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Repeated dose oral toxicity and toxicokinetic of KDS2010, a new drug for Parkinson's disease, was investigated after 4-week repeated oral administration at 30, 50, 75, or 100 mg/kg/day in rats. Body weight and body weight gain decreased in rats of both sexes in the 75 and 100 mg/kg groups, and food consumption was reduced in male rats of the 75 and 100 mg/kg male groups. Histological alterations were observed in the kidney (urothelial hyperplasia, inflammatory cell infiltration in the renal pelvis, tubular vacuolation/degeneration, basophilic tubules, and hyaline droplets in the proximal tubules) of the 75 and 100 mg/kg male groups and the 50 and 100 mg/kg female groups. The 75 and 100 mg/kg male groups showed adverse effect in the testes (degeneration/exfoliation of germ cells, seminiferous tubules atrophy) and epididymis (cellular debris, oligospermia). These changes were partially recovered after a 2-week recovery period. However, basophilic tubules and hyaline droplets in the proximal tubules in the kidney and germ cell degeneration/exfoliation in the testis were not recovered. In toxicokinetics study, systemic exposure to KDS2010 increased proportionally in both sexes by in a dose -dependent manner. In addition, repeated administration for 4 weeks led to increased tendency of systemic exposure in both sexes compared with that in Day 1. In conclusion, KDS2010 was shown to target the kidney and testis with a no-observed-adverse-effect level of 50 and 30 mg/kg/day for males and females, respectively.

Spinal muscular atrophy and hereditary motor and sensory neuropathies are characterized by muscle weakness and atrophy caused by the degenerations of peripheral motor and sensory nerves. Recent advances in genetics have resulted in the identification of missense mutations in TRPV4 in patients with these hereditary neuropathies. Neurodegeneration caused by Ca(2+) overload due to the gain-of-function mutation of TRPV4 was suggested as the molecular mechanism for the neuropathies. Despite the importance of TRPV4 mutations in causing neuropathies, the precise role of TRPV4 in the sensory/motor neurons is unknown. Here, we report that TRPV4 mediates neurotrophic factor-derived neuritogenesis in developing peripheral neurons. TRPV4 was found to be highly expressed in sensory and spinal motor neurons in early development as well as in the adult, and the overexpression or chemical activation of TRPV4 was found to promote neuritogenesis in sensory neurons as well as PC12 cells, whereas its knockdown and pharmacologic inhibition had the opposite effect. More importantly, nerve growth factor or cAMP treatment up-regulated the expression of phospholipase A(2) and TRPV4. Neurotrophic factor-derived neuritogenesis appears to be regulated by the phospholipase A(2)-mediated TRPV4 pathway. These findings show that TRPV4 mediates neurotrophic factor-induced neuritogenesis in developing peripheral nerves. Because neurotrophic factors are essential for the maintenance of peripheral nerves, these findings suggest that aberrant TRPV4 activity may lead to some types of pathology of sensory and motor nerves.

From January 1995 to December 2000, medical records of 196 patients were collected from 14 hospitals nationwide and were reviewed retrospectively. We evaluated the clinicopathologic characteristics of malignant germ cell tumors in the ovaries of South Korean women and determined the prognostic factors affecting recurrence. The mean patient age was 23.8 years (range, 4-63 years), and the median follow-up period was 67 months (range, 1-128 months). The distribution of the International Federation of Gynecology and Obstetrics stage was as follows: 128 cases (65.3%) in stage I, 27 cases (13.8%) in stage II, 39 cases (19.9%) in stage III, and 2 cases (1.0%) in stage IV. Histologically, immature teratoma was the most common tumor type (n = 68), followed by dysgerminoma (n = 54), endodermal sinus tumor (n = 38), mixed form (n = 24), and choriocarcinoma (n = 12). A fertility-sparing operation was performed in 134 patients, staging operation in 43 patients, and hysterectomy and bilateral salpingo-oophorectomy in 19 patients. Postoperative chemotherapy was administered in 166 patients, and the most common regimen was bleomycin, etoposide, and cisplatin (n = 120). Recurrence was observed in 13 patients (6.8%) and was influenced by the stage of the tumor and patient age (>40 years). The 5-year survival rate was 96.7%. During the follow-up period, 20 patients had 22 pregnancies that resulted in 17 normal deliveries at term and 5 abortions. The results of this study demonstrate that most malignant germ cell tumors of the ovary in Korean women are detected in the early stage and have excellent survival outcomes with conservative operation and platinum-based chemotherapy.

Standard abdominoplasty techniques involve a low horizontal or W skin excision, muscle plication, and umbilical transposition. Newer techniques include suction-assisted lipectomy, the use of high lateral tension with fascial suspension, and external oblique muscle advancement. The author has modified these traditional procedures and added new techniques to improve the aesthetic and functional results of the abdominoplasty procedure. This modification provides a comprehensive approach to abdominal wall aesthetic improvement and rehabilitation. The comprehensive approach described includes four components: the "U-M dermolipectomy," "V umbilicoplasty," the rectus abdominis "myofascial release," and suction-assisted lipectomy. The patient is marked while standing for areas of suction lipectomy and undermining. The lower incision is designed as an open U with the lateral limbs placed inside the bikini line. The upper incision is a lazy M with the higher peaks located at the level of the flanks. Subcutaneous hydration is achieved to perform suction along the flanks, waistline, and iliac areas. Gentle suction of the flaps is also performed. The umbilicus is cored out in a heart shape. The flaps within the U-M marks are excised, and the undermining is performed to the xiphoid and costal margins. The rectus diastasis is marked, and the anterior rectus fascia is incised at the junction of the medial third with the central third of the width of the rectus sheath. Horizontal figure-eight plication sutures by using the lateral fascial edge enable easier infolding of the central tissue. The new recipient of the umbilicus is made by an incision in a V shape on the abdominal flap. The umbilicus is telescoped, and the triangular flap of the abdomen is sutured to the triangular defect of the umbilicus. Skin flap fixation to the umbilicus relieves tension in the lower portion of the flap. The upper skin flap, which is cut in an M manner, provides lateral tension and matches the length of the lower flap. A standard fascial suspension is used and closure is performed in layers. The techniques described here are intertwined procedures. Each facilitates the accomplishment of the other procedure, and they complement each other. They all attain the 12 objectives of the abdominoplasty described. These combined techniques have been used in 104 patients in a period of 11 years. Complications were minimal and easily manageable, except for one patient who required excision of a pseudobursa and retightening of the lower quadrants of the abdominal wall musculature to correct extreme lordosis. A comprehensive approach for the treatment of complex abdominal wall aesthetic and functional defects is presented. These require thoughtful integration of the four components mentioned. This approach has allowed predictable, reproducible, and aesthetically pleasing results.

Purpose To evaluate the efficacy and toxicity of concurrent chemoradiation with paclitaxel and carboplatin in patients with high-risk cervical cancer. Methods and Materials Patients after radical hysterectomy for cervical cancer, with at least 1 high-risk characteristic, were administered paclitaxel 135 mg/m2, carboplatin area under the curve = 5 every 3 weeks for 3 cycles concomitant with radiation therapy as adjuvant treatment. Results This prospective study enrolled 71 consecutive patients. Sixty-six patients (93%) completed the planned treatment. The majority of grade 3/4 neutropenia or nonhematologic toxicities were usually self-limited. Diarrhea grades 3/4 were observed in 4 patients (5.6%). One patient developed anaphylactic shock after infusion of paclitaxel. With a median follow-up of 57 months, recurrences occurred in 16 patients. Multivariable analysis indicated that common iliac lymph node involvement is an independent risk factor for disease recurrence (odds ratio 13.48; 95% confidence interval 2.93-62.03). In the intent-to-treat population (n=71), the estimated 5-year disease-free survival and overall survival rates were 77.3% and 80.3% respectively. In the per-protocol population (n=62), disease-free survival was 78.9% and overall survival was 83.9%. Conclusions Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and seems to be effective for patients who undergo radical hysterectomy. Therefore, a prospective, randomized controlled study should be designed to evaluate efficacy of this approach for patients with high-risk cervical cancer.

The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.

Objective The objective of the study was to analyze the characteristics of cervical cancer associated with pregnancy. Study Design Forty patients with cervical cancer associated with pregnancy were retrospectively identified between 1995-2003. Three controls for each case were matched on the basis of age, stage, histology, and date of treatment. Results Sampling of cervical cytology after the second trimester was the most common cause of delayed diagnosis. Among 12 patients who delayed treatment for fetal maturity, 2 died of disease. There was no difference in overall survival between pregnant and nonpregnant patients with stage Ib tumors. In contrast to nonpregnant patients, the depth of stromal invasion was not correlated with the incidence of lymph vascular space involvement and lymph node metastasis in pregnant patients. Conclusion Thorough evaluation is warranted before deciding whether to delay treatment until fetal maturity. Pregnancy does not adversely affect the prognosis of early-stage cervical cancer significantly.

Objective(s). The aim of this study was to evaluate the effects of neoadjuvant chemotherapy and radical hysterectomy on long-term survival in stage IB–IIB locally advanced cervical cancer by conducting a 10-year follow-up. Methods. Between August 1983 and May 1990, 80 locally advanced, stage IB–IIB cervical cancer patients with tumor diameter greater than or equal to 4 cm were treated with neoadjuvant VBP chemotherapy (cisplatin, vinblastine, and bleomycin) followed by radical hysterectomy with pelvic lymphadenectomy. After this therapeutic modality, patients were followed for more than 10 years. Ten-year survival rates and factors affecting recurrence after this therapy were evaluated. Results. Of 80 patients, 75 (93.7%) showed a reduction in tumor size after neoadjuvant chemotherapy. At pathologic examination, stage reduction was noted in 53 (66.2%) patients and 20 patients (25%) showed no residual or microinvasive cervical tumor. Pelvic lymph node metastases were found in 17 patients (21.3%). During the 10-year follow up, 2 patients were lost and 16 patients recurred. Overall 5-year and 10-year disease-free actual survival rates were 82.0 (64/78) and 79.4% (62/78), respectively. Clinical stage, initial tumor size, clinical response, and residual tumor size were not risk factors for recurrence after this therapy. However, pelvic lymph node metastasis was a significant risk factor for recurrence. Conclusion(s). Neoadjuvant VBP chemotherapy followed by radical hysterectomy in locally advanced, stage IB–IIB cervical cancer patients seemed to improve the long-term survival rate for these patients compared to that of conventional therapy. However, randomized controlled trials are needed to confirm this result.

Murine monoclonal antibody FEN-1 was derived by immunizing Balb/c mice with an affinity-purified endometrioid ovarian cancer-associated antigen recovered from ascites-derived immune complexes. Splenic lymphocytes from the immunized mouse were fused with the myeloma cells SP2/0-AG14 in the presence of PEG 1500. The hybrid cultures were screened for production of immunoglobulins reactive with an extract preparation of an endometrioid ovarian tumor by enzyme-linked immunosorbent assay and flow cytometry. One of the hybrids secretes a monoclonal antibody of the IgG3 subtype designated FEN-1, which reacts with 100% of endometrioid ovarian cancer containing adenoacanthoma by indirect immunoperoxidase on paraffin-embedded tissue. No detectable levels of antigen were found in squamous metaplasia associated with nonendometrioid tumors, and no reactivity occurred against endometrial adenocarcinomas, endometriosis, or normal ovary and endometrium. The antibody does not cross-react with mucinous tumors, nonepithelial tumors of the ovary, or gastrointestinal tissue. This antibody may be used as an aid in the diagnosis of nonmucinous ovarian carcinomas by immunohistology.

Objective : To assess the ability of risk of malignancy index (RMI) based on ultrasound findings, serum levels of CA 125, and menopausal status to discriminate between benign and malignant ovarian masses for preoperative screening. Methods : A retrospective study was conducted of 255 women with ovarian masses admitted for operation at the Department of Obstetrics and Gynecology, Hanyang University Hospital between 1999 and 2003. The sensitivity and specificity of serum levels of CA 125, ultrasound findings, and menopausal status were calculated both separately and combined into a RMI to diagnose malignancy. Results : There were significant preoperative differences of ultrasound findings, serum CA 125 level, serum CA 19-9 level, platelet count and menopausal status between benign and malignant ovarian masses (P

The Sertoli-Leydig cell tumor is a rare sex cord stromal tumor that has low grade malignancy and low bilateral occurrence rate. About two third of recurrence appears within 1 year after the initial treatment and most common recurrence sites are intraperitoneal cavity and retroperitoneal lymph nodes. The frequency of malignant transformation is high in the poor differentiated cell type, retiform pattern, and tumor rupture. In young women with stage I, unilateral salpingo-oophorectomy is performed to preserve uterus and reproductive function. In more advanced stages, hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection are performed and occasionally chemotherapy can be combined. We experienced a rare case of malignant metastasis in Sertoli-Leydig cell tumor, and presented with a brief review of literature.

Peritoneal pregnancies are classified as primary and secondary. Primary implantation on the peritoneum is extremely rare in extrauterine pregnancy and is a potentially life-threatening variation of ectopic pregnancy within the peritoneal cavity, representing a grave risk to maternal health. Secondary abdominal pregnancies are by far the most common and result from tubal abortion or rupture, or less often, after uterine rupture with subsequent implantation within abdomen. Early diagnosis and appropriate surgical management, regardless of stage of gestation, appear to be important in achieving good results. We report a case of primary peritoneal pregnancy in a 28-year-old woman, who had severe lower abdominal pain one day before laparotomy for a preoperative diagnosis of ectopic pregnancy. The conceptus was implanted on the left uterosacral ligament. A fresh embryo of approximately 8 weeks' gestation was found in the conceptus.

The effect of preoperative adjuvant chemotherapy on the 2-year survival rate of patients with locally advanced cervical cancer (stages Ib and II with bulky tumour) was evaluated. The 54 patients first received initial chemotherapy of vinblastine, bleomycin, and cis-platinum in a combined regimen (VBP) and then radical hysterectomy. The overall histologic response rate to chemotherapy of the primary tumor confirmed in the surgical specimen was 81% including microscopic or no evidence of disease (41%, Grade III or IV). A lower than expected incidence of lymph node metastasis (20%) was found. All nodal metastasis was noted in patients with Grades I or II (P = 0.0034). Median follow-up was 36 months (range 26-60 months). Three recurrences (6%) appeared and those patients died of the disease within 24 months. Thus the 2-year tumour-free survival rate was 94%. The patients who had positive nodes more often experienced recurrence (27 vs 0%) and a lower 2-year survival rate (72 vs 100%) (P = 0.0067). All of these recurrences were found in patients with three or more positive nodes. This preliminary study suggest that preoperative adjuvant chemotherapy (VBP) is effective (1) in reducing tumour volume or the stage of the disease, (2) in curing the lymph node involvement, and (3) in improving the 2-year tumour-free survival rate. A prospective randomized study comparing radical surgery alone with preoperative adjuvant chemotherapy followed by radical surgery is in progress.