Biomedical subjects

A Ahr

Publications and source records attributed to A Ahr.

At least 19 recordsLinked to original sources

PubMed2006

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.

Adult↗

PubMed2006

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.

Adult↗

PubMed2006

[Integrin expression in eutopic and ectopic endometrium].

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.

Biopsy↗

PubMed2006

[Identification of preeclampsia by cDNA-gene expression profiling in human placentas and serum -- a pilot study].

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.

Adult↗

PubMed2006

[Management of abnormal uterine bleeding].

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.

Algorithms↗

PubMed2006

[Cervical cancer screening of HIV-positive women: is a prolongation of the screening interval meaningful?].

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.

Adolescent↗

PubMed2006

[Risk factors for recurrence of vulvar intraepithelial neoplasia 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.

Adult↗

PubMed2005

[Management of HIV-positive pregnancies -- results from a retrospective study].

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.

Female↗

PubMed2004

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.

Fallopian Tube Patency Tests↗

PubMed2003

[Anesthetic regimen for HIV positive parturients undergoing elective cesarean section].

OBJECTIVE: Worldwide, 50 million people are infected with the human immunodeficiency virus (HIV), and 43% are women. Perinatal vertical transmission of HIV accounts for most new pediatric cases. Elective Cesarean delivery, combined antiretroviral therapy perioperatively and abandonment of breast-feeding postoperatively reduces vertical HIV transmission. However, the incidence of maternal and neonatal morbidity perioperatively is relatively unknown. The goal of the present study was to prospectively record perioperative maternal and neonatal complications in the largest HIV positive collective undergoing elective Cesarean section with spinal anesthesia published to date. METHODS: From 1999-2001, 54 HIV positive parturients were enrolled in this study. All parturients received IV zidovudine therapy (2 mg/kg body weight) perioperatively. Spinal anesthesia was performed using 60 mg of 4% hyperbaric mepivacaine plus 5 microg sufentanil intrathecally. Sensory, analgesic and motor block characteristics, the incidence of maternal hypotension, postoperative maternal complications as well as neonatal outcome were recorded. RESULTS: Short-term hypotension occurred in 65% of the parturients. Intraoperatively, one parturient died following amniotic fluid embolism. In 17% of the parturients, postoperative complications headed by wound healing impairment, bronchitis and pneumonia requiring prolonged antibiotic therapy were observed. To date, after a minimum observation period of 8 months, only one infant (1.8%) is HIV positive. CONCLUSION: Intrathecal mepivacaine combined with sufentanil in HIV positive parturients undergoing elective Cesarean section is an appropriate anesthetic option. Postoperative maternal morbidity was 17%. Neonatal outcome showed no evidence of neonatal depression.

Adult↗

PubMed2003

Mepivacaine for spinal anesthesia in parturients undergoing elective cesarean delivery: maternal and neonatal plasma concentrations and neonatal outcome.

OBJECTIVE: Worldwide, long-acting bupivacaine is most commonly used for spinal anesthesia in parturients undergoing elective Cesarean delivery. However, advances in surgical technique and shorter duration of surgery make short-acting local anesthetic like mepivacaine appropriate, particularly if combined with opioids to enhance postoperative maternal pain relief. MATERIAL AND METHODS: We assessed the effect of 4% hyperbaric mepivacaine (60 mg) plus 10 microg fentanyl for spinal anesthesia in 11 parturients undergoing elective Cesarean delivery. Sensory, motor and analgesic block characteristics, neonatal outcome (Apgar scores, umbilical cord blood analysis, neurologic and adaptive capacity score) as well as fetal and maternal mepivacaine plasma concentrations at delivery were determined (HPLC/UV). RESULTS: Motor block (Induction-Bromage 0) duration lasted 113 +/- 20 min. Effective analgesia (VAS < or = 40) was 128 +/- 35 min. Maternal and fetal mepivacaine free plasma concentration were 0.18 +/- 0.05 microg/ml and 0.10 +/- 0.03 microg/ml, respectively. The fetal to maternal (UV/MV)-ratio for mepivacaine free plasma concentration was 0.56. Apgar scores, NACScores and the umbilical blood analysis showed no evidence of neonatal depression. CONCLUSIONS: Particularly with short duration of surgery (21 +/- 5 min) intrathecal mepivacaine combined with fentanyl offers a favorable clinical alternative in parturients undergoing elective Cesarean delivery.

Anesthesia, Spinal↗

PubMed2002

[Isolated decrease of haptoglobin during pregnancy: diagnosis by chance or pathological? ].

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.

Adult↗

PubMed2002

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.

Animals↗

PubMed2001

Molecular classification of breast cancer patients by gene expression profiling.

For many tumors, pathological subclasses exist which have to be further defined by genetic markers to improve therapy and follow-up strategies. In this study, cDNA array analyses of breast cancers have been performed to classify tumors into categories based on expression patterns. Comparing purified normal ductal epithelial cells and corresponding tumour tissues, the expression of only a small fraction of genes was found to be significantly changed. A subset of genes repeatedly found to be differentially expressed in breast cancers was subsequently employed to perform a classification of 82 normal and malignant breast specimens by cluster analysis. This analysis identifies a subgroup of transcriptionally related tumours, designated class A, which can be further subdivided into A1 and A2. Correlation with classical clinicopathological parameters revealed that subgroup A1 was characterized by a high number of node-positive tumours (14 of 16). In this subgroup there was a disproportionate number of patients who had already developed distant metastases at the time of diagnosis (25% in this subgroup, compared with 5% among the rest of the samples). Taken together, the use of these differentially expressed marker genes in conjunction with sample clustering algorithms provides a novel molecular classification of breast cancer specimens, which facilitates the identification of patients with a higher risk of recurrence.

Breast Neoplasms↗

PubMed2001

[Amniotic fluid embolism as an obstetric emergency--description of the syndrome and a case with fatal outcome].

Amnotic fluid embolism is an incompletely understood obstetric emergency presenting with the acute onset of hypoxia, hypotension and severe coagulopathy. Up to 86% of the cases are fatal, maternal death occurs within the first hour of symptom onset in 50% of the patients. This report describes the case of a 29-year-old, HIV-positive patient undergoing elective cesarean section who died despite immediate onset of cardiopulmonary resuscitation. The epidemiology of amniotic fluid embolism, clinical presentation, differential diagnosis, pathology and possible treatment are discussed.

Adult↗

PubMed2000

Cervical intraepithelial neoplasia in human immunodeficiency virus-positive patients.

Cervical intraepithelial neoplasia (CIN) is common in patients positive for human immunodeficiency virus (HIV). The questions are whether the management of CIN in these patients should be different from that of HIV-negative women, whether there are any prognostic factors to indicate the course of CIN, and whether the latter is influenced by antiretroviral therapy. A total of 267 HIV-seropositive women were counseled and examined in our colposcopic clinic. Of that number, 53 patients died during the observation period; 74% of these patients were immunosuppressed (CD4 count < 200 cells/mm3), and 45% were given diagnoses of CIN. The incidence of CIN was significantly higher in patients with CD4 less than 200 cells/mm3. Neither the route of HIV infection nor the HPV status nor smoking habits correlated with CIN. CIN relapse was histologically confirmed in 28% of patients who underwent complete surgical removal. Immune status plays an important role in HIV-positive women not only with respect to survival but with respect to CIN.

Adult↗

PubMed1999

Cross-reactive staining of normal bone-marrow cells by monoclonal antibody 2E11.

The monoclonal antibody (MAb) 2E11 is commonly used for detection of microdisseminated epithelial cells in bone marrow of cancer patients. Surprisingly, in an earlier report 2E11 was shown to bind to mononuclear cells in bone marrow in 61% of healthy donors. In the present study we tested whether this cross-reaction with non-epithelial bone-marrow cells can be characterized further. In addition, we analyzed the influence of 2E11 concentration on the staining of mononuclear cells. We performed immunocytochemical double stainings of bone-marrow aspirations from breast-cancer patients using 2E11/A45-B/B3 (MAb against cytokeratin 8, 18, 19) and 2E11/CD45 (MAb against CD45-leukocyte common antigen), while tumor cell lines MCF-7 and K526 as well as bone marrow from breast-cancer patients were treated with different concentrations of 2E11. A portion of 2E11-positive cells was characterized as hematopoietic cells by CD-45-binding, while others were identified as epithelial cells by A45-B/B3-binding. We defined a concentration of 2E11 to immunolabel epithelial cells and distinguish hematopoietic cells. Higher concentrations of 2E11 enhance staining of hematopoietic cells, to match that of epithelial cells. We conclude that 2E11 shows cross-reactivity to epitopes displayed by hematopoietic cells. However, specific staining of epithelial cells can be achieved. As long as there is no antibody available which is highly specific for epithelial cells, detection of microdisseminated tumor cells in bone marrow by antigen-antibody reaction should be verified morphological criteria.

Antibodies, Monoclonal↗

PubMed1999

Expression of p16 and lack of pRB in primary small cell lung cancer.

The retinoblastoma protein (pRB), p16, and cyclin D1 are major components of the RB pathway, which controls the G1 checkpoint of the cell cycle. Proper regulation of this pathway is crucial for normal cell proliferation. Abnormal forms of these proteins have been found in various types of malignant tumours. In the present report, immunohistochemical techniques were applied to study the expression of pRB, p16, and cyclin D1 in 161 samples of primary small cell lung cancer (SCLC) and 20 samples of non-small cell lung cancer (NSCLC). While pRB and cyclin D1 staining was negative in 161 specimens of SCLC, expression of p16 was observed in 153 samples. In contrast to SCLC, 16 out of 20 NSCLC cases exhibited pRB expression and 15 showed cyclin D1 expression, but only very weak p16 staining was found in five samples. These observations could provide additional criteria for the distinction between SCLC and NSCLC. Furthermore, these findings, based on primary tissues, implicate different mechanisms in the tumourigenesis of SCLC and NSCLC.

Adenocarcinoma↗