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ABSTRACT: The purpose of the present study was to determine the incidence of increased levels of D-dimer and associated factors in preoperative patients with gynecological cancer. Furthermore, we determined the incidence and risk factors associated with preoperative venous thromboembolism (VTE). Overall, 456 patients with invasive gynecological cancer scheduled to undergo surgery were recruited. Preoperative plasma D-dimer levels were measured and patients whose plasma D-dimer concentration exceeded the pre-set cut-off value underwent computed tomography scanning. The incidence of elevated D-dimer and VTE was identified as significantly higher in patients with ovarian cancer. Multivariate analysis revealed that advanced age, low hemoglobin levels and elevated C-reactive protein (CRP) levels were independent factors for preoperative elevations in plasma D-dimer levels. Advanced age was an independent risk factor for preoperative VTE. Massive ascites and the presence of co-morbidities were independent risk factors for preoperative VTE in ovarian cancer. Advanced age and stage were independent risk factors for preoperative VTE in endometrial cancer. Advanced age was an independent risk factor for preoperative VTE in cervical cancer. Plasma D-dimer levels and the incidence of preoperative VTE were higher in patients with ovarian cancer compared with those with other gynecological cancers. Advanced age, low hemoglobin levels and elevated CRP levels were significant factors associated with elevated plasma D-dimer levels and age was an independent risk factor for preoperative VTE in gynecological cancer.
Oncology letters 01/2013; 5(1):299-304. · 0.11 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the changes in plasma soluble fibrin (SF) levels over time in gynecologic cancer patients following surgery. Furthermore, we examined the duration of the coagulation stage and determined a suitable duration for which thromboprophylaxis with anticoagulant agents should be administered. We retrospectively studied 311 patients with invasive gynecologic cancer who underwent surgery at Okayama University Hospital, Japan. The plasma SF levels were measured serially prior to the operation and on postoperative days 0, 1, 3, 5, 7, 10, 14, 21 and 28. The plasma SF levels increased rapidly, peaked on postoperative day 1 and then decreased. The SF levels of patients with venous thromboembolism (VTE) were significantly different from those of VTE-negative patients on postoperative days 0-10. The SF levels on each day did not significantly differ between patients treated with chemical anticoagulants and those treated mechanically. The plasma SF levels were elevated (≥7.0 μg/ml) in 159 of the 311 patients (51.1%) on one of the days when these levels were measured. Among the patients with elevated plasma SF levels, 110 patients (69.2%) peaked on days 0-3 and only 9 patients (5.7%) peaked on days 21-28. Although only 1 of the 14 patients (7.1%) who showed peak levels on day 14 had undergone chemotherapy following surgery, 8 of the 9 patients (88.9%) whose levels peaked on days 21-28 had undergone chemotherapy following surgery (P= 0.0002). In conclusion, the plasma SF levels increased rapidly, peaked on postoperative day 1 and then decreased. These levels peaked within 14 days of surgery in most cases. Therefore, chemical thromboprophylaxis may be administered for at least up to 14 days following surgery.
Oncology letters 11/2012; 4(5):1122-1124. · 0.11 Impact Factor
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ABSTRACT: PURPOSE: The purpose of this study was to investigate the prognostic value of the minimum apparent diffusion coefficient (ADCmin) derived from diffusion-weighted MR imaging and of the maximum standardized uptake value (SUVmax) derived from PET/CT imaging of the primary tumour in patients with endometrial cancer. METHODS: SUVmax reflects the highest tumour metabolism rate and ADCmin reflects the highest cellularity, and both parameters have been used for tumour grading and prediction of prognosis. The correlations between prognosis and SUVmax and ADCmin of the primary tumour were determined in 131 patients with endometrial cancer. The patients were divided into groups based on ADCmin and SUVmax cut-off values to predict recurrence and survival, which were derived from receiver operating characteristic curves. Disease-free survival (DFS) and overall survival (OS) of the groups were analysed using the Kaplan-Meier method, and differences between survival curves were evaluated using the log-rank test. RESULTS: The median DFS and OS times of all patients were 19.2 and 20.5 months (follow-up periods 1-70 months for both DFS and OS), respectively. Patients with high SUVmax had significantly lower DFS (P < 0.0001) and OS (P = 0.0092) than patients with low SUVmax. Multivariate analysis showed that high SUVmax was an independent prognostic factor for both DFS (P = 0.0161) and OS (P = 0.0232). CONCLUSION: The SUVmax of the primary tumour derived from PET/CT imaging could be an important prognostic indicator of recurrence and survival in patients with endometrial cancer.
European Journal of Nuclear Medicine 09/2012; · 4.53 Impact Factor
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ABSTRACT: OBJECTIVE: The purpose of this study is to investigate the correlation of the max, mean and minimal apparent diffusion coefficient values (ADCmax, ADCmean, and ADCmin) on diffusion weighted imaging findings with prognostic factors in cervical cancer. METHODS: A cohort of 80 cervical cancer patients underwent pelvic magnetic resonance imaging (MRI) within the 2 to 4weeks prior to radical hysterectomy. The optimal cutoff value for segregating disease free survival (DFS) was determined by receiver operating characteristic (ROC) curve analysis. We used ROC curve analyses to evaluate whether preoperative ADCmax, ADCmean, ADCmin on MRI predicted the risk group of recurrence. RESULTS: Analyses of ROC curves identified an optimal The ROC curves identified an optimal ADCmax, ADCmean, and ADCmin cutoff values of 1.122×10(-3)mm(2)/s, 0.852×10(-3)mm(2)/s, 0.670×10(-3)mm(2)/s and for predicting the recurrence of cervical cancer. The patients categorized into the lower ADCmean or ADCmin groups showed the shorter disease free survivals compared with the higher ADCmean or ADCmin, respectively (P<0.0001 or P=0.0210). In particular, the ADCmean of primary cervical cancer was an independent predictive factor for disease recurrence by a multivariate analysis (P=0.0133). CONCLUSIONS: The ADCmean of primary cervical cancer calculated by MRI could be an important factor for identifying patients with a risk of disease recurrence.
Gynecologic Oncology 08/2012; · 3.89 Impact Factor
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ABSTRACT: Aim: To evaluate whether pregnant women with chronic kidney disease (CKD) adapt poorly to increases in renal blood flow. This can exacerbate renal function and impair perinatal outcome, as there is a major interplay between CKD and preeclampsia (PE). Methods: We analyzed the outcomes of 90 pregnant women with preexisting CKD. The estimated glomerular filtration rate (eGFR) was measured along with the levels of angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor, which might act in the pathophysiology of PE. Results: In pregnancies with CKD, PE and preterm delivery were increased and the increased blood pressure worsened the perinatal outcomes much more than the increased proteinuria. All pregnancies with severe renal insufficiency were delivered preterm because of impaired renal function. The eGFR was correlated significantly with 24-hour creatinine clearance (r = 0.830). Significant differences in sFlt-1 and placental growth factor levels were found between severe PE without any complications and severe superimposed PE (p < 0.05), and between women with and without declining renal function in superimposed PE (p < 0.01). Conclusion: Pregnancies with CKD have a high risk of obstetrical complications. The eGFR might serve for evaluating renal function during pregnancy. Angiogenic factors might be potential markers for a differential diagnosis between PE and worsening renal function.
Gynecologic and Obstetric Investigation 07/2012; · 1.28 Impact Factor
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ABSTRACT: Fontan operation is performed to provide palliation for patients with many forms of highly complex congenital heart disease that cannot support a biventricular circulation. Increasing numbers of women who have undergone these connections in childhood are now reaching their childbearing years, and some are becoming pregnant. The low flow and fixed cardiac output of a Fontan circulation poses a number of problems during pregnancy. Here, we report two cases of pregnancy and delivery with Fontan circulation. Case 1, who underwent Fontan procedure for congenital pulmonary atresia with intact vertical septum at age 7, delivered a male infant weighing 1073 g by cesarean section at 28(6/7) weeks due to massive genital bleeding. Case 2 underwent Fontan procedure for double inlet left ventricle and delivered by vacuum extraction a male infant weighing 2142 g, while monitoring central venous pressure at 37(5/7) weeks. The former had ascites and dose of diuretic had to be added at early pregnancy, and the latter had no adverse cardiac and obstetric events. These cases suggest that patients after adequate Fontan palliation could complete pregnancy without long-term cardiac sequelae, but might be complicated with cardiac or obstetrical events. Intensive care should be required with specialists, including a neonatologist, anesthesiologist and cardiologist. We have added a literature review of pregnancy with Fontan circulation, referring to previous reports.
Journal of Obstetrics and Gynaecology Research 06/2012; · 0.94 Impact Factor
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ABSTRACT: The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance even during pregnancy, while exposure to a high-fat diet (HFD) in utero in mice can induce a type 2 diabetes phenotype that can be transmitted to the progeny. Therefore, we examined whether treatment with a CAR ligand during pregnancy could prevent hypertension, insulin resistance, and hyperlipidemia in the offspring from HFD-induced obese pregnant mice (OH mice). We employed four groups of offspring from HFD-fed and control diet-fed pregnant mice with or without treatment with a CAR ligand. Treatment with a CAR ligand during pregnancy improved glucose tolerance and the levels of triglyceride and adipocytokine and restored the changes induced by HFD with amelioration of hypertension in the adult OH mice. This treatment also increased adiponectin mRNA expression, suppressed leptin expression in adipose tissues of OH mice, and abolished the effect of HFD on the epigenetic modifications of the genes encoding adiponectin and leptin in the offspring during immaturity and adulthood. Our data suggest that CAR might be a potential therapeutic target to prevent metabolic syndrome in adulthood of offspring exposed to an HFD in utero.
AJP Endocrinology and Metabolism 05/2012; 303(2):E293-300. · 4.75 Impact Factor
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ABSTRACT: BACKGROUND: Extracellular matrix metalloproteinase inducer (Emmprin/CD147) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. METHODS: Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. In addition, the biological functions and inhibitory effects of an emmprin knockdown were investigated in HEC-50B and KLE endometrial cancer cell lines. RESULTS: The levels of emmprin expression were significantly increased in the endometrial cancer specimens compared with the normal endometrium and endometrial hyperplasia specimens (p<0.05). The disease-free survival (DFS) and overall survival (OS) rates of patients with high emmprin expression were significantly higher than those of patients with low emmprin expression (DFS: p<0.001; OS: p<0.001). Emmprin knockdown by the siRNA led to cell proliferation, migration and invasion through TGF-beta, EGF, NF-B, VEGF, MMP-2, and MMP-9 expression, which in turn resulted in increased levels of E-cadherin and reduced levels of Vimentin and Snail in endometrial cancer. CONCLUSIONS: The present findings suggest that low emmprin expression might be a predictor of favorable prognosis in endometrial cancer patients, and that emmprin may represent a potential therapeutic target for endometrial cancer.
BMC Cancer 05/2012; 12(1):191. · 3.01 Impact Factor
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ABSTRACT: We generated novel truncated insulin-like growth factor I receptors (IGF-IRs) designated as 126/STOP, 223/STOP and 325/STOP in order to establish shorter soluble IGF-IRs than previously reported 486/STOP without abrogating the same antitumor effects. Stable transfection of 223/STOP and 325/STOP, but not 126/STOP caused inhibition of anchorage-independent growth of CaOV-3 ovarian cancer cells in vitro. This antitumor effect was reproduced when we used recombinant proteins of these constructs, suggesting a bystander effect of these shorter truncated IGF-IRs. Tumorigenesis in vivo of CaOV-3 cells tranfected with 223/STOP or 325/STOP was strictly inhibited, and inoculation of these cells in nude mice caused massive apoptosis exclusively in vivo. Phosphorylations of IGF-IR and Akt, but not Erk were attenuated in 223/STOP- or 325/STOP-transfected CaOV-3 cells, and downregulations of IGF-IR and Akt phosphorylation seemed to play at least a partial role in the anti-tumor effect of these novel truncated IGF-IRs. Since 223/STOP and 325/STOP are smaller in size than previously reported 486/STOP, and they retain the same antitumor effects, they could be good candidates for clinical application in the future.
Cancer biology & therapy 05/2012; 13(7):559-66. · 2.64 Impact Factor
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Sharula,
Chebib Chekir,
Yayoi Emi,
Fujimi Arai,
Yukako Kikuchi,
Aiko Sasaki,
Miwa Matsuda,
Keiko Shimizu,
Kazuhiro Tabuchi,
Yasuhiko Kamada, Yuji Hiramatsu,
Mikiya Nakatsuka
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ABSTRACT: Male-to-female (MTF) transsexuals are treated with estrogen with and without progestin through a variety of routes. The aim of this study is to evaluate the arterial stiffness in MTF transsexuals undergoing hormonal treatment.
We evaluated the arterial stiffness in 156 MTF transsexuals (22 untreated and 129 treated with estrogen only or plus progestin) using a volume-plethysmographic apparatus equipped with a multi-element applanation tonometry sensor.
MTF transsexuals treated with parenteral estrogen were significantly older than untreated MTF transsexuals. Hematocrit, uric acid and activated partial thromboplastin time in treated MTF transsexuals were significantly lower than in untreated MTF transsexuals. The level of high-density lipoprotein cholesterol in MTF transsexuals treated with oral estrogen was significantly higher than in untreated MTF transsexuals or those treated with parenteral estrogen with and without progestin. The systolic blood pressure in MTF transsexuals treated with estrogen only is significantly lower than that in untreated MTF transsexuals. The brachial-ankle pulse wave velocity was significantly decreased in MTF transsexuals treated with estrogen compared to that in untreated MTF transsexuals or in those treated with estrogen plus progestin. The carotid augmentation index in MTF transsexuals treated with oral estrogen was significantly lower than that in MTF transsexuals treated with parenteral estrogen or oral estrogen plus progestin.
Estrogen treatment is likely to have some beneficial effects on lipid metabolism and vascular function in MTF transsexuals; however, progestin administered with estrogen may have adverse effects on arterial stiffness.
Journal of Obstetrics and Gynaecology Research 04/2012; 38(6):932-40. · 0.94 Impact Factor
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ABSTRACT: Preeclampsia may be due to an excess of circulating anti-angiogenic growth factors derived from the placenta, but metabolic syndrome-like disorders may also set off a cascade of placental and systemic inflammation and oxidative stress. We present a case of severe superimposed preeclampsia with obesity, diabetes and a mild imbalance of angiogenic factors, in which diet therapy ameliorated the preeclamptic signs while improving the adiponectin level. A 41-year-old pregnant woman with obesity and diabetes was referred to our hospital because of severe proteinuria and hypertension at 22 weeks of gestation. After administration of insulin and hydralazine with diet therapy, her hypertension and proteinuria were ameliorated with a 15-kg weight loss. Her adiponectin level was low and her leptin level was high, but her angiogenic factor levels were within the normal ranges for pregnant women at admission. The diet therapy ameliorated her hypertension and proteinuria while improving her adiponectin level as she achieved weight loss. This case suggests that diet therapy for obese preeclampsia patients with a mild imbalance of anti-and pro-angiogenic factors may play an important role in managing preeclampsia. Measurements of maternal adipocytokines and angiogenic factors may be important to distinguish the main cause of preeclampsia, i.e., poor placentation or maternal constitutional factors, for managing preeclampsia in patients with obesity.
Acta medica Okayama 04/2012; 66(2):171-5. · 0.84 Impact Factor
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ABSTRACT: The links between obesity in parents and their offspring and the role of genes and a shared environment are not completely understood. Adipocytokines such as leptin and adiponectin play important roles in glucose and lipid metabolism. Therefore, we examined whether the offspring from dams exposed to a high-fat diet during pregnancy (OH mice) exhibited hypertension, insulin resistance, and hyperlipidemia along with epigenetic changes in the expression of adipocytokine genes. OH mice were significantly heavier than the offspring of dams exposed to a control diet during pregnancy (OC mice) from 14 wk of age after an increased caloric intake from 8 wk. OH mice exhibited higher blood pressure and worse glucose tolerance than the OC mice at 24 wk. Total triglyceride and leptin levels were significantly higher and the adiponectin level was significantly lower in OH compared with OC mice at 12 wk of age. This was associated with changes in leptin and adiponectin expression in white adipose tissue. There were lower acetylation and higher methylation levels of histone H3 at lysine 9 of the promoter of adiponectin in adipose tissues of OH mice at 2 wk of age as well as at 12 and 24 wk of age compared with OC mice. In contrast, methylation of histone 4 at lysine 20 in the leptin promoter was significantly higher in OH compared with OC mice. Thus, exposure to a high-fat diet in utero might cause a metabolic syndrome-like phenomenon through epigenetic modifications of adipocytokine, adiponectin, and leptin gene expression.
Endocrinology 03/2012; 153(6):2823-30. · 4.46 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate prognostic factors for epithelial ovarian cancer. We found that the pretreatment values of maximum standardized uptake (SUVmax) of the primary tumor by positron emission tomography/computed tomography (PET/CT), tumor marker CA125 and C-reactive protein (CRP) were correlated with clinical characteristics and prognosis for such patients. The clinical parameters and prognoses and their correlations with SUVmax of primary tumor, CA125 and CRP were examined for 51 patients with primary ovarian cancer. The SUVmax of the primary tumor had a statistically significant association with stage (p = 0.010) and histology (p = 0.001). CA125 was significant associated with stage (p = 0.011), histology (p = 0.005) and lymph node metastasis (p = 0.025). CRP was also significantly associated with stage (p = 0.049). Disease-free survival rates of patients exhibiting a high SUVmax, CA125 and CRP were significantly lower than those exhibiting a low SUVmax, CA125 and CRP levels (p = 0.008, 0.034, and 0.037, respectively). Furthermore, overall survival rates of patients exhibiting a high SUVmax were significantly lower than those exhibiting a low SUVmax (p = 0.049).The high SUVmax of primary tumor is an important factor for identifying ovarian cancer patients with a predictor for poor prognosis.
Acta medica Okayama 02/2012; 66(1):53-60. · 0.84 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate whether preoperative measurements of the minimum apparent diffusion coefficient (ADCmin) on magnetic resonance imaging (MRI) and the tumor marker CA125 are correlated with the clinical characteristics and prognosis of patients with endometrial cancer.
The distribution of cases that scored positive for each of the biological parameters examined and the correlations with the ADCmin of the primary tumor and the serum tumor marker CA125 were examined for 111 patients with preoperative assessment of primary endometrial cancer.
There were significant correlations between the ADCmin of the primary tumor and the FIGO stage (P=0.001), depth of myometrial invasion (P<0.001), cervical involvement (P=0.003), lymph node metastasis (P=0.027), ovarian metastasis (P<0.001), peritoneal cytology (P=0.027) and tumor maximum size (P<0.001). The disease-free survival (DFS) rate of patients with high serum CA125 was significantly lower than that of patients with low serum CA125 (P=0.0395). The DFS rate of patients with a low ADCmin of the primary tumor was significantly lower than that of patients with a high ADCmin of the primary tumor (P<0.001). In particular, the ADCmin of the primary tumor was an independent factor for disease recurrence in a multivariate analysis (P=0.019).
The present findings indicate that a low preoperative ADCmin of the primary tumor is an important predictive factor for identifying endometrial cancer patients with a risk of disease recurrence.
Gynecologic Oncology 02/2012; 124(2):335-9. · 3.89 Impact Factor
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ABSTRACT: Elevated maternal serum uric acid is associated with small-for-gestational-age (SGA) fetuses. We investigated whether uric acid concentrations in normotensive pregnant women are correlated with fetal growth and related to kidney function.
We carried out a case-control study using 40 patients who delivered SGA fetuses identified from the perinatal database and 80 patients who delivered appropriate-for-gestational-age (AGA) fetuses as the controls at Okayama University Hospital. Blood pressure, serum uric acid and creatinine level were measured in the patients' third trimester.
Maternal serum uric acid (p = 0.0003) and creatinine (p < 0.0001) concentrations, as well as systolic and diastolic blood pressures (p =0.014 and 0.037, respectively), were significantly increased in the SGA group. There was a strong negative correlation between serum uric acid levels and birth weights (r = -0.59; p = 0.006) and a significant positive correlation between maternal serum uric acid and creatinine levels (r = 0.43; p < 0.05) in cases of severe SGA (<5th percentile). Multiple linear regression analysis indicated that uric acid is an independent risk factor for SGA.
Increasing maternal uric acid concentrations were associated with slightly impaired kidney function and SGA in normotensive pregnant women.
Gynecologic and Obstetric Investigation 01/2012; 73(2):162-7. · 1.28 Impact Factor
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ABSTRACT: Adiponectin was reported recently to have roles in the pathophysiology of preeclampsia. Moreover, elevation of adiponectin and brain natriuretic peptide (BNP) has been observed in preeclampsia. We examined the possible links between adiponectin and BNP in the pathophysiology of preeclampsia. We performed a cross-sectional study in 56 preeclampsia patients and 56 controls matched for gestational age and body mass index. The BNP, leptin, and adiponectin levels were measured by ELISA, and their mRNA expressions were evaluated in omental adipose tissue by real-time PCR. The effects of BNP on adiponectin and leptin mRNA expression and secretion were investigated in primary cultures of adipocytes from obese and normal-weight women. The BNP, adiponectin, and leptin levels were significantly higher in preeclampsia patients compared with controls. The adiponectin level was increased significantly in normal-weight preeclampsia patients compared with overweight preeclampsia patients. Adiponectin mRNA expression was increased significantly in adipose tissues of preeclampsia patients compared with controls and was also increased significantly in normal-weight preeclampsia patients compared with overweight preeclampsia patients, whereas leptin was not. BNP and adiponectin showed significant positive correlations in both normal-weight and overweight preeclampsia patients. BNP had a significantly weaker effect on adiponectin in overweight compared with normal-weight preeclampsia patients. Moreover, BNP had a weaker effect on adiponectin production in adipocytes from overweight women compared with adipocytes from normal-weight women using primary culture of human adipocytes. These data suggested that BNP may play a role in hyperadiponectinemia of preeclampsia patients. The weaker effect of BNP on adiponectin production may participate in the pathophysiology of overweight preeclampsia patients.
AJP Endocrinology and Metabolism 01/2012; 302(6):E687-93. · 4.75 Impact Factor
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ABSTRACT: Introduction. The objective is to report a case of Cornelia de Lange syndrome (CdLS) diagnosed by detailed observations using three-dimensional sonography. Case Report. A 33-year-old healthy multipara was referred to our hospital at 34-week gestation after severe fetal growth restriction, congenital heart anomaly, and antebrachium abnormality were diagnosed during the third trimester. Further sonography diagnosis on cardiac abnormalities diagnosed the existence of ventricular septal defect in the outflow tract, atrioventricularis communis, and truncus arteriosus communis where the pulmonary artery branched from the common arterial trunk. As for abnormalities of the forearms, ectrodactylia and monodactylism were suspected and the abnormalities were observed sterically by using three-dimensional sonography. A 1986 g (1.07 percentile) male newborn was delivered by assisted breech extraction at 37-week gestation. After birth, from characteristic facies including bushy eyebrow, broad nasal bridge, micrognathia, and abnormalities of the forearms (ectrodactylia and monodactylism), the case was diagnosed with CdLS. Conclusion. Through detailed observation including abnormalities of fingers, we could exemplify this very rare disease as an antenatal diagnoses for fetal growth retardation.
Case reports in obstetrics and gynecology. 01/2012; 2012:568351.
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ABSTRACT: The objectives of this study were to determine if measurements of the maximum standardized uptake value (SUVmax) by positron emission tomography/computed tomography and minimum apparent diffusion coefficient (ADCmin) by magnetic resonance imaging are correlated with the clinical characteristics and prognosis of primary cervical cancer.
The correlations between biological parameters and prognosis and SUVmax and ADCmin of the primary tumour were determined in 66 patients with cervical cancer before radiotherapy or concurrent chemoradiotherapy.
There were significant correlations between SUVmax of the primary tumour and FIGO stage (p = 0.036), tumour maximum size (p = 0.018) and pelvic lymph node metastasis (p = 0.044). The median durations of disease-free survival (DFS) and overall survival (OS) were 16.1 and 19.2 months, respectively. The DFS and OS of patients exhibiting high SUVmax of the primary tumour were significantly lower than those of patients exhibiting low SUVmax of the primary tumour (p = 0.0171 and p = 0.0367). The OS of patients exhibiting low ADCmin of the primary tumour was significantly lower than that of patients exhibiting high ADCmin of the primary tumour (p = 0.0376). The DFS and OS of patients exhibiting high SUVmax together with low ADCmin of the primary tumour were significantly lower (p = 0.003 and p = 0.001). Multivariate analyses showed that high SUVmax together with low ADCmin of the primary tumour was an independent prognostic factor for both DFS (p = 0.0030) and OS (p = 0.0036).
High SUVmax together with low ADCmin of the primary tumour is an important predictive factor for identifying patients with cervical cancer who have a poor prognosis.
European Journal of Nuclear Medicine 11/2011; 39(2):283-90. · 4.53 Impact Factor
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ABSTRACT: Normal pregnancy is characterized by insulin resistance, which contributes to the development of gestational diabetes mellitus and preeclampsia by incompletely understood mechanisms. The constitutive androstane receptor (CAR) may participate in insulin resistance in pregnancy, and sex steroids, estradiol (E(2)) and progesterone, may also be involved. We applied glucose and insulin tolerance tests and measured the expression of gluconeogenic and lipogenic genes in the livers of oophorectomized mice treated with E(2) and progesterone with or without CAR ligands. We also investigated how E(2) and progesterone affected CAR-mediated signaling and the activity of transcription factors in gluconeogenesis in vitro. Mice with the concentrations of E(2) and progesterone within normal physiological range during pregnancy exhibited increased insulin resistance along with increased expression of gluconeogenic and lipogenic genes, and CAR activation rescued the abnormal glucose metabolism. In HepG2 cells, CAR ligands suppressed the gluconeogenic and lipogenic gene expression in the presence of E(2) and/or progesterone. DNA affinity immunoblotting and chromatin immunoprecipitation assay revealed that CAR ligand enhanced the recruitment of the gluconeogenic transcription factors, forkhead box O1 (FOXO1) and hepatocyte nuclear factor 4α (HNF4α), but sex steroids suppressed these recruitments on the CAR responsive element. Moreover, CAR ligand suppressed the recruitment of FOXO1 and HNF4α on their responsive element in gluconeogenic gene promoters and E(2) and progesterone augmented these recruitments on their responsive element. Taken together, these findings suggest that the activation of CAR-mediated signaling may ameliorate insulin resistance under relatively high concentrations of E(2) and progesterone, which were compatible with pregnancy via decreased activities of transcription factors in gluconeogenesis in combination with CAR.
Journal of Molecular Endocrinology 07/2011; 47(2):229-39. · 3.48 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate if preoperative measurements of the maximum standardized uptake valve (SUVmax) on positron emission tomography/computed tomography (PET/CT) and tumor marker CA125 are correlated with clinical characteristics and prognosis in patients with endometrial cancer.
The distribution of cases that scored positive for each of the biological parameters examined and the correlations with the SUVmax of the primary tumor and the serum tumor marker CA125 were examined for 106 patients with preoperative assessment of primary endometrial cancer.
There were significant correlations between the SUVmax of the primary tumor and the FIGO stage (P=0.030), histology (P=0.025), depth of myometrial invasion (P=0.031) and tumor maximum size (P<0.001). The serum CA125 level was significantly associated with the FIGO stage (P=0.050). The disease-free survival (DFS) and overall survival (OS) rates of patients exhibiting a high SUVmax of the primary tumor were significantly lower than those of patients exhibiting a low SUVmax of the primary tumor (P=0.049, and P=0.039, respectively). Furthermore, the DFS and OS rates of patients exhibiting a high SUVmax of the primary tumor were significantly lower than those of patients exhibiting a low SUVmax of the primary tumor at advanced stages (stages III-IV) (P=0.032 and P=0.023, respectively). In particular, the SUVmax of the primary tumor was an independent prognostic factor for OS by a multivariate analysis (P=0.025).
The present findings indicate that for patients with endometrial cancer, a high preoperative SUVmax of the primary tumor is an important predictive factor for identifying endometrial cancer patients with a poor prognosis.
Gynecologic Oncology 07/2011; 123(1):82-7. · 3.89 Impact Factor