ショウサン ショウシカ ジダイ ノ サンフジンカ イリョウ ノ ヤクワリ

For recent 30 years, the number of the times of pregnancy and delivery which Japanesewomen experienced has decreased continuously. These decreases have influenced women’shealth and reproductive functions and are caused for the increment of several diseases.It has been reported that the incidence of appearance of endometriosis and uterinefibromas are increased in parallel with decrement of the number of times of pregnancy anddelivery. Furthermore, we have well-known that these decrements also increase the incidenceof occurrence of uterine endometrial cancer, ovarian cancer and breast cancer in malignantdiseases.The length of life in Japanese women is remarkably extended, and the women’s life periodafter menopause is considerably longer because the average of age of menopause inthem is not changed. After menopause, women’s reproductive function is remarkably suppressedand its activity of production of estrogen is diminished. Low level estrogen is dueto a lot of diseases, for example, climacteric syndrome, osteoporosis, hyper cholesterolnemia,etc.Recent progress in treatment for sterility is remarkably. But, on the other hand, it alsooccurs a lot of problems. Positive treatment for sterility is caused to some side effects,multipregnancy and ovarian hyperstimulation syndrome. The treatment for old agedwomen is due to increasing babies with malformation. The assisted reproductive technologyhas serious ethical and economical problems.These situations require gynecologists to know the change of women’s health and reproductivefunction by decreasing the number of the times of pregnancy and delivery and tobe a general physician for women through their whole life

Human Papilloma Virus (HPV) and cervical cancer

Epidemiological and experimental studies have clearly shown that high-risk HPV infection is the main etiologic factor for cervical cancer. Recent studies have indicated that the E6 and E7 gene products play a critical role in cervical carcinogenesis. The E6 and E7 products interfere with the p53 and pRB functions, respectively, and deregulate the cell cycle. The HPV DNA is integrated into the host’s chromosomes with disruption of the E2gene. This disruption promotes the expression of E6 and E7, leading to the accumulation of DNA damage and the development of cervical cancer. The study of the immune response against HPV has been hampered by the lack of a cell culture system for the virus. A breakthrough was made by the discovery that a major capsid protein L1 self-assembles into virus-like particles (VLP) when expressed in eukaryotic systems. Clinical trials of VLP-based vaccines are in progress, and DNA vaccines for the HPV surface protein genes are under development. The E7 and E6 oncoproteins are attractive targets for cancer immunotherapy because their expression is required to maintain the oncogenicity of cervical cancer cells. Cancer immunotherapy for cervical cancer with vaccinations of E7 peptides or dendritic cell-based immunotherapy is moving toward clinical trials

トクシマ ダイガク ニオケル コウド イリョウ ノ シエン キバン セイビ

Establishment of new modality of treatment, diagnosis and prevention of various diseases is an important role of university hospital. In this article, restrictions and guidelines for clinical investigations in Japan are reviewed and supporting system for promotion of clinical trials, now being organized at Tokushima University Hospital, is introduced. The main division in the supporting system of clinical trials is the Clinical Trial Center for Developmental Therapeutics. It was first organized as the Clinical Trial Center for New Drugs and Therapeutic in 1999 under the leadership of Prof. Saburo Sone. Five nurses work as clinical research coordinator (CRC) and coordinates close communication among participants, sponsor and investigators, and plays a crucial role in the efficient progress of clinical trials. Pharmacists and officers also contribute for promotion of clinical trials in the center. The supporting field is now being expanded from the support for clinical trial for drug approval to clinical trials conducted by investigators. For example, one pharmacist supports technically the project of dendritic cell-based vaccination against various malignancies in newly-constructed room. Based on the experience, our task is to grow the center to academic research organization. We are now dealing the following issues ; 1) promotion of clinical trials conducted by investigators, 2) scientific clinical trials of food, 3) setup of network of clinical trials in Tokushima prefecture with general physicians and other institutions

View of physicians on and barriers to patient enrollment in a multicenter clinical trial: experience in a Japanese rural area

<p>Abstract</p> <p>Background</p> <p>Clinical trials in the general practice setting are important for providing evidence on the effectiveness and safety of different agents under various conditions. In conducting these trials, the participation of physicians and patient recruitment are important issues. Various investigations in the literature have reported views and attitudes of physicians on various types of clinical trials. Nevertheless, there is still little information concerning physicians participating in a clinical trial and among them, those who could not recruit any patients (unsuccessful physician recruiters).</p> <p>Methods</p> <p>In 2003, we collaborated in a large-scale multicenter study of Japanese hypertensive patients (COPE Trial). In Tokushima University Hospital and 18 other medical institutions, we investigated the views and attitudes of unsuccessful physician recruiters in comparison with successful physician recruiters, using a questionnaire.</p> <p>Results</p> <p>The questionnaire was provided by mail to 47 physicians and 27 (57%) responded. The response rate was 79% for successful physician recruiters compared to 43% (P = 0.014) for unsuccessful physician recruiters. More successful physician recruiters (73%) than unsuccessful physician recruiters (42%) stated they had participated and enrolled patients in previous multicenter clinical trials. A significantly higher number of successful physician recruiters than unsuccessful physician recruiters (42%; P = 0.040) considered the presence of a support system with clinical research coordinators (CRC) as the reason for participation (80%). A large number of unsuccessful physician recruiters experienced difficulty in obtaining informed consent (67%), whereas a significantly smaller number of successful physician recruiters experienced such difficulty (20%; P = 0.014). The difficulties experienced by unsuccessful physician recruiters in the trial were as follows: inability to find possible participants (100%), difficulty in obtaining informed consent (58%), cumbersome procedures (58%), difficulty in long-term follow up (33%), and insufficient tools for explanation and obtaining informed consent (8%).</p> <p>Conclusion</p> <p>This survey showed that successful physician recruiters consider a support system with CRC of value, and that they are skillful in obtaining informed consent. These views and attitudes may have originated from past experience involving clinical trials. In this regard, we need to develop an infrastructure to enlighten physicians on this support system for the promotion of clinical trials.</p

Trend in maternal-child health services

In Japan, outcome measures for maternal and child health measures such as maternal, perinatal, and infant mortality have consistently shown a trend toward improvement. On the other hand, the problems of the declining birth rate, child abuse, and domestic violence have become evident since the 1990s. In terms of Japan’s maternal and child health, it is necessary to take measures to preserve mental health of mothers and children, and also to respond to family issues such as abuse and violence. The services needed such as comprehensive support centers for families with children and new postpartum care programs have been established. It is necessary to further improve the competence of doctors, public health nurses, and midwives working in the maternal and child health field and to promptly construct a cooperation system in the community

"See and treat" LEEP biopsy for cervical intraepithelial neoplasia grade 2/3

Purpose of investigation: To evaluate the safety and efficacy of loop electrosurgical excision procedure (LEEP) biopsy using a "see-and-treat" strategy, and compare outcomes after "LEEP biopsy, inpatient LEEP and ablation, and inpatient conization with cervical intraepithelial neoplasia (CIN) grade 2/3. Materials and Methods: The authors performed a retrospective study including 300 women with CIN2/3 who were followed up ≥ 6 months following outpatient LEEP/inpatient LEEP and ablation/inpatient conization. Recurrence, additional treatment for recurrence, pregnancy, and term delivery following treatment were evaluated. Results: During the median follow-up duration of 22 months, recurrences were significantly more common following LEEP biopsy (39%) compared to LEEP and ablation (13%) and conization (16%) and were managed by repeat LEEP. Pregnancy and full-term delivery rates following LEEP biopsy were significantly higher. Conclusion: "See-and-treat" LEEP biopsy was safely performed in the outpatient department. Pregnancy rates and full-term deliveries following LEEP biopsy appear favorable

Utility of laparoscopic surgery for pelvic abscesses

骨盤内膿瘍に対する治療は，抗生剤による薬物療法が主体であるが，抗生剤無効例や，消化管から発生した膿瘍との鑑別を要する症例では外科的アプローチが必要となる。骨盤内膿瘍の場合，炎症による癒着が強いことが多く，手術は比較的難易度が高い。しかし，高度の炎症で疲弊した患者の負担を軽減するために，近年では腹腔鏡手術が積極的に導入されており，当院でも可能な限り腹腔鏡手術で対応している。抗生剤による治療が無効であった付属器膿瘍に対して腹腔鏡下手術を施行した4症例について報告する。4例とも輸血を要するような出血はなく，また他臓器損傷もなかった。術後は，速やかに炎症所見が改善し特に問題なく経過した。 骨盤内膿瘍に対する腹腔鏡手術は，ドレナージによりすみやかな炎症軽減が可能であり，かつ低侵襲であることから有用性は高い。一方で，（汎発性腹膜炎などで，）腸管麻痺を伴う症例では，腸管の膨隆のため腹腔鏡下の視野確保が困難であり，腹腔鏡手術の適応は慎重であるべきであると考える。Tubo-ovarian abscesses are classically treated with broad-spectrum antibiotics. Frequently, this approach fails, and surgical intervention becomes necessary. In recent years, laparoscopic surgery was positively introduced, and in our hospital, laparoscopic surgery, which is minimally invasive for patients, is selected as much as possible. We performed laparoscopy for four patients with tubo-ovarian abscess that did not improve with antibiotic treatment. No hemorrhage damage to other internal organs was noted in any of the patients. Inflammation was improved immediately, and postoperative progress was good. Usually, surgery for tubo-ovarian abscess is often technically difficult and associated with complications. For peritonitis accompanied with intestinal tract paralysis, it is difficult to secure the field of vision with the laparoscope, and therefore, the indications for laparoscopic surgery should be carefully considered before conducting the surgery

Activin stimulated follicular growth

As the follicular environment transits from being activin dominant to inhibin dominant during folliculogenesis, it is assumed that activin plays an important role in the early stage of follicular growth. We examined the effects of activin on morphological, biochemical and molecular changes in isolated preantral follicles. Preantral follicles were mechanically isolated from 14-day old female C57BL/6 mice. Each follicle was cultured and observed for 14 days using an in vitro follicle culture system containing FSH, FSH + activin A and FSH + inhibin in the culture medium. We subsequently examined FSH receptor (FSH-R) mRNA expression in isolated follicle cultures with or without activin on days 0 and 2. Activin was observed to significantly stimulate follicle enlargement on days 2, 4, 6 and 8, accelerate morphological changes and increase estradiollevels in culture medium on days 4, 12 and 14. In contrast, inhibin did not alter follicular growth. Additionally, activin stimulated the expression of FSH-R mRNA in isolated granulosa cells. It was demonstrated that activin stimulated the growth of preantral follicles, mainly during the early stage of folliculogenesis, by inducing FSH-R expression, in an isolated follicle culture system

Role of clinical research coordinators in promoting clinical trials of drugs for surgical patients

<p>Abstract</p> <p>Background</p> <p>Clinical trials play a central role in the establishment of clinical evidence, and the important role of clinical research coordinators (CRCs) in various processes of clinical trials is now widely recognized. In Japan, many CRCs work under the discretion of their hospital and support clinical trials in various areas. Modification of CRC activity pursuant to the types of clinical trials may make roles of the CRC more effective and meaningful. In the present study, we examine the dedicated role of the CRC considering the specialty of a registration trial of a drug for surgical patients used during the operation period.</p> <p>Methods</p> <p>In 2006, we had a chance to support a registration trial of a drug for surgical patients used during the operation period. Regarding the mental and emotional status of possible participants in the present registration trial, we collected data from the perspective of CRCs by focus group interviews involving four CRCs working under the discretion of Tokushima University Hospital. The four CRCs were all nurses and had 7, 4.5, 1, or 0.5 years experience as CRCs, respectively.</p> <p>Results</p> <p>In contrast to clinical trials of drugs for chronic diseases, these often anxious patients must decide whether or not to enter the trial simultaneously with the decision to undergo surgery itself, and all in a relatively limited time after receiving explanation of the trial. Therefore, special attention should be paid to the mental and emotional status of possible participants. Additionally, the cooperation of the relatively large surgical and nursing staff becomes important. In such situations, the following contributions of CRCs were considered to be useful for the harmonious procedure of clinical trials: 1) providing a precise explanation of the trial to the participant and key persons, 2) understanding the needs of the investigators and appropriately assigning themselves roles, and 3) communicating between the investigators and surgical and nursing staff.</p> <p>Conclusion</p> <p>Further study is warranted to evaluate the benefit of the intervention provided by dedicated CRCs in running high quality clinical trials involving surgical patients.</p

Effect of hospitalization on fetal growth

Objective : We aimed to demonstrate the effect of prolonged hospitalization on fetal growth in cases of threatened preterm labor (TPL). Methods : In this retrospective cohort study, we included women who received prenatal care for TPL but delivered their child after 36 weeks of gestation. These were compared with a control group of healthy pregnant women and fetuses delivered at term. Fetal growth was compared using biparietal diameter, abdominal circumference (AC), femur length, and estimated fetal weight (EFW) assessed using ultrasonography at 18, 26, 30, and 36 weeks of gestation. Neonatal parameters at birth were also compared. Results : In total, we enrolled 228 control women and 114 women with TPL who were treated with hospitalization, including bed rest. The AC at 30 and 36 weeks of gestation and EFW at 36 weeks of gestation were smaller in women treated with bed rest than for normal pregnant women. The mean duration of pregnancy was shorter in the hospitalization group than in the control group. Neonatal weight, length, head circumference, and chest circumference at birth were smaller after prolonged hospitalization for TPL than after normal pregnancy. Conclusion : Prolonged hospitalization for threatened preterm labor is associated with impaired fetal growth, particularly AC