Klaus Reisenberger

Hyperemesis Gravidarum Associated With Helicobacter pylori Seropositivity

Objective To test the hypothesis that infection with Helicobacter pylori is associated with hyperemesis gravidarum. Methods From January 1995 to November 1996 we enrolled 105 patients with hyperemesis gravidarum in a prospective study. The Helicobacter serum Immunoglobulin (Ig) G concentrations in these patients were compared with those in asymptomatic gravidas matched for week of gestation. Results Positive serum IgG concentrations were found in 95 of the 105 hyperemesis patients (90.5%) compared with 60 of 129 controls (46.5%). A χ2 test showed statistical significance (P < .001). The mean (± standard deviation) index percentages of the IgG titers were 74.2 ± 23.6% in the hyperemesis group and 24.3 ± 4.4% in the control group (P < .01, Student t test). Conclusion Infection with H pylori may cause hyperemesis gravidarum.

Cytokine and prostaglandin production by amnion cells in response to the addition of different bacteria

OBJECTIVE Our goal was to evaluate the effect of Escherichia coli, Bacteroides fragilis, Mycoplasma hominis, and Staphylococcus aureus on cytokine and prostaglandin production by amnion cells in vitro. STUDY DESIGN Amnion cells were obtained from women undergoing elective cesarean section before the onset of labor and cultured in a primary cell culture. Confluent amnion cells were incubated with heat-inactivated bacteria in different concentrations (10(1) to 10(6) colony-forming units/ml) for 48 hours. Samples for quantification of interleukin-1 beta, interleukin-6, interleukin-8, tumor necrosis factor-alpha, and prostaglandin E2 were collected at 6, 12, 24, and 48 hours. RESULTS Under basal conditions, minor amounts of interleukin-6 and interleukin-8 were detectable. Incubation of amnion cells with E. coli enhanced the secretion of interleukin-8 and also induced an transient increase of prostaglandin E2 in a dose-dependent manner. B. fragilis produced an increase in the secretion of interleukin-6 and interleukin-8. M. hominis and S. aureus did not cause an increase in either interleukin-6, interleukin-8, or prostaglandin E2. CONCLUSION The gram-negative bacteria E. coli and B. fragilis stimulated interleukin-6 and interleukin-8 to a greater degree than the other bacteria investigated in this study. This finding may be of clinical interest in the onset of preterm birth.

Transfer of erythropoietin across the placenta perfused in vitro

Objective The purpose of this study was to investigate the placental passage of erythropoietin in a placental perfusion model ex vivo. Methods In an open system 18 placentas were perfused on both the maternal and the fetal side. Erythropoietin and a reference substance were added to either the maternal or fetal perfusion medium. In the first series of experiments, radiolabeled erythropoietin was added to the perfusion medium in four different concentrations to help determine the transfer rate of erythropoietin. Based on the results of these experiments unlabeled erythropoietin was added to the perfusate in three different concentrations. Radiolabeled erythropoietin was used in addition to erythropoietin because measuring radioactivity in a gamma counter is less expensive than measuring by immunoassay. Results Accumulation of radioactivity in the venous portion of the fetal circuit was only 3.21% of the activity added to the maternal circuit. No evidence of transfer of erythropoietin to the contralateral compartment was noted, regardless of whether the test substance was added maternally or fetally. These results were independent of the concentration used. The reference compound antipyrine showed a mean transfer rate of 27.9%, which is in keeping with previous results. Conclusion There is no transport of erythropoietin across fetal membranes. This finding is particularly remarkable in view of results published recently indicating the placenta as a site of erythropoietin production. The lack of its transport across the human placenta is most likely due to its high molecular weight.

Influence of intratumoral basic fibroblast growth factor concentration on survival in ovarian cancer patients

Since basic fibroblast growth factor (bFGF) is considered as a potent mitogen that stimulates the growth of ovarian cancer cells, we evaluated the role of bFGF as a prognostic marker in patients with epithelial ovarian cancer. bFGF was quantified from the tumor cytoplasm of 76 patients with FIGO stage I-III ovarian cancer by a human FGF basic immunoassay (R&D Systems). After a mean follow-up period of 42 months, 50 patients were found to be free of tumor while 26 patients had died of the disease. The median bFGF concentration was 352.9 pg/mg (range 27.4-26600 pg/mg). After dichotomization cytoplasmic expression of bFGF was found to be low in 44 tumors (< or =500 pg/mg) and high in 32 tumors (>500 pg/mg). The probability of overall survival was 38.8 and 58.5% in the low bFGF and high bFGF groups, respectively (log-rank P = 0.0066). In multivariate analysis, residual tumor after initial surgery and bFGF, but not histologic grade or stage of the disease, independently influenced the overall survival probability. Furthermore, tumors with high cytoplasmic expression of bFGF revealed a much greater stromal content. Therefore, we hypothesize that bFGF may induce a fibroblastic response which causes tumors with a high bFGF to be less aggressive than those with less stromal tissue.

The transfer of interleukin-8 across the human placenta perfused in vitro.

Objective To assess the placental transfer of interleukin (IL)-8 in vitro. Methods Eighteen placentas obtained immediately after delivery were perfused with a mixture of 125I-Iabeled IL-8 (IL-8*) and unlabeled IL-8 in two different concentrations. Antipyrine was coinfused in all experiments as a reference compound. Fetal-to-maternal and maternal-to-fetal perfusions were performed. Radioactivity was measured in a gamma counter at the end of each perfusions experiment. In four experiments, unlabeled IL-8 was analyzed in addition to labeled IL-8 to exclude a change in the IL-8/IL8* ratio resulting from membrane transfer. Results Two of the 18 experiments had to be discarded because of poor transfer of antipyrine. There was only faint accumulation of radioactivity in the transplacental compartment, regardless of whether the test substance was added maternally or fetally. Because measurement of unlabeled IL-8 yielded negative results, the radioactivity is clearly attributable to free iodine 125, which is generated during IL radiolabeling or which disassociates from IL-8 in small amounts after radiolabeling. Conclusion Interleukin-8 does not appear to cross the placenta by simple diffusion, regardless of the concentration or the perfusion rate. The impermeability of the placenta to the diffusion of IL-8 might explain why there is insufficient correlation between serum and amniotic fluid cytokine concentration of pregnant women and the presence of the amnion infection syndrome.

Concomitant use of glucocorticoids: A comparison of two metaanalyses on antibiotic treatment in preterm premature rupture of membranes

OBJECTIVE This study was performed to investigate whether the demonstrated beneficial effects of antibiotics on maternal and neonatal morbidity are altered when glucocorticoids are part of the treatment of preterm premature rupture of membranes. STUDY DESIGN We performed a metaanalysis of five published, randomized trials of antibiotic treatment in preterm premature rupture of membranes in which glucocorticoids were used as additional treatments and compared the results with those of a previously published metaanalysis of antibiotic treatment in preterm premature rupture of membranes, which excluded studies with concomitant glucocorticoids. Primary outcomes included chorioamnionitis, postpartum endometritis, neonatal sepsis, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal mortality. A logistic regression analysis was performed to test whether glucocorticoids significantly influenced the effect of antibiotic treatment. RESULTS Among the 509 patients from five trials on antibiotic and glucocorticoid treatment published between 1986 and 1993 antibiotic therapy did not show any significant effect on any of the outcomes analyzed. In contrast, antibiotic therapy without concomitant use of glucocorticoids significantly reduced the odds of chorioamnionitis, postpartum endometritis, neonatal sepsis, and intraventricular hemorrhage by 62%, 50%, 68%, and 50%, respectively. The logistic regression analysis showed that glucocorticoids significantly diminished the effect of antibiotic treatment on chorioamnionitis and neonatal sepsis. CONCLUSION Glucocorticoids appear to diminish the beneficial effects of antibiotics in the treatment of preterm premature rupture of membranes. A careful selection of patients who are likely to benefit from both therapies is therefore recommended.

Placental passage of angiotensin-converting enzyme inhibitors

OBJECTIVE Placental passage of the angiotensin-converting enzyme inhibitors temocapril and enalapril was investigated in a placental perfusion model. STUDY DESIGN In an open system a placental lobe was perfused on both the maternal and the fetal side with a blood-free medium containing the test substances plus a reference substance on the maternal side. Six placentas were perfused with temocapril and five with enalapril. The drugs were measured by gas chromatography-mass spectrometry. RESULTS Both angiotensin-converting enzyme inhibitors crossed the human placenta in the maternal-fetal direction in similar quantities. Temocapril showed the same pharmacokinetic characteristics as enalapril. CONCLUSIONS This was the first study to quantify the placental transfer of angiotensin-converting enzyme inhibitors. These antihypertensive agents should not be taken during pregnancy, to avoid any potential hazards to the fetus.

In vitro cytokine and prostaglandin production by amnion cells in the presence of bacteria

OBJECTIVE Our goal was to evaluate the effect of group B streptococci on cytokine and prostaglandin production by amnion cells in vitro. STUDY DESIGN Amnion cells from placentas obtained immediately after primary cesarean section were incubated for 48 hours with heat-inactivated group B streptococci at increasing concentrations. Samples for quantification of interleukin-1 beta, interleukin-6, interleukin-8, tumor necrosis factor-alpha, and prostaglandin E2 were collected at 6, 12, 24, and 48 hours. RESULTS Basal cytokine production was not demonstrable for any of the cytokines investigated. Incubation of amnion cells with bacterial antigen led to a significant increase in interleukin-6 and interleukin-8 production, whereas secretion of interleukin-1 beta and tumor necrosis factor-alpha was not enhanced. In contrast to cytokines, basal prostaglandin E2 production was measurable but failed to increase after addition of antigen. CONCLUSION Amnion cells can be stimulated to secrete interleukin-6 and interleukin-8 in response to streptococcal antigen. However, this rise in cytokines does not induce an increase in prostaglandin E2. This may be explained by the lack of interleukin-1 and tumor necrosis factor-alpha production, two cytokines that have been shown to activate prostaglandin E2 secretion by amnion cells.

The passage of granulocyte-macrophage colony-stimulating factor across the human placenta perfused in vitro.

Objective: The purpose of this study was to investigate the placental passage of granulocyte-macrophage colony-stimulating factor in a placental perfusion model ex vivo. Methods: In an open system, 11 placentas were perfused on both the maternal and the fetal side immediately after delivery. Granulocyte-macrophage colony-stimulating factor was added to the maternal perfusion medium in concentrations from 10-55 μg/mL. Maternal and fetal samples were taken, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was measured by enzyme-linked immunosorbent assay. Results: Accumulation of granulocyte-macrophage colony-stimulating factor in the fetal circuit averaged 2.42% of the concentration added initially to the arterial portion of the maternal circuit. Conclusion: There is only low transfer of GM-CSF across the fetal membranes. This finding is particularly remarkable in view of recently published results suggesting that administration of recombinant granulocyte growth factors to pregnant women with imminent preterm delivery helps prevent neonatal sepsis.

Thromboxane and Prostacyclin Production of Trophoblast Cells After Very Low-Density Lipoprotein Incubation

Objective: To test the effects of native VLDL (nVLDL) and oxidized VLDL (oxVLDL) on thromboxane and prostacyclin release from syncytiotrophoblasts in an in vitro model.Study Design: After isolation and Percoll centrifugation, three series of syncytiotrophoblast cell cultures were prepared for determination of thromboxane B2 (T×B2) and 6-keto prostaglandin (PG)lα, the stable metabolites of thromboxane and prostacyclin: a standard cell culture, a cell culture incubated with nVLDL, and a cell culture incubated with ox VLDL. Samples were taken at 2 and 24 h of incubation, and the changes in concentration were compared among cultures.Results: Production of T×B2 decreased in the standard cell culture (P = 0.0001), but increased after incubation with nVLDL (P = 0.01) or ox VLDL. Release of 6-keto PG1α remained largely unchanged in the standard cell culture, but increased in nVLDL (P = 0.02) and oxVLDL incubated cells. Comparisons among cell cultures showed that the production of T×B2 was significantly higher in ...