bluuebunny/crossref_metadata_2025 huggingface dataset:
The IgE Antigen Receptor: A Key Regulator for the Production of IgE Antibodies
Authors: Achatz Gernot , Luger Elke , Geisberger Roland , Achatz-Straussberger Gertrude , Breitenbach Michael , Lamers Marinus
Published: April 2003

Immunoglobulins in general form a substantial component of serum proteins, and play a role in homeostatic mechanisms, a first line of defense against pathogenic organisms and in immunological memory. In the secreted form, immunoglobulins represent the effector arm of the humoral immune system. However, immunoglobulins are not only secreted, but can also be expressed on the surface of a B lymphocyte (membrane immunoglobulin), and, in this physical state, most likely convey signals to steer the B cell along its differentiation pathway. A step forward in the understanding of the role of membrane immunoglobulins other than membrane IgM or IgD was achieved with two mouse lines with mutations in the epsilon heavy chain gene. In IgEΔM1M2 mice serum IgE is reduced to less than 10% of normal mice, while IgEKVKΔtail mice show a reduction of 50%, reflecting a serious impairment of the IgE-mediated immune response. We think that the cytoplasmic tail of IgE is involved in a signal transduction which leads to the expression of high quantities and qualities of secreted IgE immunoglobulins.
Interleukin-4 Induces a Switch of Human Intestinal Mast Cells from Proinflammatory Cells to Th2-Type Cells
Authors: Bischoff Stephan C. , Sellge Gernot , Manns Michael P. , Lorentz Axel
Published: April 2003

Background: During the last years, mast cells have been recognized as a potent cellular source of multiple cytokines. However, little is known about the regulation of cytokine production by mature human mast cells derived from mucosal sites. Methods: Human mast cells were isolated from intestinal mucosa and cultured for 14 days in the presence of stem cell factor (SCF) alone or in combination with IL-4. Mast cells were then stimulated by IgE receptor cross-linking or bacterial infection and cytokine production was examined by RT-PCR and ELISA. Results: We found that human intestinal mast cells produce proinflammatory cytokines such as TNF-α, IL-1β and IL-6 without further stimulation. Stimulation of the cells with gram-negative bacteria (Escherichia coli and others) caused an upregulation of TNF-α expression. Following IgE receptor cross-linking, we found additional expression of the Th2 cytokines IL-3, IL-5 and IL-13. Interestingly, mRNA for IL-3, IL-5 and IL-13 was also expressed in unstimulated mast cells provided they were cultured in the presence of SCF and IL-4. Moreover, IL-4 rendered mast cells capable of releasing IL-5 in response to bacterial challenge. Conclusion: In the presence of the mast cell survival factor SCF, mature human mast cells produce predominantly proinflammatory cytokines, whereas in the presence of SCF and IL-4, mast cells produce not only proinflammatory but also Th2 cytokines.
The Role of STAT1 in Activation of IL-3- and IL-5-Induced Eosinophils by Interferon Gamma
Authors: Ochiai K. , Otaka K. , Ito M. , Tomioka H.
Published: April 2003

Tyrosine phosphorylation of STAT1α in eosinophils after IFN-γ stimulation has been shown, but the biological significance of eosinophil STAT1α activation in transmitting the signals through the IFN-γ receptor remains unknown. The purpose of this study is to determine whether STAT1 is involved in the regulation of eosinophils by IFN-γ-IFN-γ receptor interaction. rhIL-3- and rhIL-5-induced eosinophils from CD34+ cells of cord blood on day 28 of culture were used. The cells were washed and further incubated in IL-3- and IL-5-free medium for 48 h. The induced eosinophils constitutively expressed CD69 and lost this expression after a further 48-hour incubation without the cytokines. IFN-γ significantly upregulated CD69 expression on the 48-hour incubated cells. In inhibitory experiments on STAT1, a phosphorothioate oligo antisense DNA against STAT1α was added to IL-3- and IL-5-containing medium from day 15 to day 28 of culture. The oligo DNAs altered neither the expressions of myeloid cell marker CD9 and 13 nor the expression of IFN-γ receptor on the cells. The added STAT1α antisense, but not sense, DNA significantly reduced STAT1α mRNA expression in the cells. The STAT1 antisense also significantly inhibited IFN-γ-induced CD69 expression on the 48-hour incubated eosinophils. In conclusion, these results indicate that IFN-γ induces CD69 expression in the induced eosinophils through STAT1α, suggesting that STAT1α may play a significant role in eosinophil regulation by IFN-γ.
New Aspects of Itch Pathophysiology: Component Analysis of Atopic Itch Using the ‘Eppendorf Itch Questionnaire’
Authors: Darsow U. , Scharein E. , Simon D. , Walter G. , Bromm B. , Ring J.
Published: April 2003

Itch represents a leading symptom in dermatological practice with many psychophysiological aspects. Instruments for qualitative registration of these central nervous factors and evaluation of therapeutic measures are still missing. We analyzed in detail the subjective itch sensation in 108 patients with acute atopic eczema with a new questionnaire developed in analogy to the McGill pain questionnaire. The descriptors with the highest load in atopic itch and the most frequent reaction patterns in atopic eczema patients were identified. Itch intensity (mean VAS 62%) and eczema severity (SCORAD mean 41 points) showed a different frequency distribution pattern with a correlation of r = 0.33 (p < 0.05). Principal component analysis of the itch questionnaire data was performed and compared with the standardized SCORAD severity index for the patients with atopic eczema. Three main factors of atopic itch explained 58% of the total variance: (1) ‘suffering’ (correlation with SCORAD, r = 0.6); (2) ‘phasic intensity’ (correlation with SCORAD, r = 0.4), and (3) ‘ecstatic’ component (associated with certain active reaction patterns). In conclusion, the complete description of itch has to consider different factors, which may be described on a more general level by three main components. Two of these are correlated with objective criteria of disease activity.
Theophylline at Therapeutic Concentrations Inhibits NF-κB Activation in Human Lung Mast Cells
Authors: Sagara Hironori , Makino Sohei , Chibana Naomi , Ota Mayumi , Holgate Stephen T. , Church Martin K. , Fukuda Takeshi
Published: April 2003

Inflammation of the airways is a cardinal feature of asthma. It has recently been recognized that mast cells may contribute to this process by cytokine secretion. Activation of a number of transcription factors, such as NF-ĸB, results in the de novo synthesis of a wide spectrum of cytokines including TNFα, IL-8 and GM-CSF. We have assessed the activation of NF-ĸB by exposure of purified lung mast cells to TNFα (5 ng/ml), SCF (10 ng/ml) and anti-IgE (1 µg/ml). Mast cells were identified by cytospin immunocytochemistry using the antitryptase antibody AA-1 and activated NF-ĸB visualized by the antibody 2c7 (Upjohn) which recognizes a site revealed only on its dissociation from I-ĸB. In addition, the effects of theophylline and other modulatory drugs have been examined on NF-ĸB activation and consequential cytokine secretion. Results show that TNFα increased the percentage of cells staining positive for activated NF-ĸB from 8.4 ± 4.8 to 63 ± 4.5 within 15 min. Anti-IgE caused a slow increase from 4.3 ± 0.4 to 45.4 ± 13.3% at 4 h. Theophylline at 20 µg/ml decreased TNFα and anti-IgE induced NF-ĸB activation by 37.3 ± 2.1 and 25.3 ± 1.3%, respectively. Secretion of TNFα, IL-8 and GM-CSF was also inhibited by 20 µg/ml theophylline. The suppression of NF-ĸB activation indicates that theophylline, in addition to its bronchodilator actions, has anti-inflammatory activity which is likely to be pertinent to the treatment of bronchial asthma.
Preliminary Evidence for ‘Aberrant’ Expression of the Leukocyte Integrin LFA-1 (CD11a/CD18) on Conjunctival Epithelial Cells of Patients with Mite Allergy
Authors: Pesce G. , Ciprandi G. , Buscaglia S. , Fiorino N. , Salmaso C. , Riccio A.M. , Canonica G.W. , Bagnasco M.
Published: April 2003

Background: We have previously shown aberrant expression of the ‘leukocyte’ integrin LFA-1 on epithelial cells in chronic autoimmune thyroiditis. In the present study we investigated whether conjunctival epithelial cells, which bear the adhesion molecule ICAM-1 on their surface during allergic inflammation, may also aberrantly express its natural ligand, the ‘leukocyte’ integrin LFA-1. Methods: We studied 13 patients with rhinoconjunctivitis allergic to mites, chronically exposed to the allergen, 11 patients allergic to pollen tested out of the pollen season and 8 normal volunteers. Single and double immunocytochemical staining of conjunctival smears was employed. Results: LFA-1 staining on epithelial cells was demonstrated in 12/13 patients allergic to mites and not in normal controls or in patients allergic to pollen tested out of the pollen season. The epithelial localization of LFA-1 was confirmed by double staining with anti-LFA-1 and anti-cytokeratin antibodies (both immunocytochemical and immunofluorescence). Conclusions: Coexpression of LFA-1 and ICAM-1 during persistent allergen stimulation may be relevant for interaction between epithelial cells and activated effector cells, such as eosinophils, which bear on their surface both ICAM-1 and its β2 integrin ligands.
Eosinophil Transmigration across VCAM-1-Expressing Endothelial Cells Is Upregulated by Antigen-Stimulated Mononuclear Cells
Authors: Nagata Makoto , Yamamoto Hideaki , Tabe Kazuaki , Sakamoto Yoshio
Published: April 2003

Background: Adhesion to and transmigration across endothelial cells expressing vascular cell adhesion molecule 1 (VCAM-1) may be key steps in the development of selective eosinophil accumulation at the allergic inflammation sites. There is evidence that cytokines/chemokines produced by CD4+ T cells play a prominent role in these processes. Objective: The objective of this study was to evaluate whether eosinophil migration across human pulmonary microvascular endothelial cells (HPMEC) expressing VCAM-1 is modulated by the supernatants of antigen-stimulated mononuclear cells obtained from atopic asthmatics. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from Dermatophagoides farinae(Df)-sensitive asthmatic subjects and cultured for 96 h at 37°C in the presence or absence of 1 µg/ml Df antigen. Eosinophils were isolated from blood of healthy subjects and placed on the HPMEC monolayers cultured on a transwell filter (3-µm pore size) stimulated with IL-4 plus TNF-α (both at 100 pM, 24 h) The supernatants of PBMC were then applied to the lower compartment and the transmigration of eosinophils was examined. Results: The supernatants of PBMC stimulated with Df significantly enhanced the eosinophil transmigration across VCAM-1-expressing HPMEC (% migration: 7.6 ± 0.6 by the supernatants of PBMC cultured without Df vs. 12.3 ± 1.2 by the PBMC cultured with Df, p < 0.01, n = 8). The enhanced migration, but not spontaneous migration, was blocked by the anti-α4 integrin antibody. Moreover, the enhanced transmigration was blocked by anti-CCR3 antibody. Conclusion: The antigen-stimulated PBMC from atopic asthmatics produce an activity to induce eosinophil migration across VCAM-1-expressing endothelial cells. This activity appears to involve CCR3 as an essential molecule.
Expression of VLA-4 on Eosinophils Decreases in Patients with Eosinophilia
Authors: Kayaba Hiroyuki , Yamada Yoshiyuki , Cui Chang-hao , Saito Norihiro , Honda Kohei , Kobayashi Yoshimi , Urayama Osamu , Chihara Junichi
Published: April 2003

Background: It is assumed that the very late antigen-4 (VLA-4) plays a key role in selective migration and accumulation of eosinophils to the allergic inflammatory focus. The regulatory mechanism for VLA-4 expression is poorly understood, as is its relationship between other adhesion molecules. Objective: The aim of the study was to elucidate the relationship between VLA-4 expression and the activation of eosinophils. Methods: The surface expression of VLA-4, Mac-1, ICAM-1, CD4, CD25, CD69, CD89, IL-5 receptor and GM-CSF receptor on eosinophils isolated from the peripheral blood of 15 patients with eosinophilia and 16 healthy volunteers was measured. Results: The surface expression of VLA-4 presented in mean fluorescent intensity by flow-cytometric analysis showed a significant decrease in the patients with eosinophilia (>700 eosinophils/µl) compared to that of the subjects without eosinophilia. On the other hand, the surface expression of Mac-1 was significantly increased in the patients with eosinophilia. There was an inverse correlation between the expression of VLA-4 and that of Mac-1 (r = –0.81) on the eosinophils obtained from the patients with eosinophilia. Conclusion: The changes on the surface expressions of Mac-1 and VLA-4 may be indicating the activation of eosinophils in the patients with eosinophilia and may contribute to their migration to the allergic inflammatory focus.
The Role of Interleukin-10 in the Generation of CD4+ and CD8+ Memory T Cells (Expressing a CD44+, CD62L– Phenotype) and Their Contribution to the Regulation of Immunoglobulin E Antibody Formation
Authors: Arps Volker , Kölsch Eckehart
Published: April 2003

Background: Immunization of mice with low doses of protein antigens like keyhole limpet hemocyanin (KLH) results in high immunoglobulin (Ig) E Ab titers in the sera of those mice while the application of high doses leads to the production of only marginal amounts of IgE but high levels of IgG2a and IgG1 antibodies. The aim of these studies is to elucidate the role of interleukin-10 (IL-10) in the generation of memory T cells and their contribution to the production of IgE Ab. Methods: Both IL-10-deficient mice and control mice were immunized repeatedly with KLH. Serum levels of KLH-specific Ab were measured. The frequencies of memory T cells were determined by flow cytometry and the role of CD4+ and CD8+ T cells was evaluated. Results: IL-10-deficient mice show an augmented production of IgE in vivo. They exhibit enhanced ratios of CD4+:CD8+ memory T cells with a CD44+, CD62L– phenotype with a significantly raised generation of CD4+ memory T cells. On the other hand, the development of CD8+ memory T cells is reduced moderately in IL-10-deficient mice, which is an interesting fact since it has been shown that primed CD8+ T cells suppress IgE Ab production at least in vitro. The ratios of total CD4+:CD8+ T cells are augmented in IL-10-deficient mice compared to wild-type mice and in K01 mice compared to K100 mice in vivo. Conclusions: The elevated ratios of CD4+:CD8+ T cells indicate a higher capacity to provide B cell help, which results in a strongly elevated IgE response in IL-10-deficient mice. These altered ratios are furthermore interesting in view of the regulatory role of CD8+ T cells which provide a suppressive potential regarding IgE Ab production as shown in vitro. The capacity of IL-10 to suppress IgE Ab production by reduction of the CD4+:CD8+ memory T cell ratio opens new possibilities in the interference with allergic disorders.
Wasp Venom Rush Immunotherapy Induces Transient Downregulation of B Cell Surface Molecule Expression
Authors: Roever Anne C. , Henz Beate M. , Worm Margitta
Published: April 2003

Background: Little is known about the involvement of B cells in venom immunotherapy (VIT). To elucidate changes in the B cell phenotype during this process, we examined the expression of several surface molecules on peripheral B cells before and during VIT. Methods: 15 venom-allergic patients with a history of systemic reactions after a wasp sting and venom-specific skin test reactivity as well as serum IgE were investigated before VIT (day 1), 1 day after reaching a maintenance dose of 100 µg (day 6) during inpatient rush VIT, and again on day 26 during continued outpatient maintenance therapy. Changes in the serum levels of total IgE, allergen-specific IgE (sIgE) and sIgG4 were measured by ELISA. Expression of several surface molecules on double-labelled B cells was studied by flow cytometry of peripheral blood mononuclear cells. Results: Levels of total IgE, sIgE and sIgG4 showed a significant increase after 26 days of VIT. On day 6, cell surface expression of HLA- II-DR, CD5, CD32 and CD54 was decreased in intensity and numbers of positive cells compared to day 1, while on day 26, expression of these molecules approached again baseline levels. Furthermore, a trend to decreased CD23 was noted on day 6. No changes were observed for CD40, CD86, CD95 and HLA-I-ABC. Conclusion: These data show that during initiation of rush VIT, B cell expression of surface molecules involved in T-B cell cooperation and antigen presentation is downmodulated. B cells may thus be additional direct or indirect targets of high-dose antigen therapy and contribute to the persistence of TH1 responses during maintenance VIT treatment.
Prediction of Smallness for Gestational Age by Maternal Serum Human Chorionic Gonadotropin Levels and by Uterine Artery Doppler Study
Authors: Miyakoshi Kei , Tanaka Mamoru , Gabionza Danilo , Ishimoto Hitoshi , Miyazaki Toyohiko , Yoshimura Yasunori
Published: April 2003

Objectives: To compare the utility of maternal serum human chorionic gonadotropin (MShCG) levels with that of uterine artery Doppler study in predicting small for gestational age (SGA) birth and pregnancy-induced hypertension (PIH). Methods: MShCG assay and uterine artery Doppler study were performed in 359 consecutive pregnant women with singleton pregnancies. MShCG levels ≧2.0 multiples of the median at 15–18 weeks’ gestation were considered to be elevated. An abnormal uterine artery Doppler velocimetry at 21–24 weeks’ gestation was defined as a mean pulsatility index above the 95th percentile or the presence of an early diastolic notch in either uterine artery. The predictive values of MShCG levels and uterine artery Doppler velocimetry were evaluated for the risk of SGA birth and PIH. Results: Forty-one subjects gave birth to SGA infants, and 20 developed PIH. Patients with MShCG elevation or abnormal uterine artery Doppler velocimetry showed a significantly higher incidence of SGA infants than the controls. The sensitivity and specificity of MShCG elevation for SGA birth were 17.1 and 93.4%, respectively, compared with abnormal uterine artery Doppler velocimetry, which had 24.4 and 94.3%, respectively. There was no significant difference between these methods. Elevated levels of MShCG and abnormal uterine artery Doppler velocimetry were not associated with PIH. Conclusion: Elevated levels of second-trimester MShCG were as sensitive and specific in predicting SGA births as abnormal uterine artery Doppler velocimetry.
Intrauterine Treatment of Fetal Goitrous Hypothyroidism Controlled by Determination of Thyroid-Stimulating Hormone in Fetal Serum
Authors: Grüner Christian , Kollert Anja , Wildt Ludwig , Dörr Helmut G. , Beinder Ernst , Lang Norbert
Published: April 2003

We report a rare case of fetal goitrous hypothyroidism complicated by polyhydramnios and preterm labor in a mother without thyroid gland pathology. The diagnosis was made in the 26th week by ultrasound and cordocentesis [TSH 170 µU/ml, free T4 0.2 ng/dl]. The therapeutic regime required repeated fetal blood sampling for determination of thyroid hormones. Five intra-amniotic administrations of 250 µg levothyroxine (LT4) weekyl were initiated. Because of the persisting goiter and the elevated level of TSH (128 µU/ml in 32 weeks) in the fetal serum the dosage had to be adjusted to 500 µg LT4 in the next five injections. TSH in fetal serum declined to 49.2 µU/ml in 36 weeks. Normal fetal growth and an uncomplicated course of pregnancy between the 27th and 37th week of gestation were observed. Monitoring of intrauterine therapy by determination of TSH in fetal serum may provide more reliable data than measuring TSH in amniotic fluid. A review of 15 cases of fetal goitrous hypothyroidism in the English literature is presented.
A Case of Massive Subchorionic Thrombohematoma Diagnosed by Ultrasonography and Magnetic Resonance Imaging
Authors: Kojima Kazuhisa , Suzuki Yoshikatsu , Makino Aiko , Murakami Isamu , Suzumori Kaoru
Published: April 2003

Massive subchorionic thrombohematoma is uncommon but associated with a poor perinatal prognosis. Placental enlargement was detected in a 25-year-old Japanese primipara woman with fetal growth retardation and oligohydramnios at 23 weeks’ gestation. Ultrasonography (USG) showed an abnormal sonolucency within the placenta at 28 weeks’ gestation, but could not give an unequivocal differentiation from placental abnormalities such as hematomas, cysts and other tumors. Magnetic resonance imaging (MRI) pointed to a large hematoma in the subchorionic region. Simultaneously, the amniotic fluid was brownish colored. From these findings, it was possible to have prenatal diagnosis of massive subchorionic thrombohematoma. At 32 weeks’ gestation, the fetus died in utero and was stillborn 3 days later. Pathological findings for the placenta revealed a large hematoma diffused between the villous chorion and the chorionic plate, with wide necrosis of placental tissue, likely due to formation of multiple thrombi. The clinical and pathological findings were compatible with massive subchorionic thrombohematoma. MRI might be useful for the detection of massive subchorionic thrombohematoma and help its clinical management in combination with USG and pulse Doppler imaging.
Is Intracytoplasmic Sperm Injection Itself an Indication to Perform Preimplantation Genetic Diagnosis (PGD)?
Authors: Ludwig M. , Geipel A. , Berg C. , Gembruch U. , Schwinger E. , Diedrich K.
Published: April 2003

Intracytoplasmic sperm injection (ICSI) provides the only sufficient treatment to overcome severe forms of male infertility. However, male infertility is linked to several genetic problems as an increased number of chromosomal aberrations, cystic fibrosis transmembrane conductance regulator gene mutations, Y-chromosome microdeletions, and androgen receptor mutations. Therefore, these couples are at a higher risk of transmitting genetic problems to their offspring compared to the general population. A proposed increased number of gonosomal aberrations in the offspring possibly results from the ICSI technique itself. This led in general to a worldwide agreement to counsel those couples to undergo invasive prenatal diagnosis in order to exclude chromosome abnormalities, especially gonosomal aberrations. In this paper the genetic risks of these couples and the possible implications of ICSI itself are discussed. Preimplantation genetic diagnosis may be considered a procedure of choice in these cases, but substantial ethical problems arise when such a screening is sought. An alternative procedure of prenatal diagnosis in these couples seems to be ‘genetic sonography’, i.e. high-resolution ultrasound with measurement of nuchal translucency at the end of the first trimester, and detailed fetal evaluation at 18–22 weeks of gestation.
Fetomaternal Transfusion and Pregnancy Outcome after Cordocentesis
Authors: Sikovanyecz János , Horváth Emese , Sallay Éva , Gellén János , Pál Attila , Szabó János
Published: April 2003

Objective: To study the extent of fetomaternal transfusion and the outcome of pregnancy after cordocentesis. Material and Methods: 268 women underwent percutaneous fetal umbilical cord blood sampling for fetal karyotyping between 15 and 26 gestations of weeks. Complete follow-up was available in 221 (82.5%) of the cases. Cordocentesis was performed under continuous real-time ultrasound guidance. The duration of the procedure and the post-procedural bleeding time was counted in seconds. Fetomaternal transfusion was calculated by using the measurements of the maternal serum levels of α-fetoprotein before and after the procedure. The data were analyzed by Student’s t and multiple regression tests. Results: The maximum and mean amounts of fetomaternal transfusion were 1.067 and 0.061 ml, respectively. Twenty percent or more α-fetoprotein elevation was in 35.4% of the cases. Positive correlation was found between bleeding time after cordocentesis and fetomaternal transfusion (r = 0.174, p < 0.0129) as well as between the duration of the procedure (r = 0.165, p < 0.0171) and the amount of fetomaternal transfusion. Comparing the cordocentesis at the placental insertion site and at the free cord loop, a smaller amount of fetomaternal transfusion was observed (p < 0.0123) in the latter. Transplacental passage was associated with a higher amount of fetomaternal transfusion (p < 0.0067). No association was found between the extent of fetomaternal transfusion and the outcome of pregnancy. The fetal loss related to the cordocentesis was 0.50%. Conclusions: The extent of fetomaternal transfusion was influenced by the subsequent four parameters: procedural time, bleeding time, puncture site and transplacental penetration. The lack of the association between the degree of fetomaternal transfusion and the outcome of pregnancy, along with the low (0.50%) post-procedural fetal loss rate, suggest that cordocentesis is clinically a safe procedure.
Endoscopic Documentation of Unintentional Perforation of the Dividing Membrane during Amnioreduction for Twin-Twin Transfusion Syndrome
Authors: Cooper Rachel , Bornick Patricia W. , Allen Mary , Quintero Rubén
Published: April 2003

Objective: The purpose of this report is to document endoscopically the occurrence of unintentional piercing of the dividing membrane in a monochorionic twin pregnancy with twin-twin transfusion syndrome (TTTS). Materials and Methods: The dividing membrane was visualized endoscopically during laser therapy in a patient with TTTS who had previously undergone therapeutic amniocentesis. The donor twin had no visible bladder, but the amniotic fluid volume had normalized after amniocentesis. Results: The suspected membrane perforation was identified endoscopically during laser surgery. Five areas of vascular communications were identified and photocoagulated. Conclusions: Sonographic evidence of normalization of the amniotic fluid volumes after therapeutic amniocentesis with persistent nonvisualization of the bladder of the donor twin should not be interpreted as a sign of improvement of TTTS, but rather as indirect evidence of unintentional perforation of the dividing membrane. This complication can be confirmed endoscopically.
Prenatal Diagnosis and Postnatal Outcome of Congenital Megalourethra
Authors: Perrotin Franck , Ayeva-Derman Michael , Lardy Hubert , Cloarec Sylvie , Lansac Jacques , Body Gilles
Published: April 2003

We present 2 cases of congenital megalourethra diagnosed by prenatal ultrasound scan during the second trimester of pregnancy. The first one was associated with features suggesting prune belly syndrome (PBS) in contrast to the other one. Fetal urine biochemistry and fetal serum β2-microglobulin was used to rule out severe renal impairment that would have led to postnatal renal failure soon after birth. In both cases, after extensive counselling, the parents opted against termination of pregnancy and in both cases vaginal delivery of a live neonate occurred. Postnatal follow-up demonstrated that the two infants were found to have mildly altered renal function without any physical or mental development delay. Association with features of PBS didn’t seem to influence the severity of renal function impairment however, but PBS may influence parents’ decision regarding termination because of additional corrective surgery and further infertility.
Prevalence of Tetraploid Metaphases in Semidirect and Cultured Chorionic Villi
Authors: Noomen Petra , van den Berg Cardi , de Ruyter Jacqueline L.M. , van Opstal Diane , Los Frans J.
Published: April 2003

Objective: Investigation of the normal frequency of tetraploid metaphases in semidirect (STC) and cultured (LTC) chorionic villi. Methods: Fifty metaphases in STC- and in LTC-villi slides of 100 women of advanced maternal age were screened for tetraploidy. Results: Up to three tetraploid metaphases were encountered in 27% of the STC-villi preparations; the scores fitted a Poisson distribution. In all LTC-villi preparations tetraploid cells were seen; the scores fitted a log-Gaussian distribution. Conclusions: On the basis of these distributions, we propose a protocol for the management of tetraploid metaphases in chorionic villi, strongly reducing the number of prenatal follow-up investigations.
Outcome in Prenatally Diagnosed Fetal Agenesis of the Corpus callosum
Authors: Goodyear P.W.A. , Bannister C.M. , Russell S. , Rimmer S.
Published: April 2003

This study of the outcome and prognostic factors in prenatally diagnosed agenesis of the corpus callosum (ACC) was undertaken to see if there are any differences between subgroups, what relationship they have to neurodevelopmental outcome and whether this information aids the counselling of parents of fetuses with the condition. The outcome of 14 prenatally diagnosed fetuses with ACC and 61 postnatally diagnosed patients was assessed in terms of clinical problems, developmental milestones and neurological signs; each patient was then given a score out of 10, 0 being a normal outcome and 10 being the worst outcome, i.e. death or termination of pregnancy. Comparing patients diagnosed pre- and postnatally, several similarities were found indicating that the postnatal group can provide useful information about the prenatal group. There was a higher incidence of ACC in males than females. In the prenatally diagnosed patients complete ACC was more common than partial ACC, although this might be because partial ACC was easily missed. Complete ACC has a worse prognosis than partial ACC (p = 0.001), and when associated with other anomalies, especially of the central nervous system, the outcome is very bad (p < 0.01). The only neurodevelopmentally normal patients were in the isolated partial ACC group. This study highlights the need to perform a detailed review of fetal anatomy and the desirability of determining the karyotype of the fetus in all newly diagnosed cases of ACC so that as much information as possible is available before parents are counselled about the likely outcome.
Bonding and Coping with Loss: Examining the Construction of an Intervention for Multifetal Pregnancy Reduction Procedures
Authors: Britt David W. , Mans Mary , Risinger Samantha T. , Evans Mark I.
Published: April 2003

Multifetal pregnancy reduction is a medical procedure by which pregnancies usually with three or more embryos are reduced in number early in gestation to improve their medical outcomes. A socially constructed intervention used as part of these procedures at Wayne State University is described. The intervention has as its goals the reduction of anxiety in the woman undergoing such a procedure and the refocusing of attention on the surviving ‘twins’ or singleton. Case materials from 36 cases are examined in detail to document how the intervention is being accomplished in practice, and how it may break down.
Growing of Caecum and Vermiform Appendix during the Fetal Period
Authors: Malas M.A. , Gökçimen A. , Sulak O.
Published: April 2003

Objective: The aim of this study is to investigate the growing of the caecum and the vermiform appendix during the fetal period in human fetuses and the relation between growing and shape of the caecum and the localization of the vermiform appendix. Methods: 40 male and 40 female externally normal-looking fetuses were studied between 10 and 40 weeks of gestation and were subdivided into fetuses of the 1st, 2nd, and 3rd trimesters and full-term fetuses. The parameters of interest included covering of the caecum with peritoneum, shape of the caecum (long tube, symmetric saccule, asymmetric saccule, extremely large right side – atypical), axial length and width of the caecum localization of the vermiform appendix, length of vermiform appendix and length of the meso-appendix. Results: There was a difference in covering of the caecum with peritoneum between males and females; the caecum was predominantly tube shaped during the fetal period, with the asymmetric saccule towards the end of the fetal period; the localization of the vermiform appendix was subcaecal (39%) during the fetal period and postileal (34%) in female fetuses and subcaecal (48%) in male fetuses – the localization of the vermiform appendix changed according to the caecum shape during the fetal period; we found significant differences in the measurements of vermiform appendix, meso-appendix, and caecum among 1st-, 2nd-, and 3rd-trimester fetuses and full-term fetuses. Conclusions: There was an increase in the measurements for vermiform appendix, meso-appendix, and caecum with increasing gestational age; the localization of the vermiform appendix depended on the shape of the caecum, was different from that of adults and different between sexes, and there was also a significant difference in covering of the caecum with peritoneum between both sexes.
Outcome of the Prenatally Diagnosed Congenital Cystic Adenomatoid Lung Malformation: A Canadian Experience
Authors: Laberge J.M. , Flageole H. , Pugash D. , Khalife S. , Blair G. , Filiatrault D. , Russo P. , Lees G. , Wilson R.D.
Published: April 2003

Congenital cystic adenomatoid malformation of the lung (CCAM) is diagnosed by prenatal ultrasonography with an increasing frequency but controversy persists as to its prognosis and prenatal management. Method: A multi-institutional study of cases of CCAM diagnosed antenatally identified by ultrasonographers and by a review of hospital charts. Results: We obtained 48 cases from five centers. We estimate the incidence of CCAM at 1:25,000 to 1:35,000 pregnancies. The incidence of voluntary abortions was 15% (7/48), of spontaneous abortions 2% (1/41) and of postnatal death 10% (4/40). One of the postnatal deaths was from trisomy 18. Of the 7 aborted fetuses, 2 had multiple malformations and 1 had severe hydrops and oligohydramnios; the other 4 had a large mass with mediastinal displacement but without hydrops. When pregnancy was allowed to continue, 56% of the lesions regressed spontaneously, even though one third of these had initial progression. In 17 cases (42%) the mediastinal shift corrected itself, sometimes by simple growth of the fetus but most often by a decrease in the size of the lung mass. In 1 fetus, repeated needle decompressions followed by double-pigtail catheter drainage of large cysts allowed regression of hydrops. Despite this, neonatal death occurred from pulmonary hypoplasia. Conclusion: CCAM can lead to fetal or neonatal demise from hydrops, lung hypoplasia, prematurity or severe associated malformations, but has a good prognosis in the majority of cases.
Effects of Intra-Amniotic Meconium Exposure on the Fetal Rat: Development of a Pathogenic Model
Authors: Blackwell Sean C. , Hallak Mordechai , Hotra John W. , Hassan Sonia S. , Berry Stanley M. , Sorokin Yoram
Published: April 2003

Objective: To develop an in vivo animal model for the study of the effects of intrauterine meconium exposure on the fetus. Methods: Timed pregnant Long-Evans rats were purchased on gestational day (GD) 12 and allowed to acclimate for at least 48 h prior to surgery. Laparotomy was performed and both uterine horns were exteriorized through the abdominal incision. A 26-gauge needle was used to inject either 0.1-cm3 sterile normal saline or a 20% meconium suspension into each individual gestational sac. The uterus was returned to the abdomen and the incision was closed. On GD 21 (term = 21 days) a cesarean section was completed and the number and viability of fetuses in each horn were recorded. Results: A total of 14 animals were involved in this pilot study. One rat underwent sham surgery with only intra-amniotic saline injection and 13/15 fetuses survived to term. Two animals that underwent surgery on day 18 expired <24 h postinjection. Eleven maternal animals were injected on GD 20 and underwent cesarean delivery at term; survival rates for saline-injected animals were 71.2% compared to 66.2% for meconium-exposed fetuses. Conclusion: We have established an in vivo animal model that allows for the examination of the effects of prolonged intrauterine meconium exposure on the fetus.
A Fetal Wolff-Parkinson-White Syndrome Diagnosed Prenatally by Magnetocardiography
Authors: Hosono Takayoshi , Chiba Yoshihide , Shinto Mika , Kandori Akihiko , Tsukada Keiji
Published: April 2003

We report a case of fetal Wolff-Parkinson-White (WPW) syndrome diagnosed prenatally by magnetocardiography (MCG). At 32 weeks’ gestation, the fetus was diagnosed to have a paroxysmal supraventricular tachycardia by ultrasonography and direct fetal electrocardiogram (ECG). Transplacental fetal therapy by maternal oral administration of propranolol resolved the fetal tachyarrhythmia. Although the wave forms of the fetal MCG at 32 weeks’ gestation were normal, the fetal MCG at 35 weeks’ gestation showed a short PR interval and a long QRS complex duration with a delta wave, indicating WPW syndrome. The findings of the fetal MCG were confirmed by the postnatal ECG. MCG made the prenatal diagnosis of WPW syndrome possible.
Ontogenesis of Villi and Fetal Vessels in the Human Placenta
Authors: Challier Jean-Claude , Vervelle Christian , Uzan Serge
Published: April 2003

The ontogenesis of the villous and vascular arborescence in normal pregnancy is reviewed. The emergence of the villi and the fetal vessels is described from early pregnancy to term together with the specializations of the villi, vessels and capillaries observed in the last trimester. The expression, localization and role of the angiogenic growth factors (FGF, VEGF, PLGF, HGF) are described and discussed. Pathological pregnancies with hyper- and hypocapillarization are related to altered oxygenation. The potential roles of growth factors are presented and hypotheses proposed which may provide a molecular basis for the development of the most frequent placental pathologies.
Gastroschisis Complicated by Midgut Atresia, Absorption of Bowel, and Closure of the Abdominal Wall Defect
Authors: Ogunyemi Dotun
Published: April 2003

We present a case of gastroschisis that was associated with progressive resorption of the extra-abdominal bowel loops and dilation of intra-abdominal bowel loops. After preterm delivery at 32 weeks, a small paraumbilical remnant was present. There was complete atresia of most of the jejunum, ileum, cecum, and the proximal half of the transverse colon. At laparotomy, the jejunum was anastomosed to the transverse colon. The neonate developed short gut syndrome and eventually received a liver and intestinal transplant.
Acardiac Twin with Preserved Brain
Authors: Petersen Bodil Laub , Broholm Helle , Skibsted Lillian , Græm Niels
Published: April 2003

The fatal acardiac syndrome is a rare complication of monochorionic twinning and is reported in 1 of 35,000 births. It is caused by arterioarterial and venovenous placental anastomoses leading to circulatory predominance of 1 twin. The donor ‘pump’ twin provides circulation for itself and for the recipient acardiac twin. The acardiac twin is usually grossly abnormal with severe reduction anomalies of the upper part of the body. We report a twin pregnancy, where a recipient twin initially by ultrasound was misdiagnosed as dead. In the third trimester the supposedly dead twin presented as an edematous acardiac twin without peripheral reduction defects and a nearly normally developed brain. An acardiac twin with a nearly normal external appearance and an almost normally developed brain, nourished by a surviving twin brother, has not previously been described in the literature.
Congenital Cataract in Triplet Pregnancy after IVF with Frozen Embryos: Prenatal Diagnosis and Management
Authors: Cengiz Bora , Baxi Laxmi
Published: April 2003

Unilateral congenital cataract was diagnosed at the 2nd trimester ultrasonography in a triplet pregnancy following in vitro fertilization (with frozen embryos). Congenital cataract could be hereditary or related to metabolic and infectious disorders. To our knowledge this is the first antenatal diagnosis of the disorder in triplets after IVF with frozen embryos.
Prenatal Diagnosis of Steroid 21-Hydroxylase Deficiency by Allele-Specific Amplification
Authors: Theodoropoulou Marily , Barta Csaba , Szoke Melinda , Guttman András , Staub Maria , Niederland Tamás , Sólyom János , Fekete György , Sasvari-Szekely Maria
Published: April 2003

Objective: Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency (21-OHD) is the most common cause of ambiguous genitalia in females at birth. Here, we report the first prenatal diagnosis of 21-OHD by DNA analysis in Hungary. Methods: Allele-specific amplification (ASA) of the DNA obtained by chorionic villus sampling was performed. Results: The fetus had a homozygous nonsense mutation (Gln318Stop), suggesting a salt-wasting phenotype. Dexamethasone treatment of the mother was started on the 8th gestational week and, as the fetus was an affected female, it was continued until term. The newborn had normal external genitalia at birth, and severe salt-wasting crisis and postnatal virilization was prevented by mineralo- and glucocorticoid replacement therapy. Conclusion: 21-OHD was genotyped by ASA, and virilization of the fetus was prevented by antenatal dexamethasone therapy.
Sepsis in Second Trimester of Pregnancy due to an Infected Myoma
Authors: Grüne Barbara , Zikulnig Elisa , Gembruch Ulrich
Published: April 2003

Considering the high incidence of uterine myomata in women in reproductive age, myomata are only found in 2% of all pregnancies. Although they frequently lead to complications in pregnancy, cases of pyomyomata during pregnancy are rarely reported. A 44-year-old gravida 1 in her 26th week of gestation was admitted to the hospital for septic temperatures of unknown cause. A 12-cm leiomyoma with solid structures of heterogenic sonographic pattern and cystic spaces had been documented on a prior first trimester sonogram. The myoma now appeared with the same size but an increased echogenicity of the liquid parts. Ultrasound guided aspiration of the fluid within the myoma showed an infection with Klebsiella pneumoniae. A cesarian section with myo- mectomy confirmed the diagnosis of a pyomyoma.
Pulmonary Atresia with Hypoplastic Right Ventricle
Authors: Fröber R. , Kohoutek T. , Kähler Ch. , Beensen V. , Hauschild R. , Schulze E. , Linss W.
Published: April 2003

An unusual case of pulmonary atresia with an aberrant karyotype of 46,XX,t(6;8)(p21.2;q11.2) is reported. Fetal ultrasonic examination at the 20th week of gestation revealed a hypoplastic right ventricle and an intact interventricular septum. Authors summarize their postnatal findings in fetal heart and the large adjacent vessels with special reference to the pathogenesis of this rare congenital heart defect. The observation delineates right-ventricular outflow tract obstruction associated with an abnormal pulmonary blood supply. The anatomy of the systemic pulmonary collaterals was studied and correlated with multifocal disorders in the system of the pharyngeal arch arteries in the early embryonic development.
First-Trimester Diagnosis of Sirenomelia
Authors: Carbillon L. , Seince N. , Largillière C. , Bucourt M. , Uzan M.
Published: April 2003

We report a case of sirenomelia diagnosed at 13 gestational weeks. This rare malformation sequence is characterized by fusion and rotation of the lower limbs to various degrees and anorectal atresia, usually associated with absence of bladder and agenesis or dysgenesis of the kidneys. Diagnosis is commonly made later in the second trimester of pregnancy with oligohydramnios as the alerting sign. Survival is extremely rare, and only possible in the absence of bilateral renal agenesis. In view of the dismal prognosis, early diagnosis allows for earlier and less traumatic therapeutic abortion.
Evaluation of Two-Dimensional versus Three-Dimensional Ultrasound in Obstetric Diagnostics: A Prospective Study
Authors: Scharf Alexander , Ghazwiny Marjan Farasaty , Steinborn Andrea , Baier Peter , Sohn Christof
Published: April 2003

Objectives: We aimed to find answers to the following questions: What are the technical and biological prerequisites for easily obtainable three-dimensional (3D) images? What are the visualization rates for various fetal organ systems? What is the potential for assessing fetal malformations? What are the psychological effects of 3D imaging on the expectant mothers? Methods: Between January and June 1998, 433 pregnant women were prospectively examined with two-dimensional (2D) and 3D sonography. Results: 3D visualization in healthy fetuses was inferior in quality to 2D visualization, which also accounted for the comparison of 3D imaging versus 2 D imaging among fetuses affected with malformations. In only 1 case did 3D imaging yield a slightly better description of the given malformation. This did not result in a different therapeutical approach. Concerning the psychological effect of 3D imaging, a marked approval of the 3D method was recorded. Conclusions: These results show that the image information acquired by 3D ultrasound technology is nearly always inferior to the image information obtained by conventional 2D imaging. 3D imaging can be useful for specific malformations under the condition that these examinations be performed in specific ultrasound departments. Thus, a clearly defined range of indications can be assigned to 3D imaging.
Visualisation and Measurement of Tracheal Diameter in the Sheep Fetus: An Ultrasound Study with Stereomicroscopic Correlation
Authors: Kalache Karim D. , Nishina Hidenori , Ojutiku Dale , Hanson Mark A.
Published: April 2003

Objective: There is no information on ultrasonographic visualisation of the upper airways in the sheep fetus, but this species permits to examine the accuracy of ultrasonography in measuring the inner tracheal diameter. This was the aim of our study. Methods: Transabdominal ultrasonography to visualise the trachea was attempted in 16 unsedated Welsh Mountain ewes with a singleton pregnancy at 70 (SD 2) days gestation (term 148 days). The ultrasonographically measured inner tracheal diameter was compared with the actual inner tracheal diameter obtained by stereomicroscopy post-mortem. Results: High-resolution ultrasonography permitted clear imaging of the fetal trachea in 87% (14/16) of the cases analysed. The ultrasound measurements were smaller than the corresponding stereomicroscopic measurements, the mean ± SD difference between the measurements being 0.40 ± 0.12 mm. Conclusions: Improvements in ultrasound have led to increased interest in the assessment of the trachea in human fetuses. Our study in the ovine fetus at mid gestation shows that optimal views of the fetal trachea allowing accurate measurements can be obtained in almost all the cases.
Sonographic Cervical Volumetry in Higher Order Multiple Gestation
Authors: Strauss Alexander , Heer Ivo , Fuchshuber Susanne , Janssen Udo , Hillemanns Peter , Hepp Hermann
Published: April 2003

Objective: The aim of this study of multifetal pregnancies was the comparison of three-dimensional (3D) volumetry of the cervix, conventional sonographic cervical length measurement and clinical assessment. Methods: 10 mothers were investigated in an observational study between 5/1999 and 9/2000. A total of 34 consecutive 2D- and 3D-transabdominal ultrasound measurements were performed. Results: Volumetry of the cervix was possible in all 34 exams. 2D-cervical length assessment could not be obtained in 6% because the presenting fetal part obstructed the sonographic plane. Both methods allowed equal judgement of the configuration of the cervix. A significant correlation was found between mean 2D-cervical length (28.7 mm, 7.7 SD) and mean cervical volume (30.0 cm3, 16.0 SD). Parity, subjective preterm labor or need of tocolytics showed no correlation with any biometrical parameter studied. Conclusion: Volumetry was superior for the assessment of cervical biometry and conformation in women when the transabdominal 2D-plane was obstructed. When cervical length was obtainable by a conventional scan, the technically more complex 3D-imaging did not provide further information.