Biomedical subjects

M Friedrich

Publications and source records attributed to M Friedrich.

At least 19 recordsLinked to original sources

PubMed2007

Prognostic significance of clusterin immunoreactivity in breast cancer.

Clusterin (CLU) is involved in a variety of biological processes and has been found to be expressed even in many human malignancies, including breast cancer. Currently, there are only few data on the prognostic value of CLU in breast cancer. We therefore evaluated the relationship between CLU expression and clinicopathological parameters as well as relapse-free survival (RFS) and metastasis-free survival (MFS) of 141 breast cancer patients using the monoclonal antibody 7D1. CLU expression was found in 26% of cases and correlated significantly with high histological tumor grade and high Ki-67 labeling index (p=0.026 and p=0.010, respectively). Univariate Cox regression analysis revealed that CLU expression was tendentiously associated with RFS (p=0.068; relative risk [RR]: 1.77) and MFS (p=0.122; RR: 1.57). In a multivariate analysis, tumor grade, stage, estrogen receptor status and patients age (concerning RFS) as well as grade and lymph node status (concerning MFS) were identified as significant independent prognosticators. CLU expression showed an independent prognostic relevance concerning prediction of RFS by trend (p=0.110; RR: 1.81). We conclude from our data that estimation of CLU immunoreactivity may be helpful as a supplementary criterion to better assess the tumors propensity to relapse in selected cases of breast carcinoma.

Adult↗

PubMed2006

[Fluorescence diagnosis and photodynamic therapy with 5-aminolevulinic acid induced protoporphyrin IX in gynecology: an overview].

Fluorescence diagnosis and photodynamic therapy with 5-aminolevulinic acid induced protoporphyrin IX are promising new options in the diagnosis and therapy of diseases in a wide spectrum of medical disciplines such as urology, dermatology, gastroenterology, surgery, neurosurgery and gynecology. The techniques are based on the application of the heme biomolecule precursor 5-aminolevulinic acid which induces the endogenous accumulation of the photosensitizer protoporphyrin IX in designated tissues. After external excitation with blue light a strong red fluorescence can be initiated particularly in tumorous tissues. In gynecology many studies have been performed evaluating the usefulness of fluorescence based detection of cervical dysplasias, breast cancer, endometrial diseases, ovarian cancer and endometriosis. This work aims on the principles of fluorescence detection as an important tool in biomedical optical imaging and its current status in gynecology.

Aminolevulinic Acid↗

PubMed2006

The glycosylation of pregnancy-associated glycoproteins and prolactin-related protein-I in bovine binucleate trophoblast giant cells changes before parturition.

Binucleate trophoblast giant cells (BNC) in the bovine placenta produce glycoproteins, which are delivered into the mother after fusion of BNC with uterine epithelial cells. During most time of pregnancy, BNC produce pregnancy-associated glycoproteins (PAGs) and prolactin-related protein-I (PRP-I) with asparagine-linked lactosamine-type glycans terminating with N-acetyl-galactosamine. We show by lectin histochemistry that terminal N-acetyl-galactosamine (detected by Dolichos biflorus agglutinin, DBA) in placentomal BNC is greatly reduced prior to parturition, while lactosamine-type N-glycans (detected by Phaseolus vulgaris leucoagglutinin, PHA-L) remain unaltered. The change in DBA-staining showed no statistically significant differences between placentomes of cows with and without retention of fetal membranes. Western blots revealed that, at parturition the apparent molecular mass of PAGs and PRP-I is 1-2 kDa lower than in late pregnancy. These changes are due to alterations of asparagine-linked glycans, since the molecular weight of the peptide backbones after enzymatical release of asparagine-linked glycans is identical at late pregnancy and parturition. Lectin western blots showed a reduction of terminal N-acetyl-galactosamine on PAGs at parturition. A lectin sandwich-ELISAwas used to differentiate DBA- and PHA-L-binding PAGs in sera of pregnant and non-pregnant cows. The values for DBA-binding PAGs at parturition were not significantly different from non-pregnancy, while the values for PHA-L-binding PAGs were significantly higher at parturition. The peripartal changes of PAG- and PRP-I-glycosylation could alter functional properties of these proteins and might therefore be considered for functional studies. The differentiation of PAG glycoforms in maternal serum could be valuable for a further optimization of PAG-based pregnancy diagnosis in cattle.

Animals↗

PubMed2005

Is there an interaction between interleukin-10 and interleukin-22?

Interleukin(IL)-10 and IL-22 are structurally related cytokines. Their heterodimeric receptors consist of the cytokine-specific chains IL-10R1 and IL-22R1, respectively, and the common chain IL-10R2. This study focused on the question of whether IL-10 modulates IL-22 effects and vice versa. This question is important because IL-10 and IL-22 exert anti- and proinflammatory effects, respectively, and, as we show here, are simultaneously present in both systemic and local inflammation. The revealed lacking concomitance of IL-10R1 and IL-22R1 on identical cells excluded any possible interaction between IL-10 and IL-22 apart from the competition for IL-10R2. To study this competition, monocytes and hepatocytes were chosen. The dependence of the cytokine action on IL-10R2 was verified. Interestingly, no influence of IL-22 on IL-10 effects was observed. The same was true when IL-22 was used in complex with IL-22-binding protein. Similarly, no influence of IL-10 was found on IL-22 action. This missing competition seemed to be due to a lack of binding between IL-10R2 and the native cytokines in the absence of their corresponding R1 chain. However, IL-10R2 interacted with defined IL-10- and IL-22-derived peptides supporting the hypothesis that cytokine binding to its corresponding R1 chain creates a binding site on this cytokine for IL-10R2.

Animals↗

PubMed2005

[Treatment of breast cancer patients with brain metastases].

Treatment of patients with brain metastases is based on an interdisciplinary approach. It is essential to perform a differenciated indication for procedures with consideration of all therapeutical options like modalities of radiotherapy, surgery and oncology. In the case of multiple brain metastases the whole brain radiotherapy is the standard of treatment, while in case of a single or solitary brain metastasis surgical procedures followed by radiotherapy should be preferred.

Brain Neoplasms↗

PubMed2005

[Metastatic breast cancer: options for metastasectomy].

Usually, the therapy of metastatic breast cancer consists of chemotherapy or endocrine therapy, because even in the case of isolated metastases in one organ, diffuse tumor cell dissemination exists, so that local surgical treatment does not seem sensible. Particurlarly in patients with hepatic or pulmonary metastases the indication for hepatic or pulmonary metastasectomy should be individualized, as hepatic or pulmonary metastases usually develop during a phase of disease, when extrahepatic or -pulmonary metastases also can be detected. Only in patients with long disease-free interval, with isolated hepatic or pulmonary metastases, and the possibility of R0-resection is hepatic or pulmonary metastasectomy a therapeutic option in selected cases.

Breast Neoplasms↗

PubMed2005

Relationship between chemotherapy with paclitaxel, cisplatin, vinorelbine and titanocene dichloride and expression of proliferation markers and tumour suppressor gene p53 in human ovarian cancer xenografts in nude mice.

PURPOSE: In this study the relationship between therapy with paclitaxel, cisplatin, vinorelbine and titanocene dichloride and of the expression of proliferation markers (ki67 and S-phase fraction) and tumour suppressor gene p53 was analyzed using a human ovarian cancer xenograft model. METHODS: Biopsy material from one human ovarian cancer was expanded and transplanted into 102 nude mice. The mice were divided into six groups with different intraperitoneal treatments with paclitaxel, cisplatin, vinorelbine, titanocene dichloride and a control group treated with 0.9% saline solution. After the observation period the tumours were extracted and immunohistochemically stained with monoclonal antibodies against ki67 and p53. The S-phase-fraction was identified by flow cytometry. RESULTS: There where no statistically significant differences. Regarding the treatment groups, the vinorelbine-group showed the highest percentage (53.3%) and the titanocene dichloride-3x40 mg/kg-group the lowest percentage (7.1%) of ki67-positive specimens, whereas in the control group 35.7% of the specimens were positively stained for ki67. The results for the expression of p53 were similar. The vinorelbine-group had the highest percentage of p53-positive specimens (60%), in both titanocene-groups no specimen showed a positive staining for p53 and in the control group 7.1% of the specimens were positively stained for p53. The mean S-phase-fraction was 14.48% (SD +/- 3.98), no statistically significant relation between S-phase-fraction and expression of p53 (p = 0.883) or of ki67 (p = 0.351) could be shown. The change of tumour volume was independent of the results for ki67, p53 and the S-phase-fraction. CONCLUSION: Although, as previously published, a significant difference of tumour volume change occurred between the treatment groups, in this study we could not find a relation between this change of tumour volume and the expression of p53 or ki67. The absolute number of p53- and ki67-positive staining specimens was too small for statistical analysis, therefore the relevance of the differences between the different treatment groups and the control remains unclear. The results for the S-phase-fraction showed no correlation between the change of tumour volume, different treatment protocols or the expression of p53- and ki67. Our findings contribute to the controversy of the influence of chemotherapy on the expression of proliferation markers and p53.

Animals↗

PubMed2004

Doppler ultrasound of the uterine artery in the prediction of severe complications during low-risk pregnancies.

AIM: The aim of this prospective study was to assess the role of uterine artery colour Doppler waveform analysis in the prediction of adverse pregnancy outcome such as preeclampsia, intrauterine growth retardation, placental abruption or a combination of outcome parameters. METHODS: Various uterine artery Doppler ultrasound parameters (RI>0.58, RI>0.7 and unilateral or bilateral notching) were tested. A second objective was to compare the predictive power of uterine artery Doppler ultrasound at 19-22 gestational weeks and 23-26 weeks' gestation for an adverse pregnancy outcome. RESULTS: The mean time of delivery was 39+0 weeks of gestation. Eight newborns (2%) were delivered before 34 weeks of gestation. The mean birth weight was 3,240 g. Dystrophic fetuses (<10% percentile) were registered in 35 cases (10%). In 31 of the 346 women (9%) a cesarean section was performed because of abnormal fetal heart recording. Preeclampsia was diagnosed in 17 cases (5%). In 5 cases (1.4%) a placental abruption and 2 (0.6%) intrauterine fetal deaths were diagnosed. The sensitivity of notching for the prediction of preeclampsia was 88% and for the prediction of a severe pregnancy complication (preeclampsia and/or intrauterine growth retardation and/or intrauterine fetal death and/or placental abruption) at any gestational age was 62% with relative risks of 9.7 and 2.2, respectively. The sensitivity of notching for severe pregnancy complications requiring delivery before 34 weeks was 64% with a relative risk of 2.4. The sensitivity of notching in the uterine arteries for developing an IUGR was 56% with a relative risk of 1.7. CONCLUSION: The predictive value of uterine artery Doppler for adverse pregnancy outcome in a low-risk population is of limited diagnostic value. Performing uterine artery Doppler studies at 23-26 weeks' gestation instead of 19-22 weeks' gestation increases the predictive value for adverse pregnancy outcomes.

Abruptio Placentae↗

PubMed2004

The value of uterine artery Doppler ultrasound in the prediction of severe complications in a risk population.

AIM: The aim of this prospective study was to assess the role of uterine artery color Doppler waveform analysis in the prediction of adverse pregnancy outcome such as preeclampsia, intrauterine growth retardation, placental abruption or a combination of outcome parameters in risk pregnancies (n=52). METHODS: Various uterine artery Doppler ultrasound parameters (resistance index (RI)>0.58, RI>0.7 and uni/bilateral or bilateral notching) were tested. The mean time of delivery was 37+1 weeks' gestation. Six newborns (12%) were delivered before 34 weeks of gestation. The mean birth weight was 2,910 g. Dystrophic fetuses (<10% percentile) were registered in 7 cases (13%). In 11 of the 52 women (21%) a cesarean section was performed because of abnormal fetal heart recording. RESULTS: Preeclampsia was diagnosed in 4 cases (8%). In 4 cases (8%) an intrauterine fetal death was diagnosed. Placental abruption did not occur. The sensitivity of notching for the prediction of preeclampsia and for the prediction of a severe pregnancy complication was 75 and 69% with relative risks of 2.7 and 2.0. The sensitivity of notching in the uterine arteries for developing an intrauterine growth retardation (IUGR) was 71% with a relative risk of 2.2. The sensitivity of RI>0.58 in the uterine arteries for developing an IUGR was 67% with a relative risk of 5.4. The sensitivity of RI>0.58 for the prediction of preeclampsia, of intrauterine death and for the prediction of a severe pregnancy complication was 50, 75 and 80% with relative risks of 2.7, 8.1 and 10.9 respectively. CONCLUSION: The results of this study suggest that Doppler ultrasound of the uterine artery in the second trimester of gestation is a useful method to predict abnormal outcomes in risk pregnancies, with high negative predictive values.

Adult↗

PubMed2004

Reference values of fetal ductus venosus, inferior vena cava and hepatic vein blood flow velocities and waveform indices during the second and third trimester of pregnancy.

OBJECTIVE: Our objective was to establish reference values for ductus venosus, inferior vena cava and hepatic vein flow velocities during ventricular systole (S-wave) and diastole (D-wave), the lowest forward velocity during atrial contraction (a-wave), the intensity-weighted mean flow velocity (Vmean) and different calculated indices. METHODS: Venous flow velocity waveforms were obtained from 329 singleton pregnancies at 20-42 weeks of gestation by pulsed-wave color Doppler. Reference values were constructed by means of a quadratic regression model after logarithmic transformation of original data. RESULTS: With advancing gestational age the peak velocity index for the vein (PVIV) and pulsatility index for the vein (PIV) decreased whereas blood flow velocities increased. Blood flow velocities were highest in the ductus venosus and lowest in the right hepatic vein. Values for PVIV and PIV were highest in the hepatic vein and lowest in the ductus venosus. During atrial contraction there was a blood flow towards the fetal heart in the ductus venosus, whereas in the inferior vena cava and in the hepatic vein blood flow was either in the opposite from the fetal heart (reverse flow), or there was absent flow (zero flow) or flow was towards the fetal heart (positive flow). CONCLUSIONS: The reference ranges and calculated velocities established in this study may be utilized in studies dealing with the role of ductus venosus and inferior vena cava blood flow in fetuses with chromosomal abnormalities or congenital heart disease as well as hypoxic conditions. We speculate, that the reduction in PVIV and PIV with advancing gestational age may reflect a decrease in cardiac afterload as a result of maturation of diastolic ventricular function.

Blood Flow Velocity↗

PubMed2004

Intratumoral methotrexate kinetics in a patient with intracranial anaplastic ependymoma.

Little is known about intratumoral anticancer drug concentration in childhood brain tumors. We were able to measure methotrexate (MTX) tumor concentrations directly in a cystic anaplastic ependymoma. Cyst fluid was obtained by puncture of a subgaleal Rickham reservoir connected to a catheter in the tumor cyst. MTX concentrations were determined by fluorescence polarization immunoassay and compared to serum concentrations. Maximum MTX concentrations in tumor and CSF were found at the end of MTX infusion. Twenty-four hour after MTX infusion the mean tumor concentration was significantly higher than in the serum indicating MTX retention and accumulation in the tumor cyst. An AUC(tumor)/AUC(serum) ratio of 1.95 was obtained. In response to the applied multiagent chemotherapy the clinical condition of our patient improved and the tumor showed partial response on MRI. Cystic ependymomas might benefit from high dose MTX especially because of drug retention in the tumor cyst.

Antimetabolites, Antineoplastic↗

PubMed2004

Detection of coronary artery disease by magnetic resonance myocardial perfusion imaging with various contrast medium doses: first European multi-centre experience.

AIMS: Magnetic resonance (MR) first-pass myocardial perfusion imaging during hyperaemia detects coronary artery stenoses in humans with test sensitivity depending on contrast medium (CM)-induced signal change in myocardium. In this prospective multi-centre study, the effect of CM dose on myocardial signal change and on diagnostic performance was evaluated using a stress-only approach. METHODS AND RESULTS: Ninety-four patients with known or suspected coronary artery disease (CAD) were randomised to 0.05,0.10, or 0.15 mmol/kg body weight of an extravascular CM (Gd-DTPA) and X-ray coronary angiography was performed within 30 days prior/after the MR examination. A multi-slice MR technique with identical hardware and software in all centres was used during hyperaemia (adenosine 0.14 mg/kg/min) to monitor myocardial CM wash-in kinetics and data were analysed semi-automatically in a core laboratory. Protocol violations resulted in 80 complete studies with CAD (defined as > or =1 vessel with diameter stenosis > or =50% on quantitative coronary angiography) present in 19/29, 13/24, and 20/27 patients for doses 1, 2, and 3, respectively. In normal myocardium, the upslope increased with CM dose (overall-p<0.0001, ANOVA). For CAD detection the area under the receiver operator characteristics curve for subendocardial data (3 slices with quality score<4 representing 86% of cases) was 0.91+/-0.07 and 0.86+/-0.08 for doses 2 and 3, respectively, and was lower for dose 1 (0.53+/-0.13, p<0.01 and p<0.02 vs. doses 2 and 3, respectively). Corresponding sensitivities/specificities (95% confidence intervals) for pooled doses 2/3 were 93% (77-99%; ns vs. dose 1) and 75% (48-92%;p<0.05 vs. dose 1), respectively. CONCLUSIONS: With increasing doses of CM, a higher signal response in the myocardium was achieved and consequently this stress-only protocol, with CM doses of 0.10-0.15 mmol/kg combined with a semi-automatic analysis, yielded a high diagnostic performance for the detection of CAD.

Analysis of Variance↗

PubMed2004

Changes of jugular venous blood temperature associated with measurements of cerebral blood flow using the transcerebral double-indicator dilution technique.

BACKGROUND AND OBJECTIVE: The transcerebral double-indicator dilution technique is a recently developed method to measure global cerebral blood flow at bedside. It is based on bolus injection of ice-cold indocyanine green dye and simultaneous recording of resulting thermo- and dye-dilution curves in the aorta and the jugular bulb. However, with this method 40 mL of ice-cold solution is administered as a bolus. Therefore, this prospective clinical study was performed to elucidate the effects of repeated administration of indicator on absolute blood temperature and on cerebral blood flow and metabolism. METHODS: The investigation was performed in nine male patients scheduled for elective coronary artery bypass grafting. Absolute blood temperature was measured in the jugular bulb and in the aorta before and after repeated measurements using the transcerebral double-indicator dilution technique. RESULTS: During the investigated time course, the blood temperature in the jugular bulb, compared to the aorta, was significantly higher with a mean difference of 0.21 degrees C. The administration of an ice-cold bolus reduced the mean blood temperature by 0.06 degrees C in the jugular bulb as well as in the aorta. After the transcerebral double-indicator dilution measurements a temperature recovery to baseline conditions was not observed during the investigated time period. Cerebral blood flow and cerebral metabolism did not change during the investigated time period. CONCLUSIONS: Repeated measurements with the transcerebral double-indicator dilution technique do not affect absolute jugular bulb blood temperatures negatively. Global cerebral blood flow and metabolism measurements remain unaltered. However, accuracy and resolution of this technique is not high enough to detect the effect of minor changes of physiological variables.

Aged↗

PubMed2004

Electrophysiological evidence for delayed mismatch response in infants at-risk for specific language impairment.

The present study investigated whether delayed auditory processing typically found in children with specific language impairment (SLI) can already be observed in the event-related potentials of 2-month-old infants. Infants with and without a family history of SLI were tested in a passive auditory oddball paradigm with CV-syllables differing in vowel duration. For the long syllable, a positive mismatch response occurred in the difference wave between deviant and standard. Its amplitude was higher in infants during quiet sleep than in awake infants, although its peak latency remained unaffected by alertness. Awake infants showed an adultlike mismatch negativity preceding the positivity. Risk for SLI was reflected in the latency of the positive mismatch response, which was delayed in infants with risk compared to infants without risk. This latency difference suggests that 2-month-old infants at risk for SLI are already affected in processing an auditory stimulus change of duration.

Acoustic Stimulation↗

PubMed2004

Changes in vascular endothelial growth factor (VEGF) after chemoendocrine therapy in breast cancer.

PURPOSE: Angiogenesis has been proposed as a possible target for anticancer treatment, either by inhibition of the production of angiogenic factors or by inhibition of endothelial cell proliferation. The impact of preoperative chemoendocrine therapy is unknown in the regulation of angiogenic factors, but recent reports suggest that anticancer drugs have antiangiogenic activity. METHODS: The expression of two angiogenic factors VEGF and Angiopoetin-1 were quantified at different concentrations of doxorubicin, docetaxel, tamoxifen, exemestane and letrozol on MCF-7 and T47D cells. RESULTS: Low-drug concentrations led to increased VEGF-A gene transcription whereas high (10-fold increased) drug concentrations suppressed gene expression. A similar cell reaction was observed for VEGF protein with a smaller variety in the extent of modulation. Incubation of MCF-7 cells to different drugs showed a similar dose-dependent modulation of Angiopoietin-1 gene expression with enhancement at low-drug concentrations. CONCLUSION: Treatment of breast cancer cells following a preoperative protocol showed a dose-dependent expression of VEGF and Angiopoetin-1. Only high-drug concentrations were followed by a decreased secretion of both factors whereas low concentrations induced up-regulation of VEGF and Angiopoietin 1.

Androstadienes↗

PubMed2004

Taxanes in the first-line chemotherapy of metastatic breast cancer: review.

Taxanes belong to the most effective agents in the treatment of advanced and non-hormone responsive breast cancer. Several recently published phase III studies have examined the role of taxane-anthracycline combinations in the first line treatment of metastatic breast cancer. Especially, patients with symptomatic visceral spread seem to benefit from taxanes containing polychemotherapy that is adequately dosed. Polychemotherapy with taxanes appears to be more effective than monotherapy. But at present, there are no adequate data concerning the comparison of taxane-monotherapy and anthracycline-containing polychemotherapy. New hopeful results with respect to efficacy and toxicity are reported from the docetaxel-capecitabine polychemotherapy. Thus, the combination of anthracyclines (adriamycin, doxorubicin) and taxanes (docetaxel, paclitaxel) is a promising tool in the treatment of metastatic breast cancer. New interesting combinations are under investigation.

Anthracyclines↗

PubMed2004

Sentinel node identification and intraoperative lymphatic mapping. First results of a pilot study in patients with endometrial cancer.

INTRODUCTION: To minimize the surgical morbidity after lymphadenectomy, sentinel node biopsy (SLNB) has become fundamental in the management of different malignancies. We decided to evaluate sentinel lymph node (SNL) biopsies also in patients with endometrial cancer undergoing hysterectomy with lymphadenectomy. METHODS: In the setting of a prospective study we developed a technique for sentinel node biopsy of ten patients with histologically confirmed endometrial cancer. Prior to surgery 99m Tc Nanocol was injected in the peritumoral region by hysteroscopy. Six hours later lymphoscintigraphy was performed to identify the draining lymph nodes. During surgery we first detected the sentinel lymph node by a hand-held gamma tracer and then removed it. Surgery was completed by the standard therapy of total hysterectomy, bilateral salpingo-oophorectomy and pelvic and/or para-aortic lymphadenectomy. RESULTS: Scintigraphic identification was possible in eight out of ten patients. Intraoperative identification of sentinel lymph nodes was possible in seven out of eight patients. In five patients we found the sentinel lymph nodes in the pelvic region while the other two patients had bilateral sentinel nodes in the pelvic and para-aortic region. Histologically confirmed microscopic tumor metastases of the SLNs and para-aortic lymph nodes were only found in one case. The sentinel lymph nodes from the other six patients were free of tumor and accurately reflected the pathological status. CONCLUSION: The identification of sentinel lymph nodes in endometrial cancer is a practical and safe method. In order to improve this technique as a standard procedure for staging of endometrial cancer further studies with a larger number of patients have to be done.

Adenocarcinoma, Clear Cell↗

PubMed2004

Hepatic metastasectomy as a cytoreductive strategy for the treatment of liver metastases in breast cancer: review of literature.

The resection of liver metastases in breast cancer patients is a controversial therapeutical approach. No data of prospective randomized trials are available, thus evidence for the potential role of hepatic metastasectomy rests on retrospective studies with a small number of patients. Techniqual advances however have rendered hepatic metastasectomy safe and the long-term results of some studies possibly support the role of a surgical approach in selected patients.

Breast Neoplasms↗