation use inflammatory processes; thus, studying SAA in this context is of interest.OBJECTIVES:We investigated the expression and localization of SAA in ovarian developing follicles and its levels in follicular fluids.METHODS AND PARTICIPANTS:Nonradioactive in situ hybridization and immunohistochemical staining were applied on ovarian paraffin tissue sections. ELISA and RT-PCR were applied on follicular aspirates and blood samples from women undergoing controlled ovarian stimulation for in vitro fertilization.RESULTS:Expression of SAA mRNA and protein was found in follicular cells at all stages of follicular development, from primordial and primary follicles through antral follicles and corpora lutea. Expression was observed in granulosa, theca and luteal cells, and oocytes. Expression of SAA was also found in granulosa cells recovered from follicular aspirates. The SAA protein was detected in follicular fluids. Its levels were somewhat lower than in peripheral blood with strong correlation between the two compartments and with significant correlation with patient's body mass index. High follicular fluid SAA levels were associated with reduced pregnancy rate.CONCLUSIONS:SAA is locally produced in ovarian developing follicles and is a constituent of follicular fluids, suggesting its role within the follicular environment. Elevated follicular SAA levels are associated with decreased pregnancy rate and may signify lower reproductive performance.
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Novel strategies that target the epidermal growth factor receptor (EGFR) have led to the clinical development of monoclonal antibodies, which treat metastatic colorectal cancer (mCRC) but only subgroups of patients with increased wild type KRAS and EGFR gene copy, respond to these agents. Furthermore, resistance to EGFR blockade inevitably occurred, making future therapy difficult. Novel bio-imaging (BOI) methods may assist in quantization of EGFR in mCRC tissue thus complementing the immunohistochemistry methodology, in guiding the future treatment of these patients. The aim of the present study was to explore the usefulness of near infrared-labeled EGF (EGF-NIR) for bio-imaging of CRC using in vitro and in vivo orthotopic tumor CRC models and ex vivo human CRC tissues. We describe the preparation and characterization of EGF-NIR and investigate binding, using BOI of a panel of CRC cell culture models resembling heterogeneity of human CRC tissues. EGF-NIR was specifically and selectively bound by EGFR expressing CRC cells, the intensity of EGF-NIR signal to background ratio (SBR) reflected EGFR levels, dose-response and time course imaging experiments provided optimal conditions for quantization of EGFR levels by BOI. EGF-NIR imaging of mice with HT-29 orthotopic CRC tumor indicated that EGF-NIR is more slowly cleared from the tumor and the highest SBR between tumor and normal adjacent tissue was achieved two days post-injection. Furthermore, images of dissected tissues demonstrated accumulation of EGF-NIR in the tumor and liver. EGF-NIR specifically and strongly labeled EGFR positive human CRC tissues while adjacent CRC tissue and EGFR negative tissues expressed weak NIR signals. This study emphasizes the use of EGF-NIR for preclinical studies. Combined with other methods, EGF-NIR could provide an additional bio-imaging specific tool in the standardization of measurements of EGFR expression in CRC tissues.
Serum amyloid A (SAA) is an acute phase protein which is expressed primarily in the liver as a part of the systemic response to various injuries and inflammatory stimuli; its expression in ovarian tumors has not been described. Here, we investigated the expression of SAA in human benign and malignant ovarian epithelial tumors. Non-radioactive in situ hybridization applied on ovarian paraffin tissue sections revealed mostly negative SAA mRNA expression in normal surface epithelium. Expression was increased gradually as epithelial cells progressed through benign and borderline adenomas to primary and metastatic adenocarcinomas. Similar expression pattern of the SAA protein was observed by immunohistochemical staining. RT-PCR analysis confirmed the overexpression of the SAA1 and SAA4 genes in ovarian carcinomas compared with normal ovarian tissues. In addition, strong expression of SAA mRNA and protein was found in the ovarian carcinoma cell line OVCAR-3. Finally, patients with ovarian carcinoma had high SAA serum levels, which strongly correlated with high levels of CA-125 and C-reactive protein. Enhanced expression of SAA in ovarian carcinomas may play a role in ovarian tumorigenesis and may have therapeutic application.
Objective: To define the role of prostaglandins (PG) in the endometrium of patients with repeated failure of embryo implantation. Prostaglandins are produced after the sequential oxidation of arachidonic acid by cyclooxygenases (COX-1 and COX-2) and terminal PG synthases.Design: Case-control study.Setting: In vitro fertilization unit at a university hospital.Patient(s): Thirty-four women, comprising of 19 patients with repeated IVF failure and 15 controls with proven fertility.Intervention(s): Endometrial expression levels of the enzymes responsible for the PG synthesis were compared between the two groups.Main Outcome Measure(s): Cytosolic phospholipase A2 (cPLA(2 alpha)) expression and activity were assessed by Western blot. Expression of cyclooxygenase-2, secretory phospholipase A2 group IIA, V, and IB (sPLA(2)-IIA, sPLA(2)-V, sPLA(2)-IB), glypican-1, PG E synthase, PG E receptors, and lysophosphatidic acid receptor 3 (LPA3) was measured by real-time polymerase chain reaction (PCR). Localization of COX-2, sPLA2-IIA, and LPA3 within the secretory endometrium was detected by immunohistochemistry.Result(s): Patients displaying recurrent implantation failure expressed reduced levels of cPLA(2 alpha) and COX-2 compared with controls. In response to this deficiency, sPLA(2)-IIA was found to be overexpressed. Interestingly, LPA3, which is known to converge on the cPLA(2)-arachidonic acid-COX-PG signaling pathway, was also decreased in these patients.Conclusion(s): Prostaglandin synthesis appears to be disrupted in patients with repeated IVF failure compared with fertile controls. We therefore suggest that reduced PG synthesis in the human endometrium may lead to poor endometrial receptivity. (Fertil Steril (R) 2010;94:1271-8. (C) 2010 by American Society for Reproductive Medicine.)
Pilonidal disease is common among adolescents and adults, mainly located in the sacral area. Pilonidal disease involving the clitoris is extremely rare and has not been described in premenarcheal girls. We present a case of a recurrent pilonidal periclitoral cyst in an 8-year-old girl which was surgically treated.
Objective: To determine the predictive value and the quality of supernatant sperm (SS) achieved by a simple laboratory technical modification after testicular sperm extraction (TESE).Design: A retrospective analysis.Setting: An IVF unit in a university medical center.Patient(s): Azoospermic patients undergoing TESE between January 2001 and December 2006.Intervention(s): Before the. mechanical shredding, the testicular specimen in toto was placed in medium. The medium was spun and the pellet resuspended and transferred for SS detection. Then a wet preparation of the testicular tissue was shredded roughly and inspected for tissue sperm (TS) as described.Main Outcome Measure(s): Detection of SS versus TS, fertilization and pregnancy rates (PR) after intracytoplasmic sperm injection (ICSI) with SS versus TS.Result(s): The SS was detected in all specimens where TS was eventually found, independent of their testicular pathology. When the supernatant was spermatozoa-negative, no spermatozoa were detected in the tissue. For embryos derived from ICSI the fertilization rate of SS was significantly higher than TS (52% vs. 44%), whereas the PR was comparable.Conclusion(s): The SS serves as an excellent predictor of TESE outcome and as a superior source for fertilization. This modified technique enables faster decision of TESE outcome and an easier switch to donor sperm when available. (Fertil Steril (R) 2009;91:281-4. (c) 2009 by American Society for Reproductive Medicine.)
OBJECTIVE:Patients with vulvar vestibulitis syndrome (VVS) and control subjects were tested for a polymorphism in the gene coding for the NALP3 component of inflammasomes, cytoplasmic structures regulating interleukin (IL)-1beta production.STUDY DESIGN:DNA from 143 women with VVS and 182 control women were tested for a length polymorphism in intron 4 of the gene (CIAS1) that codes for NALP3. Vestibular tissue was examined for NALP3 expression. Whole blood cultures were tested for Candida albicans-induced IL-1beta production.RESULTS:The allele 12 frequency was higher in control subjects than in the patients with VVS (P = .02). Among patients with VVS and a self-reported history of recurrent vulvovaginal candidiasis (RVVC), the allele 7 frequency was 43.9% as compared with 30.8% in patients with no history of RVVC and 26.9% in control women (P = .035 vs other patients and .001 vs control subjects). NALP3 was identified in vestibular tissue. C albicans-induced IL-1beta production was reduced in samples from women with the 7,7 genotype (P = .030).CONCLUSION:Polymorphism in the CIAS1 gene may play a central role in the triggering of VVS in a subset of patients.
Despite extensive efforts toward elucidation of the molecular pathway controlling cytotrophoblast (CTB) invasion to the uterine decidua, it remains poorly defined. There are striking similarities between tumor cell invasion and cytotrophoblast implantation to the deciduas whereby the role of Protease Activated Receptors (PARs) and wnt signaling is well recognized. We examine here consequences of modulation of PAR1 and PAR2 expression and function on CTB invasion and β‐catenin stabilization. Toward this end, we utilized a model system of extravillous trophoblast (EVT) organ culture and various placenta cell lines (e.g., JAR and HTR‐8/Svneo). Activation of PAR1 induces EVT invasion while hPar1‐Si RNA and PAR1 antagonist SCH79797—effectively inhibited it. In parallel, the Wnt inhibitor Dickkopf‐1 (Dkk1) similarly inhibited it. Nuclear localization of β‐catenin is seen only after PAR1 activation, and is markedly reduced following the application of hPar1‐Si RNA construct and PAR1 antagonist in CTBs. In contrast, PAR2 elicited a low cytoplasmic β‐catenin level as also proliferation and invasion. In the non‐activated CTBs in‐comparison, β‐catenin appeared limited to the membrane pools. Concomitantly, a temporal regulated pattern of Wnt‐4, 5a, 7b, 10a, 10b expression is seen along PAR1 appearance. Enforced expression of Wnt antagonists, Secreted Frizzled Related Proteins ; SFRP2 & 5 ; into HTR‐8/Svneo, resulted with a markedly reduced nuclear β‐catenin levels, similar to the effect obtained by hPar1‐Si RNA treatment. Identification of PAR1 downstream target/s may nonetheless contribute to the formation of a future platform system for eliciting a firm placenta‐uterus interactions and to the definition of late pregnancy outcomes. J. Cell. Physiol. 218: 512–521, 2009. © 2008 Wiley‐Liss, Inc.
The aetiology of cryptorchidism is still undiscernible in the majority of cases. It has long been argued that cryptorchidism reflects a primary testicular maldevelopment, where the contralateral scrotal testis also suffers from aspermatogenesis and low spermatogonia count. The aim of the study was to determine the reproductive outcome of ex-cryptorchid men with azoospermia post-orchidopexy after testicular sperm extraction (TESE) and intracytoplasmatic sperm injection (ICSI). In a retrospective analysis, we compared the sperm retrieval, fertilization, pregnancy and live birth rates after ICSI of consecutive ex-cryptorchid azoospermic patients (n = 15) undergoing TESE between Jan 2000 and Dec 2007 vs. non-cryptorchid azoospermic men (n = 142). Sperm retrieval rate of ex-cryptorchid men by TESE (66%) was comparable with non-cryptorchid men (47%) (p = 0.15) despite significantly higher FSH levels (30.7 +/- 25.4 vs. 17.9 +/- 14.8 respectively) (p = 0.018) and a more prevalent histopathology diagnosis of aspermatogenesis (75% vs. 40%, p = 0.046). Fertilization (43.3%), pregnancy (30%) and live birth (20%) rates after TESE-IVF-ICSI in the ex-cryptorchid group were not different from the non-cryptorchid group (48.7, 43 and 29%, p = 0.26, p = 0.21, p = 0.29 respectively). We conclude that the reproductive outcome of ex-cryptorchid men with azoospermia post-orchidopexy employing TESE-IVF-ICSI is comparable with non-cryptorchid azoospermic men.