Development of a chip-based multiplexed immunoassay using liposomal nanovesicles and its application in the detection of pathogens causing female lower genital tract infections.

OBJECTIVE: Cervicovaginitis is a highly prevalent disease that is a burden on healthcare globally. Immediate and adequate treatment can eradicate the infection and block subsequent complications. The feasibility of achip-based multiplexed immunoassay using liposomal nanovesicles was tested. MATERIALS AND METHODS: A multiplexed immunoassay chip containing five antibodies for five pathogens (Chlamydia trachomatis, Escherichia coli, Neisseria gonorrhoeae, Streptococcus agalactiae, and Candida albicans) was established and tested. Four patients with spiking of candidiasis were enrolled. The difference between positive and negative readings was evaluated using the paired Student t test. RESULTS: The detection threshold of Candida in this microarray was 100,000 CFU/mL in a vaginal sample, and the time required for the whole procedure was 3 hours. The testing of the four patients showed 100% for both sensitivity and specificity. CONCLUSION: This microarray chip was a rapid, easy, inexpensive and sensitive tool for detecting female lower genital tract Candida infection in a one-time vaginal sampling process, although the data on the four other pathogens were still unavailable. A larger population study is encouraged to test the validity of this multiplexed immunoassay chip.

Reproductive performance of severely symptomatic women with uterine adenomyoma who wanted preservation of the uterus and underwent combined surgical-medical treatment.

OBJECTIVE: To assess the factors associated with future pregnancy and successful delivery in women who were treated for uterine adenomyoma with combination (surgical-medical) therapy using ultramini- or mini-laparotomy conservative surgery and gonadotropin-releasing hormone agonist. MATERIALS AND METHODS: One hundred and two women were evaluated. Items for analysis included: age, body mass index, and conception history; clinical symptoms of dysmenorrhea and menorrhagia; tumor location and preoperative serum level of cancer antigen 125 (CA125); the intraoperative findings of the weight of the removed tumor, and the uterine cavity opening. RESULTS: After excluding those patients using contraception or searching for an assisted reproductive technique, a total of 56 women were enrolled for analysis. Twenty-three (41.1%) women had 27 clinical pregnancies after 3 years of follow-up; 15 went on to deliver a healthy live-born child; two delivered preterm but healthy babies; seven had elective abortions; four had spontaneous abortions; and one had an ectopic pregnancy. The women who had a successful delivery during the 3-year follow-up after treatment tended to be younger, with a lower body mass index, lower baseline analgesic usage score, and lower preoperative serum level of CA125, be nulliparous, and with an adenoma in an anterior location. The linear regression model showed that age and baseline analgesic usage score were independent predictors of successful delivery and accounted for 56.5% of the total variance related to successful delivery. CONCLUSION: Age was an important factor associated with future successful delivery, therefore, caution should be taken in considering the maintenance of future fertility in older women treated with surgical-medical therapy.

Typical and atypical clinical presentation of uterine myomas.

Myoma is the most common benign neoplasm that can occur in the female reproductive system, most frequently seen in women in their 50s. Although the majority of myomas are asymptomatic, some patients have symptoms and/or signs of varying degrees. Typical myoma-related symptoms or signs include: (1) menstrual disturbances like menorrhagia, dysmenorrhea and intermenstrual bleeding, (2) pelvic pain unrelated to menstruation, (3) compression symptoms, similar to a sensation of bloatedness, urinary frequency and constipation, (4) subfertility status such as recurrent abortion, preterm labor, dystocia with an increased incidence of Cesarean section, and postpartum hemorrhage, and (5) cosmetic problems due to increased abdominal girth However, there are undoubtedly some clinical presentations secondary to uterine myomas are not so specific, such as: (1) uncommon compression-related symptoms, (2) cardiac symptom and atypical symptoms secondary to vascular involvement or dissemination, (3) abdominal symptoms mimicking pelvic carcinomatosis, (4) dyspnea, (5) pruritus, (6) hiccup or internal bleeding, and (7) vaginal protruding mass or uterine inversion. Familiarization with these symptoms and awareness of other unusual or atypical presentations of uterine myomas will remind clinical practitioners of their significance, and of the necessity of follow-up examinations and individualized management to fit the needs and childbirth desires of the patients.

Metronomic therapy for gynecologic cancers.

Systemic administration of cytotoxic drugs is the primary treatment strategy for patients with advanced cancer. The effect of cytotoxic drugs is to disrupt the DNA of the cells, rendering them unable to replicate and finally killing them; therefore, the fundamental role of a wide range of treatment regimens is typically to induce lethal toxicity in the largest possible number of cancer cells. However, these cytotoxic drugs also damage the normal cells of the host, which limits the dose of the cytotoxic drug. Thus, cancer patients are usually treated at or near the maximum tolerated dose with the implicit intent of eradicating (curing) the tumor after balancing between efficacy in tumor killing and toxicity to the host. With significantly improving patient care, most efforts are focused on the corollary, "The higher the dose, the better." However, the concept that cancer could be considered as a chronic disease and might be treated like other chronic diseases to achieve a status called tumor dormancy is gaining popularity. In addition, there has been increasing interest in putting more effort into administering cytotoxic drugs on a more continuous basis, with a much shorter break period, or none at all, and generally lower doses of various cytotoxic drugs or combinations with other newer, targeted therapies, like anti-angiogenesis agents. This practice has come to be known as metronomic chemotherapy. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor type applications. This review will explore recent studies that have addressed the mechanism of metronomic chemotherapy in the management of various tumors, especially gynecologic cancers.

Review of myomectomy.

Uterine fibroids (also called leiomyomas or myomas) are the most common disorder among women of reproductive age, with an incidence of between 20% and 80%; they are often detected incidentally in routine healthy examinations, through bimanual pelvic and/or ultrasound examination, because uterine fibroids are rarely associated with symptoms. Sometimes, uterine fibroids may be complicated by a variety of symptoms, including menstrual disturbance (e.g., menorrhagia, dysmenorrhea, intermenstrual bleeding), pressure symptoms, bloated sensation, increased urinary frequency, bowel disturbance, or pelvic pain; therefore definite treatment is requested. Hysterectomy may be the first choice for women who have completed their child-birth; however, many women may prefer to keep the uterus if the uterine fibroids-related symptoms can be appropriately controlled. Among these conservative therapies, myomectomy may be one of the most popular methods for the woman who would like to preserve her future fertility, as the majority of symptoms can be relieved by myomectomy; this contributes to the value of this review. This review addresses the use of myomectomy in the management of symptomatic uterine fibroids.

Rupture of a pregnant unscarred uterus in an early secondary trimester: a case report and brief review.

Rupture of a pregnant uterus in early pregnancy and an unscarred uterus are extremely rare, and some non-specific symptoms might appear before this occurrence. We report the case of a multiparous woman (gravida 3, para 2) with uterine fundal rupture in her early second trimester (17+ weeks of gestational age), who presented upper abdominal discomfort and vomiting for 3 days, and progressed into sudden acute abdomen and shock. During emergent laparotomy, the entire amniotic sac was found in the peritoneal cavity with a rupture of the uterine fundus. Although we could not confirm that the appearance of upper gastrointestinal symptoms and severe vomiting was associated with uterine rupture in this pregnant woman, abdominal symptoms or signs might be a hint or cause of severe catastrophic pregnancy-related complications.

Hormone therapy for younger patients with endometrial cancer.

The relationship between hormones and endometrial cancer is well known because disease states, such as chronic anovulation and endogenous estrogen production from hormone-secreting tumors (for example, granulosa cell tumor of the ovary), are related to excess estrogen, and unopposed estrogen use might lead to endometrial overgrowth, hyperplasia, and subsequent development of endometrial carcinoma. Therefore, the possibility of using antihormone therapy in endometrial carcinoma and/or its precancer lesions, such as simple hyperplasia with and without atypia and complex hyperplasia with and without atypia, is always supposed, as in the management of breast cancer. In addition, if women in whom endometrial cancer is diagnosed are very young, some critical issues should be considered, including the possibility of ovary preservation-partial preservation of fertility and the possibility of both ovary and uterus preservation-complete preservation of fertility. Other factors are also important to consider and include oncologic risk, appropriateness of candidates for treatment, type of hormone use, response rate of hormonal therapy, appropriate surveillance, and additional counseling for issues such as anxiety about relapse and metastasis, distress about side effects, advice of the family, advice of the medical staff, and economic burden. This review will be focused on updated information and recent knowledge of the use of hormones in the management of younger women with endometrial cancer who want fertility preservation.

Are we satisfied with the tools for the diagnosis of gonococcal infection in females?

Gonorrhea (Neisseria gonorrhoeae) is a common sexually transmitted infection in women, with a heavy burden on female and neonatal health, because sequelae occur, such as female infertility, ectopic pregnancy, neonatal ophthalmitis and infection, and chronic pelvic pain. Prompt and appropriate antibiotic treatment can cure infection and avoid complications. However, adequate treatment is not easy, because early and rapid identification of gonorrhea is interfered with by many factors, including the complicated mixed microflora of the vagina and cervix, non-user-friendly culture systems, and lack of immediate availability of results, even with a combination of subjective complaint and high clinical suspicion. A PubMed search was conducted using the major headings of "gonorrhoea and diagnostic tool" and "Neisseria gonorrhoeae and diagnostic tool", before the end of 2010. Recently available methods for the diagnosis of gonorrhea infection in women were included, including traditional tools and advanced technology. Traditional tools such as microscopic examination and microbial culture have been used broadly; unfortunately, they have relatively lower specificity or sensitivity, and most importantly, "see-and-treat" is impossible for these infected women. Advances in technology, such as antigen detection by immunoassay and nucleic acid amplification tests (NAATs), have achieved major progress in the diagnosis of gonorrhea, because of their accuracy, convenience and time-saving aspects. However, NAATs are expensive, making their acceptance impossible in developing countries. Detection of pathogens including N. gonorrheae using microarray chips is viewed as a possible solution, because it is a relatively rapid, easy, inexpensive and sensitive tool, which makes an "identify-and-treat" or point-of-care policy possible. A rapid and affordable tool with high sensitivity and specificity for detection of gonorrhea in developing countries is still not available at the time of writing. To make a point-of-care policy possible, advanced technology for aiding diagnosis of gonorrhea is encouraged and appreciated.

Diagnosis of Chlamydia infection in women.

OBJECTS: Chlamydia (Chlamydia trachomatis) is a common sexually transmitted infection that places a heavy burden on women and neonatal health. To avoid severe sequelae such as female infertility, ectopic pregnancy, neonatal infection, such as ophthalmitis, and chronic pelvic pain prompt and appropriate antibiotic treatment seems the best policy in treating this group of patients. However, adequate treatment is not easy because many factors can interfere with an early and rapid identification of Chlamydia infection, including complicated mixed microflora of the vagina and cervix, a nonuser-friendly detection system, and the time required for identification, even with the combination of specific complaints and a high level of clinical alertness. When dealing with a female patient in a point-of-care (POC) clinic, we need to find the best strategy to provide the most efficient way to detect this infection. MATERIALS AND METHODS: Totally five traditional methods and advanced technologies used for the diagnosis of Chlamydia infection in women were reviewed. A criterion proposed by World Health Organization with an acronym of ASSURED, representing affordable price, high sensitivity, high specificity, user-friendly design, rapid process, minimal equipment, and delivered-or-not, was used to reexamine these tools if they are the best tools. A multiplexed microchip-based immunoassay was evaluated as a potential tool. The ASSURED score was compared and a Chi-square test with a p value less than 0.05 was considered significant. RESULTS: Traditional methods, such as symptoms approach, microscopic examination, and microorganism culture that have been broadly used once, are affordable, simple, and equipment-free but their relatively low sensitivity and specificity limit their use as a test of POC setting for these infected women. On the other hand, advanced technologies, such as antigen detection by immunoassay and nucleic acid amplification tests, have contributed to major progress in the diagnosis of Chlamydia because of its accuracy, convenience, and time saving. However, nucleic acid amplification tests are too expensive, so they cannot be accepted as a screening tool in a developing country. The only significant finding with p value less than 0.01 was achieved when a more sensitive immunoassay system developed successfully as a test of POC setting. CONCLUSIONS: Eventually, advances in laboratory techniques will satisfy our needs to detect Chlamydia infection economically and instantly. Microarray chips might be a relatively rapid, easy, inexpensive, and sensitive tool to detect many pathogens, including Chlamydia, using a one-time vaginal sampling process, which might make a POC policy possible.

Myomectomy for uterine myomas through ultramini-laparotomy.

Uterine fibroids are the most common benign tumors in the female reproductive tract during the reproductive years. Among the options in the treatment spectrum, myomectomy is always considered one of the best choices in the management of women with symptomatic uterine fibroids who wish to preserve future fertility. Myomectomy through conventional exploratory laparotomy may be the most familiar surgical approach. However, with the advances being made in techniques and instruments, there are many alternative approaches to myomectomy, including mini-laparotomy, ultramini-laparotomy, laparoscopy, laparoscopy-aided, and vaginal and hysteroscopic approaches. The focus of this review article is limited to discussing the use of the ultramini-laparotomy approach to completing myomectomy in the management of the uterine fibroids.

Nonsteroidal anti-inflammatory drugs for wounds: pain relief or excessive scar formation?

The inflammatory process has direct effects on normal and abnormal wound healing. Hypertrophic scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of fibroblasts and excess accumulation of extracellular matrix during wound healing. Two cytokines--transforming growth factor-beta (TGF-beta) and prostaglandin E2 (PGE2)--are lipid mediators of inflammation involving wound healing. Overproduction of TGF-beta and suppression of PGE2 are found in excessive wound scarring compared with normal wound healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) or their selective cyclooxygenase-2 (COX-2) inhibitors are frequently used as a pain-killer. However, both NSAIDs and COX-2 inhibitors inhibit PGE2 production, which might exacerbate excessive scar formation, especially when used during the later proliferative phase. Therefore, a balance between cytokines and medication in the pathogenesis of wound healing is needed. This report is a literature review pertaining to wound healing and is focused on TGF-beta and PGE2.

Adenomyosis and its variance: adenomyoma and female fertility.

Extensive adenomyosis (adenomyosis) or its variance, localized adenomyosis (adenomyoma) of the uterus, is often described as scattered, widely-distributed endometrial glands or stromal tissue found throughout the myometrium layer of the uterus. By definition, adenomyosis consists of epithelial as well as stromal elements, and is situated at least 2.5 mm below the endometrialmyometrial junction. However, the diagnosis and clinical significance of uterine adenomyosis and/or adenomyoma remain somewhat enigmatic. The relationship between infertility and uterine adenomyosis and/or adenomyoma is still uncertain, but severe endometriosis impairs the chances of successful pregnancy when using artificial reproductive techniques. To date, there is no uniform agreement on the most appropriate therapeutic methods for managing women with uterine adenomyosis and/or adenomyoma who want to preserve their fertility. Fertility has been restored after successful treatment of adenomyosis using multiple modalities, including hormonal therapy and conservative surgical therapy via laparoscopy or exploratory laparotomy, uterine artery embolization, and other methods, including a potential but under-investigated procedure, magnetic resonance-guided focused ultrasound. This review will explore recent publications that have addressed the use of different approaches in the management of subfertile women with uterine adenomyosis and adenomyoma.

Port wound closure assisted by Foley catheter: an easier way to provide fascia security.

AIM: Specific laparoscopy-related complications, such as incisional hernia (trocar hernia) or hemorrhage, are worthy of our special attention. Preventing and managing these complications safely and efficiently are important, suggesting that a definite closure of the 10-12 mm port wound after laparoscopy is needed; for this, a newer, simpler method was used. METHODS: Ninety-six patients with benign ovarian tumor warranting laparoscopic surgery were enrolled into the study. Forty-eight patients (50%) underwent a Foley catheter-assisted port wound closure (Foley group) and the remaining patients (50%) underwent a conventional port would closure (control group). The outcome was measured by comparing operative time, the amount of suture material used (difficulty of wound closure), therapeutic efficacy (hernia), postoperative complications (bleeding, hematoma, and wound pain by a self-reported six-point verbal numeric rating scale (VNRS-6)) and anesthesia use as measured by an analgesic usage score (AUS), and dissatisfaction with the cosmetic results, in both groups. RESULTS: The general characteristics of the patients were similar in both groups. There were no statistical differences in mean operative time, therapeutic efficacy, and postoperative complications between the two groups. However, the amount of extra suture material needed was significantly less in the Foley group compared to the control group (1.04 +/- 0.08 vs 1.29 +/- 0.44, P = 0.015, and 4.2 vs 25%, P = 0.02, respectively). CONCLUSION: Wound closure with the assistance of a Foley catheter offers an easy and secure way to close a 10-12 mm port wound.