Accuracy of Fetal Weight Estimation in Women with Diet Controlled Gestational Diabetes.

Purpose: To evaluate whether ultrasound accuracy of estimated fetal weight (EFW) differs in women with diet controlled gestational diabetes mellitus (GDM) compared to nondiabetic pregnant women. Material and Methods: We included 363 patients, 121 patients with diet controlled GDM and 242 patients with a normal oral glucose tolerance test (oGTT). Each case of diet controlled GDM was matched with 2 unaffected controls. All patients were screened/diagnosed for GDM by means of an oGTT. Both groups received ultrasound examination including fetal biometry, using Hadlock's Formula, within 7 days to delivery. After birth, gestational age, birthweight and Apgar scores were collected from each newborn. Results: There was a good correlation between EFW and birth weight (coefficient = 0.747, p < 0.001 by Pearson correlation, even after adjustment for glucose status). Regression analyses, including noGDM/GDM, maternal age, maternal body mass index, birth weight and time interval between ultrasound and delivery revealed that only fetal birth weight significantly influences weight difference between ultrasound EFW and actual birth weight at term. Conclusion: Our data suggests that ultrasound accuracy of EFW using Hadlock's Formula at term does not differ in women with diet controlled GDM compared to women with normal glucose tolerance.

What does magnetic resonance imaging add to the prenatal ultrasound diagnosis of facial clefts?

OBJECTIVE: Ultrasound is the modality of choice for prenatal detection of cleft lip and palate. Because its accuracy in detecting facial clefts, especially isolated clefts of the secondary palate, can be limited, magnetic resonance imaging (MRI) is used as an additional method for assessing the fetus. The aim of this study was to investigate the role of fetal MRI in the prenatal diagnosis of facial clefts. METHODS: Thirty-four pregnant women with a mean gestational age of 26 (range, 19-34) weeks underwent in utero MRI, after ultrasound examination had identified either a facial cleft (n = 29) or another suspected malformation (micrognathia (n = 1), cardiac defect (n = 1), brain anomaly (n = 2) or diaphragmatic hernia (n = 1)). The facial cleft was classified postnatally and the diagnoses were compared with the previous ultrasound findings. RESULTS: There were 11 (32.4%) cases with cleft of the primary palate alone, 20 (58.8%) clefts of the primary and secondary palate and three (8.8%) isolated clefts of the secondary palate. In all cases the primary and secondary palate were visualized successfully with MRI. Ultrasound imaging could not detect five (14.7%) facial clefts and misclassified 15 (44.1%) facial clefts. The MRI classification correlated with the postnatal/postmortem diagnosis. CONCLUSIONS: In our hands MRI allows detailed prenatal evaluation of the primary and secondary palate. By demonstrating involvement of the palate, MRI provides better detection and classification of facial clefts than does ultrasound alone.

Mode of delivery is associated with maternal and fetal endocrine stress response.

OBJECTIVE: To determine whether mode of delivery is associated with the endocrine stress response in mother and child. DESIGN: Prospective observational study. SETTING: Tertiary care centre, University hospital. POPULATION: A total of 103 nulliparous women with uncomplicated singleton pregnancies at term undergoing either spontaneous labour for vaginal delivery or delivering by caesarean section without labour. Thirty women delivered vaginally without any pain relief, 21 women delivered vaginally with epidural anaesthesia, 23 women had ventouse extraction and 29 women underwent caesarean section with epidural analgesia. METHODS: After delivery, maternal and umbilical cord blood was collected for determination of different stress-associated hormones. MAIN OUTCOME MEASURES: Concentrations of epinephrine (EP), norepinephrine (NOR), adrenocorticotropic hormone (ACTH), cortisol (CORT), prolactin (PRL), corticotropin-releasing factor and beta-endorphin (BE). RESULTS: Caesarean section was associated with significantly lower maternal concentrations of EP, NOR, ACTH, CORT, PRL and BE and lower newborn levels of EP, NOR and CORT compared with all other modes of delivery. Concentrations of EP, ACTH and BE differed significantly in newborns delivered by normal vaginal delivery, vaginal delivery with epidural anaesthesia and ventouse extraction. CONCLUSIONS: The mode of delivery and analgesia used during birth are associated with maternal and fetal endocrine stress responses.

Evaluation of neoplastic human mast cells by tryptase-immunoelectron microscopy.

AIMS: To analyse and characterize the ultrastructural morphology of normal tissue mast cells (MC) and neoplastic bone marrow MC. METHODS: We have examined the ultrastructure and cytomorphological features of MC derived from cord blood cells, neoplastic bone marrow MC in patients with systemic mastocytosis (SM, n = 4), myelomastocytic leukaemia (MML, n = 2), mast cell leukaemia (MCL, n = 2) and tryptase-positive acute myeloid leukaemia (AML, n = 4). RESULTS: Based on their ultrastructure and morphology, four distinct cell types could be delineated: (i) mature well-granulated tissue MC exhibiting a round central nucleus; (ii) atypical MC type I with oval nuclei, hypogranulated cytoplasm, and prominent surface projections; (iii) immature atypical MC with bi- or polylobed nuclei (atypical MC type II = promastocytes); and (iv) metachromatic blasts. Type I atypical MC were detected in a patient with indolent SM, whereas type II MC and metachromatic blasts were primarily found in MML, MCL and tryptase-positive AML. In all samples examined, the identity of MC could be reconfirmed by immunoelectron microscopy, irrespective of the stage of cell maturation or the disease variant, all types of MC contained tryptase in their cytoplasmic granules. CONCLUSION: Immunoelectron microscopy may be a helpful approach in confirming the identity of neoplastic MC in myeloid neoplasms.

Effects of various statins on cytokine-dependent growth and IgE-dependent release of histamine in human mast cells.

BACKGROUND: Statins are inhibitors of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase, a key enzyme in mevalonic acid (MVA)-dependent signaling. Recent data suggest that statins exhibit profound inhibitory effects on growth and function of various immune cells. In the present study, we examined the in vitro effects of five different statins on primary human mast cells (MCs), MC progenitors, and the human MC line HMC-1. METHODS: Histamine release experiments were conducted on isolated MCs using statins and an anti-immunoglobulin E (IgE) antibody. Culture experiments were performed with stem cell factor (SCF) and interleukin (IL)-6, and cord blood-derived progenitors. RESULTS: Preincubation of primary lung MCs with cerivastatin or atorvastatin (1-50 microM) for 24 h resulted in inhibition of anti-IgE-induced release of histamine. The effects of both statins were dose-dependent. Moreover, both statins, and to a lesser degree lovastatin, were found to inhibit the SCF-induced differentiation of MCs from their progenitors. The other statins tested (simvastatin, pravastatin) did not affect mediator release or growth of MCs. CONCLUSIONS: Cerivastatin and atorvastatin act as inhibitors of growth and function of human MCs.

Gestational diabetes mellitus is associated with increased C-reactive protein concentrations in the third but not second trimester.

OBJECTIVE: Serum C-reactive protein (CRP) concentrations were measured longitudinally throughout pregnancy to test the hypothesis that CRP could relate more closely to glucose tolerance than to adiposity. METHODS: The CRP concentrations in pregnant women with normal glucose tolerance (NGT) and those with gestational diabetes mellitus (GDM) were measured at the same time as the oral glucose tolerance test (OGTT), at the 24th and 28th weeks of gestation and between the 37th and 38th weeks of gestation. RESULTS: At the end of the third trimester, women with GDM had significantly higher CRP levels than women with NGT [median (interquartile range), 9.7 mg L(-1) (5.4-16.0) and 5.7 mg L(-1) (5.1-7.2); P < 0.001, respectively], but at the time of the diagnostic OGTT no significant difference between the two groups was observed. This was owing to a significant increase of CRP in women with GDM between the time of the OGTT and the 37th-38th gestational weeks [median (interquartile range), 1.9 mg L(-1) (-2.2, 6.7); P = 0.01]; whereas, no change in CRP was found in women with NGT [median (interquartile range), -0.1 mg L(-1) (-2.4, 3.1); P = 0.76]. Multiple linear regression analysis showed only a significant independent influence of GDM (P < 0.001) on maternal CRP concentrations in the 37th-38th gestational weeks and a significant influence of body mass index (P < 0.007), but no influence of GDM at the time of the OGTT. CONCLUSION: These data suggest that in women with gestational diabetes the CRP concentration is primarily related to the degree of adiposity until the second trimester and that thereafter impaired glucose metabolism appears to be the predominant predictor of changes in CRP.

Detection of differentiation- and activation-linked cell surface antigens on cultured mast cell progenitors.

BACKGROUND: Mast cells (MC) are multifunctional effector cells of the immune system. They derive from uncommitted CD34(+) hemopoietic progenitor cells (HPC). Depending on the stage of maturation and the environment, MC variably express differentiation- and activation-linked antigens. Little is known, however, about the regulation of expression of such antigens in immature human MC. METHODS: We analyzed expression of CD antigens on human MC grown from cord blood-derived CD34(+) HPC. The HPC were isolated by magnetic cell sorting (MACS) and FACS to >97% purity, and were cultured in stem cell factor (SCF) and interleukin (IL)-6 with or without additional cytokines (IL-4 or IL-10) in serum-free medium. The cell surface phenotype of MC was determined by monoclonal antibodies and flow cytometry. RESULTS: Cultured MC progenitors were found to react with antibodies against various CD antigens including CD58, CD63, CD117, CD147, CD151, CD203c, and CD172a, independent of the growth factors used and time-point investigated (days 14-42). CD116 [granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSFRalpha)] and CD123 (IL-3Ralpha) were expressed on MC precursors on day 14, but disappeared thereafter. Cultured MC did not express CD2, CD3, CD5, CD10, CD19, or CD25. Addition of IL-10 to MC cultures showed no effect on expression of CD antigens. However, IL-4 was found to promote expression of CD35 and CD88 on cultured MC without changing expression of other CD antigens. CONCLUSIONS: Most MC antigens may already be expressed at an early stage of mastopoiesis. Whereas IL-3R and GM-CSFRs are lost during differentiation of MC, these cells may acquire complement receptors (CD35, CD88) under the influence of distinct cytokines.

Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women.

BACKGROUND: Catechol-O-methyltransferase (COMT) is the principal enzyme in the conjugation pathway for hydroxylated estrogens. We hypothesize that blood 17beta-estradiol (E(2)) and estrone (E(1)) levels in postmenopausal women receiving an oral E(2) preparation are dependent on the enzyme activity of COMT. METHODS: To determine the influence of this enzyme on E(2) serum levels three groups of 12 selected from 159 healthy normotensive postmenopausal women were selected according to their codon 158 COMT genotype (COMT(HH), COMT(HL), COMT(LL)) which is known to be associated with enzyme activity. All selected women received one 2 mg tablet estradiol valerate and blood samples were taken before treatment and after 1, 3 and 48 h. RESULTS: After 3 h the serum levels of E(2) were significantly higher in women with the COMT(LL) genotype (median 69 pg/ml, range 58-91) and the COMT(HL) genotype (median 69 pg/ml, range 43-84) compared with women with the COMT(HH) genotype (median 45 pg/ml, range 15-68, P < 0.005). In a univariate analysis of variance, considering age, body weight, and COMT genotype, body weight (P = 0.034) and COMT genotype (P < 0.001) were independently related to the increase of serum E(2) levels, whereas age was not. CONCLUSIONS: Our data demonstrate that serum E(2) levels significantly correlate with the COMT genotype. Differences in COMT genotype might be involved in causing variable effects of estrogens on diseases such as hormone-dependent cancers, coronary heart disease and on efficacy of hormone replacement therapy.

Expression, epitope analysis, and functional role of the LFA-2 antigen detectable on neoplastic mast cells.

Recent data suggest that mast cells (MCs) in patients with systemic mastocytosis or mast cell leukemia express a CD2-reactive antigen. To explore the biochemical nature and function of this antigen, primary MCs as well as the MC line HMC-1 derived from a patient with mast cell leukemia were examined. Northern blot experiments revealed expression of CD2 messenger RNA in HMC-1, whereas primary nonneoplastic MCs did not express transcripts for CD2. In cell surface staining experiments, bone marrow (BM) MCs in systemic mastocytosis (n = 12) as well as HMC-1 cells (30%-80%) were found to express the T11-1 and T11-2 (but not T11-3) epitopes of CD2. By contrast, BM MCs in myelodysplastic syndromes and nonhematologic disorders (bronchiogenic carcinoma, foreskin phimosis, uterine myeomata ) were consistently CD2(-). All MC species analyzed including HMC-1 were found to express LFA-3 (CD58), the natural ligand of CD2. To study the functional role of CD2 on neoplastic MCs, CD2(+) and CD2(-) HMC-1 cells were separated by cell sorting. CD2(+) HMC-1 cells were found to form spontaneous aggregates and rosettes with sheep erythrocytes in excess over CD2(-) cells, and a T11-1 antibody inhibited both the aggregation and rosette formation. Moreover, exposure of CD2(+) HMC-1 cells to T11-1 or T11-2 antibody was followed by expression of T11-3. In addition, stimulation of neoplastic MCs through T11-3 and a second CD2 epitope resulted in histamine release. These data show that neoplastic MCs express functionally active CD2. It is hypothesized that expression of CD2 is associated with pathologic accumulation and function of MCs in systemic mastocytosis.

Three- versus two-dimensional ultrasound for nuchal translucency thickness measurements: comparison of feasibility and levels of agreement.

We have determined feasibility and levels of agreement for visualizing the nuchal translucency within a time limit with three-dimensional (3D) and two-dimensional (2D) transvaginal ultrasound. A total of 213 women of median gestational age 13 weeks (range 11-14 weeks) undergoing first-trimester nuchal translucency (NT) thickness measurements with 2D transabdominal ultrasound were included in the study. Additionally all women underwent 2D and 3D transvaginal NT examination within a time limit of 90 s. These two methods were compared with each other and with our standard method (2D transabdominal ultrasound) with respect to visualization of fetal nuchal fold and to the levels of agreement. The nuchal fold was visualized by 3D and 2D transvaginal ultrasound in 85.9% (95% CI: 80.5%, 90.3%) and 25.8% (95% CI: 20.1%, 32.2%), respectively (p<0.001). There was a statistically significant underestimation of the NT by 2D transabdominal as compared with 3D transvaginal ultrasound of 0.1 mm (p<0.001), and by 3D transvaginal as compared with 2D transvaginal ultrasound of even 0.1 mm (p<0.001). 3D transvaginal ultrasound of the nuchal fold has increased feasibility to 2D transvaginal ultrasound within a short examination time and with minimal, but significant, measurement differences.

Treatment of keratoconjunctivitis sicca with topical androgen.

OBJECTIVE: Androgens have been reported to influence lipid production of sebaceous glands and even many ocular tissues. The effect of topical androgen therapy on a 54-year-old patient with keratoconjunctivitis sicca (KCS) and decreased lipid phase of the tear film is reported. METHODS: For assessment of the lipid phase of the tear film, break up time (BUT) and lipid layer thickness (LLT) were monitored during 6 months before treatment as well as 3 months while using a daily topical androgen therapy. RESULTS: During the topical androgen therapy the pathological lipid phase of the tear film was completely restored indicated by the normalisation of the values of BUT and LLT. CONCLUSION: These findings are consistent with animal experiments indicating that topical administered androgen can restore the decreased lipid phase of the tear film. This may open up new therapeutic strategies for KCS.

The influence of cotinine on interleukin 6 expression in smokers with cervical preneoplasia.

BACKGROUND: Several epidemiological investigations have shown that cigarette smoking leads to increased serum IL-6 levels and is a risk factor for cervical cancer. METHODS: We examined the levels of interleukin 6 (IL-6) and the amount of cotinine in the cervical fluid of 78 women and compared the presence of human papillomavirus (HPV) in smokers and nonsmokers. RESULTS: The results of our study showed that IL-6 levels were higher in the cervical mucus of smokers than in nonsmokers. Fourteen percent of smokers were in the category with highest IL-6 levels compared to 6% of nonsmokers. However, our IL-6 results were not significant as they were probably influenced by the higher rates of HPV infection in smokers (17 cases) than in nonsmokers (4 cases). Significant findings showed that smokers had a higher prevalence of squamous intraepithelial lesions (SILs) than nonsmokers. Smokers' cotinine levels also exceeded those of nonsmokers: 13.95 ng/ml compared with 5.00 ng/ml. However, less IL-6 activity was evident in smokers with high-grade SILs and HPV infection of high-risk types. CONCLUSION: Our results suggest that smoking has a stimulatory effect on the production of IL-6 in the cervix. Furthermore, smokers show a higher genital HPV infection rate and a higher prevalence of SILs.

Human papillomavirus in the cervix and placenta.

OBJECTIVE: To determine the prevalence and association of human papillomavirus (HPV) infection in the cervices and placentas of pregnant women. METHODS: Cervical samples were taken from 179 of 226 women who had placental biopsies because of abnormal ultrasound findings or were older than 35 years, to detect HPV infections with hybrid capture II tests. Polymerase chain reaction (PCR) was done on placental tissue of 147 of the 226 women to detect HPV DNA. RESULTS: We found 44 of 179 women (24.6%, 95% confidence interval 18.3, 31.0) to test positive for HPV in their cervices. Logistic regression analyses showed decreased prevalence of HPV infection with increased maternal age (P =.039). The HPV DNA E6 PCR from the villus tissue was negative in the 147 cases examined. However, a significant contingency coefficient between low-risk HPV infection and elevated risk of chromosome aberration was found (φ = V = 0.15, P =.050). CONCLUSION: The infection rate of 24.6% in women without clinical symptoms of HPV infection was high, but there seemed to be no virus transmission to the placenta in women with subclinical infections. Low-risk cervical HPV infection might be associated with a slightly higher risk of abnormal fetal karyotype.

Ultrasound imaging of Bartholin's cysts.

In a prospective, randomized study, Bartholin's cysts were depicted in 36 patients by means of ultrasound imaging. Patients were requested to return for a follow-up US examination after surgery. We were able to show that Bartholin's cysts can easily be expressed with ultrasonographic techniques. In clinical practice, this approach may not only help to improve diagnostics, but may also make therapy measurable and, for the first time, objectifiable.

Progesterone and neurology.

Neurological diseases are frequently observed in perimenopausal women and can be characterized by their gender-specific occurrence. These observations raise the question whether sex steroids are also involved in neurological diseases. Epidemiological data have shown that in Austria in 1993, the prescription rate of psychotropics, hypnotics, and analeptics for women aged 50-55 years increased over 300% compared to other age groups. In males of the same age, an increase of the prescription rate was not observed. Molecular pharmacology research over the last ten years has shown that sex steroids may interact with the central nervous system via GABA receptors as well as with the peripheral nervous system. These observations confirm the epidemiological finding that neurological and psychological functions may also be directly influenced by sex steroids and their metabolites.