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Biomedical subjects

Klaus Friese

Publications and source records attributed to Klaus Friese.

At least 19 recordsLinked to original sources
PubMed2007

Expression of the inhibin/activin subunits (-alpha, -betaA and -betaB) in normal and carcinogenic endometrial tissue: possible immunohistochemical differentiation markers.

Inhibins (INH) are dimeric glycoproteins, composed of an alpha-subunit (INH-alpha) and one of two possible beta-subunits (INH-betaA or -betaB), with substantial roles in human reproduction and in endocrine-responsive tumors. The aims of this study were to determine the frequency and tissue distribution of INH-alpha, -betaA and -betaB in normal and malignant endometria. Samples were obtained from normal (n=46), atrophic (n=8) and endometrioid carcinoma tissue (EC; G1=93; G2=32; G3=14). INH-alpha was significantly higher in normal compared to malignant endometrial tissue, showing a cyclical variation throughout the menstrual cycle. EC G3 did not express this subunit. INH-betaA and -betaB showed specific staining reactions within the tumor cells. The highest intensity of INH-betaA was observed in the normal secretory phase compared to adenocarcinomas (p<0.05). For INH-betaB, the significantly highest expression was noted in EC G3 compared to EC G2 (p<0.05) and atrophic endometrial tissue. In conclusion, INH-alpha, -betaA and -betaB were immunolabeled in normal and malignant endometria. INH-alpha was expressed in a declining relationship in the transition from normal to tumor tissue, suggesting a tumor suppressive function in EC. A high expression of INH-betaB was observed in EC G3 compared to G2, suggesting an important role in the progression of endometrial carcinogenesis. However, the utilization of these subunits as specific tumor markers still remains unclear.

Biomarkers, Tumor↗
PubMed2006

Aesthetic result among breast cancer patients undergoing autologous breast reconstruction versus breast conserving therapy.

PURPOSE: Following breast-conserving surgery or mastectomy followed by autologous breast reconstruction, breast cancer patients were studied to discover their satisfaction with the aesthetic results of the two treatment strategies. PATIENTS AND METHODS: One hundred and thirty-four breast cancer patients were included in this study. Sixty-four underwent breast-conserving surgery followed by radiotherapy. Mastectomy was performed in 70 patients with immediate or late reconstruction. To evaluate the quality of the aesthetic results in both groups we designed a questionnaire assessing different cosmetic categories. RESULTS: Patients in both therapy groups showed a very high satisfaction with their cosmetic results; the patients undergoing breast reconstruction were even more satisfied than the patients who had breast-conserving therapy. CONCLUSION: Our study demonstrated that breast reconstruction with autologous tissue offers an opportunity to support patients with advanced breast cancer who were confronted with mastectomy, showing a high degree of satisfaction with the cosmetic results.

Breast Neoplasms↗
PubMed2006

Obstetrical and gynecological writing and publishing in Europe.

OBJECTIVE: To assess the number and quality of scientific articles published by authors from the European Union (EU) and Germany in the field of obstetrics and gynecology. STUDY DESIGN: Scientific articles published during the years 1980-2003 covered by the Journal Citation Report (JCR) were considered, with a focus on the impact factor (IF), authors' origin, journal country and publishing language. RESULTS: In 2003, there are 53 journals listed by the JCR for the field category 'obstetrics and gynecology', with altogether 3201 publications listed in the Science Citation Index (SCI). From the year 1980, the total number of publications increased persistently. Looking at the top 20 journals in the field of obstetrics and gynecology, there are 12 journals from the US, 8 from Europe. None of these journals has an IF>10 but 30 journals show an IF>1. Over the last 25 years, a growing importance of the English language as scientific language can be observed. CONCLUSION: These data indicate an important role of European research in the field of obstetrics and gynecology comparable to that of US-American research. The English language is gaining importance as scientific language, displacing other languages and contributing to a loss of impact of non-English journals.

Bibliometrics↗
PubMed2006

Placental transfer and pharmacokinetics of lopinavir and other protease inhibitors in combination with nevirapine at delivery.

BACKGROUND: Antiretroviral combination therapies, including nevirapine (NVP) and protease inhibitors (PI), are increasingly used in the treatment and for the prophylaxis of vertical HIV-1 transmission in HIV-1 infected pregnant women. OBJECTIVE: To determine pharmacokinetics and placental transfer of NVP and different PI in pregnancy we measured drug levels in maternal and foetal compartments at the day of delivery. DESIGN AND METHODS: We conducted a prospective study in 40 eligible HIV-1 infected pregnant women who gave birth in our hospital. A pre-dose to 6 h post-dose steady-state pharmacokinetic analysis (n = 35) of the drugs on the day of the scheduled Caesarean section was performed. In addition cord blood and amniotic fluid drug levels were measured (n = 40). RESULTS: In all women NVP plasma concentrations (n = 20) were below the recommended level. PI plasma concentrations (nelfinavir, n = 5; saquinavir, n = 3; lopinavir, n = 10; ritonavir, n = 13) were extremely variable. Cord blood and amniotic fluid drug levels suggested that NVP passes the placenta unrestricted whereas PI were detected in smaller concentrations in the foetal compartment. CONCLUSIONS: Because of the changed pharmacokinetics of antiretroviral drugs in pregnancy therapeutic drug monitoring could be important and dose adjustment should be considered. The minimal placental transfer of PI is desirable from the perspective that the foetus is protected from potentially teratogenic agents. However, it is not known if antiretroviral compounds in the foetal compartment contribute to the risk reduction of vertical HIV-1 transmission, and whether the property of missing placental transfer is in fact beneficial for the newborn.

Amniotic Fluid↗
PubMed2006

Prognostic impact of Thomsen-Friedenreich tumor antigen and disseminated tumor cells in the bone marrow of breast cancer patients.

PURPOSE: The Thomsen-Friedenreich antigen (TF, CD176) is a specific oncofetal carbohydrate epitope (Gal beta1-3GalNAc alpha-O-Ser/Thr) expressed on the surface of various carcinomas. It mediates endothelium adhesion and formation of metastases. As it also causes immune response, its prognostic impact is indeterminate. The presence of disseminated tumor cells in the bone marrow of breast cancer patients (DTC-BM) indicates worse prognosis. We examined the expression of TF in primary breast cancer tissue of 265 patients with known BM status at the time of first diagnosis. METHODS: BM aspiration, cytospin preparation and immunocytochemical staining with the anti-Cytokeratin antibody A45 B/B3 was done following a standardised protocol. TF expression was examined immunohistochemically on Tissue Micro Arrays (TMA) with the anti-TF antibody A78-G/A7. Evaluation was done using the immunoreactive score (IRS). RESULTS: Median IRS for TF expression was 2 (0-12). 68 of 265 patients (25.7%) showed DTC-BM with a median of 2/2 x 10(6) cells (1-1500). There was no correlation between TF expression and DTC-BM. After a median follow up of 60.1 months (7-119), the detection of DTC-BM showed prognostic significance for overall survival (OS, p = 0.034), whereas TF positivity (IRS > 2) indicated prolonged disease-free (p = 0.01), distant disease-free (p = 0.005), and overall survival (p = 0.005). DISCUSSION: Patients with TF-positive tumors had a significantly better prognosis. Dissemination routes, TF-mediated metastasis formation, and the immunogeneity of TF might determine the prognostic impact of TF expression in different tumor entities. Further characterisation of primary tumors and DTC-BM could help to improve the biological understanding of metastases and develop targeted therapies.

Adult↗
PubMed2006

Management of skin-sparing mastectomy: results of a survey of German hospitals.

BACKGROUND: The aim of this study was to evaluate the current management of skin-sparing mastectomy in German hospitals and to determine its oncologic safety. For this purpose, 100 surgeons were surveyed regarding their use of skin-sparing mastectomy. RESULTS: Almost all surveyed hospitals performed skin-sparing mastectomy. Most of them believe that the recurrence rate is equal to that of conventional mastectomy. 95% regard inflammatory cancer as a contraindication to skin-sparing surgery. Most of the hospitals thin out the skin without leaving any macroscopic glandular tissue behind, and 73% leave the nipple-areola complex (NAC) on the basis of frozen sections. Volume replacement is most commonly done with latissimus dorsi muscle flaps and pedicled TRAM flaps. In 76% of the surveyed hospitals, reconstruction after mastectomy is performed by the gynecological department. CONCLUSION: Skin-sparing mastectomy is considered to be the best cosmetic option for breast reconstruction in selected breast cancer patients. At present, statistical proof of its oncologic safety is lacking. The surgical techniques used for skin-sparing mastectomy have not yet been standardized. In order to achieve standardization, careful discussion-making and evaluation remain important.

Breast Neoplasms↗
PubMed2006

Binding of galectin-1 (gal-1) to the Thomsen-Friedenreich (TF) antigen on trophoblast cells and inhibition of proliferation of trophoblast tumor cells in vitro by gal-1 or an anti-TF antibody.

Galectin-1 (gal-1), a member of the mammalian beta-galactoside-binding proteins, recognizes preferentially Galbeta1-4GlcNAc sequences of several cell surface oligosaccharides. We demonstrate histochemically that the lectin recognizes appropriate glycotopes on the syncytiotrophoblast and extravillous trophoblast layer from second trimester human placenta and on BeWo chorion carcinoma cells. Gal-1 binding to BeWo cells was diminished by the Thomsen-Friedreich (TF)-disaccharide (Galbeta1-3GalNAc-) conjugated to polyacrylamide (TF-PAA). Gal-1 also inhibited BeWo cell proliferation in a concentration-dependent manner. Similar antiproliferative effects were also observed with an anti-TF monoclonal antibody (mAb, A78-G/A7). Therefore, we conclude that ligation of Galbeta1-4GlcNAc and Galbeta1-3GalNAc epitopes on BeWo cells may have regulatory effects on cell proliferation.

Antibodies↗
PubMed2006

Plasma- and urine concentrations of nitrite/nitrate and cyclic Guanosinemonophosphate in intrauterine growth restricted and preeclamptic pregnancies.

BACKGROUND: The Nitric Oxide (NO) system plays an important role in the establishment and maintenance of the feto-placental circulation. Research on the pathogenesis of preeclampsia in several studies has established the involvement of the NO-system in preeclampsia and fetal intrauterine growth restriction (IUGR). In the presented study we analyzed the urine and plasma concentrations of nitrite/nitrate, the stable endproducts of NO and its second messenger, cyclic Guanosinemonophosphate (cGMP) in normal, preeclamptic and IUGR pregnancies. PATIENTS AND METHODS: In total 76 patients were investigated in a prospective study for repeated determination of plasma and urinary levels of nitrate/nitrite and cGMP: 49 patients with a normal course of pregnancy, 14 patients with fetal IUGR and 13 patients with preeclampsia were included into the study. Plasma and urine Nitrite/Nitrate-concentrations were determined using a Colorimetric Assay (Cayman Inc., USA), concentrations of the second messenger cGMP in plasma and urinary samples were determined with a J(125)-Radio-Immuno-Assay (ibl Inc., Germany). The Stat View Program (Abacus Concepts, Inc., Berkeley, CA, 1992-1998) was used for statistical analysis, a P value <0.05 was considered significant. RESULTS: Analyzing the data with the Kruskall-Wallis test a significance was reached for Plasma Nitrite/Nitrate (P=0.0236), plasma cGMP (P=0.004) and urinary nitrite/nitrate (P=0.032). No significance was seen for urinary cGMP (P=0.656). Comparing normal and preeclamptic and normal and IUGR pregnancies the following significant differences were seen (Mann-Whitney U test): In preeclamptic pregnancies urine nitrite/nitrate concentration was significantly lower compared to normal pregnancies (P=0.009) No significant difference between normal and preeclamptic pregnancies for plasma nitrite/nitrate (P=0.819) and plasma-cGMP (P=0.072) could be observed. In IUGR pregnancies plasma nitrite/nitrate and the plasma-cGMP concentrations were both significantly lower compared to normal pregnancies (P=0.0077 and 0.0066) in IUGR-pregnancies. No significance was reached when analyzing urine-Nitrite/Nitrate (P=0.7). CONCLUSION: Whereas in preeclampsia a reduced urinary nitrite/nitrate was analyzed, IUGR pregnancies showed reduced plasma nitrite/nitrate and cGMP. A reduced release of NO into the maternal circulation might lead to the presented findings and be involved in the pathogenesis of preeclampsia and fetal IUGR.

Birth Weight↗
PubMed2006

Pregnancy-associated breast cancer -- special features in diagnosis and treatment.

For obvious psychological reasons it is difficult to associate pregnancy -- a life-giving period of our existence -- with life-threatening malignancies. Symptoms pointing to malignancy are often ignored by both patients and physicians, and this, together with the greater difficulty of diagnostic imaging, probably results in the proven delay in the detection of breast cancers during pregnancy. The diagnosis and treatment of breast cancer are becoming more and more important, as the fulfillment of the desire to have children is increasingly postponed until a later age associated with a higher risk of carcinoma, and improved cure rates of solid tumors no longer exclude subsequent pregnancies. The following article summarizes the special features of the diagnosis and primary therapy of pregnancy-associated breast cancer with particular consideration of cytostatic therapy.

Abnormalities, Drug-Induced↗
PubMed2006

Inhibin/activin subunits beta-A (-betaA) and beta-B (-betaB) are differentially localised in normal, hyperplastic and malignant human endometrial tissue.

Inhibins (INHs) are dimeric glycoproteins composed of an alpha (-alpha) subunit and one of two possible beta (beta-) subunits (betaA or betaB). The aims of this study were to determine the frequency and distribution of INH beta (betaA and betaB) subunits in normal, hyperplastic and malignant human endometrium. Endometrial tissue was obtained from normal, hyperplastic (simple, complex and atypical) and endometrioid adenocarcinoma (EC) and INH-alpha, -betaA and -betaB were labelled using immunohistochemistry and immunofluorescence. INH-betaA and -betaB labelling was increased significantly between the proliferative and secretory phase (p<0.05). The lowest labelling was demonstrated in EC, being significantly lower than in secretory phase (p<0.01) and in simple, complex and atypical hyperplastic tissue (p<0.05). For inhibin-betaB, the most intense labelling was noted in atypical hyperplasia compared to EC (p<0.05). A strong colocalisation of inhibin-alpha and -betaA could be demonstrated in malignant endometrial tissue, suggesting the production of inhibin A within the tumour. Additionally, only limited colocalisation of inhibin-betaB with -alpha subunit could be observed, suggesting the synthesis of activin B rather than inhibin B in malignant endometrium. In conclusion, INH-betaA and -betaB were labelled in normal, hyperplastic and malignant endometrium. Hyperplastic tissue labelled more intensely than EC for the presence of INH-betaA and -betaB, suggesting a substantial function in endometrial pathogenesis and an important role in endometrial carcinogenesis.

Endometrial Neoplasms↗
PubMed2006

Expression of estrogen receptor-alpha, estrogen receptor-beta and placental endothelial and inducible NO synthase in intrauterine growth-restricted and normal placentals.

BACKGROUND: Nitric oxide seems to play important roles in the physiology of placental blood circulation, although their expression in pathological placentas and their role is still unclear. Therefore, the aim of this study was to investigate the expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta) and the endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) in intrauterine growth-restricted (IUGR) placentas, hemolysis, elevated liver enzymes, low platelets (HELLP) placentas and in normal healthy control placentas. METHODS: Slides of paraffin-embedded placental tissue were obtained after delivery from patients diagnosed with IUGR, HELLP and normal term placentas and analyzed for eNOS and iNOS, as well as ERalpha/beta expression. Intensity of immunohistochemical reaction was analyzed using a semi-quantitative score, and statistical analysis was performed. In addition, Western blot experiments were performed for comparison of staining intensities obtained by immunohistochemistry and Western blot. RESULTS: Expression of eNOS and iNOS is significantly reduced in trophoblast cells of placentas with HELLP. However, ERbeta expression in HELLP placentas demonstrated a significantly elevated expression intensity compared to normal controls. ERalpha expression was not significantly different in all three pathologies investigated. CONCLUSIONS: We speculate that the increased ERbeta expression in both syncytiotrophoblast and extravillous trophoblast cells represents accelerated proliferation of placental tissue or can be seen as a compensatory effect in HELLP placentas.

Estrogen Receptor alpha↗
PubMed2006

Glycodelin A is expressed differentially in normal human endometrial tissue throughout the menstrual cycle as assessed by immunohistochemistry and in situ hybridization.

OBJECTIVE: To [1] evaluate glycodelin A immunolabeling in normal endometrium with specific monoclonal (mAb) and polyclonal peptide (pAb) antibodies, [2] to assess glycodelin messenger RNA (mRNA) by in situ hybridization, and [3] to conduct deglycosylation experiments to evaluate the recognized epitope of the mAb vs. pAb. DESIGN: Retrospective immunohistochemical analysis. SETTING: University institute and hospital in Germany. PATIENT(S): Normal human endometrial tissue from the proliferative (PP), early secretory, and late secretory phases were obtained from patients undergoing surgery for benign diseases. INTERVENTION(S): Generation of a pAb in rabbit, immunohistochemistry, and in situ hybridization. MAIN OUTCOME MEASURE(S): Semiquantitative and computerized analysis. RESULT(S): A statistically significant increase of the glycodelin A immunolabeling in the late secretory phase compared with PP was demonstrated by using the mAb. Polyclonal-peptide antibody immunolabeling also showed a rise between the PP and late secretory phases, but without statistical significance. In situ hybridization demonstrated a statistically significantly higher mRNA content during the early secretory phase compared with during PP. CONCLUSION(S): Glycodelin was demonstrated in normal endometrium at the protein and mRNA levels. The mAb may be more useful in assessing glycodelin expression in endometrium, because it probably can bind to glycodelin A-unique glycan structures, in contrast to the peptide pAb. This is of major interest because it may reveal possible structural and functional relationships in different parts of this molecule and elucidate possible functions of this glycoprotein in human endometrial tissue.

Adult↗
PubMed2006

Expression of the proliferation marker Ki-67 and of p53 tumor protein in trophoblastic tissue of preeclamptic, HELLP, and intrauterine growth-restricted pregnancies.

The human placenta owns the biochemical machinery to proliferate throughout gestation. The aim of this study was to investigate the expression of the proliferation marker Ki-67 in trophoblastic tissue of intrauterine growth retarded (IUGR) placentas, preeclamptic, HELLP, and in normal trophoblastic tissue. Slides of paraffin-embedded trophoblastic tissue of patients with IUGR, preeclamptic patients, HELLP patients, and normal term placentas were incubated with monoclonal antibodies against Ki-67 and p53. Staining reaction was performed with the ABC reagent. Intensity of immunohistochemical reaction on the slides was analyzed using a semiquantitative score. Identification of Ki-67-expressing cells was done by immunofluorescence double staining with Ki-67 and cytokeratin antibodies. Expression of Ki-67 and p53 are significantly elevated in cytotrophoblastic cells of placentas with HELLP as investigated by immunohistochemistry and double immunofluorescence. However, preeclamptic cytotrophoblastic tissue on the other hand showed no significantly different expression intensity of Ki-67 compared with normal placental tissue controls and no changes in p53 expression compared with controls. In IUGR cytotrophoblastic cells, we found no statistically significant change in Ki-67 expression but a statistically significant down-regulation of p53. An elevated proliferation of cytotrophoblastic cells seems to be related to HELLP, and this enhanced proliferation seems to be controlled by p53.

Antibodies, Monoclonal↗
PubMed2006

Doppler sonography of the uterine and the cubital arteries in normal pregnancies, preeclampsia and intrauterine growth restriction: evidence for a systemic vessel involvement.

AIMS: The decrease in uterine resistance during normal pregnancy is known to be related to invading trophoblast cells which derive from placental tissue. Uterine and peripheral resistance is elevated in preeclampsia. The aim of the present study was to prospectively examine uterine and peripheral resistance in pregnancies complicated by preeclampsia (PE), fetal intrauterine growth restriction (IUGR) and pregnancy induced hypertension (PIH). METHODS: Sixty-seven women with normal pregnancies, 17 with PE, 12 with IUGR underwent Doppler sonographic investigation of the uterine and the cubital arteries. The Pulsatility Index (PI) was calculated for each vessel. Statistical analysis was performed and a P-value <0.05 was considered significant. RESULTS: Patients with preeclampsia and IUGR showed a significant higher resistance at the placental (mean PI 1.267 and 1.063), nonplacental (mean PI 1.631 and 1.124) and cubital artery (mean PI 3,777 and 3.995) compared to the normal pregnancy group (mean PI 0.678; 0.859 and 2.95 respectively). Mean birth weight in the PE group was 1409 g, in the IUGR group 1649 g and 3419 g in the normal pregnancy group. CONCLUSIONS: Pregnancies with IUGR are associated with elevated peripheral resistance in the maternal arterial system as seen in pregnancies with preeclampsia. Our findings encourage to further investigate the maternal vascular system in high risk pregnancies.

Arteries↗
PubMed2005

Prognostic relevance of disseminated tumor cells in the bone marrow and biological factors of 265 primary breast carcinomas.

INTRODUCTION: The prognostic significance of disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients has been demonstrated in many studies. Yet, it is not clear which of the primary tumors' biological factors predict hematogenous dissemination. We therefore examined 'tissue micro arrays' (TMAs) of 265 primary breast carcinomas from patients with known bone marrow (BM) status for HER2, Topoisomerase IIalpha (Top IIa), Ki 67, and p53. METHODS: BM analysis was performed by cytospin preparation and immunocytochemical staining for cytokeratin (CK). TMAs were examined by immunohistochemistry (IHC) for HER2, Top IIa, Ki 67 and p53, and fluorescence in situ hybridization (FISH) for HER2. RESULTS: HER2 (2+/3+) was positive in 35/167 (21%) cases (FISH 24.3%), Top IIa (>10%) in 87/187 (46%), Ki 67 in 52/184 (28%) and p53 (>5%) in 61/174 cases (34%). Of 265 patients, 68 (25.7%) showed DTC-BM with a median of 2/2 x 106 cells (1 to 1,500). None of the examined factors significantly predicted BM positivity. Significant correlation was seen between HER2 IHC and Top IIa (p = 0.06), Ki 67 (p = 0.031), and p53 (p < .001). Top IIa correlated with Ki 67 and p53, and Ki 67 also with p53 (p = 0.004). After a median follow-up of 60.5 months (7 to 255), the presence of DTC-BM showed prognostic relevance for overall survival (p = 0.03), whereas HER2 (IHC, p = 0.04; FISH, p = 0.03) and Ki 67 (p = 0.04) correlated with disease free survival, and HER2 with distant disease free survival (IHC, p = 0.06; FISH, p = 0.05). DISCUSSION: The congruence of the examined factors' expression rates indicates a causal line of suppressor, proliferation, and mitosis markers, and growth factor receptors. Hematogenous tumor cell spread seems to be an independent process. The examination of these factors on DTC-BM is the aim of ongoing research.

Adult↗
PubMed2005

Failure of Implanon contraception in a patient taking carbamazepin for epilepsia.

Until now, no pregnancies have been reported in association with the implantable hormonal contraceptive Implanon (Organon, Roseland, NJ, USA), resulting in a pearl index of 0. We present a 24-year-old patient who conceived despite the correct application of Implanon for one and a half year. The patient was concurrently taking carbamazepin for epilepsia. Special care should be taken to patients demanding hormonal contraceptives while taking carbamezepin. Even Implanon seems to possibly fail in this combination.

Adult↗