Visceral Leishmaniasis in a Twin Pregnancy: A Case Report and Review of the Literature.

Visceral leishmaniasis (VL), often referred to as kala-azar, is quite rare in developed countries during pregnancy. Only few studies have evaluated its impact on perinatal outcome. It is caused primarily by Leishmania donovani or Leishmania infantum and presents with a wide spectrum of clinical manifestations from cutaneous ulcers to multisystem disease. Differential diagnosis is challenging as symptoms and signs are insidious, mimicking other diseases. Misdiagnosis can result in severe adverse perinatal outcomes, even maternal/neonatal death. Early treatment with liposomal amphotericin-B (LAmB) is currently the first choice with adequate effectiveness. We report a rare case of VL in a twin pregnancy with onset at the second trimester, presenting with periodic fever with rigors, right flank pain, and gradual dysregulation of all three cell lines. The positive rK39 enzyme-linked immunosorbent assay test confirmed the diagnosis. Treatment with LAmB resulted in clinical improvement within 48 h and in the delivery of two late-preterm healthy neonates with no symptoms or signs of vertical transmission. The one-year follow-up, of the mother and the neonates, was negative for recurrence. To our knowledge, this is the first reported case of VL in a twin pregnancy, and consequently treatment and perinatal outcome are of great importance.

The Burden of Non-Alcoholic Fatty Liver Disease in Adolescents with Polycystic Ovary Syndrome: A Case-Control Study.

The aim of this case-control study was to assess the burden of non-alcoholic fatty liver disease (NAFLD) in adolescents with polycystic ovary syndrome (PCOS) and its associations with insulin resistance, hyperandrogenism, and other metabolic characteristics of the syndrome. A total of 87 Caucasian adolescent girls (47 with PCOS and 40 controls), aged 12.3-20.4 years, underwent blood sampling for glucose metabolism, hormonal and lipid profile, gynecological and liver ultrasound, and liver elastography. Indices of insulin resistance, liver steatosis, and liver fibrosis were calculated. NAFLD diagnosed by ultrasound was more prevalent in adolescents with PCOS than controls (22.7% vs. 6.1%, p = 0.046), and was also verified by liver steatosis indices. The latter was not apparent for hepatic fibrosis, as assessed by Fibroscan® and calculated indices. The homeostatic model assessment for insulin resistance (HOMA-IR) was found to predict NAFLD diagnosis by the liver fat score (LFS) index (ß = 0.709, p = 0.002). Adolescents with PCOS and high free androgen index (FAI) presented worse NAFLD than those adolescents with PCOS and lower FAI. In addition, adolescents with PCOS and concurrent NAFLD had worse insulin sensitivity indices (HOMA-IR, QUICKI, and glucose to insulin ratio) than adolescents with PCOS alone. Adolescent insulin resistance could be considered a confounder of the association between PCOS and NAFLD.

Dietary patterns are associated with arterial stiffness and carotid atherosclerosis in postmenopausal women.

PURPOSE: The increase in cardiovascular risk after the menopausal transition remains partly explained until today. Further research is needed to identify risk factors potentially modifiable by primary prevention practices. This cross-sectional study, part of a larger prospective project, aims to investigate possible associations between dietary patterns and indices of vascular structure and function among healthy postmenopausal women. METHODS: Postmenopausal women (n = 310) without clinically overt cardiovascular disease were recruited consecutively from a University Menopause Clinic over three years. Dietary intake was assessed by a validated food frequency questionnaire and the MedDietScore. In addition, we assessed anthropometric/biochemical parameters, including the Triglyceride-glucose index (TyG-Index), body fat distribution [triceps skinfold (TSF), mid-upper arm circumference (MUAC)] and physical activity. The vascular assessment included carotid-femoral pulse wave velocity (PWV), carotid and femoral-artery intima-media thickness (IMT) and atheromatous plaques presence. RESULTS: Consumption of non-refined cereals was associated with carotid-bulb IMT (R2 = 5.5% b-coefficient = -0.142; p = 0.011), adjusting for age, physical activity, lipids, systolic blood pressure, smoking, body mass index, insulin resistance, and daily energy intake. PWV was associated with the intake of total dairy products (R2 = 27.3%, b-coefficient = -0.117; p = 0.017). Higher red meat consumption was related to a greater TyG-index (Model 1, R2 = 14.3%, b-coefficient=0.121; p = 0.048), an association mediated by total daily energy intake. Higher consumption of alcohol, as well as the MedDietScore, were inversely associated with TSF measurements, significant after Bonferroni correction. CONCLUSION: Dietary patterns are associated with metabolic indices and subclinical atherosclerosis in postmenopausal women independently of traditional cardiovascular risk factors, total energy intake or physical activity.

Impact of Maternal Food Restriction on Heart Proteome in Appropriately Grown and Growth-Restricted Wistar-Rat Offspring.

OBJECTIVE: Fetal growth restriction is associated with increased postnatal cardiovascular morbidity. The alterations in heart physiology and structure caused by in utero nutrient deprivation have not been extensively studied. We aim to investigate the impact of maternal food restriction on the cardiac proteome of newborn rats with normal (non-fetal growth-restricted (FGR)) and reduced (FGR) birth weight. METHODS: On day 14 of gestation, 10 timed pregnant rats were randomized into two nutritional groups: (a) Standard laboratory diet and (b) 50% global food restriction. Pups born to food-restricted mothers were subdivided, based on birthweight, into fetal growth-restricted (FGR) and non-FGR, while pups born from normally nourished mothers were considered controls. Rat neonates were euthanized immediately after birth and the hearts of 11 randomly selected male offspring (n = 4 FGR, n = 4 non-FGR, n = 3 control group) were analyzed using quantitative proteomics. RESULTS: In total, 7422 proteins were quantified (q < 0.05). Of these, 1175 were differentially expressed in FGR and 231 in non-FGR offspring vs. control with 151 common differentially expressed proteins (DEPs) between the two groups. Bioinformatics analysis of DEPs in FGR vs. control showed decreased integrin and apelin cardiac fibroblast signaling, decreased muscle contraction and glycolysis, and over-representation of a protein network related to embryonic development, and cell death and survival. CONCLUSION: Our study illustrates the distinct proteomic profile of FGR and non-FGR offspring of food-restricted dams underlying the importance of both prenatal adversities and birth weight in cardiac physiology and development.

Ovarian volume is associated with adiposity measures and bone mineral density in postmenopausal women.

INTRODUCTION: The present study aimed to assess the association between ovarian volume and demographic and anthropometric parameters, as well as sex hormones and bone mineral density (BMD) in postmenopausal women. METHODS: 161 healthy postmenopausal women participated in this cross-sectional study. Fasting venous blood samples were obtained for biochemical/hormonal assessment. Anthropometric parameters included body mass index (BMI) and waist-to-hip ratio (WHR). Ultrasonography was used to estimate the average ovarian volume for each participant. BMD was measured in the femoral neck (FN) and the lumbar spine (LS) using DXA. RESULTS: Mean ovarian volume increased linearly with increasing quartiles of BMI (Q1:0.985±0.25, Q2: 1.11±0.29, Q3: 1.07±0.28, Q4: 1.19±0.38, p-value for linear trend 0.013). Ovarian volume correlated positively with BMI (r=0.128, p-value=0.038), FN BMD (r=0.233, p-value=0.003), FN T-score (r=0.223, p-value=0.004) and FN Z-score (r=0.171, p-value=0.027). Multivariate analysis showed that ovarian volume was predicted by WHR (b-coefficient=0.157, p-value=0.047) and SHBG (b-coefficient= -0.160, p-value=0.042), independently of age and BMI. Finally, FN BMD was predicted by ovarian volume, independently of age, menopausal age and BMI. CONCLUSION: Ovarian volume was positively and independently associated with adiposity indexes and femoral BMD in postmenopausal women. Lower SHBG levels were associated with higher ovarian volume. Insulin resistance may mediate these results. The significance of these findings should be assessed in larger prospective studies.

Serum irisin concentrations in lean adolescents with polycystic ovary syndrome.

OBJECTIVE: To explore differences in irisin concentrations between lean adolescents with PCOS and age- and body mass index (BMI)-matched controls and examine the associations of irisin with core features of the syndrome. DESIGN: Cross-sectional study. PATIENTS: Lean females with PCOS, aged 13-21 years. MEASUREMENTS: Physical, hormonal and sonographic assessment. Irisin concentrations were measured with ELISA. RESULTS: Participants included in total 39 sedentary females (mean ± SD; age 17.3 ± 2.1 years, BMI 20.7 ± 1.3 Kg/m2 ), 23 adolescents with PCOS and 16 controls. Adolescents with PCOS compared to controls had significantly elevated concentrations of fasting serum irisin (mean ± SD; PCOS, 1.7 ± 1.0 µg/mL vs controls, 1.0 ± 0.4 µg/mL; P = .007), luteinizing hormone (LH), oestradiol, testosterone, Δ4-androstenedione, 17-hydroxyprogesterone, glucose, as well as free androgen index, Ferriman-Gallwey score and mean ovarian volume (MOV). For the total sample, circulating irisin was positively correlated with MOV (r = .332, P = .041), glucose (r = .428, P = .007), insulin (rs  = .369, P = .021) and HOMA-IR (rs  = .422, P = .007) and negatively correlated with QUICKI (r = -.329, P = .041). Follicle-stimulating hormone (B = 0.295, Beta = .342, P = .042) and MOV (B = 0.182, Beta = 0.821, P = .001) were positive predictors, and LH (B = -0.108, Beta = -0.523, P = .010) and testosterone (B = -0.431, Beta = -0.457, P = .032) were negative predictors of irisin concentrations, whereas irisin positively predicted fasting glucose (B = 0.262, Beta = 0.428, P = .007). In the PCOS group, irisin concentrations were positively correlated with HOMA-IR (rs  = .416, P = .048) but negatively correlated with LH (rs  = -.499, P = .015), testosterone (r = -.585, P = .003), free androgen index (r = -.426, P = .048) and Ferriman-Gallwey score (r = -.533, P = .015). CONCLUSIONS: Irisin was associated with the adolescents' metabolic and reproductive characteristics and the hyperandrogenic phenotype of the syndrome. Much research is needed to ascertain mechanisms of elevated serum irisin in adolescent PCOS.

Placenta and Umbilical Cord Cause in Antepartum Deaths.

Stillbirth is a sudden and painful event for parents and obstetrical specialists as well. It is, therefore, of greatest importance to be able to give answers for the cause in order to plan a subsequent pregnancy. The aim of this retrospective study is to estimate the placental and umbilical cord cause of intrauterine death in relation to different gestational ages. The study took place on the Medical Birth Registry of Aretaieio Hospital, National and Kapodistrian University, Athens, Greece. We include a total of 19,283 pregnancies from 1998 to 2012. In this study period, 431 embryonic deaths occurred. The clinical history was documented on admission at delivery. Conditions thought to be associated with the intrauterine fetal death were recorded. Gestational age was calculated from the last menstrual period as well as with the three-trimester system. The autopsy, placenta and umbilical cord examination were performed by the same laboratory of pathology in Aretaieio University Hospital. We found that the majority of stillbirths occurred in the second trimester. We examined placenta and umbilical cord in all cases. The most frequent histologic abnormalities were those indicated placental vascular insufficiency. As far as the umbilical cord is concerned we found that the inflammatory disorder was the most common in antepartum deaths. A single umbilical artery was significantly related to gestational diabetes and congenital embryonic anomalies. Finally, our results showed steady declines in antepartum deaths during 1998-2012. As a result, we reached the conclusion that in order to reduce the fetal death rate, we have to insist on the autopsy of the placenta and umbilical cord in order to gain the appropriate information in counseling the parents.

Assessment of the antiosteoporotic treatment initiation: A retrospective observational study in Greece.

OBJECTIVE: A study to retrospectively assess the decision to implement treatment for osteoporosis based on Greek version of FRAX tool. METHODS: The study population was 1000 postmenopausal women aged 45 or above, excluding those with medical conditions demanding specific osteoporosis management. Data were collected regarding their medical history and additionally, risk factors incorporated in FRAX questionnaire. FRAX score was estimated at the time of the anti-osteoporotic treatment initiation. RESULTS: The mean age of the study sample was 58.5±8.79 years. 46.8% of the participating osteopenic women had initiated treatment for osteoporosis at their first consultation while the 80.6% met the current national intervention threshold of FRAX tool. CONCLUSION: Stemming from our results there is an indication that women who are borderline eligible for treatment and seek consultation for osteoporosis are likely to be given treatment regardless of the potential benefit. One cannot ignore the fact that a clinician's good clinical judgment is of the utmost importance and under no circumstances can be replaced by any prognostic assessment tool.

Protein expression in the brain of rat offspring in relation to prenatal caloric restriction.

OBJECTIVE: Intrauterine growth restriction (IUGR) has been associated with decreased supply of crucial substrates to the fetus and affects its growth and development by temporarily or permanently modifying gene expression and function. However, not all neonates born by calorie restricted mothers are IUGR and there are no reports regarding their brain protein expression vis-à-vis that of their IUGR siblings. Here, we investigated the expression of key proteins that regulate growth and development of the brain in non-IUGR newborn pups versus IUGR siblings and control pups. METHODS: Rat brain proteins were isolated from each group upon delivery and separated by two-dimensional gel electrophoresis (2-DE). RESULTS: 14-3-3 Protein, calreticulin, elongation factor, alpha-enolase, fascin, heat-shock protein HSP90 and pyruvate kinase isozymes were significantly increased (p < 0.05) in samples obtained from IUGR newborn pups compared to non-IUGR. Conversely, collapsin response mediator proteins, heat-shock70 and peroxiredoxin2 were decreased in IUGR group compared to non-IUGR. CONCLUSIONS: In our experimental study, IUGR pups showed an altered proteomic profile compared to their non-IUGR siblings and non-IUGR controls. Thus, not all offspring of calorie-restricted mothers become IUGR with the accompanying alterations in the expression of proteins. The differentially expressed proteins could modulate alterations in the energy balance, plasticity and maturation of the brain.

A randomized controlled trial for cervical priming using vaginal misoprostol prior to hysteroscopy in women who have only undergone cesarean section.

PURPOSE: To evaluate the efficacy of misoprostol administrated vaginally on cervical priming and its complications prior to diagnostic or operative hysteroscopy in women who have undergone at least one cesarean section and who have never delivered vaginally before and/or had other transcervical procedure. METHODS: A total of 55 patients undergoing hysteroscopy for various intra-uterine lesions were included in this study and were randomly allocated to two groups finally. Thirty patients in the study group were given 200 µg misoprostol vaginally 12 h before the procedure, whereas 25 patients in the control group did not receive any cervical priming. The countered outcome included the cervical width detected with Hegar dilatators and complication rates. RESULTS: Mean cervical width was greater in the study group (6.6 ± 1.3) than in the control group (5.1 ± 0.9). Complications and failure rates were lower in the study group. CONCLUSION: Application of 200 µg misoprostol vaginally 12 h before hysteroscopy softens the cervix, reduces cervical resistance and consequently the need for cervical dilatation, with only mild side effects.

Serum lipid levels and bone mineral density in Greek postmenopausal women.

Contradictory results have been reported regarding a relationship between serum lipid levels and bone mineral density. The purpose of this study was to further investigate a possible relationship between those parameters in Greek postmenopausal women. A total of 591 patients followed at a tertiary hospital were examined for seven different lipid factors in relation to dual-emission X-ray absorptiometry measurements at the lumbar spine. Lipoprotein-a was the only lipid measurement that univariately showed an almost significant trend of association with bone mass category (analysis of variance [ANOVA] p value 0.062 for Ln(Lipoprotein-a)). In multiple regression, it was noted that a non-significant negative trend of association of high density lipoprotein (HDL) cholesterol and Apolipoprotein AI with lumbar T-score (p value 0.058 and 0.075, respectively). In age subgroup analysis, Lipoprotein-a and Ln(Lipoprotein-a) presented a negative correlation with lumbar T-score for women with age ≥ 53 years (p value 0.043 and 0.070, respectively), while a negative correlation of HDL and Apolipoprotein AI levels with lumbar T-score remained in women with age < 53 years (p value 0.039 and 0.052, respectively). The findings do not support a strong relationship between lipid levels and bone mass measurements.

Additive effect of depressed mood and vasomotor symptoms on postmenopausal insomnia.

OBJECTIVE: The aim of this study was to investigate the role of vasomotor and mood symptoms on insomnia in postmenopausal women. METHODS: One hundred sixty-three postmenopausal women, not receiving hormone therapy, attending a menopause clinic at the University of Athens, Greece, were included in this cross-sectional study. Climacteric symptoms were assessed by Greene's scale, whereas psychological morbidity was measured by Zung Self-Assessment Depression Scale, Symptom Checklist-90-R, and Athens Insomnia Scale. RESULTS: Vasomotor symptoms were significantly associated with insomnia (P = 0.001). When depressive symptomatology was added to the logistic regression analysis, the predictive ability of the model was significantly improved as defined by the increase in the log likelihood (P < 0.001) and the increase in the area under the receiver operating characteristic curve. CONCLUSIONS: Insomnia in postmenopausal women attending a menopause clinic is related both to the effects of vasomotor symptoms and depressive symptomatology. Mood symptoms seem to affect sleep independently of vasomotor symptoms, suggesting that depression should be carefully assessed and treated in postmenopausal women with insomnia.

Adnexal torsion during pregnancy: report of four cases and review of the literature.

Adnexal torsion is a rare cause of acute abdominal pain during pregnancy. It is frequently associated with ovarian stimulation for in vitro fertilization (IVF) or with ovarian masses, mainly of functional origin. The clinical, laboratory and imaging findings are non-specific. The authors present four cases with adnexal torsion diagnosed during the first trimester of pregnancy. The clinical picture, the mode of diagnosis, and the therapeutic approach are discussed. In two cases, the adnexa was removed, because there was extensive hemorrhage and ischemia. In the other two cases, unwinding of the adnexa was carried out and the ovary was preserved. The diagnosis of adnexal torsion is difficult, especially during pregnancy, and occasionally remains a diagnostic dilemma. It necessitates a prompt surgical intervention, because any delay leads to irreversible ovarian necrosis, so that adnexectomy is ultimately required.

Sonohysterography is superior to transvaginal sonography for the diagnostic approach of irregular uterine bleeding in women of reproductive age.

PURPOSE: To evaluate and compare the accuracy of transvaginal sonography (TVS) and sonohysterography (SHG) in the investigation of women of reproductive age presenting with irregular uterine bleeding (IUB). METHODS: This prospective study included 104 women presenting with IUB. All patients underwent TVS, SHG, and hysteroscopy, during which endometrial biopsies were obtained and any endometrial mass was treated with hysteroscopic surgery. Statistical analysis was performed by calculating the sensitivity, specificity, and positive and negative predictive values of TVS and SHG in diagnosing endometrial polyp, submucous myoma and all endometrial pathologies (polyp, submucous myoma, endometrial hyperplasia, and endometrial carcinoma) with the histopathological report of the tissues obtained by hysteroscopy serving as the end point for the analysis. RESULTS: The sensitivity, specificity, and positive and negative predictive values, respectively of TVS were 61.2%, 90.9%, 85.7%, and 72.5% for diagnosing endometrial polyps; 75.0%, 92.0%, 63.1%, and 95.3% for diagnosing submucous myomas; and 75.0%, 80.6%, 87.9%, and 63.0% for diagnosing any kind of pathology. The corresponding diagnostic values of SHG were 83.7%, 96.4%, 95.3%, and 86.9% for polyps; 87.5%, 98.9%, 93.3%, and 97.8% for submucous myomas; and 88.2%, 91.7%, 95.2%, and 80.5% for any kind of pathology. CONCLUSIONS: SHG showed superior sensitivity, specificity, and positive and negative predictive values compared with TVS in diagnosing intrauterine lesions in women of reproductive age with IUB.

Endogenous sex steroids and bone mineral density in healthy Greek postmenopausal women.

The aim of this study was to assess the association of endogenous sex steroids with bone mineral density (BMD) in healthy postmenopausal women not on hormone therapy. A total of 884 postmenopausal women aged 42-71 years were studied in a cross-sectional design. Parameters assessed were follicle-stimulating hormone, luteinizing hormone, estradiol, total testosterone, sex hormone-binding globulin, free estrogen index (FEI), free androgen index (FAI), Delta4-androstendione (Delta4A), dehydroepiandrosterone sulfate (DHEAS), bone alkaline posphatase, and bone mineral density at the lumbar spine (L-BMD) and femoral neck (N-BMD). Estradiol and FEI associated positively with both L-BMD and N-BMD (r = 0.21-0.47, P < 0.01). These associations remained significant after adjustment for age, years since menopause, and body mass index. FAI correlated positively with both L-BMD and N-BMD (r = 0.18 and 0.33, respectively; P < 0.01). At the multivariate analysis, however, FAI remained the significant determinant only for N-BMD. Delta4A associated positively with N-BMD (r = 0.27, P = 0.001), whereas DHEAS showed no association with BMD at either site. Thus, endogenous steroids are significant determinants of postmenopausal BMD. Endogenous estradiol may be more important for lumbar spine BMD, whereas endogenous androgens are associated mainly with femoral neck BMD.

The effect of raloxifene and tibolone on the uterine blood flow and endometrial thickness: a transvaginal Doppler study.

OBJECTIVES: To evaluate and compare the effect of different than classical hormone therapy medications, such as raloxifene and tibolone, on the uterine arteries and endometrium of postmenopausal women using transvaginal ultrasonography. METHODS: The prospective study included 62 healthy, postmenopausal women recruited from the Menopausal Clinic of the 2nd Department of Obstetrics and Gynecology of the University of Athens. Subjects were randomly allocated to receive raloxifene HCl in a daily dose of 60 mg orally (Group A-31 women) or tibolone in a daily dose of 2.5 mg orally (Group B-31 women). The study period was 6 months and all subjects were assessed using transvaginal ultrasonography before treatment initiation as well as after 3 and 6 months for evaluation of the endometrial thickness and the pulsatility (PI) and resistance (RI) indices at the level of the uterine arteries. RESULTS: No significant differences in RI, PI and endometrial thickness were observed in the raloxifene group during the 6-month treatment. In the tibolone group, PI and RI values decreased linearly from baseline to the end of the study, whereas the endometrial thickness was significantly increased during the first 3 months remaining unaltered thereafter. Comparisons between the two study groups revealed significant percent change of values in the pre-treatment to month-3 period and no difference with regard to pre-treatment, month-3 and month-6 absolute values. CONCLUSION: Raloxifene and tibolone exert dissimilar effects on uterine blood supply parameters and endometrial thickness.