bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Weather Conditions and the Incidence of Emergency Gynecological Consultations
Authors: Bianchi-Demicheli Francesco , Lüdicke Frank , Spinedi Fosco , Major Attila L. , Kulier Regina , Campana Aldo , Gyr Thomas
Published: April 2003

Objective: This study examined the influence of weather conditions on the incidence of outpatient emergency consultations at the Department of Obstetrics and Gynecology at the Regional Hospital in Lugano, Switzerland. Study Design: The medical records of all women who attended the outpatient emergency unit at the Department for Obstetrics and Gynecology over the 1-year study period were reviewed. The final diagnosis was pelvic pain of unidentified origin in 180 cases, menorrhagia and/or metrorrhagia in 95 cases, threatened abortion in 56 cases and spontaneous abortion in 54 cases. The meteorological factors considered were atmospheric pressure, temperature, humidity and global radiation. A logistic regression model was used to correlate the occurrence of symptoms with the chosen weather factors. Results: High mean daily temperature was found to be a significant predictor of pelvic pain (p < 0.001). A rise in barometric pressure compared to the previous day increased the probability of menorrhagia and/or metrorrhagia (p = 0.001). Higher minimal temperature (p = 0.011) and an increase in atmospheric pressure (p = 0.006) were identified as positive predictors of threatened abortion. None of the meteorological factors considered seemed to influence the frequency of spontaneous abortions. Conclusion: Meteorological factors such as temperature and barometric change appear to affect the probability of emergency admissions for gynecological symptoms including uterine bleeding, threatened abortion and pelvic pain.
Plasma Levels of Soluble Fas during Normal Pregnancy
Authors: Hoshimoto Kazunori , Hayashi Masatoshi , Ohkura Takeyoshi
Published: April 2003

The Fas/Fas ligand system could reportedly help to identify a mechanism for maternal immunotolerance of the fetus in human pregnancy. However, there are few reports on soluble Fas (sFas) which is an inhibitor of apoptosis during normal pregnancy. Therefore, ascertaining plasma sFas levels during pregnancy would be of interest. The subjects studied were 10 nonpregnant healthy women and 20 healthy pregnant women in the first and third trimester with singleton gestations. The plasma sFas was measured by sandwich enzyme-linked immunosorbent assay. The mean concentration of sFas was significantly decreased in normal pregnant women in the first trimester compared to age-matched control subjects, and it did not differ significantly between normal pregnant women in the third trimester and age-matched control subjects. From these results, we presume that the decreased plasma sFas plays an important role in maternal immunotolerance in the first trimester of pregnancy.
Serum Nitric Oxide and Glutathione Levels in Preeclamptic and Normotensive Women during Labor
Authors: Yanık Filiz F. , Amanvermez Ramazan , Koçak İdris , Yanık Ali , Çelik Cemil
Published: April 2003

This study was performed on 38 preeclamptic women, including 26 severely preeclamptic and eclamptic cases, as well as 50 normotensive pregnant controls. Twenty cases in the preeclamptic group and 34 cases in the control group were in labor. Serum nitric oxide levels were measured as total nitrites after reduction of nitrates to nitrites. Among the control subjects, nitric oxide levels were significantly lower in the cases in labor when compared to those not in labor (p < 0.05), but glutathione levels were not significantly different (p >0.05). Among the preeclamptic patients, although nitric oxide levels were not significantly different between the cases in and not in labor (p > 0.05), glutathione levels were significantly higher in the latter group (p < 0.05). Thus, in preeclamptic patients there might be a compensatory increase in nitric oxide production during labor in order to maintain the systemic circulation. Glutathione levels might also be increased to compensate for the marked oxidative stress.
Intrapartum Prediction of Macrosomia: Accuracy of Abdominal Circumference Estimation
Authors: Al-Inany Hesham , Alaa Nadin , Momtaz Mohamed , Abdel Badii Mona
Published: April 2003

Objective: To evaluate the accuracy of abdominal circumference (AC) estimation of macrosomia early in labor and whether a cutoff value could be detected. Design: A prospective clinical trial. Setting: The Department of Obstetrics and Gynecology, Cairo University. Participants: One hundred pregnant females presenting in early labor with clinical impression of macrosomia were examined by ultrasound, and those babies with abdominal circumference more or equal to 35 cm were recruited for the study. Interventions: Every woman was considered as her own control, and fetal weight was calculated using the formula of Shepard et al. The accuracy of abdominal circumference in prediction of macrosomia was evaluated using the Receiver operating characteristic curve. Results: A cutoff value of AC ≧37 cm was found to have a sensitivity of 77%, a specificity of 75%, a positive likelihood ratio of 3.1 and a negative likelihood ratio of 0.3. Conclusion: Intrapartum ultrasonographic evaluation of abdominal circumference for suspected macrosomic babies in early labor is an easy, practical method that should be adopted in decision making.
Relation between Serum Uric Acid and Plasma Adenosine Levels in Women with Preeclampsia
Authors: Suzuki Shunji , Yoneyama Yoshio , Sawa Rintaro , Otsubo Yasuo , Takeuchi Tsutomu , Araki Tsutomu
Published: April 2003

The aim of this study was to examine the relationship between plasma adenosine and serum uric acid levels in women with preeclampsia. Maternal arterial blood sampling was performed to measure serum uric acid and plasma adenosine levels in 20 pregnant women complicated by preeclampsia and 22 normal pregnant women at 33–38 weeks of gestation. The average plasma adenosine levels were 0.31 ± 0.12 µmol/l in the normal pregnant group and 0.45 ± 0.11 µmol/l in the preeclampsia group. The mean serum uric acid level in women with preeclampsia was 5.9 ± 0.60 mg/dl, significantly higher than in the normal pregnant women (4.4 ± 0.69 mg/dl). Positive correlations were found between serum uric acid and plasma adenosine levels in both the group with (r2 = 0.38, p < 0.05) and the group without (r2 = 0.54, p < 0.05) preeclampsia. There was also a significant correlation between serum uric acid and plasma adenosine levels on the whole (r2 = 0.59, p < 0.05). Our results suggest that increased adenosine is a contributing source of preeclamptic hyperuricemia.
Prognostic Factors and Failure Pattern in Lymph Node-Negative Stage IB and II Cervical Carcinoma Treated with Radical Hysterectomy and Postoperative Irradiation
Authors: Aoki Y. , Watanabe M. , Sasaki M. , Sato T. , Kase H. , Aida H. , Kurata H. , Tanaka K.
Published: April 2003

The aim was to determine the prognostic factors and recurrence pattern in stages IB and II cervical carcinoma patients with negative pelvic lymph nodes. 224 patients with stages IB and II cervical carcinoma underwent radical hysterectomy (RH) from 1982 through 1995. Of 161 patients with negative lymph nodes, 65 patients received postoperative irradiation (RT) and 96 patients were given no further therapy according to surgical pathological findings. The overall 5-year disease-free survival was 94.1%. Two of 96 RH patients (2%) and 10 of 65 RH + RT patients (15%) had recurrence in pelvic and distant sites almost equally. Multivariate analysis revealed deep cervical invasion as the only independent prognostic factor. The 5-year disease-free survival was 98.8% for patients with shallow invasion and 85.8% for patients with deep invasion (p < 0.0001). It is worthwhile to develop new strategies for the lymph node-negative patients with deep stromal invasion.
Implications of a High Placental Ratio in Pregnancies with Appropriate-for-Gestational Age Neonates
Authors: Lao Terence T. , Wong Wai Ming
Published: April 2003

Objective: To determine the relationship between the placental weight to birth weight ratio (placental ratio) with maternal pre-pregnancy weight, gestational weight gain, and neonatal outcome in non-diabetic pregnancies resulting in appropriate-for-gestational age (AGA) infants. Methods: A retrospective study was performed on 593 patients with singleton pregnancies, normal results in the 75-gram oral glucose tolerance test and who delivered AGA newborns within a 1-year period. The patients were categorized into high placental ratio (> mean +1 SD based on previous data, n = 113 or 19.1%) and normal ratio groups for the comparison of maternal and neonatal anthropometric parameters. Results: The high placental ratio group had a higher pre-pregnancy weight, body mass index, placental weight, and incidence of low Apgar score, but decreased absolute and percentage gestational weight gain, gestational age, and birth weight. After controlling for pre-pregnancy weight and gestational age, only the correlation between placental weight and percent weight gain remained significant. Conclusion: Our finding suggests that a high placental ratio can identify AGA newborns who are disproportionately small relative to maternal size, and may reflect some form of fetal growth impairment.
Is the Zona pellucida Thickness of Metaphase-II Oocytes in an IVF/ICSI Program Influenced by the Patient’s Age?
Authors: Nawroth Frank , Müller Pia , Wolf Christian , Sudik Roland
Published: April 2003

Zona pellucida (Z.p.) thickness is believed to be considerably influenced by hormonal stimulation. Assessments of the influence of the patient’s age on Z.p. thickness have been at variance. In our study we wanted to investigate, among several other parameters, the age of the patient as a possible factor influencing Z.p. thickness. Prior to intracytoplasmatic sperm injection (ICSI) we determined the mean thickness of the Z.p. of 843 metaphase-II oocytes from 100 patients, which had been obtained after ovarian stimulation in an in vitro fertilization (IVF)/ICSI program. The mean thickness of the Z.p. was significantly positively correlated with the age of the patient (p = 0.000, r = 0.129). When the intraindividual mean values of Z.p. thickness (n = 100) were used, a positive correlation with age (p = 0.174, r = 0.137) remained. However, this correlation was no longer significant. It is concluded that, beside other factors, a thicker Z.p. could be responsible for the possibly lower fertilization rate of older patients in a conventional IVF program.
Abnormal Nonstress Test yet Otherwise Reassuring Biophysical Profile in a Compromised Fetus with Severe Antepartum Intracranial Hemorrhage
Authors: Sherer David M. , Kogan Melanie G.
Published: April 2003

The fetal biophysical profile (BPP), a widely accepted modality of assessment of fetal well-being, significantly shortens the time required to document reassuring fetal testing and exhibits lower false-positive and false-negative rates than conventional nonstress testing. We describe a case in which a patient presenting for fetal testing due to suspected fetal growth restriction at 29 weeks of gestation with recent onset of decreased fetal movements exhibited a concerning nonreactive nonstress test. BPP assessment revealed active fetal tone, movements, breathing movements and amniotic fluid volume (BPP score 8/8). Despite the reassuring BPP, continued abnormal nonstress testing led to subsequent abdominal delivery of an acidotic infant with evidence of a massive antepartum intracranial insult consisting of frontal intraparenchymal hemorrhage and a right temporal-occipital cortical infarction. This case exhibits limitations of the BPP.
Pelvic Tuberculosis Mimicking Signs of Abdominopelvic Malignancy
Authors: Ozalp S. , Yalcin O.T. , Tanir H.M. , Kabukcuoglu S. , Akcay A.
Published: April 2003

We discuss the clinical presentation and consequences of pelvic tuberculosis in the context of 3 cases having developed typical signs and symptoms of ascites and abdominal mass. These cases are reported to emphasize the difficulty of early diagnosis and treatment of the disease.
Influence of Preeclampsia or Maternal Intake of Omega–3 Fatty Acids on the Vasoactive Effect of Prostaglandin F-Two-Alpha in Human Umbilical Arteries
Authors: Haugen Guttorm , Helland Ingrid
Published: April 2003

The vasoactive effect of prostaglandin F2α (PGF2α) was studied in in vitro perfused human umbilical arteries following maternal dietary supplementation with ω–3 fatty acids or in pregnancies complicated by a moderate degree of preeclampsia. In most preparations PGF2α induced a biphasic pressure response with a transient dilatation followed by a constrictory response. The pressure increase was significant in both groups, but no significant differences in the constrictory response or in the proportions of preparations displaying dilatatory responses were observed when compared to appropriate control groups. In conclusion, neither preeclampsia nor dietary supplementation with cod-liver oil had any significant effect on the vasoactive response to PGF2α in umbilical cord arteries.
Paraneoplastic Cerebellar Degeneration: Neurological Symptoms Pointing to Occult Ovarian Cancer
Authors: Geomini Peggy M.A.J. , Dellemijn Paul L.I. , Bremer Gérard L.
Published: April 2003

Paraneoplastic cerebellar degeneration with anti-Yo antibodies is a rare but disabling neurodegenerative disease that may point to an occult ovarian cancer. Symptoms usually accompanying paraneoplastic cerebellar degeneration include truncal and limb ataxia, dysarthria, dysphagia, nystagmus, vertigo, and diplopia. The pathogenesis of paraneoplastic neurological syndromes is unknown. Treatment results of the neurological symptoms are disappointing. The present case illustrates how neurological symptoms pointed to an occult ovarian cancer.
Doppler Study of the Uterine Arteries and Ovarian Stroma in Patients with Polycystic Ovary Syndrome
Authors: Resende Adriana Vitor , Mendes Maria Célia , Dias de Moura Marcos , Mendonça Hérica Cristina , Gomes Premoli Ana Cristina , Reis Rosana Maria , Berezowski Aderson Tadeu
Published: April 2003

Doppler analysis of the uterine arteries and ovarian stroma was performed by transvaginal ultrasound in 24 patients with polycystic ovary syndrome (PCOS) and 22 ovulatory women. Vascularization of the ovarian stroma was more abundant in patients with PCOS than in control women, but no significant difference in the mean pulsatility index (PI) was observed between groups (1.14 ± 0.28 for the PCOS group and 1.05 ± 0.19 for the control group). The mean PI of the uterine arteries was significantly higher in the PCOS group (PI = 3.7 ± 0.8) than in the control group (PI = 2.9 ± 0.4). In the patients with PCOS, no correlation was observed between PI and luteinizing hormone, testosterone or androstenedione levels. Obesity had no effect on uterine artery PI, with no significant differences in this index when the 3 groups were subdivided into obese and non-obese groups.
Results of a Prospective Comparative Study of Transvaginal Hydrolaparoscopy and Chromolaparoscopy in the Diagnostics of Infertility
Authors: Nawroth Frank , Foth Dolores , Schmidt Torsten , Römer Thomas
Published: April 2003

Transvaginal hydrolaparoscopy (THL) was evaluated in comparison with the already established chromolaparoscopy in the detection of tubal factors, adhesions as well as endometriosis. 43 infertile patients without previous pelvic operations and with an inconspicuous clinical examination were included in a prospective comparative study of THL and chromolaparoscopy. THL succeeded in 40 patients (93.0%). Both methods showed 100% agreement with regard to tubal factors and adhesions. However, only 72/80 tubes (90.0%) could be portrayed by THL. In contrast to this, THL failed to identify 8 of 10 laparoscopically verified endometrioses (isolated endometriosis of the bladder peritoneum in 2). No complications occurred with THL. THL could be the method of choice for the clarification of mechanical infertility factors in symptom-free patients with no suspicion of pelvic pathologies. Tubal pathologies and/or adhesions (visible during THL) should be indications for laparoscopy. In the case of inconspicuous genitals during THL and a still unfulfilled desire for offspring postoperatively, laparoscopy should be considered in order to exclude the possibility of unidentified endometriosis. Retroflexio uteri should at least be a relative contraindication for THL. Further studies are necessary to evaluate the role of THL in the diagnostic concept of infertility in the future.
Effect of Betamethasone on Computerized Cardiotocographic Parameters in Preterm Growth-Restricted Fetuses with and without Cerebral Vasodilation
Authors: Frusca Tiziana , Soregaroli Mirella , Valcamonico Adriana , Scalvi Luisa , Bonera Raffaella , Bianchi Umberto
Published: April 2003

Objective: To verify the effects of maternal corticosteroid administration on fetal behavior and heart rate variation using computerized cardiotocography (cCTG) in a selected group of growth retarded fetuses. Study Design: Fifty singleton pregnancies complicated by fetal growth restriction were enrolled in the study before 34 weeks of gestation. All of them received two intramuscular injections of 12 mg of betamethasone 24 h apart. Fetal heart rate was recorded by cCTG before the first injection, and every 24 h for the 3 days following the end of the treatment. After Doppler evaluation of cerebral circulation, fetuses were divided into a group with and a group without signs of cerebral vasodilation. Basal heart rate, short- and long-term variation, percentage of time spent in high variability, fetal movements and percentage of small accelerations were evaluated. Results: Basalfetal heart rate did not show significant changes. Short-term variation and percentage of time spent in high variability significantly decreased in fetuses with but not in fetuses without vasodilation. Long-term variation and fetal movements significantly decreased in both groups. Conclusions: Maternal administration of betamethasone in growth-retarded fetuses with cerebral vasodilation is associated with significant but transitory modifications of fetal heart rate variation.
Pregnancy-Associated Changes in Peripheral Blood Lymphocyte Subpopulations in Normal Kuwaiti Women
Authors: Mahmoud F. , Abul H. , Omu A. , Al-Rayes S. , Haines D. , Whaley K.
Published: April 2003

It has recently been reported that healthy pregnancy is associated with systemic immunosuppression. The aim of this study was to evaluate the numbers and distribution of lymphocyte subpopulations in normal, healthy pregnant Kuwaiti women. Thirty-four healthy normotensive women in the 3rd trimester of pregnancy were studied using flow cytometry to define lymphocyte subpopulations and were compared with 16 non-pregnant women. A decrease in the absolute numbers of lymphocytes was observed affecting T cells (CD3+, CD4+, CD8+), B cells (CD19+), and natrural killer cells (CD16+/CD56+). When analyzed as a percentage of the total lymphocyte population, there was a significant decrease in B cells and an increase in CD4+ T cells. The T cell population revealed increased expression of CD25 on CD4+ and CD8+ cells, of HLA-DR on CD8+ cells, and of CD54 on CD4+ T cells. The reduced number of lymphocytes suggests that Kuwaiti females may be immunosuppressed in the 3rd trimester of pregnancy. The presence of activated CD4+ T cells could indicate the expression of a regulatory suppressor T cell population, as Treg cells are CD4+CD25+, and suppressor T cells are thought to be CD8+. Future work is required to explore the significance of these T cell populations in pregnancy.
Serum Leptin and Somatotropin Components Correlate with Neonatal Birth Weight
Authors: Ochoa Raquel , Zárate Arturo , Hernández Marcelino , Galván Rosa , Basurto Lourdes
Published: April 2003

Objective: To determine whether cord sera leptin and components of the somatotropin axis – growth hormone (GH), total (t) and free (f) insulin-like growth factor (IGF), IGF-binding protein-3 (IGFBP-3), and insulin – correlate with birth weight. Design: Cross-sectional study of 22 newborns, 12 with normal birth weight (NBW) and 10 with low birth weight (LBW), in a population of healthy mothers with an apparent normal pregnancy. Methods: Paired mother–neonate blood samples were obtained at vaginal delivery in order to measure leptin and the somatotropin axis components. Results: In all cases maternal blood concentrations of leptin, t and fIGF-I, its carrier protein IGFBP-3, and insulin were higher than in the cord sera of the newborns, regardless of their birth weight. On the contrary, maternal GH levels were lower than in their neonates. LBW neonates had decreased levels of leptin, tIGF-I, and IGFBP-3 as compared with those levels in NBW offspring; however, GH concentrations were higher in LBW neonates. Birth weight showed a significant correlation with cord sera leptin, tIGF-I, IGFBP-3, and GH; nevertheless birth weight was neither interrelated with fIGF-I nor with insulin levels. Conclusion: These data demonstrate that birth weight is significantly correlated with both leptin and some components of the somatotropin axis; on the other hand, no correlation was observed between leptin concentrations and each one of the components of the somatotropin axis. It is suggested that fetal leptin and the somatotropin axis cooperate in intrauterine growth and birth weight.
Relation between Plasma Endothelin 1 Levels and T Helper 1: T Helper 2 Cell Immunity in Women with Preeclampsia
Authors: Kuwajima Toyohiko , Suzuki Shunji , Yoneyama Yoshio , Sawa Rintaro , Asakura Hirobumi , Araki Tsutomu
Published: April 2003

The aim of this study was to investigate the relationship between plasma endothelin 1 (ET-1) levels and T helper (Th)-1:Th2 cell immunity in women with preeclampsia. The percentage of Th1 and Th2 cells and the Th1:Th2 cell ratios in peripheral blood from 11 normal pregnant women and 11 patients with preeclampsia at 29–34 weeks of gestation were calculated using flow cytometry. The plasma ET-1 level was also determined using a modified radioimmunoassay. The plasma ET-1 concentrations and the Th1:Th2 cell ratios in normal pregnancies were significantly lower than those in patients with preeclampsia. Negative correlations were found between plasma ET-1 levels and Th2 cells in both the preeclamptic pregnancy groups and in the normal pregnant women. Our results indicate that elevated ET-1 levels are associated with a Th1:Th2 imbalance in preeclampsia.
Laparoscopic Conservation of the Ovaries in Cases with Massive Ovarian Oedema
Authors: Kocak Müberra , Caliskan Eray , Haberal Ali
Published: April 2003

Two women, one 27 years old (case 1) and the other 20 years old (case 2), were evaluated due to right lower quadrant pain. The lactate dehydrogenase level was increased in case 1 and the dihydroepiandostrone level was increased in both cases. Preoperative transvaginal ultrasonography revealed solid masses, but the tumour markers were within normal limits. At laparoscopy, oedematous ovaries were diagnosed in both cases. Untwisting of the ovaries and laparoscopic wedge resection combined with frozen section analysis resulted in conservation of the ovaries in both cases. The patients are symptom-free after 1 year of follow-up.
Kommunikative Kompetenz bei der Ultraschalluntersuchung in der Schwangerschaft
Authors: Götzmann L. , Romann C. , Schönholzer S.M. , Klaghofer R. , Zimmermann R. , Buddeberg C.
Published: April 2003

Fragestellung: 293 Ärztinnen und Ärzte der allgemeinärztlichen und gynäkologischen Grundversorgung in der deutschsprachigen Schweiz wurden zu ihrer Informationspraxis bei der pränatalen Ultraschalluntersuchung befragt. Die Fragen bezogen sich auf Informationen über die Untersuchungsmethode sowie auf die Information der schwangeren Frau, wenn eine fetale Fehlbildung festgestellt wird. Methodik: Im Januar 2000 wurde ein Fragebogen an 500 Inhaberinnen und Inhaber des Fertigkeitsausweises für die Ultraschalluntersuchung in der Schwangerschaft versandt. Die Rücklaufquote betrug 59,2%. Ergebnisse: 90,1% der Ärztinnen und Ärzte gaben an, dass sie bei der Routine-Ultraschalluntersuchung ein Informationsgespräch anbieten würden. 50,2% erwähnten bei einer offen formulierten Frage das Screening nach fetalen Fehlbildungen als Bestandteil ihres Informationsgesprächs. Ärztinnen erwähnten diesen Screeningaspekt signifikant häufiger als Ärzte. Bei der Mitteilung einer Fehlbildungsdiagnose wurden als häufigste Schwierigkeit die Überforderungssituation der schwangeren Frau, aber auch eigene Gefühle von Hilflosigkeit genannt. Die subjektive emotionale Belastung wurde als hoch angegeben, Ärztinnen mit eigener Erfahrung als Mutter beurteilten sich als am stärksten belastet. Schlussfolgerungen: Das Screening nach fetalen Fehlbildungen ist ein schwieriges und häufig vernachlässigtes Thema bei der Information über die pränatale Ultraschalluntersuchung. Die Mitteilung einer Fehlbildungsdiagnose belastet nicht nur die Eltern, sondern auch die Ärzte und Ärztinnen emotional und erfordert von diesen eine hohe kommunikative Kompetenz. Diese kommunikativen Aspekte sollten in der Ausbildung zur Ultraschalluntersuchung in der Schwangerschaft berücksichtigt werden.
Psychologische Aspekte der Langzeitkontrazeption
Authors: Ringler Marianne
Published: April 2003

In den letzten Jahren wurden einige grossangelegte Studien über die psychischen Folgen der Sterilisation publiziert. Diese ergeben auch im interkulturellen Vergleich ein relativ einheitliches Bild und erlauben eine fundierte Definition von Risikofaktoren einer späteren Unzufriedenheit mit der Tubensterilisation. Diese sind: Alter der Patientin unter 30 Jahren, Partnerschaftskonflikte, der Eingriff erfolgt bis 1 Jahr post partum oder post interruptionem, mangelnde Entscheidungsautonomie bzw. Druck Dritter, mangelnde Information über den Eingriff und seine Konsequenzen, präoperativer Disstress und geringe familiäre Kohäsion und Anpassungsfähigkeit. Als unumgängliche Bestandteile der «Aufklärungspflicht» des Arztes in der Beratung sind neben den zuvor genannten Kriterien zu nennen: Irreversibilität, Applikation in Relation zur Lebensgestaltung und ihre Auswirkungen auf die seelische Balance unter Einbeziehung der Motive für eine Langzeitkontrazeption. Eine solche umfassende Information, die auf Verständnis basiert, führt zu einer Kompetenzerweiterung der beratenen Personen und damit letztlich zu autonomen Entscheidungen, die als seelische Voraussetzungen für die Zufriedenheit mit jedweder Empfängnisverhütungsmethode gelten.
Use of Intravascular Ultrasound in Clinical Trials
Authors: Kuecherer Helmut F.
Published: April 2003

Intravascular ultrasound (IVUS) permits detailed, high-resolution tomographic imaging of coronary architecture and enables the characterization of atherosclerotic lesions and plaque distribution. This unique value of IVUS easily explains and justifies why IVUS has found easy access to the clinical repertoire of a standard catheterization laboratory. Despite this fact, the contribution of IVUS findings relative to the total number of procedures performed in clinical catheterization laboratories can be considered small, and IVUS is seen primarily as an optional tool accompanying diagnostic or interventional procedures and as a mandatory tool mostly in angiographically ambiguous ostial or bifurcational lesions. In clinical trials, IVUS is used to assess changes that occur in vascular dimensions (remodeling) and plaque distribution during the disease process, during percutaneous interventions and at follow-up. One of the unique features of IVUS is that it is the only method to study remodeling in vivo. A standard image acquisition protocol is commonly applied to ensure premium quality of images and quantitative data. Motorized pullback devices are necessary to obtain reproducible length and volumetric measurements and provide uniform image acquisition. Ultrasound images are analyzed using manual tracing of acoustic interfaces. Since manual tracing is subjective, objective methods are currently being developed to minimize observer involvement. Fully automated segmentation of luminal and medial-adventitial boundaries has recently been demonstrated, but is still regarded as an experimental method. In the design of stent trials, IVUS is partially used to evaluate the effects of stent deployment on patient outcome. IVUS-guided stent implantation has been shown to result in less frequent clinically driven target vessel revascularization than angiographic guidance alone, although mortality and infarct rate are not affected. A current focus is on serial observation of plaque burden in lipid-lowering therapy.
Does Higher Concordance in Monozygotic Twins Than in Dizygotic Twins Suggest a Genetic Component?
Authors: Guo Sun-Wei
Published: April 2003

It is widely regarded that twins can be used as a natural experiment to subject hypotheses to empirical testing regarding the contributions of genetic factors to phenotypic variability in human traits, especially behavioral traits. In genetic epidemiology, a higher concordance rate in monozygotic (MZ) twins than in dizygotic (DZ) twins is often taken as prima facie evidence for a genetic component. While twins studies have been used to estimate the contributions of genetic factors to phenotypic variability in human traits, the corresponding methodology that allows the estimation entails several crucial assumptions. The most critical is that MZ and DZ twins are equally similar environmentally. Although MZ twins are genetically more similar than DZ twins, they are often environmentally more similar. This paper demonstrates that, even in the complete absence of any genetic factor and of any biases, the greater environmental similarity alone in MZ twins can result in higher concordance rate in MZ twins than in DZ twins. This is especially true when there are multiple environmental factors, which may have multiple exposure levels and/or interact strongly, although each of them may be of low risk. This may serve as a sobering antidote to the uncritical reliance on twin studies without examining the validity of the underlying assumptions.
Identification of a Founder Mutation in the Protoporphyrinogen Oxidase Gene in Variegate Porphyria Patients from Chile
Authors: Frank Jorge , Aita Vincent M. , Ahmad Wasim , Lam HaMut , Wolff Carlos , Christiano Angela M.
Published: April 2003

Variegate porphyria (VP; OMIM 176200) is characterized by a partial defect in the activity of protoporphyrinogen oxidase (PPO), the seventh enzyme of the porphyrin-heme biosynthetic pathway. The disease is usually inherited as an autosomal dominant trait displaying incomplete penetrance. In an effort to characterize the spectrum of molecular defects in VP, we identified 3 distinct mutations in 6 VP families from Chile by PCR, heteroduplex analysis, automated sequencing, restriction enzyme digestion and haplotyping analysis. The mutations consisted of 2 deletions and 1 missense mutation, designated 1239delTACAC, 1330delT and R168H. The occurrence of the missense mutation R168H had been reported previously in American, German and Dutch VP families, suggesting that this may represent a frequent recurrent mutation. Interestingly, the mutation 1239delTACAC was found in patients from 4 unrelated families living in different parts of Chile, suggesting that it might represent a common mutation in Chile. Haplotype analysis using 15 microsatellite markers which closely flank the PPO gene on chromosome 1q22, spanning approximately 21 cM, revealed the presence of R168H on different haplotypes in 6 VP patients from 3 unrelated families. In contrast, we found the occurrence of 1239delTACAC on the same chromosome 1 haplotype in 11 mutation carriers from 4 unrelated families with VP. These findings are consistent with R168H representing a hotspot mutation and 1239delTACAC existing as a founder mutation in the PPO gene. Our data comprise the first genetic studies of the porphyrias in South America and will streamline the elucidation of the genetic defects in VP patients from Chile by allowing an initial screening for the founder mutation 1239delTACAC.
Absence of Association between a Variant of the Mast Cell Chymase Gene and Atopic Dermatitis in an Italian Population
Authors: Pascale E. , Tarani L. , Meglio P. , Businco L. , Battiloro E. , Cimino-Reale G. , Verna R. , D’Ambrosio E.
Published: April 2003

Atopic dermatitis (AD) is a chronic dermatitis which belongs to the group of atopy-related diseases together with asthma and rhinitis. IgE and mast cell chymase (MCC) play a key role in atopic or allergic inflammation of the skin. An association between AD and a genetic variant of the MCC has been reported in a Japanese population, but failure of confirmation has rendered this association questionable. We have tested for genetic association to an MCC variant in relation to AD in an Italian population. No significant association was found between AD and MCC genotypes. These data suggest that BstXI MCC polymorphism may not be involved in AD.
The Score Statistic of the LD-Lod Analysis: Detecting Linkage Adaptive to Linkage Disequilibrium
Authors: Huang Jian , Jiang Yanming
Published: April 2003

We study the properties of a modified lod score method for testing linkage that incorporates linkage disequilibrium (LD-lod). By examination of its score statistic, we show that the LD-lod score method adaptively combines two sources of information: (a) the IBD sharing score which is informative for linkage regardless of the existence of LD and (b) the contrast between allele-specific IBD sharing scores which is informative for linkage only in the presence of LD. We also consider the connection between the LD-lod score method and the transmission-disequilibrium test (TDT) for triad data and the mean test for affected sib pair (ASP) data. We show that, for triad data, the recessive LD-lod test is asymptotically equivalent to the TDT; and for ASP data, it is an adaptive combination of the TDT and the ASP mean test. We demonstrate that the LD-lod score method has relatively good statistical efficiency in comparison with the ASP mean test and the TDT for a broad range of LD and the genetic models considered in this report. Therefore, the LD-lod score method is an interesting approach for detecting linkage when the extent of LD is unknown, such as in a genome-wide screen with a dense set of genetic markers.
Combination of Linkage Evidence in Complex Inheritance
Authors: Zhang W. , Collins A. , Morton N.E.
Published: April 2003

The central problem of complex inheritance is to combine evidence from data that typically differ in markers, phenotypes, ascertainment, and other factors, without sacrificing the reliability that lods have given to linkage mapping for major loci. Here we evaluate 5 possible solutions on 200 replicates simulated in Genetic Analysis Workshop 10. Two methods differ from less efficient ones by distinguishing the tails of a normal distribution. Maximum likelihood scores (currently implemented only for the BETA model) and the approach of Self and Liang perform about as well as pooling samples, which is not feasible with heterogeneous data. With moderately heterogeneous data the Self and Liang method appears to be more efficient than maximum likelihood scores. Although improvements are being made in sample design and statistical analysis, the problem of combining linkage evidence from multiple data sets appears to have been solved. Allelic association presents different problems not yet addressed.
Sample Size Requirement for Detecting Interference under the Chi-Square Model
Authors: Lin Shili
Published: April 2003

The chi-square model (CHS) of recombination has been studied extensively, in recent years, for its ability of capturing the process and estimating the level of crossover interference. Exploration thus far shows that this model yields much better fits to human genetic data than Haldane’s no-interference model, and the explicit level of interference can be easily estimated as well. This paper provides calculations of sample sizes required to detect interference under CHS for a variety of settings. Two data types, fully informative meioses and phase-unknown backcross families, are studied. Under each setting, we calculate the number of meioses/families needed to ensure that the expected log-likelihood difference between the χ2 interference model and Haldane’s no-interference model exceeds a prespecified threshold. It is found that joint consideration of multiple (more than three) markers dramatically reduces the number of meioses/families needed when compared to an analysis based on three-point data, a traditional setting for detecting interference using three-point tests. The results indicate that the numbers of meioses needed to detect interference under CHS are well within the reach of most genetic mapping studies.
Linkage Analysis of Alpha 1-Antitrypsin Deficiency: Lessons for Complex Diseases
Authors: Silverman Edwin K. , Mosley Jonathan D. , Rao D.C. , Palmer Lyle J. , Province Michael A. , Elston Robert C. , Weiss Scott T. , Campbell Edward J.
Published: April 2003

Objectives: Severe alpha 1-antitrypsin (A1AT) deficiency is the one proven genetic risk factor for chronic obstructive pulmonary disease (COPD). Familial aggregation has been demonstrated for COPD among individuals who do not have A1AT deficiency, but linkage analysis of COPD has not been reported. To investigate the optimal phenotype definitions and analytical methods for the linkage analysis of COPD, we examined a set of 28 A1AT- deficient families containing 155 individuals. We have used the protease inhibitor (PI) type as a genetic marker rather than a disease gene, and we have performed linkage analysis between PI type and serum A1AT level and spirometry-related phenotypes. Methods: Linkage analysis was performed on the quantitative phenotypes forced expiratory volume at 1 s (FEV1 as % predicted), the ratio of FEV1 to forced vital capacity (FEV1/FVC as % predicted), and serum A1AT level using the variance component approach in SOLAR, the generalized estimating equation approach in RELPAL, and the model-based classical lod score method in LINKAGE. Linkage analysis with qualitative A1AT and spirometry phenotypes was performed using a model-based method (LINKAGE) and a model-free method (GENEHUNTER). Adjustments for smoking effects were investigated under each method. Results: All of the methods demonstrated linkage of PI type to serum A1AT level. Interestingly, however, the other quantitative phenotypes provided only weak evidence for linkage of PI type to lung disease. Better evidence for linkage of lung disease to PI type was found using a moderate or a mild threshold for the definition of airflow obstruction. Conclusions: For linkage analysis of spirometry phenotypes in A1AT deficiency, qualitative phenotypes provided stronger evidence for linkage than quantitative phenotypes. Possible contributors to the stronger evidence for linkage to qualitative spirometry phenotypes include the ascertainment scheme and the nonnormality of the pulmonary function data in PI Z subjects. This study provides guidelines for studies of the genetics of COPD unrelated to A1AT deficiency.
Blockade of CD28/B7 Interaction Suppresses Allergic Eosinophilic Inflammation in Mice
Authors: Kasai Masaaki , Kumano Koutaro , Kurasawa Kazuhiro , Nakao Atsuhito , Saito Yasushi , Iwamoto Itsuo
Published: April 2003

To determine whether the costimulatory signal via CD28/B7 interaction is required for causing allergic inflammation, we examined the effect of administration of CTLA4-Ig, a fusion protein of the extracellular domain of CTLA4 and human IgG1-constant region, at the time of sensitization, on antigen-induced eosinophil infiltration in the trachea of sensitized mice, on IL-2, IFN-γ, IL-4 and IL-5 production in the airways of the mice and on antigen-specific IgE synthesis in the mice. Administration of CTLA4-Ig at the time of sensitization suppressed antigen-induced eosinophil infiltration into the trachea and antigen-specific IgE production in mice. Furthermore, CTLA4-Ig administration at the time of sensitization suppressed not only IL-2 production but also IFN&hyphenγ and Th2 cytokine IL-4 and IL-5 production in the airways. Because allergic inflammation requires CD4+ T cells producing Th2-type cytokines IL-4 and IL-5, our results suggest that the costimulatory signal via CD28/B7 interaction is important for the generation and activation of Th2 cells and thereby for the development of allergic inflammation.
RANTES Augments Eosinophil Lucigenin-Dependent Chemiluminescence
Authors: Chihara Junichi , Kakazu Tomokazu , Higashimoto Ikkou , Saito Norihiro , Honda Kohei , Tsuda Akira , Kayaba Hiroyuki , Kamada Yumiko , Oyamada Hajime , Urayama Osamu
Published: April 2003

Background: RANTES (regulated on activation, normal T expressed and secreted) has been shown to possess chemotactic activity for eosinophils. Eosinophils have been considered to play a key role in the allergic inflammation through the release of inflammatory molecules such as radical oxygen products. Thus, in this study, we examined the effect of RANTES on radical oxygen products from eosinophils. Methods: Eosinophils were isolated from heparinized venous blood of patients with bronchial asthma by the modified CD16-negative depletion method. Radical oxygen products were examined in terms of lucigenin-dependent chemiluminescence. To a mixture of 50 µl of eosinophils (2×106/ml) and 50 µl of lucigenin (5×10–4M), 50 µl of calcium ionophore A23187 (final concentration 10–5M) was added, and radical oxygen products were determined for 600 s. Results: RANTES treatment resulted in the enhancement of peak value (0.64±0.23 RLU) and integrated value (119.08±20.52 RLU) as compared to untreated cells (0.15±0.03 RLU, 29.48±8.92 RLU, respectively). Conclusion: We could conclude that RANTES might play an important role in the pathogenesis of allergic inflammation through involvement in selective eosinophil infiltration and eosinophil activation by augmentation of eosinophil oxidative metabolism.
Whole-Blood Flow-Cytometric Analysis of Eosinophil EG2 Expression as a Marker of the Pathological Conditions of Asthma
Authors: Kuwasaki Tomoe , Chihara Junichi , Kayaba Hiroyuki , Kamata Yumiko , Oyamada Hazime , Saito Norihiro , Shioya Takanobu , Sasaki Masahiro , Kagaya Manabu , Tsuda Akira
Published: April 2003

Using a simple technique detecting the eosinophil fraction in whole-blood flow cytometry, we measured intracellular antigen EG2 (a monoclonal antibody to eosinophil cationic protein) in 56 asthmatic patients (26 during an attack and 30 during an asymptomatic period) and 22 healthy subjects to determine whether EG2 reflects the pathological stages of allergy. Methods: In brief, preparations of the sample included the following procedures: (1) hemolyzation of heparinized or EDTA-mixed whole blood; (2) fixation of white blood cells with 0.4% parabenzoquinone (PBQ) or paraformaldehyde (PFA); (3) permeabilizing the cell membrane with n-octyl-β-D-glucopyranoside, and (4) staining of intracellular EG2 antigen with monoclonal EG2 antibody and FITC-labeled secondary antibody. Results: In PBQ-fixed samples, there was a clearer boundary of the eosinophil fraction with a higher yield and purity than in those fixed with PFA. The number of EG2-positive eosinophils was significantly greater in subjects during attacks than in asymptomatic patients. In addition, when compared with normal controls, asthmatic subjects had significantly greater numbers of EG2-positive eosinophils regardless of their current condition. Conclusion: Eosinophil intracellular EG2 may indicate the pathological stage of asthma. This simple technique for analysing the properties of eosinophils using whole-blood flow cytometry would save time and labor in laboratories.
Human Umbilical Vein Endothelial Cells Support Interleukin-3- and Interleukin-5-Induced Eosinophil Differentiation from Cord Blood CD34+ Cells
Authors: Ochiai Kenichi , Omura Miho , Mochizuki Akinori , Ito Motohiro , Tomioka Hisao
Published: April 2003

Background: Human umbilical vein endothelial cells (HUVEC) are an important source of hematopoietic cytokines, and interleukin-3 (IL-3)- and IL-5-induced eosinophil differentiation from CD34+ cells has been observed. To show the supportive effects of endothelial cells on eosinophil differentiation, we examined the effects of cocultured HUVEC on IL-3 and IL-5-induced eosinophil differentiation from human umbilical cord blood CD34+ cells. Methods: CD34+ cells were obtained from the heparinized umbilical vein blood of 10 volunteers using a CD34-conjugated magnetic bead positive direct selection procedure. With HUVEC in Transwell, CD34+ cells were then cultured for 14–28 days. In neutralizing experiments on HUVEC-derived cytokines, antibodies to both stem cell factor (SCF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) were added to the cell cultures. Results: Cocultured HUVEC upregulated IL-3 and IL-5-induced eosinophil differentiation from CD34+ cells on day 28 of culture by 75.0%. The eosinophilopoietic effect of HUVEC was significantly only when the cells were present in the culture from day 15 to day 28. Addition of anti-SCF antibody or anti-GM-CSF monoclonal antibody to the culture significantly suppressed HUVEC-combined IL-3- and IL-5-induced eosinophil differentiation on day 28 of culture by 49.2 and 55.0%, respectively. Conclusions: These results indicate that several cytokines including GM-CSF and SCF from HUVEC promote IL-3- and IL-5-induced eosinophil differentiation from CD34+ cells.
A Rapid and Simple Photometric Assay for Quantification of Eosinophil Chemotaxis
Authors: Nagase Hiroyuki , Yamaguchi Masao , Jibiki Sayaka , Yamada Hirokazu , Ohta Ken , Kawasaki Hiroshi , Yoshie Osamu , Yamamoto Kazuhiko , Morita Yutaka , Hirai Koichi
Published: April 2003

Various methods have been devised to assay eosinophil chemotaxis. In this review, we introduced a rapid and sensitive eosinophil chemotactic assay system based on eosinophil peroxidase (EPO) determination. Eosinophils were semipurified by dextran sedimentation followed by Percoll gradient centrifugation. Eosinophil migration was measured by the Boyden blind-well chamber technique using a 96-well multiwell chamber and polycarbonate membrane filter. The number of migrated eosinophils was assessed by determination of the EPO activity of drop-off cells, and photometric measurement was performed with a microtiter plate reader. The contribution of neutrophil peroxidase to the assay is negligible, and the assay is sensitive enough to detect 200 eosinophils. The method is both less tedious and less laborious than conventional manual methods, and it allows a large number of samples to be analyzed within 4 h. When eosinophils were exposed to 15 chemokines and their migration was assayed using this method, we found that only CC chemokine receptor 3 ligands, such as eotaxin, induced significant eosinophil migration.
Induction of Apoptosis in Bronchial Eosinophils: Beneficial or Harmful?
Authors: Yamashita Naomi , Tajima Makoto , Nakano Junichi , Arioka Hitoshi , Arai Hidenori , Miyasaka Tadashi , Kubota Shigeru , Kawashima Ruji , Ohta Ken
Published: April 2003

Background: Prominent eosinophil infiltration takes place in asthmatic bronchi, and damages bronchial epithelial cells. Aim: This study was designed to investigate whether induction of apoptosis in infiltrated cells in the airways is beneficial or harmful. Methods: A/J mice, which are genetically predisposed to be hyperresponsive to acetylcholine, were immunized with ovalbumin (OA) and alum. Thereafter, they were subjected to a 2-week regimen of OA inhalation, during which they were also administered either hamster anti-mouse Fas monoclonal antibody or hamster IgG (sham control) intranasally. Pulmonary function was then analyzed using whole-body plethysmography. Results: Inhalation of OA increased both airway responsiveness to acetylcholine and infiltration of eosinophils. Administration of anti-Fas antibody induced apoptosis in the infiltrating eosinophils and abolished the increase in airway responsiveness to acetylcholine. Conclusion: Induction of apoptosis in eosinophils infiltrating asthmatic bronchi has a beneficial effect on airway hyperresponsiveness.