Delivery after an obstetric anal sphincter tear.

PURPOSE: The present study aimed to assess the risk of obstetric anal sphincter injuries (OASIS) of a subsequent delivery after the previous OASIS in countries with low (Finland) and high rates (Norway and Sweden) of OASIS. METHODS: This population-based case-control study included women who experienced OASIS 1997-2002. 26,598 women with OASIS were included from countries with low (Finland) and high (Norway and Sweden) OASIS incidences. Each case was matched with one background-adjusted control without OASIS. A follow-up data, including all subsequent deliveries between 1998 and 2011 were then collected. Statistics significances were calculated using chi-square test, test for relative proportions and Students t test, where appropriate. RESULTS: OASIS in the first birth was associated with increased recurrences in subsequent births, 6.9% vs. 1.7% in Norway (p < 0.001); 4.5% vs. 0.7 (p < 0.001) in Sweden; and 2.1% vs. 0.8% in Finland (p = 0.038). In Norway, more than two deliveries occurred in 4.8% of cases and 6.2% of controls (p = 0.001), 4.2% vs. 5.1% in Sweden (p < 0.001), and 5.7% vs. 6.3% in Finland (p = 0.572). For women with OASIS in a previous delivery, the rates of cesarean deliveries in subsequent pregnancies were 16.4% (7.9% for controls) in Norway, and 16.3% (6.0% for controls) in Sweden, and 50.2% (14.2% for controls) in Finland. In all countries, the differences between cases and controls were significant (p < 0.001). CONCLUSION: Next deliveries after OASIS are associated with increased frequency of new OASIS, more cesarean deliveries, and less subsequent deliveries in the high-risk population than women without previous OASIS.

Risk factors for obstetric anal sphincter injury after a successful multicentre interventional programme.

OBJECTIVE: To evaluate and compare the risk profile of sustaining obstetric anal sphincter injuries (OASIS) and associated risks in five risk groups (low to high), after the OASIS rate was reduced from 4.6% to 2.0% following an interventional programme. The main focus of the intervention was on manual assistance during the final part of second stage of labour. DESIGN: A multicentre interventional cohort study with before and after comparison. SETTING: Four Norwegian obstetric departments. SAMPLE: A total of 40,154 vaginal deliveries in 2003-09. METHODS: Pre-intervention and postintervention analyses. The associations of OASIS with possible risk factors were estimated using odds ratios obtained by logistic regression. MAIN OUTCOME MEASURE: Risk factors of OASIS. RESULTS: The risk of sustaining OASIS decreased by 59% (odds ratio [OR] 0.41; 95% confidence interval [95% CI] 0.36-0.46) after the intervention. Associations with obstetric risks for OASIS were largely unchanged after the intervention, including first vaginal delivery (OR 3.84; 95% CI 2.90-5.07), birthweight ≥ 4500 g (OR 4.42; 95% CI 2.68-7.27), forceps delivery (OR 3.54; 95% CI 1.99-6.29) and mediolateral episiotomy (OR 0.89; 95% CI 0.70-1.12). However, the highest reduction of OASIS, (65%), was observed in group 0 (low-risk) (OR 0.35; 95% CI 0.24-0.51), and a 57% (OR 0.43; 95% CI 0.35-0.52), 61% (OR 0.39; 95% CI 0.31-0.48), and 58% (OR 0.42; 95% CI 0.30-0.60) reduction in groups with one, two and three risk factors, respectively. No change was observed in the group with four risk factors. CONCLUSION: After the intervention the most significant decrease of OASIS was observed in low-risk births, although the main risk factors for OASIS remained unchanged.

Blood pressure rises more in pre-eclampsia than normal pregnancy when acral skin is locally cooled.

OBJECTIVE: Investigate blood pressure response to acral skin vasoconstriction in healthy and pre-eclamptic pregnancies. METHODS: Healthy women were investigated from gestational week 8 to 52 weeks postpartum and pre-eclampsia subjects at diagnosis. Finger artery ultrasound Doppler, forearm laser Doppler fluximetry and photoplethysmographic blood pressure were recorded. Hand cooling to 19 °C induced vasoconstriction. RESULTS: Acral skin vasoconstriction increases blood pressure from 16 weeks until 12 weeks postpartum (p ≤ 0.01), with greatest responses in pre-eclampsia (p=0.047). Forearm skin perfusion is higher in pre-eclampsia (p=0.04). CONCLUSION: Acral skin vasoconstriction raises blood pressure in pregnancy, particularly in pre-eclampsia. Pregnancy accentuates important functional differences within skin.

Episiotomy characteristics and risks for obstetric anal sphincter injuries: a case-control study.

OBJECTIVES: To investigate the association between the geometrical properties of episiotomy and obstetric anal sphincter injuries (OASIS) because episiotomies angled at 40-60° are associated with fewer OASIS than episiotomies with more acute angles. DESIGN: Case-control study. SETTING: University Hospital of North Norway, Tromsø and Nordland Hospital, Bodø, Norway. SAMPLE: Seventy-four women who had one vaginal birth and episiotomy. Cases (n = 37) have sustained OASIS at birth, while controls (n = 37) had not. The groups were matched for instrumental delivery. METHODS: Two groups of women with history of only one vaginal birth were compared. Episiotomy scar was identified and photographed and relevant measures were taken. Data were analysed using conditional logistic analysis. MAIN OUTCOME MEASURES: Mean episiotomy angle, length, depth, incision point. RESULTS: The risk of sustaining OASIS decreased by 70% (odds ratio [OR] 0.30; 95% CI 0.14-0.66) for each 5.5-mm increase in episiotomy depth, decreased by 56% (OR 0.44; 95% CI 0.23-0.86) for each 4.5-mm increase in the distance from the midline to the incision point of the episiotomy, and decreased by 75% (OR 0.25; 95% CI 0.10-0.61) for each 5.5-mm increase in episiotomy length. Lastly, there was no difference in mean angle between groups but there was a "U-shaped" association between angle and OASIS (OR 2.09; 95% CI 1.02-4.28) with an increased risk (OR 9.00; 95% CI 1.1-71.0) of OASIS when the angle was either smaller than 15° or >60°. CONCLUSION: The present study showed that scarred episiotomies with depth > 16 mm, length > 17 mm, incision point > 9 mm lateral of midpoint and angle range 30-60° are significantly associated with less risk of OASIS. Shrinkage of tissue must be considered.

Core body temperature and the thermoneutral zone: a longitudinal study of normal human pregnancy.

AIM: Using a longitudinal study design, we investigated changes in maternal core temperature and ambient temperatures before and after a localized cooling procedure to the right hand. METHODS: Fifteen pregnant women participated. The experiments were sequentially performed for 21 month periods on each subject: from the 8th week of gestation to 1 year after delivery on seven separate occasions (gestational weeks 8, 16, 26, 36 and 12, 24, 52 weeks post-partum). The experiments were conducted in a climactic chamber, allowing ambient temperature adjustment to each subjects' thermoneutral zone determined using Doppler ultrasound of the digital artery. RESULTS: Maternal core temperature decreased from 37.1 °C (week 8) towards term, reaching a nadir (36.4 °C) at 12 weeks post-partum (P < 0.001). The ambient temperature required to reach the thermoneutral zone changed significantly from 26.5 °C (week 8) falling to its lowest point: 23.0 °C (week 36) (P < 0.001), then stabilized from 24 weeks post-partum. CONCLUSION: Maternal core temperature is highest in the first trimester but falls during pregnancy to a nadir 3 months post-partum. The ambient temperature required to reach the thermoneutral zone was 4 °C lower at 36 weeks of gestation compared with early pregnancy and late post-partum. Human temperature regulation is altered in pregnancy and for at least 3 months post-partum.

High frequency of cross-reacting antibodies against 2009 pandemic influenza A(H1N1) virus among the elderly in Finland.

Since May 2009, the pandemic influenza A(H1N1) virus has been spreading throughout the world. Epidemiological data indicate that the elderly are underrepresented among the ill individuals. Approximately 1,000 serum specimens collected in Finland in 2004 and 2005 from individuals born between 1909 and 2005, were analysed by haemagglutination-inhibition test for the presence of antibodies against the 2009 pandemic influenza A(H1N1) and recently circulating seasonal influenza A viruses. Ninety-six per cent of individuals born between 1909 and 1919 had antibodies against the 2009 pandemic influenza virus, while in age groups born between 1920 and 1944, the prevalence varied from 77% to 14%. Most individuals born after 1944 lacked antibodies to the pandemic virus. In sequence comparisons the haemagglutinin (HA) gene of the 2009 pandemic influenza A(H1N1) virus was closely related to that of the Spanish influenza and 1976 swine influenza viruses. Based on the three-dimensional structure of the HA molecule, the antigenic epitopes of the pandemic virus HA are more closely related to those of the Spanish influenza HA than to those of recent seasonal influenza A(H1N1) viruses. Among the elderly, cross-reactive antibodies against the 2009 pandemic influenza virus, which likely originate from infections caused by the Spanish influenza virus and its immediate descendants, may provide protective immunity against the present pandemic virus.

Cerebrovascular response to normal pregnancy: a longitudinal study.

We used a longitudinal study design (gestational weeks 8, 15, 22, 29, and 36 and 12 wk postpartum ) to investigate the effect of normal pregnancy on cerebral autoregulation and pressor response. Blood flow velocities in the right internal carotid artery, end-tidal CO2, and mean arterial pressure (MAP) were simultaneously and continuously recorded in 16 healthy pregnant women during standardized hyperventilation and handgrip. Blood flow velocities were recorded using Doppler ultrasound sampled beat by beat using the ECG signal. The results demonstrate that the vasoconstrictor response to hyperventilation is unchanged during pregnancy. During standardized handgrip, MAP showed a statistically significant increase during pregnancy that did not affect cerebral blood flow. A statistically significant reduction in the MAP response to handgrip was seen in week 36. In conclusion, pregnancy has no impact on cerebral autoregulation. There is an impact on the pressor response resulting in a blunted reaction at week 36, probably caused by a fall in the baroreflex set point.

Thermal response to submaximal exercise before, during and after pregnancy: a longitudinal study.

BACKGROUND: Heat stress in early pregnancy is known to have a teratogenic effect. Exercise produces excess heat and during pregnancy might therefore present a theoretical risk of malformations. Our aim was to assess the thermal response to exercise of healthy pregnant women in a longitudinal study. METHODS: Fourteen women were examined before pregnancy, and followed five times during, and twice after pregnancy, using a submaximal bicycle test with a target heart rate of 85% of the predicted age-adjusted maximum. The main aim was to present reference values. RESULTS: The temperature at submaximal work load declined continuously from preconception to postpartum levels (37.8 degrees C vs. 36.9 degrees C, p = 0.04). The difference between peak and basal core temperature fell from 0.6 degrees C to 0.05 degrees C at 29 and 36 weeks of gestation, reaching preconception levels at 24 weeks after delivery (0.8 degrees C lower). CONCLUSION: During submaximal exercise the temperature response seemed to provide thermal protection for the embryo and the fetus.

The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat brain.

Memantine is a medium-affinity uncompetitive N-methyl-d-aspartate receptor antagonist and has been clinically used as a neuroprotective agent to treat Alzheimer's and Parkinson's diseases. We have examined the effect of memantine (ip 5-50 mg/kg; 4 h) on the expression of brain-derived neurotrophic factor (BDNF) and trkB receptor mRNAs in rat brain by in situ hybridization. Memantine at a clinically relevant dose markedly increased BDNF mRNA levels in the limbic cortex, and this effect was more widespread and pronounced at higher doses. Effects of memantine on BDNF mRNA were also reflected in changes in BDNF protein levels. Moreover, memantine induced isoforms of the BDNF receptor trkB. Taken together, these data suggest that the neuroprotective properties of memantine could be mediated by the increased endogenous production of BDNF in the brain. These findings may open up new possibilities of pharmacologically regulating the expression of neurotrophic factors in the brain.

[Suspected large fetus in the last period of pregnancy--a difficult problem]. / Mistanke om stort foster i siste del av svangerskapet--et vanskelig problem.

BACKGROUND: In pregnancy surveillance a large symphysis-to-fundus measure raises several questions concerning delivery. MATERIAL AND METHODS: We review various problems with large for gestation age foetuses, also called macrosomic foetuses. We have performed literature searches mainly through PuBMed, which includes the Medline database. The clinical problem is discussed from the primary care provider's point of view and from those of the patient and the obstetrician. RESULTS: Macrosomia is defined as foetal weight above the 90th percentile, birth weight above 4000 g or 4500 g, or birth weight over + 2 SD of the mean birthweight by age. The diagnosis is difficult, even with various sonographic procedures. Abdominal circumference alone appears to have the same diagnostic value as the use of a combination of biparietal diameter, femur length and abdominal circumference. INTERPRETATION: Based on the literature, labour should not be induced or caesarean section performed in non-diabetic pregnancies unless the estimated foetal weight is above 5000 g. A great number of caesarean sections would have to be performed to avoid a single case of plexus brachialis paresis due to difficult shoulder delivery. The best policy is to await spontaneous birth or to induce birth after the completion of 42 weeks. In pregnancies complicated by diabetes mellitus, there are reasons for selective induction of labour if macrosomia is suspected, and for caesarean section if the calculated birth weight is above 4000 g. As the problem of difficult shoulder delivery cannot be completely avoided, each department should have a strategy to handle such a situation. Various procedures for managing the difficult shoulder delivery are described.

Regulation of IL-18 expression in virus infection.

Since its discovery as an interferon (IFN)-gamma-inducing factor, it has become evident that interleukin (IL)-18 plays a crucial role in the generation of protective immunity against microbial infections. Macrophages are the major source of biologically active IL-18, and they express constitutively IL-18 mRNA and proIL-18 protein. Microbial infections enhance the IL-18 gene expression in macrophages but post-translational processing of proIL-18, rather than transcriptional activation, is predominant in the regulation of IL-18 secretion. This review summarizes the current knowledge of proinflammatory and immunomodulatory properties of IL-18, and focuses on the role of caspases in the proteolytic activation of IL-18 in response to virus infection.

Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression.

Despite vaccines and antiviral substances influenza still causes significant morbidity and mortality world wide. Better understanding of the molecular mechanisms of influenza virus replication, pathogenesis and host immune responses is required for the development of more efficient means of prevention and treatment of influenza. Influenza A virus, which replicates in epithelial cells and leukocytes, regulates host cell transcriptional and translational systems and activates, as well as downregulates apoptotic pathways. Influenza A virus infection results in the production of chemotactic (RANTES, MIP-1 alpha, MCP-1, MCP-3, and IP-10), pro-inflammatory (IL-1 beta, IL-6, IL-18, and TNF-alpha), and antiviral (IFN-alpha/beta) cytokines. Cytokine gene expression is associated with the activation of NF-kappa B, AP-1, STAT and IRF signal transducing molecules in influenza A virus-infected cells. In addition of upregulating cytokine gene expression, influenza A virus infection activates caspase-1 enzyme, which is involved in the proteolytic processing of proIL-1 beta and proIL-18 into their biologically active forms. Influenza A virus-induced IFN-alpha/beta is essential in host's antiviral defence by activating the expression of antiviral Mx, PKR and oligoadenylate synthetase genes. IFN-alpha/beta also prolongs T cell survival, upregulates IL-12 and IL-18 receptor gene expression and together with IL-18 stimulates NK and T cell IFN-gamma production and the development of Th1-type immune response.

Virus infection induces proteolytic processing of IL-18 in human macrophages via caspase-1 and caspase-3 activation.

There is increasing evidence that IL-18 is a key pro-inflammatory cytokine and an important mediator of Th1 immune response. The main source of IL-18 is macrophage-like cells. In the present study we have investigated IL-18 protein expression in primary human macrophages in response to influenza A and Sendai virus infections. Macrophages constitutively expressed proIL-18 but produced biologically active IL-18 only after virus infection. The IL-18 release was due to virus infection-induced proteolytic processing of 24-kDa proIL-18 into its mature 18-kDa form. ProIL-18 processing required active caspase-1 enzyme and the release of mature IL-18 was blocked with a caspase-1-specific inhibitor. Caspase-3 inhibitor also reduced IL-18 production in response to virus infection. Inactive proforms of caspase-1 and caspase-3 were basally expressed in macrophages, and virus infection induced the cleavage of procaspases into their mature forms. Besides increasing the expression of caspase proteins, virus infection enhanced caspase mRNA expression in macrophages. The enhancement of caspase gene expression was abrogated by anti-IFN-alpha antibody. Furthermore, IFN-alpha and IFN-gamma could induce caspase gene expression. These results imply that interferons are involved in virus-induced caspase activation that leads to proIL-18 processing and subsequent release of mature IL-18.

Influenza A and sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages.

Chemokines regulate leukocyte traffic and extravasation into the site of inflammation. Here we show that influenza A- or Sendai virus-infected human macrophages produce MIP-1alpha, MIP-1beta, RANTES, MCP-1, MCP-3, MIP-3alpha, IP-10, and IL-8, whereas no upregulation of MIP-3beta, eotaxin, or MDC production was detected. Influenza A virus was a better inducer of MCP-1 and MCP-3 production than Sendai virus, whereas MIP-1alpha, MIP-1beta, RANTES, MIP-3alpha, and IL-8 were induced preferentially by Sendai virus. Infection in the presence of protein synthesis inhibitor indicated that ongoing protein synthesis was required for influenza A virus-induced expression of MCP-1, MCP-3, and IP-10 genes, whereas Sendai virus-induced chemokine mRNA expression took place in the absence of de novo protein synthesis. Neutralization of virus-induced IFN-alpha/beta resulted in downregulation of virus-induced IP-10, MCP-1, and MCP-3 mRNA expression. IFN-alpha or IFN-gamma were found to directly enhance MCP-1, MCP-3, and IP-10 mRNA expression. Both influenza A and Sendai viruses similarly activated transcription factor NF-kappaB. In contrast to NF-kappaB, IRFs and STATs, the other transcription factors involved in the regulation of chemokine gene expression, were differentially activated by these viruses. Influenza A virus more efficiently activated ISGF3 complex formation and Stat1 DNA-binding compared to Sendai virus, which in turn was a more potent activator of IRF-1. Our results show that during viral infections macrophages predominantly produce monocyte and Th1 cell attracting chemokines. Furthermore, virus-induced IFN-alpha/beta enhanced chemokine gene expression in macrophages emphasizing the role of IFN-alpha/beta in the development of Th1 immune responses.

A comparison of the hemodynamic effects of paracervical block and epidural anesthesia for labor analgesia.

BACKGROUND: Both paracervical block (PCB) and epidural analgesia are sometimes associated with hemodynamic effects potentially harmful to the well-being of the fetus. Our study was designed to test the hypothesis that PCB would have a more profound effect on maternal and fetal blood flow than epidural analgesia. METHODS: Forty-four healthy primiparous parturients were randomized to receive either PCB (n=21) or epidural analgesia (n= 23) with 25 or 30 mg of bupivacaine, respectively, for labor analgesia. Maternal blood pressure and fetal heart rate were recorded. Blood flow was measured using a color Doppler device. The blood flow measurements consisted of assessment of the pulsatility indices (PI) of the right maternal femoral artery and the main branch of the uterine artery (placental side), the umbilical artery and the fetal middle cerebral artery. The measurements were performed before administration of analgesia and approximately 15-20 min later after the onset of analgesia. RESULTS: Both methods provided in general good analgesia, but rescue medication was required more often after PCB. Epidural analgesia decreased maternal blood pressure more than PCB and the PI of maternal femoral artery decreased after onset of epidural analgesia, indicating epidural-induced vasodilation. The PI of the uterine artery increased after the onset of PCB, indicating vasoconstriction of this artery. No significant adverse effects or differences in the well-being of the newborn were observed, as indicated by similar Apgar scores and pH-status. CONCLUSION: There were small differences in the effects of PCB and epidural analgesia on uteroplacental circulation as well as on maternal hemodynamics. PCB may have a vasoconstrictive effect on the uterine artery. This and the fact that the parturients required rescue analgesia more frequently after PCB than after epidural block speaks for the feasibility of the latter in obstetrics.

Inflammatory responses in influenza A virus infection.

Influenza A virus causes respiratory tract infections, which are occasionally complicated by secondary bacterial infections. Influenza A virus replicates in epithelial cells and leukocytes resulting in the production of chemokines and cytokines, which favor the extravasation of blood mononuclear cells and the development of antiviral and Th1-type immune response. Influenza A virus-infected respiratory epithelial cells produce limited amounts of chemokines (RANTES, MCP-1, IL-8) and IFN-alpha/beta, whereas monocytes/macrophages readily produce chemokines such as RANTES, MIP-1alpha, MCP-1, MCP-3, IP-10 and cytokines TNF-alpha, IL-1beta, IL-6, IL-18 and IFN-alpha/beta. The role of influenza A virus-induced inflammatory response in relation to otitis media is being discussed.

Impaired antiviral response in human hepatoma cells.

Hepatitis B, C, and D viruses can infect liver cells and in some individuals establish a chronic phase of infection. Presently, relatively little information is available on the antiviral mechanisms in liver cells. Because no good in vitro model infection systems for hepatitis viruses are available, we have used influenza A, Sendai, and vesicular stomatitis (VSV) viruses to characterize interferon (IFN) responses and IFN-induced antiviral mechanisms in human hepatoma cell lines. HepG2 or HuH7 cells did not show any detectable IFN-alpha/beta production in response to influenza A or Sendai virus infections. Treatment of cells with IFN-alpha resulted in upregulation of IFN-alpha-inducible Mx, 2',5'-oligoadenylate synthetase (OAS) and HLA class I gene expression but only with exceptionally high levels of IFN-alpha (>/=100 IU/ml). Accordingly, high pretreatment levels of IFN-alpha, 1000 IU/ml for influenza A and VSV and 100 IU/ml for Sendai virus, were required before any detectable antiviral activity against these viruses was seen. IFN-gamma had some antiviral effect against influenza A virus but appeared to be ineffective against VSV and Sendai virus. IFN-gamma upregulated HLA class I protein expression, whereas Mx or OAS expression levels were not increased. There was a modest upregulation of HLA class I expression during Sendai virus infection, whereas influenza A virus infection resulted, after an initial weak upregulation, in a clear decrease in HLA class I expression at late times of infection. The results suggest that hepatoma cells may have intrinsically poor ability to produce and respond to type I IFNs, which may contribute to their inability to efficiently resist viral infections.

Lack of induction by rhinoviruses of systemic type I interferon production or enhanced MxA protein expression during the common cold.

To study whether MxA protein expression is systemically upregulated during rhinovirus infection, blood specimens were collected from 40 patients with common cold and MxA expression in mononuclear cells analyzed by flow cytometry. None of the patients with a confirmed rhinovirus infection (n = 15) or with an infection of unknown etiology (n = 20) had elevated expression of the MxA protein (median fluorescence intensity, 549 and 582, respectively) when compared to healthy controls (n = 11, median 590). Patients with influenza infections had significantly elevated values (n = 5, median 750), and interferon could be detected only in serum samples from influenza patients. In conclusion, expression of MxA in blood lymphocytes and an apparently systemic type I interferon response is not induced during rhinovirus infection or during most other cases of common cold in young adult patients.

Screening for endometrial cancer in asymptomatic postmenopausal women with conventional and colour Doppler sonography.

OBJECTIVE: To evaluate endometrial thickness and uterine arterial flow measurement as predictors of endometrial cancer. DESIGN: Prospective study among a cohort of women invited to age-adjusted, population-based breast cancer screening by mammography. SETTING: City of Turku, Finland. POPULATION: 1074 postmenopausal women aged 57-61 years (mean 59 years). METHODS: Conventional and colour Doppler sonography. Endometrial biopsy was taken when the endometrial thickness (double layer) was > or = 4.0 mm, if the uterine artery pulsatility index was < or = 1.0 or if there was a fluid accumulation in the endometrial cavity. MAIN OUTCOME MEASURES: Detection of endometrial cancer in endometrial biopsy. Record linkage with the files of the Finnish Cancer Registry three and a half years after the first ultrasound examination. Major statistical results are based on the analysis of variance and logistic regression models. RESULTS: An endometrial biopsy was taken from 291 women (27%). One woman had endometrial tuberculosis, three an endometrial polyp, 16 endometrial hyperplasia, three endometrial carcinoma (Stage Ib), and one had cervical carcinoma (Stage Ib). One woman was diagnosed as having endometrial cancer Stage Ib two and a half years after screening; she had refused further examination after a positive screen. A second endometrial cancer (Stage Ib) was diagnosed three years after a negative screening result. CONCLUSION: Transvaginal sonography is confirmed to have a very high sensitivity for the detection of early endometrial carcinoma, but the specificity remains low. If endometrial cancer is to be detected at an early stage, further examinations should be carried out when the endometrial thickness is > or = 4.0 mm, especially when the woman has risk factors such as obesity, late menopause or current use of hormonal replacement therapy. Doppler sonography does not improve the detection of premalignant and malignant endometrial lesions compared with normal ultrasound.