Unravelling nicotinic receptor and ligand features underlying neonicotinoid knockdown actions on the malaria vector mosquito Anopheles gambiae.

With the spread of resistance to long-established insecticides targeting Anopheles malaria vectors, understanding the actions of compounds newly identified for vector control is essential. With new commercial vector-control products containing neonicotinoids under development, we investigate the actions of 6 neonicotinoids (imidacloprid, thiacloprid, clothianidin, dinotefuran, nitenpyram and acetamiprid) on 13 Anopheles gambiae nicotinic acetylcholine receptor (nAChR) subtypes produced by expression of combinations of the Agα1, Agα2, Agα3, Agα8 and Agß1 subunits in Xenopus laevis oocytes, the Drosophila melanogaster orthologues of which we have previously shown to be important in neonicotinoid actions. The presence of the Agα2 subunit reduces neonicotinoid affinity for the mosquito nAChRs, whereas the Agα3 subunit increases it. Crystal structures of the acetylcholine binding protein (AChBP), an established surrogate for the ligand-binding domain, with dinotefuran bound, shows a unique target site interaction through hydrogen bond formation and CH-N interaction at the tetrahydrofuran ring. This is of interest as dinotefuran is also under trial as the toxic element in baited traps. Multiple regression analyses show a correlation between the efficacy of neonicotinoids for the Agα1/Agα2/Agα8/Agß1 nAChR, their hydrophobicity and their rate of knockdown of adult female An. gambiae, providing new insights into neonicotinoid features important for malaria vector control.

Positron emission tomography with the glucose analog [F]-fluoro-2-deoxy-D-glucose for evaluating pelvic lymph node metastasis in uterine corpus cancer: comparison with CT and MRI findings.

OBJECTIVE: The aims of this study were to investigate the ability of positron emission tomography (PET) with the glucose analog [(18)F]-fluoro-2-deoxy-D-glucose (FDG) to detect pelvic lymph node metastasis of uterine corpus cancer and to perform a retrospective comparison with computed tomography (CT) and magnetic resonance imaging (MRI) findings. METHODS: Forty-six patients with uterine corpus cancer scheduled for surgery, including bilateral pelvic and/or para-aortic lymphadenectomy, were eligible for this study. CT and MRI of the pelvis and abdomen were performed in all patients within 2 weeks preceding whole-body FDG-PET. FDG-PET images were analyzed visually for objective assessment of regional tracer uptake. The sensitivity and specificity of each imaging modality for detecting pelvic lymph node metastasis were determined, respectively. RESULTS: Eleven (7 with myometrial invasion less than 1/2, 4 with myometrial invasion over 1/2) of the 46 patients (23.9%) were revealed to have pelvic lymph node metastasis. The sensitivity and specificity for detecting pelvic lymph node metastasis in patients with uterine corpus cancer by FDG-PET were 31.3% and 96.1% by lymph node region, respectively, and 36.4% and 91.4% by patient, respectively. No significant difference was noted among each imaging modality with sensitivity or specificity. Moreover, the sensitivity and specificity for detecting pelvic lymph node metastasis in 29 patients with endometrioid adenocarcinomas by FDG-PET were 28.6% and 96.1% by lymph node region, respectively, and 50% and 92% by patient, respectively. No significant difference was noted among each imaging modality in terms of sensitivity or specificity. Among 11 patients with pathologically positive pelvic lymph node metastasis, three out of four patients with myometrial invasion over 1/2 were diagnosed as pelvic lymph node metastasis positive by all diagnostic modalities, however, only one of seven patients with myometrial invasion less than 1/2 was diagnosed as pelvic lymph node metastasis positive by PDF-PET and CT. MRI could not detect pelvic lymph node metastasis in patients with myometrial invasion less than 1/2. CONCLUSIONS: We suggest that current imaging modalities including FDG-PET cannot change medical management of patients with uterine corpus cancer before surgery.

Does three-dimensional power Doppler ultrasound improve the diagnostic accuracy for the prediction of adnexal malignancy?

OBJECTIVE: The aim of the present study was to investigate the diagnostic accuracy of three-dimensional power Doppler ultrasound (3DPD) in the differentiation between benign and malignant adnexal masses and evaluate 3DPD for assessing malignancy in comparison with two-dimensional transvaginal gray-scale sonography (2DTVS), magnetic resonance imaging (MRI) and positron emission tomography (PET). SUBJECTS AND METHODS: Thirty-six patients with suspicious adnexal masses were included in this study. 2DTVS and 3DPD were performed preoperatively. MRI and PET examinations were also carried on within two weeks of initial sonography. All the results of diagnostic imaging techniques were evaluated separately. Final diagnosis was confirmed by the postoperative histopathology. The mature cystic teratomas and endometriomas with typical gray-scale sonographic appearance were excluded from the study. RESULTS: Of the 36 patients, 25 had a malignancy, 5 had a borderline tumor, and 6 had a benign mass. Sensitivity of 2DTVS, 3DPD, MRI and PET were 96.7%, 76.7%, 96.7% and 83.3%, respectively. The sensitivity of 2DTVS was as high as that of MRI, and both of them were significantly higher than those of 3DPD and PET, respectively. There were no significant differences both in specificity and accuracy among these 4 techniques. CONCLUSION: 3DPD did not improve the diagnostic accuracy for the prediction of malignancy in adnexal masses. 2DTVS may still remain an important modality for the prediction of adnexal malignancy.

A case of non-hodgkin's lymphoma of the ovary: usefulness of 18F-FDG PET for staging and assessment of the therapeutic response.

Primary ovarian lymphoma as the initial manifestation is rare. A 27-year-old woman presented to our hospital with the symptoms of lower abdominal fullness and pollakisuria. CT scan and MRI revealed bilateral ovarian tumors, which showed heterogeneous masses. 18F-FDG PET revealed strong uptake by the abdominal masses, and the maximum standardized uptake value (SUVmax) was 12.5. Abnormal uptake was not shown by other regions. An exploratory laparotomy was performed. Histological findings revealed diffuse large B-cell lymphoma. The clinical stage was IV according to the Ann Arbor system. International prognostic index (IPI) was 3 (high-intermediate risk). Chemotherapy was administered consisting of three courses of an R-CHOP regimen, and 18F-FDG PET and CT scan revealed no signs of involvement 3 months after initiation of the chemotherapy. 18F-FDG PET was a useful method for staging and assessment of the therapeutic response in primary ovarian lymphoma.

Deep inferior epigastric perforator (DIEP) flap for vulvar reconstruction after radical vulvectomy: a less invasive and simple procedure utilizing an abdominal incision wound.

For vulvar reconstruction following radical vulvectomy in a 71-year-old woman with a large vulvar cancer, we applied the deep inferior epigastric perforator flap (DIEP flap), a typical perforator flap, which could be performed by utilizing an abdominal incision wound without producing another surgical scar and had less donor site morbidity because of a minimal sacrifice of muscles. The surgical procedures were less invasive and simple, and morphologically and functionally satisfactory results were obtained: no recurrence of cancer, a well-preserved vulvar morphology with less donor site scarring, and no functional disturbance such as dysuria and abdominal hernia. We consider that the DIEP flap is the first choice for vulvar reconstruction following radical vulvectomy. Even in radical vulvectomy without an abdominal incision wound, the DIEP flap with an anatomically reliable vascular pedicle can be an effective option.

Laparoscopy-assisted intrapelvic sonography with a high-frequency, real-time miniature transducer to assess the ovary: a preliminary report.

OBJECTIVE: Our purpose was to evaluate the normal and pathologic internal textures of the ovary using laparoscopy-assisted intrapelvic sonography (LAIPS) with a specially developed 20-MHz flexible catheter-based high-resolution real-time miniature (2.4 mm in outer diameter) ultrasound transducer in patients with gynecologic disorders and infertile women. METHODS: 30 women (19 patients with gynecologic disorders and normal menstrual cycles (2 adenomyoses, 1 cervical cancer, 5 fibromyomas, 5 simple ovarian cysts, 1 endometriosis, 3 benign cystic teratomas, and 2 endometriomas), and 11 patients with infertility including 4 with polycystic ovarian syndrome, PCOS) were studied by intrapelvic sonography using a high-frequency real-time miniature transducer with pelvic saline effusion and laparoscopy. RESULTS: In the normal ovary in the mid-follicular phase, follicles were depicted more distinctly than with transvaginal sonography (TVS). In the late-follicular phase, cumulus oophorus formations were visualized in 6 of 9 patients (54.5%), but were not clear using TVS. In the luteal phase, the corpus luteum was noted in 9 of 12 patients (75%) by both TVS and LAIPS. In patients with PCOS, the thickened capsule of the ovary was distinguished clearly especially in the peripheral type, in which numerous small cysts were aligned in the subcapsular region of the ovary, whereas it could not be detected by TVS. In all 4 cases with PCOS (8 ovaries), the ovarian capsular thickness could be measured by means of LAIPS. In subjects with benign cystic teratoma, minimal high echoic lesions were depicted. In subjects with endometrioma, a diffuse coarse-granular internal texture was visualized. However, depiction of internal structures in large pathologic ovarian lesions was markedly limited because of the shallow scanning range of the high-frequency transducer. CONCLUSION: LAIPS with a high-frequency real-time miniature transducer might be a useful diagnostic modality to evaluate the normal physiologic textures of the ovary, as well as those with PCOS.

Antenatal three-dimensional sonographic features of early amnion rupture sequence.

BACKGROUND: Early amnion rupture sequence is rare, and its antenatal three-dimensional sonographic features have not been reported. CASE: A 24-year-old japanese woman, gravida 1, para 0, was referred to our sonography clinic during her 16th week of gestation because of multiple fetal anomalies. Three-dimensional sonography clearly showed scalp adhesion, skull defect, abdominal wall disruption, amputation of the right hand, kyphoscoliosis, and clubfeet. Delivery was induced at 17 weeks of gestation. Autopsy showed a 166 gram male fetus and confirmed the prenatal diagnosis of early amnion rupture sequence. CONCLUSION: Three-dimensional sonography provides further information for sonographers. This includes unique identification of the displayed anatomic plane, realistic and reliable depiction of multiple fetal anomalies, and visualization of complex fetal anomalies.

Optic nerve arteriovenous malformation causing optic apoplexy: case report.

OBJECTIVE AND IMPORTANCE: Vascular malformations in the optic pathway are rare. Only one case of pathologically confirmed arteriovenous malformation (AVM) of the optic nerve has been reported previously. We document the case of a patient with an optic nerve AVM who presented with optic apoplexy that was diagnosed with the use of magnetic resonance imaging. CLINICAL PRESENTATION: A 15-year-old girl developed left visual disturbance of sudden onset while playing badminton. A magnetic resonance imaging scan disclosed left optic nerve swelling and intraoptical hemorrhage, although an angiogram did not reveal abnormal vessels. INTERVENTION: The patient underwent total removal of the hematoma and tangles of the abnormal vessels in the left optic nerve, which was diagnosed pathologically as an AVM. The patient recovered visual acuity, but the left visual field defect remained unchanged. CONCLUSION: Along with cavernous malformations and optic gliomas, AVMs can be a rare cause of optic nerve apoplexy. T2-weighted magnetic resonance imaging is useful in rendering the diagnosis of an optic nerve AVM, observed as a mass lesion consisting of serpiginous, tangled, low-intensity bands. Early surgical treatment is recommended to obtain a rapid recovery.

Nuchal translucency thickness and fetal cardiac flow velocity in normal fetuses at 11-13 weeks of gestation.

OBJECTIVE: To investigate the relationship between nuchal translucency thickness and cardiac flow velocity in normal fetuses at 11-13 weeks of gestation. SUBJECTS AND METHODS: Eighteen normal pregnancies were prospectively studied with transvaginal sonography and pulsed and color Doppler ultrasound. Flow velocities at the fetal atrioventricular valves (mitral and tricuspid valve) and outflow tract levels (ascending aorta and pulmonary artery), and at the descending aorta were recorded. Nuchal translucency thickness was also measured. RESULTS: Mitral peak velocity during early diastolic filling correlated with gestational age. Mitral peak velocities during early diastolic filling and atrial contraction, tricuspid peak velocity during early diastolic filling, ascending aorta peak velocity, and pulmonary artery peak velocity correlated well with nuchal translucency thickness. There was an inverse correlation between umbilical artery pulsatility index and gestational age. CONCLUSIONS: These results suggest that the increase of nuchal translucency thickness in normal fetuses at 11-13 weeks of gestation may be the consequence of changes in fetal cardiac functions.

Survivin expression and its correlation with cell proliferation and prognosis in epithelial ovarian tumors.

Survivin is a new member of the inhibitors of apoptosis proteins (IAP) family, selectively overexpressed in common human cancers but not in normal adult tissues, and associated with aggressiveness of the disease and unfavorable outcomes. Recent study also found that survivin expression is associated with cell proliferation. In order to gain insight into the role of survivin in ovarian tumors, we investigated the expression of survivin in a group of epithelial ovarian tumors, and examined the relationship of its expression with cell proliferation and clinical outcome. Immunohistochemical analysis was performed in 103 cases of epithelial ovarian tumors. Twenty-six of the 103 cases were evaluated by Western blot analysis. The results showed that survivin overexpression was detected in 21.2% (7 of 33) of benign tumors, 47.8% (11 of 23) of borderline tumors, and 51.1% (24 of 47) of ovarian carcinomas. The positive ratio was significantly higher in malignant or borderline tumors than in benign tumors, and the overexpression of survivin was significantly correlated with the size of residual disease. A positive correlation between survivin expression and proliferative activity of tumor cell measured by PCNA index was found. Kaplan-Meier analysis demonstrated that the patients with survivin overexpression have a short overall survival. These findings suggest that survivin overexpression may play a pivotal role in the progression of ovarian tumors and may provide an important prognostic implication for epithelial ovarian carcinomas.

Reciprocal effects of tamoxifen on hormonal cytology in postmenopausal women.

OBJECTIVE: To evaluate the estrogenic effect of tamoxifen (TAM) therapy in postmenopausal women. STUDY DESIGN: The subjects were 26 postmenopausal women. The maturation index (MI), maturation value (MV) and karyopyknotic index (KPI) were evaluated based on hormonal cytology. Endometrial cytologic examinations and transvaginal ultrasonography were also performed. RESULTS: Of the 26 patients, 16 had low estrogenic activity from the viewpoint of hormonal cytology before TAM administration. During administration, their mean MV rose significantly, from 25.8 +/- 17.7 to 68.8 +/- 13.2, (mean +/- SD) and their mean KPI rose from 9.0 +/- 8.3 to 47.1 +/- 23.1. In contrast, among the 10 patients with high estrogenic activity, mean MV and KPI decreased from 62.9 +/- 8.4 and 27.2 +/- 16.9 to 58.4 +/- 7.7 and 17.7 +/- 16.1, respectively, with TAM administration. Mean endometrial thickness increased more significantly with TAM administration in the low estrogenic activity group than in the high estrogenic activity group. CONCLUSION: TAM had a reciprocal effect; no additional estrogenic effect was seen in patients with high estrogenic activity. Conversely, an estrogenic effect was seen in those with low estrogenic activity. An individualized gynecologic evaluation based on hormonal cytology is useful in selecting patients who will be more susceptible to TAM-induced endometrial abnormality.

Three-dimensional sonographic features of nuchal edema.

OBJECTIVE: To describe the three-dimensional (3D) sonographic features of nuchal edema in the early second trimester of pregnancy. METHODS: From 16 to 22 weeks of gestation 5 cases with nuchal edema were studied using transabdominal 3D sonography. RESULTS: Nuchal edema could be easily imaged with both two-dimensional and 3D sonography; however, visualization of the continuity and curvature of structures was more easily accomplished with 3D sonography. Before 20 weeks of gestation, the skin has a transparent structure, so the bony structures are clearly identified. 3D sonography allowed visualization of nuchal edema in all three dimensions at the same time, providing an improved overview and a more clearly defined demonstration of the adjusted anatomical planes. CONCLUSION: These results suggest that 3D sonography provides a novel means of visualizing nuchal edema in utero.

Expression of p57kip2 and its clinical relevance in epithelial ovarian tumors.

BACKGROUND: The aim of this study was to elucidate the expression of p57kip2 in a series of benign, borderline and malignant ovarian tumors, to evaluate its relationship with other G1 regulators of the cell cycle and to determine whether p57kip2 expression is associated with progression and prognosis of epithelial ovarian tumors. MATERIALS AND METHODS: Immunohistochemical analysis was performed in 103 cases of epithelial ovarian tumors. Twenty-six of the 103 cases were evaluated by Western blot analysis. RESULTS: The study demonstrated that high p57kip2 expression was detected in 63.6% (21 out of 33) of benign tumors, 52.2% (12 out of 23) of borderline tumors and 40.4% (19 out of 47) of ovarian carcinomas. The positive ratio of p57kip2 expression was decreased from benign to borderline to malignant tumors, whilst statistical significance was observed between benign and malignant tumors. Low p57kip2 expression was significantly associated with high tumor grades, advanced clinical stages and cyclin E overexpression. Kaplan-Meier analysis demonstrated that the patients with low p57kip2 expression had a short overall survival. When the combined phenotype of p57kip2 and p27kip1 was analyzed, the patients with both p57kip2 and p27kip1 low expression had a lower overall survival rate. CONCLUSION: These findings suggest that decreased p57kip2 expression may play a pivotal role in the progression of ovarian tumors and provide an important prognostic implication for epithelial ovarian carcinomas.