Direct evidence for transplacental allergen transfer.

Allergies are increasing, and despite deeper insights into the immunologic basis of these diseases, preventive measures are not yet efficient. As the induction of allergic diseases is often triggered in early childhood, perinatal or prenatal preventive strategies would be beneficial. We investigated the transfer of inhalant and nutritive allergens across the human placenta. For this purpose, the maternal side of a placental cotyledon was perfused in vitro with an allergen-containing medium, and a specific ELISA was used to detect the allergens on the fetal side. Both allergens evaluated, birch pollen major allergen Bet v1 and the milk allergen beta-lactoglobulin, could be shown to cross the placenta. The nutritive allergen beta-lactoglobulin was not only transferred across the placenta in all eight experiments, but was also detectable within the first minutes of perfusion. The peak allergen concentration on the fetal side could be increased by addition of human immunoglobulin. For the inhalant allergen Bet v1, transfer was observed in two of 10 placental experiments, and only if human immunoglobulin was added. A pulsatility wave with a frequency of 30-35 min suggested an active transfer mechanism. We conclude that allergens are actively and selectively transferred across the placenta. Therefore, controlled maternal allergen exposure might offer new ways to induce tolerance to specific allergens in the fetus.

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 micrograms/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.

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.

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.

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 chi2 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.

The influence of vascular space involvement on the prognosis of patients with stage IB cervical carcinoma: correlation of results from hematoxylin and eosin staining with results from immunostaining for factor VIII-related antigen.

BACKGROUND: There is controversy over the question of whether the involvement of vascular spaces influences the prognosis of patients with carcinoma of the uterine cervix. The aim of the current study was to compare patterns of vascular space involvement determined by hematoxylin and eosin (H & E) staining with those patterns determined by immunostaining for factor VIII-related antigen (F8-RA) with regard to their prognostic impact on the disease free survival (DFS) and overall survival (OS) of patients with clinical Stage IB cervical carcinoma. Staining for F8-RA is known to highlight blood vessels predominantly, whereas the presence of tumor cell emboli in vascular spaces of H & E-stained sections mainly indicates lymphatic vessel invasion. METHODS: The authors analyzed data on 163 patients for whom vascular space involvement (VSI) was determined by H & E (VSI/H & E) and F8-RA (VSI/F8) staining from the same block in two separate runs. RESULTS: The median follow-up period was 85 months (range, 5-170 months). The 25% quantile for OS was 109 months (median not reached; range, 5-170 months). The overall rates of VSI/H & E and VSI/F8 were 29.4% and 24.5%, respectively. The findings obtained by H & E and F8-RA staining were concurrent in 60.7% of cases. Lymph node involvement and VSI/F8 remained independent prognostic factors for DFS and OS. Due to a highly significant correlation of pelvic lymph node status with both VSI/H & E and tumor size, the last two parameters failed to retain a significant value. For lymph node negative patients, the estimated OS probability was 92% for those without VSI/F8 and 62% for those with VSI/F8. CONCLUSIONS: VSI/F8 may provide additional information on the outcome of clinical Stage IB cervical carcinoma. Lymph node negative patients with VSI/F8 positive tumors may benefit from more intense postsurgical treatment. Further trials involving larger series of patients are necessary to confirm these findings.

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.

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.

[Varicella infection at the time of cesarean section]. / Varizelleninfektion zum Zeitpunkt einer Sectio caesarea.

Report on a twin pregnancy terminated by Caesarean section in the 35th pregnancy week due to retardation and pathological Doppler findings in the umbilical artery and fetal aorta. At the time of Caesarean section the mother suffered from florid varicella infection. The newborns treated with varicella hyperimmunoglobulin and acyclovir developed abortive varicella exanthema without further complications.

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.

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-labeled 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 perfusion experiment. In four experiments, unlabeled IL-8 was analyzed in addition to labeled IL-8 to exclude a change in the IL-8/IL-8* 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 concentrations of pregnant women and the presence of the amnion infection syndrome.

Gemeprost for first trimester missed abortion.

In 87 patients with a missed abortion prior to 13 weeks, the application of a prostaglandin (PG) E1 derivative (1 mg gemeprost, Cergem) was compared to conventional surgical termination of pregnancy by cervical dilatation and curettage. In 33 patients with PGE1 application, complete expulsion of the abnormal pregnancy occurred after an average of 2.8 +/- 1.5 vaginal suppositories. PGE1 treatment was effective in 76.7%, and surgical management was effective in 90.9% of patients. Sixty percent of the patients in the PGE1 group required analgesia because of uterine pain in comparison to 4.5% in the surgical group. The possibility of medical termination with synthetic PG derivatives should be further investigated.

[Good sense and nonsense in tocolysis]. / Sinn und Unsinn der Tokolyse.

The present paper tries to evaluate the importance of tocolysis with beta-sympathomimetic drugs twenty years after their introduction into obstetrics. Intrauterine resuscitation and short-term tocolysis have proven to be very effective during this period of time. Because of potential side effects long-term tocolysis has to be considered dangerous and apparently not effective. Oral and prophylactic tocolysis are ineffective. When considering prevention of premature delivery one has to be aware of the fact that premature contractions are only ostensible symptoms of a complex event.

[Actinomycosis and intrauterine spiral. 4 case reports]. / Aktinomykose und Intrauterinspirale. 4 Kasuistiken.

Genital actinomycotic infections are relatively rare and show a strong coincidence with long term IUD application. Two patients without symptoms, where diagnosis was made by means of Papanicolaou smears, were compared with two patients, where removal of a tubovarian mass led to diagnosis. A general agreement about diagnosis and especially screening tests are still missing, but there seems to be a consensus regarding the types of IUD, the duration of use, and the sexual behaviour of the patients.

Uncomplicated urinary tract infections in pregnant and non-pregnant women.

Urinary tract infections (UTIs) are still one of the most common bacterial infections in pregnant and non-pregnant women. It is estimated that about 10-20% of all women suffer from a UTI at some point in life. The presence of UTI is defined as the existence of urinary symptoms such as frequency of urination and dysuria with or without bacteriuria or pyuria. The prevalence of bacteriuria in females varies from less than 1% in infants to 10% and more in older women. There are major differences in the clinical features between young and elderly women depending on the different pathogenesis, microbiology and general condition. Especially for elderly women, symptomatic and asymptomatic bacteriuria presents a risk factor for bacteraemia, sepsis and also increased mortality. During pregnancy, the prevalence of bacteriuria does not change but there are some changes in the pathogenesis that increase the rate of pyelonephritis. Asymptomatic bacteriuria rarely resolves spontaneously during this time. For non-pregnant women, short therapy strategies are recommended, preferably 3 days of trimethoprim-sulphamethoxazole (TMP/SMX) or quinolones. In pregnant women, therapy with amoxycillin or an oral cephalosporin is considered optimal.

[Therapy of infections in gynecology]. / Therapie von Infektionen in der Gynäkologie.

Infections of the female genitals are among the most common conditions seen by primary care physicians. Approximately 75% of all women experience at least one episode of vaginitis during their reproductive life. Bacterial flora of the female genital tract is complex and dynamic. Those organisms which may cause gynecological infections in the appropriate setting are often present at a different stage in the woman's life as normal flora. The treatment of gynecological infections is dependent on the symptoms of the patient, the pathogen, and the medical history with regard to recurrences of the same disease. Since identification of the pathogen is often difficult, empirical therapy is administered frequently, which requires detailed knowledge of the most common bacterial pathogens and the resistance pattern of these organisms. An accurate initial diagnosis is the best basis for appropriate therapy, especially in view of the fact that once empirical antibiotic therapy has been administered, signs and symptoms are modified and the site of infection is rendered much more obscure.