Gene expression of topoisomerase II alpha (TOP2A) by microarray analysis is highly prognostic in estrogen receptor (ER) positive breast cancer.

INTRODUCTION: Overexpression of Topoisomerase II alpha (TOP2A) has been implicated with gene amplification of the 17q21 amplicon and consecutively with ErbB2 overexpression and amplification. However, gene amplification does not necessarily correlate with RNA and protein expression. There is growing evidence that TOP2A protein expression is a strong prognostic and TOP2A gene amplification might be a predictive marker (particularly for the use of anthracyclines). METHODS: Large scale analysis was performed using Affymetrix microarray data from n = 1,681 breast cancer patients to evaluate TOP2A expression. RESULTS: TOP2A expression showed a strong correlation with tumor size (chi(2)-test, P < 0.001), grading (P < 0.001), ErbB2 (P < 0.001) and Ki67 expression (P < 0.001) as well as nodal status (P = 0.042). Survival analysis revealed a significant prognostic value in ER positive (n = 994; log rank P < 0.001), but not in ER negative breast cancer patients (n = 369, P = 0.35). The prognostic impact of TOP2A expression was independent of Ki67 expression in ER positive tumors (P = 0.002 and P = 0.007 for high and low Ki67, respectively). Moreover a worse prognosis of high TOP2A expressing tumors was found in the subgroup of ErbB2 negative tumors (P < 0.001) and a trend among ErbB2 positive tumors (P = 0.11). The prognostic value of TOP2A was independent of whether the patients were untreated or had received adjuvant therapy. In multivariate Cox regression analysis including standard parameters TOP2A emerged to be the top prognostic marker (HR 2.40, 95% CI 1.68-3.43, P < 0.001). CONCLUSION: TOP2A expression is an independent prognostic factor in ER positive breast cancer and could be helpful for risk assessment in ER positive breast cancer patients.

Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response.

Gene expression analysis in breast cancer patients undergoing neoadjuvant chemotherapy is an interesting tool for identification of gene signatures and new markers to predict tumor response. However, the detection of predictive markers strongly depends on the drugs used in the specific therapeutic setting. There is growing evidence that topoisomerase II-alpha (TOPO IIalpha) is a marker for anthracycline-, and microtubule-associated protein tau (MAPT) for taxane sensitivity. HER-2 has been described as a marker of both anthracycline and taxane sensitivity. We performed gene expression profiling of 50 patients within the GEPARTRIO study, an anthracycline and taxane neoadjuvant chemotherapy trial. Here we investigate the predictive value of TOPO IIalpha, MAPT and HER-2 mRNA expression for pathological complete response (pCR) in this setting. Interestingly, HER-2 gene expression was strongly predictive of pCR (P=0.017) as well as overall response (P=0.037) and clinical complete response (cCR, P=0.050). In contrast, for both TOPO IIalpha and MAPT no correlation with pCR was observed in our sample group.

Prognostic value of cathepsin D in breast cancer: comparison of immunohistochemical and immunoradiometric detection methods.

AIM: To test whether immunoradiometric or immunohistochemical detection of lysosomal protease cathepsin D in breast cancer is more predictive of outcome. METHODS: Tumour tissues from 270 primary breast cancer patients were evaluated for the expression of cathepsin D using immunohistochemistry (IH; paraffin embedded tissues) and an immunoradiometric assay (IRMA; cytosol from frozen tissues). Immunohistochemical scores were based on immunoreaction in tumour cells and tumour associated macrophages. RESULTS: IRMA values (cut off 40 fmol/mg cell protein) correlated significantly with IH values. Recorded incidences of positive immunoreaction in tumour cells using two different cut off values were 52% and 35%, respectively. Macrophages stained positive in 31% of tissues. Combined evaluation of tumour cells and macrophages resulted in positivity rates of 59% and 48%, respectively. Node status was the only variable found to correlate with cathepsin D expression. IH results correlated significantly with clinical outcome (median observation time 68 months) in node negative patients (n = 120) but not in node positive patients (n = 145). Cathepsin D positivity as measured by IRMA was not related to clinical outcome in either group. On multivariate analysis in the node negative group, IH detection of cathepsin D appeared to be the only independent factor indicating prognosis. For node positive patients, tumour grade, size, and receptor status were of prognostic relevance. CONCLUSIONS: Because of the simple methodology and the minimal amount of tissue used for analysis, immunohistochemistry was preferred to immunoradiometry for cathepsin D measurement; it also provided more predictive data with respect to prognosis.

Immunohistochemical detection of epidermal growth factor receptor lacks prognostic significance for breast carcinoma.

OBJECTIVE: We sought to determine whether the immunohistochemical detection of epidermal growth factor receptor (EGF-R) in primary cancer tissues is of prognostic significance in patients with breast carcinoma. METHODS: Paraffin-embedded tissues from 244 study subjects with primary breast carcinomas were tested immunohistochemically for the presence of EGF-R and were compared in a retrospective study with clinical outcome. RESULTS: Epidermal growth factor receptor was detected in the tumors of 49 (20.1%) of the 244 study subjects. The incidence of EGF-R detection was comparable in subjects with disease-free lymph nodes (T1-4, N0, M0, n = 111; EGF-R present 22.5%) or those whose nodes contained carcinoma (T1-4, N+, M0, n = 133; EGF-R present 18.9%). No reliable correlation was found in either group between EGF-R detection and clinical, functional, or morphologic prognostic indicators that included age, menopausal status, tumor size, tumor grade, nodal status, and hormone receptor status. Relapse-free survival and overall survival (median observation time 62.5 months) did not differ between patients with EGF-R-positive or EGF-R-negative breast carcinoma specimens. CONCLUSIONS: In our experience, the immunohistochemical determination of EGF-R in routine formalin-fixed, paraffin-embedded tumor specimens fails to provide useful information concerning the prognosis of patients with primary breast carcinoma.

Comparative prognostic value of Cathepsin D and urokinase plasminogen activator, detected by immunohistochemistry, in primary breast carcinoma.

The lysosomal protease Cathepsin D and the serine protease urokinase plasminogen activator (uPA) are suspected to indicate poor prognosis in primary breast carcinoma. We tested Cathepsin D and uPA immunohistochemically in 281 surgical specimens of primary ductal infiltrating breast carcinomas. Staining was evaluated, taking intracytoplasmic immunoreactions into account, in tumour cells and tumour infiltrating macrophages. Positivity was established in 48.4% and 58.0% of tissue samples for cathepsin D and uPA respectively (co-expression: 67.6%). In patients with cathepsin D- or uPA-positive tumours, relapses were more frequent and disease-free survival was shorter irrespective of nodal status, receptor status or menopausal status, (median observation time 74 months). However, this trend was statistically significant only for cathepsin D. With stepwise cox regression analysis, borderline significance (p = 0.07) was calculated for cathepsin D only in node-negative patients. The combination of cathepsin D with uPA measurements did not enhance its prognostic value. Immunohistochemical detection of Cathepsin D could potentially be used to identify patients with poor prognosis in the group of node negative breast cancer patients.

Immunocytochemical and molecular strategies for the detection of micrometastases in patients with solid epithelial tumours: a review.

This review focuses on diagnostic approaches to identify patients with minimal residual epithelial cancer. Epithelial malignancies are the most common forms of cancer in Western industrialized countries. The failure to reduce the mortality of patients with epithelial tumours is probably a result of the early dissemination of cancer cells to secondary sites, which is usually missed by conventional diagnostic procedures used for tumour staging. Therefore, over the past 10 years, sensitive assays have been developed to detect individual carcinoma cells disseminated to regional lymph nodes or distant organs. Among the distant organs, the bone marrow has been identified as the most important site for the detection of haematogeneously spread cancer cells. With regard to detection techniques, most investigators have used either immunocytochemical assays with a variety of 'epithelial-specific' cytoskeleton and membrane antigens, or molecular methods based on the polymerase-chain reaction. At present, almost all data on the prognostic significance of micrometastatic cells in bone marrow are based on immunocytochemical analyses, whereas the promising new molecular assays still need to be validated in clinical trials.

Predictive value of impaired uterine transport function assessed by negative hysterosalpingoscintigraphy (HSSG).

BACKGROUND: Hysterosalpingoscintigraphy (HSSG) has given insight into the dynamics of rapid sperm transport inside the female genital tract. RESULTS: While there is an increase of an ipsilateral transport on the side bearing the dominant follicle in 70% of the subjects in the periovulatory phase, 15% of the patients do not demonstrate transport to the fallopian tubes (negative HSSG). In these patients the pregnancy rate achieved spontaneously or by intrauterine insemination is significantly reduced compared to the patients who showed an intact transport mechanism confirmed by positive HSSG. On the other hand, by means of assisted reproductive techniques (ART), pregnancy rates were higher in the group of patients showing negative HSSG (P < 0.0005). CONCLUSIONS: Our data clearly indicate that HSSG is a helpful method to evaluate the integrity of the utero-tubal transport mechanism. As pregnancy rates remain low in patients with negative HSSG, this result should be considered as an indication for IVF-treatment even in patients with patent fallopian tubes and normozoospermia of the partner.

Cytology of ascitic fluid in a patient with metastasizing malignant Brenner tumor of the ovary. A case report.

BACKGROUND: Transitional cell ("Brenner") tumors represent about 2% of all ovarian neoplasms. Brenner tumors are almost always benign. Malignant Brenner tumors of the ovary resemble urothelial carcinomas and are extremely rare. CASE: A 77-year-old, white female presented with malignant Brenner tumor in both ovaries as well as lung and abdominal metastases. The cytology of the ascitic fluid revealed many activated mesothelial cells and three-dimensional cell clusters arranged in a papillary pattern. The round to oval nuclei displayed mild anisokaryosis and hyperchromasia but had a quite evenly dispersed opaque or finely granular nucleoplasm. Enfoldings of the nuclear membrane gave them the appearance of so-called coffee bean nuclei. The cytoplasm stained light bluish. CONCLUSION: Knowledge of the cytologic features of ascitic fluid might allow a preoperative diagnosis of malignant, or at least proliferating, ovarian Brenner tumor.

Ovarian cancer antigen CA 125 influences adhesion of human and mammalian cell lines in vitro.

Despite the widespread use of CA 125 for diagnostic and therapeutic evaluation of ovarian cancer function, the molecular nature of CA 125 is only poorly understood. It has been shown that CA 125 enhances the invasiveness of a benign endometriotic cell line in vitro. The invasiveness of cells is controlled by proteolytic activity, cell motility and cell adhesion. Therefore, we determined the influence of CA 125 on the cell adhesion of human carcinoma cell lines in vitro. In all tested human and mammalian cell lines (HECIA, AN3-CA, RL95-2, SK-OV-3, OAW-42, PA-1, HeLa, MCF7, T-47D, A-673, RT112, EJ28, EEC 145, CHO, MDBK, MDCK. LLC-PK1) the cell adhesion in vitro was significantly impaired by CA 125 in a time-dependent manner. Treatment of cells with trypsin diminished the effect of CA 125 on cell adhesion for two hours. By inhibition of protein synthesis with cycloheximide (2 microg/ml) the influence of trypsin on the anti-adhesive effect of CA 125 was significantly prolonged. The results suggest that the ovarian cancer antigen CA 125 influences cell adhesion in vitro.

Prognostic impact of thymidine phosphorylase expression in breast cancer--comparison of microarray and immunohistochemical data.

Contrary findings exist according to the prognostic and predictive impact of thymidine phosphorylase (TP) expression in breast cancer. Goal of our study was to investigate TP expression on the mRNA level by microarray analysis in a large cohort of 1781 breast cancers and to analyse its prognostic impact. Furthermore we compared mRNA expression and immunohistochemical data to explain discrepancies between different studies. The prognostic value of TP mRNA expression was analysed among n=622 untreated patients. Strong expression in the subgroup of n=213 ER-negative cancer correlates with improved survival (P=0.012). In contrast, no difference in survival was detected in the ER-positive group. We also failed to observe a prognostic value of TP mRNA among n=435 endocrine-treated patients as well as n=111 CMF-treated patients. In an unsupervised analysis, TP clustered together with genes expressed in immune cells. Moreover, among normal tissues the highest TP mRNA expression was found in tissues of the immune system. The profile of TP expression in breast cancers correlates to a metagene of interferon induction whereas the expression of TP among normal tissues correlates to a metagene for macrophages. When comparing microarray data with immunohistochemistry from the same n=51 samples, there was no correlation with stained carcinoma cells. In contrast, the correlation with stromal staining was highly significant (P<0.001). Thus TP mRNA from microarray mainly reflects expression in stromal and immune cells. This could account for discrepant results from mRNA and IHC studies. In conclusion, the tumour infiltrating immune cells seem to be a major source of TP expression and predict a favourable prognosis in ER-negative breast cancer. Our data point to a role of TP in host immune response.

Prenatal ultrasound assessment and fetal heart monitoring: analysis of dizygotic twins discordant for body stalk anomaly in the third trimester of pregnancy.

We describe a case of dizygotic twin pregnancy which was referred to our centre because of a discordant anomaly of one of the twins. The ultrasound examination revealed a large extra-abdominal mass (liver and bowel) with micromelia, severe kyphoscoliosis and a short umbilical cord of the second dizygotic discordant twin. These ultrasound findings were diagnosed as body stalk anomaly. Body stalk anomaly in twins is extremely rare. This is, to our knowledge, one of the few documented cases reported on dizygotic twins discordant for this anomaly. This finding, in association with a decrease of amniotic fluid volume, may be attributed to early amniotic membrane rupture as the primary event in the pathogenesis of body stalk anomaly.

[Management of abnormal uterine bleeding]. / Ursachen und Therapie von uterinen Blutungsstörungen.

Bleeding disorders are one of the most frequent gynecological problems. The causes of bleeding disorders, and their frequency in particular, vary depending on the age of the woman affected. In premenopause and perimenopause, the most frequent causes are hormonal, in up to 90 % of cases, as well as organic changes in the uterus such as myomas, adenomyosis uteri, or endometrial polyps, in up to 70 % of cases. Coagulation defects cause increased bleeding, particularly in girls and young women, with no other recognizable cause. The treatment of bleeding disorders is causally based, although if the woman does not wish to have children, the therapeutic algorithm in many cases leads to similar symptomatic measures. The following therapeutic approaches, listed in order of increasing efficacy, are mainly used in the treatment of increased bleeding: gestagen, estrogen-gestagen combination, levonorgestrel (Mirena) and endometrial ablation or myoma enucleation, with comparable success rates, and finally hysterectomy. Embolization of the uterine artery in myomas or adenomyosis uteri, nonsteroidal anti-inflammatory drugs, and antifibrinolytic agents represent alternatives that may be useful in individual cases. The paper provides an overview of the various causes, useful diagnostic measures, and treatment options in uterine bleeding disorders.

[Integrin expression in eutopic and ectopic endometrium]. / Integrinexpression im eutopen und ektopen Endometrium von Endometriosepatientinnen.

The significance of retrograde menstruation as a risk factor for endometriosis has been confirmed by numerous clinical observations. Integrins mediate both cell-cell and cell-matrix adhesion, and it is therefore suspected that integrins are involved in the development of endometriosis. Using immunohistochemistry, integrin expression in eutopic and ectopic endometrium is examined in endometriosis patients and control individuals. In nearly all cases, the glandular epithelial cells in the endometrium showed expression of alpha (2-), alpha (3)-, alpha (6)- and alpha (v)- integrin and a low percentage of expression of alpha (1)-, alpha (4)-, and alpha (5)-integrin. In comparison with eutopic endometrium, ectopic endometrium shows reduced expression of alpha (2)- and alpha (v)-integrin. Since no differences in alpha (2)- and alpha (v)-integrin expression were observed in eutopic endometrium between endometriosis patients and control individuals, it may be suspected that the reduced expression of these in ectopic endometrium is explained by influences in the altered environment -- e. g., in the peritoneal fluid -- on the ectopic endometrium.

[Risk factors for recurrence of vulvar intraepithelial neoplasia III (VIN III)]. / Risikofaktoren der Rezidivhäufigkeit von vulvären intraepithelialen Neoplasien Grad III (VIN III).

OBJECTIVE: The incidence of vulvar intraepithelial neoplasia (VIN) has increased in the last decades. The therapy of VIN is the in toto resection. Still some patients develop VIN recurrence. The aim of this retrospective study is the identification of risk factors for VIN recurrence. MATERIAL AND METHODS: 68 Patients with VIN III has been examined in an univariate and multivariate analysis for the following parameters (follow-up: median 27 months): age, HPV, HIV, multicentricity, resection margins (1-4 mm, 5-9 mm, > or = 10 mm). RESULTS: In the univariate analysis positive HPV and HIV status correlated with VIN recurrence. Also resection margins < 5 mm showed a significant correlation with VIN recurrence. Multivariate analysis demonstrated that HPV, HIV and resection margins < 5 mm are independent risk factors. No statistically association was found for age and multicentricity. CONCLUSION: The aim of VIN therapy must be the total resection with a negative resection margin of > or = 5 mm. HPV- and/or HIV-positive patients have a significantly higher risk for VIN recurrence and need therefore an intensive follow up.

[Identification of preeclampsia by cDNA-gene expression profiling in human placentas and serum -- a pilot study]. / Identifikation von Präeklampsiepatientinnen mittels cDNA-Genexpressionsprofilen an humanen Plazentaproben und Serum -- eine Pilotstudie.

OBJECTIVE: Preeclampsia is associated with significant maternal and fetal morbidity and mortality. The etiology remains unclear. For the accurate diagnosis and the prevention of preeclampsia it seems to be important to find a diagnostic tool that identifies risk patients before symptoms occur. With a new approach, the cDNA-Array analysis, human placentas and blood from preeclamptic and healthy pregnant women were examined for differentially expressed genes to find typical genes expression profiles. MATERIAL AND METHODS: In this pilot study, cDNA array analysis with a 19 200 gene array of placenta and blood samples from three preeclamptic patients have been performed to classify this samples based on expression patterns. RESULTS: Comparing normal placenta and blood from healthy delivered women (n = 4), a subset of 200 genes repeatedly found to be differentially expressed in preeclampsia. The placenta and blood samples from preeclampsia were accurately grouped by their individual gene expression patterns. CONCLUSIONS: These results suggest that the use of cDNA array is a tool to identify gene expression patterns in preeclampsia. With this set of differentially expressed genes in conjunction with sample clustering algorithms the identification of preeclampsia in placenta or blood samples is possible.

[Cervical cancer screening of HIV-positive women: is a prolongation of the screening interval meaningful?]. / Zervixkarzinom-Früherkennung bei HIV-positiven Frauen--Ist eine Verlängerung des Screeningintervalls sinnvoll?

OBJECTIVE: Cervical cancer screening guidelines stated recently that the screening interval of healthy women can be extended up to 3 years. Can those recommendations be applied for high risk populations? MATERIAL AND METHODS: In a prospective setting 305 HIV-positive women have been enrolled in this analysis between September 2000 and December 2003. Patients have been characterized according to HPV (human papilloma virus) prevalence, CIN (cervical intraepithelial neoplasia) incidence and CD4 cell count. RESULTS: 41 % of all HIV-positive women were HPV positive (oncogene subtypes). In patients with diminished CD4 cells the HPV prevalence increased to 60 % (54/90). CIN was found in 27 % (83/305) women. CIN was more frequent by HPV-positive women with a CD4 cell count < 200 mm (3) (52 %, 38/72). The CIN incidence was also high in HIV-positive women with negative HPV infection and diminished CD4 cell count (39 %, 7/18 vs.7 %, 11/161). CONCLUSIONS: The current cervical cancer screening guidelines are not helpful in HIV-positive women. The CIN incidence is significantly higher as in the HIV-positive population. For this reason this high risk population as e. g. HIV-infected women need an intensive care of diagnostic tools and short screening intervals to detect CIN.

Gene expression profiles of breast cancer obtained from core cut biopsies before neoadjuvant docetaxel, adriamycin, and cyclophoshamide chemotherapy correlate with routine prognostic markers and could be used to identify predictive signatures.

BACKGROUND: Neoadjuvant administration of chemotherapy provides a unique opportunity to monitor response to treatment in breast cancer and assesses response exactly. Global gene expression profiling by microarrays has been used as a valuable tool for the identification of prognostic and predictive marker genes. Even though this technology is now wide spread and relatively standardized, there are only few data available which compare established parameters with expression values to determine reliability of this method. Therefore we analyzed gene expression data of pretreatment biopsies of breast cancer patients and compared them with the results of the immunohistochemical receptor expression for ER/ PR and Her-2, as well as FISH testing for HER-2 amplification. We analyzed the change of expression of these markers before and after neoadjuvant chemotherapy. Furthermore we evaluated the predictive significance of prognostic gene signatures as described by Sorlie, van't Veer and Ahr for response to neoadjuvant chemotherapy. METHODS: Pretherapeutic core biopsies were obtained from 70 patients undergoing neoadjuvant TAC chemotherapy within the GEPARTRIO-trial. Samples were characterized according to standard pathology including ER, PR and HER2 IHC and amount of cancer cells. Only biopsies with more than 80 % tumor cells were considered for further examination. RNA was isolated and expression profiling performed using Affymetrix Hg U133 Arrays (22 500 genes). GeneData's Expressionist software was used for bioinformatic analyses. RESULTS: More than two thirds of the biopsies yielded sufficient amounts (> 5 microg) of RNA for expression profiling and high quality data were obtained for 50 samples. Unsupervised clustering broadly revealed a correlation with hormone receptor status. When ER-alpha, PR and HER2 as analyzed by immunohistochemistry were compared to the corresponding mRNA data from gene chips more than 90 % concordance was observed. We could observe a switch of receptor expression for ER, PR or HER-2 from positive to negative and vice versa in 16/35 cases (45.7 %) and 5/22 cases (22.7 %) respectively. The prognostic marker sets of Sorlie, van't Veer and Ahr could not discriminate responders from non-responders in our patient group. CONCLUSIONS: Our results demonstrate that reliable expression profiles can be achieved by using limited amounts of tissue obtained during neoadjuvant chemotherapy. Microarray data capture conventional prognostic markers but might contain additional informative gene sets correlated with treatment outcome. Prognostic marker sets are not suitable to predict tumor response in the neoadjuvant setting, suggesting the necessity of class prediction methods to identify marker sets predictive for the type of therapy used.

[Management of HIV-positive pregnancies -- results from a retrospective study]. / Geburtshilfliches Management bei HIV-positiven Schwangeren: Ergebnisse einer retrospektiven Analyse an einem integrativen Zentrum.

OBJECTIVE: The management of HIV-positive pregnancies was investigated in conjunction to pre-, peri and postpartal complications and the HIV transmission rate. PATIENTS AND METHODS: Retrospective study of 88 HIV-positive patients who were delivered at the Dept. of Obstetrics and Gynaecology during 1.1.1997-31.12.2001. RESULTS: HIV-positive patients showed significantly more prepartal complications, compared to control group. Low CD4-cell count (< or = 200/microl) or high viral load (> 10 000 HIV-copies/ml) was not associated with increased risk for transmission relevant complications. The overall HIV-transmission rate was 3.4 % (3/89 newborns; with ART 2.5 % [2/85], without ART 33.3 % [1/3]). The transmission rate increased with complications during pregnancy (7.7 % [2/26] vs. 1.6 % [1/61]). Newborns delivered < or = 35 (th) week of gestation showed a transmission rate of 5.3 % compared to 2.9 % of newborns delivered after the 35 (th) week of gestation. 98 % of the patients were delivered by cesarean section (primary: n = 71, prior: n = 15), spontaneously: n = 2). 97 % of patients (85/88) were treated with antiretroviral therapy (ART). No differences were found in the postpartal complication rate of HIV-positive to -negative patients. None of the newborns was breast fed. CONCLUSIONS: Treatment of this risk-pregnancies in HIV experienced centers significantly reduces the risk of HIV transmission.

[Premature rupture of fetal membranes: problems and obstetric management]. / Der vorzeitige Blasensprung: Problematik und geburtshilfliches Management.

The treatment of a premature rupture of the foetal membrane (prom) has up to now been a subject of controversy. Depending on the stage of gestation, the prompt birth ensuing as a result of prom, involves the risk of immaturity of the child. Conservative waiting by contrast, exposes mother and child to a potential risk of infection. The retrospective study presented, summarises the strategies for treating prom used at the Cologne University Department of Obstetrics and Gynaecology during the period from 1984 to 1989, and attempts to develop from these data proposals for the treatment of prom. With an increase in latency of over 24 hours between prom and delivery, the maternal and neonatal rate of infection also increased significantly. An effective result of a prophylaxis with antibiotics could only be shown in the reduction of incidence of infection in the mother. An effect on the neonatal rate of infection could not be seen. Inducing prepartually lung-maturity with glucocorticoides or ambroxol resulted in a significant decrease of the RDS-rate in new born children up to the 34th week of gestation. Beyond the 34th week of gestation, this effect could not be found. Whereas after completion of the 37th week of gestation, the preferred treatment used by doctors is allowing the shortest possible time of latency between prom and delivery, the expected pulmonary immaturity before the 34th week of gestation has to be treated by prolonging the pregnancy and inducing pulmonary maturity under antibiotic prophylaxis and at the same time controlling infection.(ABSTRACT TRUNCATED AT 250 WORDS)

[Isolated decrease of haptoglobin during pregnancy: diagnosis by chance or pathological? ]. / Isolierter Haptoglobinabfall in der Schwangerschaft: Zufallsbefund oder pathologisch? - Diskutiert anhand eines Fallberichtes -

Haptoglobin is an acute-phase-protein, which is important in many diseases like infections, trauma and neoplasma. An increase in haptoglobin is induced by cytocines like IL-6 und IL-1. The normal range for plasmatic haptoglobin is 50-220 mg/dl. During pregnancy the most likely diagnosis is the HELLP- Syndrome (hemolysis, elevated liver enzymes and low platelets), followed by rare diagnoses like viral hepatitis or favism. We report about a 31-year-old III-gravida 0-para at 31 weeks of gestation with a decrease of haptoglobin over a period of 6 weeks (cut off: < 13 mg/dl) and without any clinical signs of preeclampsia. Liver enzymes were constantly slightly elevated without any progress, other laboratory test results were normal. The patient had a caesarean section at 37 weeks of gestation. Serum haptoglobin returned to normal values within three days after delivery. The reason for the decrease of haptoglobin in our case remains uncertain. Further studies need to focus on the differential diagnosis of a decrease of haptoglobin as well as an isolated decrease of haptoglobin during pregnancy and on the valid ranges of the different haptoglobin subtypes.