G. Knöpfle

Percutaneous Fetoscopic Patch Coverage of Spina Bifida Aperta in the Human – Early Clinical Experience and Potential

Objective: The current operative approach for fetal repair of spina bifida aperta requires maternal laparotomy and hysterotomy. Following technical feasibility studies in sheep, we performed percutaneous fetoscopic patch coverage of this lesion in 3 human fetuses between 23 + 4 and 25 + 3 weeks of gestation. Methods and Results: Whereas the patch detached in the first case 3 weeks after the procedure, it covered the exposed neural tissue in the 2 other fetuses beyond their delivery. Two of the three children survived, but 1 unexpectedly died from a ventilation problem in its 3rd week of life. In 1 of the 2 survivors, ventriculoperitoneal shunt insertion was delayed. Conclusions: Percutaneous fetoscopic patch coverage of spina bifida aperta is feasible in human fetuses and offers a substantial reduction of maternal trauma compared to open fetal repair. Further clinical experience is now required before the efficacy of the new approach to protect the exposed neural tissue from mechanical and chemical damage and to improve hindbrain herniation can be evaluated.

Absence of ductus venosus-importance of umbilical venous drainage site.

To evaluate the conditions associated with absent ductus venosus (ADV) diagnosed by prenatal ultrasonography.

Prenatal diagnosis of persistent left superior vena cava and its associated congenital anomalies

To evaluate the associated conditions and the outcome of persistent left superior vena cava (PLSVC) detected in fetal life.

Prenatal diagnosis of genetically determined early manifestation of autosomal dominant polycystic kidney disease

SummaryA case of an unusually early manifestation of autosomal dominant polycystic kidney disease (ADPKD) is reported that was prenatally diagnosed by ultrasound. The ultrasonographic picture showed greatly enlarged kidneys and increased echogenicity that was indistinguishable from cases of autosomal recessive polycystic kidney disease or Meckel syndrome without further information. Because of two further cases of early manifestation of ADPKD within the family reported (brother and cousin), as well as several other “familial” cases reported in the literature, we postulate that genetic factors are involved (modifying alleles). When repeated observations of “familial” cases of early manifestations of ADPKD are made, genetic counseling should be considered.

Prenatal diagnosis of atrioventricular canal malformations with up-to-date echocardiographic technology: report of 14 cases

Fourteen fetuses with atrioventricular canal malformations were examined by two-dimensional echocardiography, pulsed-wave Doppler echocardiography, and color Doppler flow mapping. Eleven fetuses had complete and three fetuses had partial atrioventricular canal malformations. Nonimmune hydrops fetalis was associated with six cases, and fetal arrhythmia was seen in three cases. With two-dimensional echocardiography, the atrioventricular canal malformations could be diagnosed accurately. The inclusion of color Doppler flow mapping, however, provided additional hemodynamic information that was important from the prognostic point of view. Incompetence of atrioventricular valves could be demonstrated in 10 of 14 cases by Doppler echocardiography. In nine cases, detailed Doppler echocardiographic evaluation of the regurgitation jet was possible. The proportion of systolic time during which atrioventricular valve insufficiency was demonstrated was related to the occurrence of nonimmune hydrops fetalis. When insufficiency of atrioventricular valves was associated with hydrops (four cases), a pansystolic insufficiency was always present. In cases without hydrops (five), regurgitation was confined to early systole. Thus a reliable method for semiquantitative evaluation of the degree of insufficiency seems to have been found. Moreover, an association appeared to exist between the occurrence of hydrops fetalis and the proportion of atrial area that was taken up by regurgitant jet area, as determined by planimetry in the four-chamber view. Prenatal diagnosis was confirmed by autopsy or neonatal cardiac evaluation. Only one neonate survived in our series. Two were stillborn, four died during the neonatal period, two died during infancy, and pregnancy was electively terminated prematurely in five cases. Eight fetuses were found to have a karyotypic abnormality.

Stomatin is mis-trafficked in the erythrocytes of overhydrated hereditary stomatocytosis, and is absent from normal primitive yolk sac-derived erythrocytes

The 32 kD lipid‐raft‐associated membrane protein ‘stomatin’ is deficient from the erythrocyte membrane in the Na+–K+ leaky haemolytic anaemia, overhydrated hereditary stomatocytosis (OHSt). To date, no mutation in the gene coding for this protein has so far been found in OHSt. In this study, we have analysed the distribution of stomatin in both cultured erythroid cells from OHSt patients and in normal embryological and fetal erythroid development. In erythroid cell cultures from OHSt patients, stomatin‐immunoreactivity (stomatin‐IR) was present in progenitor cells but remained restricted to the area of the multivesicular complexes and the nucleus in the developing cells and was not seen in the plasma membrane. This could be consistent with the idea that stomatin is an innocent passenger in a more fundamental trafficking abnormality. In normal embryonic development, we found that, in extraembryonic (yolk sac) erythropoiesis, neither the nucleated red cells nor their enucleated mature derivatives displayed any stomatin‐IR. In contrast, all haemangiopoietic progenitor cells of intraembryonic haematopoiesis, starting with the mesodermal precursors in the aorta–gonad–mesonephros region, exhibited strong stomatin‐IR. The significance of this observation on these poorly understood cells is currently unclear.

Fetal pericardial teratoma causing cardiac insufficiency: prenatal diagnosis and therapy

A 35-year-old Caucasian primigravida was referred at 25 + 0 weeks’ gestation with the diagnosis of a fetal heart tumor. B-mode sonography demonstrated a large, partly solid and partly cystic tumor arising from the surface of the right atrium next to the heart base and a massive pericardial effusion (distance from the heart to the pericardium, 10 mm; Figure 1). The tumor itself measured 28 × 21 × 29 mm. Based on the typical appearance and location a tentative diagnosis of pericardial teratoma was made. The cardiothoracic circumference ratio was 0.56 (heart biometry included neither the teratoma nor the effusion) and sequential analysis of the cardiac anatomy revealed no further anomalies. There were no signs of congestive heart failure at the time of the first presentation. Thus there was no atrioventricular (AV) valve insufficiency and ascites; the flow profiles in the ductus venosus were normal (pulsatility index for veins (PVIV) – defined as (systole – a-wave)/diastole – was 0.596); and there was a normal amount of amniotic fluid (amniotic fluid index (AFI) was 20.6 cm). Follow-up sonograms at weekly intervals showed an increase in the pulsatility indices of the ductus venosus (PVIV, 0.721) as well as an increase in the amount of amniotic fluid (AFI, 24.2 cm) at 26 + 2 weeks’ gestation. At 28 + 2 weeks’ gestation growth of the tumor (now measuring 24 × 38 × 33 mm) was noticed as well as the presence of ascites and an increase of pulsatility in the ductus venosus blood flow pattern (PVIV, 1.00). A pericardiocentesis was performed under sonographic

Developmental changes in the expression of transcription factors GATA-1, -2 and -3 during the onset of human medullary haematopoiesis

Summary. Regulation of gene expression during the ontogeny of haematopoiesis in the human fetal bone marrow is poorly understood. Studies in mice demonstrated that GATA‐1, ‐2 and ‐3 play pivotal roles in haematopoiesis. In this study, we identified GATA‐1‐, GATA‐2‐ and GATA‐3‐expressing cells in bone marrow sections and analysed the expression of GATA‐transcription factors during the development of human fetal bone marrow haematopoiesis using semiquantitative reverse transcription‐polymerase chain reaction (RT‐PCR). We showed that GATA‐1, ‐2 and ‐3 were expressed only in haematopoietic cells in the bone marrow. RT‐PCR analysis demonstrated that (1) GATA‐1 expression significantly increased during gestation; (2) GATA‐2 expression peaked at the onset of medullary haematopoiesis, declined thereafter, and remained at a constant level after 30 weeks post conception; and (3) GATA‐3 expression revealed no changes during development. The results indicated that the onset of medullary haematopoiesis in humans is accompanied by high expression of GATA‐2, reflecting high proliferation rates of early haematopoietic progenitor cells, whereas expression of GATA‐1 mirrors haematopoietic activity.

Gliomatosis peritonei with endometriosis externa.

A case of gliomatosis peritonei developed 9 years after the removal of an immature ovarian teratoma is reported. An unique association of gliomatosis with endometriosis externa was found without the usual symptoms of endometriosis. The prognosis of gliomatosis is generally excellent and depends on the histological grade of the primary tumor and on the presence of organ metastasis or immature tumor elements in the implants. Pathogenetical aspects of both lesions are discussed briefly.

Flow analysis in the pulmonary trunc in fetuses with tetralogy of Fallot by colour Doppler flow mapping; two case reports

Prenatal diagnosis of tetralogy of Fallot by two-dimensional echocardiography, which is based on demonstration of a ventricular septal defect and a large overriding aorta, is difficult. In the majority of cases the main pulmonary artery is small. In utero, there is no pathologically increased degree of the physiological right-ventricular hypertrophy. Colour Doppler flow mapping of reverse flow from the descending aorta via the ductus arteriosus into the main pulmonary artery is easily demonstrated, and provides an indirect sign of severe right-ventricular outlet obstruction. The technique also differentiates between pulmonary stenosis and atresia; the stenotic jet, even small, is identified by demonstration of high velocities and turbulences in the main pulmonary artery.