Hans K. Weitzel

Feto-Feto-Fetal Triplet Transfusion Syndrome (FFFTTS)

We report a case of feto-feto-fetal-transfusion-syndrome (FFFTS) in a spontaneous monochorionic triamniotic triplet pregnancy primarily diagnosed at 17 weeks of gestation. During the course of pregnancy, sequentially two triplets appeared as donor. Symptoms of a recipient (polyhydramnios, tricuspid valve insufficiency, and ascites) were present in the third triplet. The second of the donor twins died in utero at 25 weeks. At 27 weeks, a cesarean section was performed mainly due to pre-eclampsia. The first donor triplet developed normally, whereas the recipient showed periventricular leucomalacia and neurological impairment.

Therapy of metastatic breast cancer with humanized antibodies against the HER2 receptor protein.

Abstract The HER2 protein, a member of the epidermal growth factor family, is encoded by the protooncogene c-erbB-2. Its overexpression, occurring in approximately one-third of all breast carcinomas, is associated with a poor prognosis. A humanized mouse antibody against HER2 has been developed by genetic engineering. Here an unspecific human IgG was connected to the recognizing mouse IgG fragment. The allergization typical for allogeneic antibodies does not take place in this context. The effectiveness of this antibody has been confirmed by two international prospective phase III trials that tested it alone and combined with chemotherapy. Both modes of application increased the response rates and the time to progression. Side-effects were rare except for a high rate of cardiac dysfunction when the antibody was combined with anthracyclines. The effectiveness and negligible side-effects of the chimeric antibody against HER2 (Herceptin) render it a valuable tool in the treatment of breast cancer.

Expression and Function of Egf-Related Peptides and Their Receptors in Gynecological Cancer - From Basic Science to Therapy?

Abstract EGF-related peptides and their receptors play an important, but not fully understood role, both, in epithelial physiology and pathophysiology but also in human tumor carcinogenesis and tumor behavior, respectively. Overexpression of EGF-related growth factors from normal epithelium to carcinomas has been demonstrated for several human tissues such as breast, endometrium, cervix and ovary. Additionally, the differential overexpression of EGFR or erb 5-2 in various malignancies has already proven to be efficacious in stratifying patients with respect to a poor prognosis. These data suggest that EGF-related growth factors, erb B receptors or signaling proteins that function either upstream or downstream from these receptors may represent novel targets for selective tumor therapy. in the future, conventional chemotherapy regimes will ultimately be wedded to more biologically-oriented therapies. One important target for these novel therapeutic approaches in solid tumors will be the EGF-related growth factors and their receptors.

Prediction of Fetal Distress and Poor Outcome in Intrauterine Growth Retardation – A Comparison of Fetal Heart Rate Monitoring Combined with Stress Tests and Doppler Ultrasound

One hundred and three intrauterine growth retardation (IUGR) pregnancies were scheduled for pulsed Doppler ultrasound of the common carotid and the umbilical artery, nonstress and contraction stress tests (NST/CST) as well as vibroacoustic stimulation tests (VAST). The last examinations < 3 days before birth were compared by receiver-operator characteristics: Results of the resistance indices of fetal common carotid/umbilical artery and NST were more predictive of later fetal distress during labour, compared to CST and VAST (p < 0.001/< 0.01). Similar results were found for the prediction of low pH and Apgar values, though differences were less pronounced. Our results suggest that stressful examinations should be abolished from mother and fetus in the supervision of IUGR.

Gestational age dependence of 11β-hydroxysteroid dehydrogenase and its relationship to the enzymes of phosphatidylcholine synthesis in lung and liver of fetal rat

Increase in fetal surfactant synthesis and lung maturity is caused by the glucocorticoidal induction of enzymes required for phosphatidylcholine (PC) synthesis towards the end of gestation. The regulation of gestational age-dependent induction of PC synthesis by glucocorticoids is still unclear. Since 11-beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity and its metabolising capacity for glucocorticoids have been suggested to play a central role in this regulation, we measured the gestational age-dependent changes in 11 beta-HSD and PC synthesizing enzymes in lung and liver of fetal rat. The activity of cholinephosphate cytidyltransferase (CCT; key enzyme in PC synthesis), choline phosphotransferase (CPT) and lysolecithin acyltransferase (LAT) were found to increase gradually in the lung towards the end of gestation, reached peak values at term followed by a decrease of activity reaching finally adult levels. Only CK activity exhibited constant levels until term followed by a slight increase after the birth. In comparison with the lung, the liver enzymes followed a similar pattern, but at a higher rate of activity except for CCT which was higher in the lung. The activity of 11 beta-HSD in fetal lung microsomes was detectable from day 20 and increased towards the end of gestation in the lung and liver of the rat. Oxidase activity was always found to exceed the reductase activity. The activity of 11 beta-HSD continued to increase after delivery and reached peak levels in adult animals in both organs. In order to test the hypothesis, whether 11 beta-HSD activity and PC synthesis are induced by increasing endogenous glucocorticoidal levels, we examined on day 19 of gestation the effect of dexamethasone (DEXA) on enzymatic activities (11 beta-HSD, CCT) and on [14C]choline incorporation in phosphatidylcholine in fetal lung organoid cultures. Additionally, changes in CCT activity in fetal lungs after maternal administration of DEXA were measured. DEXA accelerated 11 beta-HSD and CCT activities as well as [14C]choline incorporation. We conclude, that endogenous glucocorticoids induce PC synthesis as well as 11 beta-HSD activity in lung and liver of the fetal rat. Fetal PC synthesis is not altered by increasing 11 beta-HSD levels, because the increase of free serum corticosterone levels apparently exceeds the metabolising capacity of 11 beta-HSD towards term.

Clinical aspects of antenatal glucocorticoid treatment for prevention of neonatal respiratory distress syndrome

Main indications for antenatal administration glucocorticoid to pregnant women are premature contractions, hemorrhage during pregnancy, conditions of fetal distress and maternal diseases. There are some absolute or relative contraindications as well: severe forms of preeclampsia, diabetes mellitus, premature rupture of membranes, maternal and/intrauterine infections. In a retrospective evaluation of the data obtained at our institution of 637 nonrandomized cases from the years 1980-1985, we could demonstrate the dependence of the therapeutic results on the sex of the newborn. The RDS incidence is significantly different after betamethasone prophylaxis. It was 1/25 (4%) in girls compared to 13/31 (42%) in boys. A marked reduction of the RDS incidence is only detectable after betamethasone therapy from the 32nd to the 34th week of gestation. Thus we recommend RDS prophylaxis for all patients with premature contraction, mainly between the 32nd and 34th week of pregnancy. In addition, it should be given in cases of confirmed lung immaturity. Special restrictions are necessary in cases of preeclampsia, eclampsia, diabetes and confirmed maternal infections. In the group of diabetes or preeclampsia patients an RDS prophylaxis should only be given, if at all, when it can be performed under intensive care conditions.

Indication and results of insulin therapy for gestational diabetes mellitus

The aim of this study was to determine whether amniotic fluid insulin concentration (AFI) is a better parameter than mean maternal blood glucose values (MBG) for deciding about insulin therapy in patients with gestational diabetes. MBGs were calculated on the base of 9 blood glucose levels during a 24 hour period after one week of diet therapy. In a prospective trial between 1987 and 1989 in Karlsburg, 123 gestational diabetic patients were randomized into two groups. Treatment was either based on the concentration of AFI or MBG levels. In a second series in Berlin, 103 patients were offered amniocentesis. 81 patients agreed and 22 refused. Treatment was then analogous to that in Karlsburg. In both groups of the randomized population, strict metabolic control was achieved. There was no difference regarding pregnancy complications. Earlier labor induction and higher cesarean section rates were seen in the non-invasive group (p < 0.05). The incidence of diabetic fetopathy and neonatal hypoglycemia was significantly lower in the invasive group (p < 0.01), even though the metabolic control parameters did not differ between the two groups. The results in Berlin correspond to these findings. In conclusion, AFI enables the recognition of any hyperinsulinism reaction to the maternal metabolic situation. We recommend the additional measurement of the AFI concentration between 28 and 36 weeks as the direct fetal parameter for deciding about insulin treatment.

Successful Treatment of Primary Fetal Hydrothorax by Long-Time Drainage from Week 23

We report on a case of unilateral primary fetal hydrothorax leading to nonimmunological fetal hydrops (NIHF). The NIHF was treated successfully by inserting two consecutive intrauterine catheters at 23 weeks gestation. The first catheter was dislocated through the uterine wall to the maternal peritoneal cavity. At 36 weeks gestation, the mother had a spontaneous onset of labor after premature rupture of membranes and a normal vaginal delivery of a healthy infant with good perinatal outcome. Shunting of PFHT has rarely been described up to now. This case report supports observations of previous authors that early shunting of pleural effusions may prevent progression of NIHF as well as postnatal pulmonary hypoplasia. Unexpected perinatal complications of fetus, mother or both should not be neglected.

Acute onset of blindness during labor: report of a case of transient cortical blindness in association with HELLP syndrome.

The coincidence of HELLP syndrome and cortical blindness is an uncommon but very dramatic event, for the patient as well as the obstetrician. This report describes the first case of HELLP-syndrome-associated cortical blindness occuring suddenly in the third stage of labour. There were only modest correlates of cortical blindness in cerebral CT, MRI and angiography findings, but no signs of a posterior leucoencephalopathy syndrome. Mother and baby were discharged from hospital to outpatient care in good health on the 12th day.

Hyperemesis in late pregnancy - should we think of cancer? A case report

Gastric cancer is unusual during pregnancy. The diagnosis may be delayed because specific symptoms are similar to typical pregnancy associated complaints. Our therapeutic management with palliative chemotherapy and later gastrectomy differs from other known cases, where surgical resection has been the treatment of choice. Surgery appears to have no influence on the prognosis of gastric cancer patients with hepatic metastases.