Accuracy of classification of breast ultrasound findings based on criteria used for BI-RADS.

OBJECTIVE: To assess the accuracy of categorization of breast ultrasound findings based on scoring for malignancy using the sonographic breast imaging-reporting and data system (BI-RADS). METHODS: Breast ultrasound was performed in 2462 patients between 2001 and 2004 at our unit. Sonographic findings were scored using analog criteria as in BI-RADS for breast ultrasound (mass shape, margin, orientation, posterior acoustic features, lesion boundary, echo pattern). Each lesion was described using these features and classified into categories 1 to 5 according to the BI-RADS for breast ultrasound. Categorization and biopsy results were compared. RESULTS: In twenty-two (0.9%) patients breast ultrasound could not be evaluated because of extreme density of tissue. Normal breast ultrasound belonging to Category 1 was found in 871 (35.4%) patients. Simple cysts classified as Category 2 were observed in 712 (28.9%) women. In 491 (19.9%) patients, apparently benign solid masses (Category 3) were found. Suspicious masses were observed in 225 (9.1%) women and masses highly suggestive of malignancy were found in 141 (5.7%) patients (Categories 4 and 5, respectively). Histological examinations were available from 84 (17.1%) masses that had been classified by BI-RADS as Category 3, in 97 (43.1%) from Category 4 and 106 (75.2%) from Category 5. Accordingly, the rate of malignant findings was 1.2% (n = 1) in Category 3, 17% (n = 16) in Category 4 and 94% (n = 100) in Category 5. CONCLUSION: Scoring breast ultrasound findings for malignancy based on criteria used for BI-RADS breast ultrasound has a high accuracy, comparable to that obtained by BI-RADS for mammography.

Fetoscopic direct fetal cardiac access in sheep : An important experimental milestone along the route to human fetal cardiac intervention.

BACKGROUND: Fetal cardiac interventions by direct ultrasound-guided approaches or open fetal cardiac surgery have been fraught with technical difficulties, as well as with significant maternal and fetal morbidity in humans. Therefore, the purpose of our study in sheep was to assess the feasibility and potential of fetoscopic direct fetal cardiac access. METHODS AND RESULTS: In 15 anesthetized pregnant ewes (88 to 109 days of gestation; term, 145 days), 3 to 4 trocars were percutaneously placed in the uterus. Using videofetoscopic equipment, we assessed the feasibility of achieving direct fetal cardiac access. Minimally invasive direct fetal cardiac access by operative fetoscopy was achieved in 10 of the 15 fetal sheep. In 7 fetuses, the approach was successfully tested for fetal cardiac pacing (n=5) or antegrade fetal cardiac catheterization (n=2). Access was not achieved in 5 fetuses because of bleeding complications (n=2) or because the fetoscopic setup could not be established (n=3). All but 2 fetal sheep were alive at the end of the procedure. Acute fetal demise resulted from maternal hypotension or kinking of the fetal inferior caval vein by sternal suspension. Six ewes continued gestation; 3 of these went to term, with a normal fetal outcome. Two ewes died from septicemia 3 and 7 days after the procedure, and 1 ewe aborted 1 month after the procedure. CONCLUSIONS: Minimally invasive direct fetal cardiac access by operative fetoscopy is feasible in fetal sheep. The fetoscopic approach carries important potential for fetal cardiac pacing, antegrade fetal valvuloplasties, and resection of fetal intrapericardial teratomas in human fetuses.

Multimodal fetal transesophageal echocardiography for fetal cardiac intervention in sheep.

BACKGROUND: The overall performance of available mechanical intravascular ultrasound catheters for fetal transesophageal echocardiography during fetoscopic fetal cardiac interventions in sheep has been limited by radioelectronic interference, low system frame rates, and low acoustic outputs. Therefore, a more reliable device is desired for human fetoscopic surgical procedures. METHODS AND RESULTS: We assessed the potential of a newly available 10-French phased-array intravascular ultrasound catheter for multimodal fetal transesophageal echocardiography in 5 fetal sheep between 78 and 98 days of gestation (term, 145 to 150 d). The intravascular ultrasound catheter was easily inserted through the mouth into the esophagus in all 5 sheep fetuses (mean weight, 600 g), and it permitted high-quality 2D imaging of the fetal heart in vertical imaging planes that were validated by MRI. Color Doppler and pulsed Doppler imaging permitted clear assessment of fetal cardiovascular flows and recording of velocity-time integral tracings of the fetal heart and great vessels. The vertical imaging planes were particularly useful to demonstrate interventional material inside the fetal heart and great vessels. CONCLUSIONS: Our early experience with the phased-array intravascular ultrasound catheter indicates that multimodal fetal transesophageal echocardiography has now become possible in these smallest of patients.

Fetoscopic transesophageal electrocardiography and stimulation in fetal sheep: a minimally invasive approach aimed at diagnosis and termination of therapy-refractory supraventricular tachycardias in human fetuses.

BACKGROUND: Therapy-refractory supraventricular tachycardia commonly results in hydrops and death in human fetuses. The purpose of this study in fetal sheep was to assess the feasibility of a minimally invasive fetoscopic approach for fetal transesophageal electrocardiography and stimulation aimed at diagnosis and termination of these tachycardias. METHODS AND RESULTS: We studied a total of 10 fetal sheep (87 to 103 days of gestation; term=145 days). We entered the amniotic cavity using a percutaneous fetoscopic approach and placed various electrophysiology catheters into the fetal esophagus. We recorded the number of animals in which fetoscopic transesophageal electrocardiography and stimulation were successful and assessed pacing success and thresholds for different catheters. In addition, we monitored for potential adverse effects from stimulation and for other complications of the operation. Recording of transesophageal electrocardiograms was successful in all fetal sheep. Capture during stimulation was successfully documented by additional fetal bipolar surface electrocardiograms in 7 fetuses. In fetuses in which fetal surface electrocardiograms were not recorded, pacing stimulus artifacts interfered with documentation of capture. Although stimulation thresholds were high, the maternal rhythm was not affected by fetal stimulation. CONCLUSIONS: Fetoscopic fetal transesophageal electrocardiography and stimulation are feasible in fetal sheep. This minimally invasive approach might have the potential to improve diagnosis and management of therapy-refractory supraventricular tachycardias in human fetuses.

Platelet glycoprotein complex Ia/IIa antibodies cause neonatal alloimmune thrombocytopenia but do not inhibit megakaryopoiesis and platelet recovery after allogeneic cord blood stem cell transplantation.

A sibling cord blood (CB) transplantation was performed in a boy with Wiskott-Aldrich syndrome. The CB (31 x 10(6) CD34(+) cells) derived from a newborn sister with neonatal alloimmune thrombocytopenia (NAIT) with 40,000 platelets/microl, caused by a maternal anti-HPA-5b and HLA-A2 antibody. Maternal serum did not inhibit clonogenicity after in vitro testing of megakaryopoiesis. Accordingly, this CB was accepted for sibling transplantation. The transplantation showed a good course with fast and sustained hematopoietic reconstitution (granulocytes >500/microl on day +16, platelets >50,000/microl on day +30). This case demonstrates a successful CB transplantation from a donor suffering from NAIT.

Is there a seasonal variation in the frequency of gastroschisis?

PURPOSE: There have been conflicting reports on the incidence of gastroschisis and its seasonal variation. Studies have found an increased risk of gastroschisis in deliveries occurring in the winter months in the northern hemisphere. Other studies have not found a seasonal variation. To evaluate the existence of a seasonal variation in the incidence of gastroschisis in our patients, a retrospective database analysis was conducted. MATERIALS AND METHODS: Second and third trimester pregnancy screening was performed on 8031 patients between October 2001 und September 2005. Patients were evaluated throughout the year separately for their expected date of delivery and date of conception during the summer months (April-September) and the winter months (October-March). RESULTS: We diagnosed 17 fetuses having gastroschisis with a mean gestational age at diagnosis of 24 weeks (range 11-33). The number of second and third trimester screening examinations and the number of patients with an expected date of delivery was not different during summer and winter months, 3980 vs. 4051. The expected date of birth (corrected for early ultrasound measurement) of fetuses with gastroschisis was more common during the winter months (n=11) than during summer months (n=6). However, this difference is not statistically significant (p=0.21) as was also the case for the date of conception. CONCLUSION: There seems to be no seasonal variation in the frequency of gastroschisis depending on the estimated date of birth or date of conception.

Implications of low vascular flow resistance in the umbilical artery--difference between the second and third trimester of pregnancy.

PURPOSE: An abnormally high (above 95th percentile) pulsatility index (PI) in the umbilical artery (UA) indicates impaired fetal outcome, whereas the impact of an ''abnormally'' low (below 5th percentile) PI in the second trimester is unknown. MATERIALS AND METHODS: Between 2001 and 2004, second trimester pregnancy screening was performed at our institution on 5220 patients, and additional UA Doppler ultrasound on 547 (10.5%) of these patients, between 16th and 25th week of pregnancy. Files were available for analysis in our electronic database (PIA Fetal Database (GE, USA)). To evaluate the association of a UA PI below the 5th percentile in the second trimester of pregnancy with fetal anomalies and outcome, a retrospective database analysis was conducted. RESULTS: In 25 fetuses (3.6%), a UA PI below the 5th percentile was found. In 7 of these fetuses (28%), abnormalities of the urogenital tract were diagnosed. There were multiple pregnancies in 7 cases (28%), consisting of two triplets, each including one fetus with malformation, as well as five monochorial twin pregnancies, including 2 fetuses with malformations. In 11 pregnancies (44%), second trimester screening showed no anomalies. CONCLUSION: Only in 11 cases (44%) of fetuses with UA PI below 5th percentile in the second trimester, course and outcome of pregnancy were favourable, if defined as live birth without fetal malformations and uneventful neonatal period. The aetiology of an abnormally low UA PI in the second trimester seems to be diverse. Possible aetiological mechanisms will be discussed.

Does vaginal bleeding influence first-trimester markers for Down syndrome?

OBJECTIVES: To examine the effect of early vaginal bleeding on first-trimester screening markers for Down syndrome. METHODS: A retrospective study was conducted on 1755 normal singleton fetuses that underwent first-trimester combined screening for Down syndrome on the basis of ultrasound and maternal serum markers. Fetal delta-nuchal translucency (NT), maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta-hCG were compared between pregnancies with (n = 252) and without (n = 1503) an episode of vaginal bleeding. Subgroup analysis for the intensity of bleeding (spotting n = 191; light n = 32; heavy n = 29) was performed. RESULTS: The median +/- SD (log(10)) for delta-NT, multiple of medians (MoM) PAPP-A and MoM free beta-hCG (corrected for maternal weight, smoking and ethnicity) was - 0.17 +/- 0.62, 1.10 +/- 0.28, 1.1 +/- 0.28 and - 0.15 +/- 0.51, 0.98 +/- 0.26, 0.94 +/- 0.3 in pregnancies with and without a history of early vaginal bleeding, which were not significantly different. Exclusion of patients with spotting from the vaginal bleeding group revealed significantly higher maternal serum free beta-hCG MoM values (median +/- SD (log(10))) compared to patients without bleeding, 1.29 +/- 0.27 vs 0.96 +/- 0.3(p = 0.011). Screen-positive (cut off of 1:350) rate after combined first-trimester screening was 28.1% in patients with light vaginal bleeding and 8.4% in patients without bleeding (p = 0.001). CONCLUSIONS: Light vaginal bleeding before first-trimester combined screening for Down syndrome leads to a higher screen-positive rate after combined first trimester screening, without a significant difference in serum levels of the screening markers.

[Pruritus in pregnancy. A frequent diagnostic and therapeutic challenge]. / Pruritus in der Schwangerschaft. Eine häufige diagnostische und therapeutische Herausforderung.

Pruritus is the leading dermatological symptom during pregnancy. Besides preexisting or acquired dermatoses, there are a number of pregnancy-specific dermatological diseases such as PEP (polymorphic eruption of pregnancy, previously named PUPPP), pemphigoid (herpes) gestationis, and pruritus gravidarum that are accompanied by severe itching and scratching. Because of potential effects on the fetus, the treatment of pruritus in pregnancy requires prudent consideration. The use of topical and systemic treatments depends on the underlying aetiology of pruritus and the stage and status of the skin. In general, emollients, topical anti-pruritics and topical corticosteroids appear to be the safest options for localised forms of pruritus in pregnancy whereas systemic treatments and/or UV phototherapy are adequate for generalized pruritus. Systemic corticosteroids and a restricted number of antihistamines may be administered in severe cases. This paper highlights the major aetiologies of pruritus during pregnancy and points out the cornerstones of antipruritic therapy in recognition of our own clinical experiences and the current literature.

[Radiotherapy in tubal carcinomas]. / Strahlentherapie beim Tubenkarzinom.

PURPOSE: Cancer of the fallopian tube is one of the rarest gynecological malignancies. The treatment of choice for this tumor is not well defined because of its very low incidence. The preferred primary treatment is surgical resection consisting of abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy. The value and extent of adjuvant radiotherapy is unclear so far. This retrospective analysis shows the experience at our clinic, which will be discussed in comparison with the existing literature. PATIENTS AND METHODS: From 1967 to 1994, 9 patients were treated at the Clinic and Polyclinic for Radiotherapy--Radio-Oncology of the University of Münster with adjuvant radiotherapy following surgery for carcinoma of the fallopian tube. The staging according to FIGO yielded 2/9 stage I, 4/9 stage II and 3/9 stage III patients. In 5/9 patients the tumor could be resected completely. In 3/9 cases the pelvis alone, in 5/9 cases the pelvis and para-aortal region were irradiated with doses ranging from 45 Gy to 50 Gy. In 1/9 cases the target volume comprised the whole abdomen. The treatment results were acquired retrospectively by analysis of the patients' records and inquiries among their general practitioners. RESULTS: Median survival of our patients was 25 months, 6/9 developed recurrence after a median time of 10.5 months. All of these were localized in the abdominal cavity; 1 patient also developed liver metastases. All patients with recurrent tumor died from their disease within a median period of 9 months. Of the other 3/9 patients, 2/3 died after 6 and 36 months, and 1 patient is still alive after 42 months; all of them without any sign of recurrence. CONCLUSION: Adjuvant radiotherapy of carcinoma of the fallopian tube seems to be indicated with the exception of little invasive tumors of FIGO stage I. From our findings, the target volume should comprise the whole abdomen. A smaller treatment volume (pelvis alone or plus the para-aortal region) can only be of any use in a palliative situation or as a salvage therapy.

Autologous red cells derived from cord blood: collection, preparation, storage and quality controls with optimal additive storage medium (Sag-mannitol).

To investigate whether packed red cells (PRCs) prepared from autologous cord blood-packed red cells (AC-PRCs) could be used as an alternative for homologous-packed red cells (H-PRCs), we developed a system to collect and prepare AC-PRCs and determined standard storage parameters during 35 days of storage in extended storage medium (Sag-mannitol). We collected and fractionated cord blood from 390 newborns. The amount and quality of the AC-PRCs were analysed. The bacterial contamination rate was 1.84%. Twelve AC-PRCs were stored for 35 days, and standard laboratory parameters were measured at day 1 and day 35. The initial laboratory parameters of the AC-PRCs were similar to the parameters of the H-PRCs. After 35 days, the AC-PRCs displayed an increased haemolysis rate compared to H-PRCs (1.1 versus 0.2%) and also a significant decreased adenosine triphosphate value (1.2 versus 2.3 micromol L(-1)). Haemoglobin, haematocrit and pH were comparable in both groups. AC-PRCs meet the quality criteria for H-PRCs after 35 days. Utilizing a closed collection system for cord blood and an extended storage medium will increase safety and quality and facilitate the routine transfusion of autologous red cells derived from cord blood.

A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants.

UNLABELLED: This study was carried out to assess the feasibility of late cord clamping of 45 s in preterm infants delivered mainly by caesarean section and the effects on postpartal adaptation and anaemia of prematurity. Prior to delivery, 40 infants of < 33 gestational weeks were randomised to either 20 s or 45 s of late cord clamping. After the first shoulder was delivered, oxytocin was given intravenously to the mother in order to enhance placento-fetal transfusion while the infant was held below the level of the placenta. The 20 infants in group 1 (20 s) had a mean birth weight of 1070 g and a mean gestational age of 29 + 4/7 weeks versus 1190 g and 30 weeks in group 2 (45 s). On day 42 of life there were ten infants without transfusions in group 2 versus three in group 1 (P < 0.05). Out of the 20 infants in group 1, 19 and 15/19 in group 2 were delivered by caesarean section. There were no significant differences in Apgar scores, temperature on admission, heart rate, blood pressure and requirements for artificial ventilation. CONCLUSION: Delayed cord clamping of 45 s is feasible and safe in preterm infants below 33 weeks of gestation. It is possible to perform the procedure at caesarean section deliveries and it should be performed whenever possible. It reduces the need for packed red cell transfusions during the first 6 weeks of life.

Plasma and membrane Ca2+ and Mg2+ concentrations in normal pregnancy and in preeclampsia.

OBJECTIVE: Changes in intracellular Ca2+ and Mg2+ concentrations seem to be involved in the pathogenesis of preeclampsia, whereas the role of cell membranes has not been studied in detail yet. To investigate the changes in Ca2+ and Mg2+ metabolism in normal pregnancy and preeclampsia, plasma and membrane Ca2+ and Mg2+ concentrations were determined in a clinical study as compared to healthy subjects. STUDY DESIGN: 25 healthy female subjects, 22 untreated healthy pregnant and 20 preeclamptic women were investigated. In each patient, plasma and membrane Ca2+ and Mg2+ content were measured. Ca2+ and Mg2+ concentrations were measured by atomic absorption spectroscopy. Erythrocyte membranes were chosen for membranous Ca2+ and Mg2+ determination. RESULTS: Plasma Mg2+ concentrations were significantly lowered in the healthy pregnant group and the preeclamptic group as compared to controls (p < 0.0001). In erythrocyte membranes, Mg2+ content was found significantly decreased in the preeclamptic women as compared to healthy subjects (p < 0.001). In plasma Ca2+ concentrations there was a significant decrease in the preeclamptic group as compared to controls or healthy pregnant women (p < 0.05). Membranous Ca2+ content was significantly increased in the preeclamptic group versus controls or healthy pregnant women (p < 0.001). CONCLUSION: Lowered plasma and membrane Mg2+ concentrations in preeclampsia may contribute to the development of hypertension in pregnancy. Additionally, a disturbed Ca2+ homeostasis is observed in preeclampsia.

Operative techniques and strategies for minimally invasive fetoscopic fetal cardiac interventions in sheep.

BACKGROUND: Recent efforts to develop procedures for fetoscopic fetal cardiac interventions have been prompted by the development of severe secondary damage to the fetal heart due to semilunar valvar obstructions and the poor outcome of therapy-refractory fetal arrhythmias. The purpose of our manuscript is to analyze and share our experience with the creation of an operative setup for these procedures in sheep. METHODS: We studied a total of 48 fetal sheep between 81 and 106 days of gestation (term, 145 days). After entering the amniotic cavity by a percutaneous approach, we performed various fetoscopic fetal cardiac procedures. We analyzed the success of percutaneous fetal access, methods of trocar support, the incidence and management of trocar dislodgement or accidental insertion into the chorioamniotic space, problems related to amniotic insufflation and trocar placement, as well as techniques for fetal posturing and uterine closure. RESULTS: Percutaneous fetal access was achieved in all sheep. The use of resterilizable trocars substantially decreased the costs of our procedures. Utilizing a percutaneous transuterine purse-string suture for trocar support helped to minimize the number of nonabsorbable T-fasteners remaining inside the uterus postoperatively. As complications such as trocar dislodgement, insertion of the trocar into the chorioamniotic space, and problems with intraamniotic insufflation and gas loss were mastered, conversion to an open operative approach was never required. A novel strategy that we devised for percutaneous fetal posturing permitted adequate fetal posturing with ease and minimal trauma to the fetal skin. CONCLUSION: As operative techniques have become more refined, the feasibility of performing fetoscopic fetal cardiac interventions in human fetuses now depends mainly on technical improvements in imaging and interventional catheters, as well as advances in pacemaker equipment.

Simultaneous in utero assessment of AV nodal and ventricular electrophysiologic parameters in the fetal sheep heart.

BACKGROUND: Fetal tachyarrhythmias are usually of supraventricular origin. To investigate whether specific electrophysiologic properties of the fetal heart contribute to this preponderance by either favoring supraventricular tachycardias or by rendering ventricular tachycardias unlikely, we measured fetal electrophysiologic parameters in utero using transuterine fetal transesophageal electrocardiograms in fetal sheep. Since overdrive pacing may help to establish the mechanism of an arrhythmia and may be used to treat fetal tachycardias, different modes of transesophageal pacing in utero were also assessed. METHODS AND RESULTS: Decapolar electrophysiology catheters were fetoscopically inserted into the esophagus of 9 fetal sheep (pregnancy duration 94- 105 days, term = 145 days). Electrocardiograms were recorded simultaneously from all adjacent bipoles and from two pacing wires sutured onto the fetal shoulders. Pacing was attempted either via two adjacent electrodes of the intraesophageal catheter or via the most distal and most proximal electrode. Fetal cycle length, PQ, and QT intervals were close to (approx. 75 %), but fetal QRS duration was < 20 % of maternal values, thus shifting the relation between activation and repolarization towards longer excitation wave lengths. Fetal QT dispersion was small (< or = 10 ms). Atrial pacing was achieved in all fetuses using distant electrodes, and with lower thresholds when compared to closely spaced bipolar electrodes (p < 0.05). CONCLUSIONS: (I) An altered relation between ventricular activation and repolarization and a low dispersion of ventricular repolarization may protect the fetal heart against ventricular reentrant tachycardias. (II) Relatively normal fetal AV nodal conduction delay already provides one of the prerequisites for supraventricular reentrant tachycardias involving the AV node at this stage of fetal development. (III) High-rate esophageal pacing of the fetal atria is best achieved using widely spaced bipolar pacing electrodes.